U.S. patent application number 15/705318 was filed with the patent office on 2018-01-11 for molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto.
This patent application is currently assigned to Dow AgroSciences LLC. The applicant listed for this patent is Dow AgroSciences LLC. Invention is credited to Erich W. Baum, Zoltan L. Benko, Nakyen Choy, Gary D. Crouse, John F. Daeuble, SR., Kyle A. DeKorver, David A. Demeter, Joseph D. Eckelbarger, Ronald J. Heemstra, Ricky Hunter, Daniel I. Knueppel, Fangzheng Li, Timothy P. Martin, Jeffrey Nissen, Michelle Riener, Ronald Ross, JR., Thomas C. Sparks, Tony K. Trullinger, Peter Vednor, Frank J. Wessels, Maurice C. Yap.
Application Number | 20180007911 15/705318 |
Document ID | / |
Family ID | 55806802 |
Filed Date | 2018-01-11 |
United States Patent
Application |
20180007911 |
Kind Code |
A1 |
Martin; Timothy P. ; et
al. |
January 11, 2018 |
Molecules having pesticidal utility, and intermediates,
compositions, and processes, related thereto
Abstract
This disclosure relates to the field of molecules having
pesticidal utility against pests in Phyla Arthropoda, Mollusca, and
Nematoda, processes to produce such molecules, intermediates used
in such processes, pesticidal compositions containing such
molecules, and processes of using such pesticidal compositions
against such pests. These pesticidal compositions may be used, for
example, as acaricides, insecticides, miticides, molluscicides, and
nematicides. This document discloses molecules having the following
formula ("Formula One"). ##STR00001##
Inventors: |
Martin; Timothy P.;
(Noblesville, IN) ; Eckelbarger; Joseph D.;
(Carmel, IN) ; Ross, JR.; Ronald; (Zionsville,
IN) ; DeKorver; Kyle A.; (Lafayette, IN) ;
Heemstra; Ronald J.; (Fishers, IN) ; Knueppel; Daniel
I.; (Zionsville, IN) ; Vednor; Peter;
(Farmington Hills, MI) ; Hunter; Ricky;
(Westfield, IN) ; Demeter; David A.; (Fishers,
IN) ; Trullinger; Tony K.; (Westfield, IN) ;
Baum; Erich W.; (Greenwood, IN) ; Benko; Zoltan
L.; (Indianapolis, IN) ; Choy; Nakyen;
(Carmel, IN) ; Crouse; Gary D.; (Noblesville,
IN) ; Daeuble, SR.; John F.; (Carmel, IN) ;
Li; Fangzheng; (Carmel, IN) ; Nissen; Jeffrey;
(Indianapolis, IN) ; Riener; Michelle; (Watertown,
MA) ; Sparks; Thomas C.; (Greenfield, IN) ;
Wessels; Frank J.; (Indianapolis, IN) ; Yap; Maurice
C.; (Zionsville, IN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Dow AgroSciences LLC |
Indianapolis |
IN |
US |
|
|
Assignee: |
Dow AgroSciences LLC
Indianapolis
IN
|
Family ID: |
55806802 |
Appl. No.: |
15/705318 |
Filed: |
September 15, 2017 |
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9795140 |
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15705318 |
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62148814 |
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62148818 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C07C 323/41 20130101;
C07C 2601/14 20170501; C07D 207/273 20130101; C07C 311/08 20130101;
C07D 205/04 20130101; C07D 207/10 20130101; C07D 231/12 20130101;
A01N 43/653 20130101; C07C 237/42 20130101; C07D 233/36 20130101;
A01N 37/34 20130101; C07C 233/63 20130101; C07D 213/89 20130101;
A01N 41/10 20130101; C07D 305/08 20130101; A01N 43/40 20130101;
C07C 255/29 20130101; C07C 237/22 20130101; C07C 255/60 20130101;
A01N 43/82 20130101; C07C 271/66 20130101; C07C 381/10 20130101;
C07C 317/40 20130101; C07D 209/49 20130101; C07D 213/84 20130101;
C07C 233/65 20130101; C07C 311/46 20130101; C07D 213/56 20130101;
C07D 213/75 20130101; C07D 249/08 20130101; C07D 487/04 20130101;
A01N 53/00 20130101; C07D 277/30 20130101; C07D 307/52 20130101;
A01N 43/707 20130101; C07C 2601/04 20170501; C07D 263/26 20130101;
C07D 295/32 20130101; C07C 317/28 20130101; C07D 277/36 20130101;
C07D 307/33 20130101; C07C 255/46 20130101; C07D 285/06 20130101;
C07C 2601/02 20170501; A01N 43/90 20130101; C07D 231/56 20130101;
A01N 43/60 20130101; C07C 317/14 20130101; C07C 331/12 20130101;
C07D 215/38 20130101; C07D 235/30 20130101; A01N 37/22 20130101;
C07C 259/10 20130101; C07C 323/42 20130101; C07C 2601/08 20170501;
C07D 241/20 20130101; C07D 309/14 20130101; C07C 323/59 20130101;
C07D 233/80 20130101; C07D 331/04 20130101; C07D 333/48 20130101;
C07D 207/452 20130101; C07D 215/227 20130101; C07C 255/57 20130101;
C07D 253/07 20130101; C07D 333/36 20130101; C07D 333/60 20130101;
C07C 271/28 20130101; C07D 261/12 20130101; C07D 213/81 20130101;
C07C 317/50 20130101 |
International
Class: |
A01N 53/00 20060101
A01N053/00; C07D 333/60 20060101 C07D333/60; C07C 233/63 20060101
C07C233/63; C07C 233/65 20060101 C07C233/65; C07C 237/22 20060101
C07C237/22; C07D 333/48 20060101 C07D333/48; C07D 307/52 20060101
C07D307/52; C07D 307/33 20060101 C07D307/33; C07D 277/36 20060101
C07D277/36; C07D 277/30 20060101 C07D277/30; C07D 263/26 20060101
C07D263/26; C07D 261/12 20060101 C07D261/12; C07D 253/07 20060101
C07D253/07; C07D 241/20 20060101 C07D241/20; C07D 235/30 20060101
C07D235/30; C07D 233/80 20060101 C07D233/80; C07D 233/36 20060101
C07D233/36; C07D 231/56 20060101 C07D231/56; C07D 215/38 20060101
C07D215/38; C07D 215/227 20060101 C07D215/227; C07D 213/89 20060101
C07D213/89; C07D 213/84 20060101 C07D213/84; C07D 213/56 20060101
C07D213/56; C07D 209/49 20060101 C07D209/49; C07D 207/452 20060101
C07D207/452; C07D 207/273 20060101 C07D207/273; C07D 205/04
20060101 C07D205/04; C07C 381/10 20060101 C07C381/10; C07C 331/12
20060101 C07C331/12; C07C 323/59 20060101 C07C323/59; C07C 323/42
20060101 C07C323/42; C07C 323/41 20060101 C07C323/41; C07C 317/50
20060101 C07C317/50; C07C 317/40 20060101 C07C317/40; C07C 317/28
20060101 C07C317/28; C07C 317/14 20060101 C07C317/14; C07C 311/46
20060101 C07C311/46; C07C 311/08 20060101 C07C311/08; C07C 271/66
20060101 C07C271/66; C07C 271/28 20060101 C07C271/28; C07C 259/10
20060101 C07C259/10; C07C 255/60 20060101 C07C255/60; C07C 255/57
20060101 C07C255/57; C07C 255/46 20060101 C07C255/46; C07C 255/29
20060101 C07C255/29; C07C 237/42 20060101 C07C237/42; C07D 487/04
20060101 C07D487/04 |
Claims
1. A molecule having the following formula ##STR00650## wherein:
(A) R.sup.1 is selected from the group consisting of H, F, Cl, Br,
I, CN, NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.3-C.sub.6)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.1-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2; (B) R.sup.2 is
selected from the group consisting of H, F, Cl, Br, I, CN,
NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.3-C.sub.6)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.1-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2; (C) R.sup.3 is
selected from the group consisting of H, F, Cl, Br, I, CN,
NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.3-C.sub.6)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.3-C.sub.6)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.1-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2; (D) R.sup.4 is
selected from the group consisting of H, F, Cl, Br, I, CN,
NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.3-C.sub.6)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.3-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2; (E) R.sup.5 is
selected from the group consisting of H, F, Cl, Br, I, CN,
NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.3-C.sub.6)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.1-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2; (F) R.sup.6 is
selected from the group consisting of H and (C.sub.1-C.sub.4)alkyl;
(G) R.sup.7 is selected from the group consisting of H, F, Cl, Br,
and I; (H) R.sup.8 is selected from the group consisting of F, Cl,
Br, and I; (I) R.sup.9 is selected from the group consisting of H
and (C.sub.1-C.sub.4)alkyl; (J) R.sup.10 is selected from the group
consisting of H, (C.sub.1-C.sub.4)alkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl(C.sub.1-C.sub.4)alkoxy,
C(.dbd.O)(C.sub.1-C.sub.4)alkyl, and
(C.sub.1-C.sub.4)alkoxyC(.dbd.O)(C.sub.1-C.sub.4)alkyl; (K)
R.sup.11 is selected from the group consisting of H, F, Cl, Br, I,
CN, NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.3-C.sub.6)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.1-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2; (L) R.sup.12 is
selected from the group consisting of H, F, Cl, Br, I, CN,
NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.3-C.sub.6)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.1-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2; (M) R.sup.13 is
selected from the group consisting of H, F, Cl, Br, I, CN,
NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.3-C.sub.6)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.1-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2; (N) R.sup.14 is
selected from the group consisting of H, F, Cl, Br, I, CN,
NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.3-C.sub.6)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.1-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2; (O) R.sup.15 is
selected from the group consisting of (Q), H,
(C.sub.1-C.sub.4)alkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl(C.sub.1-C.sub.4)alkoxy,
C(.dbd.O)(C.sub.1-C.sub.4)alkyl, and
(C.sub.1-C.sub.4)alkoxyC(.dbd.O)(C.sub.1-C.sub.4)alkyl; (P)
R.sup.16 is selected from the group consisting of (Q),
(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl-O--(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl(C.sub.3-C.sub.8)cycloalkyl,
(C.sub.1-C.sub.8)alkylphenyl, (C.sub.2-C.sub.8)alkenyl,
(C.sub.2-C.sub.8)alkynyl, (C.sub.1-C.sub.8)haloalkyl,
(C.sub.1-C.sub.8)alkyl-S--(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl-S(O)--(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl-S(O).sub.2--(C.sub.1-C.sub.8)alkyl,
O-phenyl, O--(C.sub.2-C.sub.5)alkenyl,
O--(C.sub.1-C.sub.8)alkyl(C.sub.3-C.sub.8)cycloalkyl,
O--(C.sub.1-C.sub.8)alkylphenyl,
(C.sub.1-C.sub.8)alkyl-O--(C.sub.1-C.sub.8)alkyl(C.sub.3-C.sub.8)cycloalk-
yl, (C.sub.1-C.sub.8)alkyl-O--(C.sub.1-C.sub.8)haloalkyl,
(C.sub.1-C.sub.8)alkyl-C(.dbd.O)NH--(C.sub.1-C.sub.8)haloalkyl,
(C.sub.1-C.sub.8)alkyl-NHC(O)--(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl-S--(C.sub.1-C.sub.8)haloalkyl,
(C.sub.1-C.sub.8)alkyl-S(O)--(C.sub.1-C.sub.8)haloalkyl,
(C.sub.1-C.sub.8)alkyl-S(O).sub.2--(C.sub.1-C.sub.8)haloalkyl, and
(C.sub.1-C.sub.8)alkyl-S(O).sub.2--NH.sub.2, wherein each alkyl,
alkenyl, alkynyl, cycloalkyl, haloalkyl, and phenyl, may be
optionally substituted with one or more substituents selected from
the group consisting of F, Cl, Br, I, CN, OH, NH.sub.2, NO.sub.2,
(C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)alkoxy,
(C.sub.1-C.sub.8)haloalkyl, N((C.sub.1-C.sub.8)alkyl).sub.2,
C(O)O(C.sub.1-C.sub.8)alkyl, benzothioenyl,
2,3-dihydro-1H-imidazolonyl, furanyl, pyrazolyl, pyridinyl,
thiazolyl, and triazolyl; (Q) R.sup.15 and R.sup.16 together can
optionally form a 2- to 5-membered saturated or unsaturated,
hydrocarbyl link, which may contain one or more heteroatoms
selected from the group consisting of nitrogen, sulfur, and oxygen,
wherein said hydrocarbyl link may be optionally substituted with
one or more substituents selected from the group consisting of F,
Cl, Br, I, CN, NH.sub.2, and NO.sub.2; (R) Q.sup.1 and Q.sup.2 are
each independently selected from the group consisting of O and S;
and N-oxides, agriculturally acceptable acid addition salts, salt
derivatives, solvates, ester derivatives, crystal polymorphs,
isotopes, resolved stereoisomers, and tautomers, of the molecules
of Formula One.
2. A molecule according to claim 1, wherein R.sup.2 is selected
from the group consisting of H, F, and Cl.
3. A molecule according to claim 1, wherein R.sup.3 is selected
from the group consisting of H, F, and Cl.
4. A molecule according to claim 1, wherein R.sup.4 is F or Cl.
5. A molecule according to claim 1, wherein R.sup.1, R.sup.5,
R.sup.6, R.sup.9, R.sup.10, R.sup.11, R.sup.12, and R.sup.14 are
each independently H.
6. A molecule according to claim 1, wherein R.sup.7 is selected
from the group consisting of Cl and Br.
7. A molecule according to claim 1, wherein R.sup.8 is selected
from the group consisting of Cl and Br.
8. A molecule according to claim 1, wherein R.sup.13 is selected
from the group consisting of H, Cl, and CF.sub.3.
9. A molecule according to claim 1, wherein R.sup.15 is selected
from the group consisting of H and CH.sub.3.
10. A molecule according to claim 1, wherein R.sup.16 is selected
from the group consisting of CH.sub.2, CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2OCH.sub.2CH.sub.2, CH.sub.3,
CH.sub.2CH.sub.3, CH.sub.2CH.sub.2CH.sub.3,
CH.sub.2CH.sub.2CH.sub.2CH.sub.3,
CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.3,
CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.3,
CH.sub.2CH(CH.sub.3).sub.2, CH.sub.2cyclopropyl,
CH.sub.2CH.sub.2cyclopropyl, CH.sub.2cyclobutyl, CH.sub.2phenyl,
CH.sub.2CH.sub.2phenyl, CH.sub.2C.dbd.CH, CH.sub.2C.dbd.CH,
CH.sub.2CF.sub.3, CH.sub.2CHF.sub.2, CH.sub.2CH.sub.2CF.sub.3,
CH.sub.2CF.sub.2CF.sub.3, CH.sub.2CH.sub.2CH.sub.2CF.sub.3,
CH.sub.2CH.sub.2CF.sub.2CF.sub.3, CH.sub.2CF.sub.2CF.sub.2CF.sub.3,
CH.sub.2CH.sub.2CH.sub.2CH.sub.2F, CH.sub.2CH.sub.2SCH.sub.3,
CH.sub.2CH.sub.2S(O)CH.sub.3, CH.sub.2CH.sub.2S(O).sub.2CH.sub.3,
C(CH.sub.3).sub.2CH.sub.2S(O).sub.2CH.sub.3, Ophenyl,
OCH.sub.2CH.dbd.CH.sub.2, OCH.sub.2cyclopropyl, OCH.sub.2phenyl,
CH.sub.2CH.sub.2OCH.sub.2cyclopropyl,
CH.sub.2CH.sub.2CH.sub.2OCH.sub.2CF.sub.3,
CH.sub.2C(.dbd.O)NHCH.sub.2CF.sub.3, or
CH.sub.2CH.sub.2NHC(.dbd.O)CH.sub.3, wherein each CH.sub.2,
CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2CH.sub.2, cyclopropyl, cyclobutyl, and
phenyl, may be optionally substituted with one or more substituents
selected from the group consisting of F, Cl, CN, C(CH.sub.3).sub.3,
CF.sub.3, OCH.sub.3, OCH.sub.2CH.sub.3, N(CH.sub.3).sub.2, and
pyridinyl.
11. A molecule according to claim 1, wherein R.sup.15 and R.sup.16
together are --CH.sub.2CH.sub.2CF.sub.2CH.sub.2--.
12. A molecule according to claim 1, wherein Q.sup.1 and Q.sup.2
are O.
13. A molecule according to claim 1, wherein: (A) R.sup.1 is H; (B)
R.sup.2 is selected from the group consisting of H and Cl; (C)
R.sup.3 is selected from the group consisting of H and Cl; (D)
R.sup.4 is Cl; (E) R.sup.5 is H; (F) R.sup.6 is H; (G) R.sup.7 is
selected from the group consisting of Cl and Br; (H) R.sup.6 is
selected from the group consisting of Cl and Br; (I) R.sup.9 is H;
(J) R.sup.10 is H; (K) R.sup.11 is H; (L) R.sup.12 is H; (M)
R.sup.13 is selected from the group consisting of H, Cl, and
CF.sub.3; (N) R.sup.14 is H; (O) R.sup.15 is selected from the
group consisting of H and CH.sub.3; (P) R.sup.16 is selected from
the group consisting of CH.sub.2, CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2OCH.sub.2CH.sub.2, CH.sub.3,
CH.sub.2CH.sub.3, CH.sub.2CH.sub.2CH.sub.3,
CH.sub.2CH.sub.2CH.sub.2CH.sub.3,
CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.3,
CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.3,
CH.sub.2CH(CH.sub.3).sub.2, CH.sub.2cyclopropyl,
CH.sub.2CH.sub.2cyclopropyl, CH.sub.2cyclobutyl, CH.sub.2phenyl,
CH.sub.2CH.sub.2phenyl, CH.sub.2C.dbd.CH, CH.sub.2C.dbd.CH,
CH.sub.2CF.sub.3, CH.sub.2CHF.sub.2, CH.sub.2CH.sub.2CF.sub.3,
CH.sub.2CF.sub.2CF.sub.3, CH.sub.2CH.sub.2CH.sub.2CF.sub.3,
CH.sub.2CH.sub.2CF.sub.2CF.sub.3, CH.sub.2CF.sub.2CF.sub.2CF.sub.3,
CH.sub.2CH.sub.2CH.sub.2CH.sub.2F, CH.sub.2CH.sub.2SCH.sub.3,
CH.sub.2CH.sub.2S(O)CH.sub.3, CH.sub.2CH.sub.2S(O).sub.2CH.sub.3,
C(CH.sub.3).sub.2CH.sub.2S(O).sub.2CH.sub.3, Ophenyl,
OCH.sub.2CH.dbd.CH.sub.2, OCH.sub.2cyclopropyl, OCH.sub.2phenyl,
CH.sub.2CH.sub.2OCH.sub.2cyclopropyl,
CH.sub.2CH.sub.2CH.sub.2OCH.sub.2CF.sub.3,
CH.sub.2C(.dbd.O)NHCH.sub.2CF.sub.3, and
CH.sub.2CH.sub.2NHC(.dbd.O)CH.sub.3, wherein each CH.sub.2,
CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2CH.sub.2, cyclopropyl, cyclobutyl, and
phenyl, may be optionally substituted with one or more substituents
selected from the group consisting of F, Cl, CN, C(CH.sub.3).sub.3,
CF.sub.3, OCH.sub.3, OCH.sub.2CH.sub.3, N(CH.sub.3).sub.2, and
pyridinyl; and (Q) R.sup.15 and R.sup.16 together are preferably a
4-membered saturated, hydrocarbyl link, wherein said hydrocarbyl
link is substituted with one or more F. (R) Q.sup.1 and Q.sup.2 are
O.
14. A molecule according to claim 1 wherein said molecule is
selected from the group consisting of F1 through F75, F78, F79, F84
through F88, F91 through F100, F102 through F109, F111 through
F135, PF1 through PF7, and PF10 through PF16.
15. A molecule according to claim 1 wherein said molecule is
selected from the group consisting of F4, F15, F28, F30, F35, F38,
F39, F40, F44, F45, F46, F47, F49, and P16.
16. A composition comprising (a) a molecule according to claim 1
and (b) an active ingredient.
17. A composition comprising (a) a molecule according to claim 13
and (b) an active ingredient.
18. A process to control a pest said process comprising applying to
a locus, a pesticidally effective amount of a molecule according to
claim 1.
19. A process according to claim 18 wherein said pest is a chewing
pest.
20. A process according to claim 18 wherein said pest is a
sap-feeding pest.
Description
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application is a continuation of, and claims the
benefit of, U.S. nonprovisional application Ser. No. 15/092,646,
which was filed on Apr. 7, 2016, now allowed, which claims the
benefit of, and priority from, U.S. provisional application Ser.
Nos. 62/148,830; 62/148,837; 62/148,809; 62/148,814; 62/148,818;
and 62/148,824; all of which were filed on Apr. 17, 2015. The
entire contents of all of the above-identified applications are
hereby incorporated by reference into this application.
FIELD OF THIS DISCLOSURE
[0002] This disclosure relates to the field of molecules having
pesticidal utility against pests in Phyla Arthropoda, Mollusca, and
Nematoda, processes to produce such molecules, intermediates used
in such processes, pesticidal compositions containing such
molecules, and processes of using such pesticidal compositions
against such pests. These pesticidal compositions may be used, for
example, as acaricides, insecticides, miticides, molluscicides, and
nematicides.
BACKGROUND OF THIS DISCLOSURE
[0003] "Many of the most dangerous human diseases are transmitted
by insect vectors" (Rivero et al.). "Historically, malaria, dengue,
yellow fever, plague, filariasis, louse-borne typhus,
trypanomiasis, leishmaniasis, and other vector borne diseases were
responsible for more human disease and death in the 17.sup.th
through the early 20.sup.th centuries than all other causes
combined" (Gubler). Vector-borne diseases are responsible for about
17% of the global parasitic and infectious diseases. Malaria alone
causes over 800,000 deaths a year, 85% of which occur in children
under five years of age. Each year there are about 50 to about 100
million cases of dengue fever. A further 250,000 to 500,000 cases
of dengue hemorrhagic fever occur each year (Matthews). Vector
control plays a critical role in the prevention and control of
infectious diseases. However, insecticide resistance, including
resistance to multiple insecticides, has arisen in all insect
species that are major vectors of human diseases (Rivero et al.).
Recently, more than 550 arthropod species have developed resistance
to at least one pesticide (Whalon et al.). Furthermore, the cases
of insect resistance continue to exceed by far the number of cases
of herbicide and fungicide resistance (Sparks et al.).
[0004] Each year insects, plant pathogens, and weeds, destroy more
than 40% of all food production. This loss occurs despite the
application of pesticides and the use of a wide array of
non-chemical controls, such as, crop rotations, and biological
controls. If just some of this food could be saved, it could be
used to feed the more than three billion people in the world who
are malnourished (Pimental).
[0005] Plant parasitic nematodes are among the most widespread
pests, and are frequently one of the most insidious and costly. It
has been estimated that losses attributable to nematodes are from
about 9% in developed countries to about 15% in undeveloped
countries. However, in the United States of America a survey of 35
States on various crops indicated nematode-derived losses of up to
25% (Nicol et al.).
[0006] It is noted that gastropods (slugs and snails) are pests of
less economic importance than other arthropods or nematodes, but in
certain places, they may reduce yields substantially, severely
affecting the quality of harvested products, as well as,
transmitting human, animal, and plant diseases. While only a few
dozen species of gastropods are serious regional pests, a handful
of species are important pests on a worldwide scale. In particular,
gastropods affect a wide variety of agricultural and horticultural
crops, such as, arable, pastoral, and fiber crops; vegetables; bush
and tree fruits; herbs; and ornamentals (Speiser).
[0007] Termites cause damage to all types of private and public
structures, as well as to agricultural and forestry resources. In
2005, it was estimated that termites cause over US$50 billion in
damage worldwide each year (Korb).
[0008] Consequently, for many reasons, including those mentioned
above, there is an on-going need for the costly (estimated to be
about US$256 million per pesticide in 2010), time-consuming (on
average about 10 years per pesticide), and difficult, development
of new pesticides (CropLife America).
CERTAIN REFERENCES CITED IN THIS DISCLOSURE
[0009] CropLife America, The Cost of New Agrochemical Product
Discovery, Development & Registration, and Research &
Development predictions for the Future, 2010. [0010] Drewes, M.,
Tietjen, K., Sparks, T. C., High-Throughput Screening in
Agrochemical Research, Modern Methods in Crop Protection Research,
Part I, Methods for the Design and Optimization of New Active
Ingredients, Edited by Jeschke, P., Kramer, W., Schirmer, U., and
Matthias W., p. 1-20, 2012. [0011] Gubler, D., Resurgent
Vector-Borne Diseases as a Global Health Problem, Emerging
Infectious Diseases, Vol. 4, No. 3, p. 442-450, 1998. [0012] Korb,
J., Termites, Current Biology, Vol. 17, No. 23, 2007. [0013]
Matthews, G., Integrated Vector Management: Controlling Vectors of
Malaria and Other Insect Vector Borne Diseases, Ch. 1, p. 1, 2011.
[0014] Nicol, J., Turner S., Coyne, L., den Nijs, L., Hocksland,
L., Tahna-Maafi, Z., Current Nematode Threats to World Agriculture,
Genomic and Molecular Genetics of Plant--Nematode Interactions, p.
21-43, 2011. [0015] Pimental, D., Pest Control in World
Agriculture, Agricultural Sciences--Vol. II, 2009. [0016] Rivero,
A., Vezilier, J., Weill, M., Read, A., Gandon, S., Insect Control
of Vector-Borne Diseases: When is Insect Resistance a Problem?
Public Library of Science Pathogens, Vol. 6, No. 8, p. 1-9, 2010.
[0017] Sparks T. C., Nauen R., IRAC: Mode of action classification
and insecticide resistance management, Pesticide Biochemistry and
Physiology (2014) available online 4 Dec. 2014. [0018] Speiser, B.,
Molluscicides, Encyclopedia of Pest Management, Ch. 219, p.
506-508, 2002. [0019] Whalon, M., Mota-Sanchez, D., Hollingworth,
R., Analysis of Global Pesticide Resistance in Arthropods, Global
Pesticide Resistance in Arthropods, Ch. 1, p. 5-33, 2008.
DEFINITIONS USED IN THIS DISCLOSURE
[0020] The examples given in these definitions are generally
non-exhaustive and must not be construed as limiting this
disclosure. It is understood that a substituent should comply with
chemical bonding rules and steric compatibility constraints in
relation to the particular molecule to which it is attached. These
definitions are only to be used for the purposes of this
disclosure.
[0021] The phrase "active ingredient" means a material having
activity useful in controlling pests, and/or that is useful in
helping other materials have better activity in controlling pests,
examples of such materials include, but are not limited to,
acaricides, algiddes, antifeedants, avicides, bactericides, bird
repellents, chemosterilants, fungicides, herbicide safeners,
herbicides, insect attractants, insect repellents, insecticides,
mammal repellents, mating disrupters, molluscicides, nematicides,
plant activators, plant growth regulators, rodenticides,
synergists, and virucides (see alanwood.net). Specific examples of
such materials include, but are not limited to, the materials
listed in active ingredient group alpha.
[0022] The phrase "active ingredient group alpha" (hereafter
"AIGA") means collectively the following materials:
[0023] (1) (3-ethoxypropyl)mercury bromide, 1,2-dibromoethane,
1,2-dichloroethane, 1,2-dichloropropane, 1,3-dichloropropene,
1-MCP, 1-methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol,
2,3,3-TPA, 2,3,5-tri-iodobenzoic acid, 2,3,6-TBA, 2,4,5-T,
2,4,5-TB, 2,4,5-TP, 2,4-D, 2,4-DB, 2,4-DEB, 2,4-DEP, 2,4-DES,
2,4-DP, 2,4-MCPA, 2,4-MCPB, 2iP, 2-methoxyethylmercury chloride,
2-phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP, 3,6-dichloropicolinic acid,
4-aminopyridine, 4-CPA, 4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol,
8-hydroxyquinoline sulfate, 8-phenylmercurioxyquinoline, abamectin,
abamectin-aminomethyl, abscisic acid, ACC, acephate, acequinocyl,
acetamiprid, acethion, acetochlor, acetofenate, acetophos,
acetoprole, acibenzolar, acifluorfen, aclonifen, ACN, acrep,
acrinathrin, acrolein, acrylonitrile, acypetacs, afidopyropen,
afoxolaner, alachlor, alanap, alanycarb, albendazole, aldicarb,
aldicarb sulfone, aldimorph, aldoxycarb, aldrin, allethrin,
allicin, allidochlor, allosamidin, alloxydim, allyl alcohol,
allyxycarb, alorac, alpha-cypermethrin, alpha-endosulfan,
alphamethrin, altretamine, aluminium phosphide, aluminum phosphide,
ametoctradin, ametridione, ametryn, ametryne, amibuzin,
amicarbazone, amicarthiazol, amidithion, amidoflumet,
amidosulfuron, aminocarb, aminocyclopyrachlor, aminopyralid,
aminotriazole, amiprofos-methyl, amiprophos, amiprophos-methyl,
amisulbrom, amiton, amitraz, amitrole, ammonium sulfamate, amobam,
amorphous silica gel, amorphous silicon dioxide, ampropylfos, AMS,
anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone,
antu, apholate, aramite, arprocarb, arsenous oxide, asomate,
aspirin, asulam, athidathion, atraton, atrazine, aureofungin,
avermectin B1, AVG, aviglycine, azaconazole, azadirachtin,
azafenidin, azamethiphos, azidithion, azimsulfuron, azinphosethyl,
azinphos-ethyl, azinphosmethyl, azinphos-methyl, aziprotryn,
aziprotryne, azithiram, azobenzene, azocyclotin, azothoate,
azoxystrobin, bachmedesh, barban, barbanate, barium
hexafluorosilicate, barium polysulfide, barium silicofluoride,
barthrin, basic copper carbonate, basic copper chloride, basic
copper sulfate, BCPC, beflubutamid, benalaxyl, benalaxyl-M,
benazolin, bencarbazone, benclothiaz, bendaqingbingzhi, bendiocarb,
bendioxide, benefin, benfluralin, benfuracarb, benfuresate,
benmihuangcaoan, benodanil, benomyl, benoxacor, benoxafos,
benquinox, bensulfuron, bensulide, bensultap, bentaluron, bentazon,
bentazone, benthiavalicarb, benthiazole, benthiocarb, bentranil,
benzadox, benzalkonium chloride, benzamacril, benzamizole,
benzamorf, benzene hexachloride, benzfendizone, benzimine,
benzipram, benzobicyclon, benzoepin, benzofenap, benzofluor,
benzohydroxamic acid, benzomate, benzophosphate, benzothiadiazole,
benzovindiflupyr, benzoximate, benzoylprop, benzthiazuron,
benzuocaotong, benzyl benzoate, benzyladenine, berberine,
beta-cyfluthrin, beta-cypermethrin, bethoxazin, BHC, bialaphos,
bicyclopyrone, bifenazate, bifenox, bifenthrin, bifujunzhi,
bilanafos, binapacryl, bingqingxiao, bioallethrin,
bioethanomethrin, biopermethrin, bioresmethrin, biphenyl, bisazir,
bismerthiazol, bismerthiazol-copper, bisphenylmercury
methylenedi(x-naphthalene-y-sulphonate), bispyribac, bistrifluron,
bisultap, bitertanol, bithionol, bixafen, blasticidin-S, borax,
Bordeaux mixture, boric acid, boscalid, BPPS, brassinolide,
brassinolide-ethyl, brevicomin, brodifacoum, brofenprox,
brofenvalerate, broflanilide, brofluthrinate, bromacil,
bromadiolone, bromchlophos, bromethalin, bromethrin, bromfenvinfos,
bromoacetamide, bromobonil, bromobutide, bromociclen, bromocyclen,
bromo-DDT, bromofenoxim, bromofos, bromomethane, bromophos,
bromophos-ethyl, bromopropylate, bromothalonil, bromoxynil,
brompyrazon, bromuconazole, bronopol, BRP, BTH, bucarpolate,
bufencarb, buminafos, bupirimate, buprofezin, Burgundy mixture,
busulfan, busulphan, butacarb, butachlor, butafenacil, butam,
butamifos, butane-fipronil, butathiofos, butenachlor,
butene-fipronil, butethrin, buthidazole, buthiobate, buthiuron,
butifos, butocarboxim, butonate, butopyronoxyl, butoxycarboxim,
butralin, butrizol, butroxydim, buturon, butylamine, butylate,
butylchlorophos, butylene-fipronil, cacodylic acid, cadusafos,
cafenstrole, calciferol, calcium arsenate, calcium chlorate,
calcium cyanamide, calcium cyanide, calcium polysulfide,
calvinphos, cambendichlor, camphechlor, camphor, captafol, captan,
carbam, carbamorph, carbanolate, carbaril, carbaryl, carbasulam,
carbathion, carbendazim, carbendazol, carbetamide, carbofenotion,
carbofuran, carbon disulfide, carbon tetrachloride, carbonyl
sulfide, carbophenothion, carbophos, carbosulfan, carboxazole,
carboxide, carboxin, carfentrazone, carpropamid, cartap, carvacrol,
carvone, CAVP, CDAA, CDEA, CDEC, cellocidin, CEPC, ceralure,
cerenox, cevadilla, Cheshunt mixture, chinalphos,
chinalphos-methyl, chinomethionat, chinomethionate, chiralaxyl,
chitosan, chlobenthiazone, chlomethoxyfen, chloralose, chloramben,
chloramine phosphorus, chloramphenicol, chloraniformethan,
chloranil, chloranocryl, chlorantraniliprole, chlorazifop,
chlorazine, chlorbenside, chlorbenzuron, chlorbicyclen,
chlorbromuron, chlorbufam, chlordane, chlordecone, chlordimeform,
chlorempenthrin, chloretazate, chlorethephon, chlorethoxyfos,
chloreturon, chlorfenac, chlorfenapyr, chlorfenazole,
chlorfenethol, chlorfenidim, chlorfenprop, chlorfenson,
chlorfensulphide, chlorfenvinphos, chlorfenvinphos-methyl,
chlorfluazuron, chlorflurazole, chlorflurecol, chlorfluren,
chlorflurenol, chloridazon, chlorimuron, chlorinate, chlor-IPC,
chlormephos, chlormequat, chlormesulone, chlormethoxynil,
chlornidine, chlornitrofen, chloroacetic acid, chlorobenzilate,
chlorodinitronaphthalenes, chlorofenizon, chloroform,
chloromebuform, chloromethiuron, chloroneb, chlorophacinone,
chlorophos, chloropicrin, chloropon, chloropropylate,
chlorothalonil, chlorotoluron, chloroxifenidim, chloroxuron,
chloroxynil, chlorphonium, chlorphoxim, chlorprazophos,
chlorprocarb, chlorpropham, chlorpyrifos, chlorpyrifos-methyl,
chlorquinox, chlorsulfuron, chlorthal, chlorthiamid, chlorthiophos,
chlortoluron, chlozolinate, chitosan, cholecalciferol, choline
chloride, chromafenozide, cicloheximide, cimectacarb, cimetacarb,
cinerin I, cinerin II, cinerins, cinidon-ethyl, cinmethylin,
cinosulfuron, cintofen, ciobutide, cisanilide, cismethrin,
clacyfos, clefoxydim, clenpirin, clenpyrin, clethodim, climbazole,
cliodinate, clodinafop, cloethocarb, clofencet, clofenotane,
clofentezine, clofenvinfos, clofibric acid, clofop, clomazone,
clomeprop, clonitralid, cloprop, cloproxydim, clopyralid,
cloquintocet, cloransulam, closantel, clothianidin, clotrimazole,
cloxyfonac, cloxylacon, clozylacon, CMA, CMMP, CMP, CMU, codlelure,
colecalciferol, colophonate, copper 8-quinolinolate, copper
acetate, copper acetoarsenite, copper arsenate, copper carbonate,
basic, copper hydroxide, copper naphthenate, copper oleate, copper
oxychloride, copper silicate, copper sulfate, copper sulfate,
basic, copper zinc chromate, coumachlor, coumafene, coumafos,
coumafuryl, coumaphos, coumatetralyl, coumethoxystrobin,
coumithoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol,
cresylic acid, crimidine, crotamiton, crotoxyfos, crotoxyphos,
crufomate, cryolite, cue-lure, cufraneb, cumyleron, cumyluron,
cuprobam, cuprous oxide, curcumenol, CVMP, cyanamide, cyanatryn,
cyanazine, cyanofenphos, cyanogen, cyanophos, cyanthoate,
cyantraniliprole, cyanuric acid, cyazofamid, cybutryne,
cyclafuramid, cyclanilide, cyclaniliprole, cyclethrin, cycloate,
cycloheximide, cycloprate, cycloprothrin, cyclopyrimorate,
cyclosulfamuron, cycloxydim, cycluron, cyenopyrafen, cyflufenamid,
cyflumetofen, cyfluthrin, cyhalofop, cyhalothrin, cyhexatin,
cymiazole, cymoxanil, cyometrinil, cypendazole, cypermethrin,
cyperquat, cyphenothrin, cyprazine, cyprazole, cyproconazole,
cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyromazine,
cythioate, cytrex, daimuron, dalapon, daminozide, dayoutong,
dazomet, DBCP, d-camphor, DCB, DCIP, DCPA, DCPTA, DCU, DDD, DDPP,
DDT, DDVP, debacarb, decafentin, decamethrin, decarbofuran, deet,
dehydroacetic acid, deiquat, delachlor, delnav, deltamethrin,
demephion, demephion-O, demephion-S, demeton, demeton-methyl,
demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl,
demeton-S-methyl sulphone, demeton-S-methylsulphon, DEP,
depallethrine, derris, desmedipham, desmetryn, desmetryne,
d-fanshiluquebingjuzhi, diafenthiuron, dialifor, dialifos,
diallate, diamidafos, dianat, diatomaceous earth, diatomite,
diazinon, dibrom, dibutyl phthalate, dibutyl succinate, dicamba,
dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone,
dichloralurea, dichlorbenzuron, dichlorfenidim, dichlorflurecol,
dichlorflurenol, dichlormate, dichlormid, dichloromethane,
dicloromezotiaz, dichlorophen, dichlorprop, dichlorprop-P,
dichlorvos, dichlozolin, dichlozoline, diclobutrazol, diclocymet,
diclofop, diclomezine, dicloran, diclosulam, dicofol, dicophane,
dicoumarol, dicresyl, dicrotophos, dicryl, dicumarol, dicyclanil,
dicyclonon, dieldrin, dienochlor, diethamquat, diethatyl, diethion,
diethion, diethofencarb, dietholate, diethon, diethyl
pyrocarbonate, diethyltoluamide, difenacoum, difenoconazole,
difenopenten, difenoxuron, difenzoquat, difethialone, diflovidazin,
diflubenzuron, diflufenican, diflufenicanil, diflufenzopyr,
diflumetorim, dikegulac, dilor, dimatif, dimefluthrin, dimefox,
dimefuron, dimehypo, dimepiperate, dimetachlone, dimetan,
dimethacarb, dimethachlone, dimethachlor, dimethametryn,
dimethenamid, dimethenamid-P, dimethipin, dimethirimol, dimethoate,
dimethomorph, dimethrin, dimethyl carbate, dimethyl disulfide,
dimethyl phthalate, dimethylvinphos, dimetilan, dimexano,
dimidazon, dimoxystrobin, dimpylate, dimuron, dinex, dingjunezuo,
diniconazole, diniconazole-M, dinitramine, dinitrophenols,
dinobuton, dinocap, dinocap-4, dinocap-6, dinocton, dinofenate,
dinopenton, dinoprop, dinosam, dinoseb, dinosulfon, dinotefuran,
dinoterb, dinoterbon, diofenolan, dioxabenzofos, dioxacarb,
dioxathion, dioxation, diphacin, diphacinone, diphenadione,
diphenamid, diphenamide, diphenyl sulfone, diphenylamine,
diphenylsulphide, diprogulic acid, dipropalin, dipropetryn,
dipterex, dipymetitrone, dipyrithione, diquat, disodium
tetraborate, disosultap, disparlure, disugran, disul, disulfiram,
disulfoton, ditalimfos, dithianon, dithicrofos, dithioether,
dithiometon, dithiopyr, diuron, dixanthogen, d-limonene, DMDS,
DMPA, DNOC, dodemorph, dodicin, dodine, dofenapyn, doguadine,
dominicalure, doramectin, DPC, drazoxolon, DSMA, d-trans-allethrin,
d-trans-resmethrin, dufulin, dymron, EBEP, EBP, ebufos,
ecdysterone, echlomezol, EDB, EDC, EDDP, edifenphos, eglinazine,
emamectin, EMPC, empenthrin, enadenine, endosulfan, endothal,
endothall, endothion, endrin, enestroburin, enilconazole,
enoxastrobin, ephirsulfonate, EPN, epocholeone, epofenonane,
epoxiconazole, eprinomectin, epronaz, EPTC, erbon, ergocalciferol,
erlujixiancaoan, esdepallethrine, esfenvalerate, ESP, esprocarb,
etacelasil, etaconazole, etaphos, etem, ethaboxam, ethachlor,
ethalfluralin, ethametsulfuron, ethaprochlor, ethephon,
ethidimuron, ethiofencarb, ethiolate, ethion, ethiozin, ethiprole,
ethirimol, ethoate-methyl, ethobenzanid, ethofumesate,
ethohexadiol, ethoprop, ethoprophos, ethoxyfen, ethoxyquin,
ethoxysulfuron, ethychlozate, ethyl formate, ethyl pyrophosphate,
ethylan, ethyl-DDD, ethylene, ethylene dibromide, ethylene
dichloride, ethylene oxide, ethylicin, ethylmercury
2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercury
bromide, ethylmercury chloride, ethylmercury phosphate, etinofen,
ETM, etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole,
etrimfos, etrimphos, eugenol, EXD, famoxadone, famphur, fenac,
fenamidone, fenaminosulf, fenaminstrobin, fenamiphos, fenapanil,
fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole,
fenbutatin oxide, fenchlorazole, fenchlorphos, fenclofos,
fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenidin,
fenitropan, fenitrothion, fenizon, fenjuntong, fenobucarb,
fenolovo, fenoprop, fenothiocarb, fenoxacrim, fenoxanil,
fenoxaprop, fenoxaprop-P, fenoxasulfone, fenoxycarb, fenpiclonil,
fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph,
fenpyrazamine, fenpyroximate, fenquinotrione, fenridazon, fenson,
fensulfothion, fenteracol, fenthiaprop, fenthion, fenthion-ethyl,
fentiaprop, fentin, fentrazamide, fentrifanil, fenuron,
fenuron-TCA, fenvalerate, ferbam, ferimzone, ferric phosphate,
ferrous sulfate, fipronil, flamprop, flamprop-M, flazasulfuron,
flocoumafen, flometoquin, flonicamid, florasulam, fluacrypyrim,
fluazifop, fluazifop-P, fluazinam, fluazolate, fluazuron,
flubendiamide, flubenzimine, flubrocythrinate, flucarbazone,
flucetosulfuron, fluchloralin, flucofuron, flucycloxuron,
flucythrinate, fludioxonil, fludndthyl, fluenetil, fluensulfone,
flufenacet, flufenerim, flufenican, flufenoxuron, flufenoxystrobin,
flufenprox, flufenpyr, flufenzine, flufiprole, fluhexafon,
flumethrin, flumetover, flumetralin, flumetsulam, flumezin,
flumiclorac, flumioxazin, flumipropyn, flumorph, fluometuron,
fluopicolide, fluopyram, fluorbenside, fluoridamid,
fluoroacetamide, fluoroacetic acid, fluorochloridone, fluorodifen,
fluoroglycofen, fluoroimide, fluoromide, fluoromidine,
fluoronitrofen, fluoroxypyr, fluothiuron, fluotrimazole,
fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate,
flupyradifurone, flupyrsulfuron, fluquinconazole, fluralaner,
flurazole, flurecol, flurenol, fluridone, flurochloridone,
fluromidine, fluroxypyr, flurprimidol, flursulamid, flurtamone,
flusilazole, flusulfamide, flutenzine, fluthiacet, fluthiamide,
flutianil, flutolanil, flutriafol, fluvalinate, fluxapyroxad,
fluxofenim, folpel, folpet, fomesafen, fonofos, foramsulfuron,
forchlorfenuron, formaldehyde, formetanate, formothion,
formparanate, fosamine, fosetyl, fosmethilan, fospirate,
fosthiazate, fosthietan, frontalin, fthalide, fuberidazole,
fucaojing, fucaomi, fujunmanzhi, fulumi, fumarin, funaihecaoling,
fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr, furan
tebufenozide, furathiocarb, furcarbanil, furconazole,
furconazole-cis, furethrin, furfural, furilazole, furmecyclox,
furophanate, furyloxyfen, gamma-BHC, gamma-cyhalothrin, gamma-HCH,
genit, gibberellic acid, gibberellin A3, gibberellins, gliftor,
glitor, glucochloralose, glufosinate, glufosinate-P, glyodin,
glyoxime, glyphosate, glyphosine, gossyplure, grandlure,
griseofulvin, guanoctine, guazatine, halacrinate, halauxifen,
halfenprox, halofenozide, halosafen, halosulfuron, haloxydine,
haloxyfop, haloxyfop-P, haloxyfop-R, HCA, HCB, HCH, hemel, hempa,
HEOD, heptachlor, heptafluthrin, heptenophos, heptopargil,
herbimycin, herbimycin A, heterophos, hexachlor, hexachloran,
hexachloroacetone, hexachlorobenzene, hexachlorobutadiene,
hexachlorophene, hexaconazole, hexaflumuron, hexafluoramin,
hexaflurate, hexalure, hexamide, hexazinone, hexylthiofos,
hexythiazox, HHDN, holosulf, homobrassinolide, huancaiwo,
huanchongjing, huangcaoling, huanjunzuo, hydramethylnon,
hydrargaphen, hydrated lime, hydrogen cyanamide, hydrogen cyanide,
hydroprene, hydroxyisoxazole, hymexazol, hyquincarb, IAA, IBA, IBP,
icaridin, imazalil, imazamethabenz, imazamox, imazapic, imazapyr,
imazaquin, imazethapyr, imazosulfuron, imibenconazole, imicyafos,
imidacloprid, imidaclothiz, iminoctadine, imiiprothrin, inabenfide,
indanofan, indaziflam, indoxacarb, inezin, infusorial earth,
iodobonil, iodocarb, iodofenphos, iodomethane, iodosulfuron,
iofensulfuron, ioxynil, ipazine, IPC, ipconazole, ipfencarbazone,
iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol,
IPSP, IPX, isamidofos, isazofos, isobenzan, isocarbamid,
isocarbamide, isocarbophos, isocil, isodrin, isofenphos,
isofenphos-methyl, isofetamid, isolan, isomethiozin, isonoruron,
isopamphos, isopolinate, isoprocarb, isoprocil, isopropalin,
isopropazol, isoprothiolane, isoproturon, isopyrazam, isopyrimol,
isothioate, isotianil, isouron, isovaledione, isoxaben,
isoxachlortole, isoxadifen, isoxaflutole, isoxapyrifop, isoxathion,
isuron, ivermectin, ixoxaben, izopamfos, izopamphos, japonilure,
japothrins, jasmolin I, jasmolin II, jasmonic acid,
jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan,
jiecaoxi, jinganmycin A, jodfenphos, juvenile hormone I, juvenile
hormone II, juvenile hormone III, kadethrin, kappa-bifenthrin,
kappa-tefluthrin, karbutilate, karetazan, kasugamycin, kejunlin,
kelevan, ketospiradox, kieselguhr, kinetin, kinoprene, kiralaxyl,
kresoxim-methyl, kuicaoxi, lactofen, lambda-cyhalothrin, latilure,
lead arsenate, lenacil, lepimectin, leptophos, lianbenjingzhi, lime
sulfur, lindane, lineatin, linuron, lirimfos, litlure, looplure,
lufenuron, luxiancaolin, lvdingjunzhi, lvfumijvzhi, lvxiancaolin,
lythidathion, M-74, M-81, MAA, magnesium phosphide, malathion,
maldison, maleic hydrazide, malonoben, maltodextrin, MAMA,
mancopper, mancozeb, mandestrobin, mandipropamid, maneb, matrine,
mazidox, MCC, MCP, MCPA, MCPA-thioethyl, MCPB, MCPP, mebenil,
mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-P, medimeform,
medinoterb, medlure, mefenacet, mefenoxam, mefenpyr, mefluidide,
megatomoic acid, melissyl alcohol, melitoxin, MEMC, menazon,
MEP, mepanipyrim, meperfluthrin, mephenate, mephosfolan, mepiquat,
mepronil, meptyldinocap, mercaptodimethur, mercaptophos,
mercaptophos thiol, mercaptothion, mercuric chloride, mercuric
oxide, mercurous chloride, merphos, merphos oxide, mesoprazine,
mesosulfuron, mesotrione, mesulfen, mesulfenfos, mesulphen,
metacresol, metaflumizone, metalaxyl, metalaxyl-M, metaldehyde,
metam, metamifop, metamitron, metaphos, metaxon, metazachlor,
metazosulfuron, metazoxolon, metconazole, metepa, metflurazon,
methabenzthiazuron, methacrifos, methalpropalin, metham,
methamidophos, methasulfocarb, methazole, methfuroxam,
methibenzuron, methidathion, methiobencarb, methiocarb,
methiopyrisulfuron, methiotepa, methiozolin, methiuron,
methocrotophos, metholcarb, methometon, methomyl, methoprene,
methoprotryn, methoprotryne, methoquin-butyl, methothrin,
methoxychlor, methoxyfenozide, methoxyphenone, methyl apholate,
methyl bromide, methyl eugenol, methyl iodide, methyl
isothiocyanate, methyl parathion, methylacetophos,
methylchloroform, methyldithiocarbamic acid, methyldymron,
methylene chloride, methyl-isofenphos, methylmercaptophos,
methylmercaptophos oxide, methylmercaptophos thiol, methylmercury
benzoate, methylmercury dicyandiamide, methylmercury
pentachlorophenoxide, methylneodecanamide, methylnitrophos,
methyltriazothion, metiozolin, metiram, metiram-zinc, metobenzuron,
metobromuron, metofluthrin, metolachlor, metolcarb, metometuron,
metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone,
metriam, metribuzin, metrifonate, metriphonate, metsulfovax,
metsulfuron, mevinphos, mexacarbate, miechuwei, mieshuan,
miewenjuzhi, milbemectin, milbemycin oxime, milneb, mima2nan,
mipafox, MIPC, mirex, MNAF, moguchun, molinate, molosultap,
momfluorothrin, monalide, monisuron, monoamitraz, monochloroacetic
acid, monocrotophos, monolinuron, monomehypo, monosulflram,
monosulfuron, monosultap, monuron, monuron-TCA, morfamquat,
moroxydine, morphothion, morzid, moxidectin, MPMC, MSMA, MTMC,
muscalure, myclobutanil, myclozolin, myricyl alcohol,
N-(ethylmercury)-p-toluenesulphonanilide, NAA, NAAm, nabam,
naftalofos, naled, naphthalene, naphthaleneacetamide, naphthalic
anhydride, naphthalophos, naphthoxyacetic acids, naphthylacetic
acids, naphthylindane-1,3-diones, naphthyloxyacetic acids,
naproanilide, napropamide, napropamide-M, naptalam, natamycin,
NBPOS, neburea, neburon, nendrin, neonicotine, nichlorfos,
niclofen, niclosamide, nicobifen, nicosulfuron, nicotine, nicotine
sulfate, nifluridide, nikkomycins, NIP, nipyraclofen, nipyralofen,
nitenpyram, nithiazine, nitralin, nitrapyrin, nitrilacarb,
nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl,
nobormide, nonanol, norbormide, norea, norflurazon, nornicotine,
noruron, novaluron, noviflumuron, NPA, nuarimol, nuranone, OCH,
octachlorodipropyl ether, octhilinone, o-dichlorobenzene, ofurace,
omethoate, o-phenylphenol, orbencarb, orfralure, orthobencarb,
ortho-dichlorobenzene, orthosulfamuron, oryctalure, orysastrobin,
oryzalin, osthol, osthole, ostramone, ovatron, ovex, oxabetrinil,
oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon,
oxapyrazone, oxasulfuron, oxathiapiprolin, oxaziclomefone,
oxine-copper, oxine-Cu, oxolinic acid, oxpoconazole, oxycarboxin,
oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyenadenine,
oxyfluorfen, oxymatrine, oxytetracycline, oxythioquinox, PAC,
paclobutrazol, paichongding, pallethrine, PAP,
para-dichlorobenzene, parafluron, paraquat, parathion,
parathion-methyl, parinol, Paris green, PCNB, PCP, PCP-Na,
p-dichlorobenzene, PDJ, pebulate, pedinex, pefurazoate, pelargonic
acid, penconazole, pencycuron, pendimethalin, penfenate, penflufen,
penfluron, penoxalin, penoxsulam, pentachlorophenol,
pentachlorophenyl laurate, pentanochlor, penthiopyrad, pentmethrin,
pentoxazone, perchlordecone, perfluidone, permethrin, pethoxamid,
PHC, phenamacril, phenamacril-ethyl, phenaminosulf, phenazine
oxide, phenetacarbe, phenisopham, phenkapton, phenmedipham,
phenmedipham-ethyl, phenobenzuron, phenothiol, phenothrin,
phenproxide, phenthoate, phenylmercurlurea, phenylmercury acetate,
phenylmercury chloride, phenylmercury derivative of pyrocatechol,
phenylmercury nitrate, phenylmercury salicylate, phorate,
phosacetim, phosalone, phosametine, phosazetim, phosazetin,
phoscyclotin, phosdiphen, phosethyl, phosfolan, phosfolan-methyl,
phosglycin, phosmet, phosnichlor, phosphamide, phosphamidon,
phosphine, phosphinothricin, phosphocarb, phosphorus, phostin,
phoxim, phoxim-methyl, phthalide, phthalophos, phthalthrin,
picarbutrazox, picaridin, pidoram, picolinafen, picoxystrobin,
pimaricin, pindone, pinoxaden, piperalin, piperazine, piperonyl
butoxide, piperonyl cyclonene, piperophos, piproctanly,
piproctanyl, piprotal, pirimetaphos, pirimicarb, piriminil,
pirimioxyphos, pirimiphos-ethyl, pirimiphos-methyl, pival,
pivaldione, plifenate, PMA, PMP, polybutenes, polycarbamate,
polychlorcamphene, polyethoxyquinoline, polyoxin D, polyoxins,
polyoxorim, polythialan, potassium arsenite, potassium azide,
potassium cyanate, potassium ethylxanthate, potassium naphthenate,
potassium polysulfide, potassium thiocyanate, pp'-DDT, prallethrin,
precocene I, precocene II, precocene III, pretilachlor,
primidophos, primisulfuron, probenazole, prochloraz, proclonol,
procyazine, procymidone, prodiamine, profenofos, profluazol,
profluralin, profluthrin, profoxydim, profurite-aminium,
proglinazine, prohexadione, prohydrojasmon, promacyl, promecarb,
prometon, prometryn, prometryne, promurit, pronamide, propachlor,
propafos, propamidine, propamocarb, propanil, propaphos,
propaquizafop, propargite, proparthrin, propazine, propetamphos,
propham, propiconazole, propidine, propineb, propisochlor,
propoxur, propoxycarbazone, propyl isome, propyrisulfuron,
propyzamide, proquinazid, prosuler, prosulfalin, prosulfocarb,
prosulfuron, prothidathion, prothiocarb, prothioconazole,
prothiofos, prothoate, protrifenbute, proxan, prymidophos,
prynachlor, psoralen, psoralene, pydanon, pyflubumide, pymetrozine,
pyracarbolid, pyraclofos, pyraclonil, pyraclostrobin, pyraflufen,
pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin,
pyrasulfotole, pyraziflumid, pyrazolate, pyrazolynate, pyrazon,
pyrazophos, pyrazosulfuron, pyrazothion, pyrazoxyfen, pyresmethrin,
pyrethrin I, pyrethrin II, pyrethrins, pyribambenz-isopropyl,
pyribambenz-propyl, pyribencarb, pyribenzoxim, pyributicarb,
pyriclor, pyridaben, pyridafol, pyridalyl, pyridaphenthion,
pyridaphenthione, pyridate, pyridinitril, pyrifenox,
pyrifluquinazon, pyriftalid, pyrimntaphos, pyrimethanil,
pyrimicarbe, pyrimidifen, pyriminobac, pyriminostrobin,
pyrimiphos-ethyl, pyrimiphos-methyl, pyrimisulfan, pyrimitate,
pyrinuron, pyriofenone, pyriprole, pyripropanol, pyriproxyfen,
pyrisoxazole, pyrithiobac, pyrolan, pyroquilon, pyroxasulfone,
pyroxsulam, pyroxychlor, pyroxyfur, qincaosuan, qingkuling,
quassia, quinacetol, quinalphos, quinalphos-methyl, quinazamid,
quinclorac, quinconazole, quinmerac, quinoclamine, quinomethionate,
quinonamid, quinothion, quinoxyfen, quintiofos, quintozene,
quizalofop, quizalofop-P, quwenzhi, quyingding, rabenzazole,
rafoxanide, R-diniconazole, rebemide, reglone, renriduron,
rescalure, resmethrin, rhodethanil, rhodojaponin-III, ribavirin,
rimsulfuron, rizazole, R-metalaxyl, roddthanil, ronnel, rotenone,
ryanla, sabadilla, saflufenacil, saijunmao, saisentong,
salicylanilide, salifluofen, sanguinarine, santonin,
S-bioallethrin, schradan, scilliroside, sebuthylazine, secbumeton,
sedaxane, selamectin, semiamitraz, sesamex, sesamolin, sesone,
sethoxydim, sevin, shuangjiaancaolin, shuangjianancaolin,
S-hydroprene, siduron, sifumijvzhi, siglure, silafluofen,
silatrane, silica aerogel, silica gel, silthiofam, silthiopham,
silthiophan, silvex, simazine, simeconazole, simeton, simetryn,
simetryne, sintofen, S-kinoprene, slaked lime, SMA, S-methoprene,
S-metolachlor, sodium arsenite, sodium azide, sodium chlorate,
sodium cyanide, sodium fluoride, sodium fluoroacetate, sodium
hexafluorosilicate, sodium naphthenate, sodium o-phenylphenoxide,
sodium orthophenylphenoxide, sodium pentachlorophenate, sodium
pentachlorophenoxide, sodium polysulfide, sodium silicofluoride,
sodium tetrathiocarbonate, sodium thiocyanate, solan, sophamide,
spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat,
spiroxamine, stirofos, streptomycin, strychnine, sulcatol,
sulcofuron, sulcotrione, sulfallate, sulfentrazone, sulfiram,
sulfluramid, sulfodiazole, sulfometuron, sulfosate, sulfosulfuron,
sulfotep, sulfotepp, sulfoxaflor, sulfoxide, sulfoxime, sulfur,
sulfuric acid, sulfuryl fluoride, sulglycapin, sulphosate,
sulprofos, sultropen, swep, tau-fluvalinate, tavron, tazimcarb,
TBTO, TBZ, TCA, TCBA, TCMTB, TCNB, TDE, tebuconazole, tebufenozide,
tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron,
tecloftalam, tecnazene, tecoram, tedion, teflubenzuron, tefluthrin,
tefuryltrione, tembotrione, temefos, temephos, tepa, TEPP,
tepraloxydim, teproloxydim, terallethrin, terbacil, terbucarb,
terbuchlor, terbufos, terbumeton, terbuthylazine, terbutol,
terbutryn, terbutryne, terraclor, terramicin, terramycin,
tetcyclacis, tetrachloroethane, tetrachlorvinphos, tetraconazole,
tetradifon, tetradisul, tetrafluron, tetramethrin,
tetramethylfluthrin, tetramine, tetranactin, tetraniliprole,
tetrapion, tetrasul, thallium sulfate, thallous sulfate,
thenylchlor, theta-cypermethrin, thiabendazole, thiacloprid,
thiadiazine, thiadifluor, thiamethoxam, thiameturon, thiapronil,
thiazafluron, thiazfluron, thiazone, thiazopyr, thicrofos,
thicyofen, thidiazimin, thidiazuron, thiencarbazone,
thifensulfuron, thifluzamide, thimerosal, thimet, thiobencarb,
thiocarboxime, thiochlorfenphim, thiochlorphenphime,
thiocyanatodinitrobenzenes, thiocyclam, thiodan,
thiodiazole-copper, thiodicarb, thiofanocarb, thiofanox,
thiofluoximate, thiohempa, thiomersal, thiometon, thionazin,
thiophanate, thiophanate-ethyl, thiophanate-methyl, thiophos,
thioqulnox, thiosemicarbazide, thiosultap, thiotepa, thioxamyl,
thiram, thiuram, thuringiensin, tiabendazole, tiadinil, tiafenacil,
tiaojiean, TIBA, tifatol, tiocarbazil, tioclorim, tioxazafen,
tioxymid, tirpate, TMTD, tolclofos-methyl, tolfenpyrad, tolprocarb,
tolpyralate, tolyfluanid, tolylfluanid, tolylmercury acetate,
tomarin, topramezone, toxaphene, TPN, tralkoxydim, tralocythrin,
tralomethrin, tralopyril, transfluthrin, transpermethrin,
tretamine, triacontanol, triadimefon, triadimenol, triafamone,
triallate, tri-allate, triamiphos, triapenthenol, triarathene,
triarimol, triasulfuron, triazamate, triazbutil, triaziflam,
triazophos, triazothion, triazoxide, tribasic copper chloride,
tribasic copper sulfate, tribenuron, tribufos, tributyltin oxide,
tricamba, trichlamide, trichlopyr, trichlorfon, trichlormetaphos-3,
trichloronat, trichloronate, trichlorotrinitrobenzenes,
trichlorphon, triclopyr, triclopyricarb, tricresol, tricyclazole,
tricyclohexyltin hydroxide, tridemorph, tridiphane, trietazine,
trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron,
trifludimoxazin, triflumezopyrim, triflumizole, triflumuron,
trifluralin, triflusulfuron, trifop, trifopsime, triforine,
trihydroxytriazine, trimedlure, trimethacarb, trimeturon,
trinexapac, triphenyltin, triprene, tripropindan, triptolide,
tritac, trithialan, triticonazole, tritosulfuron, trunc-call,
tuoyelin, uniconazole, uniconazole-P, urbacide, uredepa, valerate,
validamycin, validamycin A, valifenalate, valone, vamidothion,
vangard, vaniliprole, vernolate, vinclozolin, vitamin D3, warfarin,
xiaochongliulin, xinjunan, xiwojunan, xiwojunzhi, XMC, xylachlor,
xylenols, xylylcarb, xymiazole, yishijing, zarilamid, zeatin,
zengxiaoan, zengxiaolin, zeta-cypermethrin, zinc naphthenate, zinc
phosphide, zinc thiazole, zinc thiozole, zinc trichlorophenate,
zinc trichlorophenoxide, zineb, ziram, zolaprofos, zoocoumarin,
zoxamide, zuoanjunzhi, zuocaoan, zuojunzhi, zuomihuanglong,
.alpha.-chlorohydrin, .alpha.-ecdysone, .alpha.-multistriatin,
.alpha.-naphthaleneacetic acids, and .beta.-ecdysone;
[0024] (2) the following molecules [0025] (a)
N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoro-
propyl)thio)propanamide (hereafter "AI-1")
[0025] ##STR00002## [0026] (b)
(3S,6S,7R,8R)-8-benzyl-3-(3-((isobutyryloxy)
methoxy)-4-methoxypicolinamido)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl
isobutyrate (hereafter "AI-2")
##STR00003##
[0027] (3) a molecule known as Lotilaner that has the following
structure
##STR00004##
and
[0028] (4) the following molecules in Table A
TABLE-US-00001 TABLE A Structure of M#-active ingredients M#
Structure M1 ##STR00005## M2 ##STR00006## M3 ##STR00007## M4
##STR00008## M5 ##STR00009## M6 ##STR00010##
[0029] As used in this disclosure, each of the above is an active
ingredient. For more information consult the "Compendium of
Pesticide Common Names" located at Alanwood.net and various
editions, including the on-line edition, of "The Pesticide Manual"
located at bcpcdata.com.
[0030] A particularly preferred selection of active ingredients are
1,3 dichloropropene, chlorpyrifos, hexaflumuron, methoxyfenozide,
noviflumuron, spinetoram, spinosad, and sulfoxaflor (hereafter
"AIGA-2").
[0031] Additionally, another particularly preferred selection of
active ingredients are acequinocyl, acetamiprid, acetoprole,
avermectin, azinphos-methyl, bifenazate, bifenthrin, carbaryl,
carbofuran, chlorfenapyr, chlorfluazuron, chromafenozide,
clothianidin, cyfluthrin, cypermethrin, deltamethrin,
diafenthiuron, emamectin benzoate, endosulfan, esfenvalerate,
ethiprole, etoxazole, fipronil, flonicamid, fluacrypyrim,
gamma-cyhalothrin, halofenozide, indoxacarb, lambda-cyhalothrin,
lufenuron, malathion, methomyl, novaluron, permethrin, pyridalyl,
pyrimidifen, spirodiclofen, tebufenozide, thiacloprid,
thiamethoxam, thiodicarb, tolfenpyrad, and zeta-cypermethrin
(hereafter "AIGA-3").
[0032] The term "alkenyl" means an acyclic, unsaturated (at least
one carbon-carbon double bond), branched or unbranched, substituent
consisting of carbon and hydrogen, for example, vinyl, allyl,
butenyl, pentenyl, and hexenyl.
[0033] The term "alkenyloxy" means an alkenyl further consisting of
a carbon-oxygen single bond, for example, allyloxy, butenyloxy,
pentenyloxy, hexenyloxy.
[0034] The term "alkoxy" means an alkyl further consisting of a
carbon-oxygen single bond, for example, methoxy, ethoxy, propoxy,
isopropoxy, butoxy, isobutoxy, and tertbutoxy.
[0035] The term "alkyl" means an acyclic, saturated, branched or
unbranched, substituent consisting of carbon and hydrogen, for
example, methyl, ethyl, propyl, isopropyl, butyl, and
tertbutyl.
[0036] The term "alkynyl" means an acyclic, unsaturated (at least
one carbon-carbon triple bond), branched or unbranched, substituent
consisting of carbon and hydrogen, for example, ethynyl, propargyl,
butynyl, and pentynyl.
[0037] The term "alkynyloxy" means an alkynyl further consisting of
a carbon-oxygen single bond, for example, pentynyloxy, hexynyloxy,
heptynyloxy, and octynyloxy.
[0038] The term "aryl" means a cyclic, aromatic substituent
consisting of hydrogen and carbon, for example, phenyl, naphthyl,
and biphenyl.
[0039] The term "biopesticide" means a microbial biological pest
control agent that, in general, is applied in a similar manner to
chemical pesticides. Commonly they are bacterial, but there are
also examples of fungal control agents, including Trichoderma spp.
and Ampelomyces quisqualis. One well-known biopesticide example is
Bacillus species, a bacterial disease of Lepidoptera, Coleoptera,
and Diptera. Biopesticides include products based on
entomopathogenic fungi (e.g. Metarhizium anisopliae),
entomopathogenic nematodes (e.g. Steinernema feltiae), and
entomopathogenic viruses (e.g. Cydia pomonella granulovirus). Other
examples of entomopathogenic organisms include, but are not limited
to, baculoviruses, protozoa, and Microsporidia. For the avoidance
of doubt, biopesticides are active ingredients.
[0040] The term "cycloalkenyl" means a monocyclic or polycyclic,
unsaturated (at least one carbon-carbon double bond) substituent
consisting of carbon and hydrogen, for example, cyclobutenyl,
cyclopentenyl, cyclohexenyl, norbornenyl, bicyclo[2.2.2]octenyl,
tetrahydronaphthyl, hexahydronaphthyl, and octahydronaphthyl.
[0041] The term "cycloalkenyloxy" means a cycloalkenyl further
consisting of a carbon-oxygen single bond, for example,
cyclobutenyloxy, cyclopentenyloxy, norbornenyloxy, and
bicyclo[2.2.2]octenyloxy.
[0042] The term "cycloalkyl" means a monocyclic or polycyclic,
saturated substituent consisting of carbon and hydrogen, for
example, cyclopropyl, cyclobutyl, cyclopentyl, norbornyl,
bicyclo[2.2.2]octyl, and decahydronaphthyl.
[0043] The term "cycloalkoxy" means a cycloalkyl further consisting
of a carbon-oxygen single bond, for example, cyclopropyloxy,
cyclobutyloxy, cyclopentyloxy, norbornyloxy, and
bicyclo[2.2.2]octyloxy.
[0044] The term "halo" means fluoro, chloro, bromo, and iodo.
[0045] The term "haloalkoxy" means an alkoxy further consisting of,
from one to the maximum possible number of identical or different,
halos, for example, fluoromethoxy, trifluoromethoxy,
2,2-difluoropropoxy, chloromethoxy, trichloromethoxy,
1,1,2,2-tetrafluoroethoxy, and pentafluoroethoxy.
[0046] The term "haloalkyl" means an alkyl further consisting of,
from one to the maximum possible number of, identical or different,
halos, for example, fluoromethyl, trifluoromethyl,
2,2-difluoropropyl, chloromethyl, trichloromethyl, and
1,1,2,2-tetrafluoroethyl.
[0047] The term "heterocyclyl" means a cyclic substituent that may
be aromatic, fully saturated, or partially or fully unsaturated,
where the cyclic structure contains at least one carbon and at
least one heteroatom, where said heteroatom is nitrogen, sulfur, or
oxygen. Examples are:
[0048] (1) aromatic heterocyclyl substituents include, but are not
limited to, benzofuranyl, benzoisothiazolyl, benzoisoxazolyl,
benzothienyl, benzothiazolyl, benzoxazolyl, cinnolinyl, furanyl,
imidazolyl, indazolyl, indolyl, isoindolyl, isoquinolinyl,
isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl,
phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl,
pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl,
quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl,
triazinyl, and triazolyl;
[0049] (2) fully saturated heterocyclyl substituents include, but
are not limited to, piperazinyl, piperidinyl, morpholinyl,
pyrrolidinyl, tetrahydrofuranyl, tetra hydropyranyl, tetra
hydrothiophenyl, tetrahydrothiophenyl-oxide, tetra
hydrothiophenyl-dioxide;
[0050] (3) partially or fully unsaturated heterocyclyl substituents
include, but are not limited to, 4,5-dihydro-isoxazolyl,
4,5-dihydro-oxazolyl, 4,5-dihydro-1H-pyrazolyl,
2,3-dihydro-[1,3,4]-oxadiazolyl, 2,5-dioxoimidazolidinyl,
2,4-dioxo-1,3-diazaspiro[4.4]nonanylisoxazolidinonyl,
oxazolidinonyl, imidazolidinonyl, isoxazolidinonyl, pyrrolidinonyl,
1,2,3,4-tetrahydro-quinolinyl, and thioxothiazolidinonyl; and
[0051] (4) Additional examples of heterocyclyls include the
following:
##STR00011##
[0052] The term "locus" means a habitat, breeding ground, plant,
seed, soil, material, or environment, in which a pest is growing,
may grow, or may traverse. For example, a locus may be: where
crops, trees, fruits, cereals, fodder species, vines, turf, and/or
ornamental plants, are growing; where domesticated animals are
residing; the interior or exterior surfaces of buildings (such as
places where grains are stored); the materials of construction used
in buildings (such as impregnated wood); and the soil around
buildings.
[0053] The phrase "MoA Material" means an active ingredient having
a mode of action ("MoA") as indicated in IRAC MoA Classification v.
7.3, located at irac-online.org., which describes the following
groups.
[0054] (1) Acetylcholinesterase (AChE) inhibitors, includes the
following active ingredients alanycarb, aldicarb, bendiocarb,
benfuracarb, butocarboxim, butoxycarboxim, carbaryl, carbofuran,
carbosulfan, ethiofencarb, fenobucarb, formetanate, furathiocarb,
isoprocarb, methiocarb, methomyl, metolcarb, oxamyl, pirimicarb,
propoxur, thiodicarb, thiofanox, triazamate, trimethacarb, XMC,
xylylcarb, acephate, azamethiphos, azinphos-ethyl, azinphos-methyl,
cadusafos, chlorethoxyfos, chlorfenvinphos, chlormephos,
chlorpyrifos, chlorpyrifos-methyl, coumaphos, cyanophos,
demeton-S-methyl, diazinon, dichlorvos/DDVP, dicrotophos,
dimethoate, dimethylvinphos, disulfoton, EPN, ethion, ethoprophos,
famphur, fenamiphos, fenitrothion, fenthion, fosthiazate,
heptenophos, imicyafos, isofenphos, isopropyl
O-(methoxyaminothio-phosphoryl) salicylate, isoxathion, malathion,
mecarbam, methamidophos, methidathion, mevinphos, monocrotophos,
naled, omethoate, oxydemeton-methyl, parathion, parathion-methyl,
phenthoate, phorate, phosalone, phosmet, phosphamidon, phoxim,
pirimiphos-methyl, profenofos, propetamphos, prothiofos,
pyraclofos, pyridaphenthion, quinalphos, sulfotep, tebupirimfos,
temephos, terbufos, tetrachlorvinphos, thiometon, triazophos,
trichlorfon, vamidothion.
[0055] (2) GABA-gated chloride channel antagonists, includes the
following active ingredients chlordane, endosulfan, ethiprole, and
fipronil.
[0056] (3) Sodium channel modulators, includes the following active
ingredients acrinathrin, allethrin, d-cis-trans allethrin, d-trans
allethrin, bifenthrin, bioallethrin, bioallethrin S-cyclopentenyl,
bioresmethrin, cycloprothrin, cyfluthrin, beta-cyfluthrin,
cyhalothrin, lambda-cyhalothrin, gamma-cyhalothrin, cypermethrin,
alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin,
zeta-cypermethrin, cyphenothrin [(1R)-trans-isomers], deltamethrin,
empenthrin [(EZ)-(1R)-isomers], esfenvalerate, etofenprox,
fenpropathrin, fenvalerate, flucythrinate, flumethrin,
tau-fluvalinate, halfenprox, imiprothrin, kadethrin, permethrin,
phenothrin [(1R)-trans-isomer], prallethrin, pyrethrins
(pyrethrum), resmethrin, silafluofen, tefluthrin, tetramethrin,
tetramethrin [(1R)-isomers], tralomethrin, and transfluthrin, and
methoxychlor.
[0057] (4) Nicotinic acetylcholine receptor (nAChR) agonists,
includes the following active ingredients [0058] (4A) acetamiprid,
clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid,
thiamethoxam, [0059] (4B) nicotine, [0060] (4C) sulfoxaflor, [0061]
(4D) flupyradifurone, [0062] (4E) triflumezopyrim and
dicloromezotiaz.
[0063] (5) Nicotinic acetylcholine receptor (nAChR) allosteric
activators, Includes the following active ingredients spinetoram
and spinosad.
[0064] (6) Chloride channel activators, includes the following
active ingredients abamectin, emamectin benzoate, lepimectin, and
milbemectin.
[0065] (7) Juvenile hormone mimics, includes the following active
ingredients hydroprene, kinoprene, methoprene, fenoxycarb, and
pyriproxyfen.
[0066] (8) Miscellaneous nonspecific (multi-site) inhibitors,
includes the following active ingredients methyl bromide,
chloropicrin, sulfuryl fluoride, borax, and tartar emetic.
[0067] (9) Modulators of Chordotonal Organs, includes the following
active ingredients pymetrozine and flonicamid.
[0068] (10) Mite growth inhibitors, includes the following active
ingredients clofentezine, hexythiazox, diflovidazin, and
etoxazole.
[0069] (11) Microbial disruptors of insect midgut membranes,
includes the following active ingredients Bacillus thuringiensis
subsp. Israelensis, Bacillus thuringiensis subsp. aizawai, Bacillus
thuringiensis subsp. Kurstaki, Bacillus thuringiensis subsp.
tenebrionenis, Bt crop proteins (Cry1Ab, Cry1Ac, Cry1Fa, Cry1A.105,
Cry2Ab, Vip3A, mCry3A, Cry3Ab, Cry3Bb, Cry34Ab1/Cry35Ab1), and
Bacillus sphaericus.
[0070] (12) Inhibitors of mitochondrial ATP synthase, includes the
following active ingredients tetradifon, propargite, azocyclotin,
cyhexatin, fenbutatin oxide, and diafenthiuron.
[0071] (13) Uncouplers of oxidative phosphorylation via disruption
of the proton gradient, includes the following active ingredients
chlorfenapyr, DNOC, and sulfluramid.
[0072] (14) Nicotinic acetylcholine receptor (nAChR) channel
blockers, includes the following active ingredients bensultap,
cartap hydrochloride, thiocyclam, and thiosultap-sodium.
[0073] (15) Inhibitors of chitin biosynthesis, type 0, includes the
following active ingredients bistrifluron, chlorfluazuron,
diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron,
lufenuron, novaluron, noviflumuron, teflubenzuron, and
triflumuron.
[0074] (16) Inhibitors of chitin biosynthesis, type 1, includes the
following active ingredient buprofezin.
[0075] (17) Moulting disruptor, Dipteran, includes the following
active ingredient cyromazine.
[0076] (18) Ecdysone receptor agonists, includes the following
active ingredients chromafenozide, halofenozide, methoxyfenozide,
and tebufenozide.
[0077] (19) Octopamine receptor agonists, includes the following
active ingredient amitraz.
[0078] (20) Mitochondrial complex III electron transport
inhibitors, includes the following active ingredients
hydramethylnon, acequinocyl, and fluacrypyrim.
[0079] (21) Mitochondrial complex I electron transport inhibitors,
includes the following active ingredients fenazaquin,
fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad, tolfenpyrad,
and rotenone.
[0080] (22) Voltage-dependent sodium channel blockers, includes the
following active ingredients indoxacarb and metaflumizone.
[0081] (23) Inhibitors of acetyl CoA carboxylase, includes the
following active ingredients spirodiclofen, spiromesifen, and
spirotetramat.
[0082] (24) Mitochondrial complex IV electron transport inhibitors,
includes the following active ingredients, aluminium phosphide,
calcium phosphide, phosphine, zinc phosphide, and cyanide.
[0083] (25) Mitochondrial complex II electron transport inhibitors,
includes the following active ingredients cyenopyrafen and
cyflumetofen. and
[0084] (28) Ryanodine receptor modulators, includes the following
active ingredients chlorantraniliprole, cyantraniliprole, and
flubendiamide.
[0085] Groups 26 and 27 are unassigned in this version of the
classification scheme. Additionally, there is a Group UN that
contains active ingredients of unknown or uncertain mode of action.
This group includes the following active ingredients, azadirachtin,
benzoximate, bifenazate, bromopropylate, chinomethionat, cryolite,
dicofol, pyridalyl, and pyrifluquinazon.
[0086] The term "pest" means an organism that is detrimental to
humans, or human concerns (such as, crops, food, livestock, etc.),
where said organism is from Phyla Arthropoda, Mollusca, or
Nematoda. Particular examples are ants, aphids, bed bugs, beetles,
bristletails, caterpillars, cockroaches, crickets, earwigs, fleas,
flies, grasshoppers, grubs, hornets, killer bees, leafhoppers,
lice, locusts, maggots, mites, moths, nematodes, planthoppers,
psyllids, sawflies, scales, silverfish, slugs, snails, spiders,
springtails, stink bugs, symphylans, termites, thrips, ticks,
wasps, whiteflies, and wireworms.
[0087] Additional examples are pests in
[0088] (1) Subphyla Chelicerata, Myriapoda, and Hexapoda.
[0089] (2) Classes of Arachnida, Symphyla, and Insecta.
[0090] (3) Order Anoplura. A non-exhaustive list of particular
genera includes, but is not limited to, Haematopinus spp.,
Hoplopleura spp., Linognathus spp., Pediculus spp., Polyplax spp.,
Solenopotes spp., and Neohaematopinis spp. A non-exhaustive list of
particular species includes, but is not limited to, Haematopinus
asini, Haematopinus suis, Linognathus setosus, Linognathus ovillus,
Pediculus humanus capitis, Pediculus humanus humanus, and Pthirus
pubis.
[0091] (4) Order Coleoptera. A non-exhaustive list of particular
genera includes, but is not limited to, Acanthoscelides spp.,
Agriotes spp., Anthonomus spp., Apion spp., Apogonia spp.,
Araecerus spp., Aulacophora spp., Bruchus spp., Cerostema spp.,
Cerotoma spp., Ceutorhynchus spp., Chaetocnema spp., Colaspis spp.,
Ctenicera spp., Curculio spp., Cyclocephala spp., Diabrotica spp.,
Dinoderus spp., Gnathocerus spp., Hemicoelus spp., Heterobostruchus
spp., Hypera spp., Ips spp., Lyctus spp., Megascelis spp.,
Meligethes spp., Mezium spp., Niptus spp., Otiorhynchus spp.,
Pantomorus spp., Phyllophaga spp., Phyllotreta spp., Ptinus spp.,
Rhizotrogus spp., Rhynchites spp., Rhynchophorus spp., Scolytus
spp., Sphenophorus spp., Sitophilus spp., Tenebrio spp., and
Tribolium spp. A non-exhaustive list of particular species
includes, but is not limited to, Acanthoscelides obtectus, Agrilus
planipennis, Ahasverus advena, Alphitobius diaperinus, Anoplophora
glabripennis, Anthonomus grandis, Anthrenus verbasci, Anthrenus
falvipes, Ataenius spretulus, Atomaria linearis, Attagenus
unicolor, Bothynoderes punctiventris, Bruchus pisorum,
Callosobruchus maculatus, Carpophilus hemipterus, Cassida vittata,
Cathartus quadricollis, Cerotoma trifurcata, Ceutorhynchus
assimilis, Ceutorhynchus napi, Conoderus scalaris, Conoderus
stigmosus, Conotrachelus nenuphar, Cotinis nitida, Crioceris
asparagi, Cryptolestes ferrugineus, Cryptolestes pusillus,
Cryptolestes turcicus, Cylindrocopturus adspersus, Deporaus
marginatus, Dermestes lardarius, Dermestes maculatus, Epilachna
varivestis, Euvrilletta peltata, Faustinus cubae, Hylobius pales,
Hylotrupes bajulus, Hypera postica, Hypothenemus hampei, Lasioderma
serricome, Leptinotarsa decemlineata, Limonius canus, Liogenys
fuscus, Liogenys suturalis, Lissorhoptrus oryzophilus, Lophocateres
pusillus, Lyctus planlcollis, Maecolaspis joliveti, Melanotus
communis, Meligethes aeneus, Melolontha melolontha, Necrobia
rufipes, Oberea brevis, Oberea linearis, Oryctes rhinoceros,
Oryzaephilus mercator, Oryzaephilus surinamensis, Oulema melanopus,
Oulema oryzae, Phyllophaga cuyabana, Polycaon stoutti, Popillia
japonica, Prostephanus truncatus, Rhyzopertha dominica, Sitona
lineatus, Sitophilus granarius, Sitophilus oryzae, Sitophilus
zeamais, Stegobium paniceum, Tenebroides mauritanicus, Tribolium
castaneum, Tribolium confusum, Trogoderma granarium, Trogoderma
variabile, Xestoblum rufovillosum, and Zabrus tenebrioides.
[0092] (5) Order Dermaptera. A non-exhaustive list of particular
species includes, but is not limited to, Forficula auricularia.
[0093] (6) Order Blattaria. A non-exhaustive list of particular
species includes, but is not limited to, Blattella germanica,
Blattella asahinai, Blatta orientalis, Blatta lateralis,
Parcoblatta pennsylvanica, Periplaneta americana, Periplaneta
australasiae, Periplaneta brunnea, Periplaneta fuliginosa,
Pycnoscelus surinamensis, and Supella longipalpa.
[0094] (7) Order Diptera. A non-exhaustive list of particular
genera includes, but is not limited to, Aedes spp., Agromyza spp.,
Anastrepha spp., Anopheles spp., Bactrocera spp., Ceratitis spp.,
Chrysops spp., Cochliomyia spp., Contarinia spp., Culex spp.,
Culicoides spp., Dasineura spp., Della spp., Drosophila spp.,
Fannia spp., Hylemya spp., Liriomyza spp., Musca spp., Phorbia
spp., Pollenia spp., Psychoda spp., Simulium spp., Tabanus spp.,
and Tipula spp. A non-exhaustive list of particular species
includes, but is not limited to, Agromyza frontella, Anastrepha
suspensa, Anastrepha ludens, Anastrepha obliqua, Bactrocera
cucurbitae, Bactrocera dorsalis, Bactrocera invadens, Bactrocera
zonata, Ceratitis capitata, Dasineura brassicae, Della platura,
Fannia canicularis, Fannia scalaris, Gasterophilus intestinalis,
Gracillia perseae, Haematobia irritans, Hypoderma lineatum,
Liriomyza brassicae, Melophagus ovinus, Musca autumnalis, Musca
domestica, Oestrus ovis, Oscinella frit, Pegomya betae, Plophila
casei, Psila rosae, Rhagoletis cerasi, Rhagoletis pomonella,
Rhagoletis mendax, Sitodiplosis mosellana, and Stomoxys
calcitrans.
[0095] (8) Order Hemiptera. A non-exhaustive list of particular
genera includes, but is not limited to, Adelges spp., Aulacaspis
spp., Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastes spp.,
Chionaspis spp., Chrysomphalus spp., Coccus spp., Empoasca spp.,
Euschistus spp., Lepidosaphes spp., Lagynotomus spp., Lygus spp.,
Macrosiphum spp., Nephotettix spp., Nezara spp., Nilaparvata spp.,
Philaenus spp., Phytocoris spp., Piezodorus spp., Planococcus spp.,
Pseudococcus spp., Rhopalosiphum spp., Salssetia spp., Therioaphis
spp., Toumeyella spp., Toxoptera spp., Trialeurodes spp., Triatoma
spp., and Unaspis spp. A non-exhaustive list of particular species
includes, but is not limited to, Acrosternum hilare, Acyrthosiphon
pisum, Aleyrodes proletella, Aleurodicus dispersus, Aleurothrixus
floccosus, Amrasca biguttula biguttula, Aonidiella aurantii, Aphis
gossypii, Aphis glycines, Aphis pomi, Aulacorthum solani,
Bactericera cockerelli, Bagrada hilaris, Bemisia argentifolii,
Bemisia tabaci, Blissus leucopterus, Bolsea trivittata,
Brachycorynella asparagi, Brevennia rehi, Brevicoryne brassicae,
Cacopsylla pyri, Cacopsylla pyricola, Calocoris norvegicus,
Ceroplastes rubens, Cimex hemipterus, Cimex lectularius, Dagbertus
fasciatus, Dichelops furcatus, Diuraphis noxia, Diaphorina citri,
Dysaphis plantaginea, Dysdercus suturellus, Edessa meditabunda,
Eriosoma lanigerum, Eurygaster maura, Euschistus conspersus,
Euschistus heros, Euschistus servus, Halyomorpha halys, Helopeltis
antonii, Helopeltis theivora, Icerya purchasi, Idioscopus
nitidulus, Laodelphax striatellus, Leptocorisa oratorius,
Leptocorisa varicomis, Lygus hesperus, Maconellicoccus hirsutus,
Macrosiphum euphorbiae, Macrosiphum granarium, Macrosiphum rosae,
Macrosteles quadrilineatus, Mahanarva frimbiolata, Megacopta
cribraria, Metopolophium dirhodum, Mictis longicornis, Myzus
persicae, Nephotettix cincticeps, Neurocolpus longirostris, Nezara
viridula, Nilaparvata lugens, Parlatoria pergandii, Parlatoria
ziziphi, Peregrinus maidis, Phylloxera vitifoliae, Physokermes
piceae, Phytocoris californicus, Phytocoris relativus, Piezodorus
guildinii, Poecilocapsus lineatus, Psallus vaccinicola, Pseudacysta
perseae, Pseudococcus brevipes, Quadraspidiotus perniciosus,
Rhopalosiphum maidis, Rhopalosiphum padi, Saissetia oleae,
Scaptocoris castanea, Schizaphis graminum, Sitobion avenae,
Sogatella furcifera, Trialeurodes vaporariorum, Trialeurodes
abutiloneus, Unaspis yanonensis, and Zulia entrerriana.
[0096] (9) Order Hymenoptera. A non-exhaustive list of particular
genera includes, but is not limited to, Acromyrmex spp., Atta spp.,
Camponotus spp., Diprion spp., Dolichovespula spp., Formica spp.,
Monomorium spp., Neodiprion spp., Paratrechina spp., Pheidole spp.,
Pogonomyrmex spp., Polistes spp., Solenopsis spp., Technomyrmex,
spp., Tetramorium spp., Vespula spp., Vespa spp., and Xylocopa spp.
A non-exhaustive list of particular species includes, but is not
limited to, Athalia rosae, Atta texana, Caliroa cerasi, Cimbex
americana, Iridomyrmex humilis, Linepithema humile, Mellifera
Scutellata, Monomorium minimum, Monomorium pharaonis, Neodiprion
sertifer, Solenopsis invicta, Solenopsis geminata, Solenopsis
molesta, Solenopsis richtery, Solenopsis xyloni, Tapinoma sessile,
and Wasmannia auropunctata.
[0097] (10) Order Isoptera. A non-exhaustive list of particular
genera includes, but is not limited to, Coptotermes spp.,
Cornitermes spp., Cryptotermes spp., Heterotermes spp., Kalotermes
spp., Incisitermes spp., Macrotermes spp., Marginitermes spp.,
Microcerotermes spp., Procomitermes spp., Reticulitermes spp.,
Schedorhinotermes spp., and Zootermopsis spp. A non-exhaustive list
of particular species includes, but is not limited to, Coptotermes
acinaciformis, Coptotermes curvignathus, Coptotermes frenchi,
Coptotermes formosanus, Coptotermes gestroi, Cryptotermes brevis,
Heterotermes aureus, Heterotermes tenuis, Incisitermes minor,
Incisitermes snyderi, Microtermes obesi, Nasutitermes corniger,
Odontotermes formosanus, Odontotermes obesus, Reticulitermes
banyulensis, Reticulitermes grassel, Reticulltermes flavipes,
Reticulitermes hageni, Reticulitermes hesperus, Reticulitermes
santonensis, Reticulitermes speratus, Reticulitermes tibialis, and
Reticulitermes virginicus.
[0098] (11) Order Lepidoptera. A non-exhaustive list of particular
genera includes, but is not limited to, Adoxophyes spp., Agrotis
spp., Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilo
spp., Chrysodeixis spp., Colias spp., Crambus spp., Diaphania spp.,
Diatraea spp., Earias spp., Ephestia spp., Epimecis spp., Feltia
spp., Gortyna spp., Hellcoverpa spp., Hellothis spp., Indarbela
spp., Lithocolletis spp., Loxagrotis spp., Malacosoma spp.,
Nemapogon spp., Peridroma spp., Phyllonorycter spp., Pseudaletia
spp., Plutella spp., Sesamia spp., Spodoptera spp., Synanthedon
spp., and Yponomeuta spp. A non-exhaustive list of particular
species includes, but is not limited to, Achaea janata, Adoxophyes
orana, Agrotis ipsilon, Alabama argillacea, Amorbia cuneana,
Amyelois transitella, Anacamptodes defectaria, Anarsia lineatella,
Anomis sabulifera, Anticarsia gemmatalis, Archips argyrospila,
Archips rosana, Argyrotaenia citrana, Autographa gamma, Bonagota
cranaodes, Borbo cinnara, Bucculatrix thurberiella, Capua
reticulana, Carposina niponensis, Chlumetla transversa,
Choristoneura rosaceana, Cnaphalocrocis medinalis, Conopomorpha
cramerella, Corcyra cephalonica, Cossus cossus, Cydia caryana,
Cydia funebrana, Cydia molesta, Cydia nigricana, Cydia pomonella,
Darna diducta, Diaphanla nitidalis, Diatraea saccharalls, Diatraea
grandiosella, Earias insulana, Earias vittella, Ecdytolopha
aurantianum, Elasmopalpus lignosellus, Ephestia cautella, Ephestia
elutella, Ephestia kuehniella, Epinotia aporema, Epiphyas
postvittana, Erionota thrax, Estigmene acrea, Eupoecilla
ambiguella, Euxoa auxiliaris, Galleria mellonella, Grapholita
molesta, Hedylepta indicata, Helicoverpa armigera, Helicoverpa zea,
Hellothis virescens, Hellula undalls, Keiferia lycopersicella,
Leucinodes orbonalis, Leucoptera coffeella, Leucoptera
malifoliella, Lobesla botrana, Loxagrotis albicosta, Lymantria
dispar, Lyonetia clerkella, Mahasena corbetti, Mamestra brassicae,
Manduca sexta, Maruca testulalis, Metisa plana, Mythimna unipuncta,
Neoleucinodes elegantalis, Nymphula depunctalis, Operophtera
brumata, Ostrinia nubilalis, Oxydla vesulia, Pandemis cerasana,
Pandemis heparana, Papllio demodocus, Pectinophora gossyplella,
Peridroma saucia, Perileucoptera coffeella, Phthorimaea
operculella, Phyllocnistis citrella, Phyllonorycter blancardella,
Pieris rapae, Plathypena scabra, Platynota idaeusalis, Plodia
interpunctella, Plutella xylostella, Polychrosis viteana, Prays
endocarpa, Prays oleae, Pseudaleta unipuncta, Pseudoplusia
includens, Rachiplusla nu, Scirpophaga incertulas, Sesamia
inferens, Sesamia nonagrioides, Setora nitens, Sitotroga
cerealella, Sparganothis pilleriana, Spodoptera exigua, Spodoptera
frugiperda, Spodoptera eridania, Thedcla basilides, Tinea
pellionella, Tineola bisselliella, Trichoplusia ni, Tuta absoluta,
Zeuzera coffeae, and Zeuzea pyrina.
[0099] (12) Order Mallophaga. A non-exhaustive list of particular
genera includes, but is not limited to, Anaticola spp., Bovicola
spp., Chelopistes spp., Goniodes spp., Menacanthus spp., and
Trichodectes spp. A non-exhaustive list of particular species
includes, but is not limited to, Bovicola bovis, Bovicola caprae,
Bovicola ovis, Chelopistes meleagridis, Goniodes dissimilis,
Goniodes gigas, Menacanthus stramineus, Menopon gallinae, and
Trichodectes canis.
[0100] (13) Order Orthoptera. A non-exhaustive list of particular
genera includes, but is not limited to, Melanoplus spp. and
Pterophylla spp. A non-exhaustive list of particular species
includes, but is not limited to, Acheta domesticus, Anabrus
simplex, Gryllotalpa africana, Gryllotalpa australis, Gryllotalpa
brachyptera, Gryllotalpa hexadactyla, Locusta migratoria,
Microcentrum retinerve, Schistocerca gregaria, and Scudderia
furcata.
[0101] (14) Order Psocoptera. A non-exhaustive list of particular
species includes, but is not limited to, Liposcelis decolor,
Liposcelis entomophila, Lachesilla quercus, and Trogium
pulsatorum.
[0102] (15) Order Siphonaptera. A non-exhaustive list of particular
species includes, but is not limited to, Ceratophyllus gallinae,
Ceratophyllus niger, Ctenocephalides canis, Ctenocephalides felis,
and Pulex irritans.
[0103] (16) Order Thysanoptera. A non-exhaustive list of particular
genera includes, but is not limited to, Caliothrips spp.,
Frankliniella spp., Scirtothrips spp., and Thrips spp. A
non-exhaustive list of particular species includes, but is not
limited to, Frankliniella bispinosa, Frankliniella fusca,
Frankliniella occidentalis, Frankliniella schultzei, Frankliniella
tritici, Frankliniella williamsi, Heliothrips haemorrhoidalis,
Rhipiphorothrips cruentatus, Scirtothrips citri, Scirtothrips
dorsalis, Taeniothrips rhopalantennalis, Thrips hawaiiensis, Thrips
nigropilosus, Thrips orientalis, Thrips palmi, and Thrips
tabaci.
[0104] (17) Order Thysanura. A non-exhaustive list of particular
genera includes, but is not limited to, Lepisma spp. and Thermobia
spp.
[0105] (18) Order Acarina. A non-exhaustive list of particular
genera includes, but is not limited to, Acarus spp., Aculops spp.,
Argus spp., Boophilus spp., Demodex spp., Dermacentor spp.,
Epitrimerus spp., Eriophyes spp., Ixodes spp., Oligonychus spp.,
Panonychus spp., Rhizoglyphus spp., and Tetranychus spp. A
non-exhaustive list of particular species includes, but is not
limited to, Acarapis woodi, Acarus siro, Aceria mangiferae, Aculops
lycopersici, Aculus pelekassi, Aculus schlechtendali, Amblyomma
americanum, Brevipalpus obovatus, Brevipalpus phoenicis,
Dermacentor variabilis, Dermatophagoides pteronyssinus,
Eotetranychus carpini, Liponyssoides sanguineus, Notoedres cati,
Oligonychus coffeae, Oligonychus ilicis, Omithonyssus bacoti,
Panonychus citri, Panonychus ulmi, Phyllocoptruta oleivora,
Polyphagotarsonemus latus, Rhipicephalus sanguineus, Sarcoptes
scabiei, Tegolophus perseaflorae, Tetranychus urticae, Tyrophagus
longior, and Varroa destructor.
[0106] (19) Order Araneae. A non-exhaustive list of particular
genera includes, but is not limited to, Loxosceles spp.,
Latrodectus spp., and Atrax spp. A non-exhaustive list of
particular species includes, but is not limited to, Loxosceles
reclusa, Latrodectus mactans, and Atrax robustus.
[0107] (20) Class Symphyla. A non-exhaustive list of particular
species includes, but is not limited to, Scutigerella
immaculata.
[0108] (21) Subclass Collembola. A non-exhaustive list of
particular species includes, but is not limited to, Bourletiella
hortensis, Onychiurus armatus, Onychiurus fimetarius, and
Sminthurus viridis.
[0109] (22) Phylum Nematoda. A non-exhaustive list of particular
genera includes, but is not limited to, Aphelenchoides spp.,
Belonolaimus spp., Criconemella spp., Ditylenchus spp., Globodera
spp., Heterodera spp., Hirschmanniella spp., Hoplolaimus spp.,
Meloidogyne spp., Pratylenchus spp., and Radopholus spp. A
non-exhaustive list of particular species includes, but is not
limited to, Dirofilaria immitis, Globodera pallida, Heterodera
glycines, Heterodera zeae, Meloidogyne incognita, Meloidogyne
javanica, Onchocerca volvulus, Pratylenchus penetrans, Radopholus
similis, and Rotylenchulus reniformis.
[0110] (23) Phylum Mollusca. A non-exhaustive list of particular
species includes, but is not limited to, Arion vulgaris, Cornu
aspersum, Deroceras reticulatum, Limax flavus, Milax gagates, and
Pomacea canaliculata.
[0111] A particularly preferred pest group to control is
sap-feeding pests. Sap-feeding pests, in general, have piercing
and/or sucking mouthparts and feed on the sap and inner plant
tissues of plants. Examples of sap-feeding pests of particular
concern to agriculture include, but are not limited to, aphids,
leafhoppers, moths, scales, thrips, psyllids, mealybugs, stinkbugs,
and whiteflies. Specific examples of Orders that have sap-feeding
pests of concern in agriculture include but are not limited to,
Anoplura and Hemiptera. Specific examples of Hemiptera that are of
concern in agriculture include, but are not limited to, Aulacaspis
spp., Aphrophora spp., Aphis spp., Bemisia spp., Coccus spp.,
Euschistus spp., Lygus spp., Macrosiphum spp., Nezara spp., and
Rhopalosiphum spp.
[0112] Another particularly preferred pest group to control is
chewing pests. Chewing pests, in general, have mouthparts that
allow them to chew on the plant tissue including roots, stems,
leaves, buds, and reproductive tissues (including, but not limited
to flowers, fruit, and seeds). Examples of chewing pests of
particular concern to agricultural include, but are not limited to,
caterpillars, beetles, grasshoppers, and locusts. Specific examples
of Orders that have chewing pests of concern in agriculture include
but are not limited to, Coleoptera and Lepidoptera. Specific
examples of Coleoptera that are of concern in agriculture include,
but are not limited to, Anthonomus spp., Cerotoma spp., Chaetocnema
spp., Colaspis spp., Cydocephala spp., Diabrotica spp., Hypera
spp., Phyllophaga spp., Phyllotreta spp., Sphenophorus spp.,
Sitophilus spp.
[0113] The phrase "pesticidally effective amount" means the amount
of a pesticide needed to achieve an observable effect on a pest,
for example, the effects of necrosis, death, retardation,
prevention, removal, destruction, or otherwise diminishing the
occurrence and/or activity of a pest in a locus. This effect may
come about when pest populations are repulsed from a locus, pests
are incapacitated in, or around, a locus, and/or pests are
exterminated in, or around, a locus. Of course, a combination of
these effects can occur. Generally, pest populations, activity, or
both are desirably reduced more than fifty percent, preferably more
than 90 percent, and most preferably more than 99 percent. In
general, a pesticidally effective amount, for agricultural
purposes, is from about 0.0001 grams per hectare to about 5000
grams per hectare, preferably from about 0.0001 grams per hectare
to about 500 grams per hectare, and it is even more preferably from
about 0.0001 grams per hectare to about 50 grams per hectare.
DETAILED DESCRIPTION OF THIS DISCLOSURE
[0114] This document discloses molecules of Formula One
##STR00012##
wherein:
[0115] (A) R.sup.1 is selected from the group consisting of H, F,
Cl, Br, I, CN, NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.3-C.sub.5)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.1-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2;
[0116] (B) R.sup.2 is selected from the group consisting of H, F,
Cl, Br, I, CN, NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.3-C.sub.6)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.1-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2;
[0117] (C) R.sup.3 is selected from the group consisting of H, F,
Cl, Br, I, CN, NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.3-C.sub.6)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.1-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2;
[0118] (D) R.sup.4 is selected from the group consisting of H, F,
Cl, Br, I, CN, NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.5)alkenyl,
(C.sub.3-C.sub.6)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.3-C.sub.6)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.1-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2;
[0119] (E) R.sup.5 is selected from the group consisting of H, F,
Cl, Br, I, CN, NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.3-C.sub.6)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.1-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2;
[0120] (F) R.sup.6 is selected from the group consisting of H and
(C.sub.1-C.sub.4)alkyl;
[0121] (G) R.sup.7 is selected from the group consisting of H, F,
Cl, Br, and I;
[0122] (H) R.sup.8 is selected from the group consisting of F, Cl,
Br, and I;
[0123] (I) R.sup.9 is selected from the group consisting of H and
(C.sub.1-C.sub.4)alkyl;
[0124] (J) R.sup.10 is selected from the group consisting of H,
(C.sub.1-C.sub.4)alkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl(C.sub.1-C.sub.4)alkoxy,
C(.dbd.O)(C.sub.1-C.sub.4)alkyl, and
(C.sub.1-C.sub.4)alkoxyC(.dbd.O)(C.sub.1-C.sub.4)alkyl;
[0125] (K) R.sup.11 is selected from the group consisting of H, F,
Cl, Br, I, CN, NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.3-C.sub.6)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.1-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2;
[0126] (L) R.sup.12 is selected from the group consisting of H, F,
Cl, Br, I, CN, NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.3-C.sub.6)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.1-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2;
[0127] (M) R.sup.13 is selected from the group consisting of H, F,
Cl, Br, I, CN, NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.3-C.sub.6)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.1-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2;
[0128] (N) R.sup.14 is selected from the group consisting of H, F,
Cl, Br, I, CN, NH.sub.2, NO.sub.2, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.6)cycloalkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.3-C.sub.6)cycloalkenyl, (C.sub.2-C.sub.4)alkynyl,
(C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.3-C.sub.6)halocycloalkyl, (C.sub.2-C.sub.4)haloalkenyl,
(C.sub.3-C.sub.6)halocycloalkenyl, (C.sub.1-C.sub.4)haloalkoxy,
S(C.sub.1-C.sub.4)alkyl, S(O)(C.sub.1-C.sub.4)alkyl,
S(O).sub.2(C.sub.1-C.sub.4)alkyl, S(C.sub.1-C.sub.4)haloalkyl,
S(O)(C.sub.1-C.sub.4)haloalkyl,
S(O).sub.2(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl-S(O).sub.2NH.sub.2, and
(C.sub.1-C.sub.4)haloalkyl-S(O).sub.2NH.sub.2;
[0129] (O) R.sup.15 is selected from the group consisting of (Q),
H, (C.sub.1-C.sub.4)alkyl, (C.sub.2-C.sub.4)alkenyl,
(C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.4)alkyl(C.sub.1-C.sub.4)alkoxy,
C(.dbd.O)(C.sub.1-C.sub.4)alkyl, and
(C.sub.1-C.sub.4)alkoxyC(.dbd.O)(C.sub.1-C.sub.4)alkyl;
[0130] (P) R.sup.16 is selected from the group consisting of (Q),
(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl-O--(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl(C.sub.3-C.sub.8)cycloalkyl,
(C.sub.1-C.sub.8)alkylphenyl, (C.sub.2-C.sub.8)alkenyl,
(C.sub.2-C.sub.8)alkynyl, (C.sub.1-C.sub.8)haloalkyl,
(C.sub.1-C.sub.8)alkyl-S--(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl-S(O)--(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl-S(O).sub.2--(C.sub.1-C.sub.8)alkyl,
O-phenyl, O--(C.sub.2-C.sub.8)alkenyl,
O--(C.sub.1-C.sub.8)alkyl(C.sub.3-C.sub.8)cycloalkyl,
O--(C.sub.1-C.sub.8)alkylphenyl,
(C.sub.1-C.sub.8)alkyl-O--(C.sub.1-C.sub.8)alkyl(C.sub.3-C.sub.8)cycloalk-
yl, (C.sub.1-C.sub.8)alkyl-O--(C.sub.1-C.sub.8)haloalkyl,
(C.sub.1-C.sub.8)alkyl-C(.dbd.O)NH--(C.sub.1-C.sub.8)haloalkyl,
(C.sub.1-C.sub.8)alkyl-NHC(O)--(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl-S--(C.sub.1-C.sub.8)haloalkyl,
(C.sub.1-C.sub.8)alkyl-S(O)--(C.sub.1-C.sub.8)haloalkyl,
(C.sub.1-C.sub.8)alkyl-S(O).sub.2--(C.sub.1-C.sub.8)haloalkyl, and
(C.sub.1-C.sub.8)alkyl-S(O).sub.2--NH.sub.2, [0131] wherein each
alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, and phenyl, may be
optionally substituted with one or more substituents selected from
the group consisting of F, Cl, Br, I, CN, OH, NH.sub.2, NO.sub.2,
(C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)alkoxy,
(C.sub.1-C.sub.8)haloalkyl, N((C.sub.1-C.sub.8)alkyl).sub.2,
C(O)O(C.sub.1-C.sub.5)alkyl, benzothioenyl,
2,3-dihydro-1H-imidazolonyl, furanyl, pyrazolyl, pyridinyl,
thiazolyl, and triazolyl;
[0132] (Q) R.sup.15 and R.sup.16 together can optionally form a 2-
to 5-membered saturated or unsaturated, hydrocarbyl link, which may
contain one or more heteroatoms selected from the group consisting
of nitrogen, sulfur, and oxygen, [0133] wherein said hydrocarbyl
link may be optionally substituted with one or more substituents
selected from the group consisting of F, Cl, Br, I, CN, NH.sub.2,
and NO.sub.2;
[0134] (R) Q.sup.1 and Q.sup.2 are each independently selected from
the group consisting of O and S; and
[0135] N-oxides, agriculturally acceptable acid addition salts,
salt derivatives, solvates, ester derivatives, crystal polymorphs,
isotopes, resolved stereoisomers, and tautomers, of the molecules
of Formula One.
[0136] The molecules of Formula One may exist in different
geometric or optical isomeric or different tautomeric forms. One or
more centers of chirality may be present in which case molecules of
Formula One may be present as pure enantiomers, mixtures of
enantiomers, pure diastereomers or mixtures of diastereomers. It
will be appreciated by those skilled in the art that one
stereoisomer may be more active than the other stereoisomers.
Individual stereoisomers may be obtained by known selective
synthetic procedures, by conventional synthetic procedures using
resolved starting materials, or by conventional resolution
procedures. There may be double bonds present in the molecule, in
which case compounds of Formula One may exist as single geometric
isomers (cis or trans, E or Z) or mixtures of geometric isomers (ds
and trans, E and Z). Centers of tautomerisation may be present.
This disclosure covers all such isomers, tautomers, and mixtures
thereof, in all proportions.
[0137] In another embodiment the molecules of Formula One, the
carboxamido, and the phenyl, which are bonded to the cyclopropane,
are in the R,R configuration. This embodiment may be used in
combination with the other embodiments of R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9,
R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15,
R.sup.16, Q.sup.1, and Q.sup.2.
[0138] In another embodiment R.sup.1 is H or F. This embodiment may
be used in combination with the other embodiments of R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9,
R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15,
R.sup.16, Q.sup.1, and Q.sup.2.
[0139] In another embodiment R.sup.2 is selected from the group
consisting of H, F, and Cl. This embodiment may be used in
combination with the other embodiments of R.sup.1, R.sup.3,
R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10,
R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16,
Q.sup.1, and Q.sup.2.
[0140] In another embodiment R.sup.3 is selected from the group
consisting of H, F, and Cl. This embodiment may be used in
combination with the other embodiments of R.sup.1, R.sup.3,
R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10,
R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16,
Q.sup.1, and Q.sup.2.
[0141] In another embodiment R.sup.4 is F or Cl. This embodiment
may be used in combination with the other embodiments of R.sup.1,
R.sup.2, R.sup.3, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9,
R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15,
R.sup.16, Q.sup.1, and Q.sup.2.
[0142] In another embodiment R.sup.5 is H or F. This embodiment may
be used in combination with the other embodiments of R.sup.1,
R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8,
R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14,
R.sup.15, R.sup.16, Q.sup.1, and Q.sup.2.
[0143] In another embodiment R.sup.6 is H. This embodiment may be
used in combination with the other embodiments of R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9,
R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15,
R.sup.16, Q.sup.1, and Q.sup.2.
[0144] In another embodiment R.sup.7 is selected from the group
consisting of Br and Cl. This embodiment may be used in combination
with the other embodiments of R.sup.1, R.sup.2, R.sup.3, R.sup.4,
R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11,
R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16, Q.sup.1, and
Q.sup.2.
[0145] In another embodiment R.sup.8 is selected from the group
consisting of Br and Cl. This embodiment may be used in combination
with the other embodiments of R.sup.1, R.sup.2, R.sup.3, R.sup.4,
R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11,
R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16, Q.sup.1, and
Q.sup.2.
[0146] In another embodiment R.sup.9 is H. This embodiment may be
used in combination with the other embodiments of R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9,
R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15,
R.sup.16, Q.sup.1, and Q.sup.2.
[0147] In another embodiment R.sup.10 is H. This embodiment may be
used in combination with the other embodiments of R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9,
R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15,
R.sup.16, Q.sup.1, and Q.sup.2.
[0148] In another embodiment R.sup.11 is H. This embodiment may be
used in combination with the other embodiments of R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9,
R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15,
R.sup.16, Q.sup.1, and Q.sup.2.
[0149] In another embodiment R.sup.12 is H. This embodiment may be
used in combination with the other embodiments of R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9,
R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15,
R.sup.16, Q.sup.1, and Q.sup.2.
[0150] In another embodiment R.sup.13 is selected from the group
consisting of H, Cl, and (C.sub.1-C.sub.4)haloalkyl. This
embodiment may be used in combination with the other embodiments of
R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7,
R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14,
R.sup.15, R.sup.16, Q.sup.1, and Q.sup.2.
[0151] In another embodiment R.sup.13 is selected from the group
consisting of H, Cl, and CF.sub.3. This embodiment may be used in
combination with the other embodiments of R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9,
R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15,
R.sup.16, Q.sup.1, and Q.sup.2.
[0152] In another embodiment R.sup.14 is H. This embodiment may be
used in combination with the other embodiments of R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9,
R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15,
R.sup.16, Q.sup.1, and Q.sup.2.
[0153] In another embodiment R.sup.15 is selected from the group
consisting of H and (C.sub.1-C.sub.4)alkyl. This embodiment may be
used in combination with the other embodiments of R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9,
R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15,
R.sup.16, Q.sup.1, and Q.sup.2.
[0154] In another embodiment R.sup.15 is selected from the group
consisting of H and CH.sub.3. This embodiment may be used in
combination with the other embodiments of R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9,
R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15,
R.sup.16, Q.sup.1, and Q.sup.2.
[0155] In another embodiment R.sup.16 is selected from the group
consisting of (C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl-O--(C.sub.1-C.sub.8)alkyl,
(C.sub.3-C.sub.8)alkyl(C.sub.3-C.sub.8)cycloalkyl,
(C.sub.1-C.sub.8)alkylphenyl, (C.sub.2-C.sub.8)alkenyl,
(C.sub.2-C.sub.8)alkynyl, (C.sub.1-C.sub.8)haloalkyl,
(C.sub.1-C.sub.8)alkyl-S--(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl-S(O)--(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl-S(O).sub.2--(C.sub.1-C.sub.8)alkyl,
O-phenyl, O--(C.sub.2-C.sub.8)alkenyl,
O--(C.sub.1-C.sub.8)alkyl(C.sub.3-C.sub.8)cycloalkyl,
O--(C.sub.1-C.sub.8)alkylphenyl,
(C.sub.1-C.sub.8)alkyl-O--(C.sub.1-C.sub.8)alkyl(C.sub.3-C.sub.8)cycloalk-
yl, (C.sub.1-C.sub.8)alkyl-O--(C.sub.1-C.sub.8)haloalkyl,
(C.sub.1-C.sub.8)alkyl-C(.dbd.O)NH--(C.sub.1-C.sub.8)haloalkyl, and
(C.sub.1-C.sub.8)alkyl-NHC(O)--(C.sub.1-C.sub.8)alkyl,
[0156] wherein each alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl,
and phenyl, may be optionally substituted with one or more
substituents selected from the group consisting of F, Cl, I, CN,
(C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)alkoxy,
(C.sub.1-C.sub.5)haloalkyl, N((C.sub.1-C.sub.8)alkyl).sub.2, and
pyridinyl. This embodiment may be used in combination with the
other embodiments of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5,
R.sup.6, R.sup.7, R.sup.8, R.sup.9, Q.sup.1, R.sup.10, R.sup.11,
R.sup.12, R.sup.13, R.sup.14, Q.sup.2, and R.sup.15.
[0157] In another embodiment R.sup.16 is selected from the group
consisting of CH.sub.2, CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2OCH.sub.2CH.sub.2, CH.sub.3,
CH.sub.2CH.sub.3, CH.sub.2CH.sub.2CH.sub.3,
CH.sub.2CH.sub.2CH.sub.2CH.sub.3,
CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.3,
CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.3,
CH.sub.2CH(CH.sub.3).sub.2, CH.sub.2cyclopropyl,
CH.sub.2CH.sub.2cyclopropyl, CH.sub.2cyclobutyl, CH.sub.2phenyl,
CH.sub.2CH.sub.2phenyl, CH.sub.2C.dbd.CH, CH.sub.2C.dbd.CH,
CH.sub.2CF.sub.3, CH.sub.2CHF.sub.2, CH.sub.2CH.sub.2CF.sub.3,
CH.sub.2CF.sub.2CF.sub.3, CH.sub.2CH.sub.2CH.sub.2CF.sub.3,
CH.sub.2CH.sub.2CF.sub.2CF.sub.3, CH.sub.2CF.sub.2CF.sub.2CF.sub.3,
CH.sub.2CH.sub.2CH.sub.2CH.sub.2F, CH.sub.2CH.sub.2SCH.sub.3,
CH.sub.2CH.sub.2S(O)CH.sub.3, CH.sub.2CH.sub.2S(O).sub.2CH.sub.3,
C(CH.sub.3).sub.2CH.sub.2S(O).sub.2CH.sub.3, Ophenyl,
OCH.sub.2CH.dbd.CH.sub.2, OCH.sub.2cyclopropyl, OCH.sub.2phenyl,
CH.sub.2CH.sub.2OCH.sub.2cyclopropyl,
CH.sub.2CH.sub.2CH.sub.2OCH.sub.2CF.sub.3,
CH.sub.2C(.dbd.O)NHCH.sub.2CF.sub.3, and
CH.sub.2CH.sub.2NHC(.dbd.O)CH.sub.3,
[0158] wherein each CH.sub.2, CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2,
cyclopropyl, cyclobutyl, and phenyl, may be optionally substituted
with one or more substituents selected from the group consisting of
F, Cl, CN, C(CH.sub.3).sub.3, CF.sub.3, OCH.sub.3,
OCH.sub.2CH.sub.3, N(CH.sub.3).sub.2, and pyridinyl. This
embodiment may be used in combination with the other embodiments of
R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7,
R.sup.8, R.sup.9, Q.sup.1, R.sup.10, R.sup.11, R.sup.12, R.sup.13,
R.sup.14, Q.sup.2, and R.sup.15.
[0159] In another embodiment R.sup.15 and R.sup.16 together are a
4-membered saturated, hydrocarbyl link,
[0160] wherein said hydrocarbyl link is substituted with one or
more F. This embodiment may be used in combination with the other
embodiments of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5,
R.sup.6, R.sup.7, R.sup.8, R.sup.9, Q.sup.1, R.sup.10, R.sup.11,
R.sup.12, R.sup.13, R.sup.14 and Q.sup.2.
[0161] In another embodiment R.sup.15 and R.sup.16 together are
--CH.sub.2CH.sub.2CF.sub.2CH.sub.2--. This embodiment may be used
in combination with the other embodiments of R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9,
Q.sup.1, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, and
Q.sup.2.
[0162] In another embodiment Q.sup.1 is O. This embodiment may be
used in combination with the other embodiments of R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9,
R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15,
R.sup.16, and Q.sup.2.
[0163] In another embodiment Q.sup.2 is O. This embodiment may be
used in combination with the other embodiments of R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9,
R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15,
R.sup.16, and Q.sup.1.
[0164] In another embodiment:
[0165] (A) R.sup.1 is H;
[0166] (B) R.sup.2 is selected from the group consisting of H and
Cl;
[0167] (C) R.sup.3 is selected from the group consisting of H and
Cl;
[0168] (D) R.sup.4 is Cl;
[0169] (E) R.sup.5 is H;
[0170] (F) R.sup.6 is H;
[0171] (G) R.sup.7 is selected from the group consisting of Cl and
Br;
[0172] (H) R.sup.8 is selected from the group consisting of Cl and
Br;
[0173] (I) R.sup.9 is H;
[0174] (J) R.sup.10 is H;
[0175] (K) R.sup.11 is H;
[0176] (L) R.sup.12 is H;
[0177] (M) R.sup.11 is selected from the group consisting of H, Cl,
and CF.sub.3;
[0178] (N) R.sup.14 is H;
[0179] (O) R.sup.15 is selected from the group consisting of H and
CH.sub.3;
[0180] (P) R.sup.16 is selected from the group consisting of
CH.sub.2, CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2OCH.sub.2CH.sub.2, CH.sub.3,
CH.sub.2CH.sub.3, CH.sub.2CH.sub.2CH.sub.3,
CH.sub.2CH.sub.2CH.sub.2CH.sub.3,
CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.3,
CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.3,
CH.sub.2CH(CH.sub.3).sub.2, CH.sub.2cyclopropyl,
CH.sub.2CH.sub.2cyclopropyl, CH.sub.2cyclobutyl, CH.sub.2phenyl,
CH.sub.2CH.sub.2phenyl, CH.sub.2C.dbd.CH, CH.sub.2C.dbd.CH,
CH.sub.2CF.sub.3, CH.sub.2CHF.sub.2, CH.sub.2CH.sub.2CF.sub.3,
CH.sub.2CF.sub.2CF.sub.3, CH.sub.2CH.sub.2CH.sub.2CF.sub.3,
CH.sub.2CH.sub.2CF.sub.2CF.sub.3, CH.sub.2CF.sub.2CF.sub.2CF.sub.3,
CH.sub.2CH.sub.2CH.sub.2CH.sub.2F, CH.sub.2CH.sub.2SCH.sub.3,
CH.sub.2CH.sub.2S(O)CH.sub.3, CH.sub.2CH.sub.2S(O)CH.sub.3,
C(CH.sub.3).sub.2CH.sub.2S(O).sub.2CH.sub.3, Ophenyl,
OCH.sub.2CH.dbd.CH.sub.2, OCH.sub.2cyclopropyl, OCH.sub.2phenyl,
CH.sub.2CH.sub.2OCH.sub.2cyclopropyl,
CH.sub.2CH.sub.2CH.sub.2OCH.sub.2CF.sub.3,
CH.sub.2C(.dbd.O)NHCH.sub.2CF.sub.3, and
CH.sub.2CH.sub.2NHC(.dbd.O)CH.sub.3, [0181] wherein each CH.sub.2,
CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2CH.sub.2, cyclopropyl, cyclobutyl, and
phenyl, may be optionally substituted with one or more substituents
selected from the group consisting of F, Cl, CN, C(CH.sub.3).sub.3,
CF.sub.3, OCH.sub.3, OCH.sub.2CH.sub.3, N(CH.sub.3).sub.2, and
pyridinyl; and
[0182] (Q) R.sup.15 and R.sup.16 together are a 4-membered
saturated, hydrocarbyl link,
[0183] wherein said hydrocarbyl link is substituted with one or
more F.
[0184] (R) Q and Q.sup.2 are O.
[0185] In another embodiment:
[0186] (A) R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.11,
R.sup.12, R.sup.13, and R.sup.14 are each independently selected
from the group consisting of H, Cl, and
(C.sub.1-C.sub.4)haloalkyl;
[0187] (B) R.sup.6 and R.sup.9 are H;
[0188] (C) R.sup.7 is Cl;
[0189] (D) R.sup.8 is Cl;
[0190] (E) Q.sup.1 and Q.sup.2 are O;
[0191] (F) R.sup.10 is H;
[0192] (G) R.sup.15 is selected from the group consisting of (I),
H, and (C.sub.1-C.sub.4)alkyl;
[0193] (H) R.sup.16 is selected from the group consisting of (I),
(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl-O--(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl(C.sub.3-C.sub.8)cycloalkyl,
(C.sub.1-C.sub.8)alkylphenyl, (C.sub.2-C.sub.8)alkenyl,
(C.sub.2-C.sub.8)alkynyl, (C.sub.1-C.sub.8)haloalkyl,
(C.sub.1-C.sub.8)alkyl-S--(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl-S(O)--(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl-S(O).sub.2--(C.sub.1-C.sub.8)alkyl, Ophenyl,
O--(C.sub.2-C.sub.8)alkenyl,
O--(C.sub.1-C.sub.8)alkyl(C.sub.3-C.sub.8)cycloalkyl,
O--(C.sub.1-C.sub.8)alkylphenyl,
(C.sub.1-C.sub.8)alkyl-O--(C.sub.1-C.sub.8)alkyl(C.sub.3-C.sub.8)cycloalk-
yl, (C.sub.1-C.sub.8)alkyl-O--(C.sub.1-C.sub.8)haloalkyl,
(C.sub.1-C.sub.8)alkyl-C(.dbd.O)NH--(C.sub.1-C.sub.8)haloalkyl, and
(C.sub.1-C.sub.8)alkyl-NHC(O)--(C.sub.1-C.sub.8)alkyl,
[0194] wherein each alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl,
and phenyl, may be optionally substituted with one or more
substituents selected from the group consisting of F, Cl, CN,
(C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)alkoxy,
(C.sub.1-C.sub.8)haloalkyl, and N((C.sub.1-C.sub.8)alkyl).sub.2;
and
[0195] (I) R.sup.15 and R.sup.16 together can optionally form a 2-
to 5-membered saturated, hydrocarbyl link,
[0196] wherein said hydrocarbyl link may be optionally substituted
with one or more substituent selected from the group consisting of
F, Cl, Br, and I.
[0197] In another embodiment:
[0198] (A) R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.11,
R.sup.12, R.sup.13, and R.sup.14 are each independently selected
from the group consisting of H, Cl, and
(C.sub.1-C.sub.4)haloalkyl;
[0199] (B) R.sup.6 and R.sup.9 are H;
[0200] (C) R.sup.7 is Cl;
[0201] (D) R.sup.8 is Cl;
[0202] (E) Q.sup.1 and Q.sup.2 are O;
[0203] (F) R.sup.10 is H;
[0204] (G) R.sup.15 is selected from the group consisting of (I),
H, and (C.sub.1-C.sub.4)alkyl;
[0205] (H) R.sup.16 is selected from the group consisting of (I),
(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl-O--(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl(C.sub.3-C.sub.8)cycloalkyl,
(C.sub.1-C.sub.8)alkylphenyl, (C.sub.2-C.sub.8)alkenyl,
(C.sub.2-C.sub.8)alkynyl, (C.sub.1-C.sub.8)haloalkyl,
(C.sub.1-C.sub.8)alkyl-S--(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl-S(O)--(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkyl-S(O).sub.2--(C.sub.1-C.sub.8)alkyl,
O--(C.sub.2-C.sub.8)alkenyl,
O--(C.sub.1-C.sub.8)alkyl(C.sub.3-C.sub.8)cycloalkyl,
O--(C.sub.1-C.sub.8)alkylphenyl,
(C.sub.1-C.sub.8)alkyl-O--(C.sub.1-C.sub.8)alkyl(C.sub.3-C.sub.8)cycloalk-
yl, (C.sub.1-C.sub.8)alkyl-O--(C.sub.1-C.sub.8)haloalkyl,
(C.sub.1-C.sub.8)alkyl-C(.dbd.O)NH--(C.sub.1-C.sub.8)haloalkyl, and
(C.sub.1-C.sub.8)alkyl-NHC(O)--(C.sub.1-C.sub.8)alkyl,
[0206] wherein each alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl,
and phenyl, may be optionally substituted with one or more
substituents selected from the group consisting of F, Cl, CN,
(C.sub.1-C.sub.8)alkoxy, and (C.sub.1-C.sub.8)haloalkyl; and
[0207] (I) R.sup.15 and R.sup.16 together can optionally form a 2-
to 5-membered saturated, hydrocarbyl link,
[0208] wherein said hydrocarbyl link may be optionally substituted
with one or more substituent selected from the group consisting of
F, Cl, Br, and I.
Preparation of Cyclopropyl Carboxylic Adds
[0209] Stilbenes 1-1, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4,
R.sup.5, R.sup.6, and R.sup.9 are as previously disclosed, may be
treated with a base such as sodium hydroxide in the presence of a
carbene source such as chloroform or bromoform and a phase transfer
catalyst such as N-benzyl-N,N-diethylethanaminium chloride in a
polar protic solvent such as water at temperatures from about
0.degree. C. to about 40.degree. C. to provide diaryl cyclopropanes
1-2, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6,
R.sup.7, R.sup.8, and R.sup.9 are as previously disclosed (Scheme
1, step a). Treatment of diaryl cyclopropanes 1-2 with a transition
metal such as ruthenium(III) chloride in the presence of a
stoichiometric oxidant such as sodium periodate in a solvent
mixture preferably water, ethyl acetate, and acetonitrile at
temperatures from about 0.degree. C. to about 40.degree. C. may
provide cyclopropyl carboxylic acids 1-3, wherein R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, and R.sup.9
are as previously disclosed (Scheme 1, step b).
##STR00013##
[0210] In yet other embodiments, 1-3 may be prepared from the aryl
ketone 1.5-1, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R are
as previously disclosed, and R.sup.6 is methyl. The acetophenone
1.5-1 may be reacted in a first step with a stabilized phosphonate
carbanion, generated by treating a phosphonate, such as ethyl
2-(diethoxyphosphoryl)-acetate with a strong base like sodium
hydride or potassium tert-butoxide in a polar aprotic solvent, such
as tetrahydrofuran at a temperature from about 0.degree. C. to
about 5.degree. C. (Scheme 1.5, step a). This reaction, like many
others involving the treatment of aldehydes or ketones with
stabilized phosphonate carbanions to give olefins, will be readily
recognized by one skilled in the art as the Homer-Wadsworth-Emmons
olefination. In a second step, the .alpha.,.beta.-unsaturated ester
1.5-2, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and
R.sup.6 are as defined above, may be treated with a reducing agent,
for example a metal hydride like diisobutylaluminum hydride, in an
aromatic hydrocarbon solvent like toluene at a temperature from
about -78.degree. C. to about 22.degree. C. to give the
intermediate primary alcohol 1.5-3 (Scheme 1.5, step b), wherein
R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 are as
defined above and R.sup.9 is as previously disclosed. Protection of
the primary alcohol 1.5-3 is required for the successful completion
of subsequent chemical transformations, and a wide variety of
protecting group strategies could be utilized. For example,
treating the alcohol 1.5-3 with 3,4-dihydro-2-H-pyran in the
presence of a catalytic amount of an organic acid, such as
para-toluenesulfonic acid monohydrate, in an aprotic solvent like
diethyl ether from a temperature of about 0.degree. C. to about
ambient temperature affords the tetrahydro-2-H-pyran (THP)
protected alcohol 1.5-4 (Scheme 1.5, step c), wherein R.sup.1,
R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.9 are as
defined above. The THP-protected styryl intermediate may be
converted to the THP-protected cyclopropane intermediate 1.5-5,
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and
R.sup.9 are as defined above and R.sup.7 and R.sup.8 are as
previously disclosed, by treatment with carbene source such as
chloroform in the presence of a base, such as sodium or potassium
hydroxide, and a catalyst such as tetrabutylammonium
hexafluorophosphate at a temperature from about 25 to about
45.degree. C. (Scheme 1.5, step d). Deprotection of the
THP-protected cyclopropane intermediate 1.5-5, wherein R.sup.1,
R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, and
R.sup.9 are as defined above, can be achieved by treatment with a
catalytic amount of an organic acid, such as para-toluenesulfonic
acid monohydrate, in polar, protic solvent, such as methanol, at a
temperature of about 22.degree. C. to give the cyclopropyl methanol
intermediate 1.5-6 (Scheme 1.5, step e). Oxidation of the primary
alcohol intermediate 1.5-6, wherein R.sup.1, R.sup.2, R.sup.3,
R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, and R.sup.9 are as
defined above, can be achieved using a wide range of reagents and
conditions known in the art (Figadere, B. and Franck, X.,
"Carboxylic Acids: Synthesis from Alcohols" Science of Synthesis
2006, (20a) pp 173-204), many of which offer differential
functional group compatibility and selectivity. For example,
treating the alcohol intermediate 1.5-6 with solutions of chromium
trioxide in solutions of dilute sulfuric acid and acetone, Jones
reagent, affords the cyclopropyl carboxylic acid 1-3, wherein
R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7,
R.sup.8, and R.sup.9 are as defined above (Scheme 1.5, step f).
##STR00014##
Preparation of Stilbenes
[0211] Stilbenes 1-1 may be prepared by several different methods
as outlined in Scheme 2. Phenyl carbonyls 2-1, wherein R.sup.1,
R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 are as previously
disclosed, may be treated with alkoxy benzyl phosphonates 2-2 in
the presence of a base such as sodium methoxide in a polar aprotic
solvent such as N,N-dimethylformamide at temperatures from about
-10.degree. C. to about 30.degree. C. and subsequently heated to
40.degree. C. to about 80.degree. C. to provide stilbenes 1-1
(Scheme 2, step a).
##STR00015##
[0212] Aryl halides 2-3, wherein R.sup.1, R.sup.2, R.sup.3,
R.sup.4, and R.sup.5 are as previously disclosed, may be treated
with vinylbenzenes 2-4, wherein R.sup.6 and R.sup.9 are as
previously disclosed, in the presence of a transition metal
catalyst such as palladium(II) acetate and a bisphosphine ligand
such as 1,1'-bis(diphenylphosphino)ferrocene in a basic solvent
such as triethylamine at temperatures from about 60.degree. C. to
about 100.degree. C. to provide stilbenes 1-1 (Scheme 2, step b).
Alternatively, aryl halides 2-3 may be treated with vinylboronates
2-5, wherein R.sup.6 and R.sup.9 are as previously disclosed, in
the presence of a transition metal catalyst such as
tetrakis(triphenylphosphine)palladium(0) and a base such as
potassium carbonate in a solvent mixture such as
1,2-dimethoxyethane and water at temperatures from about 60.degree.
C. to about 100.degree. C. to provide stilbenes 1-1 (Scheme 2, step
c).
[0213] In yet another embodiment, stilbenes 1-1 may also be
prepared by the Wittig olefination method (Chalal, M.;
Vervandier-Fasseur, D.; Meunier, P.; Cattey, H.; Hierso, J.-C.
Tetrahedron 2012, 68, 3899-3907) as outlined in Scheme 2.5. Phenyl
carbonyls 2-1, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, and
R.sup.5 are as previously disclosed and R.sup.6 is H, may be
treated with alkoxy benzyl triphenylphosphonium chlorides 2.5-2 in
the presence of a base such as n-butyl lithium in a polar aprotic
solvent such as tetrahydrofuran at temperatures from about
-78.degree. C. to ambient temperature to provide stilbenes 1-1
(Scheme 2.5, step a).
##STR00016##
Preparation of Cyclopropyl Amides
[0214] Cyclopropyl amides 3-3, wherein Q.sup.1 is O, and R.sup.1,
R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8,
R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, Q.sup.2,
and R.sup.15, and R.sup.16 are as previously disclosed, may be
prepared by treatment with amines or amine salts 3-2, wherein
R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, Q.sup.2, and
R.sup.15, and R.sup.16 are as previously disclosed, and activated
carboxylic acids 3-1, wherein A is an activating group, and
R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7,
R.sup.8, and R.sup.9 are as previously disclosed, with a base, such
as triethylamine, diisopropylethylamine, 4-methylmorpholine, or
4-dimethylaminopyridine in an anhydrous aprotic solvent such as
dichloromethane, tetrahydrofuran, 1,2-dichloroethane,
dimethylformamide, or any combination thereof, at temperatures
between about 0.degree. C. and about 120.degree. C. (Scheme 3, step
a).
[0215] Activated carboxylic acids 3-1 may be an acid halide, such
as an acid chloride, an acid bromide, or an acid fluoride; a
carboxylic ester, such as a para-nitrophenyl ester, a
pentafluorophenyl ester, an ethyl (hydroxyiminio)cyanoacetate
ester, a methyl ester, an ethyl ester, a benzyl ester, an
N-hydroxysuccinimidyl ester, a hydroxybenzotriazol-1-yl ester, or a
hydroxypyridyltriazol-1-yl ester; an O-acylisourea; an acid
anhydride; or a thioester. Acid chlorides may be prepared from the
corresponding carboxylic acids by treatment with a dehydrating
chlorinating reagent, such as oxalyl chloride or thionyl chloride.
Activated carboxylic esters 3-1 may be prepared from carboxylic
acids in situ with a uronium salt, such as
1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium
3-oxid hexafluorophosphate (HATU),
O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium
hexafluorophosphate (HBTU), or
(1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbeni-
um hexafluorophosphate (COMU). Activated carboxylic esters 3-1 may
also be prepared from carboxylic acids in situ with a phosphonium
salt such as benzotriazol-1-yl-oxytripyrrolidinophosphonium
hexafluorophosphate (PyBop). Activated carboxylic esters 3-1 may
also be prepared from carboxylic acids in situ with a coupling
reagent such as 1-(3-dimethylamino propyl)-3-ethylcarbodiimide, or
dicyclohexylcarbodiimide in the presence of a triazole such as
hydroxybenzotriazole.monohydrate (HOBt) or
1-hydroxy-7-azabenzotriazole (HOAt). O-Acylisoureas may be prepared
with a dehydrating carbodimide such as 1-(3-dimethylamino
propyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide. Activated
carboxylic esters 3-1 may also be prepared from carboxylic acids in
situ with a coupling reagent such as
2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP) in
the presence of a triazole such as 1-hydroxy-7-azabenzotriazole
(HOAt). Activated carboxylic esters 3-1 may also be prepared from
carboxylic acids in situ with a coupling reagent such as
2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide
(T3P.RTM.) in the presence of a base such as pyridine.
[0216] Cyclopropyl amides 3-3, wherein R.sup.16 contains a sulfide
and R.sup.15 is as previously disclosed, may be oxidized to the
corresponding sulfoxide or sulfone by treatment with about one
equivalent of meta-chloroperoxybenzoic acid in a polar aprotic
solvent such as dichloromethane (sulfoxide) or about two
equivalents of meta-chloroperoxybenzoic acid (sulfone) at
temperatures between about 0.degree. C. to about 40.degree. C.
Alternatively, cyclopropyl amides 3-3, wherein R' contains a
sulfide may be oxidized to the corresponding sulfoxide or sulfone
by treatment with one equivalent of sodium perborate in a protic
solvent such as acetic acid (sulfoxide) or two equivalents of
sodium perborate (sulfone). Preferably, the oxidation will be
performed at temperatures between about 40.degree. C. to about
100.degree. C. using about 1.5 equivalents of sodium perborate to
provide chromatographically separable mixtures of sulfoxide and
sulfone cyclopropyl amides 3-3.
##STR00017##
[0217] Cyclopropyl amides 4-3, wherein Q.sup.2 is O, and R.sup.1,
R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8,
R.sup.9, Q.sup.1, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14,
R.sup.15, and R.sup.16 are as previously disclosed, may be prepared
by treatment with amines or amine salts 4-2, wherein R.sup.15 and
R.sup.16 are as previously disclosed, and activated carboxylic
acids 4-1, wherein A is an activating group, and R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9,
Q.sup.1, R.sup.10, R.sup.11, R.sup.12, R.sup.13, and R.sup.14 are
as previously disclosed, with a base, such as triethylamine,
diisopropylethylamine, 4-methylmorpholine, or
4-dimethylaminopyridine in an anhydrous aprotic solvent such as
dichloromethane, tetrahydrofuran, 1,2-dichloroethane,
dimethylformamide, or any combination thereof, at temperatures
between about 0.degree. C. and about 120.degree. C. (Scheme 4, step
a).
[0218] Activated carboxylic acids 4-1 may be an acid halide, such
as an acid chloride, an acid bromide, or an acid fluoride; a
carboxylic ester, such as a para-nitrophenyl ester, a
pentafluorophenyl ester, an ethyl (hydroxyiminio)cyanoacetate
ester, a methyl ester, an ethyl ester, a benzyl ester, an
N-hydroxysuccinimidyl ester, a hydroxybenzotriazol-1-yl ester, or a
hydroxypyridyltriazol-1-yl ester; an O-acylisourea; an acid
anhydride; or a thioester. Acid chlorides may be prepared from the
corresponding carboxylic acids by treatment with a dehydrating
chlorinating reagent, such as oxalyl chloride or thionyl chloride.
Activated carboxylic esters 4-1 may be prepared from carboxylic
acids in situ with a uronium salt, such as
1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium
3-oxid hexafluorophosphate (HATU),
O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium
hexafluorophosphate (HBTU), or
(1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbeni-
um hexafluorophosphate (COMU). Activated carboxylic esters 4-1 may
also be prepared from carboxylic acids in situ with a phosphonium
salt such as benzotriazol-1-yl-oxytripyrrolidinophosphonium
hexafluorophosphate (PyBop). Activated carboxylic esters 4-1 may
also be prepared from carboxylic acids in situ with a coupling
reagent such as 1-(3-dimethylamino propyl)-3-ethylcarbodiimide, or
dicyclohexylcarbodiimide in the presence of a triazole such as
hydroxybenzotriazole.monohydrate (HOBt) or
1-hydroxy-7-azabenzotriazole (HOAt). O-Acylisoureas may be prepared
with a dehydrating carbodimide such as 1-(3-dimethylamino
propyl)-3-ethylcarbodiimide or dicyclohexylcarbodiimide. Activated
carboxylic esters 4-1 may also be prepared from carboxylic acids in
situ with a coupling reagent such as
2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP) in
the presence of a triazole such as 1-hydroxy-7-azabenzotriazole
(HOAt). Activated carboxylic esters 4-1 may also be prepared from
carboxylic acids in situ with a coupling reagent such as
2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide
(T3P.RTM.) in the presence of a base such as pyridine.
##STR00018##
[0219] In some embodiments, 1-3 may be prepared from the
.alpha.,.beta.-unsaturated aldehyde 5-1, wherein R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.9 are as previously.
It will be understood by one skilled in the art that compound 5-1
may be synthesized via Aldol condensation (see Yoshikawa, M.;
Kamei, T. PCT Int. Appl. 2010123006, 2010) of an appropriately
substituted, commercially available aldehyde and acetaldehyde.
Treatment of 5-1 with a (C.sub.1-C.sub.6)alkyl orthoformate, in the
presence of an acid whose pH is 0-5 such as hydrobromic acid,
N-bromosuccinimide, hydrochloric acid, N-chlorosuccinimide, and
pyridinium p-toluenesulfonate (PPTS), in a (C.sub.1-C.sub.6)alkanol
solvent, at a temperature from 0.degree. C. to ambient and under
ambient pressure provides the acetal 5-2, wherein R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.9 are as previously
disclosed and R.sup.a is a (C.sub.1-C.sub.6)alkyl or R.sup.a and
R.sup.a taken together can form a cyclic acetal (Scheme 5, step a).
The acetal 5-2 may be converted to the cyclopropyl acetal 5-3,
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6,
R.sup.7, R.sup.8, R.sup.9, and R.sup.a are as previously disclosed,
by treatment with a carbene source such as a haloform, for example,
bromoform or chloroform, in the presence of an inorganic base, such
as sodium or potassium hydroxide or sodium or potassium carbonate,
and a phase-transfer catalyst such as benzyl triethylammonium
chloride, (-)-N-dodecyl-N-methylephedrinium bromide,
tetramethylammonium bromide, tetrapropylammonium bromide,
tetrabutylammonium tetrafluoroborate, tetramethylammonium chloride
or tetrabutylammonium hexafluorophosphate at a temperature from
about ambient temperature up to below the boiling point of the
haloform (Scheme 5, step b). Caution: Step B is an exothermic
reaction and careful control of the exotherm should be exercised
when conducting this reaction. The cyclopropyl acetal 5-3 may be
transformed into the aldehyde 5-4, wherein R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, and R.sup.9
are as previously disclosed, in a polar solvent selected from the
group consisting of acetone, acetonitrile, methanol, ethanol,
nitromethane, N,N-dimethylformamide, dimethyl sulfoxide, ethyl
acetate, tetrahydrofuran and 1,4-dioxane, in the presence of an
aqueous mineral acid selected from the group consisting of nitric
acid, hydrochloric acid, hydrobromic acid, and sulfuric acid
(Scheme 5, step c) at ambient temperature. The cyclopropyl acid
1-3, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6,
R.sup.7, R.sup.8, and R.sup.9 are as previously disclosed, may be
obtained by oxidation of the aldehyde 5-4 with oxidants such sodium
permanganate or potassium permanganate, or under Pinnick oxidation
conditions in a polar aprotic solvent selected from the group
consisting of acetone, acetonitrile, N,N-dimethylformamide,
dimethyl sulfoxide, ethyl acetate, tetrahydrofuran and 1,4-dioxane
at a temperature from about 0.degree. C. to about ambient
temperature (Scheme 5, step d). Standard safety precautions should
be exercised because an exotherm may occur when conducting this
reaction.
##STR00019##
[0220] It will be understood by those skilled in the art that, in
some embodiments, the cyclopropyl acid 1-3, wherein R.sup.1,
R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, and
R.sup.9 are as previously disclosed, may be resolved into its (R,R)
and (S,S) enantiomers via a method such as that in Kovalenko V. N.,
Kulinkovich O. G. Tetrahedron: Asymmetry 2011, 22, 26 (Scheme 6,
step a).
##STR00020##
EXAMPLES
[0221] These examples are for illustration purposes and are not to
be construed as limiting this disclosure to only the embodiments
disclosed in these examples.
[0222] Starting materials, reagents, and solvents that were
obtained from commercial sources were used without further
purification. Anhydrous solvents were purchased as Sure/Seal.TM.
from Aldrich and were used as received. Melting points were
obtained on a Thomas Hoover Unimelt capillary melting point
apparatus or an OptiMelt Automated Melting Point System from
Stanford Research Systems and are uncorrected. Examples using "room
temperature" or "ambient temperature" were conducted in climate
controlled laboratories with temperatures ranging from about
20.degree. C. to about 24.degree. C. Molecules are given their
known names, named according to naming programs within ISIS Draw,
ChemDraw, or ACD Name Pro. If such programs are unable to name a
molecule, such molecule is named using conventional naming rules.
.sup.1H NMR spectral data are in ppm (.delta.) and were recorded at
300, 400, 500, or 600 MHz; .sup.13C NMR spectral data are in ppm
(.delta.) and were recorded at 75, 100, or 150 MHz, and .sup.19F
NMR spectral data are in ppm (.delta.) and were recorded at 376
MHz, unless otherwise stated.
Example 1: Preparation of
trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxylic
acid (C1)
##STR00021##
[0224] Ruthenium(III) chloride (0.080 g, 0.39 mmol) was added to a
stirred mixture of
trans-1,3-dichloro-5-(-2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzen-
e (C22) (2.8 g, 7.7 mmol) and sodium periodate (33 g, 160 mmol) in
water:ethyl acetate:acetonitrile (8:1:1, 155 mL) at 23.degree. C.
The resulting biphasic brown mixture was vigorously stirred at
23.degree. C. for 5 hours. The reaction mixture was diluted with
water (1000 mL) and extracted with dichloromethane (4.times.200
mL). The combined organic layers were dried over magnesium sulfate,
filtered, and concentrated. The residue was diluted with a sodium
hydroxide solution (1 M, 100 mL) and washed with diethyl ether
(4.times.50 mL). The aqueous layer was adjusted to pH 2, using
concentrated hydrochloric acid, and extracted with dichloromethane
(3.times.50 mL). The combined organic layers were dried over
magnesium sulfate, filtered, and concentrated to afford the title
product as a light brown powder (0.78 g, 34%): mp 117-120.degree.
C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 13.38 (br s, 1H),
7.52-7.65 (m, 3H), 3.57 (d, J=8.5 Hz, 1H), 3.50 (d, J=8.5 Hz, 1H);
IR (thin film) 3083 (s), 3011 (s), 1731 (s), 1590 (w), 1566 (s),
1448 (w), 1431 (m), 1416 (m) cm.sup.-1.
[0225] The following compounds were prepared in like manner to the
procedure outlined in Example 1:
trans-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropanecarboxylic
acid (C2)
##STR00022##
[0227] Isolated as a yellow powder (1.5 g, 39%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.31 (d, J=0.7 Hz, 2H), 3.40 (d, J=8.2 Hz,
1H), 2.86 (d, J=8.3 Hz, 1H); .sup.13C NMR (101 MHz, CDCl.sub.3)
.delta. 171.05, 134.55, 132.44, 131.75, 128.89, 61.18, 39.26,
37.14; ESIMS m/z 333 ([M-H].sup.-).
trans-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropanecarboxylic
acid (C3)
##STR00023##
[0229] Isolated as a pale yellow solid (3.2 g, 51%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.47 (d, J=8.3 Hz, 1H), 7.37 (d,
J=1.6 Hz, 1H), 7.12 (ddd, J=8.3, 2.1, 0.6 Hz, 1H), 3.43 (d, J=8.3
Hz, 1H), 2.86 (d, J=8.3 Hz, 1H); .sup.13C NMR (101 MHz, CDCl.sub.3)
.delta. 171.52, 132.91, 132.76, 132.29, 130.66, 130.62, 128.02,
61.48, 39.65, 37.13; ESIMS m/z 298 ([M-H].sup.-).
Example 2: Preparation of
trans-2,2-dichloro-3-(4-(trifluoromethyl)phenyl)cyclopropanecarboxylic
acid (C4)
##STR00024##
[0231] To a stirred mixture of
trans-1-(2,2-dichloro-3-(4-(trifluoromethyl)phenyl)cyclopropyl)-4-methoxy-
benzene (C25) (3.50 g, 9.60 mmol) and sodium periodate (30.8 g, 144
mmol) in water:ethyl acetate:acetonitrile (8:1:1, 200 mL) was added
ruthenlum(III) chloride (0.100 g, 0.400 mmol) at 23.degree. C. The
resulting mixture was vigorously stirred at 23.degree. C. for about
5 hours. The reaction mixture was diluted with dichloromethane and
washed with water. The combined organic layers were dried over
sodium sulfate, filtered, and concentrated. Purification by flash
column chromatography provided the title compound as an off-white
solid (0.630 g, 38%): mp 100-102.degree. C.; .sup.1H NMR (400 MHz,
DMSO-d.sub.6) .delta. 13.43 (brs, 1H), 7.77-7.73 (m, 2H), 7.67-7.64
(m, 2H), 3.55 (d, J=8.8 Hz, 1H), 3.44 (d, J=8.8 Hz, 1H); ESIMS m/z
347 ([M-H].sup.-).
[0232] The following compounds were prepared in like manner to the
procedure outlined in Example 2:
trans-2,2-Dichloro-3-(3-(trifluoromethyl)phenyl)cyclopropane
carboxylic acid (C5)
##STR00025##
[0234] Isolated as an off-white solid (0.81 g, 33%): mp
86-88.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 13.37
(brs, 1H), 7.83 (s, 1H), 7.76-7.69 (m, 2H), 7.65-7.59 (m, 1H),
3.59-3.51 (m, 2H); ESIMS m/z 297 ([M-H].sup.-).
trans-2,2-Dichloro-3-(3-chloro-4-(trifluoromethoxy)phenyl)cyclopropanecarb-
oxylic acid (C6)
##STR00026##
[0236] Isolated as an off-white solid (0.3 g, 19%): mp
134-136.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
13.45 (brs, 1H), 7.82 (d, J=1.6 Hz, 1H), 7.60-7.53 (m, 2H),
3.53-3.47 (m, 2H); ESIMS m/z 347 ([M-H].sup.-).
trans-2,2-Dichloro-3-(2,4,5-trichlorophenyl)cyclopropanecarboxylic
acid (C7)
##STR00027##
[0238] Isolated as an off-white solid (0.267 g, 18%): mp
189-192.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
13.44 (brs, 1H), 8.01 (s, 1H), 7.82 (s, 1H), 3.52 (d, J=8.2 Hz,
1H), 3.29 (d, J=8.2 Hz, 1H); ESIMS m/z 333 ([M-H].sup.-).
trans-3-(3,5-bis(trifluoromethyl)phenyl)-2,2-dichlorocyclopropanecarboxyli-
c acid (C8)
##STR00028##
[0240] Isolated as an off-white solid (0.5 g, 31%): mp
112-114.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
13.43 (brs, 1H), 8.22 (s, 2H), 8.08 (s, 1H), 3.80-3.71 (m, 2H);
ESIMS m/z 365 ([M-H].sup.-).
trans-2,2-dichloro-3-(3,5-dibromophenyl)cyclopropanecarboxylic acid
(C9)
##STR00029##
[0242] Isolated as an off-white solid (0.5 g, 24%): mp
157-159.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
13.36 (brs, 1H), 7.81 (d, J=1.5 Hz, 2H), 7.72 (d, J=1.5 Hz, 2H),
3.57-3.53 (m, 1H), 3.51-3.47 (m, 1H); ESIMS m/z 387
([M-H].sup.-).
trans-2,2-Dichloro-3-(3-chloro-5-(trifluoromethyl)phenyl)cyclopropanecarbo-
xylic acid (C10)
##STR00030##
[0244] Isolated as an off-white solid (0.73 g, 28%): mp
113-115.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
13.39 (brs, 1H), 7.91 (s, 1H), 7.86 (s, 1H), 7.84 (s, 1H),
3.69-3.60 (m, 2H); ESIMS m/z 333 ([M-H].sup.-).
trans-2,2-Dichloro-3-(3,5-dichloro-4-fluorophenyl)cyclopropanecarboxylic
acid (C11)
##STR00031##
[0246] Isolated as an off-white solid (0.539 g, 34%): .sup.1H NMR
(400 MHz, DMSO-d.sub.6): .delta. 13.37 (brs, 1H), 7.71 (d, J=6.4
Hz, 2H), 3.42 (s, 2H); ESIMS m/z 317 ([M-H].sup.-).
trans-3-(4-Bromo-3,5-dichlorophenyl)-2,2-dichlorocyclopropanecarboxylic
acid (C12)
##STR00032##
[0248] Isolated as an off-white solid (0.100 g, 10%): .sup.1H NMR
(400 MHz, DMSO-d.sub.6) .delta. 13.37 (brs, 1H), 7.76 (s, 3H), 3.57
(d, J=8.8 Hz, 1H), 3.48 (d, J=8.8 Hz, 1H); ESIMS m/z 377
([M-H].sup.-).
trans-3-(3-Bromo-5-chlorophenyl)-2,2-dichlorocyclopropanecarboxylic
acid (C13)
##STR00033##
[0250] Isolated as an off-white solid (0.4 g, 25%): mp
161-163.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
13.38 (br s, 1H), 7.70 (d, J=5.3 Hz, 2H), 7.66-7.52 (m, 1H),
3.59-3.43 (m, 2H); ESIMS m/z 341 ([M-H].sup.-).
trans-2,2-Dichloro-3-(3-chloro-5-fluorophenyl)cyclopropanecarboxylic
acid (C14)
##STR00034##
[0252] Isolated as an off-white solid (0.700 g, 25%): mp
138-140.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
13.38 (brs, 1H), 7.46 (s, 1H), 7.42 (td, J=2.0, 8.7 Hz, 1H), 7.37
(d, J=9.8 Hz, 1H), 3.52 (q, J=8.5 Hz, 2H); ESIMS m/z 281
([M-H].sup.-).
trans-2,2-Dichloro-3-(4-chloro-3-fluorophenyl)cyclopropanecarboxylic
acid (C15)
##STR00035##
[0254] Isolated as an off-white solid (0.500 g, 20%): mp
140-142.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
13.40 (brs, 1H), 7.59 (m, 1H), 7.55 (d, J=8.4 Hz, 1H), 7.33 (dd,
J=2.0, 8.4 Hz, 1H), 3.55-3.38 (m, 2H); ESIMS m/z 281
([M-H].sup.-).
trans-2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropanecarboxylic
acid (C16)
##STR00036##
[0256] Isolated as an off-white solid (1.0 g, 53%): mp
121-123.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
13.35 (brs, 1H), 7.71 (dd, J=2.0, 7.2 Hz, 1H), 7.53-7.35 (m, 2H),
3.50-3.41 (m, 2H); ESIMS m/z 281 ([M-H].sup.-).
trans-2,2-Dichloro-3-(3-chloro-5-methylphenyl)cyclopropanecarboxylic
acid (C17)
##STR00037##
[0258] Isolated as an off-white solid (1.0 g, 42%): mp
124-126.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
13.33 (brs, 1H), 7.30 (s, 1H), 7.23 (s, 1H), 7.21 (s, 1H), 3.38 (s,
2H), 2.31 (s, 3H); ESIMS m/z 277 ([M-H].sup.-).
trans-2,2-Dichloro-3-(3,5-dichloro-4-methylphenyl)cyclopropanecarboxylic
acid (C18)
##STR00038##
[0260] Isolated as an off-white solid (0.8 g, 40%): mp
181-183.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
13.40 (s, 1H), 7.56 (s, 2H), 3.53-3.50 (m, 1H), 3.46-3.43 (m, 1H),
2.40 (s, 3H); ESIMS m/z 311 ([M-H].sup.-).
trans-2,2-Dichloro-3-(3,4-dichloro-5-methylphenyl)cyclopropanecarboxylic
acid (C19)
##STR00039##
[0262] Isolated as an off-white solid (0.73 g, 45%): mp
157-159.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
13.40 (s, 1H), 7.59 (d, J=2.0 Hz, 1H), 7.44 (d, J=1.6 Hz, 1H), 3.43
(q, J=8.5 Hz, 2H), 2.39 (s, 3H); ESIMS m/z 311 ([M-H].sup.-).
trans-2,2-Dichloro-3-(4-(perfluoroethyl)phenyl)cyclopropanecarboxylic
acid (C20)
##STR00040##
[0264] Isolated as an off-white solid (0.020 g, 10%): mp
116-118.degree. C.; .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 7.63
(d, J=8.1 Hz, 2H), 7.42 (d, J=8.1 Hz, 2H), 3.53 (d, J=8.4 Hz, 1H),
2.94 (d, J=8.4 Hz, 1H); ESIMS m/z 347 ([M-H].sup.-).
trans-2,2-dichloro-3-(4-ethoxyphenyl)cyclopropanecarboxylic acid
(C21)
##STR00041##
[0266] Isolated as an off-white solid (0.025 g, 5%): mp
129-130.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.16
(d, J=8.4 Hz, 2H), 6.88 (d, J=8.31 Hz, 2H), 4.03 (q, J=6.8 Hz, 2H),
3.41 (d, J=8.0 Hz, 1H), 2.81 (d, J=8.0 Hz, 1H), 1.41 (t, J=6.8 Hz,
3H); ESIMS m/z 273 ([M-H].sup.-).
Example 3: Preparation of
trans-1,3-dichloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzene
(C22)
##STR00042##
[0268] Aqueous sodium hydroxide (50%, 6.8 mL, 130 mmol) was added
to a stirred solution of
(E)-1,3-dichloro-5-(4-methoxystyryl)benzene (C43) (2.4 g, 8.6 mmol)
and N-benzyl-N,N-diethylethanaminium chloride (0.20 g, 0.86 mmol)
in chloroform (14 mL, 170 mmol) at 23.degree. C. The resulting
biphasic, dark brown mixture was vigorously stirred at 23.degree.
C. for 24 hours. The reaction mixture was diluted with water (200
mL) and extracted with dichloromethane (2.times.100 mL). The
combined organic layers were dried over magnesium sulfate,
filtered, and concentrated to afford the title product as a brown
oil (2.8 g, 90%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.34
(t, J=1.8 Hz, 1H), 7.21-7.30 (m, 4H), 6.93 (m, 2H), 3.83 (s, 3H),
3.14 (d, J=8.5 Hz, 1H), 3.08 (d, J=8.5 Hz, 1H); IR (thin film) 3075
(w), 2934 (w), 2836 (w), 1724 (w), 1640 (w), 1609 (m), 1584 (m),
1568 (s), 1513 (s) cm.sup.-1.
[0269] The following compounds were prepared in like manner to the
procedure outlined in Example 3:
trans-1,
2,3-Trichloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benz-
ene (C23)
##STR00043##
[0271] Isolated as a dark foam (4.7 g, 100%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.40 (d, J=0.6 Hz, 2H), 7.29-7.22 (m, 2H),
6.96-6.89 (m, 2H), 3.83 (s, 3H), 3.12 (d, J=8.8 Hz, 1H), 3.06 (d,
J=8.7 Hz, 1H); .sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 159.46,
135.08, 134.23, 130.91, 129.85, 129.16, 125.42, 114.02, 64.67,
55.32, 39.62, 38.48.
trans-1,2-Dichloro-4-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzene
(C24)
##STR00044##
[0273] Isolated as an orange-red oil (7.6 g, 99%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.47 (d, J=4.9 Hz, 1H), 7.45 (bs, 1H),
7.30-7.23 (m, 2H), 7.21 (dd, J=8.2, 1.9 Hz, 1H), 6.96-6.90 (m, 2H),
3.83 (s, 3H), 3.11 (app. q, J=8.8 Hz, 2H); .sup.13C NMR (101 MHz,
CDCl.sub.3) .delta. 159.39, 134.90, 132.62, 131.99, 130.90, 130.40,
129.90, 128.33, 125.81, 113.98, 64.94, 55.33, 39.52, 38.75.
Example 4: Preparation of
trans-1-(2,2-dichloro-3-(4-(trifluoromethyl)phenyl)cyclopropyl)-4-methoxy-
benzene (C25)
##STR00045##
[0275] To a stirred solution of
(E)-1-methoxy-4-(4-(trifluoromethyl)styryl)benzene (C46) (4.00 g,
14.0 mmol) and N-benzyl-N,N-diethylethanaminium chloride (0.320 g,
14.0 mmol) in chloroform (23.1 g, 288 mmol), was added aqueous
sodium hydroxide (50%, 8.64 g, 216 mmol) in water (17 mL) at
23.degree. C., and the resulting mixture was vigorously stirred at
23.degree. C. for 16 hours. The reaction mixture was diluted with
water and extracted with dichloromethane. The combined organic
layers were dried over sodium sulfate, filtered, and concentrated.
Purification by flash column chromatography provided the title
compound as an off-white solid (3.70 g, 68%): .sup.1H NMR (300 MHz,
CDCl.sub.3) .delta. 7.65 (d, J=8.4 Hz, 2H), 7.49 (d, J=8.4 Hz, 2H),
7.29 (d, J=8.4 Hz, 2H), 6.94 (d, J=8.4 Hz, 2H), 3.83 (s, 3H), 3.19
(s, 2H); ESIMS m/z 361 ([M+H].sup.+).
[0276] The following compounds were prepared in like manner to the
procedure outlined in Example 4:
trans-1-(2,2-Dichloro-3-(4-methoxyphenyl)cyclopropyl)-3-(trifluoromethyl)b-
enzene (C26)
##STR00046##
[0278] Isolated as a brown liquid (3.5 g, 67%): .sup.1H NMR (300
MHz, CDCl.sub.3) .delta. 7.62-7.50 (m, 4H), 7.29 (d, J=9.0 Hz, 2H),
6.94 (d, J=9.0 Hz, 2H), 7.35-7.25 (m, 3H), 7.97-6.88 (m, 1H), 3.83
(s, 3H), 3.19 (m, 2H); ESIMS m/z 361 ([M+H].sup.+).
trans-2-Chloro-4-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-1-(trifluor-
omethoxy)benzene (C27)
##STR00047##
[0280] Isolated as an off-white solid (2.5 g, 65%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.57 (d, J=2.0 Hz, 1H), 7.44 (d,
J=8.8 Hz, 1H), 7.35-7.25 (m, 3H), 7.97-6.88 (m, 1H), 3.84 (s, 3H),
3.15-3.05 (m, 2H); ESIMS m/z 411 ([M+H].sup.+).
trans-1,2,4-Trichloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benze-
ne (C28)
##STR00048##
[0282] Isolated as a brown liquid (2.0 g, 58%): EIMS m/z 394
([M].sup.+).
trans-1-(2,2-Dichloro-3-(4-methoxyphenyl)cyclopropyl)-3,5-bis(trifluoromet-
hyl)benzene (C29)
##STR00049##
[0284] Isolated as a brown liquid (3.0 g, 61%): EIMS m/z 428
([M].sup.+).
trans-1,3-Dibromo-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benzene
(C30)
##STR00050##
[0286] Isolated as a brown liquid (3.0 g, 57%): .sup.1H NMR (300
MHz, CDCl.sub.3) .delta. 7.64 (s, 1H), 7.45 (s, 2H), 7.25 (d, J=9.0
Hz, 2H), 6.92 (d, J=9.0 Hz, 1H), 3.83 (s, 3H), 3.15-3.05 (m, 2H);
ESIMS m/z 453 ([M+H].sup.+).
trans-1-Chloro-3-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-5-(trifluor-
omethyl)benzene (C31)
##STR00051##
[0288] Isolated as a brown solid (4.0 g, 74%): .sup.1H NMR (300
MHz, CDCl.sub.3) .delta. 7.64 (s, 1H), 7.45 (s, 1H), 7.42 (s, 1H),
7.26 (d, J=9.0 Hz, 2H), 6.93 (d, J=9.0 Hz, 1H), 3.83 (s, 3H),
3.15-3.05 (m, 2H); ESIMS m/z 395 ([M+H].sup.+).
trans-1,3-Dichloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-2-fluor-
obenzene (C32)
##STR00052##
[0290] Isolated as a brown solid (1.6 g, 54%): .sup.1H NMR (300
MHz, CDCl.sub.3) .delta. 7.32 (d, J=6.0 Hz, 2H), 7.30 (d, J=9.0 Hz,
1H), 6.93 (d, J=9.0 Hz, 1H), 3.83 (s, 3H), 3.12-3.05 (m, 2H); ESIMS
m/z 297 ([M+H].sup.+).
trans-2-Bromo-1,3-dichloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-
benzene (C33)
##STR00053##
[0292] Isolated as an off-white solid (1.5 g, 44%): .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 7.36 (d, J=9.0 Hz, 2H), 7.20 (s, 2H),
6.93 (d, J=9.0 Hz, 2H), 3.83 (s, 3H), 3.15-3.05 (m, 2H); ESIMS m/z
439 ([M+H].sup.+).
trans-1-Bromo-3-chloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)benz-
ene (C34)
##STR00054##
[0294] Isolated as an off-white solid (2.5 g, 50%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.49 (s, 1H), 7.30 (s, 1H), 7.28-7.24
(m, 3H), 6.92 (d, J=8.0 Hz, 2H), 3.92 (s, 3H), 3.01 (q, J=8.8 Hz,
2H); ESIMS m/z 405 ([M+H].sup.+).
trans-1-Chloro-3-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-5-fluoroben-
zene (C35)
##STR00055##
[0296] Isolated as a brown liquid (3.5 g, 67%): ESIMS m/z 345
([M+H].sup.+).
trans-1-Chloro-4-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-2-fluoroben-
zene (C36)
##STR00056##
[0298] Isolated as an off-white solid (2.5 g, 65%): ESIMS m/z 345
([M+H].sup.+).
trans-2-Chloro-4-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-1-fluoroben-
zene (C37)
##STR00057##
[0300] Isolated as a brown liquid (2.0 g, 58%): ESIMS m/z 345
([M+H].sup.+).
trans-1-Chloro-3-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-5-methylben-
zene (C38)
##STR00058##
[0302] Isolated as an off-white solid (3.0 g, 47%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.27 (d, J=8.8 Hz, 2H), 7.14 (s, 2H),
7.06 (s, 1H), 6.92 (d, J=8.8 Hz, 2H), 3.82 (s, 3H), 3.10 (q, J=8.8
Hz, 2H), 2.36 (s, 3H); ESIMS m/z 341 ([M+H].sup.+).
trans-1,3-Dichloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-2-methy-
lbenzene (C39)
##STR00059##
[0304] Isolated as a brown liquid (2.5 g, 80%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.25 (d, J=8.0 Hz, 2H), 7.17 (d, J=8.8 Hz,
1H), 6.92 (d, J=8.0 Hz, 2H), 6.88 (d, J=8.8 Hz, 1H), 3.82 (s, 3H),
3.12-3.03 (m, 2H), 2.47 (s, 3H); ESIMS m/z 375 ([M+H].sup.+).
trans-1,2-Dichloro-5-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-3-methy-
lbenzene (C40)
##STR00060##
[0306] Isolated as a Brown liquid (4.0 g, 90%): ESIMS m/z 375
([M+H].sup.+).
trans-1-(2,2-Dichloro-3-(4-(perfluoroethyl)phenyl)cyclopropyl)-4-methoxybe-
nzene (C41)
##STR00061##
[0308] Isolated as an off-white solid (0.5 g, 46%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.60-7.50 (m, 4H), 7.47 (d, J=8.0 Hz,
2H), 6.92 (d, J=8.0 Hz, 2H), 3.82 (s, 3H), 3.20 (s, 2H); ESIMS m/z
411 ([M+H].sup.+).
trans-4,4'-(3,3-Dichlorocyclopropane-1,2-diyl)bis(ethoxybenzene)
(C42)
##STR00062##
[0310] Isolated as an off-white solid (1.5 g, 45%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.27 (d, J=8.0 Hz, 4H), 6.90 (d,
J=8.0 Hz, 4H), 4.04 (q, J=6.8 Hz, 4H), 3.09 (s, 2H), 1.42 (t, J=6.8
Hz, 6H); ESIMS m/z 351 ([M+H].sup.+).
Example 5: Preparation of
(E)-1,3-dichloro-5-(4-methoxystyryl)benzene (C43)
##STR00063##
[0312] Sodium methoxide powder (98%, 0.63 g, 11 mmol) was added to
a stirred solution of 3,5-dichlorobenzaldehyde (2.0 g, 11 mmol) and
diethyl 4-methoxybenzylphosphonate (2.0 mL, 11 mmol) in dry
N,N-dimethylformamide (38 mL) at 23.degree. C. The resulting
heterogeneous dark blue mixture was heated to 80.degree. C.,
resulting in a dark brown mixture, and stirred for 24 hours. The
cooled reaction mixture was diluted with water (500 mL) and
extracted with diethyl ether (3.times.100 mL). The combined organic
layers were diluted with hexane (150 mL) and washed with water (300
mL). The organic layer was dried over magnesium sulfate, filtered,
and concentrated to afford the title product as a light brown oil
(2.4 g, 75%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.44 (m,
2H), 7.34 (d, J=2 Hz, 2H), 7.20 (t, J=2 Hz, 1H), 7.06 (d, J=16.5
Hz, 1H), 6.91 (m, 2H), 6.82 (d, J=16.5 Hz, 1H), 3.84 (s, 3H); IR
(thin film) 2934 (w), 2835 (w), 1724 (w), 1637 (w), 1605 (m), 1581
(m), 1558 (m), 1511 (s) cm.sup.-1.
[0313] The following compounds were prepared in like manner to the
procedure outlined in Example 5:
(E)-1,2,3-Trichloro-5-(4-methoxystyryl)benzene (C44)
##STR00064##
[0315] Isolated as an off-white solid (3.7 g, 31%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.49-7.46 (m, 2H), 7.47-7.39 (m, 2H),
7.04 (d, J=16.3 Hz, 1H), 6.93-6.89 (m, 2H), 6.78 (d, J=16.3 Hz,
1H), 3.84 (s, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) .delta.
159.46, 135.08, 134.23, 130.91, 129.85, 129.16, 125.42, 114.02,
64.67, 55.32, 39.62, 38.48; EIMS m/z 313 ([M].sup.+).
(E)-1,2-Dichloro-4-(4-methoxystyryl)benzene (C45)
##STR00065##
[0317] Isolated as an off-white solid (6.0 g, 53%): mp
91-94.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.56
(d, J=2.0 Hz, 1H), 7.46-7.42 (m, 2H), 7.39 (d, J=8.4 Hz, 1H), 7.29
(dd, J=8.4, 2.1 Hz, 1H), 7.04 (d, J=16.2 Hz, 1H), 6.93-6.88 (m,
2H), 6.85 (d, J=16.3 Hz, 1H), 3.84 (s, 3H); .sup.13C NMR (101 MHz,
CDCl.sub.3) .delta. 159.75, 137.86, 132.72, 130.58, 130.49, 130.12,
129.33, 127.96, 127.77, 125.37, 123.98, 114.24, 55.35; EIMS m/z 279
([M].sup.+).
Example 6: Preparation of
(E)-1-methoxy-4-(4-(trifluoromethyl)styryl)benzene (C46)
##STR00066##
[0319] To a stirred solution of diethyl 4-methoxybenzyl phosphonate
(8.89 g, 34.0 mmol) in N,N-dimethylformamide (30 mL) was added
sodium methoxide powder (1.86 g, 34.0 mmol). The reaction mixture
was stirred at room temperature for 1 hour. The reaction mixture
was cooled to 0.degree. C. and 4-(trifluoromethyl)benzaldehyde
(5.00 g, 28.0 mmol) in N,N-dimethylformamide (30 mL) was added
dropwise. The reaction mixture was stirred at 60.degree. C. for 2
hours. The reaction mixture was poured in ice cold water, filtered,
and dried to afford the title compound as an off-white solid (3.60
g, 80%): .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 7.61-7.52 (m,
4H), 7.47 (d, J=9.0 Hz, 2H), 7.14 (d, J=16.5 Hz, 1H), 6.97 (d,
J=16.5 Hz, 1H), 6.91 (d, J=9.0 Hz, 2H), 3.84 (s, 3H); ESIMS m/z 279
([M+H].sup.+).
[0320] The following compounds were prepared in like manner to the
procedure outlined in Example 6:
(E)-1-(4-Methoxystyryl)-3-(trifluoromethyl)benzene (C47)
##STR00067##
[0322] Isolated as an off-white solid (4.0 g, 85%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.72 (s, 1H), 7.64 (d, J=6.8 Hz, 1H),
7.50-7.44 (m, 4H), 7.12 (d, J=16.0 Hz, 1H), 6.98 (d, J=16.0 Hz,
1H), 6.91 (d, J=8.8 Hz, 2H), 3.84 (s, 3H); ESIMS m/z 279
([M+H].sup.+).
(E)-2-Chloro-4-(4-methoxystyryl)-1-(trifluoromethoxy)benzene
(C48)
##STR00068##
[0324] Isolated: ESIMS m/z 329 ([M+H].sup.+).
(E)-1-(4-Methoxystyryl)-3,5-bis(trifluoromethyl)benzene (C49)
##STR00069##
[0326] Isolated as an off-white solid (4.0 g, 56%): .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 7.88 (s, 2H), 7.70 (s, 1H), 7.49 (d,
J=8.4 Hz, 2H), 7.19 (d, J=16.5 Hz, 1H), 6.99 (d, J=16.5 Hz, 1H),
6.92 (d, J=8.4 Hz, 2H), 3.84 (m, 3H); ESIMS m/z 347
([M+H].sup.+).
(E)-1,3-Dibromo-5-(4-methoxystyryl)benzene (C50)
##STR00070##
[0328] Isolated as an off-white solid (2.2 g, 54%): .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 7.53 (s, 1H), 7.50 (s, 2H), 7.43 (d,
J=9.0 Hz, 2H), 7.05 (d, J=16.2 Hz, 1H), 6.90 (d, J=9.0 Hz, 2H),
6.79 (d, J=16.2 Hz, 1H), 3.80 (s, 3H); ESIMS m/z 367
([M+H].sup.+).
(E)-1-Chloro-3-(4-methoxystyryl)-5-(trifluoromethyl)benzene
(C51)
##STR00071##
[0330] Isolated as an off-white solid (4.3 g, 58%): .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 7.62 (s, 1H), 7.58 (s, 1H), 7.48-7.42
(m, 3H), 7.12 (d, J=16.2 Hz, 1H), 6.95-6.85 (m, 3H), 3.84 (s, 3H);
ESIMS m/z 313 ([M+H].sup.+).
(E)-2-Bromo-1,3-dichloro-5-(4-methoxystyryl)benzene (C52)
##STR00072##
[0332] Isolated as an off-white solid (2.8 g, 40%): .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 7.46 (s, 2H), 7.43 (d, J=9.0 Hz, 2H),
7.07 (d, J=13.5 Hz, 1H), 6.90 (d, J=9.0 Hz, 1H), 6.73 (d, J=13.5
Hz, 1H), 3.84 (s, 3H); ESIMS m/z 358 ([M+H].sup.+).
(E)-1-Bromo-3-chloro-5-(4-methoxystyryl)benzene (C53)
##STR00073##
[0334] Isolated as an off-white solid (4.0 g, 63%): .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 7.49 (s, 1H), 7.43 (d, J=8.4 Hz, 2H),
7.38 (s, 1H), 7.35 (s, 1H), 7.05 (d, J=16.5 Hz, 1H), 6.91 (d, J=8.4
Hz, 2H), 6.80 (d, J=16.5 Hz, 1H), 3.82 (s, 3H); ESIMS m/z 323
([M+H].sup.+).
(E)-1-Chloro-3-fluoro-5-(4-methoxystyryl)benzene (C54)
##STR00074##
[0336] Isolated as an off-white solid (5.0 g, 60%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.45 (d, J=8.4 Hz, 2H), 7.10-7.0 (m,
3H), 6.96-6.80 (m, 4H), 3.80 (s, 3H); ESIMS m/z 263
([M+H].sup.+).
(E)-1-Chloro-2-fluoro-4-(4-methoxystyryl)benzene (C55)
##STR00075##
[0338] Isolated as an off-white solid (7.0 g, 84%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.44 (d, J=8.0 Hz, 2H), 7.35-7.31 (m,
1H), 7.28-7.24 (m, 1H), 7.17 (dd, J=1.6, 8.0 Hz, 1H), 7.03 (d,
J=16.0 Hz, 1H), 6.90 (d, J=8.0 Hz, 1H), 7.49 (d, J=8.0 Hz, 1H),
6.86 (d, J=16.0 Hz, 1H), 3.82 (s, 3H); ESIMS m/z 263
([M+H].sup.+).
(E)-2-Chloro-1-fluoro-4-(4-methoxystyryl)benzene (C56)
##STR00076##
[0340] Isolated as an off-white solid (6.0 g, 72%): ESIMS m/z 263
([M+H].sup.+).
(E)-1-Chloro-3-(4-methoxystyryl)-5-methylbenzene (C57)
##STR00077##
[0342] Isolated as an off-white solid (5.0 g, 60%): .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 7.44 (d, J=8.4 Hz, 2H), 7.28 (s, 1H),
7.15 (s, 1H), 7.05-7.00 (m, 2H), 6.91-6.83 (m, 3H), 3.83 (s, 3H),
2.24 (s, 3H); ESIMS m/z 259 ([M+H].sup.+).
(E)-1-Methoxy-4-(4-(perfluoroethyl)styryl)benzene (C58)
##STR00078##
[0344] Isolated as an off-white solid (0.5 g, 42%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.60-7.50 (m, 4H), 7.47 (d, J=8.8 Hz,
2H), 7.15 (d, J=16.8 Hz, 1H), 6.98 (d, J=16.8 Hz, 1H), 6.92 (d,
J=8.8 Hz, 2H), 3.82 (s, 3H); ESIMS m/z 329 ([M+H].sup.+).
(E)-1,2-bis(4-ethoxyphenyl)ethene (C59)
##STR00079##
[0346] Isolated as an off-white solid (1.7 g, 34%): .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 7.40 (d, J=9.0 Hz, 4H), 6.91 (s, 2H),
6.87 (d, J=9.0 Hz, 4H), 4.05 (q, J=6.9 Hz, 4H), 1.42 (t, J=6.9 Hz,
6H); ESIMS m/z 269 ([M+H].sup.+).
Example 7: Preparation of
(E)-1,3-dichloro-2-fluoro-5-(4-methoxystyryl)benzene (C60)
##STR00080##
[0348] A stirred mixture of 5-bromo-1,3-dichloro-2-fluorobenzene
(2.00 g, 8.20 mmol), 1-methoxy-4-vinylbenzene (1.32 g, 9.80 mmol),
and triethylamine (20 mL) under argon was degassed for 5 minutes.
Palladium(II) acetate (0.0368 g, 0.164 mmol) and
1,1'-bis(diphenylphosphino)ferrocene (0.181 g, 0.328 mmol) were
added and the reaction was heated to 90.degree. C. for 16 hours.
The reaction mixture was poured into water and extracted with ethyl
acetate. The combined organic layers were dried over sodium
sulfate, filtered, and concentrated. Purification by flash column
chromatography provided the title compound as an off-white solid
(1.60 g, 67%): .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 7.41 (d,
J=8.8 Hz, 2H), 7.31 (s, 1H), 7.37 (s, 1H), 6.96 (d, J=16.0 Hz, 1H),
6.89 (d, J=8.8 Hz, 2H), 6.76 (d, J=16.0 Hz, 1H), 3.84 (s, 3H);
ESIMS m/z 297 ([M+H].sup.+).
[0349] The following compounds were prepared in like manner to the
procedure outlined in Example 7:
(E)-1,3-Dichloro-5-(4-methoxystyryl)-2-methylbenzene (C61)
##STR00081##
[0351] Isolated as an off-white solid (2.5 g, 67%): .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 7.43 (d, J=8.7 Hz, 2H), 7.38 (s, 2H),
7.02 (d, J=16.5 Hz, 1H), 6.90 (d, J=8.7 Hz, 2H), 6.79 (d, J=16.5
Hz, 1H), 3.82 (s, 3H), 2.42 (s, 3H); ESIMS m/z 293
([M+H].sup.+).
(E)-1,2-Dichloro-5-(4-methoxystyryl)-3-methylbenzene (C62)
##STR00082##
[0353] Isolated as an off-white solid (3.0 g, 55%): .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 7.50-7.40 (m, 3H), 7.24 (s, 1H), 7.02
(d, J=15.9 Hz, 1H), 6.90 (d, J=9.0 Hz, 2H), 6.81 (d, J=15.9 Hz,
1H), 3.83 (s, 3H), 2.42 (s, 3H); ESIMS m/z 293 ([M+H].sup.+).
Example 8: Preparation of
(E)-1,2,4-trichloro-5-(4-methoxystyryl)benzene (C63)
##STR00083##
[0355] To a sealed tube were added 1-bromo-2,4,5-trichlorobenzene
(3.0 g, 12 mmol), 1,2-dimethoxyethane: water (10:1, 30 mL),
(E)-2-(4-methoxystyryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(C.sub.64) (3.7 g, 14 mmol), and potassium carbonate (3.2 g, 24
mmol). The reaction mixture was degassed for 10 minutes with argon,
followed by addition of tetrakis(triphenylphosphine)palladium(0)
(0.55 g, 0.48 mmol). The reaction mixture was degassed for 10
minutes then heated at 90.degree. C. for 16 hours. The reaction
mixture was poured in to water and extracted with ethyl acetate.
The combined organic layers were dried over sodium sulfate,
filtered, and concentrated. Purification by flash column
chromatography provided the title compound as an off-white solid
(3.0 g, 80%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.73 (s,
1H), 7.50-7.45 (m, 3H), 7.20 (d, J=16.0 Hz, 1H), 7.02 (d, J=16 Hz,
1H), 6.92 (d, J=8.0 Hz, 2H), 3.84 (m, 3H); ESIMS m/z 313
([M+H].sup.+).
Example 9: Preparation of
(E)-2-(4-methoxystyryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(C64)
##STR00084##
[0357] To a 50 mL round-bottomed flask were added
1-ethynyl-4-methoxybenzene (4.0 g, 30 mmol),
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.3 g, 36 mmol),
zirconocene hydrochloride (1.2 g, 4.0 mmol), and triethylamine (2.8
mL, 15 mmol) at 0.degree. C. The reaction mixture was then stirred
at 65.degree. C. for 16 hours. The reaction mixture was poured in
water and extracted with ethyl acetate. The combined organic layers
were dried over sodium sulfate, filtered, and concentrated.
Purification by flash column chromatography provided the title
compound as an off-white semi solid (3.0 g, 38%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.43 (d, J=8.8 Hz, 2H), 7.35 (d, J=18.0
Hz, 1H), 6.86 (d, J=8.8 Hz, 2H), 6.01 (d, J=18.0 Hz, 1H), 3.81 (s,
3H), 1.30 (s, 12H).
Example 10: Preparation of 3,4,5-trichlorobenzaldehyde (C65)
##STR00085##
[0359] In an oven dried, nitrogen flushed, 500 mL round-bottomed
flask equipped with a pressure equalizing addition funnel,
5-bromo-1,2,3-trichlorobenzene (10.0 g, 38.4 mmol) was dissolved in
tetrahydrofuran (100 mL), and the resulting solution was cooled in
an ice bath under nitrogen. Isopropyl magnesium chloride (2 M
solution tetrahydrofuran, 21.1 mL, 42.3 mmol) was added dropwise
with good stirring over 15 minutes via the addition funnel. After
0.5 hours, N,N-dimethylformamide (3.72 mL, 48.0 mmol) was added to
the dark solution with stirring. After an additional 0.5 hours,
hydrochloric acid (1 N, 100 mL) was added with stirring. The layers
were separated, and the organic layer was washed with brine. The
combined aqueous layers were extracted with ether, and the combined
organics were dried over sodium sulfate, filtered, and concentrated
to afford the title compound as a white solid (10:1 mixture of
title compound to 1,2,3-trichlorobenzene, 7.96 g, 99%): .sup.1H NMR
(CDCl.sub.3) .delta. 9.91 (s, 1H), 7.88 (s, 2H); EIMS m/z 209
([M].sup.+).
Example 11: Preparation of 1-bromo-4-(perfluoroethyl)benzene
(C66)
##STR00086##
[0361] To a stirred solution of
1-(4-bromophenyl)-2,2,2-trifluoroethanone (5.00 g, 19.7 mmol) in
dichloromethane under argon were added
4-tert-butyl-2,6-dimethylphenylsulfur trifluoride (2.90 g, 11.8
mmol) and hydrogen fluoride pyridine complex (0.190 g, 9.80 mmol)
at 0.degree. C. The reaction mixture was allowed to warm to room
temperature and stirred for 16 hours. The reaction mixture was
poured into water and extracted with ethyl acetate. The combined
organic extracts were dried over sodium sulfate, filtered, and
concentrated. Purification by flash column chromatograph provided
the title compound as colorless liquid (1.00 g, 20%): .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 7.65 (d, J=9.0 Hz, 2H), 7.47 (d,
J=9.0 Hz, 2H); EIMS m/z 274 ([M].sup.+).
Example 12: Preparation of
trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxam-
ido)benzoic acid (C67)
##STR00087##
[0363] To a solution of
trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxylic
acid (C1) (0.300 g, 1.00 mmol) in dichloromethane (5.00 mL) stirred
at 0.degree. C., were added N,N-dimethylformamide (1 drop) followed
by oxalyl chloride (0.131 mL, 1.50 mmol) over 2 minutes. The ice
batch was removed and the reaction allowed to warm to room
temperature over 90 minutes. The reaction was then concentrated to
yield a yellow-orange semi-solid. The semi-solid was dissolved in
dichloromethane (3.5 mL), and the solution was added slowly to a
cooled solution of 5-amino-2-chlorobenzoic acid (0.206 g, 1.20
mmol) and triethylamine (0.209 mL, 1.50 mmol) in dichloromethane (7
mL). The ice bath was removed and the reaction was allowed to warm
to room temperature over 90 minutes. The reaction was diluted with
dichloromethane (10 mL) and washed with hydrochloric acid (0.1 N).
The resulting slurry was filtered and the solid washed with water.
The precipitated solid was dried in a vacuum oven at 40.degree. C.
to provide the title compound as a light brown solid (0.421 g,
93%): mp 234-236.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6)
.delta. 13.47 (s, 1H), 10.90 (s, 1H), 8.16 (d, J=2.3 Hz, 1H), 7.78
(dd, J=8.7, 2.4 Hz, 1H), 7.59 (m, 4H), 3.56 (dd, J=49.8, 8.5 Hz,
2H), 1.09 (m, 1H); .sup.13C NMR (101 MHz, DMSO-d.sub.6) .delta.
166.26, 165.77, 162.61, 137.57, 137.27, 134.04, 132.18, 131.44,
131.22, 127.88, 127.66, 126.40, 125.92, 122.88, 121.17, 102.37,
62.11, 38.41, 36.83; ESIMS m/z 454 ([M+H].sup.+).
Example 13: Preparation of
trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbo-
xamido)-N-methylbenzamide (F1)
##STR00088##
[0365] 5-Amino-2-chloro-N-methylbenzamide (C68) (0.072 g, 0.39
mmol) and 4-dimethylaminopyridine (0.052 g, 0.42 mmol) were
sequentially added to a stirred mixture of
trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxylic
acid (C1) (0.097 g, 0.33 mmol) and
1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.093 g, 0.49 mmol)
in 1,2-dichloroethane (3.3 mL) at room temperature. The reaction
was stirred at room temperature for 20 hours. Dichloromethane was
added and the mixture was washed with saturated aqueous sodium
bicarbonate and hydrochloric acid (1 N). The organic phase was
dried over magnesium sulfate, filtered, and concentrated.
Purification by flash column chromatography using 0-100% ethyl
acetate/hexanes as eluent provided the title compound as a yellow
oil (0.047 g, 30%).
[0366] The following compounds were prepared in like manner to the
procedure outlined in Example 13:
trans-5-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N--
methyl-2-(trifluoromethyl)benzamide (F2)
##STR00089##
[0368] Isolated as a yellow solid (0.051 g, 32%).
trans-3-(2,2-Dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamido)-N--
(2,2,2-trifluoroethyl)benzamide (F3)
##STR00090##
[0370] Isolated as a white solid (0.155 g, 62%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(2,2,2-trifluoroethyl)benzamide (F4)
##STR00091##
[0372] Isolated as a yellow solid (0.081 g, 44%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide
(F5)
##STR00092##
[0374] Isolated as a yellow solid (0.065 g, 39%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(pyridin-3-ylmethyl)benzamide (F6)
##STR00093##
[0376] Isolated as a tan powder (0.091 g, 67%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-car-
boxamido)-N-(pyridin-3-ylmethyl)benzamide (F7)
##STR00094##
[0378] Isolated as a tan powder (0.051 g, 59%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(pyridin-2-ylmethyl)benzamide (F8)
##STR00095##
[0380] Isolated as an off-white powder (0.036 g, 26%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-car-
boxamido)-N-(pyridin-2-ylmethyl)benzamide (F9)
##STR00096##
[0382] Isolated as an off-white powder (0.017 g, 20%).
trans-N-(Allyloxy)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopro-
pane-1-carboxamido)benzamide (F10)
##STR00097##
[0384] Isolated as an off-white semi-solid (0.034 g, 27%).
trans-N-(Allyloxy)-2-chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclo-
propane-1-carboxamido)benzamide (F11)
##STR00098##
[0386] Isolated as a tan semi-solid (0.021 g, 26%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(pyridin-4-ylmethyl)benzamide (F12)
##STR00099##
[0388] Isolated as a tan powder (0.100 g, 74%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-car-
boxamido)-N-(pyridin-4-ylmethyl)benzamide (F13)
##STR00100##
[0390] Isolated as an off-white powder (0.062 g, 72%).
trans-N-(Allyloxy)-2-chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopro-
pane-1-carboxamido)benzamide (F14)
##STR00101##
[0392] Isolated as a white powder (0.062 g, 49%).
trans-N-2-Chloro-N-(cyclopropylmethoxy)-5-(2,2-dichloro-3-(3,4,5-trichloro-
phenyl)cyclopropane-1-carboxamido)benzamide (F15)
##STR00102##
[0394] Isolated as a white foam (0.056 g, 56%).
trans-N-2-Chloro-N-(cyclopropylmethoxy)-5-(2,2-dichloro-3-(3,5-dichlorophe-
nyl)cyclopropane-1-carboxamido)benzamide (F16)
##STR00103##
[0396] Isolated as a white powder (0.066 g, 50%).
trans-N-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carb-
oxamido)-N-((4-fluorobenzyl)oxy)benzamide (F17)
##STR00104##
[0398] Isolated as a tan foam (0.063 g, 44%).
trans-N-2-Chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-c-
arboxamido)-N-((4-fluorobenzyl)oxy)benzamide (F18)
##STR00105##
[0400] Isolated as a tan foam (0.048 g, 35%).
trans-N-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carb-
oxamido)-N-(4-fluorophenethyl)benzamide (F19)
##STR00106##
[0402] Isolated as an off-white powder (0.119 g, 83%).
trans-N-2-Chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-c-
arboxamido)-N-(4-fluorophenethyl)benzamide (F20)
##STR00107##
[0404] Isolated as a tan powder (0.097 g, 71%).
trans-N-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carb-
oxamido)-N-((2,2-difluorocyclopropyl)methoxy)benzamide (F21)
##STR00108##
[0406] Isolated as a brown glass (0.130 g, 70%).
trans-N-2-Chloro-5-(2,2-dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carb-
oxamido)-N-((2,2-difluorocyclopropyl)methoxy)benzamide (F22)
##STR00109##
[0408] Isolated as a brown glass (0.150 g, 81%).
trans-N-2-Chloro-5-(2,2-dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-c-
arboxamido)-N-((2,2-difluorocyclopropyl)methoxy)benzamide (F23)
##STR00110##
[0410] Isolated as a tan foam (0.130 g, 73%).
trans-N-2-Chloro-N-(2-cyclopropylethyl)-5-(2,2-dichloro-3-(3,5-dichlorophe-
nyl)cyclopropane-1-carboxamido)benzamide (F24)
##STR00111##
[0412] Isolated as a tan powder (0.136 g, 78%).
trans-N-2-Chloro-N-(2-cyclopropylethyl)-5-(2,2-dichloro-3-(3,4-dichlorophe-
nyl)cyclopropane-1-carboxamido)benzamide (F25)
##STR00112##
[0414] Isolated as a tan powder (0.134 g, 77%).
trans-N-2-Chloro-N-(2-cyclopropylethyl)-5-(2,2-dichloro-3-(3,4,5-trichloro-
phenyl)cyclopropane-1-carboxamido)benzamide (F26)
##STR00113##
[0416] Isolated as a white powder (0.128 g, 77%).
Example 14: Preparation of
trans-N-benzyl-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropan-
e-1-carboxamido)benzamide (F27)
##STR00114##
[0418] To a solution of phenylmethanamine (0.024 g, 0.23 mmol) in
dichloromethane (2 mL) were added in sequence
1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.054 g, 0.28 mmol),
4-dimethylaminopyridine (0.027 g, 0.23 mmol), and
trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxam-
ido)benzoic acid (C67) (0.085 g, 0.19 mmol). The reaction mixture
was stirred at room temperature for 16 hours. Purification by flash
column chromatography using 0-20% ethyl acetate/hexanes as eluent
provided the title compound as a white solid (0.075 g, 74%).
[0419] The following compounds were prepared in like manner to the
procedure outlined in Example 14:
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(4-fluorobenzyl)benzamide (F28)
##STR00115##
[0421] Isolated as a white solid (0.072 g, 68%).
Example 15: Preparation of
trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbo-
xamido)-N-phenoxybenzamide (F29)
##STR00116##
[0423] To a solution of
trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxam-
ido)benzoic acid (C67) (0.300 g, 0.661 mmol) in dichloromethane (5
mL) stirred at 0.degree. C., were added N,N-dimethylformamide (1
drop) followed by oxalyl chloride (0.0870 mL, 0.992 mmol). The ice
batch was removed and the reaction was allowed to warm to room
temperature over 90 minutes. The reaction was concentrated and the
resultant acid chloride was dissolved in dichloromethane (5 mL) and
cooled in an ice bath. A solution of O-phenylhydroxylamine (0.108
g, 0.992 mmol) and triethylamine (0.230 mL, 1.65 mmol) in
dichloromethane (3 mL) was added dropwise. The mixture was removed
from the ice bath and warmed to room temperature over 1 hour. The
reaction mixture was allowed to stir at room temperature for 16
hours. Purification by flash column chromatography using 0-35%
ethyl acetate/hexanes as eluent followed by trituration with
dichloromethane, filtration, and drying in a vacuum oven at
40.degree. C. overnight provided the title compound as a white
solid (0.0981 g, 27%).
Example 16: Preparation of
trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbo-
xamido)-N-Isobutylbenzamide (F30)
##STR00117##
[0425] To a solution of
trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropanecarboxam-
ido)benzoic acid (C67) (0.0750 g, 0.165 mmol) in dichloromethane (1
mL) were added
1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium
3-oxid hexafluorophosphate (0.0690 g, 0.182 mmol) followed by
diisopropylethylamine (0.0280 g, 0.215 mmol), and the resulting
pale-yellow solution was stirred for 15 minutes, treated with
2-methylpropan-1-amine (0.0150 g, 0.198 mmol), and stirred at room
temperature for approximately 18 hours. The solution was washed
with hydrochloric acid (1 N), and the phases were separated and
dried by passing them through a phase separator cartridge. The
organic phase was concentrated, purified by flash column
chromatography, and dried under vacuum to provide the title
compound as a sticky, viscous, oil that slowly solidifies upon
scratching (0.0810 g, 100%).
[0426] The following compounds were prepared in like manner to the
procedure outlined in Example 16:
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-hexylbenzamide (F31)
##STR00118##
[0428] Isolated as a white solid (0.067 g, 75%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(3,4-difluorobenzyl)benzamide (F32)
##STR00119##
[0430] Isolated as a white solid (0.085 g, 85%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-pentylbenzamide (F33)
##STR00120##
[0432] Isolated as a white solid (0.072 g, 79%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(2,4-dimethoxybenzyl)benzamide (F34)
##STR00121##
[0434] Isolated as a pale-yellow solid (0.084 g, 84%).
trans-2-Chloro-N-(cyclopropylmethyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl-
)cyclopropane-1-carboxamido)benzamide (F35)
##STR00122##
[0436] Isolated as a white solid (0.074 g, 84%).
trans-N-(4-(tert-Butyl)benzyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophe-
nyl)cyclopropane-1-carboxamido)benzamide (F36)
##STR00123##
[0438] Isolated as a white solid (0.061 g, 51%).
trans-2-Chloro-N-(2-cyanoethyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cycl-
opropane-1-carboxamido)benzamide (F37)
##STR00124##
[0440] Isolated as a white solid (0.072 g, 82%).
trans-2-Chloro-N-(3-cyanopropyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyc-
lopropane-1-carboxamido)benzamide (F38)
##STR00125##
[0442] Isolated as a white solid (0.081 g, 90%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(3-(2,2,2-trifluoroethoxy)propyl)benzamide (F39)
##STR00126##
[0444] Isolated as a white solid (0.082 g, 79%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(3,3,3-trifluoropropyl)benzamide (F40)
##STR00127##
[0446] Isolated as a white solid (0.077 g, 81%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(4-(trifluoromethyl)benzyl)benzamide (F41)
##STR00128##
[0448] Isolated as a white solid (0.087 g, 82%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(2-methyl-1-(methylsulfonyl)propan-2-yl)benzamide
(F42)
##STR00129##
[0450] Isolated as a white solid (0.090 g, 88%).
trans-2-Chloro-N-(2-(cyclopropylmethoxy)ethyl)-5-(2,2-dichloro-3-(3,5-dich-
lorophenyl)cyclopropane-1-carboxamido)benzamide (F43)
##STR00130##
[0452] Isolated as a white solid (0.042 g, 44%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(3-fluoropropyl)benzamide (F44)
##STR00131##
[0454] Isolated as a white solid (0.053 g, 59%).
trans-N-Butyl-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane--
1-carboxamido)benzamide (F45)
##STR00132##
[0456] Isolated as a white solid (0.067 g, 76%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-ethylbenzamide (F46)
##STR00133##
[0458] Isolated as a white solid (0.065 g, 82%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(prop-2-yn-1-yl)benzamide (F47)
##STR00134##
[0460] Isolated as a white solid (0.043 g, 53%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(2,2-difluoroethyl)benzamide (F48)
##STR00135##
[0462] Isolated as a white solid (0.065 g, 76%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(2,2,3,3,3-pentafluoropropyl)benzamide (F49)
##STR00136##
[0464] Isolated as a white solid (0.031 g, 32%).
trans-2-Chloro-5-(2,2-chloro-3-(3,5-dichlorophenyl)cyclopropane-1-carboxam-
ido)-N-(4-(dimethylamino)butyl)benzamide(F50)
##STR00137##
[0466] Isolated as a white solid (0.031 g, 36%).
trans-2-Chloro-N-(2-chloroethyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyc-
lopropane-1-carboxamido)benzamide (F51)
##STR00138##
[0468] Isolated as a white solid (0.073 g, 86%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(2-(methylthio)ethyl)benzamide (F52)
##STR00139##
[0470] Isolated as a white solid (0.255 g, 88%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(2-methoxyethyl)benzamide (F53)
##STR00140##
[0472] Isolated as a white solid (0.064 g, 76%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(2-ethoxyethyl)benzamide (F54)
##STR00141##
[0474] Isolated as a white solid (0.066 g, 76%).
trans-N-(2-Acetamidoethyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)-
cyclopropane-1-carboxamido)benzamide (F55)
##STR00142##
[0476] Isolated as a tan solid (0.063 g, 71%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-propylbenzamide (F56)
##STR00143##
[0478] Isolated as a white solid (0.074 g, 90%).
trans-2-Chloro-N-(3-chloropropyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cy-
clopropane-1-carboxamido)benzamide (F57)
##STR00144##
[0480] Isolated as a white solid (0.084 g, 96%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(3-(2-methoxyethoxy)propyl)benzamide (F58)
##STR00145##
[0482] Isolated as a white solid (0.071 g, 75%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-methyl-N-(2,2,2-trifluoroethyl)benzamide (F59)
##STR00146##
[0484] Isolated as a white solid (0.056 g, 62%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(3,3,4,4,4-pentafluorobutyl)benzamide (F60)
##STR00147##
[0486] Isolated as a white solid (0.093 g, 94%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(2,2,3,3,4,4,4-heptafluorobutyl)benzamide (F61)
##STR00148##
[0488] Isolated as a white solid (0.054 g, 52%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-methyl-N-propylbenzamide (F62)
##STR00149##
[0490] Isolated as a white solid (0.071 g, 84%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-ethyl-N-methylbenzamide (F63)
##STR00150##
[0492] Isolated as a white solid (0.077 g, 94%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-methyl-N-(3,3,3-trifluoropropyl)benzamide (F64)
##STR00151##
[0494] Isolated as a white solid (0.083 g, 89%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-methyl-N-(prop-2-yn-1-yl)benzamide (F65)
##STR00152##
[0496] Isolated as a tan solid (0.035 g, 42%).
trans-2-Chloro-N-(cyanomethyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclo-
propane-1-carboxamido)-N-methylbenzamide (F66)
##STR00153##
[0498] Isolated as a light yellow solid (0.023 g, 28%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(2-methoxyethyl)-N-methylbenzamide (F67)
##STR00154##
[0500] Isolated as a light yellow solid (0.064 g, 74%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-methyl-N-(2-(methylthio)ethyl)benzamide (F68)
##STR00155##
[0502] Isolated as a white solid (0.069 g, 77%).
trans-2-Chloro-N-(cyclopropylmethyl)-5-(2,2-dichloro-3-(3,5-dichlorophenyl-
)cyclopropane-1-carboxamido)-N-methylbenzamide (F69)
##STR00156##
[0504] Isolated as a colorless oil (0.066 g, 77%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-((3,3-difluorocyclobutyl)methyl)benzamide (F70)
##STR00157##
[0506] Isolated as a white solid (0.074 g, 80%).
trans-2,2-Dichloro-N-(4-chloro-3-(3,3-difluoropyrrolidine-1-carbonyl)pheny-
l)-3-(3,5-dichlorophenyl)cyclopropane-1-carboxamide (F71)
##STR00158##
[0508] Isolated as a white solid (0.079 g, 88%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(4,4,4-trifluorobutyl)benzamide (F72)
##STR00159##
[0510] Isolated as a white solid (0.090 g, 97%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-((3,3-difluorocyclobutyl)methyl)-N-methylbenzamide
(F73)
##STR00160##
[0512] Isolated as a white solid (0.087 g, 92%).
Example 17a: Preparation of
trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbo-
xamido)-N-(2-(methylsulfinyl)ethyl)benzamide (F74) and
trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbo-
xamido)-N-(2-(methylsulfonyl)ethyl)benzamide (F75)
##STR00161##
[0514] To a solution of
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbo-
xamido)-N-(2-(methylthio)ethyl)benzamide (F52) (0.179 g, 0.340
mmol) in acetic acid (4 mL) was added sodium perborate tetrahydrate
(0.0840 g, 0.540 mmol), and the colorless mixture was warmed to
55.degree. C. and stirred for about 3 hours. The reaction mixture
was diluted with dichloromethane (50 mL) and neutralized by the
slow addition of saturated aqueous sodium bicarbonate. The phases
were separated and the aqueous phase was extracted with
dichloromethane, and the combined organic layers were washed with
brine, dried by passing through a phase separator cartridge, and
concentrated. Purification by flash column chromatography using
0-100% ethyl acetate/hexanes followed by 1:1
dichloromethane/methanol as eluent and drying in a vacuum oven
(house vacuum) at 47.degree. C. overnight provided (F74) as a white
solid (0.048 g, 26%) and (F75) as a white solid (0.135 g, 71%).
Example 17b: Preparation of 5-amino-2-chloro-N-methylbenzamide
(C68)
##STR00162##
[0516] To a solution of 2-chloro-N-methyl-5-nitrobenzamide (C81)
(0.280 g, 1.31 mmol) in methanol (8.70 mL) and water (4.35 mL) were
added iron powder (0.364 g, 6.52 mmol) and ammonium chloride (0.209
g, 3.91 mmol). The reaction was heated at 60.degree. C. for 2
hours. The reaction was filtered through Celite.RTM.. The filtrate
was diluted with dichloromethane and extracted with hydrochloric
acid (1 N). The combined aqueous phases were neutralized with
saturated aqueous sodium bicarbonate and extracted with
dichloromethane. The combined organic phases were dried over
magnesium sulfate, filtered, and concentrated to give the title
compound as a yellow solid (0.0720 g, 22%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.09 (d, J=8.5 Hz, 1H), 6.89 (d, J=2.9 Hz, 1H),
6.61 (dd, J=8.6, 2.9 Hz, 1H), 6.53 (s, 1H), 3.92 (s, 2H), 2.96 (d,
J=4.9 Hz, 3H); EIMS m/z 185 ([M].sup.+).
[0517] The following compounds were prepared in like manner to the
procedure outlined in Example 17b:
5-Amino-N-methyl-2-(trifluoromethyl)benzamide (C69)
##STR00163##
[0519] Isolated as a white solid (0.067 g, 75%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.43 (d, J=8.5 Hz, 1H), 6.74 (d, J=2.4 Hz,
1H), 6.71-6.66 (m, 1H), 5.76 (s, 1H), 4.07 (s, 2H), 2.98 (d, J=4.9
Hz, 3H); IR (thin film) 3465, 3350, 1612 cm.sup.-1; EIMS m/z 218
([M].sup.+).
5-Amino-2-chloro-N-(2,2,2-trifluoroethyl)benzamide (C70)
##STR00164##
[0521] Isolated as a white solid (0.067 g, 75%): .sup.1H NMR (400
MHz, DMSO-d.sub.6) .delta. 8.98 (t, J=6.3 Hz, 1H), 7.08 (d, J=8.5
Hz, 1H), 6.64-6.52 (m, 2H), 5.46 (s, 2H), 4.01 (qd, J=9.7, 6.5 Hz,
2H); IR (thin film) 3428, 3281, 1656 cm.sup.-1; ESIMS m/z 254
([M+H].sup.+).
5-Amino-2-chloro-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide
(C71)
##STR00165##
[0523] Isolated as a white solid (0.067 g, 75%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 8.03 (t, J=6.3 Hz, 1H), 7.69 (t, J=5.2 Hz,
1H), 6.68-6.58 (m, 2H), 6.51 (d, J=6.4 Hz, 1H), 4.27 (s, 2H),
3.96-3.70 (m, 4H); IR (thin film) 3307, 2941, 1693, 1647 cm.sup.-1;
ESIMS m/z 311 ([M+H].sup.+).
Example 18: Preparation of
5-amino-2-chloro-N-(pyridin-3-ylmethyl)benzamide (C72)
##STR00166##
[0525] 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride
(0.840 g, 4.40 mmol) and 4-dimethylaminopyridine (0.460 g, 3.80
mmol) were sequentially added to a stirred mixture of
5-amino-2-chlorobenzoic acid (0.500 g, 2.90 mmol) and
pyridin-3-ylmethanamine (0.360 mL, 3.50 mmol) in dichloromethane
(12 mL) at 23.degree. C. The resulting heterogeneous pink reaction
mixture was stirred at 23.degree. C. for 2 hours.
N,N-Dimethylformamide (6 mL) was added to improve solubility and
the resulting homogeneous orange solution was stirred at 23.degree.
C. for 70 hours. The reaction mixture was concentrated, and the
residue was purified by reverse phase column chromatography using
5-100% acetonitrile/water as eluent to provide the title compound
as a light brown powder (0.650 g, 86%): mp 133-136.degree. C.;
.sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 8.89 (br t, J=6 Hz,
1H), 8.55 (d, J=1.5 Hz, 1H), 8.47 (dd, J=5, 1.5 Hz, 1H), 7.73 (dt,
J=8, 1.5 Hz, 1H), 7.37 (ddd, J=8, 5, 0.8 Hz, 1H), 7.07 (d, J=8 Hz,
1H), 6.55-6.62 (m, 2H), 5.41 (br s, 2H), 4.42 (d, J=6 Hz, 2H); IR
(thin film) 3432 (m), 3340 (m), 3195 (m), 3025 (m), 1654 (s), 1626
(s), 1602 (s), 1559 (s), 1474 (s), 1439 (s), 1428 (s) cm.sup.-1;
ESIMS m/z 262 ([M+H].sup.+).
[0526] The following compounds were prepared in like manner to the
procedure outlined in Example 18:
5-Amino-2-chloro-N-(pyridin-2-ylmethyl)benzamide (C73)
##STR00167##
[0528] Isolated as a white solid (0.067 g, 75%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 8.55 (br d, J=5 Hz, 1H), 7.69 (td, J=7.5,
2 Hz, 1H), 7.52 (br s, 1H), 7.35 (d, J=7.5 Hz, 1H), 7.21 (dd,
J=7.5, 5 Hz, 1H), 7.16 (d, J=8.5 Hz, 1H), 7.04 (d, J=3 Hz, 1H),
6.67 (dd, J=8.5, 3 Hz, 1H), 4.78 (d, J=5 Hz, 2H), 3.77 (br s, 2H);
IR (thin film) 3340 (m), 3223 (m), 3055 (w), 1640 (s), 1594 (s),
1571 (s), 1520 (s), 1474 (s), 1435 (s) cm.sup.-1; ESIMS m/z 262
([M+H].sup.+).
5-Amino-2-chloro-N-(pyridin-4-ylmethyl)benzamide (C74)
##STR00168##
[0530] Isolated as a white solid (0.067 g, 75%): mp 122-125.degree.
C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.56-8.60 (m, 2H),
7.28-7.31 (m, 2H), 7.17 (d, J=8.5 Hz, 1H), 7.08 (d, J=3 Hz, 1H),
6.79 (br s, 1H), 6.69 (dd, J=8.5, 3 Hz, 1H), 4.67 (d, J=6 Hz, 2H),
3.81 (br s, 2H); IR (thin film) 3428 (w), 3240 (m), 3056 (w), 1651
(s), 1596 (s), 1543 (s), 1478 (s), 1416 (s) cm.sup.-1; ESIMS m/z
262 ([M+H].sup.+).
5-Amino-2-chloro-N-(4-fluorophenethyl)benzamide (C75)
##STR00169##
[0532] Isolated as a white solid (0.067 g, 75%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 8.32 (br t, J=5.5 Hz, 1H), 7.28 (m, 2H),
7.12 (m, 2H), 7.03 (d, J=8.5 Hz, 1H), 6.56 (dd, J=8.5, 3 Hz, 1H),
6.51 (d, J=3 Hz, 1H), 5.37 (br s, 2H), 3.39 (m, 2H), 2.79 (t, J=7.2
Hz, 2H); IR (thin film) 3482 (w), 3366 (w), 3302 (m), 3070 (w),
2946 (w), 1637 (s), 1596 (m), 1544 (m), 1508 (m), 1474 (m), 1436
(m) cm.sup.-1; ESIMS m/z 293 ([M+H].sup.+).
5-Amino-2-chloro-N-(2-cyclopropylethyl)benzamide (C76)
##STR00170##
[0534] Isolated as a white solid (0.067 g, 75%): .sup.1H NMR (400
MHz, DMSO-d.sub.6) .delta. 8.23 (br t, J=6 Hz, 1H), 7.04 (d, J=9
Hz, 1H), 6.53-6.59 (m, 2H), 5.36 (br s, 2H), 3.23 (td, J=7, 6 Hz,
2H), 1.38 (q, J=7 Hz, 2H), 0.74 (m, 1H), 0.38-0.44 (m, 2H),
0.03-0.08 (m, 2H); IR (thin film) 3281 (m), 3076 (w), 3000 (w),
2914 (w), 1634 (s), 1595 (m), 1579 (m), 1552 (m), 1476 (m), 1433
(m) cm.sup.-1; ESIMS m/z 239 ([M+H].sup.+).
Example 19: Preparation of N-(allyloxy)-5-amino-2-chlorobenzamide
(C77)
##STR00171##
[0536] 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride
(0.840 g, 4.40 mmol) and 4-dimethylaminopyridine (0.460 g, 3.80
mmol) were sequentially added to a stirred mixture of
5-amino-2-chlorobenzoic acid (0.500 g, 2.90 mmol),
O-allylhydroxylamine hydrochloride (0.380 g, 3.50 mmol), and
triethylamine (0.490 mL, 3.50 mmol) in dichloromethane (15 mL) at
23.degree. C. The resulting homogeneous gray solution was stirred
at 23.degree. C. for 48 hours. The reaction mixture was
concentrated, and the residue was purified by reverse phase flash
column chromatography using 5-100% acetonitrile/water as eluent to
provide the title compound as a light brown oil (0.440 g, 67%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.13 (d, J=9 Hz, 1H),
6.95 (d, J=2.5 Hz, 1H), 6.66 (dd, J=9, 2.5 Hz, 1H), 6.05 (m, 1H),
5.32-5.45 (m, 2H), 4.53 (d, J=6 Hz, 2H), 3.79 (br s, 2H); IR (thin
film) 3346 (w), 3214 (w), 2935 (w), 1629 (s), 1598 (s), 1575 (s),
1474 (s), 1433 (m), 1330 (m), 1271 (m) cm.sup.-1; ESIMS m/z 227
([M+H].sup.+).
[0537] The following compounds were prepared in like manner to the
procedure outlined in Example 19:
5-Amino-2-chloro-N-(cyclopropylmethoxy)benzamide (C78)
##STR00172##
[0539] Isolated as a white solid (0.067 g, 75%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.13 (d, J=8.5 Hz, 1H), 6.95 (d, J=2.5 Hz,
1H), 6.67 (dd, J=8.5, 2.5 Hz, 1H), 3.88 (br d, J=7 Hz, 2H), 3.81
(br s, 2H), 1.21 (m, 1H), 0.57-0.66 (m, 2H), 0.32-0.39 (m, 2H); IR
(thin film) 3344 (w), 3215 (w), 2936 (w), 1644 (s), 1599 (s), 1526
(m), 1474 (s), 1431 (m) cm.sup.-1; ESIMS m/z 241 ([M+H].sup.+).
5-Amino-2-chloro-N-((4-fluorobenzyl)oxy)benzamide (C79)
##STR00173##
[0541] Isolated as a white solid (0.067 g, 75%).
Example 20: Preparation of
5-amino-2-chloro-N-((2,2-difluorocyclopropyl)methoxy)benzamide
(C80)
##STR00174##
[0543] 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride
(0.900 g, 4.70 mmol) and 4-dimethylaminopyridine (0.500 g, 4.10
mmol) were sequentially added to a stirred mixture of
5-amino-2-chlorobenzoic acid (0.535 g, 3.10 mmol),
O-((2,2-difluorocyclopropyl)methyl)hydroxylamine hydrochloride
(0.500 g, 3.10 mmol), and triethylamine (0.520 mL, 3.70 mmol) in
dichloromethane (16 mL) at 23.degree. C. The resulting homogeneous
light pink solution was stirred at 23.degree. C. for 24 hours. The
reaction mixture was concentrated, and the residue was purified by
reverse phase flash column chromatography using 5-100%
acetonitrile/water as eluent to provide the title compound as a
brown semi-solid (0.560 g, 65%): .sup.1H NMR (400 MHz,
DMSO-d.sub.6) .delta. 11.51 (br s, 1H), 7.06 (d, J=8.3 Hz, 1H),
6.55-6.61 (m, 2H), 5.41 (br s, 2H), 3.96 (m, 1H), 3.85 (m, 1H),
2.08 (m, 1H), 1.67 (m, 1H), 1.39 (m, 1H); IR (thin film) 3343 (w),
3211 (w), 2937 (w), 1645 (m), 1600 (s), 1527 (m), 1472 (s), 1437
(m) cm.sup.-1; ESIMS m/z 277 ([M+H].sup.+).
Example 21: Preparation of 2-chloro-N-methyl-5-nitrobenzamide
(C81)
##STR00175##
[0545] 2-Chloro-5-nitrobenzoic acid (0.500 g, 2.48 mmol),
diisopropylethylamine (0.650 mL, 3.72 mmol), and
4-dimethylaminopyridine (0.545 g, 4.47 mmol) were sequentially
added to a stirred mixture of methanamine hydrochloride (0.251 g,
3.72 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide
hydrochloride (0.951 g, 4.96 mmol) in 1,2-dichloroethane (25 mL) at
room temperature. The reaction mixture was diluted with
dichloromethane and washed with saturated aqueous sodium
bicarbonate and hydrochloric acid (1 N). The organic phase was
dried over magnesium sulfate, filtered, and concentrated to give
the title compound as a white solid (0.283 g, 50%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 8.53 (d, J=2.7 Hz, 1H), 8.22 (dd,
J=8.8, 2.8 Hz, 1H), 7.60 (d, J=8.8 Hz, 1H), 6.21 (s, 1H), 3.08 (d,
J=4.9 Hz, 3H); EIMS m/z 215 ([M].sup.+).
[0546] The following compounds were prepared in like manner to the
procedure outlined in Example 21:
N-Methyl-5-nitro-2-(trifluoromethyl)benzamide (C82)
##STR00176##
[0548] Isolated as a white solid (0.067 g, 75%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 8.41-8.34 (m, 2H), 7.92 (d, J=8.4 Hz, 1H),
5.87 (s, 1H), 3.06 (d, J=4.9 Hz, 3H); EIMS m/z 248 ([M].sup.+).
2-Chloro-5-nitro-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide
(C83)
##STR00177##
[0550] Isolated as a white solid (0.067 g, 75%): .sup.1H NMR (400
MHz, DMSO-d.sub.6) .delta. 9.04 (t, J=5.9 Hz, 1H), 8.70 (t, J=6.3
Hz, 1H), 8.34-8.28 (m, 2H), 7.83 (d, J=8.6 Hz, 1H), 4.03-3.92 (m,
4H); IR (thin film) 3293, 3089, 1694, 1654 cm.sup.-1; ESIMS m/z 341
([M+H].sup.+).
Example 22: Preparation of
2-chloro-5-nitro-N-(2,2,2-trifluoroethyl)benzamide (C84)
##STR00178##
[0552] 2-Chloro-5-nitrobenzoic acid (0.500 g, 2.48 mmol) and
4-dimethylaminopyridine (0.394 g, 3.22 mmol) were sequentially
added to a stirred mixture of 2,2,2-trifluoroethanamine (0.295 g,
2.98 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide
hydrochloride (0.713 g, 3.72 mmol) in 1,2-dichloroethane (12 mL) at
room temperature, and the mixture was stirred at room temperature
for 1 day. The reaction mixture was diluted with dichloromethane
and washed with saturated aqueous sodium bicarbonate followed by
hydrochloric acid (1 N) to provide the title compound as a white
solid (0.379 g, 51%): .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
9.42 (t, J=6.2 Hz, 1H), 8.32 (dd, J=8.8, 2.8 Hz, 1H), 8.25 (d,
J=2.7 Hz, 1H), 7.86 (d, J=8.8 Hz, 1H), 4.13 (qd, J=9.7, 6.4 Hz,
2H); IR (thin film) 3378, 2964, 1739, 1675 cm.sup.-1; ESIMS m/z 284
([M+H].sup.+).
[0553] The following molecules in Table 1 may be prepared according
to the procedures disclosed in
TABLE-US-00002 TABLE P1 Structure and preparation method for
prophetic molecules No. Structure Prep* P1 ##STR00179## 13, 16 P2
##STR00180## 13, 16 P3 ##STR00181## 13, 16 P4 ##STR00182## 13, 16,
.sup. 17a P5 ##STR00183## 13, 16, .sup. 17a P6 ##STR00184## 13, 16,
.sup. 17a P7 ##STR00185## 13, 16, .sup. 17a P8 ##STR00186## 13, 16
P9 ##STR00187## 13, 16 P10 ##STR00188## 13, 16 P11 ##STR00189## 13,
16 P12 ##STR00190## 13, 16 P13 ##STR00191## 13, 16 P14 ##STR00192##
13, 16 P15 ##STR00193## 13, 16 P16 ##STR00194## 13, 16 Prep* means
prepare according to Example or Scheme
[0554] The following compounds were prepared in like manner to the
procedure outlined in Example 2:
trans-2,2-Dichloro-3-(3-chloro-5-(difluoromethyl)phenyl)cyclopropane-1-car-
boxylic acid (C85)
##STR00195##
[0556] Isolated as an off-white solid (2.6 g, 63%): .sup.1H NMR
(300 MHz, CDCl.sub.3) missing COOH signal .delta. 7.49 (s, 1H),
7.38 (s, 1H), 7.30 (s, 1H), 6.63 (t, J=56.0 Hz, 1H), 3.50 (d, J=8.4
Hz, 1H), 2.91 (d, J=8.0 Hz, 1H); .sup.19F NMR (282 MHz, CDCl.sub.3)
.delta. -112.04; ESIMS m/z 313 ([M-H].sup.-).
trans-2,2-Dichloro-3-(4-chloro-3-(difluoromethyl)phenyl)cyclopropane-1-car-
boxylic acid (C86)
##STR00196##
[0558] Isolated as an off-white solid (6.2 g, 69%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 10.5 (br s, 1H), 7.55 (s, 1H), 7.46
(d, J=8.0 Hz, 1H), 7.34 (d, J=8.4 Hz, 1H), 6.95 (t, J=54.8 Hz, 1H),
3.50 (d, J=8.4 Hz, 1H), 2.91 (d, J=8.4 Hz, 1H); .sup.19F NMR (376
MHz, CDCl.sub.3) .delta. -115.52; ESIMS m/z 313 ([M-H].sup.-).
trans-2,2-Dichloro-3-(3-(difluoromethyl)-5-fluorophenyl)cyclopropane-1-car-
boxylic acid (C87)
##STR00197##
[0560] Isolated as an off-white solid (5 g, 38%): .sup.1H NMR (400
MHz, CDCl.sub.3) missing COOH signal .delta. 7.23-7.21 (m, 2H),
7.11 (d, J=8.8 Hz, 1H), 6.64 (t, J=55.6 Hz, 1H), 3.51 (d, J=8.4 Hz,
1H), 2.91 (d, J=8.0 Hz, 1H); .sup.19F NMR (376 MHz, CDCl.sub.3)
.delta. -110.37; ESIMS m/z 297.19 ([M-H].sup.-).
trans-2,2-Dichloro-3-(3-(difluoromethyl)-4-fluorophenyl)cyclopropane-1-car-
boxylic acid (C88)
##STR00198##
[0562] Isolated as an off-white solid (6.0 g, 77%): .sup.1H NMR
(400 MHz, CDCl.sub.3) missing COOH signal .delta. 7.49 (d, J=6.0
Hz, 1H), 7.40 (br s, 1H), 7.17 (t, J=9.2 Hz, 1H), 6.90 (t, J=54.8
Hz, 1H), 3.49 (d, J=8.0 Hz, 1H), 2.89 (d, J=8.4 Hz, 1H); .sup.19F
NMR (376 MHz, CDCl.sub.3) .delta. -114.47, -119.69; ESIMS m/z 297
([M-H].sup.-).
trans-2,2-Dichloro-3-(3-chloro-4-(difluoromethyl)phenyl)cyclopropane-1-car-
boxylic acid (C89)
##STR00199##
[0564] Isolated as an off-white solid (3.5 g, 42%): .sup.1H NMR
(400 MHz, CDCl.sub.3) missing COOH signal .delta. 7.68 (d, J=7.6
Hz, 1H), 7.35 (s, 1H), 7.29 (d, J=8.4 Hz, 1H), 6.94 (t, J=54.8 Hz,
1H), 3.48 (d, J=8.4 Hz, 1H), 2.91 (d, J=8.4 Hz, 1H); .sup.19F NMR
(376 MHz, CDCl.sub.3) .delta. -115.46; ESIMS m/z 313
([M-H].sup.-).
trans-2,2-Dichloro-3-(4-(difluoromethyl)-3-fluorophenyl)cyclopropane-1-car-
boxylic acid (C90)
##STR00200##
[0566] Isolated as an off-white solid (4.4 g, 77%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.62 (t, J=7.6 Hz, 1H), 7.18 (d,
J=7.6 Hz, 1H), 7.06 (d, J=10.0 Hz, 1H), 6.89 (t, J=54.8 Hz, 1H),
3.50 (d, J=8.4 Hz, 1H), 2.90 (d, J=8.4 Hz, 1H); .sup.19F NMR (376
MHz, CDCl.sub.3) .delta. -114.42, -118.63; ESIMS m/z 297.15
([M-H].sup.-).
trans-2,2-Dichloro-3-(3-(difluoromethyl)phenyl)cyclopropane-1-carboxylic
acid (C91)
##STR00201##
[0568] Isolated as an off-white solid (6.2 g, 53%): .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 7.49 (br s, 2H), 7.41 (br s, 2H),
6.66 (t, J=56.0 Hz, 1H), 3.53 (d, J=8.4 Hz, 1H), 2.92 (d, J=8.0 Hz,
1H); .sup.19F NMR (282 MHz, CDCl.sub.3) .delta. -111.20; ESIMS m/z
279.20 ([M-H].sup.-).
trans-2,2-Dichloro-3-(4-(difluoromethyl)phenyl)cyclopropane-1-carboxylic
acid (C92)
##STR00202##
[0570] Isolated as an off-white solid (7 g, 61%): .sup.1H NMR (300
MHz, CDCl.sub.3) .delta. 7.53 (d, J=8.0 Hz, 2H), 7.37 (d, J=8.0 Hz,
2H), 6.66 (t, J=56.4 Hz, 1H), 3.52 (d, J=8.4 Hz, 1H), 2.92 (d,
J=8.0 Hz, 1H); .sup.19F NMR (282 MHz, CDCl.sub.3) .delta. -112.20;
ESIMS m/z 279.30 ([M-H].sup.-).
trans-2,2-Dichloro-3-(3,5-difluoro-4-methoxyphenyl)cyclopropane-1-carboxyl-
ic acid (C93)
##STR00203##
[0572] Isolated as a tan solid (0.440 g, 53%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 10.72 (s, 1H), 6.89-6.77 (m, 2H), 4.02 (t,
J=1.2 Hz, 3H), 3.39 (d, J=8.3 Hz, 1H), 2.80 (d, J=8.3 Hz, 1H);
.sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -127.43, -127.43,
-127.44; ESIMS m/z 296 ([M-H].sup.-).
cis/trans-2,2-Dichloro-3-(3,4,5-trifluorophenyl)cyclopropane-1-carboxylic
acid (C94)
##STR00204##
[0574] Isolated as a white solid (0.411 g, 53%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.72 (s, 1H), 7.06-6.74 (m, 2H), 3.46-3.23
(m, 1H), 3.01-2.74 (m, 1H); .sup.19F NMR (376 MHz, CDCl.sub.3)
.delta. -132.88, -132.94, -133.81, -133.87, -159.60, -159.65,
-159.71, -160.34, -160.39, -160.45; ESIMS m/z 284
([M-H].sup.-).
[0575] The following compounds were prepared in like manner to the
procedure outlined in Example 4:
trans-1-Chloro-3-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-5-(difluoro-
methyl)benzene (C95)
##STR00205##
[0577] Isolated as a yellow liquid (11.5 g, 69%): .sup.1H NMR (300
MHz, CDCl.sub.3): .delta. 7.47 (s, 2H), 7.39 (s, 1H), 7.28 (d,
J=8.7 Hz, 2H), 6.93 (d, J=8.7 Hz, 2H), 6.64 (t, J=56.1 Hz, 1H),
3.83 (s, 3H), 3.16 (q, J=8.7 Hz, 2H).
trans-1-Chloro-4-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-2-(difluoro-
methyl)benzene (C96)
##STR00206##
[0579] Isolated as a pale yellow solid (10.7 g, 83%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.65 (s, 1H), 7.46-7.41 (m, 2H), 7.28
(d, J=8.4 Hz, 2H), 7.10-6.83 (m, 3H), 3.83 (s, 3H), 3.18-3.13 (m,
2H).
trans-1-(2,2-Dichloro-3-(4-methoxyphenyl)cyclopropyl)-3-(difluoromethyl)-5-
-fluorobenzene (C97)
##STR00207##
[0581] Isolated as an off-white solid (16.5 g, 64%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.29 (d, J=8.8 Hz, 2H), 7.20 (d,
J=8.8 Hz, 2H), 6.93 (d, J=8.8 Hz, 2H), 6.65 (t, J=56.0 Hz, 2H),
3.83 (s, 3H), 3.16 (s, 2H).
trans-4-(2,2-Dichloro-3-(4-methoxyphenyl)cyclopropyl)-2-(difluoromethyl)-1-
-fluorobenzene (C98)
##STR00208##
[0583] Isolated as an off-white solid (10.0 g, 55%): ESIMS m/z 374
([M+H].sup.+).
trans-2-Chloro-4-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-1-(difluoro-
methyl)benzene (C99)
##STR00209##
[0585] Isolated as an off-white solid (10.0 g, 34%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.68 (d, J=8.0 Hz, 1H), 7.43 (s, 1H),
7.38 (d, J=8.4 Hz, 1H), 7.28-7.25 (m, 2H), 7.09-6.92 (m, 3H), 3.83
(s, 3H), 3.15 (q, J=12.0 Hz, 2H); ESIMS m/z 376 ([M+H].sup.+).
trans-2-Fluoro-4-(2,2-dichloro-3-(4-methoxyphenyl)cyclopropyl)-1-(difluoro-
-methyl) benzene (C100)
##STR00210##
[0587] Isolated as a pale yellow liquid (6.9 g, 58%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.31 (t, J=7.6 Hz, 1H), 7.27 (d,
J=9.2 Hz, 2H), 7.14 (d, J=10.8 Hz, 1H), 7.04-6.76 (m, 4H), 3.83 (s,
3H), 3.16 (t, J=8.8 Hz, 2H); .sup.19F NMR (376 MHz, CDCl.sub.3)
.delta. -114.14, -114.32, -119.30.
trans-1-(2,2-Dichloro-3-(4-methoxyphenyl)cyclopropyl)-3-(difluoromethyl)
benzene (C101)
##STR00211##
[0589] Isolated as a pale yellow solid (6.3 g, 95%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.50 (br s, 4H), 7.29 (d, J=8.8 Hz,
2H), 6.93 (d, J=8.0 Hz, 2H), 6.67 (t, 1H), 3.83 (s, 3H), 3.19 (s,
2H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -110.87,
-111.02.
trans-1-(2,2-Dichloro-3-(4-(difluoromethyl)phenyl)cyclopropyl)-4-methoxybe-
nzene (C102)
##STR00212##
[0591] Isolated as a white solid (14 g, 69%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.54 (d, J=8.0 Hz, 2H), 7.46 (d, J=8.0 Hz, 2H),
7.28 (t, J=8.4 Hz, 2H), 6.93 (d, J=8.0 Hz, 2H), 6.67 (t, J=56.8 Hz,
1H), 3.83 (s, 3H), 3.18 (s, 2H).
[0592] The following compounds were prepared in like manner to the
procedure outlined in Example 12:
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-methoxyphenyl)cyclopropan-
e-1-carboxamido)benzoic acid (C103)
##STR00213##
[0594] Isolated as a cream-colored solid (1.565 g, 90%): mp
227-231.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
13.48 (s, 1H), 10.89 (s, 1H), 8.16 (d, J=2.4 Hz, 1H), 7.78 (dd,
J=8.7, 2.4 Hz, 1H), 7.61 (s, 2H), 7.53 (d, J=8.7 Hz, 1H), 3.84 (s,
3H), 3.57 (d, J=8.4 Hz, 1H), 3.45 (d, J=8.5 Hz, 1H); .sup.13C NMR
(101 MHz, DMSO-d.sub.6) .delta. 166.27, 162.66, 151.18, 137.58,
131.44, 131.42, 131.22, 129.72, 128.18, 125.90, 122.87, 121.16,
62.19, 60.64, 38.51, 36.44; HRMS-ESI (m/z) [M+].sup.+ calcd for
C.sub.18H.sub.12Cl.sub.5NO.sub.4, 480.9209. found, 480.9216.
trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-c-
arboxamido)benzoic acid (C104)
##STR00214##
[0596] Isolated as a white solid (6.589 g, 93%): mp 207-210.degree.
C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 13.50 (s, 1H),
10.95 (s, 1H), 8.18 (d, J=2.5 Hz, 1H), 7.80 (dd, J=8.7, 2.5 Hz,
1H), 7.71 (d, J=7.2 Hz, 1H), 7.51 (dd, J=28.2, 8.8 Hz, 3H), 3.59
(d, J=8.4 Hz, 1H), 3.43 (d, J=8.5 Hz, 1H); .sup.13C NMR (101 MHz,
DMSO-d.sub.6) .delta. 166.22, 162.68, 158.01, 155.55, 137.53,
131.37, 131.17, 131.00, 130.95, 130.91, 129.74, 129.67, 125.86,
122.82, 121.12, 119.49, 119.32, 116.91, 116.70, 62.21, 38.49,
36.58; .sup.19F NMR
[0597] (376 MHz, DMSO-d.sub.6) .delta. -117.26; ESIMS m/z 438
([M+H].sup.+).
trans-2,3-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-ca-
rboxamido)benzoic acid (C105)
##STR00215##
[0599] Isolated as a tan solid (1.685 g, 79%): mp 231-235.degree.
C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) 13.82 (s, 1H), 11.05 (s,
1H), 8.13 (d, J=2.4 Hz, 1H), 7.97 (d, J=2.4 Hz, 1H), 7.63 (s, 1H),
7.56 (s, 2H), 3.63 (d, J=8.5 Hz, 1H), 3.50 (d, J=8.5 Hz, 1H);
.sup.13C NMR (101 MHz, DMSO-d.sub.6) .delta. 165.84, 162.96,
138.00, 137.09, 134.14, 133.98, 133.01, 127.83, 127.64, 123.41,
122.15, 119.27, 61.94, 38.37, 36.78; HRMS-ESI (m/z) [M+].sup.+
calcd for C.sub.17H.sub.9Cl.sub.6NO.sub.3, 484.8714. found,
484.8711.
trans-2,4-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-ca-
rboxamido)benzoic acid (C106)
##STR00216##
[0601] Isolated as a light-yellow solid (0.855 g, 42%): mp
263-266.degree. C.; .sup.1H NMR (500 MHz, DMSO-d.sub.6) .delta.
13.67 (s, 1H), 10.37 (s, 1H), 8.37 (s, 1H), 7.85 (s, 1H), 7.63 (s,
1H), 7.53 (d, J=1.6 Hz, 2H), 3.82 (d, J=8.6 Hz, 1H), 3.63 (d, J=8.5
Hz, 1H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 165.41,
163.35, 137.17, 133.95, 133.66, 131.17, 129.96, 128.80, 128.24,
127.74, 127.60, 126.63, 62.37, 37.24, 37.09; HRMS-ESI (m/z)
[M+].sup.+ calcd for C.sub.17H.sub.9Cl.sub.6NO.sub.3, 484.8714.
found, 484.8715.
[0602] The following compounds were prepared in like manner to the
procedure outlined in Example 13:
trans-2-Chloro-5-(2,2-dibromo-3-(3,5-dichlorophenyl)cyclopropane-1-carboxa-
mido)-N-(2,2,2-trifluoroethyl)benzamide (PF1)
##STR00217##
[0604] Isolated as a white solid (0.100 g, 32%)
[0605] The following compounds were prepared in like manner to the
procedure outlined in Example 15:
2-Chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cycopropane-1-carboxa-
mido)-N-(2-(4-fluorophenyl)propan-2-yl)benzamide (F97)
##STR00218##
[0607] Isolated as a white foam (0.086 g, 63%).
[0608] The following compounds were prepared in like manner to the
procedure outlined in Example 16:
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
-amido)-N--((R)-1-((3,3,3-trifluoropropyl)thio)propan-2-yl)benzamide
(PF2)
##STR00219##
[0610] Isolated as a white solid (0.311 mg, 91%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
-amido)-N--((R)-1-((2,2,2-trifluoroethyl)thio)propan-2-yl)benzamide
(PF3)
##STR00220##
[0612] Isolated as a white solid (0.306 g, 91%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(2-((furan-2-ylmethyl)thio)ethyl)benzamide (PF9)
##STR00221##
[0614] Isolated as a tan solid (0.064 g, 65%).
trans-Methyl-2-(2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropan-
e-1-carboxamido)benzamido)-4-(methylthio)butanoate (PF10)
##STR00222##
[0616] Isolated as a light green solid (0.052 g, 52%).
trans-N-(4-(1H-1,2,4-Triazol-1-yl)benzyl)-2-chloro-5-(2,2-dichloro-3-(3,5--
dichlorophenyl)cyclcopropane-1-carboxamido)benzamide (PF11)
##STR00223##
[0618] Isolated as a tan solid (0.077 g, 76%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
-amido)-N-(2-(thiazol-2-yl)ethyl)benzamide (PF12)
##STR00224##
[0620] Isolated as a white solid (0.032 g, 34%).
trans-N-(2-(1H-Pyrazol-1-yl)ethyl)-2-chloro-5-(2,2-dichloro-3-(3,5-dichlor-
o-phenyl)cyclopropane-1-carboxamido)benzamide (PF13)
##STR00225##
[0622] Isolated as a white solid (0.061 g, 68%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
-amido)-N-(3-sulfamoylpropyl)benzamide (PF14)
##STR00226##
[0624] Isolated as a white solid (0.023 g, 24%).
trans-N-(2-(Benzo[b]thiophen-3-yl)ethyl)-2-chloro-5-(2,2-dichloro-3-(3,5-d-
ichlorophenyl)cyclopropane-1-carboxamido)benzamide (PF15)
##STR00227##
[0626] Isolated as a tan solid (0.064 g, 63%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
-amido)-N-(3,3,3-trifluoro-2-hydroxypropyl)benzamide (PF16)
##STR00228##
[0628] Isolated as a white solid (0.055 g, 59%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(2-hydroxypropyl)benzamide (F78)
##STR00229##
[0630] Isolated as a white solid (0.036 g, 43%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-(2-(2-oxoimidazolidin-1-yl)ethyl)benzamide (F79)
##STR00230##
[0632] Isolated as a white solid (0.038 g, 41%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-methoxyphenyl)cyclopropan-
e-1-carboxamido)-N-propylbenzamide (F84)
##STR00231##
[0634] Isolated as a white solid (0.125 g, 92%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-methoxyphenyl)cyclopropan-
e-1-carboxamido)-N-ethylbenzamide (F85)
##STR00232##
[0636] Isolated as a white solid (0.126 g, 95%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-methoxyphenyl)cyclopropan-
e-1-carboxamido)-N-(2-fluoroethyl)benzamide (F86)
##STR00233##
[0638] Isolated as a white solid (0.119 g, 87%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-methoxyphenyl)cyclopropan-
e-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F87)
##STR00234##
[0640] Isolated as a white solid (0.128 g, 88%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichloro-4-methoxyphenyl)cyclopropan-
e-1-carboxamido)-N-(3,3,3-trifluoropropyl)benzamide (F88)
##STR00235##
[0642] Isolated as a white solid (0.138 g, 92%).
trans-2,3-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-ca-
rboxamido)-N-ethylbenzamide (F91)
##STR00236##
[0644] Isolated as a white solid (0.038 g, 43%).
trans-2,3-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-ca-
rboxamido)-N-(2-fluoroethyl)benzamide (F92)
##STR00237##
[0646] Isolated as a white solid (0.037 g, 40%).
trans-2,3-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-ca-
rboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F93)
##STR00238##
[0648] Isolated as a white solid (0.013 g, 13%).
trans-2,3-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-ca-
rboxamido)-N-(3,3,3-trifluoropropyl)benzamide (F94)
##STR00239##
[0650] Isolated as a white solid (0.046 g, 46%).
trans-2,3-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-ca-
rboxamido)-N-propylbenzamide (F95)
##STR00240##
[0652] Isolated as a white solid (0.061 g, 68%).
trans-2,4-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-ca-
rboxamido)-N-ethylbenzamide (F98)
##STR00241##
[0654] Isolated as a white solid (0.052 g, 57%).
trans-2,4-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-ca-
rboxamido)-N-(2-fluoroethyl)benzamide (F99)
##STR00242##
[0656] Isolated as a white solid (0.047 g, 51%).
trans-2,4-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-ca-
rboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F100)
##STR00243##
[0658] Isolated as a white solid (0.041 g, 43%).
trans-2,4-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-ca-
rboxamido)-N-propylbenzamide (F101)
##STR00244##
[0660] Isolated as a white solid (0.037 g, 40%).
trans-2,4-Dichloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-ca-
rboxamido)-N-(3,3,3-trifluoropropyl)benzamide (F102)
##STR00245##
[0662] Isolated as a white solid (0.046 g, 48%).
trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-c-
arboxamido)-N-ethylbenzamide (F103)
##STR00246##
[0664] Isolated as a white solid (0.061 g, 68%).
trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-c-
arboxamido)-N-(2-fluoroethyl)benzamide (F104)
##STR00247##
[0666] Isolated as a white solid (0.063 g, 69%).
trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-c-
arboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F105)
##STR00248##
[0668] Isolated as a white solid (0.069 g, 71%).
trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-c-
arboxamido)-N-propylbenzamide (F106)
##STR00249##
[0670] Isolated as a white solid (0.077 g, 85%).
trans-2-Chloro-5-(2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-c-
arboxamido)-N-(3,3,3-trifluoropropyl)benzamide (F107)
##STR00250##
[0672] Isolated as a white solid (0.068 mg, 65%).
[0673] The following compounds were prepared in like manner to the
procedure outlined in Example 17a:
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N--((R)-1-((3,3,3-trifluoropropyl)sulfonyl)propan-2-yl)benzamide
(PF4)
##STR00251##
[0675] Isolated as a white solid (0.0137 g, 54%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-((2R)-1-((3,3,3-trifluoropropyl)sulfinyl)propan-2-yl)benzamide
(PF5)
##STR00252##
[0677] Isolated as a white solid (0.109 g, 44%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
-amido)-N--((R)-1-((2,2,2-trifluoroethyl)sulfonyl)propan-2-yl)benzamide
(PF6)
##STR00253##
[0679] Isolated as a white solid (0.107 g, 45%).
trans-2-Chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbox-
amido)-N-((2R)-1-((2,2,2-trifluoroethyl)sulfinyl)propan-2-yl)benzamide
(PF7)
##STR00254##
[0681] Isolated as a white solid (0.120 g, 52%).
Example 23: Preparation of
2-chloro-5-(trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbo-
xamido)-N-(1-(4-fluorophenyl)ethyl)benzamide (F96)
##STR00255##
[0683] To a solution of
trans-2-chloro-5-(2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane
carboxamido)benzoic acid (C67) (0.100 g, 0.220 mmol) and
1-(4-fluorophenyl)ethan-1-amine (0.037 g, 0.220 mmol) in ethyl
acetate (3 mL) were added sequentially pyridine (0.054 mL, 0.661
mmol) and
2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide
(50% solution in ethyl acetate, 0.281 g 0.441 mmol), and the
resulting pale-yellow solution was stirred at room temperature for
approximately 12 hours. The solution was concentrated under a
stream of nitrogen, and purified by silica gel flash column
chromatography with a mobile phase of hexanes/ethyl acetate. The
pure fractions were combined and concentrated under vacuum on a
rotary evaporator to provide the title compound as a clear,
colorless oil (0.058 g, 44%).
Example 24: Preparation of
2-chloro-5-(trans-2,2-dichloro-3-(3,4-difluorophenyl)cyclopropane-1-carbo-
xamido)-N-(2,2,2-trifluoroethyl)benzamide (F108)
##STR00256##
[0685] To a solution of
5-amino-2-chloro-N-(2,2,2-trifluoroethyl)benzamide (C70) (0.071 g,
0.281 mmol) and
trans-2,2-dichloro-3-(3,4-difluorophenyl)cyclopropanecarboxylic
acid (C124) (0.075 g, 0.281 mmol) in ethyl acetate (3 mL) were
added sequentially pyridine (0.068 mL, 0.843 mmol) and
2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide
(50% solution in ethyl acetate, 0.357 g, 0.562 mmol), and the
resulting pale-yellow solution was stirred at room temperature for
approximately 14 hours. The solution was concentrated under a
stream of nitrogen, and purified by silica gel flash column
chromatography with a mobile phase of hexanes/ethyl acetate. The
pure fractions were combined and concentrated under vacuum on a
rotary evaporator to provide the title compound as a white foam
(0.083 g, 56%).
[0686] The following compounds were prepared in like manner to the
procedure outlined in Example 24:
5-(trans-3-(3-Bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxamido-
)-2-chloro-N-(2,2,2-trifluoroethyl)benzamide (F109)
##STR00257##
[0688] Isolated as a white foam (0.100 g, 75%).
2-Chloro-5-(trans-2,2-dichloro-3-(3,4-dibromophenyl)cyclopropane-1-carboxa-
mido)-N-(2,2,2-trifluoroethyl)benzamide (F111)
##STR00258##
[0690] Isolated as a white solid (0.090 g, 71%).
2-Chloro-5-(trans-2,2-dichloro-3-(3-fluoro-4-(trifluoromethyl)phenyl)cyclo-
propane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F112
##STR00259##
[0692] Isolated as a white foam (0.073 g, 53%).
5-(trans-3-(4-Bromo-3-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido-
)-2-chloro-N-(2,2,2-trifluoroethyl)benzamide (F113)
##STR00260##
[0694] Isolated as a white foam (0.086 g, 64%).
5-(trans-3-(3-Bromo-4-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1--
carboxamido)-2-chloro-N-(2,2,2-trifluoroethyl)benzamide (F114)
##STR00261##
[0696] Isolated as a white foam (0.085 g, 66%).
5-(trans-3-(4-Bromo-3-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1--
carboxamido)-2-chloro-N-(2,2,2-trifluoroethyl)benzamide (F115)
##STR00262##
[0698] Isolated as a white foam (0.095 g, 74%).
2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-4-(trifluoromethyl)phenyl)cyclo-
propane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F116)
##STR00263##
[0700] Isolated as a white foam (0.081 g, 60%).
2-Chloro-5-(trans-2,2-dichloro-3-(4-chloro-3-(trifluoromethyl)phenyl)cyclo-
propane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F117)
##STR00264##
[0702] Isolated as a white foam (0.097 g, 72%).
5-(trans-3-(3-Bromo-4-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido-
)-2-chloro-N-(2,2,2-trifluoroethyl)benzamide (F118)
##STR00265##
[0704] Isolated as a white foam (0.113 g, 83%).
2-Chloro-5-(trans-2,2-dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclo-
propane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F119)
##STR00266##
[0706] Isolated as a gold foam (0.111 g, 81%).
2-Chloro-5-(trans-2,2-dichloro-3-(4-chloro-3-fluorophenyl)cyclopropane-1-c-
arboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F120)
##STR00267##
[0708] Isolated as a white foam (0.120 g, 83%).
2-Chloro-5-(trans-2,2-dichloro-3-(3,5-difluorophenyl)cyclopropane-1-carbox-
amido)-N-(2,2,2-trifluoroethyl)benzamide (F121)
##STR00268##
[0710] Isolated as a white foam (0.058 g, 39%).
2-Chloro-5-(trans-2,2-dichloro-3-(3-fluoro-5-(trifluoromethyl)phenyl)cyclo-
propane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F122)
##STR00269##
[0712] Isolated as a white foam (0.112 g, 82%).
5-(trans-3-(3-Bromo-5-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxamido-
)-2-chloro-N-(2,2,2-trifluoroethyl)benzamide (F123)
##STR00270##
[0714] Isolated as a white solid (0.097 g, 72%).
5-(trans-3-(3-Bromo-5-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1--
carboxamido)-2-chloro-N-(2,2,2-trifluoroethyl)benzamide (F124)
##STR00271##
[0716] Isolated as a clear colorless oil (0.102 g, 80%).
2-Chloro-5-trans-(2,2-dichloro-3-(3,5-difluoro-4-methoxyphenyl)cyclopropan-
e-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F125)
##STR00272##
[0718] Isolated as a white foam (0.075 g, 80%).
2-Chloro-5-trans-(2,2-dichloro-3-(3,4,5-trifluorophenyl)cyclopropane-1-car-
boxamido)-N-(2,2,2-trifluoroethyl)benzamide (F126)
##STR00273##
[0720] Isolated as a clear colorless oil (0.052 g, 54%).
2-Chloro-5-ds-(2,2-dichloro-3-(3,4,5-trifluorophenyl)cyclopropane-1-carbox-
amido)-N-(2,2,2-trifluoroethyl)benzamide (F127)
##STR00274##
[0722] Isolated as a clear colorless oil (0.017 g, 18%).
2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-5-(difluoromethyl)phenyl)cyclop-
ropane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F128)
##STR00275##
[0724] Isolated as a yellow oil (0.063 g, 73%).
2-Chloro-5-(trans-2,2-dichloro-3-(4-chloro-3-(difluoromethyl)phenyl)cyclop-
ropane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F129)
##STR00276##
[0726] Isolated as a pale yellow oil (0.063 g, 73%).
2-Chloro-5-(trans-2,2-dichloro-3-(3-(difluoromethyl)-5-fluorophenyl)cyclop-
ropane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F130)
##STR00277##
[0728] Isolated as a yellow foam (0.051 g, 61%).
2-Chloro-5-(trans-2,2-dichloro-3-(3-(difluoromethyl)-4-fluorophenyl)cyclop-
ropane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F131)
##STR00278##
[0730] Isolated as a white foam (0.059 g, 70%).
2-Chloro-5-(trans-2,2-dichloro-3-(3-chloro-4-(difluoromethyl)phenyl)cyclop-
ropane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F132)
##STR00279##
[0732] Isolated as a yellow foam (0.068 g, 78%).
2-Chloro-5-(trans-2,2-dichloro-3-(4-(difluoromethyl)-3-fluorophenyl)cyclop-
ropane-1-carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F133)
##STR00280##
[0734] Isolated as a yellow foam (0.059 g, 70%).
2-Chloro-5-(trans-2,2-dichloro-3-(3-(difluoromethyl)phenyl)cyclopropane-1--
carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F134)
##STR00281##
[0736] Isolated as a white foam (0.058 g, 71%).
2-Chloro-5-(trans-2,2-dichloro-3-(4-(difluoromethyl)phenyl)cyclopropane-1--
carboxamido)-N-(2,2,2-trifluoroethyl)benzamide (F135)
##STR00282##
[0738] Isolated as a white foam (0.057 g, 70%).
Example 25: Preparation of
(E)-1-chloro-3-(difluoromethyl)-5-(4-methoxystyryl)benzene
(C107)
##STR00283##
[0740] To a stirred solution of (E)-3-chloro-5-(4-methoxystyryl)
benzaldehyde (C115) (13 g, 47.79 mmol) in dichloromethane (130 mL)
was added diethylaminosulfur trifluoride (31.5 mL, 238.97 mmol) at
-78.degree. C. The resulting solution was stirred for 20 hours at
room temperature. The reaction mixture was cooled to 0.degree. C.,
and a solution of saturated aqueous sodium bicarbonate was added
dropwise. The layers were separated and the aqueous layer was
extracted with dichloromethane (3.times.75 mL). The combined
organic layer was washed with water and brine, dried over sodium
sulfate, and concentrated. The crude material was purified by flash
column chromatography using 10-20% ethyl acetate in hexanes as the
eluent to afford the title compound as a pale yellow oil (13.1 g,
94%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.55 (s, 1H), 7.45
(d, J=8.8 Hz, 3H), 7.34 (s, 1H), 7.10 (d, J=16 Hz, 1H), 6.90 (t,
J=8.4 Hz, 3H), 6.61 (t, J=56.4 Hz, 1H), 3.80 (s, 3H); .sup.19F NMR
(376 MHz, CDCl.sub.3) .delta. -111.72.
[0741] The following compounds were prepared in like manner to the
procedure outlined in Example 25:
(E)-1-Chloro-2-(difluoromethyl)-4-(4-methoxystyryl) benzene
(C108)
##STR00284##
[0743] Isolated as an off-white solid (12 g, 94%): .sup.1H NMR (300
MHz, CDCl.sub.3) .delta. 7.75 (s, 1H), 7.51-7.44 (m, 3H), 7.37 (d,
J=8.4 Hz, 1H), 7.13 (d, J=6.6 Hz, 1H), 7.06 (s, 1H), 6.95-6.89 (m,
3H), 3.95 (s, 3H); .sup.19F NMR (282 MHz, CDCl.sub.3) .delta.
-115.31; ESIMS m/z 295 ([M+H].sup.+).
(E)-1-(Difluoromethyl)-3-fluoro-5-(4-methoxystyryl) benzene
(C109)
##STR00285##
[0745] Isolated as an off-white solid (20 g, 75%); .sup.1H NMR (300
MHz, CDCl.sub.3) .delta. 7.46 (d, J=8.0 Hz, 2H), 7.38 (s, 1H), 7.28
(s, 1H), 7.08 (t, J=16.2 Hz, 2H), 6.92 (t, J=15.6 Hz, 3H), 6.63 (t,
J=56.0 Hz, 1H), 3.84 (s, 3H); ESIMS m/z 279 ([M+H].sup.+).
(E)-2-(Difluoromethyl)-1-fluoro-5-(4-methoxystyryl) benzene
(C110)
##STR00286##
[0747] Isolated as an off-white solid (14.0 g, 70%): .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 7.69 (d, J=9.0 Hz, 1H), 7.57-7.53 (m,
1H), 7.45 (d, J=9.9 Hz, 2H), 7.13-7.06 (m, 2H), 7.00-6.89 (m, 4H),
3.85 (s, 3H); ESIMS m/z 279 ([M+H].sup.+).
(E)-2-Chloro-1-(Difluoromethyl)-4-(4-methoxystyryl) benzene
(C111)
##STR00287##
[0749] Isolated as an off-white solid (18.0 g, 90%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.61 (d, J=8.0 Hz, 1H), 7.51 (s, 1H),
7.47-7.43 (m, 3H), 7.14-7.07 (m, 1H), 6.94-6.80 (m, 4H), 3.85 (s,
3H); ESIMS m/z 294 ([M+H].sup.+).
(E)-1-(Difluoromethyl)-2-fluoro-4-(4-methoxystyryl) benzene
(C12)
##STR00288##
[0751] Isolated as a pale yellow solid (9 g, 55%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.54 (t, J=8.0 Hz, 1H), 7.46 (d, J=8.8 Hz,
2H), 7.32 (d, J=8.0 Hz, 1H), 7.22 (d, J=11.6 Hz, 1H), 7.11 (d,
J=16.4 Hz, 1H), 7.01-6.83 (m, 4H), 3.95 (s, 3H); .sup.19F NMR (376
MHz, CDCl.sub.3) .delta. -113.57, -114.25, -120.33; ESIMS m/z 279
([M+H].sup.+).
(E)-1-(Difluoromethyl)-3-(4-methoxystyryl) benzene (C113)
##STR00289##
[0753] Isolated as a pale yellow solid (6 g, 68%): .sup.1H NMR (300
MHz, CDCl.sub.3) .delta. 7.62-7.56 (m, 2H), 7.48-7.34 (m, 4H), 7.11
(d, J=16.5 Hz, 1H), 7.00 (s, 1H), 6.95-6.89 (t, 2H), 6.66 (t, 1H),
3.95 (s, 3H); .sup.19F NMR (282 MHz, CDCl.sub.3) .delta. -110.84;
ESIMS m/z 261 ([M+H].sup.+).
(E)-1-(Difluoromethyl)-4-(4-methoxystyryl) benzene (C114)
##STR00290##
[0755] Isolated as an off-white solid (15.4 g, 75%); .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 7.57-7.45 (m, 6H), 7.12 (d, J=15.9
Hz, 1H), 7.00-6.89 (m, 3H), 6.64 (t, J=57 Hz, 1H), 3.92 (s, 3H);
ESIMS m/z 260.17 ([M+H].sup.+).
Example 26: Preparation of (E)-3-chloro-5-(4-methoxystyryl)
benzaldehyde (C115)
##STR00291##
[0757] To a stirred solution of 3-bromo-5-chlorobenzaldehyde (20.0
g, 91.32 mmol) in dimethylacetamide, 1-methoxy-4-vinylbenzene (18.3
g, 136.9 mmol) and triethylamine (50.5 mL, 273.96 mmol) were added,
and the reaction mixture was degassed with argon for 5 minutes.
Palladium(II) acetate (410 mg, 1.83 mmol) and tri-o-tolylphosphine
(1.11 g, 3.65 mmol) were added, and the resulting reaction mixture
was heated to 100.degree. C. for 16 hours. The reaction mixture was
poured into water and extracted with ethyl acetate. The combined
organic layer was dried over sodium sulfate and concentrated under
reduced pressure. The resulting crude material was purified by
flash column chromatography using 5-10% ethyl acetate in petroleum
ether as the eluent to afford the title compound as a yellow solid
(13.5 g, 54%): .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 9.99 (s,
1H), 7.85 (s, 1H), 7.69 (s, 2H), 7.47 (d, J=8.4 Hz, 2H), 7.16 (d,
J=16.2 Hz, 1H), 6.94 (t, J=8.4 Hz, 3H), 3.84 (s, 3H); ESIMS m/z 273
([M+H].sup.+).
[0758] The following compounds were prepared in like manner to the
procedure outlined in Example 26:
(E)-2-Chloro-5-(4-methoxystyryl)benzaldehyde (C116)
##STR00292##
[0760] Isolated as a pale yellow solid (11.8 g, 27%): .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 10.45 (s, 1H), 8.02 (s, 1H), 7.62 (d,
J=6.4 Hz, 1H), 7.46-7.40 (m, 3H), 7.12 (d, J=16.4 Hz, 1H),
6.95-6.90 (m, 3H), 3.95 (s, 3H); ESIMS m/z 273 ([M+H].sup.+).
(E)-3-Fluoro-5-(4-methoxystyryl)benzaldehyde (C117)
##STR00293##
[0762] Isolated as a pale yellow solid (25 g, 57%): .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 10 (s, 1H), 7.77 (s, 1H), 7.48-7.40
(m, 4H), 7.16 (d, J=16.2 Hz, 1H), 6.94 (t, J=15.6 Hz, 3H), 3.84 (s,
3H); ESIMS m/z 275 ([M+H].sup.+).
(E)-2-Fluoro-5-(4-methoxystyryl)benzaldehyde (C118)
##STR00294##
[0764] Isolated as an off-white solid (0.25 g, 20%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 10.43 (s, 1H), 7.90 (d, J=8.4 Hz,
1H), 7.54-7.46 (m, 4H), 7.20 (d, J=16.0 Hz, 1H), 6.94-6.90 (m, 3H),
3.85 (s, 3H); ESIMS m/z 274 ([M+H].sup.+).
(E)-2-Chloro-4-(4-methoxystyryl)benzaldehyde (C119)
##STR00295##
[0766] Isolated as an off-white solid (8.0 g, 57%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 10.41 (s, 1H), 7.97 (dd, J=2.4, 6.8
Hz, 1H), 7.71-7.67 (m, 1H), 7.44 (d, J=8.0 Hz, 2H), 7.18-7.13 (m,
1H), 7.08-7.04 (m, 1H), 6.95-6.90 (m, 3H), 3.85 (s, 3H); ESIMS m/z
257 ([M+H].sup.+).
(E)-2-Fluoro-4-(4-methoxystyryl)benzaldehyde (C120)
##STR00296##
[0768] Isolated as a brown solid (15 g, 78%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 10.35 (s, 1H), 7.83 (t, J=7.6 Hz, 1H), 7.48 (d,
J=8.8 Hz, 2H), 7.35 (d, J=8.4 Hz, 1H), 7.23-7.18 (m, 2H), 6.96-6.91
(m, 3H), 3.95 (s, 3H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta.
-122.26; ESIMS m/z 257 ([M+H].sup.+).
(E)-3-(4-Methoxystyryl)benzaldehyde (C121)
##STR00297##
[0770] Isolated as a brown solid (18 g, 46%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 10.15 (s, 1H), 8.00 (s, 1H), 7.73 (d, J=7.2 Hz,
2H), 7.53-7.46 (m, 3H), 7.17 (d, J=16.8 Hz, 1H), 7.01 (d, J=16.0
Hz, 1H), 6.92 (d, J=8.8 Hz, 2H), 3.84 (s, 3H); ESIMS m/z 239
([M+H].sup.+).
(E)-4-(4-Methoxystyryl) benzaldehyde (C122)
##STR00298##
[0772] Isolated as a light brown solid (9 g, 47%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 10 (s, 1H), 7.84 (d, J=8.0 Hz, 2H), 7.61
(d, J=7.6 Hz, 2H), 7.48 (d, J=8.0 Hz, 2H), 7.23 (t, J=7.6 Hz, 1H),
7.00 (d, J=16.0 Hz, 1H), 6.92 (d, J=8.8 Hz, 2H), 3.84 (s, 3H).
Example 27: Preparation of
trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1carboxylic
acid (C1)
##STR00299##
[0774] Sodium permanganate (40% aqueous) (84 g, 236 mmol) was added
dropwise to a stirred mixture of
trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbaldehyde
(C115) (58.7 g, 196 mmol) in acetone (982 mL) at 15.degree. C. The
resulting mixture was stirred at 20.degree. C. for 2 hours. The
reaction mixture was diluted with isopropyl alcohol (20 mL) and
concentrated to remove the acetone. Celite.RTM. and aqueous
hydrochloric acid (1 N, 295 mL, 295 mmol) were added to the brown
residue. The resulting mixture was diluted with ethyl acetate (500
mL) and filtered through Celite.RTM.. The filtrate was washed with
brine (200 mL). The organic layer was dried over sodium sulfate,
filtered and concentrated. The resulting slurry was diluted with
heptane (.about.200 mL) and allowed to solidify at 20.degree. C.
The solid was collected, washed with heptane and dried to afford
the title product as a white solid (54.68 g, 91%): .sup.1H NMR (300
MHz, CDCl.sub.3) .delta. 7.36 (t, J=1.9 Hz, 1H), 7.17 (dd, J=1.9,
0.7 Hz, 2H), 3.48-3.37 (m, 1H), 2.87 (d, J=8.3 Hz, 1H); .sup.13C
NMR (400 MHz, CDCl.sub.3) .delta. 135.44, 135.28, 128.66, 127.30,
39.68, 36.88; ESIMS m/z=298.9 ([M-H]).sup.-.
[0775] The following compounds were prepared in like manner to the
procedure outlined in Example 27:
trans-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxylic
acid (C2)
##STR00300##
[0777] Isolated as a white solid (2.78 g, 95%): .sup.1H NMR (400
MHz, DMSO-d.sub.6) .delta. 13.41 (s, 1H), 7.81 (d, J=0.6 Hz, 2H),
3.62 (d, J=8.6 Hz, 1H), 3.52 (d, J=8.6 Hz, 1H); ESIMS m/z 332
([M-H].sup.-).
trans-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxylic
acid(C3)
##STR00301##
[0779] Isolated as a white solid (124 g, 82%): mp 133-135.degree.
C.: .sup.1H NMR (500 MHz, DMSO-d.sub.6) .delta. 13.39 (s, 1H), 7.76
(d, J=2.0 Hz, 1H), 7.64 (d, J=8.3 Hz, 1H), 7.44 (dd, J=8.4, 2.1 Hz,
1H), 3.49 (s, 2H). .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta.
166.34, 133.35, 130.47, 130.33, 130.09, 129.77, 128.81, 61.43,
37.00, 36.06.
trans-2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylic
acid (C16)
##STR00302##
[0781] Isolated as a white solid (165 g, 71%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 11.57 (s, 1H), 7.42 (dd, J=8.2, 7.6 Hz,
1H), 7.11-6.98 (m, 2H), 3.46 (d, J=8.2 Hz, 1H), 2.85 (d, J=8.3 Hz,
1H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -114.07; ESIMS m/z
282 ([M-H].sup.-).
[0782] In another preparation, isolated as a white powder (10.385
g, 77%): 119-121.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 11.83 (s, 1H), 7.32 (d, J=6.9 Hz, 1H), 7.16 (d, J=6.7 Hz,
2H), 3.45 (d, J=8.3 Hz, 1H), 2.85 (d, J=8.3 Hz, 1H); .sup.13C NMR
(101 MHz, CDCl.sub.3) .delta. 172.18, 159.26, 156.77, 130.95,
129.26, 129.22, 128.57, 128.50, 121.52, 121.34, 116.94, 116.73,
61.59, 39.64, 37.30; .sup.19F NMR (376 MHz, CDCl.sub.3) .delta.
-115.16; ESIMS m/z 281 [(M-H).sup.-].
trans-2,2-Dichloro-3-(3,5-dichloro-4-methoxyphenyl)cyclopropanecarboxylic
acid (C123)
##STR00303##
[0784] Isolated as an off-white solid (1.33 g, 96%): mp
161-164.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
13.35 (s, 1H), 7.63 (s, 2H), 3.83 (s, 3H), 3.52 (d, J=8.6 Hz, 1H),
3.45 (d, J=8.6 Hz, 1H); .sup.13C NMR (126 MHz, DMSO-d.sub.6)
.delta. 166.81, 151.02, 131.07, 129.63, 128.03, 61.93, 60.52,
37.22, 36.54; ESIMS m/z 329 [(M-H).sup.-].
Example 28: Preparation of
trans-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-1-carbaldehyde
(C140)
##STR00304##
[0786] Aqueous hydrochloric acid (2 N, 237 mL) was added to a
stirred solution of
1,3-dichloro-5-((trans-2,2-dichloro-3-(diethoxymethyl)cyclopropyl)benzene
(C145) (85.7 g, 227 mmol) in acetonitrile (1184 mL). The mixture
was stirred at 20.degree. C. for 16 hours. The resulting mixture
was diluted with water (200 mL) and concentrated to remove the
acetonitrile. The resulting aqueous mixture was extracted with
hexanes (600 mL). The organic layer was washed water (300 mL),
dried over anhydrous sodium sulfate, filtered and concentrated. The
crude product was purified by chromatography to afford the title
product as a yellow oil (58.7 g, 86%, purity 95%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 9.54 (d, J=4.0 Hz, 1H), 7.46-7.09 (m, 3H),
3.51 (d, J=8.0 Hz, 1H), 2.92 (dd, J=8.0, 4.0 Hz, 1H); .sup.13C NMR
(126 MHz, CDCl.sub.3) .delta. 193.41, 135.33, 135.09, 128.78,
127.34, 42.89, 39.31; IR (thin film) 3077.79, 2847.30, 1713.57,
1590.66, 1566.39, 1416.76, 1387.06. IR: 3078, 2847, 1714, 1590,
1566, 1417, 1387.
[0787] The following compounds were prepared in like manner to the
procedure outlined in Example 28:
trans-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carbaldehyde
(C141)
##STR00305##
[0789] Isolated as orange oil (143 g, 98%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 9.53 (d, J=4.1 Hz, 1H), 7.47 (d, J=8.3 Hz, 1H),
7.37 (dd, J=2.2, 0.7 Hz, 1H), 7.12 (ddd, J=8.3, 2.2, 0.7 Hz, 1H),
3.51 (dd, J=7.9, 0.8 Hz, 1H), 2.90 (dd, J=8.0, 4.1 Hz, 1H).
trans-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carbaldehyde
(C142)
##STR00306##
[0791] Isolated as a yellow solid (2.8 g, 69%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 9.55 (d, J=3.9 Hz, 1H), 7.30 (d, J=0.7 Hz,
2H), 3.48 (dt, J=8.0, 0.8 Hz, 1H), 2.92 (dd, J=7.9, 3.9 Hz,
1H).
trans-2,2-Dichloro-3-(3,5-dichloro-4-methoxyphenyl)cyclopropane-1-carbalde-
hyde (C143)
##STR00307##
[0793] Isolated as a light-yellow oil (1.346 g, 74%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 9.52 (d, J=4.0 Hz, 1H), 7.22 (s, 2H),
3.90 (s, 3H), 3.48 (d, J=8.0 Hz, 1H), 2.91 (dd, J=8.0, 4.0 Hz, 1H);
.sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 191.67, 150.58, 127.74,
127.54, 127.35, 59.76, 58.94, 41.14, 37.13; EIMS m/z 314.
trans-2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carbaldehyde
(C144)
##STR00308##
[0795] Isolated as a yellow oil (12.496 g, 71%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 9.52 (d, J=4.1 Hz, 1H), 7.33 (d, J=7.2 Hz,
1H), 7.16 (dd, J=6.8, 1.0 Hz, 2H), 3.53 (d, J=7.9 Hz, 1H), 2.90
(dd, J=7.9, 4.1 Hz, 1H); .sup.13C NMR (101 MHz, CDCl.sub.3) .delta.
193.77, 159.27, 156.78, 131.03, 129.04, 129.00, 128.66, 128.59,
121.49, 121.31, 116.95, 116.74, 61.68, 43.10, 39.25; .sup.19F NMR
(376 MHz, CDCl.sub.3) .delta. -115.01; EIMS m/z 266.
Example 29: Preparation of
1,3-dichloro-5-(trans-2,2-dichloro-3-(diethoxy-methyl)cyclopropyl)benzene
(C145)
##STR00309##
[0797] A 1 L 4-neck flask equipped with a mechanical stirrer,
condenser, temperature probe and nitrogen inlet was charged with
(E)-1,3-dichloro-5-(3,3-diethoxyprop-1-en-1-yl)benzene (C150) (40
g, 138 mmol) and CHCl.sub.3 (447 mL). Tetrabutylammonium
hexafluorophosphate(V) (1.081 g, 2.76 mmol) was added. The light
yellow solution was heated to 45.degree. C. With vigorous stirring
(.about.400 rpm), aqueous sodium hydroxide (50%, 182 mL) was added
dropwise via addition funnel (over 1 hour). After 20 hours, the
mixture was allowed to cool. The mixture was diluted with hexane
(200 mL). The organic top layer was decanted (off the aqueous lower
suspension) through Celite.RTM., washing the filtercake with hexane
(200 mL). The filtrate was washed with brine (.about.200 mL), dried
over sodium sulfate, filtered and concentrated to provide the title
compound as a brown oil (50.2 g, 97%, purity 95%): .sup.1H NMR (300
MHz, CDCl.sub.3) .delta. 7.31 (t, J=1.9 Hz, 1H), 7.15 (dd, J=1.9,
0.7 Hz, 2H), 4.59 (d, J=6.2 Hz, 1H), 3.80-3.57 (m, 4H), 2.77 (d,
J=8.5 Hz, 1H), 2.25 (dd, J=8.5, 6.2 Hz, 1H), 1.30 (t, J=7.0 Hz,
3H), 1.20 (t, J=7.1 Hz, 3H).
[0798] The following compounds were prepared in like manner to the
procedure outlined in Example 29:
1,2-Dichloro-4-(trans-2,2-dichloro-3-(diethoxymethyl)cyclopropyl)benzene
(C146)
##STR00310##
[0800] Isolated as a brown oil (184 g, 99%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.43 (d, J=8.2 Hz, 1H), 7.36 (dd, J=2.2, 0.7
Hz, 1H), 7.10 (ddd, J=8.3, 2.1, 0.7 Hz, 1H), 4.59 (d, J=6.2 Hz,
1H), 3.82-3.55 (m, 4H), 2.77 (d, J=8.5 Hz, 1H), 2.24 (dd, J=8.5,
6.3 Hz, 1H), 1.30 (t, J=7.0 Hz, 3H), 1.20 (t, J=7.1 Hz, 3H).
1,2,3-Trichloro-5-(trans-2,2-dichloro-3-(diethoxymethyl)cyclopropyl)benzen-
e (C147)
##STR00311##
[0802] Isolated as a brown oil (146 g, 93%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.29 (d, J=0.7 Hz, 2H), 4.59 (d, J=6.1 Hz, 1H),
3.82-3.54 (m, 4H), 2.75 (d, J=8.5 Hz, 1H), 2.23 (dd, J=8.5, 6.1 Hz,
1H), 1.30 (t, J=7.0 Hz, 3H), 1.20 (t, J=7.0 Hz, 3H).
trans-1,3-Dichloro-5-(2,2-dichloro-3-(diethoxymethyl)cyclopropyl)-2-methox-
ybenzene (C148)
##STR00312##
[0804] Isolated as an orange oil (2.254 g, 80%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.20 (d, J=0.5 Hz, 2H), 4.58 (d, J=6.2 Hz,
1H), 3.90 (s, 3H), 3.67 (m, 4H), 2.74 (d, J=8.5 Hz, 1H), 2.22 (dd,
J=8.5, 6.2 Hz, 1H), 1.31 (m, 3H), 1.21 (m, 3H); .sup.13C NMR (101
MHz, CDCl.sub.3) .delta. 151.87, 131.55, 129.27, 129.20, 127.21,
101.21, 62.39, 61.88, 61.68, 60.70, 37.67, 36.96, 15.34, 15.25;
EIMS m/z 387.
2-Chloro-4-(trans-2,2-dichloro-3-(diethoxymethyl)cyclopropyl)-1-fluorobenz-
ene (C149)
##STR00313##
[0806] Isolated as a brown oil (63 g, 96%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.44 (dd, J=7.0, 2.2 Hz, 1H), 7.29-7.22 (m,
1H), 7.09 (t, J=8.7 Hz, 1H), 6.62 (dd, J=16.1, 1.2 Hz, 1H), 6.14
(dd, J=16.1, 5.0 Hz, 1H), 5.05 (dd, J=4.9, 1.2 Hz, 1H), 3.70 (dq,
J=9.3, 7.0 Hz, 2H), 3.56 (dq, J=9.4, 7.1 Hz, 2H), 1.25 (t, J=7.1
Hz, 6H); .sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 158.91, 156.42,
133.65, 133.62, 130.47, 128.65, 128.07, 128.05, 126.39, 126.32,
121.26, 121.08, 116.72, 116.51, 100.93, 61.17, 15.24; .sup.19F NMR
(376 MHz, CDCl.sub.3) .delta. -116.36.
[0807] In another preparation, isolated as an amber oil (22.38 g,
88%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.31 (m, 1H), 7.13
(m, 2H), 4.59 (d, J=6.3 Hz, 1H), 3.69 (m, 4H), 2.78 (d, J=8.5 Hz,
1H), 2.23 (dd, J=8.5, 6.3 Hz, 1H), 1.30 (t, J=7.1 Hz, 3H), 1.20 (t,
J=7.1 Hz, 3H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -116.48;
EIMS m/z 295 [M-OEt].
Example 30: Preparation of
(E)-1,3-dichloro-5-(3,3-diethoxyprop-1-en-1-yl)benzene (C150)
##STR00314##
[0809] Step 1a: Acetaldehyde (120 g, 2688 mmol) was added to a
stirred mixture of 3,5-dichlorobenzaldehyde (96 g, 538 mmol) in
toluene (400 mL) at 0.degree. C. A solution of potassium hydroxide
(3.35 g, 53.8 mmol) in methyl alcohol (10 mL) was added dropwise
via addition funnel. The resulting mixture was stirred at 0.degree.
C. for 4 hours until all of the 3,5-dichlorobenzaldehyde was
consumed by thin layer chromatography. Step 1b: Ethyl acetate (500
mL) and concentrated hydrochloric acid (37% aqueous, 44.1 mL, 538
mmol) were added to the reaction mixture. The resulting mixture was
heated at 80.degree. C., and a colorless liquid was allowed to
distill (200 mL). The reaction mixture was diluted with water (500
mL) and extracted with ethyl acetate. The organic layer was washed
with brine, dried over sodium sulfate, filtered, and concentrated
to afford (E)-3-(3,5-dichlorophenyl) acrylaldehyde as a light
yellow solid (115 g) which was used directly without further
purification: .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 9.72 (dd,
J=7.4, 0.5 Hz, 1H), 7.43 (q, J=1.8 Hz, 3H), 7.35 (d, J=16.0 Hz,
1H), 6.69 (dd, J=16.0, 7.4 Hz, 1H).
[0810] Step 2: Triethoxymethane (31.4 g, 208 mmol) and
pyridin-1-ium 4-methylbenzenesulfonate (0.528 g, 2.079 mmol) were
added to a stirred solution of (E)-3-(3,5-dichlorophenyl)
acrylaldehyde (44 g, 208 mmol) in ethanol (416 mL). The resulting
mixture was stirred at 20.degree. C. for 20 hours. A solution of
saturated aqueous sodium carbonate (50 mL) was added to the
reaction mixture. The resulting mixture was concentrated at
45.degree. C. to remove the ethanol. The concentrate was diluted
with water and extracted with hexane. The organic layer was washed
with brine, dried over sodium sulfate, filtered and concentrated to
afford the title product as a light yellow oil (56.13 g, 93%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.25 (dt, J=10.6, 1.9 Hz,
3H), 6.61 (dd, J=16.1, 1.1 Hz, 1H), 6.22 (dd, J=16.1, 4.7 Hz, 1H),
5.17 (s, 1H), 5.14-5.00 (m, 1H), 3.78-3.49 (m, 4H), 1.24 (q, J=7.2
Hz, 6H); .sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 139.34, 135.14,
130.27, 129.88, 127.71, 125.08, 100.60, 61.20, 15.25.
[0811] The following compounds were prepared in like manner to the
procedure outlined in Example 30:
(E)-1,2-Dichloro-4-(3,3-diethoxyprop-1-en-1-yl)benzene(C151)
##STR00315##
[0813] Isolated as an orange oil (142 g, 91%): .sup.1H NMR (300
MHz, CDCl.sub.3) .delta. 7.48 (d, J=2.0 Hz, 1H), 7.39 (dd, J=8.3,
0.8 Hz, 1H), 6.62 (d, J=16.1 Hz, 1H), 6.20 (ddd, J=16.1, 4.9, 0.8
Hz, 1H), 5.06 (dt, J=4.9, 1.0 Hz, 1H), 3.78-3.48 (m, 4H), 1.25 (td,
J=7.1, 0.8 Hz, 6H).
(E)-1,2,3-Trichloro-5-(3,3-diethoxyprop-1-en-1-yl)benzene(C152)
##STR00316##
[0815] Isolated as an orange oil (40 g, 91%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.41 (s, 2H), 6.58 (dd, J=16.1, 1.2 Hz, 1H),
6.21 (dd, J=16.1, 4.6 Hz, 1H), 5.06 (dd, J=4.7, 1.2 Hz, 1H), 3.69
(dq, J=9.3, 7.1 Hz, 2H), 3.55 (dq, J=9.5, 7.0 Hz, 2H), 1.25 (t,
J=7.1 Hz, 6H).
(E)-1,3-Dichloro-5-(3,3-diethoxyprop-1-en-1-yl)-2-methoxybenzene
(C153)
##STR00317##
[0817] Isolated as a yellow oil (2.305 g, 56%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.32 (s, 2H), 6.56 (d, J=16.0 Hz, 1H),
6.14 (dd, J=16.1, 4.8 Hz, 1H), 5.05 (dd, J=4.8, 1.0 Hz, 1H), 3.89
(s, 3H), 3.69 (m, 2H), 3.55 (m, 2H), 1.25 (t, J=7.1 Hz, 6H);
.sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 151.75, 133.87, 129.87,
129.45, 128.85, 126.91, 100.68, 61.14, 60.73, 15.24; EIMS m/z
304.
(E)-2-Chloro-4-(3,3-diethoxyprop-1-en-1-yl)-1-fluorobenzene
(C154)
##STR00318##
[0819] Isolated as an orange oil (283 g, 84%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.44 (dd, J=7.0, 2.2 Hz, 1H), 7.29-7.22
(m, 1H), 7.09 (t, J=8.7 Hz, 1H), 6.62 (dd, J=16.1, 1.2 Hz, 1H),
6.14 (dd, J=16.1, 5.0 Hz, 1H), 5.05 (dd, J=4.9, 1.2 Hz, 1H), 3.70
(dq, J=9.3, 7.0 Hz, 2H), 3.56 (dq, J=9.4, 7.1 Hz, 2H), 1.25 (t,
J=7.1 Hz, 6H); .sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 158.91,
156.42, 133.65, 133.62, 130.47, 128.65, 128.07, 128.05, 126.39,
126.32, 121.26, 121.08, 116.72, 116.51, 100.93, 61.17, 15.24;
.sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -116.36.
[0820] In another preparation, isolated as a colorless oil (16.75
g, 64%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.43 (dd, J=7.0,
2.2 Hz, 1H), 7.25 (m, 1H), 7.07 (t, J=8.7 Hz, 1H), 6.62 (d, J=16.1
Hz, 1H), 6.13 (dd, J=16.1, 4.9 Hz, 1H), 5.05 (dd, J=4.9, 1.0 Hz,
1H), 3.70 (dq, J=9.4, 7.1 Hz, 2H), 3.56 (dq, J=9.4, 7.0 Hz, 2H),
1.25 (t, J=7.1 Hz, 5H); .sup.13C NMR (101 MHz, CDCl.sub.3) .delta.
158.91, 156.42, 133.65, 133.62, 130.47, 128.65, 128.07, 128.05,
126.39, 126.32, 121.26, 121.08, 116.72, 116.51, 100.93, 61.17,
15.24; .sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -116.36; EIMS m/z
258.
[0821] The following compounds were prepared in like manner to the
procedures outlined in Examples 27 through 30:
trans-2,2-dichloro-3-(3,4-difluorophenyl)cyclopropane-1-carboxylic
acid (C124)
##STR00319##
[0823] Isolated as a white solid (1.44 g, 67%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 8.69 (s, 1H), 7.18 (dt, J=9.9, 8.3 Hz,
1H), 7.10 (ddd, J=10.8, 7.3, 2.3 Hz, 1H), 7.01 (ddt, J=8.1, 3.8,
1.7 Hz, 1H), 3.44 (dd, J=8.4, 1.0 Hz, 1H), 2.83 (d, J=8.3 Hz, 1H);
.sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -136.40, -136.46,
-137.42, -137.48; ESIMS m/z 266 ([M-H].sup.-).
trans-3-(3-Bromo-4-chlorophenyl)-2,2-dichlorocyclopropane-1-carboxylic
acid (C125)
##STR00320##
[0825] Isolated as a white solid (1.05 g, 63%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 8.07-7.63 (m, 1H), 7.58-7.42 (m, 2H), 7.17
(dd, J=8.3, 2.1 Hz, 1H), 3.43 (d, J=8.3 Hz, 1H), 2.86 (d, J=8.3 Hz,
1H); .sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 171.46, 134.71,
133.88, 132.43, 130.42, 128.70, 122.73, 77.33, 77.22, 77.01, 76.69,
61.51, 39.50, 37.21; ESIMS m/z 343 ([M-H].sup.-).
trans-2,2-Dichloro-3-(3,4-dibromophenyl)cyclopropane-1-carboxylic
acid (C126)
##STR00321##
[0827] Isolated as a white solid (0.488 g, 57%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 8.85 (s, 1H), 7.77-7.47 (m, 2H), 7.08
(ddd, J=8.3, 2.1, 0.7 Hz, 1H), 3.57-3.25 (m, 1H), 2.86 (d, J=8.3
Hz, 1H); .sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 171.54, 133.82,
133.78, 133.08, 128.78, 125.13, 124.98, 77.33, 77.22, 77.01, 76.70,
61.41, 39.59, 37.14, 0.01; ESIMS m/z 387 ([M-H].sup.-).
trans-2,2-Dichloro-3-(3-fluoro-4-(trifluoromethyl)phenyl)cyclopropane-1-ca-
rboxylic acid (C127)
##STR00322##
[0829] Isolated as a waxy tan solid (4.09 g, 69%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.83 (s, 1H), 7.63 (t, J=7.7 Hz, 1H),
7.23-7.04 (m, 2H), 3.51 (d, J=8.3 Hz, 1H), 2.92 (d, J=8.3 Hz, 1H);
.sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -61.40, -61.43, -113.24,
-113.27; ESIMS m/z 316 ([M-H].sup.-).
trans-3-(4-Bromo-3-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxylic
acid (C128)
##STR00323##
[0831] Isolated as a white solid (0.41 g, 42%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 8.04 (s, 1H), 7.57 (dd, J=8.2, 7.1 Hz,
1H), 7.00 (ddd, J=33.6, 8.7, 2.1 Hz, 2H), 3.43 (d, J=8.3 Hz, 1H),
2.85 (d, J=8.3 Hz, 1H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta.
-106.06; ESIMS m/z 327 ([M-H].sup.-).
trans-3-(3-Bromo-4-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-car-
boxylic acid (C129)
##STR00324##
[0833] Isolated as a white solid (0.55 g, 54%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.78-7.57 (m, 2H), 7.42-7.29 (m, 1H), 3.50
(d, J=8.3 Hz, 1H), 2.93 (d, J=8.3 Hz, 1H); .sup.19F NMR (376 MHz,
CDCl.sub.3) .delta. -62.66, -62.67, -62.81; ESIMS m/z 377
([M-H].sup.-).
trans-3-(4-Bromo-3-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-car-
boxylic acid (C130)
##STR00325##
[0835] Isolated as a white solid (1.21 g, 51%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 10.87 (s, 1H), 7.74 (d, J=8.3 Hz, 1H),
7.58 (d, J=2.2 Hz, 1H), 7.30 (dd, J=8.3, 2.2 Hz, 1H), 3.49 (d,
J=8.3 Hz, 1H), 2.91 (d, J=8.3 Hz, 1H); .sup.19F NMR (376 MHz,
CDCl.sub.3) .delta. -62.77, -62.78; ESIMS m/z 377
([M-H].sup.-).
trans-2,2-Dichloro-3-(3-chloro-4-(trifluoromethyl)phenyl)cyclopropane-1-ca-
rboxylic acid (C131)
##STR00326##
[0837] Isolated as a white solid (0.778 g, 43%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 9.72 (s, 1H), 7.71 (d, J=8.2 Hz, 1H),
7.53-7.39 (m, 1H), 7.35-7.19 (m, 1H), 3.50 (d, J=8.3 Hz, 1H), 2.93
(d, J=8.3 Hz, 1H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta.
-62.63; ESIMS m/z 332 ([M-H].sup.-).
trans-2,2-Dichloro-3-(4-chloro-3-(trifluoromethyl)phenyl)cyclopropane-1-ca-
rboxylic acid (C132)
##STR00327##
[0839] Isolated as a white solid (2.02 g, 43%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.96-7.51 (m, 3H), 7.39 (dd, J=8.3, 2.2
Hz, 1H), 3.50 (d, J=8.3 Hz, 1H), 2.90 (d, J=8.3 Hz, 1H); .sup.19F
NMR (376 MHz, CDCl.sub.3) .delta. -62.75, -62.75; ESIMS m/z 332
([M-H].sup.-).
trans-3-(3-Bromo-4-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxylic
acid (C133)
##STR00328##
[0841] Isolated as a white solid (0.850 g, 44%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 8.47 (s, 1H), 7.47 (ddd, J=6.3, 2.3, 0.7
Hz, 1H), 7.32-7.08 (m, 2H), 3.44 (dd, J=8.3, 1.0 Hz, 1H), 2.84 (d,
J=8.3 Hz, 1H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -107.16;
ESIMS m/z 327 ([M-H].sup.-).
trans-2,2-Dichloro-3-(4-fluoro-3-(trifluoromethyl)phenyl)cyclopropane-1-ca-
rboxylic acid (C134)
##STR00329##
[0843] Isolated as a white solid (3.08 g, 67%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 8.18 (s, 1H), 7.64-7.39 (m, 2H), 7.24 (t,
J=9.3 Hz, 1H), 3.50 (dd, J=8.4, 1.0 Hz, 1H), 2.89 (d, J=8.3 Hz,
1H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -61.48, -61.51,
-114.23, -114.26, -114.29; ESIMS m/z 316 ([M-H].sup.-).
trans-2,2-Dichloro-3-(4-chloro-3-fluorophenyl)cyclopropane-1-carboxylic
acid (C135)
##STR00330##
[0845] Isolated as a white solid (0.96 g, 36%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 11.57 (s, 1H), 7.42 (dd, J=8.2, 7.6 Hz,
1H), 7.11-6.98 (m, 2H), 3.46 (d, J=8.2 Hz, 1H), 2.85 (d, J=8.3 Hz,
1H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -114.07; ESIMS m/z
282 ([M-H].sup.-).
trans-2,2-Dichloro-3-(3,5-difluorophenyl)cyclopropane-1-carboxylic
acid (C136)
##STR00331##
[0847] Isolated as a clear colorless oil (1.55 g, 29%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 10.44 (s, 1H), 6.82 (qd, J=6.4, 2.3
Hz, 3H), 3.44 (d, J=8.3 Hz, 1H), 2.86 (d, J=8.3 Hz, 1H); .sup.19F
NMR (376 MHz, CDCl.sub.3) .delta. -108.49, -108.69, -108.82,
-109.85; ESIMS m/z 266 ([M-H].sup.-).
trans-2,2-Dichloro-3-(3-fluoro-5-(trifluoromethyl)phenyl)cyclopropane-1-ca-
rboxylic acid (C137)
##STR00332##
[0849] Isolated as a white solid (3.7 g, 55%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 11.40 (s, 1H), 7.42-7.27 (m, 2H), 7.20
(dt, J=8.9, 2.0 Hz, 1H), 3.53 (d, J=8.3 Hz, 1H), 2.93 (d, J=8.3 Hz,
1H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -62.86, -109.49;
ESIMS m/z 316 ([M-H].sup.-).
trans-3-(3-Bromo-5-fluorophenyl)-2,2-dichlorocyclopropane-1-carboxylic
acid (C138)
##STR00333##
[0851] Isolated as a white solid (0.76 g, 47%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 11.06 (s, 1H), 7.36-7.14 (m, 2H),
7.03-6.87 (m, 1H), 3.45 (d, J=8.3 Hz, 1H), 2.87 (d, J=8.3 Hz, 1H);
.sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -109.73, -109.73; ESIMS
m/z 327 ([M-H].sup.-).
trans-3-(3-Bromo-5-(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-car-
boxylic acid (C139)
##STR00334##
[0853] Isolated as a tan solid (0.375 g, 31%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 10.52 (s, 1H), 7.77 (s, 1H), 7.62 (d,
J=1.8 Hz, 1H), 7.46 (s, 1H), 3.52 (d, J=8.2 Hz, 1H), 2.93 (d, J=8.3
Hz, 1H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -62.84; ESIMS
m/z 377 ([M-H].sup.-).
Example 31: Preparation of trans-2,2-dibromo-3-(3,5-dichlorophenyl)
cyclopropane-1-carboxylic acid (C155)
##STR00335##
[0855] To a solution of
trans-2,2-dibromo-3-(3,5-dichlorophenyl)cyclopropane-1-carbaldehyde
(C156) (1.67 g, 4.48 mmol) in acetonitrile (15.36 mL) and water
(2.5 mL) was added sodium hydrogen sulfite (3.26 g, 31.36 mmol).
The resultant solution was cooled to 0.degree. C., sodium chlorite
(3.54 g, 17.92 mmol) was added slowly, and the solution was stirred
for overnight while slowly warming to room temperature. The mixture
was then diluted with aqueous hydrochloric acid solution (1 N)
until the pH was equal to or less than 3. The mixture was then
repeatedly extracted with ethyl acetate. The combined organic
extracts were dried over sodium sulfate, filtered and concentrated
under vacuum. Purification of the crude solid by flash column
chromatography with 0-100% ethyl acetate/hexanes as eluent provided
the title compound as a light brown solid (0.91 g, 52%): .sup.1H
NMR (400 MHz, CDCl.sub.3) .delta. 7.36 (t, J=1.9 Hz, 1H), 7.17 (dd,
J=1.9, 0.8 Hz, 2H), 3.39 (d, J=8.2 Hz, 1H), 2.91 (d, J=8.2 Hz, 1H);
.sup.13C NMR (101 MHz, CDCl.sup.3) .delta. 172.15, 136.91, 135.25,
128.64, 127.29, 40.29, 37.32, 26.57; ESIMS m/z 386
([M-H].sup.-).
Example 32: Preparation of trans-2,2-dibromo-3-(3,5-dichlorophenyl)
cyclopropane-1-carbaldehyde (C156)
##STR00336##
[0857] To a solution of
(E)-1,3-dichloro-5-(3,3-diethoxyprop-1-en-1-yl)benzene (C150)
(0.500 g, 1.817 mmol) in bromoform (12.1 mL) were added
tetrabutylammonium hexafluorophosphate(V) (70.4 mg, 0.182 mmol)
followed by the careful addition of solid sodium hydroxide (1454
mg, 36.3 mmol). The mixture was heated to 90.degree. C. while
stirring overnight. The mixture was diluted with dichloromethane
and water and was extracted with additional dichloromethane. The
organic layer was then dried over sodium sulfate, filtered, and
concentrated. Purification by flash column chromatography using
0-100% ethyl acetate/hexanes as eluent provided an elutant which
was then dissolved in acetone (4 mL) and aqueous hydrochloric acid
(2 N)(1 mL, 2 mmol). The mixture was stirred overnight. The mixture
was diluted with saturated sodium bicarbonate solution until the pH
was greater than 7. The mixture was then extracted with diethyl
ether and ethyl acetate, and the combined organic layers were dried
over sodium sulfate and concentrated providing the dark brown
product (0.03 g, 4%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
9.48 (d, J=4.0 Hz, 1H), 7.37 (t, J=1.9 Hz, 1H), 7.17 (dd, J=1.9,
0.7 Hz, 2H), 3.60-3.36 (m, 1H), 2.90 (dd, J=7.9, 4.0 Hz, 1H);
.sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 194.74, 136.55, 135.31,
128.76, 127.34, 42.34, 39.84, 26.05; ESIMS m/z 343
([M-CHO].sup.-).
Example 33: Preparation of
(1R,3R)-2,2-dichloro-3-(3,5-dichlorophenyl)-cyclopropane-1-carboxylic
acid (C157)
##STR00337##
[0859] 1.sup.st resolution: (R)-1-Phenylethanamine (6.49 g, 53.0
mmol) was slowly added to a stirred solution of
rac-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-carboxylic
acid) (32.45 g, 106 mmol) in acetone (106 mL). The resulting
solution was stirred at 45.degree. C. After a solid began to
deposit, the mixture was placed at 5.degree. C. for 4 hours. The
solid was collected, washed with minimal cold acetone and dried.
The white solid salt was diluted with ethyl acetate (100 mL) and
washed with aqueous hydrochloric acid (1 N, 010 mL) and brine (30
mL). The organic layer was dried over sodium sulfate, filtered and
concentrated to afford the title product as a white solid (10.33 g,
88% enantiomeric excess "ee").
[0860] 2.sup.nd resolution: (R)-1-Phenylethanamine (3.4 g, 28 mmol)
was slowly added to a stirred solution of
rac-2,2-dichloro-3-(3,5-dichlorophenyl)cyclopropane-carboxylic
acid) (10.33 g, 88% ee) in acetone (100 mL). After 2 hours, a solid
was collected, washed with minimal cold acetone and dried. The
solid was treated with aqueous hydrochloric acid to afford the
title compound as a white solid (7.84 g, 97% ee, 24.2%): Specific
Rotation: +47.4 (10 mg/mL in acetonitrile, 589 nm, 25.2.degree.
C.); .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 7.36 (t, J=1.9 Hz,
1H), 7.17 (dd, J=1.9, 0.7 Hz, 2H), 3.48-3.37 (m, 1H), 2.87 (d,
J=8.3 Hz, 1H); .sup.13C NMR (400 MHz, DMSO-d.sub.6) .delta. 166.28,
136.40, 133.39, 127.27, 127.04, 61.36, 37.10, 35.98; ESIMS m/z
298.9 ([M-H].sup.-).
[0861] ee was determined by Chiral HPLC method as follows: Column:
CHIRALPAK.RTM. ZWIX(+), particle size 3 .mu.m, dimension 3
mm.times.150 mm, DAIC 511584; Mobile phase: 49% acetonitrile/49%
methanol/water with 50 mM formic acid and diethylamine; Flow rate:
0.5 mL/min; Time: 9 min; Temperature: 25.degree. C.
[0862] The following compounds were prepared in like manner to the
procedure outlined in Example 33:
(1R,3R)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxylic
acid (C158)
##STR00338##
[0864] Isolated as a white solid (6.7 g, 30%, 96% ee). Analytical
data are consistent with racemic acid C3.
(1R,3R)-2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylic
acid (C159)
##STR00339##
[0866] Isolated as a white solid (0.5 g, 13%, 99% ee). Analytical
data are consistent with racemic acid C16.
(1R,3R)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxylic
acid (C160)
##STR00340##
[0868] Isolated as a white solid (2 g, 29%, 99% ee). Analytical
data are consistent with racemic acid C2.
Example 34:
(1S,3S)-2,2-Dichloro-3-(3,5-dichlorophenyl)-cyclopropane-1-carboxylic
acid (C161)
##STR00341##
[0870] The mother liquor from the 1.sup.st R,R-acid resolution
(from Example 33) was concentrated and dissolved in acetone
(.about.100 mL) and warmed to 45.degree. C. With swirling,
(S)-1-phenylethanamine (5.0 g, 41.2 mmol, 0.8 eq) was added. The
resulting solution was stirred at 45.degree. C. After a solid began
to deposit, the mixture was placed at 5.degree. C. for 2 hours. A
solid was collected, washed with minimal cold acetone and
vacuum-dried at 35.degree. C. The solid was treated with aqueous
hydrochloric acid to provide the free S,S-acid as a white solid
(9.87 g, 59%, 85% ee). A second resolution of the 85% ee combined
S,S-acid (13.45 g, 41.7 mmol, 85% ee) using the same procedure with
(S)-1-phenylethanamine (3.8 g, 31.3 mmol, 0.75 eq) provided the
S,S-acid as a white solid (8.53 g, 26%, 99% ee). Specific Rotation:
-51.9 (10 mg/mL in acetonitrile, 589 nm, 25.2.degree. C.).
Analytical data are consistent with racemic acid C1
[0871] ee was determined by Chiral HPLC method as follows: Column:
CHIRALPAK.RTM. ZWIX(+), particle size 3 .mu.m, dimension 3
mm.times.150 mm, DAIC 511584; Mobile phase: 49% acetonitrile/49%
methanol/water with 50 mM formic acid and diethylamine; Flow rate:
0.5 mL/min; Time: 9 min; Temperature: 25.degree. C.
[0872] The following compounds were prepared in like manner to the
procedure outlined in Example 34:
(1S,3S)-2,2-Dichloro-3-(3,4-dichlorophenyl)cyclopropane-1-carboxylic
acid (C162)
##STR00342##
[0874] Isolated as a as a white solid (7 g, 35%, 98% ee).
Analytical data are consistent with racemic acid C3.
(1S,3S)-2,2-Dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylic
acid (C163)
##STR00343##
[0876] Isolated as a white solid (0.64 g, 27%, 98% ee). Analytical
data are consistent with racemic acid C16.
(1S,3S)-2,2-Dichloro-3-(3,4,5-trichlorophenyl)cyclopropane-1-carboxylic
acid (C164)
##STR00344##
[0878] Isolated as a white solid (0.75 g, 41%, 99% ee). Analytical
data are consistent with racemic acid C2.
[0879] It is recognized that some reagents and reaction conditions
may not be compatible with certain functionalities that may be
present in certain molecules of Formula One or certain molecules
used in the preparation of certain molecules of Formula One. In
such cases, it may be necessary to employ standard protection and
deprotection protocols comprehensively reported in the literature
and well known to a person skilled in the art. In addition, in some
cases it may be necessary to perform further routine synthetic
steps not described herein to complete the synthesis of desired
molecules. A person skilled in the art will also recognize that it
may be possible to achieve the synthesis of desired molecules by
performing some of the steps of the synthetic routes in a different
order to that described. A person skilled in the art will also
recognize that it may be possible to perform standard functional
group interconversions or substitution reactions on desired
molecules to introduce or modify substituents.
Biological Assays
[0880] The following bioassays against Beet Armyworm (Spodoptera
exigua), Cabbage Looper (Trichoplusia ni), Green Peach Aphid (Myzus
persicae), and Yellow Fever Mosquito (Aedes aegypti), are included
herein due to the damage they inflict. Furthermore, the Beet
Armyworm and Cabbage Looper are two good indicator species for a
broad range of chewing pests. Additionally, the Green Peach Aphid
is a good indicator species for a broad range of sap-feeding pests.
The results with these three indicator species along with the
Yellow Fever Mosquito show the broad usefulness of the molecules of
Formula One in controlling pests in Phyla Arthropoda, Mollusca, and
Nematoda (Drewes et al.)
Example A: Bioassays on Beet Armyworm (Spodoptera exigua, LAPHEG)
("BAW"), and Cabbage Looper (Trichoplusia ni, TRIPNI) ("CL")
[0881] Beet armyworm is a serious pest of economic concern for
alfalfa, asparagus, beets, citrus, corn, cotton, onions, peas,
peppers, potatoes, soybeans, sugar beets, sunflowers, tobacco, and
tomatoes, among other crops. It is native to Southeast Asia but is
now found in Africa, Australia, Japan, North America, and Southern
Europe. The larvae may feed in large swarms causing devastating
crop losses. It is known to be resistant to several pesticides.
[0882] Cabbage looper is a serious pest found throughout the world.
It attacks alfalfa, beans, beets, broccoli, Brussel sprouts,
cabbage, cantaloupe, cauliflower, celery, collards, cotton,
cucumbers, eggplant, kale, lettuce, melons, mustard, parsley, peas,
peppers, potatoes, soybeans, spinach, squash, tomatoes, turnips,
and watermelons, among other crops. This species is very
destructive to plants due to its voracious appetite. The larvae
consume three times their weight in food daily. The feeding sites
are marked by large accumulations of sticky, wet, fecal material,
which may contribute to higher disease pressure thereby causing
secondary problems on the plants in the site. It is known to be
resistant to several pesticides.
[0883] Consequently, because of the above factors control of these
pests is important. Furthermore, molecules that control these pests
(BAW and CL), which are known as chewing pests, will be useful in
controlling other pests that chew on plants.
[0884] Certain molecules disclosed in this document were tested
against BAW and CL using procedures described in the following
examples. In the reporting of the results, the "BAW & CL Rating
Table" was used (See Table Section).
Bioassays on BAW
[0885] Bioassays on BAW were conducted using a 128-well diet tray
assay. One to five second instar BAW larvae were placed in each
well (3 mL) of the diet tray that had been previously filled with
approximately 1.5 mL of artificial diet to which 50 .mu.g/cm.sup.2
of the test molecule (dissolved in 50 .mu.L of 90:10 acetone-water
mixture) had been applied (to each of eight wells) and then allowed
to dry. Trays were covered with a clear self-adhesive cover, vented
to allow gas exchange, and held at 25.degree. C., 14:10 light-dark
for five to seven days. Percent mortality was recorded for the
larvae in each well; activity in the eight wells was then averaged.
The results are indicated in the table entitled "Table ABC:
Biological Results" (See Table Section).
Bioassays on CL
[0886] Bioassays on CL were conducted using a 128-well diet tray
assay. one to five second instar CL larvae were placed in each well
(3 mL) of the diet tray that had been previously filled with 1 mL
of artificial diet to which 50 .mu.g/cm.sup.2 of the test molecule
(dissolved in 50 .mu.L of 90:10 acetone-water mixture) had been
applied (to each of eight wells) and then allowed to dry. Trays
were covered with a clear self-adhesive cover, vented to allow gas
exchange, and held at 25.degree. C., 14:10 light-dark for five to
seven days. Percent mortality was recorded for the larvae in each
well; activity in the eight wells was then averaged. The results
are indicated in the table entitled "Table ABC: Biological Results"
(See Table Section).
Example B: Bioassays on Green Peach Aphid (Myzus persicae, MYZUPE)
("GPA")
[0887] GPA is the most significant aphid pest of peach trees,
causing decreased growth, shriveling of the leaves, and the death
of various tissues. It is also hazardous because it acts as a
vector for the transport of plant viruses, such as potato virus Y
and potato leafroll virus to members of the nightshade/potato
family Solanaceae, and various mosaic viruses to many other food
crops. GPA attacks such plants as broccoli, burdock, cabbage,
carrot, cauliflower, daikon, eggplant, green beans, lettuce,
macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress,
and zucchini, among other crops. GPA also attacks many ornamental
crops such as carnation, chrysanthemum, flowering white cabbage,
poinsettia, and roses. GPA has developed resistance to many
pesticides. Currently, it is a pest that has the third largest
number of reported cases of insect resistance (Sparks et al.).
Consequently, because of the above factors control of this pest is
important. Furthermore, molecules that control this pest (GPA),
which is known as a sap-feeding pest, are useful in controlling
other pests that feed on the sap from plants.
[0888] Certain molecules disclosed in this document were tested
against GPA using procedures described in the following example. In
the reporting of the results, the "GPA & YFM Rating Table" was
used (See Table Section).
[0889] Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5
cm) true leaves, were used as test substrate. The seedlings were
infested with 20-50 GPA (wingless adult and nymph stages) one day
prior to chemical application. Four pots with individual seedlings
were used for each treatment. Test molecules (2 mg) were dissolved
in 2 mL of acetone/methanol (1:1) solvent, forming stock solutions
of 1000 ppm test molecule. The stock solutions were diluted
5.times. with 0.025% Tween 20 in water to obtain the solution at
200 ppm test molecule. A hand-held aspirator-type sprayer was used
for spraying a solution to both sides of cabbage leaves until
runoff. Reference plants (solvent check) were sprayed with the
diluent only containing 20% by volume of acetone/methanol (1:1)
solvent. Treated plants were held in a holding room for three days
at approximately 25.degree. C. and ambient relative humidity (RH)
prior to grading. Evaluation was conducted by counting the number
of live aphids per plant under a microscope. Percent control was
measured using Abbott's correction formula (W. S. Abbott, "A Method
of Computing the Effectiveness of an Insecticide" J. Econ. Entomol.
18 (1925), pp. 265-267) as follows. Corrected % Control=100*(X-Y)/X
where X=No. of live aphids on solvent check plants and Y=No. of
live aphids on treated plants. The results are indicated in the
table entitled "Table ABC: Biological Results" (See Table
Section).
Example C: Bioassays on Yellow Fever Mosquito (Aedes aegypti,
AEDSAE) ("YFM")
[0890] YFM prefers to feed on humans during the daytime and is most
frequently found in or near human habitations. YFM is a vector for
transmitting several diseases. It is a mosquito that can spread the
dengue fever and yellow fever viruses. Yellow fever is the second
most dangerous mosquito-borne disease after malaria. Yellow fever
is an acute viral hemorrhagic disease and up to 50% of severely
affected persons without treatment will die from yellow fever.
There are an estimated 200,000 cases of yellow fever, causing
30,000 deaths worldwide each year. Dengue fever is a nasty, viral
disease; it is sometimes called "breakbone fever" or "break-heart
fever" because of the intense pain it can produce. Dengue fever
kills about 20,000 people annually. Consequently, because of the
above factors control of this pest is important. Furthermore,
molecules that control this pest (YFM), which is known as a sucking
pest, are useful in controlling other pests that cause human and
animal suffering.
[0891] Certain molecules disclosed in this document were tested
against YFM using procedures described in the following paragraph.
In the reporting of the results, the "GPA & YFM Rating Table"
was used (See Table Section).
[0892] Master plates containing 400 .mu.g of a molecule dissolved
in 100 .mu.L of dimethyl sulfoxide (DMSO) (equivalent to a 4000 ppm
solution) are used. A master plate of assembled molecules contains
15 .mu.L per well. To this plate, 135 .mu.L of a 90:10
water/acetone mixture is added to each well. A robot is programmed
to dispense 15 .mu.L aspirations from the master plate into an
empty 96-well shallow plate ("daughter" plate). There are 6 reps
("daughter" plates) created per master. The created "daughter"
plates are then immediately infested with YFM larvae.
[0893] The day before plates are to be treated, mosquito eggs are
placed in Millipore water containing liver powder to begin hatching
(4 g. into 400 mL). After the "daughter" plates are created using
the robot, they are infested with 220 .mu.L of the liver
powder/larval mosquito mixture (about 1 day-old larvae). After
plates are infested with mosquito larvae, a non-evaporative lid is
used to cover the plate to reduce drying. Plates are held at room
temperature for 3 days prior to grading. After 3 days, each well is
observed and scored based on mortality. The results are indicated
in the table entitled "Table ABC: Biological Results" (See Table
Section).
Agriculturally Acceptable Acid Addition Salts, Salt Derivatives,
Solvates, Ester Derivatives, Polymorphs, Isotopes, and
Radionuclides
[0894] Molecules of Formula One may be formulated into
agriculturally acceptable acid addition salts. By way of a
non-limiting example, an amine function can form salts with
hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, benzoic,
citric, malonic, salicylic, malic, fumaric, oxalic, succinic,
tartaric, lactic, gluconic, ascorbic, maleic, aspartic,
benzenesulfonic, methanesulfonic, ethanesulfonic,
hydroxyl-methanesulfonic, and hydroxyethanesulfonic acids.
Additionally, by way of a non-limiting example, an acid function
can form salts including those derived from alkali or alkaline
earth metals and those derived from ammonia and amines. Examples of
preferred cations include sodium, potassium, and magnesium.
[0895] Molecules of Formula One may be formulated into salt
derivatives. By way of a non-limiting example, a salt derivative
may be prepared by contacting a free base with a sufficient amount
of the desired acid to produce a salt. A free base may be
regenerated by treating the salt with a suitable dilute aqueous
base solution such as dilute aqueous sodium hydroxide, potassium
carbonate, ammonia, and sodium bicarbonate. As an example, in many
cases, a pesticide, such as 2,4-D, is made more water-soluble by
converting it to its dimethylamine salt.
[0896] Molecules of Formula One may be formulated into stable
complexes with a solvent, such that the complex remains intact
after the non-complexed solvent is removed. These complexes are
often referred to as "solvates." However, it is particularly
desirable to form stable hydrates with water as the solvent.
[0897] Molecules of Formula One containing an acid functionality
may be made into ester derivatives. These ester derivatives can
then be applied in the same manner as the molecules disclosed in
this document are applied.
[0898] Molecules of Formula One may be made as various crystal
polymorphs. Polymorphism is important in the development of
agrochemicals since different crystal polymorphs or structures of
the same molecule can have vastly different physical properties and
biological performances.
[0899] Molecules of Formula One may be made with different
isotopes. Of particular importance are molecules having .sup.2H
(also known as deuterium) or .sup.3H (also known as tritium) in
place of .sup.1H. Molecules of Formula One may be made with
different radionuclides. Of particular importance are molecules
having .sup.14C (also known as radiocarbon). Molecules of Formula
One having deuterium, tritium, or .sup.14C may be used in
biological studies allowing tracing in chemical and physiological
processes and half-life studies, as well as, MoA studies.
Combinations
[0900] In another embodiment of this invention, molecules of
Formula One may be used in combination (such as, in a compositional
mixture, or a simultaneous or sequential application) with one or
more active ingredients.
[0901] In another embodiment of this invention, molecules of
Formula One may be used in combination (such as, in a compositional
mixture, or a simultaneous or sequential application) with one or
more active ingredients each having a MoA that is the same as,
similar to, but more likely--different from, the MoA of the
molecules of Formula One.
[0902] In another embodiment, molecules of Formula One may be used
in combination (such as, in a compositional mixture, or a
simultaneous or sequential application) with one or more molecules
having acaricidal, algicidal, avicidal, bactericidal, fungicidal,
herbicidal, insecticidal, molluscicidal, nematicidal, rodenticidal,
and/or virucidal properties.
[0903] In another embodiment, the molecules of Formula One may be
used in combination (such as, in a compositional mixture, or a
simultaneous or sequential application) with one or more molecules
that are antifeedants, bird repellents, chemosterilants, herbicide
safeners, insect attractants, insect repellents, mammal repellents,
mating disrupters, plant activators, plant growth regulators,
and/or synergists.
[0904] In another embodiment, molecules of Formula One may also be
used in combination (such as in a compositional mixture, or a
simultaneous or sequential application) with one or more
biopesticides.
[0905] In another embodiment, in a pesticidal composition
combinations of a molecule of Formula One and an active ingredient
may be used in a wide variety of weight ratios. For example, in a
two-component mixture, the weight ratio of a molecule of Formula
One to an active ingredient, the weight ratios in Table B may be
used. However, in general, weight ratios less than about 10:1 to
about 1:10 are preferred. It is also preferred sometimes to use a
three, four, five, six, seven, or more, component mixture
comprising a molecule of Formula One and an additional two or more
active ingredients.
[0906] Weight ratios of a molecule of Formula One to an active
ingredient may also be depicted as X:Y; wherein X is the parts by
weight of a molecule of Formula One and Y is the parts by weight of
active ingredient. The numerical range of the parts by weight for X
is 0<X.ltoreq.100 and the parts by weight for Y is
0<Y.ltoreq.100 and is shown graphically in TABLE C. By way of
non-limiting example, the weight ratio of a molecule of Formula One
to an active ingredient may be 20:1.
[0907] Ranges of weight ratios of a molecule of Formula One to an
active ingredient may be depicted as X.sub.1:Y.sub.1 to
X.sub.2:Y.sub.2, wherein X and Y are defined as above. In one
embodiment, the range of weight ratios may be X.sub.1:Y.sub.1 to
X.sub.2:Y.sub.2, wherein X.sub.1>Y.sub.2 and X.sub.2<Y.sub.2.
By way of non-limiting example, the range of a weight ratio of a
molecule of Formula One to an active ingredient may be between 3:1
and 1:3, inclusive of the endpoints.
[0908] In another embodiment, the range of weight ratios may be
X.sub.1:Y.sub.1 to X.sub.2: Y.sub.2, wherein X.sub.1>Y.sub.1 and
X.sub.2>Y.sub.2. By way of non-limiting example, the range of
weight ratio of a molecule of Formula One to an active ingredient
may be between 15:1 and 3:1, inclusive of the endpoints.
[0909] In another embodiment, the range of weight ratios may be
X.sub.1:Y.sub.1 to X.sub.2:Y.sub.2, wherein X.sub.1<Y.sub.1 and
X.sub.2<Y.sub.2. By way of non-limiting example, the range of
weight ratios of a molecule of Formula One to an active ingredient
may be between about 1:3 and about 1:20, inclusive of the
endpoints.
Formulations
[0910] A pesticide is many times not suitable for application in
its pure form. It is usually necessary to add other substances so
that the pesticide may be used at the required concentration and in
an appropriate form, permitting ease of application, handling,
transportation, storage, and maximum pesticide activity. Thus,
pesticides are formulated into, for example, baits, concentrated
emulsions, dusts, emulsifiable concentrates, fumigants, gels,
granules, microencapsulations, seed treatments, suspension
concentrates, suspoemulsions, tablets, water soluble liquids, water
dispersible granules or dry flowables, wettable powders, and
ultra-low volume solutions.
[0911] Pesticides are applied most often as aqueous suspensions or
emulsions prepared from concentrated formulations of such
pesticides. Such water-soluble, water-suspendable, or emulsifiable
formulations are either solids, usually known as wettable powders,
water dispersible granules, liquids usually known as emulsifiable
concentrates, or aqueous suspensions. Wettable powders, which may
be compacted to form water dispersible granules, comprise an
intimate mixture of the pesticide, a carrier, and surfactants. The
concentration of the pesticide is usually from about 10% to about
90% by weight. The carrier is usually selected from among the
attapulgite clays, the montmorillonite clays, the diatomaceous
earths, or the purified silicates. Effective surfactants,
comprising from about 0.5% to about 10% of the wettable powder, are
found among sulfonated lignins, condensed naphthalenesulfonates,
naphthalenesulfonates, alkylbenzenesulfonates, alkyl sulfates, and
non-ionic surfactants such as ethylene oxide adducts of alkyl
phenols.
[0912] Emulsifiable concentrates of pesticides comprise a
convenient concentration of a pesticide, such as from about 50 to
about 500 grams per liter of liquid dissolved in a carrier that is
either a water miscible solvent or a mixture of water-immiscible
organic solvent and emulsifiers. Useful organic solvents include
aromatics, especially xylenes and petroleum fractions, especially
the high-boiling naphthalenic and olefinic portions of petroleum
such as heavy aromatic naphtha. Other organic solvents may also be
used, such as the terpenic solvents including rosin derivatives,
aliphatic ketones such as cyclohexanone, and complex alcohols such
as 2-ethoxyethanol. Suitable emulsifiers for emulsifiable
concentrates are selected from conventional anionic and non-ionic
surfactants.
[0913] Aqueous suspensions comprise suspensions of water-insoluble
pesticides dispersed in an aqueous carrier at a concentration in
the range from about 5% to about 50% by weight. Suspensions are
prepared by finely grinding the pesticide and vigorously mixing it
into a carrier comprised of water and surfactants. Ingredients,
such as inorganic salts and synthetic or natural gums may, also be
added to increase the density and viscosity of the aqueous carrier.
It is often most effective to grind and mix the pesticide at the
same time by preparing the aqueous mixture and homogenizing it in
an implement such as a sand mill, ball mill, or piston-type
homogenizer. The pesticide in suspension might be microencapsulated
in plastic polymer.
[0914] Oil dispersions (OD) comprise suspensions of organic
solvent-insoluble pesticides finely dispersed in a mixture of
organic solvent and emulsifiers at a concentration in the range
from about 2% to about 50% by weight. One or more pesticide might
be dissolved in the organic solvent. Useful organic solvents
include aromatics, especially xylenes and petroleum fractions,
especially the high-boiling naphthalenic and olefinic portions of
petroleum such as heavy aromatic naphtha. Other solvents may
include vegetable oils, seed oils, and esters of vegetable and seed
oils. Suitable emulsifiers for oil dispersions are selected from
conventional anionic and non-ionic surfactants. Thickeners or
gelling agents are added in the formulation of oil dispersions to
modify the rheology or flow properties of the liquid and to prevent
separation and settling of the dispersed particles or droplets.
[0915] Pesticides may also be applied as granular compositions that
are particularly useful for applications to the soil. Granular
compositions usually contain from about 0.5% to about 10% by weight
of the pesticide, dispersed in a carrier that comprises clay or a
similar substance. Such compositions are usually prepared by
dissolving the pesticide in a suitable solvent and applying it to a
granular carrier, which has been pre-formed to the appropriate
particle size, in the range of from about 0.5 mm to about 3 mm.
Such compositions may also be formulated by making a dough or paste
of the carrier and molecule, and then crushing and drying to obtain
the desired granular particle size. Another form of granules is a
water emulsifiable granule (EG). It is a formulation consisting of
granules to be applied as a conventional oil-in-water emulsion of
the active ingredient(s), either solubilized or diluted in an
organic solvent, after disintegration and dissolution in water.
Water emulsifiable granules comprise one or several active
ingredient(s), either solubilized or diluted in a suitable organic
solvent that is (are) absorbed in a water soluble polymeric shell
or some other type of soluble or insoluble matrix.
[0916] Dusts containing a pesticide are prepared by intimately
mixing the pesticide in powdered form with a suitable dusty
agricultural carrier, such as kaolin clay, ground volcanic rock,
and the like. Dusts can suitably contain from about 1% to about 10%
of the pesticide. Dusts may be applied as a seed dressing or as a
foliage application with a dust blower machine.
[0917] It is equally practical to apply a pesticide in the form of
a solution in an appropriate organic solvent, usually petroleum
oil, such as the spray oils, which are widely used in agricultural
chemistry.
[0918] Pesticides can also be applied in the form of an aerosol
composition. In such compositions, the pesticide is dissolved or
dispersed in a carrier, which is a pressure-generating propellant
mixture. The aerosol composition is packaged in a container from
which the mixture is dispensed through an atomizing valve.
[0919] Pesticide baits are formed when the pesticide is mixed with
food or an attractant or both. When the pests eat the bait, they
also consume the pesticide. Baits may take the form of granules,
gels, flowable powders, liquids, or solids. Baits may be used in
pest harborages.
[0920] Fumigants are pesticides that have a relatively high vapor
pressure and hence can exist as a gas in sufficient concentrations
to kill pests in soil or enclosed spaces. The toxicity of the
fumigant is proportional to its concentration and the exposure
time. They are characterized by a good capacity for diffusion and
act by penetrating the pest's respiratory system or being absorbed
through the pest's cuticle. Fumigants are applied to control stored
product pests under gas proof sheets, in gas sealed rooms or
buildings, or in special chambers.
[0921] Pesticides may be microencapsulated by suspending the
pesticide particles or droplets in plastic polymers of various
types. By altering, the chemistry of the polymer or by changing
factors in the processing, microcapsules may be formed of various
sizes, solubility, wall thicknesses, and degrees of penetrability.
These factors govern the speed with which the active ingredient
within is released, which in turn, affects the residual
performance, speed of action, and odor of the product. The
microcapsules might be formulated as suspension concentrates or
water dispersible granules.
[0922] Oil solution concentrates are made by dissolving pesticide
in a solvent that will hold the pesticide in solution. Oil
solutions of a pesticide usually provide faster knockdown and kill
of pests than other formulations due to the solvents themselves
having pesticidal action and the dissolution of the waxy covering
of the integument increasing the speed of uptake of the pesticide.
Other advantages of oil solutions include better storage stability,
better penetration of crevices, and better adhesion to greasy
surfaces.
[0923] Another embodiment is an oil-in-water emulsion, wherein the
emulsion comprises oily globules which are each provided with a
lamellar liquid crystal coating and are dispersed in an aqueous
phase, wherein each oily globule comprises at least one molecule
which is agriculturally active, and is individually coated with a
monolamellar or oligolamellar layer comprising: (1) at least one
non-ionic lipophilic surface-active agent, (2) at least one
non-ionic hydrophilic surface-active agent, and (3) at least one
ionic surface-active agent, wherein the globules having a mean
particle diameter of less than 800 nanometers.
Other Formulation Components
[0924] Generally, when the molecules disclosed in Formula One are
used in a formulation, such formulation can also contain other
components. These components include, but are not limited to, (this
is a non-exhaustive and non-mutually exclusive list) wetters,
spreaders, stickers, penetrants, buffers, sequestering agents,
drift reduction agents, compatibility agents, anti-foam agents,
cleaning agents, and emulsifiers. A few components are described
forthwith.
[0925] A wetting agent is a substance that when added to a liquid
increases the spreading or penetration power of the liquid by
reducing the interfacial tension between the liquid and the surface
on which it is spreading. Wetting agents are used for two main
functions in agrochemical formulations: during processing and
manufacture to increase the rate of wetting of powders in water to
make concentrates for soluble liquids or suspension concentrates;
and during mixing of a product with water in a spray tank to reduce
the wetting time of wettable powders and to improve the penetration
of water into water-dispersible granules. Examples of wetting
agents used in wettable powder, suspension concentrate, and
water-dispersible granule formulations are: sodium lauryl sulfate;
sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and
aliphatic alcohol ethoxylates.
[0926] A dispersing agent is a substance that adsorbs onto the
surface of particles, helps to preserve the state of dispersion of
the particles, and prevents them from reaggregating. Dispersing
agents are added to agrochemical formulations to facilitate
dispersion and suspension during manufacture, and to ensure the
particles redisperse into water in a spray tank. They are widely
used in wettable powders, suspension concentrates, and
water-dispersible granules. Surfactants that are used as dispersing
agents have the ability to adsorb strongly onto a particle surface
and provide a charged or steric barrier to reaggregation of
particles. The most commonly used surfactants are anionic,
non-ionic, or mixtures of the two types. For wettable powder
formulations, the most common dispersing agents are sodium
lignosulfonates. For suspension concentrates, very good adsorption
and stabilization are obtained using polyelectrolytes, such as
sodium-naphthalene-sulfonate-formaldehyde-condensates.
Tristyrylphenol ethoxylate phosphate esters are also used.
Non-ionics such as alkylarylethylene oxide condensates and EO-PO
block copolymers are sometimes combined with anionics as dispersing
agents for suspension concentrates. In recent years, new types of
very high molecular weight polymeric surfactants have been
developed as dispersing agents. These have very long hydrophobic
`backbones` and a large number of ethylene oxide chains forming the
`teeth` of a `comb` surfactant. These high molecular weight
polymers can give very good long-term stability to suspension
concentrates because the hydrophobic backbones have many anchoring
points onto the particle surfaces. Examples of dispersing agents
used in agrochemical formulations are: sodium lignosulfonates;
sodium naphthalene sulfonate formaldehyde condensates;
tristyrylphenol-ethoxylate-phosphate-esters; aliphatic alcohol
ethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graft
copolymers.
[0927] An emulsifying agent is a substance that stabilizes a
suspension of droplets of one liquid phase in another liquid phase.
Without the emulsifying agent, the two liquids would separate into
two immiscible liquid phases. The most commonly used emulsifier
blends contain an alkylphenol or an aliphatic alcohol with twelve
or more ethylene oxide units and the oil-soluble calcium salt of
dodecylbenzenesulfonic acid. A range of hydrophile-lipophile
balance ("HLB") values from about 8 to about 18 will normally
provide good stable emulsions. Emulsion stability can sometimes be
improved by the addition of a small amount of an EO-PO block
copolymer surfactant.
[0928] A solubilizing agent is a surfactant that will form micelles
in water at concentrations above the critical micelle
concentration. The micelles are then able to dissolve or solubilize
water-insoluble materials inside the hydrophobic part of the
micelle. The types of surfactants usually used for solubilization
are non-ionics, sorbitan monooleates, sorbitan monooleate
ethoxylates, and methyl oleate esters.
[0929] Surfactants are sometimes used, either alone or with other
additives such as mineral or vegetable oils as adjuvants to
spray-tank mixes to improve the biological performance of the
pesticide on the target. The types of surfactants used for
bioenhancement depend generally on the nature and mode of action of
the pesticide. However, they are often non-ionics such as: alkyl
ethoxylates; linear aliphatic alcohol ethoxylates; and aliphatic
amine ethoxylates.
[0930] A carrier or diluent in an agricultural formulation is a
material added to the pesticide to give a product of the required
strength. Carriers are usually materials with high absorptive
capacities, while diluents are usually materials with low
absorptive capacities. Carriers and diluents are used in the
formulation of dusts, wettable powders, granules, and
water-dispersible granules.
[0931] Organic solvents are used mainly in the formulation of
emulsifiable concentrates, oil-in-water emulsions, suspoemulsions,
oil dispersions, and ultra-low volume formulations, and to a lesser
extent, granular formulations. Sometimes mixtures of solvents are
used. The first main groups of solvents are aliphatic paraffinic
oils such as kerosene or refined paraffins. The second main group
(and the most common) comprises the aromatic solvents such as
xylene and higher molecular weight fractions of C9 and C10 aromatic
solvents. Chlorinated hydrocarbons are useful as cosolvents to
prevent crystallization of pesticides when the formulation is
emulsified into water. Alcohols are sometimes used as cosolvents to
increase solvent power. Other solvents may include vegetable oils,
seed oils, and esters of vegetable and seed oils.
[0932] Thickeners or gelling agents are used mainly in the
formulation of suspension concentrates, oil dispersions, emulsions
and suspoemulsions to modify the rheology or flow properties of the
liquid and to prevent separation and settling of the dispersed
particles or droplets. Thickening, gelling, and anti-settling
agents generally fall into two categories, namely water-insoluble
particulates and water-soluble polymers. It is possible to produce
suspension concentrate and oil dispersion formulations using days
and silicas. Examples of these types of materials, include, but are
not limited to, montmorillonite, bentonite, magnesium aluminum
silicate, and attapulgite. Water-soluble polysaccharides in water
based suspension concentrates have been used as thickening-gelling
agents for many years. The types of polysaccharides most commonly
used are natural extracts of seeds and seaweeds or are synthetic
derivatives of cellulose. Examples of these types of materials
include, but are not limited to, guar gum; locust bean gum;
carrageenam; alginates; methyl cellulose; sodium carboxymethyl
cellulose (SCMC); and hydroxyethyl cellulose (HEC). Other types of
anti-settling agents are based on modified starches, polyacrylates,
polyvinyl alcohol, and polyethylene oxide. Another good
anti-settling agent is xanthan gum.
[0933] Microorganisms can cause spoilage of formulated products.
Therefore, preservation agents are used to eliminate or reduce
their effect. Examples of such agents include, but are not limited
to: propionic acid and its sodium salt; sorbic acid and its sodium
or potassium salts; benzoic acid and its sodium salt;
p-hydroxybenzoic acid sodium salt; methyl p-hydroxybenzoate; and
1,2-benzisothiazolin-3-one (BIT).
[0934] The presence of surfactants often causes water-based
formulations to foam during mixing operations in production and in
application through a spray tank. In order to reduce the tendency
to foam, anti-foam agents are often added either during the
production stage or before filling into bottles. Generally, there
are two types of anti-foam agents, namely silicones and
non-silicones. Silicones are usually aqueous emulsions of dimethyl
polysiloxane, while the non-silicone anti-foam agents are
water-insoluble oils, such as octanol and nonanol, or silica. In
both cases, the function of the anti-foam agent is to displace the
surfactant from the air-water interface.
[0935] "Green" agents (e.g., adjuvants, surfactants, solvents) can
reduce the overall environmental footprint of crop protection
formulations. Green agents are biodegradable and generally derived
from natural and/or sustainable sources, e.g. plant and animal
sources. Specific examples are: vegetable oils, seed oils, and
esters thereof, also alkoxylated alkyl polyglucosides.
Applications
[0936] Molecules of Formula One may be applied to any locus.
Particular loci to apply such molecules include loci where alfalfa,
almonds, apples, barley, beans, canola, corn, cotton, crucifers,
flowers, fodder species (Rye Grass, Sudan Grass, Tall Fescue, Ky.
Blue Grass, and Clover), fruits, lettuce, oats, oil seed crops,
oranges, peanuts, pears, peppers, potatoes, rice, sorghum,
soybeans, strawberries, sugarcane, sugarbeets, sunflowers, tobacco,
tomatoes, wheat (for example, Hard Red Winter Wheat, Soft Red
Winter Wheat, White Winter Wheat, Hard Red Spring Wheat, and Durum
Spring Wheat), and other valuable crops are growing or the seeds
thereof are going to be planted.
[0937] Molecules of Formula One may also be applied where plants,
such as crops, are growing and where there are low levels (even no
actual presence) of pests that can commercially damage such plants.
Applying such molecules in such locus is to benefit the plants
being grown in such locus. Such benefits, may include, but are not
limited to: helping the plant grow a better root system; helping
the plant better withstand stressful growing conditions; improving
the health of a plant; improving the yield of a plant (e.g.
increased biomass and/or increased content of valuable
ingredients); improving the vigor of a plant (e.g. improved plant
growth and/or greener leaves); improving the quality of a plant
(e.g. improved content or composition of certain ingredients); and
improving the tolerance to abiotic and/or biotic stress of the
plant.
[0938] Molecules of Formula One may be applied with ammonium
sulfate when growing various plants as this may provide additional
benefits.
[0939] Molecules of Formula One may be applied on, in, or around
plants genetically modified to express specialized traits, such as
Bacillus thuringiensis (for example, Cry1Ab, Cry1Ac, Cry1Fa,
Cry1A.105, Cry2Ab, Vip3A, mCry3A, Cry3Ab, Cry3Bb,
Cry34Ab1/Cry35Ab1), other insecticidal toxins, or those expressing
herbicide tolerance, or those with "stacked" foreign genes
expressing insecticidal toxins, herbicide tolerance,
nutrition-enhancement, or any other beneficial traits.
[0940] Molecules of Formula One may be applied to the foliar and/or
fruiting portions of plants to control pests. Either such molecules
will come in direct contact with the pest, or the pest will consume
such molecules when eating the plant or while extracting sap or
other nutrients from the plant.
[0941] Molecules of Formula One may also be applied to the soil,
and when applied in this manner, root and stem feeding pests may be
controlled. The roots may absorb such molecules thereby taking it
up into the foliar portions of the plant to control above ground
chewing and sap feeding pests.
[0942] Systemic movement of pesticides in plants may be utilized to
control pests on one portion of the plant by applying (for example
by spraying a locus) a molecule of Formula One to a different
portion of the plant. For example, control of foliar-feeding
insects may be achieved by drip irrigation or furrow application,
by treating the soil with for example pre- or post-planting soil
drench, or by treating the seeds of a plant before planting.
[0943] Molecules of Formula One may be used with baits. Generally,
with baits, the baits are placed in the ground where, for example,
termites can come into contact with, and/or be attracted to, the
bait. Baits can also be applied to a surface of a building,
(horizontal, vertical, or slant surface) where, for example, ants,
termites, cockroaches, and flies, can come into contact with,
and/or be attracted to, the bait.
[0944] Molecules of Formula One may be encapsulated inside, or
placed on the surface of a capsule. The size of the capsules can
range from nanometer size (about 100-900 nanometers in diameter) to
micrometer size (about 10-900 microns in diameter).
[0945] Molecules of Formula One may be applied to eggs of pests.
Because of the unique ability of the eggs of some pests to resist
certain pesticides, repeated applications of such molecules may be
desirable to control newly emerged larvae.
[0946] Molecules of Formula One may be applied as seed treatments.
Seed treatment may be applied to all types of seeds, including
those from which plants genetically modified to express specialized
traits will germinate. Representative examples include those
expressing proteins toxic to invertebrate pests, such as Bacillus
thuringiensis or other insecticidal toxins, those expressing
herbicide tolerance, such as "Roundup Ready" seed, or those with
"stacked" foreign genes expressing insecticidal toxins, herbicide
tolerance, nutrition-enhancement, drought tolerance, or any other
beneficial traits. Furthermore, such seed treatments with molecules
of Formula One may further enhance the ability of a plant to
withstand stressful growing conditions better. This results in a
healthier, more vigorous plant, which can lead to higher yields at
harvest time. Generally, about 1 gram of such molecules to about
500 grams per 100,000 seeds is expected to provide good benefits,
amounts from about 10 grams to about 100 grams per 100,000 seeds is
expected to provide better benefits, and amounts from about 25
grams to about 75 grams per 100,000 seeds is expected to provide
even better benefits. Molecules of Formula One may be applied with
one or more active ingredients in a soil amendment.
[0947] Molecules of Formula One may be used for controlling
endoparasites and ectoparasites in the veterinary medicine sector
or in the field of non-human-animal keeping. Such molecules may be
applied by oral administration in the form of, for example,
tablets, capsules, drinks, granules, by dermal application in the
form of, for example, dipping, spraying, pouring on, spotting on,
and dusting, and by parenteral administration in the form of, for
example, an injection.
[0948] Molecules of Formula One may also be employed advantageously
in livestock keeping, for example, cattle, chickens, geese, goats,
pigs, sheep, and turkeys. They may also be employed advantageously
in pets such as, horses, dogs, and cats. Particular pests to
control would be flies, fleas, and ticks that are bothersome to
such animals. Suitable formulations are administered orally to the
animals with the drinking water or feed. The dosages and
formulations that are suitable depend on the species.
[0949] Molecules of Formula One may also be used for controlling
parasitic worms, especially of the intestine, in the animals listed
above.
[0950] Molecules of Formula One may also be employed in therapeutic
methods for human health care. Such methods include, but are
limited to, oral administration in the form of, for example,
tablets, capsules, drinks, granules, and by dermal application.
[0951] Molecules of Formula One may also be applied to invasive
pests. Pests around the world have been migrating to new
environments (for such pest) and thereafter becoming a new invasive
species in such new environment. Such molecules may also be used on
such new invasive species to control them in such new
environments.
[0952] Before a pesticide may be used or sold commercially, such
pesticide undergoes lengthy evaluation processes by various
governmental authorities (local, regional, state, national, and
international). Voluminous data requirements are specified by
regulatory authorities and must be addressed through data
generation and submission by the product registrant or by a third
party on the product registrants behalf, often using a computer
with a connection to the World Wide Web. These governmental
authorities then review such data and if a determination of safety
is concluded, provide the potential user or seller with product
registration approval. Thereafter, in that locality where the
product registration is granted and supported, such user or seller
may use or sell such pesticide.
[0953] Molecules according to Formula One may be tested to
determine its efficacy against pests. Furthermore, mode of action
studies may be conducted to determine if said molecule has a
different mode of action than other pesticides. Thereafter, such
acquired data may be disseminated, such as by the Internet, to
third parties.
[0954] The headings in this document are for convenience only and
must not be used to interpret any portion hereof.
Tables
TABLE-US-00003 [0955] TABLE B Weight Ratios Molecule of the Formula
One:active ingredient 100:1 to 1:100 50:1 to 1:50 20:1 to 1:20 10:1
to 1:10 5:1 to 1:5 3:1 to 1:3 2:1 to 1:2 1:1
TABLE-US-00004 TABLE C active ingredient 100 X, Y X, Y X, Y (Y)
Parts by weight 50 X, Y X, Y X, Y X, Y X, Y 20 X, Y X, Y X, Y X, Y
X, Y 15 X, Y X, Y X, Y X, Y X, Y 10 X, Y X, Y 5 X, Y X, Y X, Y X, Y
3 X, Y X, Y X, Y X, Y X, Y X, Y X, Y 2 X, Y X, Y X, Y X, Y X, Y 1
X, Y X, Y X, Y X, Y X, Y X, Y X, Y X, Y X, Y 1 2 3 5 10 15 20 50
100 molecule of Formula One (X) Parts by weight
TABLE-US-00005 TABLE 2 Structure and preparation method for F and
PF Series molecules No. Structure Prep.* F1 ##STR00345## 13 F2
##STR00346## 13 F3 ##STR00347## 13 F4 ##STR00348## 13 F5
##STR00349## 13 F6 ##STR00350## 13 F7 ##STR00351## 13 F8
##STR00352## 13 F9 ##STR00353## 13 F10 ##STR00354## 13 F11
##STR00355## 13 F12 ##STR00356## 13 F13 ##STR00357## 13 F14
##STR00358## 13 F15 ##STR00359## 13 F16 ##STR00360## 13 F17
##STR00361## 13 F18 ##STR00362## 13 F19 ##STR00363## 13 F20
##STR00364## 13 F21 ##STR00365## 13 F22 ##STR00366## 13 F23
##STR00367## 13 F24 ##STR00368## 13 F25 ##STR00369## 13 F26
##STR00370## 13 F27 ##STR00371## 14 F28 ##STR00372## 14 F29
##STR00373## 15 F30 ##STR00374## 16 F31 ##STR00375## 16 F32
##STR00376## 16 F33 ##STR00377## 16 F34 ##STR00378## 16 F35
##STR00379## 16 F36 ##STR00380## 16 F37 ##STR00381## 16 F38
##STR00382## 16 F39 ##STR00383## 16 F40 ##STR00384## 16 F41
##STR00385## 16 F42 ##STR00386## 16 F43 ##STR00387## 16 F44
##STR00388## 16 F45 ##STR00389## 16 F46 ##STR00390## 16 F47
##STR00391## 16 F48 ##STR00392## 16 F49 ##STR00393## 16 F50
##STR00394## 16 F51 ##STR00395## 16 F52 ##STR00396## 16 F53
##STR00397## 16 F54 ##STR00398## 16 F55 ##STR00399## 16 F56
##STR00400## 16 F57 ##STR00401## 16 F58 ##STR00402## 16 F59
##STR00403## 16 F60 ##STR00404## 16 F61 ##STR00405## 16 F62
##STR00406## 16 F63 ##STR00407## 16 F64 ##STR00408## 16 F65
##STR00409## 16 F66 ##STR00410## 16 F67 ##STR00411## 16 F68
##STR00412## 16 F69 ##STR00413## 16 F70 ##STR00414## 16 F71
##STR00415## 16 F72 ##STR00416## 16 F73 ##STR00417## 16 F74
##STR00418## 17 F75 ##STR00419## 17 F78 ##STR00420## 16 F79
##STR00421## 16 F84 ##STR00422## 16 F85 ##STR00423## 16 F86
##STR00424## 16 F87 ##STR00425## 16 F88 ##STR00426## 16 F91
##STR00427## 16 F92 ##STR00428## 16 F93 ##STR00429## 16 F94
##STR00430## 16 F95 ##STR00431## 16 F96 ##STR00432## 23 F97
##STR00433## 15 F98 ##STR00434## 16 F99 ##STR00435## 16 F100
##STR00436## 16 F101 ##STR00437## 16 F102 ##STR00438## 16 F103
##STR00439## 16 F104 ##STR00440## 16 F105 ##STR00441## 16 F106
##STR00442## 16 F107 ##STR00443## 16 F108 ##STR00444## 24 F109
##STR00445## 24 F111 ##STR00446## 24 F112 ##STR00447## 24 F113
##STR00448## 24 F114 ##STR00449## 24 F115 ##STR00450## 24 F116
##STR00451## 24 F117 ##STR00452## 24 F118 ##STR00453## 24 F119
##STR00454## 24 F120 ##STR00455## 24 F121 ##STR00456## 24 F122
##STR00457## 24 F123 ##STR00458## 24 F124 ##STR00459## 24 F125
##STR00460## 24 F126 ##STR00461## 24 F127 ##STR00462## 24 F128
##STR00463## 24 F129 ##STR00464## 24 F130 ##STR00465## 24 F131
##STR00466## 24 F132 ##STR00467## 24
F133 ##STR00468## 24 F134 ##STR00469## 24 F135 ##STR00470## 24 PF1
##STR00471## 13 PF2 ##STR00472## 16 PF3 ##STR00473## 16 PF4
##STR00474## .sup. 17a PF5 ##STR00475## .sup. 17a PF6 ##STR00476##
.sup. 17a PF7 ##STR00477## .sup. 17a PF9 ##STR00478## 16 PF10
##STR00479## 16 PF11 ##STR00480## 16 PF12 ##STR00481## 16 PF13
##STR00482## 16 PF14 ##STR00483## 16 PF15 ##STR00484## 16 PF16
##STR00485## 16 *prepared according to example number
TABLE-US-00006 TABLE 3 Structure and preparation method for C
series molecules No. Structure Prep* C1 ##STR00486## 1 C2
##STR00487## 1 C3 ##STR00488## 1 C4 ##STR00489## 2 C5 ##STR00490##
2 C6 ##STR00491## 2 C7 ##STR00492## 2 C8 ##STR00493## 2 C9
##STR00494## 2 C10 ##STR00495## 2 C11 ##STR00496## 2 C12
##STR00497## 2 C13 ##STR00498## 2 C14 ##STR00499## 2 C15
##STR00500## 2 C16 ##STR00501## 2 C17 ##STR00502## 2 C18
##STR00503## 2 C19 ##STR00504## 2 C20 ##STR00505## 2 C21
##STR00506## 2 C22 ##STR00507## 3 C23 ##STR00508## 3 C24
##STR00509## 3 C25 ##STR00510## 4 C26 ##STR00511## 4 C27
##STR00512## 4 C28 ##STR00513## 4 C29 ##STR00514## 4 C30
##STR00515## 4 C31 ##STR00516## 4 C32 ##STR00517## 4 C33
##STR00518## 4 C34 ##STR00519## 4 C35 ##STR00520## 4 C36
##STR00521## 4 C37 ##STR00522## 4 C38 ##STR00523## 4 C39
##STR00524## 4 C40 ##STR00525## 4 C41 ##STR00526## 4 C42
##STR00527## 4 C43 ##STR00528## 5 C44 ##STR00529## 5 C45
##STR00530## 5 C46 ##STR00531## 6 C47 ##STR00532## 6 C48
##STR00533## 6 C49 ##STR00534## 6 C50 ##STR00535## 6 C51
##STR00536## 6 C52 ##STR00537## 6 C53 ##STR00538## 6 C54
##STR00539## 6 C55 ##STR00540## 6 C56 ##STR00541## 6 C57
##STR00542## 6 C58 ##STR00543## 6 C59 ##STR00544## 6 C60
##STR00545## 7 C61 ##STR00546## 7 C62 ##STR00547## 7 C63
##STR00548## 8 C64 ##STR00549## 9 C65 ##STR00550## 10 C66
##STR00551## 11 C67 ##STR00552## 12 C68 ##STR00553## 17b C69
##STR00554## 17b C70 ##STR00555## 17b C71 ##STR00556## 17b C72
##STR00557## 18 C73 ##STR00558## 18 C74 ##STR00559## 18 C75
##STR00560## 18 C76 ##STR00561## 18 C77 ##STR00562## 19 C78
##STR00563## 19 C79 ##STR00564## 19 C80 ##STR00565## 20 C81
##STR00566## 21 C82 ##STR00567## 21 C83 ##STR00568## 21 C84
##STR00569## 22 C85 ##STR00570## 2 C86 ##STR00571## 2 C87
##STR00572## 2 C88 ##STR00573## 2 C89 ##STR00574## 2 C90
##STR00575## 2 C91 ##STR00576## 2 C92 ##STR00577## 2 C93
##STR00578## 2 C94 ##STR00579## 2 C95 ##STR00580## 4 C96
##STR00581## 4 C97 ##STR00582## 4 C98 ##STR00583## 4 C99
##STR00584## 4 C100 ##STR00585## 4 C101 ##STR00586## 4 C102
##STR00587## 4 C103 ##STR00588## 12 C104 ##STR00589## 12 C105
##STR00590## 12 C106 ##STR00591## 12 C107 ##STR00592## 25 C108
##STR00593## 25 C109 ##STR00594## 25 C110 ##STR00595## 25 C111
##STR00596## 25 C112 ##STR00597## 25 C113 ##STR00598## 25 C114
##STR00599## 25 C115 ##STR00600## 26 C116 ##STR00601## 26 C117
##STR00602## 26 C118 ##STR00603## 26 C119 ##STR00604## 26 C120
##STR00605## 26 C121 ##STR00606## 26 C122 ##STR00607## 26 C123
##STR00608## 27
C124 ##STR00609## 27 C125 ##STR00610## 27 C126 ##STR00611## 27 C127
##STR00612## 27 C128 ##STR00613## 27 C129 ##STR00614## 27 C130
##STR00615## 27 C131 ##STR00616## 27 C132 ##STR00617## 27 C133
##STR00618## 27 C134 ##STR00619## 27 C135 ##STR00620## 27 C136
##STR00621## 27 C137 ##STR00622## 27 C138 ##STR00623## 27 C139
##STR00624## 27 C140 ##STR00625## 28 C141 ##STR00626## 28 C142
##STR00627## 28 C143 ##STR00628## 28 C144 ##STR00629## 28 C145
##STR00630## 29 C146 ##STR00631## 29 C147 ##STR00632## 29 C148
##STR00633## 29 C149 ##STR00634## 29 C150 ##STR00635## 30 C151
##STR00636## 30 C152 ##STR00637## 30 C153 ##STR00638## 30 C154
##STR00639## 30 C155 ##STR00640## 31 C156 ##STR00641## 32 C157
##STR00642## 33 C158 ##STR00643## 33 C159 ##STR00644## 33 C160
##STR00645## 33 C161 ##STR00646## 33 C162 ##STR00647## 33 C163
##STR00648## 33 C164 ##STR00649## 33 *prepared according to example
number
TABLE-US-00007 TABLE 4 Analytical data for molecules in Table 2 Mp
No. (.degree. C.) IR (cm.sup.-1) Mass (m/z) NMR (.sup.1H, .sup.13C,
or .sup.19F) F1 185-187 HRMS-ESI [M].sup.+ .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. calcd for 10.14 (s, 1H), 7.93 (dd, J = 8.8,
C.sub.18H.sub.14Cl.sub.5N.sub.2O.sub.2, 2.6 Hz, 1H), 7.43 (d, J =
2.6 Hz, 466.9464; found, 1H), 7.33 (t, J = 1.7 Hz, 466.9472. 1H),
7.27 (d, J = 8.8 Hz, 1H), 7.18 (dd, J = 1.8, 0.6 Hz, 2H), 6.70 (q,
J = 4.6 Hz, 1H), 3.50 (d, J = 8.2 Hz, 1H), 3.10 (d, J = 8.2 Hz,
1H), 3.05 (d, J = 4.9 Hz, 3H); .sup.13C NMR (126 MHz, DMSO-d.sub.6)
.delta. 166.32, 162.44, 137.45, 137.32, 137.18, 133.96, 130.01,
127.80, 127.59, 123.87, 120.85, 118.98, 62.04, 38.28, 36.67, 25.85
F2 (thin film) ESIMS 501 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 3274,
([M + H].sup.+) .delta. 11.09 (s, 1H), 8.45 (q, J = 4.5 Hz, 3069,
1H), 7.89-7.73 (m, 1641 3H), 7.64 (t, J = 1.8 Hz, 1H), 7.57 (dd, J
= 1.9, 0.5 Hz, 2H), 3.64 (d, J = 8.5 Hz, 1H), 3.55 (d, J = 8.5 Hz,
1H), 2.76 (d, J = 4.6 Hz, 3H) F3 244-245 ESIMS 499 .sup.1H NMR (400
MHz, DMSO-d.sub.6) ([M - H].sup.-) .delta. 10.90 (s, 1H), 9.15 (t,
J = 6.3 Hz, 1H), 8.16 (br s, 1H), 7.86 (br d, J = 8 Hz, 1H),
7.66-7.60 (m, 2H), 7.57 (d, J = 2 Hz, 2H), 7.50 (t, J = 8 Hz, 1H),
4.16-4.04 (m, 2H), 3.62 (d, J = 8.5 Hz, 1H), 3.55 (d, J = 8.5 Hz,
1H) F4 (thin film) ESIMS 536 .sup.1H NMR (400 MHz, DMSO-d.sub.6)
3249, ([M + H].sup.+) .delta. 10.90 (s, 1H), 9.22 (t, J = 6.3 Hz,
3085, 1H), 7.77 (d, J = 2.5 Hz, 1654 1H), 7.73 (dd, J = 8.7, 2.6
Hz, 1H), 7.65-7.61 (m, 1H), 7.59-7.53 (m, 2H), 7.52 (d, J = 8.7 Hz,
1H), 4.16-4.00 (m, 2H), 3.62 (d, J = 8.5 Hz, 1H), 3.50 (d, J = 8.5
Hz, 1H) F5 (thin film) ESIMS 593 .sup.1H NMR (400 MHz,
DMSO-d.sub.6) 3299, ([M + H].sup.+) .delta. 10.90 (s, 1H), 8.73 (t,
J = 6.0 Hz, 3076, 1H), 8.63 (t, J = 6.3 Hz, 1657 1H), 7.81 (d, J =
2.6 Hz, 1H), 7.74 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1.8 Hz,
1H), 7.57-7.54 (m, 2H), 7.48 (d, J = 8.7 Hz, 1H), 4.02-3.94 (m,
2H), 3.93 (d, J = 6.2 Hz, 2H), 3.61 (d, J = 8.5 Hz, 1H), 3.50 (d, J
= 8.5 Hz, 1H) F6 220-223 (thin film) ESIMS 543 .sup.1H NMR (400
MHz, DMSO-d.sub.6) 3270 (w), ([M + H].sup.+) .delta. 10.86 (br s,
1H), 9.11 (br t, 3061 (w), J = 6 Hz, 1H), 8.58 (d, J = 1.7 Hz, 1674
(s), 1H), 8.48 (dd, J = 4.8, 1.4 Hz, 1591 (m), 1H), 7.69-7.79 (m,
3H), 1538 (m), 7.63 (t, J = 1.8 Hz, 1H), 1414 (m), 7.53-7.56 (m,
2H), 7.49 (d, J = 8.6 Hz, 1367 (m) 1H), 7.39 (ddd, J = 8.1, 4.8, 1
Hz, 1H), 4.48 (br d, J = 6.7 Hz, 2H), 3.62 (d, J = 8.5 Hz, 1H),
3.50 (d, J = 8.5 Hz, 1H) F7 230-232 (thin film) ESIMS 578 .sup.1H
NMR (400 MHz, DMSO-d.sub.6) 3280 (w), ([M + H].sup.+) .delta. 10.87
(br s, 1H), 9.11 (br t, 3054 (w), J = 6 Hz, 1H), 8.58 (d, J = 1.7
Hz, 1672 (s), 1H), 8.48 (dd, J = 5, 1.5 Hz, 1593 (m), 1H), 7.79 (s,
2H), 1535 (m), 7.78-7.69 (m, 3H), 7.50 (d, J = 8.7 Hz, 1472 (m),
1H), 7.39 (ddd, J = 7.8, 1414 (m) 4.8, 0.6 Hz, 1H), 4.48 (br d, J =
6 Hz, 2H), 3.62 (d, J = 8.6 Hz, 1H), 3.52 (d, J = 8.6 Hz, 1H) F8
(thin film) ESIMS 544 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 3269 (w),
([M + H].sup.+) .delta. 10.88 (br s, 1H), 9.11 (br t, 3058 (w), J =
6 Hz, 1H), 8.53 (m, 1H), 1703 (w), 7.84-7.78 (m, 2H), 7.72 (dd,
1642 (s), J = 9, 2.5 Hz, 1H), 7.63 (t, J = 1.8 Hz, 1591 (s), 1H),
7.57-7.54 (m, 1554 (s), 2H), 7.50 (d, J = 9 Hz, 1H), 1475 (s) 7.41
(d, J = 8 Hz, 1H), 7.29 (m, 1H), 4.54 (br d, J = 6 Hz, 2H), 3.62
(d, J = 8.5 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H) F9 (thin film) ESIMS
578 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 3188 (w), ([M + H].sup.+)
.delta. 10.89 (br s, 1H), 9.11 (br t, 3053 (w), J = 6 Hz, 1H), 8.53
(m, 1H), 1695 (w), 7.84-7.78 (m, 4H), 7.73 (dd, 1637 (s), J = 9,
2.5 Hz, 1H), 7.51 (d, J = 8.5 Hz, 1609 (w), 1H), 7.41 (d, J = 8 Hz,
1589 (m), 1H), 7.29 (m, 1H), 1548 (s), 4.54 (br d, J = 6 Hz, 2H),
3.63 (d, J = 8.5 Hz, 1473 (s), 1H), 3.53 (d, J = 8.5 Hz, 1405 (s),
1H) 1320 (s) F10 (thin film) ESIMS 511 .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 3189 (w), ([M + H].sup.+) 9.16-9.04 (m, 2H),
8.02 (m, 1659 (s), 1H), 7.68 (d, J = 2.2 Hz, 1H), 1588 (s), 7.38
(d, J = 9 Hz, 1H), 1567 (m), 7.35 (t, J = 1.5 Hz, 1H), 7.22 (d, J =
1.5 Hz, 1544 (s), 2H), 6.03 (m, 1H), 1473 (s), 5.47-5.35 (m, 2H),
4.54 (br 1404 (m), d, J = 6.7 Hz, 2H), 3.54 (d, J = 8 Hz, 1323 (m)
1H), 3.04 (d, J = 8 Hz, 1H) F11 (thin film) ESIMS 544 .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 3195 (w), ([M + H].sup.+) 9.12 (br s,
2H), 8.03 (m, 1H), 1657 (s), 7.70 (d, J = 2.2 Hz, 1H), 1609 (m),
7.38 (d, J = 9 Hz, 1H), 7.35 (s, 1587 (m), 2H), 6.03 (m, 1H), 1547
(s), 5.46-5.36 (m, 2H), 4.54 (br d, J = 6.5 Hz, 1472 (s), 2H), 3.52
(d, J = 8 Hz, 1404 (s), 1H), 3.04 (d, J = 8 Hz, 1H) 1323 (m) F12
57-62 (thin film) ESIMS 544 .sup.1H NMR (400 MHz, DMSO-d.sub.6)
3267 (w), ([M + H].sup.+) .delta. 10.90 (br s, 1H), 9.14 (br t,
3062 (w), J = 6 Hz, 1H), 8.58-8.51 (m, 1648 (s), 2H), 7.81 (d, J =
2.6 Hz, 1H), 1607 (s), 7.73 (dd, J = 8.7, 2.6 Hz, 1H), 1588 (s),
7.63 (t, J = 2 Hz, 1H), 1566 (s), 7.58-7.48 (m, 3H), 7.39-7.32 (m,
1544 (s), 2H), 4.48 (d, J = 6 Hz, 2H), 1473 (s), 3.62 (d, J = 8.5
Hz, 1H), 1406 (s), 3.51 (d, J = 8.5 Hz, 1H) 1323 (s) F13 136-139
(thin film) ESIMS 578 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 3268 (w),
([M + H].sup.+) .delta. 10.90 (br s, 1H), 9.14 (t, J = 6 Hz, 3032
(w), 1H), 8.58-8.51 (m, 1658 (s), 2H), 7.83-7.77 (m, 3H), 1606 (m),
7.73 (dd, J = 8.8, 2.6 Hz, 1H), 1590 (s), 7.52 (d, J = 8.8 Hz, 1H),
1547 (s), 7.39-7.32 (m, 2H), 4.48 (d, J = 6 Hz, 1472 (s), 2H), 3.63
(d, J = 8.5 Hz, 1413 (s) 1H), 3.54 (d, J = 8.5 Hz, 1H) F14 (thin
film) ESIMS 509 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 3237 (w), ([M +
H].sup.+) .delta. 11.60 (br s, 1H), 10.91 (br 3002 (w), s, 1H),
7.77-7.66 (m, 4H), 1650 (s), 7.51 (d, J = 9 Hz, 1H), 1532 (m), 7.43
(dd, J = 9, 2 Hz, 1H), 1473 (m) 5.99 (m, 1H), 5.38 (m, 1H), 5.30
(d, J = 10.4 Hz, 1H), 4.42 (br d, J = 6 Hz, 2H), 3.60 (d, J = 8.2
Hz, 1H), 3.45 (d, J = 8.2 Hz, 1H) F15 (thin film) ESIMS 557 .sup.1H
NMR (400 MHz, CDCl.sub.3) .delta. 3256 (w), ([M + H].sup.+) 11.57
(br s, 1H), 10.89 (br s, 3004 (w), 1H), 7.80 (s, 2H), 7.77 (d, J =
2.2 Hz, 1660 (s), 1H), 7.70 (dd, J = 9, 1609 (m), 2.2 Hz, 1H), 7.51
(d, J = 9 Hz, 1588 (m), 1H), 3.72 (d, J = 7 Hz, 2H), 1548 (s), 3.63
(d, J = 8.5 Hz, 1H), 1473 (m), 3.53 (d, J = 8.5 Hz, 1H), 1.11 (m,
1404 (m), 1H), 0.58-0.52 (m, 2H), 1325 (m) 0.32-0.26 (m, 2H) F16
(thin film) ESIMS 523 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 3252 (w),
([M + H].sup.+) .delta. 11.57 (br s, 1H), 10.89 (br 3077 (w), s,
1H), 7.77 (d, J = 2.5 Hz, 1654 (s), 1H), 7.70 (dd, J = 9, 2.5 Hz,
1609 (m), 1H), 7.63 (t, J = 1.5 Hz, 1H), 1588 (s), 7.55 (d, J = 1.5
Hz, 2H), 1542 (s), 7.50 (d, J = 9 Hz, 1H), 3.72 (d, J = 7 Hz, 1473
(s), 2H), 3.62 (d, J = 8.6 Hz, 1404 (s) 1H), 3.50 (d, J = 8.6 Hz,
1H), 1.10 (m, 1H), 0.58-0.52 (m, 2H), 0.31-0.27 (m, 2H) F17 (thin
film) ESIMS 577 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 3190 (w), ([M +
H].sup.+) .delta. 11.68 (br s, 1H), 10.90 (s, 1661 (s), 1H), 7.77
(d, J = 2.3 Hz, 1H), 1605 (m), 7.68 (dd, J = 9, 2.3 Hz, 1H), 1588
(s), 7.63 (t, J = 1 Hz, 1H), 1567 (m), 7.55 (d, J = 1 Hz, 2H), 1544
(s), 7.53-7.48 (m, 3H), 7.26-7.19 (m, 2H), 1510 (s), 4.92 (s, 2H),
3.62 (d, J = 8.6 Hz, 1472 (s), 1H), 3.51 (d, J = 8.6 Hz, 1403 (s)
1H) F18 (thin film) ESIMS 611 .sup.1H NMR (400 MHz, DMSO-d.sub.6)
3186 (w), ([M + H].sup.+) .delta. 11.68 (s, 1H), 10.89 (s, 1H),
1659 (s), 7.80 (s, 2H), 7.77 (d, J = 2.4 Hz, 1606 (m), 1H), 7.68
(dd, J = 9, 2.4 Hz, 1587 (m), 1H), 7.54-7.48 (m, 3H), 1547 (s),
7.26-7.20 (m, 2H), 4.92 (s, 1510 (s), 2H), 3.63 (d, J = 8.5 Hz,
1H), 1472 (m), 3.53 (d, J = 8.5 Hz, 1H) 1403 (m) F19 (thin film)
ESIMS 575 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 3268 (w), ([M +
H].sup.+) .delta. 10.84 (br s, 1H), 8.55 (t, J = 5.5 Hz, 3070 (w),
1H), 7.76 (d, J = 2.4 Hz, 1639 (m), 1H), 7.65-7.59 (m, 1587 (m),
2H), 7.56 (d, J = 1.3 Hz, 2H), 1540 (s), 7.46 (d, J = 8.8 Hz, 1H),
1509 (s), 7.30 (m, 2H), 7.12 (m, 2H), 1472 (s), 3.62 (d, J = 8.6
Hz, 1H), 3.50 (d, J = 8.6 Hz, 1404 (m), 1H), 3.44 (m, 2H), 1320
(m), 2.81 (t, J = 7 Hz, 2H) 1220 (m), 1184 (m) F20 (thin film)
ESIMS 609 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 3424 (w), ([M +
H].sup.+) .delta. 10.85 (br s, 1H), 8.55 (t, J = 5.7 Hz, 3275 (w),
1H), 7.80 (s, 2H), 3065 (w), 7.76 (d, J = 2.6 Hz, 1H), 1644 (m),
7.62 (dd, J = 8.8, 2.6 Hz, 1H), 1588 (m), 7.46 (d, J = 8.8 Hz, 1H),
7.30 (m, 1548 (s), 2H), 7.12 (m, 2H), 3.63 (d, J = 8.5 Hz, 1509
(s), 1H), 3.53 (d, J = 8.5 Hz, 1472 (m), 1H), 3.45 (m, 2H), 1407
(m), 2.82 (t, J = 7.2 Hz, 2H) 1322 (m), 1222 (m) F21 (thin film)
HRMS-ESI (TOF) .sup.1H NMR (400 MHz, DMSO-d.sub.6) 3186 (w), [M +
H].sup.+ calcd for .delta. 11.77 (br s, 1H), 10.99 (s, 1658 (m),
C.sub.21H.sub.16Cl.sub.5F.sub.2N.sub.2O.sub.3 1H), 7.80-7.69 (m,
2H), 1588 (m), 558.9538; found 7.62 (t, J = 1.8 Hz, 1H), 7.55 (d, J
= 1.8 Hz, 1544 (m), 558.9538. 2H), 7.50 (d, J = 9 Hz, 1473 (s),
1H), 4.03 (m, 1H), 1402 (m) 3.89 (m, 1H) 3.62 (d, J = 8.5 Hz, 1H),
3.54 (d, J = 8.5 Hz, 1H), 2.10 (m, 1H), 1.69 (m, 1H), 1.41 (m, 1H)
F22 (thin film) HRMS-ESI (TOF) .sup.1H NMR (400 MHz, DMSO-d.sub.6)
3016 (w), [M + H].sup.+ calcd for .delta. 11.74 (br s, 1H), 11.04
(s, 1651 (m), C.sub.21H.sub.16Cl.sub.5F.sub.2N.sub.2O.sub.3 1H),
7.80-7.73 (m, 3H), 1588 (m), 558.9538; found 7.68 (d, J = 8.5 Hz,
1H), 7.49 (d, J = 8.8 Hz, 1545 (m), 558.9540. 1H), 7.42 (dd, J =
8.8, 1473 (s), 2 Hz, 1H), 4.02 (m, 1H), 1401 (m) 3.88 (m, 1H), 3.59
(d, J = 8.5 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H), 2.09 (m, 1H), 1.68
(m, 1H), 1.40 (m, 1H) F23 131-133 (thin film) HRMS-ESI (TOF)
.sup.1H NMR (400 MHz, DMSO-d.sub.6) 3016 (w), [M + H].sup.+ calcd
for .delta. 11.64 (br s, 1H), 11.00 (s, 1642 (m),
C.sub.21H.sub.15Cl.sub.6F.sub.2N.sub.2O.sub.3 1H), 7.83-7.67 (m,
4H),
1587 (m), 592.9148; found 7.49 (d, J = 8.8 Hz, 1H), 4.01 (m, 1548
(m), 592.9151. 1H), 3.88 (m, 1H), 3.63 (d, J = 8.5 Hz, 1472 (s),
1H), 3.57 (d, J = 8.5 Hz, 1403 (m) 1H), 2.09 (m, 1H), 1.68 (m, 1H),
1.40 (m, 1H) F24 166-168 (thin film) HRMS-ESI (TOF) .sup.1H NMR
(400 MHz, DMSO-d.sub.6) 3247 (w), [M + H].sup.+ calcd for .delta.
10.85 (br s, 1H), 8.47 (br t, 3077 (w),
C.sub.22H.sub.20Cl.sub.5N.sub.2O.sub.2 J = 5.6 Hz, 1H), 7.75 (d, J
= 2.6 Hz, 1636 (s), 520.9934; found 1H), 7.66 (dd, J = 8.7, 1588
(s), 520.9936. 2.6 Hz, 1H), 7.62 (t, J = 1.8 Hz, 1536 (s), 1H),
7.55 (d, J = 1.8 Hz, 1472 (s), 2H), 7.46 (d, J = 8.7 Hz, 1H), 1404
(s), 3.61 (d, J = 8.6 Hz, 1H), 1320 (s) 3.50 (d, J = 8.6 Hz, 1H),
3.29 (m, 2H), 1.41 (q, J = 7 Hz, 2H), 0.76 (m, 1H), 0.45-0.39 (m,
2H), 0.10-0.05 (m, 2H) F25 163-165 (thin film) HRMS-ESI (TOF)
.sup.1H NMR (400 MHz, DMSO-d.sub.6) 3248 (m), [M + H].sup.+ calcd
for .delta. 10.88 (br s, 1H), 8.47 (br t, 3080 (w),
C.sub.22H.sub.20Cl.sub.5N.sub.2O.sub.2 J = 5.6 Hz, 1H), 2914 (w),
520.9934; found 7.77-7.64 (m, 4H), 7.46 (d, J = 9 Hz, 1648 (s),
520.9941. 1H), 7.42 (dd, J = 9, 2 Hz, 1524 (s), 1H), 3.59 (d, J =
8.6 Hz, 1H), 1471 (s) 3.45 (d, J = 8.6 Hz, 1H), 3.29 (m, 2H), 1.41
(q, J = 7 Hz, 2H), 0.76 (m, 1H), 0.45-0.39 (m, 2H), 0.10-0.05 (m,
2H) F26 122-125 (thin film) HRMS-ESI (TOF) .delta. .sup.1H NMR (400
MHz, DMSO-d.sub.6) 3427 (w), [M + H].sup.+ calcd for 10.84 (br s,
1H), 8.47 (br t, 3259 (w), C.sub.22H.sub.19Cl.sub.6N.sub.2O.sub.2 J
= 5.6 Hz, 1H), 7.79 (s, 2H), 3069 (w), 554.9544; found 7.74 (d, J =
2.8 Hz, 1H), 3003 (w), 554.9553. 7.66 (dd, J = 8.7, 2.8 Hz, 1H),
1682 (s), 7.47 (d, J = 8.7 Hz, 1H), 3.62 (d, J = 8.6 Hz, 1659 (s),
1H), 3.53 (d, J = 8.6 Hz, 1612 (m), 1H), 3.29 (m, 2H), 1592 (s),
1.41 (q, J = 7 Hz, 2H), 1549 (s), 0.75 (m, 1H), 0.45-0.39 (m, 2H),
1526 (s), 0.10-0.05 (m, 2H) 1471 (s), 1412 (s) F27 189-190 ESIMS
543 .sup.1H NMR (400 MHz, Acetone- ([M + H].sup.+) d.sub.6) .delta.
10.07 (s, 1H), 8.01 (t, J = 6.2 Hz, 1H), 7.88 (d, J = 2.6 Hz, 1H),
7.76 (dd, J = 8.7, 2.6 Hz, 1H), 7.48 (s, 3H), 7.42 (t, J = 8.0 Hz,
3H), 7.34 (t, J = 7.5 Hz, 2H), 7.29-7.23 (m, 1H), 4.61 (d, J = 6.0
Hz, 2H), 3.64 (d, J = 8.4 Hz, 1H), 3.40 (d, J = 8.3 Hz, 1H);
.sup.13C NMR (101 MHz, Acetone- d.sub.6) .delta. 166.95, 163.27,
140.11, 138.68, 138.59, 138.31, 135.60, 131.13, 129.22, 128.73,
128.48, 127.85, 125.82, 122.25, 122.17, 120.62, 120.54, 62.81,
44.01, 40.10, 38.39 F28 126-127 .sup.1H NMR (400 MHz, Acetone-
d.sub.6) .delta. 10.07 (s, 1H), 8.05 (t, J = 6.1 Hz, 1H), 7.88 (d,
J = 2.5 Hz, 1H), 7.74 (dd, J = 8.8, 2.6 Hz, 1H), 7.52-7.44 (m, 5H),
7.41 (d, J = 8.7 Hz, 1H), 7.10 (t, J = 8.7 Hz, 2H), 4.60 (d, J =
6.0 Hz, 2H), 3.64 (d, J = 8.3 Hz, 1H), 3.40 (d, J = 8.3 Hz, 1H);
.sup.19F NMR (376 MHz, DMSO-d.sub.6) .delta. -117.46 F29 197 ESIMS
545 .sup.1H NMR (400 MHz, DMSO-d.sub.6) ([M + H].sup.+) .delta.
12.51 (s, 1H), 10.95 (s, 1H), 7.92 (dd, J = 4.1, 2.5 Hz, 1H), 7.81
(dd, J = 8.8, 2.6 Hz, 1H), 7.66-7.53 (m, 4H), 7.43-7.35 (m, 2H),
7.17-7.12 (m, 2H), 7.08 (t, J = 7.3 Hz, 1H), 3.65 (d, J = 8.5 Hz,
1H), 3.53 (d, J = 8.5 Hz, 1H); .sup.13C NMR (101 MHz, DMSO-d.sub.6)
.delta. 163.43, 162.70, 159.33, 137.79, 137.25, 134.05, 133.53,
130.52, 129.56, 127.88, 127.68, 124.57, 122.66, 122.05, 119.53,
112.87, 62.12, 38.44, 36.81 F30 185-187 HRMS-ESI .sup.1H NMR (400
MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta. 10.84 (s, 1H),
8.48 (t, J = 5.9 Hz, C.sub.21H.sub.20Cl.sub.5N.sub.2O.sub.2, 1H),
7.74 (d, J = 2.6 Hz, 508.9934; found, 1H), 7.68 (dd, J = 8.7, 2.6
Hz, 508.9935. 1H), 7.62 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.6 Hz,
2H), 7.47 (d, J = 8.7 Hz, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3.50 (d, J
= 8.5 Hz, 1H), 3.05 (t, J = 6.6 Hz, 2H), 1.82 (dp, J = 13.2, 6.6
Hz, 1H), 0.92 (d, J = 6.7 Hz, 6H) F31 158-160 HRMS-ESI .sup.1H NMR
(400 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta. 10.83 (s,
1H), 8.44 (t, J = 5.6 Hz, C.sub.23H.sub.24Cl.sub.5N.sub.2O.sub.2,
1H), 7.72 (d, J = 2.6 Hz, 537.0247; found, 1H), 7.67 (dd, J = 8.7,
2.6 Hz, 537.0249. 1H), 7.63 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.6
Hz, 2H), 7.46 (d, J = 8.7 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.50
(d, J = 8.5 Hz, 1H), 3.21 (q, J = 6.7 Hz, 2H), 1.49 (q, J = 7.0 Hz,
2H), 1.30 (m, 6H), 0.87 (m, 3H) F32 159-162 HRMS-ESI .sup.1H NMR
(400 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta. 10.86 (s,
1H), 9.08 (t, J = 6.0 Hz,
C.sub.24H.sub.16Cl.sub.5F.sub.2N.sub.2O.sub.2, 1H), 7.77 (d, J =
2.5 Hz, 578.9590; found, 1H), 7.71 (dd, J = 8.8, 2.6 Hz, 578.9596.
1H), 7.62 (d, J = 1.7 Hz, 1H), 7.55 (d, J = 1.5 Hz, 2H), 7.50 (d, J
= 8.7 Hz, 1H), 7.41 (m, 2H), 7.21 (s, 1H), 4.44 (d, J = 6.0 Hz,
2H), 3.61 (d, J = 8.5 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H) F33 158-160
HRMS-ESI .sup.1H NMR (400 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd
for .delta. 10.83 (s, 1H), 8.44 (t, J = 5.6 Hz,
C.sub.22H.sub.22Cl.sub.5N.sub.2O.sub.2, 1H), 7.72 (d, J = 2.5 Hz,
523.0091; found, 1H), 7.67 (dd, J = 8.7, 2.5 Hz, 523.0092. 1H),
7.63 (s, 1H), 7.55 (d, J = 1.4 Hz, 2H), 7.47 (d, J = 8.7 Hz, 1H),
3.61 (d, J = 8.5 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H), 3.21 (q, J =
6.6 Hz, 2H), 1.50 (m, 2H), 1.31 (m, 4H), 0.89 (m, 3H) F34 167-170
HRMS-ESI .sup.1H NMR (400 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd
for .delta. 10.84 (s, 1H), 8.75 (t, J = 5.7 Hz,
C.sub.26H.sub.22Cl.sub.5N.sub.2O.sub.4, 1H), 7.75 (d, J = 2.5 Hz,
602.9990; found, 1H), 7.69 (dd, J = 8.7, 2.5 Hz, 602.9958. 1H),
7.63 (s, 1H), 7.55 (d, J = 1.5 Hz, 2H), 7.47 (d, J = 8.7 Hz, 1H),
7.20 (d, J = 8.3 Hz, 1H), 6.56 (d, J = 2.2 Hz, 1H), 6.51 (dd, J =
8.3, 2.2 Hz, 1H), 4.33 (d, J = 5.8 Hz, 2H), 3.80 (s, 3H), 3.75 (s,
3H), 3.61 (d, J = 8.5 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H) F35 188-191
HRMS-ESI .sup.1H NMR (400 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd
for .delta. 10.85 (s, 1H), 8.55 (t, J = 5.7 Hz,
C.sub.21H.sub.18Cl.sub.5N.sub.2O.sub.2, 1H), 7.73 (d, J = 2.5 Hz,
506.9778; found, 1H), 7.68 (dd, J = 8.7, 2.6 Hz, 506.9780. 1H),
7.63 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.7 Hz, 2H), 7.47 (d, J =
8.7 Hz, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H),
3.14 (t, J = 6.2 Hz, 2H), 1.01 (m, 1H), 0.44 (m, 2H), 0.24 (m, 2H)
F36 222-225 HRMS-ESI .sup.1H NMR (400 MHz, DMSO-d.sub.6) [M +
H].sup.+ calcd for .delta. 10.85 (s, 1H), 8.98 (t, J = 6.0 Hz,
C.sub.28H.sub.26Cl.sub.5N.sub.2O.sub.2, 1H), 7.73 (m, 2H),
599.0405; found, 7.63 (s, 1H), 7.55 (d, J = 1.5 Hz, 599.0416. 2H),
7.49 (d, J = 8.7 Hz, 1H), 7.37 (d, J = 8.3 Hz, 2H), 7.28 (d, J =
8.3 Hz, 2H), 4.41 (d, J = 4.4 Hz, 2H), 3.61 (d, J = 8.5 Hz, 1H),
3.49 (d, J = 8.5 Hz, 1H), 1.28 (s, 9H) F37 192-194 HRMS-ESI .sup.1H
NMR (400 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta. 10.88
(s, 1H), 8.86 (t, J = 5.7 Hz,
C.sub.20H.sub.15Cl.sub.5N.sub.3O.sub.2, 1H), 7.76 (d, J = 2.5 Hz,
503.9601; found, 1H), 7.71 (dd, J = 8.7, 2.6 Hz, 503.9606. 1H),
7.63 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.7 Hz, 2H), 7.50 (d, J =
8.7 Hz, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3.48 (m, 3H), 2.77 (t, J =
6.4 Hz, 2H) F38 114-118 HRMS-ESI .sup.1H NMR (400 MHz,
DMSO-d.sub.6) [M + NH.sub.4].sup.+ calcd .delta. 10.84 (s, 1H),
8.58 (t, J = 5.6 Hz, for C.sub.21H.sub.20Cl.sub.5N.sub.3O.sub.2,
1H), 7.76 (d, J = 2.6 Hz, 536.9996; found, 1H), 7.68 (dd, J = 8.8,
2.6 Hz, 536.9997. 1H), 7.63 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.5
Hz, 2H), 7.49 (d, J = 8.7 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.50
(d, J = 8.5 Hz, 1H), 3.30 (m, 2H), 2.57 (t, J = 7.2 Hz, 2H), 1.81
(p, J = 7.0 Hz, 2H), F39 72-78 HRMS-ESI .sup.1H NMR (400 MHz,
DMSO-d.sub.6) [M + H].sup.+ calcd for .delta. 10.84 (s, 1H), 8.50
(t, J = 5.6 Hz, C.sub.22H.sub.19Cl.sub.5F.sub.3N.sub.2O.sub.3, 1H),
7.75 (d, J = 2.6 Hz, 592.9757; found, 1H), 7.67 (dd, J = 8.8, 2.6
Hz, 592.9766. 1H), 7.63 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.5 Hz,
2H), 7.48 (d, J = 8.7 Hz, 1H), 4.04 (q, J = 9.4 Hz, 2H), 3.66 (t, J
= 6.3 Hz, 2H), 3.61 (d, J = 8.5 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H),
3.29 (m, 2H), 1.78 (p, J = 6.5 Hz, 2H) F40 170-172 HRMS-ESI .sup.1H
NMR (400 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta. 10.86
(s, 1H), 8.71 (t, J = 5.7 Hz,
C.sub.20H.sub.15Cl.sub.5F.sub.3N.sub.2O.sub.2, 1H), 7.76 (d, J =
2.6 Hz, 548.9495; found, 1H), 7.69 (dd, J = 8.8, 2.6 Hz, 548.9501.
1H), 7.63 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.5 Hz, 2H), 7.49 (d, J
= 8.7 Hz, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3.48 (m, 3H), 2.54 (m, 2H)
F41 199-202 HRMS-ESI .sup.1H NMR (400 MHz, DMSO-d.sub.6) [M +
H].sup.+ calcd for .delta. 10.86 (s, 1H), 9.14 (t, J = 6.0 Hz,
C.sub.25H.sub.17Cl.sub.5F.sub.3N.sub.2O.sub.2, 1H), 7.78 (d, J =
2.6 Hz, 610.9652; found, 1H), 7.72 (m, 3H), 610.9654. 7.63 (t, J =
1.8 Hz, 1H), 7.59 (d, J = 8.1 Hz, 2H), 7.55 (d, J = 1.6 Hz, 2H),
7.51 (d, J = 8.7 Hz, 1H), 4.54 (d, J = 5.9 Hz, 2H), 3.62 (d, J =
8.5 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H) F42 120-128 HRMS-ESI .sup.1H
NMR (400 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta. 10.85
(s, 1H), 8.46 (s, 1H), C.sub.22H.sub.22Cl.sub.5N.sub.2O.sub.4S,
7.76 (dd, J = 8.8, 2.6 Hz, 1H), 586.9710; found, 7.66 (d, J = 2.6
Hz, 1H), 586.9713. 7.63 (t, J = 1.8 Hz, 1H), 7.54 (d, J = 1.5 Hz,
2H), 7.45 (d, J = 8.8 Hz, 1H), 3.82 (s, 2H), 3.61 (d, J = 8.5 Hz,
1H), 3.51 (d, J = 8.5 Hz, 1H), 3.01 (s, 3H), 1.52 (s, 6H) F43
201-203 HRMS-ESI .sup.1H NMR (400 MHz, DMSO-d.sub.6) [M + H].sup.+
calcd for .delta. 10.84 (s, 1H), 8.53 (t, J = 5.6 Hz,
C.sub.23H.sub.22Cl.sub.5N.sub.2O.sub.3, 1H), 7.74 (d, J = 2.5 Hz,
551.0040; found, 1H), 7.66 (dd, J = 8.8, 2.6 Hz, 551.0043. 1H),
7.63 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.6 Hz, 2H), 7.47 (d, J =
8.7 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.50 (m, 3H), 3.38 (q, J =
5.8 Hz, 2H), 3.26 (d, J = 6.8 Hz, 2H), 0.99 (m, 1H), 0.45 (m, 2H),
0.18 (m, 2H) F44 180-183 HRMS-ESI .sup.1H NMR (400 MHz,
DMSO-d.sub.6) [M + H].sup.+ calcd for .delta. 10.84 (s, 1H), 8.56
(t, J = 5.7 Hz,
C.sub.20H.sub.17Cl.sub.5FN.sub.2O.sub.2, 1H), 7.75 (d, J = 2.6 Hz,
512.9683; found, 1H), 7.68 (dd, J = 8.8, 2.6 Hz, 512.9686. 1H),
7.63 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.5 Hz, 2H), 7.48 (d, J =
8.7 Hz, 1H), 4.59 (t, J = 5.9 Hz, 1H), 4.47 (t, J = 5.9 Hz, 1H),
3.61 (d, J = 8.5 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H), 3.34 (d, J =
6.1 Hz, 2H), 1.89 (dt, J = 26.0, 6.3 Hz, 2H) F45 163-165 HRMS-ESI
.sup.1H NMR (400 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta.
10.83 (s, 1H), 8.44 (t, J = 5.7 Hz,
C.sub.21H.sub.20Cl.sub.5N.sub.2O.sub.2, 1H), 7.72 (d, J = 2.6 Hz,
508.9934; found, 1H), 7.67 (dd, J = 8.7, 2.6 Hz, 508.9936. 1H),
7.62 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.4 Hz, 2H), 7.47 (d, J =
8.7 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H),
3.22 (q, J = 6.5 Hz, 2H), 1.49 (p, J = 7.0 Hz, 2H), 1.37 (dt, J =
14.7, 7.1 Hz, 2H), 0.91 (t, J = 7.3 Hz, 3H) F46 194-196 HRMS-ESI
.sup.1H NMR (500 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta.
10.84 (s, 1H), 8.46 (t, J = 5.5 Hz,
C.sub.19H.sub.16Cl.sub.5N.sub.2O.sub.2, 1H), 7.74 (d, J = 2.3 Hz,
480.9621; found, 1H), 7.66 (dd, J = 8.8, 2.4 Hz, 480.9628. 1H),
7.63 (s, 1H), 7.55 (s, 2H), 7.47 (d, J = 8.7 Hz, 1H), 3.61 (d, J =
8.5 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H), 3.25 (p, J = 7.0 Hz, 2H),
1.11 (t, J = 7.2 Hz, 3H); .sup.13C NMR (126 MHz, DMSO-d.sub.6)
.delta. 165.59, 162.43, 137.47, 137.45, 137.19, 133.95, 129.97,
127.80, 127.59, 123.86, 120.75, 118.88, 62.04, 38.29, 36.67, 33.74,
14.45 F47 1.94-196 HRMS-ESI [M].sup.+ .sup.1H NMR (500 MHz,
DMSO-d.sub.6) calcd for .delta.10.86 (s, 1H), 8.95 (t, J = 5.5 Hz,
C.sub.20H.sub.14Cl.sub.5N.sub.2O.sub.2, 1H), 7.76 (d, J = 2.2 Hz,
490.9464; found, 1H), 7.69 (dd, J = 8.8, 2.3 Hz, 490.9469. 1H),
7.63 (s, 1H), 7.55 (s, 2H), 7.49 (d, J = 8.7 Hz, 1H), 4.03 (m, 2H),
3.61 (d, J = 8.5 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H), 3.16 (s, 1H);
.sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 165.62, 162.47,
137.48, 137.19, 136.53, 133.95, 130.10, 127.80, 127.59, 123.91,
121.05, 118.93, 80.59, 73.04, 62.03, 38.31, 36.67, 28.19 F48
208-210 HRMS-ESI .sup.1H NMR (500 MHz, DMSO-d.sub.6) [M + H].sup.+
calcd for .delta.10.88 (s, 1H), 8.91 (t, J = 5.9 Hz,
C.sub.19H.sub.14Cl.sub.5F.sub.2N.sub.2O.sub.2, 5 1H), 7.77 (d, J =
2.3 Hz, 16.9432; found, 1H), 7.71 (dd, J = 8.8, 2.4 Hz, 516.9438.
1H), 7.63 (s, 1H), 7.55 (s, 2H), 7.50 (d, J = 8.7 Hz, 1H), 6.13
(tt, J = 55.8, 3.7 Hz, 1H), 3.65 (m, 3H), 3.50 (d, J = 8.5 Hz, 1H);
.sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 166.61, 162.48,
137.49, 137.18, 136.52, 133.96, 130.11, 127.80, 127.60, 123.84,
121.14, 118.93, 116.10, 114.19, 112.28, 62.03, 41.30, 41.09, 40.89,
38.30, 36.67 F49 96-102 HRMS-ESI .sup.1H NMR (500 MHz,
DMSO-d.sub.6) [M + H].sup.+ calcd for .delta.10.89 (s, 1H), 9.22
(t, J = 6.3 Hz, C.sub.20H.sub.13Cl.sub.5F.sub.5N.sub.2O.sub.2, 1H),
7.77 (d, J = 2.2 Hz, 584.9306; found, 1H), 7.73 (dd, J = 8.8, 2.4
Hz, 584.9323. 1H), 7.63 (s, 1H), 7.55 (s, 2H), 7.52 (d, J = 8.7 Hz,
1H), 4.13 (td, J = 15.5, 6.2 Hz, 2H), 3.63 (d, J = 8.5 Hz, 1H),
3.50 (d, J = 8.5 Hz, 1H) F50 154-159 HRMS-ESI .sup.1H NMR (400 MHz,
DMSO-d.sub.6) [M + H].sup.+ calcd for .delta. 10.84 (s, 1H), 8.49
(t, J = 5.6 Hz, C.sub.23H.sub.25Cl.sub.5N.sub.3O.sub.2, 1H), 7.74
(d, J = 2.5 Hz, 550.0384; found, 1H), 7.66 (dd, J = 8.8, 2.6 Hz,
550.0391. 1H), 7.63 (t, J = 1.7 Hz, 1H), 7.55 (d, J = 1.6 Hz, 2H),
7.47 (d, J = 8.7 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.50 (d, J =
8.5 Hz, 1H), 3.22 (q, J = 6.2 Hz, 2H), 2.21 (t, J = 6.7 Hz, 2H),
2.10 (s, 6H), 1.47 (m, 4H); .sup.13C NMR (126 MHz, DMSO-d.sub.6)
.delta. 166.35, 163.01, 138.17, 138.04, 137.77, 134.54, 130.53,
128.39, 128.18, 124.38, 121.31, 119.46, 62.63, 59.21, 45.60, 39.29,
38.87, 37.24, 27.32, 24.87 F51 179-182 HRMS-ESI [M].sup.+ .sup.1H
NMR (500 MHz, DMSO-d.sub.6) calcd for .delta.10.87 (s, 1H), 8.75
(t, J = 5.6 Hz, C.sub.19H.sub.15Cl.sub.6N.sub.2O.sub.2, 1H), 7.77
(d, J = 2.6 Hz, 514.9231; found, 1H), 7.70 (dd, J = 8.8, 2.6 Hz,
514.9228. 1H), 7.63 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.6 Hz, 2H),
7.49 (d, J = 8.7 Hz, 1H), 3.73 (t, J = 6.1 Hz, 2H), 3.62 (d, J =
8.5 Hz, 1H), 3.56 (m, 2H), 3.50 (d, J = 8.5 Hz, 1H); .sup.13C NMR
(126 MHz, DMSO-d.sub.6) .delta. 166.21, 162.46, 137.48, 137.19,
136.92, 133.95, 130.06, 127.80, 127.59, 123.85, 121.01, 118.93,
62.05, 42.98, 40.97, 38.29, 36.66 F52 147-150 HRMS-ESI .sup.1H NMR
(500 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta. 10.85 (s,
1H), 8.60 (t, J = 5.7 Hz, C.sub.20H.sub.18Cl.sub.5N.sub.2O.sub.2S,
1H), 7.76 (d, J = 2.6 Hz, 526.9498; found, 1H), 7.69 (dd, J = 8.8,
2.6 Hz, 526.9498. 1H), 7.62 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.6
Hz, 2H), 7.48 (d, J = 8.7 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.50
(d, J = 8.5 Hz, 1H), 3.42 (q, J = 6.3 Hz, 2H), 2.64 (t, J = 7.0 Hz,
2H), 2.11 (s, 3H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta.
165.91, 162.44, 137.45, 137.19, 133.95, 130.02, 127.80, 127.59,
123.86, 120.90, 118.93, 62.05, 38.29, 38.20, 36.66, 32.41, 14.45
F53 165-167 HRMS-ESI [M].sup.+ .sup.1H NMR (500 MHz, DMSO-d.sub.6)
calcd for .delta.10.85 (s, 1H), 8.53 (t, J = 5.5 Hz,
C.sub.20H.sub.18Cl.sub.5N.sub.2O.sub.3, 1H), 7.73 (d, J = 2.6 Hz,
510.9727; found, 1H), 7.68 (dd, J = 8.7, 2.6 Hz, 510.9729. 1H),
7.63 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.6 Hz, 2H), 7.47 (d, J =
8.7 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H),
3.45 (t, J = 5.8 Hz, 2H), 3.38 (q, J = 5.4 Hz, 2H), 3.28 (s, 3H);
.sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 166.01, 162.43,
137.42, 137.25, 137.19, 133.95, 129.97, 127.80, 127.59, 123.86,
120.81, 118.91, 70.15, 62.04, 57.83, 38.69, 38.29, 36.66 F54 77-85
HRMS-ESI .sup.1H NMR (500 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd
for .delta. 10.84 (s, 1H), 8.52 (t, J = 5.6 Hz,
C.sub.21H.sub.20Cl.sub.5N.sub.2O.sub.3, 1H), 7.74 (d, J = 2.6 Hz,
524.9883; found, 1H), 7.67 (dd, J = 8.8, 2.6 Hz, 524.9890. 1H),
7.62 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.6 Hz, 2H), 7.47 (d, J =
8.7 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.48 (m, 5H), 3.38 (q, J =
5.9 Hz, 2H), 1.12 (t, J = 7.0 Hz, 3H); .sup.13C NMR (126 MHz,
DMSO-d.sub.6) .delta. 166.01, 162.42, 137.42, 137.27, 137.19,
133.95, 129.97, 127.80, 127.59, 123.86, 120.83, 118.94, 67.99,
65.27, 62.05, 38.29, 36.66, 15.02 F55 156-160 ESIMS 538 .sup.1H NMR
(500 MHz, DMSO-d.sub.6) ([M + H].sup.+) .delta.10.85 (s, 1H), 8.48
(t, J = 5.6 Hz, 1H), 7.90 (t, J = 5.6 Hz, 1H), 7.76 (d, J = 2.6 Hz,
1H), 7.67 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1.8 Hz, 1H), 7.55
(d, J = 1.7 Hz, 2H), 7.48 (d, J = 8.7 Hz, 1H), 3.61 (d, J = 8.5 Hz,
1H), 3.50 (d, J = 8.5 Hz, 1H), 3.28 (m, 2H), 3.19 (q, J = 6.3 Hz,
2H), 1.81 (s, 3H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta.
169.26, 165.99, 162.45, 137.43, 137.18, 137.16, 133.96, 130.00,
127.80, 127.59, 123.89, 120.99, 119.04, 62.05, 38.72, 38.25, 38.05,
36.67, 22.55 F56 187-190 HRMS-ESI .sup.1H NMR (500 MHz,
DMSO-d.sub.6) [M + H].sup.+ calcd for .delta.10.84 (s, 1H), 8.45
(t, J = 5.7 Hz, C.sub.20H.sub.18Cl.sub.5N.sub.2O.sub.2, 1H), 7.74
(d, J = 2.6 Hz, 494.9778; found, 1H), 7.67 (dd, J = 8.7, 2.6 Hz,
494.9779. 1H), 7.62 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.5 Hz, 2H),
7.47 (d, J = 8.7 Hz, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3.50 (d, J =
8.5 Hz, 1H), 3.19 (q, J = 6.7 Hz, 2H), 1.52 (h, J = 7.2 Hz, 2H),
0.92 (t, J = 7.4 Hz, 3H); .sup.13C NMR (126 MHz, DMSO-d.sub.6)
.delta. 165.83, 162.43, 137.59, 137.45, 137.19, 133.95, 129.95,
127.80, 127.59, 123.81, 120.70, 118.88, 62.04, 40.56, 38.30, 36.65,
22.13, 11.31 F57 94-99 HRMS-ESI .sup.1H NMR (500 MHz, DMSO-d.sub.6)
[M + H].sup.+ calcd for .delta. 10.85 (s, 1H), 8.57 (t, J = 5.6 Hz,
C.sub.20H.sub.17Cl.sub.6N.sub.2O.sub.2, 1H), 7.75 (d, J = 2.6 Hz,
528.9388; found, 1H), 7.68 (dd, J = 8.8, 2.6 Hz, 528.9388. 1H),
7.63 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.6 Hz, 2H), 7.48 (d, J =
8.7 Hz, 1H), 3.72 (t, J = 6.6 Hz, 2H), 3.61 (d, J = 8.5 Hz, 1H),
3.50 (d, J = 8.5 Hz, 1H), 3.36 (d, J = 6.9 Hz, 2H), 1.97 (m, 2H);
.sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 166.02, 162.46,
137.48, 137.28, 137.18, 133.95, 129.99, 127.80, 127.59, 123.79,
120.87, 118.88, 62.04, 42.76, 38.29, 36.66, 36.31, 31.85 F58 64-69
HRMS-ESI .sup.1H NMR (500 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd
for .delta.10.84 (s, 1H), 8.45 (t, J = 5.6 Hz,
C.sub.23H.sub.24Cl.sub.5N.sub.2O.sub.4, 1H), 7.74 (d, J = 2.6 Hz,
569.0146; found, 1H), 7.67 (dd, J = 8.8, 2.6 Hz, 569.0155. 1H),
7.62 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.7 Hz, 2H), 7.47 (d, J =
8.7 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.47 (m, 7H), 3.28 (q, J =
6.5 Hz, 2H), 3.24 (s, 3H), 1.73 (p, J = 6.6 Hz, 2H); .sup.13C NMR
(126 MHz, DMSO-d.sub.6) .delta. 165.83, 162.44, 137.46, 137.45,
137.19, 133.96, 129.97, 127.80, 127.59, 123.83, 120.79, 118.90,
71.15, 69.29, 67.90, 62.05, 57.95, 38.29, 36.66, 36.17, 29.11 F59
205-208 HRMS-ESI .sup.1H NMR (500 MHz, DMSO-d.sub.6) [M + H].sup.+
calcd for .delta.10.90 (s, 1H), 7.73 (d, J = 2.4 Hz,
C.sub.20H.sub.15Cl.sub.5F.sub.3N.sub.2O.sub.2, 1H), 7.68 (dd, J =
8.8,
548.9504; found, 2.2 Hz, 1H), 7.63 (s, 1H), 548.9495. 7.56 (d, J =
10.7 Hz, 3H), 4.40 (d, J = 44.7 Hz, 2H), 3.62 (d, J = 8.5 Hz, 1H),
3.49 (d, J = 8.5 Hz, 1H), 2.92 (s, 3H) F60 97-103 HRMS-ESI .sup.1H
NMR (500 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta.10.86
(s, 1H), 8.73 (t, J = 5.6 Hz,
C.sub.21H.sub.15Cl.sub.5F.sub.5N.sub.2O.sub.2, 1H), 7.76 (d, J =
2.6 Hz, 598.9463; found, 1H), 7.69 (dd, J = 8.8, 2.6 Hz, 598.9469.
1H), 7.62 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.5 Hz, 2H), 7.49 (d, J
= 8.7 Hz, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3.54 (q, J = 6.6 Hz, 2H),
3.50 (d, J = 8.5 Hz, 1H), 2.50 (dd, J = 3.7, 1.8 Hz, 2H); .sup.13C
NMR (126 MHz, DMSO-d.sub.6) .delta. 166.60, 163.05, 138.09, 137.76,
137.36, 134.54, 130.67, 128.38, 128.17, 124.44, 121.67, 119.43,
62.62, 38.87, 37.24, 31.99, 29.73, 29.57, 29.41 F61 109-112
HRMS-ESI .sup.1H NMR (500 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd
for .delta.10.89 (s, 1H), 9.23 (t, J = 6.3 Hz,
C.sub.21H.sub.13Cl.sub.5F.sub.7N.sub.2O.sub.2, 1H), 7.77 (d, J =
2.6 Hz, 634.9275; found, 1H), 7.74 (dd, J = 8.7, 2.6 Hz, 634.9278.
1H), 7.63 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.5 Hz, 2H), 7.52 (d, J
= 8.7 Hz, 1H), 4.17 (td, J = 16.4, 6.1 Hz, 2H), 3.62 (d, J = 8.5
Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H); .sup.13C NMR (126 MHz,
DMSO-d.sub.6) .delta. 166.81, 162.52, 137.57, 137.19, 136.11,
133.96, 130.22, 127.81, 127.60, 123.79, 121.33, 118.85, 62.04,
38.33, 36.66 F62 108-112 HRMS-ESI .sup.1H NMR (500 MHz,
DMSO-d.sub.6) [M + H].sup.+ calcd for .delta.10.85 (s, 1H), 7.65
(m, 3H), C.sub.21H.sub.20Cl.sub.5N.sub.2O.sub.2, 7.55 (t, J = 1.6
Hz, 2H), 508.9934; found, 7.51 (dd, J = 8.8, 2.9 Hz, 1H), 508.9939.
3.62 (dd, J = 8.5, 3.3 Hz, 1H), 3.48 (m, 2H), 3.05 (dt, J = 22.6,
7.0 Hz, 1H), 2.98 (s, 1.4H), 2.77 (s, 1.6H), 1.61 (h, J = 7.2 Hz,
1H), 1.48 (m, 1H), 0.92 (t, J = 7.4 Hz, 1.6H), 0.70 (t, J = 7.4 Hz,
1.4H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 166.54, 162.51,
137.96, 137.70, 137.19, 136.86, 136.52, 133.95, 129.89, 127.81,
127.59, 123.16, 122.89, 120.57, 118.11, 117.64, 62.03, 59.64,
51.19, 47.50, 39.91, 38.31, 36.71, 36.66, 35.39, 31.52, 20.66,
20.49, 19.53, 13.98, 11.05, 10.71 F63 109-113 HRMS-ESI .sup.1H NMR
(500 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta.10.85 (s,
1H), 7.68 (m, 1H), C.sub.20H.sub.18Cl.sub.5N.sub.2O.sub.2, 7.62 (m,
2H), 7.55 (s, 2H), 494.9778; found, 7.51 (dd, J = 8.8, 2.5 Hz, 1H),
494.9781. 3.61 (dd, J = 8.5, 3.2 Hz, 1H), 3.48 (m, 2H), 3.11 (m,
1H), 2.98 (s, 1.6H), 2.77 (s, 1.4H), 1.14 (t, J = 7.1 Hz, 1.5H),
1.04 (t, J = 7.1 Hz, 1.5H); .sup.13C NMR (126 MHz, DMSO-d.sub.6)
.delta. 166.27, 166.09, 162.53, 137.94, 137.75, 137.19, 136.70,
136.58, 133.95, 129.93, 129.87, 127.81, 127.59, 123.08, 123.00,
120.60, 117.63, 62.03, 59.64, 44.55, 40.91, 38.28, 36.71, 34.83,
31.07, 20.66, 13.98, 13.04, 11.65 F64 95-99 HRMS-ESI .sup.1H NMR
(500 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta.10.87 (d, J
= 2.7 Hz, 1H), C.sub.21H.sub.17Cl.sub.5F.sub.3N.sub.2O.sub.2, 7.65
(m, 3H), 7.54 (m, 3H), 562.9651; found, 3.73 (s, 1.4H), 3.61 (d, J
= 8.5 Hz, 562.9652. 1H), 3.49 (m, 1H), 3.36 (m, 0.6H), 3.02 (s,
0.9H), 2.82 (s, 2.1H), 2.64 (m, 2H); .sup.13C NMR (126 MHz,
DMSO-d.sub.6) .delta. 166.79, 166.62, 162.52, 137.97, 137.83,
137.19, 136.16, 135.76, 133.96, 129.94, 127.80, 127.60, 125.58,
123.02, 122.96, 120.83, 118.19, 117.60, 62.03, 59.64, 38.29, 36.71,
35.61, 31.46, 29.98, 29.76, 20.66, 13.98 F65 88-95 HRMS-ESI .sup.1H
NMR (500 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta.10.88
(s, 1H), 7.70 (m, 1H), C.sub.21H.sub.16Cl.sub.5N.sub.2O.sub.2, 7.65
(m, 1H), 7.62 (t, J = 1.8 Hz, 504.9621; found, 1H), 7.54 (m, 3H),
504.9620. 4.34 (s, 1.1H), 3.94 (m, 0.9H), 3.61 (d, J = 8.5 Hz, 1H),
3.49 (m, 1H), 3.34 (t, J = 2.3 Hz, 0.4H), 3.29 (t, J = 2.5 Hz,
0.6H), 3.05 (s, 1H), 2.84 (s, 2H); .sup.13C NMR (126 MHz,
DMSO-d.sub.6) .delta. 166.39, 166.35, 162.56, 162.51, 137.98,
137.87, 137.18, 135.67, 135.47, 133.95, 130.06, 130.03, 127.81,
127.59, 123.19, 123.09, 120.95, 117.65, 78.63, 78.11, 75.69, 74.50,
62.02, 38.29, 36.71, 35.08, 34.87, 31.49 F66 89-94 HRMS-ESI .sup.1H
NMR (500 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta.10.91
(m, 1H), 7.76 (m, 1H), C.sub.20H.sub.15Cl.sub.5N.sub.3O.sub.2, 7.68
(m, 1H), 7.63 (t, J = 1.8 Hz, 505.9574; found, 1H), 7.56 (m, 3H),
505.9584. 4.63 (s, 1.4H), 4.36 (dd, J = 22.2, 5.5 Hz, 0.6H), 3.61
(d, J = 8.5 Hz, 1H), 3.50 (m, J = 8.0 Hz, 1H), 3.09 (s, 0.7H), 2.90
(s, 2.3H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 167.24,
162.60, 138.04, 137.16, 134.71, 133.96, 130.12, 127.80, 127.60,
123.12, 121.33, 117.77, 116.08, 62.01, 38.28, 36.73, 35.97, 34.68
F67 224-226 HRMS-ESI .sup.1H NMR (500 MHz, DMSO-d.sub.6) [M +
H].sup.+ calcd for .delta.10.84 (m, 1H), 7.57 (m, 6H),
C.sub.21H.sub.20Cl.sub.5N.sub.2O.sub.3, 3.60 (m, 3H), 3.48 (m, 2H),
524.9883; found, 3.30 (s, 1.7H), 3.26 (m, 1H), 524.9885. 3.15 (s,
1.3H), 3.02 (s, 1.4H), 2.82 (s, 1.6H); .sup.13C NMR (126 MHz,
DMSO-d.sub.6) .delta. 166.92, 166.66, 162.51, 162.45, 137.94,
137.65, 137.19, 136.59, 136.37, 133.95, 129.92, 129.69, 127.81,
127.59, 123.13, 122.95, 120.64, 120.59, 117.62, 69.27, 62.06,
62.03, 57.99, 57.96, 54.81, 49.02, 45.73, 38.29, 36.65, 36.61 F68
94-99 HRMS-ESI .sup.1H NMR (500 MHz, DMSO-d.sub.6) [M + H].sup.+
calcd for .delta.10.86 (m, 1H), 7.76 (m,
C.sub.21H.sub.20Cl.sub.5N.sub.2O.sub.2S, 0.5H), 7.65 (m, 2.5H),
540.9655; found, 7.55 (m, 2H), 7.51 (d, J = 8.7 Hz, 540.9669. 1H),
3.62 (m, 2H), 3.49 (m, 1H), 3.26 (m, 1H), 3.01 (s, 1.4H), 2.81 (s,
1.6H), 2.75 (t, J = 7.0 Hz, 1H), 2.63 (m, 1H), 2.14 (s, 1.5H), 1.75
(d, J = 6.4 Hz, 1.5H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta.
166.70, 162.51, 137.93, 137.76, 137.19, 136.53, 136.16, 133.95,
129.90, 129.81, 127.81, 127.59, 123.11, 122.94, 120.73, 120.68,
118.58, 117.70, 62.03, 44.98, 38.29, 36.70, 36.63, 35.74, 31.69,
30.89, 30.01, 14.44, 14.11 F69 HRMS-ESI .sup.1H NMR (500 MHz,
DMSO-d.sub.6) [M + H].sup.+ calcd for .delta.10.86 (s, 1H), 7.69
(m, 1H), C.sub.22H.sub.20Cl.sub.5N.sub.2O.sub.2, 7.63 (m, 2H), 7.55
(m, 2H), 520.9934; found, 7.51 (m, 1H), 3.61 (d, J = 8.5 Hz,
520.9936. 1H), 3.48 (d, J = 8.5 Hz, 2H), 3.07 (s, 1.5H), 2.95 (m,
1H), 2.84 (s, 1.5H), 1.08 (m, 0.5H), 0.86 (m, 0.5H), 0.48 (m, 2H),
0.30 (m, 1H), 0.07 (m, 1H); .sup.13C NMR (126 MHz, DMSO-d.sub.6)
.delta. 166.48, 166.27, 162.52, 137.95, 137.74, 137.19, 136.74,
136.49, 133.95, 129.91, 127.81, 127.59, 123.14, 122.95, 120.58,
117.62, 62.03, 54.10, 49.91, 38.30, 36.68, 35.51, 31.85, 9.44,
8.89, 3.40, 3.30, 2.97, 2.84 F70 105-110 HRMS-ESI .sup.1H NMR (500
MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta.10.85 (s, 1H),
8.64 (t, J = 5.9 Hz, C.sub.22H.sub.18Cl.sub.5F.sub.2N.sub.2O.sub.2,
1H), 7.75 (d, J = 2.6 Hz, 556.9746; found, 1H), 7.68 (dd, J = 8.8,
2.6 Hz, 556.9754 1H), 7.62 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.6
Hz, 2H), 7.49 (d, J = 8.7 Hz, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3.50
(d, J = 8.5 Hz, 1H), 3.37 (t, J = 5.7 Hz, 2H), 2.63 (m, 2H), 2.40
(m, 3H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 166.29,
162.46, 137.50, 137.30, 137.18, 133.96, 130.01, 127.80, 127.59,
123.75, 120.91, 118.82, 62.04, 42.34, 38.29, 37.82, 37.65, 37.47,
36.66, 22.56, 22.50, 22.46, 22.41 F71 114-121 HRMS-ESI .sup.1H NMR
(500 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta.10.88 (m,
1H), 7.79 (m, 1H), C.sub.21H.sub.16Cl.sub.5F.sub.2N.sub.2O.sub.2,
7.63 (m, 2H), 7.55 (m, 3H), 542.9589; found, 3.93 (t, J = 13.1 Hz,
1H), 542.9591. 3.74 (t, J = 7.6 Hz, 1H), 3.61 (m, 2H), 3.49 (d, J =
8.5 Hz, 1H), 3.40 (t, J = 7.6 Hz, 1H), 2.50 (m, 2H); .sup.13C NMR
(126 MHz, DMSO-d.sub.6) .delta. 170.22, 165.39, 165.23, 162.56,
137.96, 137.17, 135.96, 135.45, 133.96, 130.20, 130.12, 127.80,
127.61, 127.38, 123.01, 122.80, 121.30, 118.06, 117.91, 62.04,
59.64, 38.25, 36.73, 20.66, 13.98 F72 115-118 HRMS-ESI .sup.1H NMR
(500 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta.10.85 (s,
1H), 8.59 (t, J = 5.7 Hz,
C.sub.21H.sub.17Cl.sub.5F.sub.3N.sub.2O.sub.2, 1H), 7.75 (d, J =
2.6 Hz, 562.9651; found, 1H), 7.68 (dd, J = 8.8, 2.6 Hz, 562.9653.
1H), 7.62 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.6 Hz, 2H), 7.49 (d, J
= 8.7 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H),
3.30 (m, 2H), 2.34 (ddt, J = 14.8, 9.1, 3.3 Hz, 2H), 1.74 (dt, J =
14.7, 6.9 Hz, 2H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta.
166.05, 162.47, 137.52, 137.27, 137.18, 133.96, 130.02, 127.81,
127.60,
123.75, 120.90, 118.84, 62.04, 59.64, 38.30, 37.62, 36.66, 30.50,
30.28, 30.06, 29.84, 21.60, 20.66, 13.98 F73 103-108 HRMS-ESI
.sup.1H NMR (500 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for
.delta.10.86 (m, 1H), 7.74 (d, J = 2.3 Hz,
C.sub.23H.sub.20Cl.sub.5F.sub.2N.sub.2O.sub.2, 0.3H), 7.68 (d, J =
2.5 Hz, 570.9903; found, 0.7H), 7.63 (m, 2H), 570.9908. 7.55 (m,
2H), 7.52 (d, J = 8.8 Hz, 1H), 3.83 (s, 0.6H), 3.62 (m, 1H), 3.49
(m, 1.6H), 3.25 (m, 0.7H), 2.99 (s, 0.9H), 2.79 (s, 2H), 2.69 (m,
1.6H), 2.55 (m, 1.3H), 2.45 (m, 1.4H), 2.17 (m, 0.9H) F74 108-111
HRMS-ESI .sup.1H NMR (500 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd
for .delta.10.88 (s, 1H), 8.76 (t, J = 5.5 Hz,
C.sub.20H.sub.18Cl.sub.5N.sub.2O.sub.3S, 1H), 7.76 (m, 1H),
542.9447; found, 7.69 (m, 1H), 7.63 (t, J = 1.7 Hz, 542.9444. 1H),
7.55 (d, J = 1.6 Hz, 2H), 7.48 (d, J = 8.7 Hz, 1H), 3.60 (m, 3H),
3.51 (d, J = 8.5 Hz, 1H), 3.04 (dt, J = 13.9, 7.2 Hz, 1H), 2.89
(dt, J = 12.7, 6.2 Hz, 1H), 2.62 (s, 3H); .sup.13C NMR (126 MHz,
DMSO-d.sub.6) .delta. 166.08, 162.46, 137.48, 137.18, 136.88,
133.95, 130.05, 127.80, 127.59, 123.87, 121.04, 118.92, 62.05,
52.82, 38.26, 38.06, 36.66, 33.07 F75 104-108 HRMS-ESI .sup.1H NMR
(500 MHz, DMSO-d.sub.6) [M + H].sup.+ calcd for .delta.10.87 (s,
1H), 8.74 (t, J = 5.6 Hz, C.sub.20H.sub.18Cl.sub.5N.sub.2O.sub.4S,
1H), 7.78 (d, J = 2.5 Hz, 558.9396; found, 1H), 7.69 (dd, J = 8.8,
2.6 Hz, 558.9402. 1H), 7.63 (t, J = 1.7 Hz, 1H), 7.55 (d, J = 1.6
Hz, 2H), 7.49 (d, J = 8.7 Hz, 1H), 3.64 (m, 3H), 3.50 (d, J = 8.5
Hz, 1H), 3.37 (t, J = 6.9 Hz, 2H), 3.06 (s, 3H); .sup.13C NMR (126
MHz, DMSO-d.sub.6) .delta. 166.09, 162.47, 137.48, 137.18, 136.68,
133.96, 130.07, 127.80, 127.59, 123.89, 121.17, 118.99, 62.05,
52.60, 40.61, 38.25, 36.67, 33.05 F78 107-112 HRMS-ESI [M+].sup.+
.sup.1H NMR (500 MHz, DMSO-d.sub.6) calcd for .delta. 10.84 (s,
1H), 8.41 (t, J = 5.8 Hz, C.sub.20H.sub.17Cl.sub.5N.sub.2O.sub.3,
1H), 7.75 (d, J = 2.6 Hz, 507.9682; found, 1H), 7.68 (dd, J = 8.8,
2.6 Hz, 507.9679. 1H), 7.63 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.4
Hz, 2H), 7.47 (d, J = 8.7 Hz, 1H), 4.70 (d, J = 4.8 Hz, 1H), 3.76
(dt, J = 11.5, 6.0 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.50 (d, J =
8.5 Hz, 1H), 3.22 (m, 1H), 3.14 (m, 1H), 1.10 (d, J = 6.2 Hz, 3H);
.sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 165.96, 162.42,
137.42, 137.40, 137.19, 133.95, 129.95, 127.80, 127.59, 123.84,
120.78, 119.00, 64.97, 62.05, 46.63, 38.29, 36.66, 21.07 F79
233-236 HRMS-ESI [M].sup.+ .sup.1H NMR (500 MHz, DMSO-d.sub.6)
calcd for .delta. 10.85 (s, 1H), 8.54 (t, J = 5.7 Hz,
C.sub.22H.sub.19Cl.sub.5N.sub.4O.sub.3, 1H), 7.73 (d, J = 2.5 Hz,
561.9900; found, 1H), 7.69 (dd, J = 8.7, 2.5 Hz, 561.9911. 1H),
7.62 (d, J = 1.7 Hz, 1H), 7.55 (d, J = 1.5 Hz, 2H), 7.47 (d, J =
8.7 Hz, 1H), 6.29 (s, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.50 (d, J =
8.5 Hz, 1H), 3.42 (m, 2H), 3.35 (d, J = 6.2 Hz, 2H), 3.22 (m, 4H);
.sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 165.95, 162.44,
162.11, 137.43, 137.25, 137.19, 133.95, 129.99, 127.80, 127.59,
123.88, 120.92, 118.95, 62.06, 44.69, 42.51, 38.26, 37.43, 36.67
F84 187-190 HRMS-ESI [M+].sup.+ .sup.1H NMR (500 MHz, DMSO-d.sub.6)
calcd for .delta. 10.83 (s, 1H), 8.45 (t, J = 5.7 Hz,
C.sub.21H.sub.19Cl.sub.5N.sub.2O.sub.3, 1H), 7.74 (d, J = 2.5 Hz,
521.9839; found, 1H), 7.67 (dd, J = 8.7, 2.5 Hz, 521.9838. 1H),
7.61 (s, 2H), 7.47 (d, J = 8.7 Hz, 1H), 3.84 (s, 3H), 3.56 (d, J =
8.5 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H), 3.19 (q, J = 6.4 Hz, 2H),
1.52 (h, J = 7.3 Hz, 2H), 0.92 (t, J = 7.4 Hz, 3H); .sup.13C NMR
(126 MHz, DMSO-d.sub.6) .delta. 165.83, 162.47, 151.07, 137.59,
137.47, 131.36, 129.95, 129.65, 128.10, 123.79, 120.70, 118.87,
62.13, 60.57, 40.57, 38.40, 36.28, 22.14, 11.32 F85 206-208
HRMS-ESI [M+].sup.+ .sup.1H NMR (500 MHz, DMSO-d.sub.6) calcd for
.delta. 10.83 (s, 1H), 8.46 (t, J = 5.5 Hz,
C.sub.20H.sub.17Cl.sub.5N.sub.2O.sub.3, 1H), 7.74 (d, J = 2.5 Hz,
507.9682; found, 1H), 7.66 (dd, J = 8.8, 2.6 Hz, 507.9687. 1H),
7.61 (s, 2H), 7.47 (d, J = 8.7 Hz, 1H), 3.84 (s, 3H), 3.56 (d, J =
8.5 Hz, 1H), 3.45 (d, J = 8.5 Hz, 1H), 3.25 (p, J = 6.9 Hz, 2H),
1.11 (t, J = 7.2 Hz, 3H); .sup.13C NMR (126 MHz, DMSO-d.sub.6)
.delta. 165.60, 162.48, 151.07, 137.47, 131.36, 129.97, 129.65,
128.11, 123.85, 120.74, 118.88, 62.12, 60.57, 38.40, 36.29, 33.74,
14.45 F86 185-188 HRMS-ESI [M+].sup.+ .sup.1H NMR (500 MHz,
DMSO-d.sub.6) calcd for .delta. 10.85 (s, 1H), 8.73 (t, J = 5.6 Hz,
C.sub.20H.sub.16Cl.sub.5FN.sub.2O.sub.3, 1H), 7.76 (d, J = 2.5 Hz,
525.9588; found, 1H), 7.69 (dd, J = 8.7, 2.5 Hz, 525.9602. 1H),
7.61 (s, 2H), 7.48 (d, J = 8.7 Hz, 1H), 4.53 (dt, J = 47.5, 5.0 Hz,
2H), 3.84 (s, 3H), 3.56 (m, 2H), 3.52 (m, 1H), 3.45 (d, J = 8.5 Hz,
1H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 166.25, 162.50,
151.07, 137.47, 137.01, 131.36, 130.03, 129.65, 128.11, 123.85,
120.93, 118.92, 82.58, 81.26, 62.12, 60.57, 38.40, 36.29; .sup.19F
NMR (471 MHz, DMSO-d.sub.6) .delta. 19.95, 19.89, 19.85, 19.83,
19.79, 19.75, 19.73, 19.69, 19.63 F87 193-196 HRMS-ESI [M+].sup.+
.sup.1H NMR (500 MHz, DMSO-d.sub.6) calcd for .delta. 10.88 (s,
1H), 9.21 (t, J = 6.3 Hz,
C.sub.20H.sub.14Cl.sub.5F.sub.3N.sub.2O.sub.3, 1H), 7.77 (d, J =
2.1 Hz, 561.9399; found, 1H), 7.73 (dd, J = 8.8, 2.1 Hz, 561.9403.
1H), 7.61 (s, 2H), 7.51 (d, J = 8.7 Hz, 1H), 4.08 (dt, J = 17.4,
9.5 Hz, 2H), 3.84 (s, 3H), 3.57 (d, J = 8.5 Hz, 1H), 3.46 (d, J =
8.5 Hz, 1H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 166.62,
162.56, 151.07, 137.56, 136.15, 131.35, 130.19, 129.65, 128.11,
125.65, 123.77, 123.43, 121.28, 118.83, 62.11, 60.57, 38.42, 36.28;
.sup.19F NMR (471 MHz, DMSO-d.sub.6) .delta. -70.42, -70.44, -70.46
F88 181-185 HRMS-ESI [M+].sup.+ .sup.1H NMR (500 MHz, DMSO-d.sub.6)
calcd for .delta. 10.85 (s, 1H), 8.71 (t, J = 5.6 Hz,
C.sub.21H.sub.16Cl.sub.5F.sub.3N.sub.2O.sub.3, 1H), 7.76 (d, J =
2.4 Hz, 575.9556; found, 1H), 7.68 (dd, J = 8.7, 2.4 Hz, 575.9562.
1H), 7.60 (s, 2H), 7.48 (d, J = 8.7 Hz, 1H), 3.84 (s, 3H), 3.56 (d,
J = 8.5 Hz, 1H), 3.46 (t, J = 8.2 Hz, 3H), 2.54 (dd, J = 11.5, 6.5
Hz, 2H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 166.00,
162.50, 151.07, 137.51, 136.84, 131.36, 130.07, 129.99, 129.65,
128.11, 127.78, 125.58, 123.84, 123.37, 121.03, 118.83, 62.13,
60.57, 38.39, 36.28, 32.43, 32.30, 32.09, 31.87, 30.85, 28.37,
24.68, 21.96; .sup.19F NMR (471 MHz, DMSO-d.sub.6) .delta. -63.75,
-63.77, -63.79 F91 254-260 HRMS-ESI [M+].sup.+ .sup.1H NMR (500
MHz, DMSO-d.sub.6) calcd for .delta. 10.99 (s, 1H), 8.57 (t, J =
5.6 Hz, C.sub.19H.sub.14Cl.sub.6N.sub.2O.sub.2, 1H), 8.01 (d, J =
2.4 Hz, 511.9186; found, 1H), 7.63 (t, J = 1.8 Hz, 511.9189. 1H),
7.59 (d, J = 2.5 Hz, 1H), 7.56 (d, J = 1.5 Hz, 2H), 3.62 (d, J =
8.5 Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H), 3.26 (p, J = 6.3 Hz, 2H),
1.11 (t, J = 7.2 Hz, 3); .sup.13C NMR (126 MHz, DMSO-d.sub.6)
.delta. 164.90, 162.85, 139.55, 138.13, 137.08, 133.97, 132.00,
127.82, 127.63, 122.06, 120.30, 117.36, 61.93, 38.36, 36.72, 33.81,
14.36 F92 235-237 HRMS-ESI [M+].sup.+ .sup.1H NMR (500 MHz,
DMSO-d.sub.6) calcd for .delta. 11.01 (s, 1H), 8.86 (t, J = 5.6 Hz,
C.sub.19H.sub.13Cl.sub.6FN.sub.2O.sub.2, 1H), 8.04 (d, J = 2.5 Hz,
529.9092; found, 1H), 7.62 (m, 2H), 529.9093. 7.56 (d, J = 1.4 Hz,
2H), 4.54 (dt, J = 47.5, 4.9 Hz, 2H), 3.62 (d, J = 8.5 Hz, 1H),
3.54 (m, 3H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 165.56,
162.87, 139.11, 138.15, 137.08, 133.97, 132.05, 127.82, 127.63,
122.05, 120.46, 117.41, 82.58, 81.26, 61.93, 54.80, 38.37, 36.72;
.sup.19F NMR (471 MHz, DMSO-d.sub.6) .delta. -69.39, -70.90 F93
210-213 HRMS-ESI [M+].sup.+ .sup.1H NMR (500 MHz, DMSO) .delta.
calcd for 11.04 (s, 1H), 9.33 (t, J = 6.3 Hz,
C.sub.19H.sub.11Cl.sub.6F.sub.3N.sub.2O.sub.2, 1H), 8.07 (d, J =
2.4 Hz, 565.8904; found, 1H), 7.63 (m, 2H), 7.56 (d, J = 1.5 Hz,
565.8902. 2H), 4.11 (dt, J = 16.4, 8.5 Hz, 2H), 3.63 (d, J = 8.5
Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H); .sup.19F NMR (471 MHz,
DMSO-d.sub.6) .delta. -70.42, -70.44, -70.46 F94 185-189 HRMS-ESI
[M+].sup.+ .sup.1H NMR (500 MHz, DMSO-d.sub.6) calcd for .delta.
11.01 (s, 1H), 8.83 (t, J = 5.7 Hz,
C.sub.20H.sub.13Cl.sub.6F.sub.3N.sub.2O.sub.2, 1H), 8.04 (d, J =
2.4 Hz, 579.9060; found, 1H), 7.63 (t, J = 1.8 Hz, 579.9043. 1H),
7.60 (d, J = 2.5 Hz, 1H), 7.56 (d, J = 1.5 Hz, 2H), 3.63 (d, J =
8.5 Hz, 1H), 3.50 (m, 3H), 2.56 (m, 2H); .sup.13C NMR (126 MHz,
DMSO-d.sub.6) .delta. 165.31, 162.88, 138.95, 138.19, 137.08,
133.97, 132.11, 129.99, 127.82, 127.78, 127.63, 125.58, 123.38,
122.04, 120.56, 117.32, 61.95, 38.36, 36.71, 32.56, 32.53, 32.50,
32.47, 32.45, 32.24, 32.02, 31.81; .sup.19F NMR (471 MHz,
DMSO-d.sub.6) .delta. -63.71, -63.74, -63.76 F95 224-227 HRMS-ESI
[M+].sup.+ .sup.1H NMR (500 MHz, DMSO-d.sub.6) calcd for .delta.
11.00 (s, 1H), 8.57 (t, J = 5.6 Hz,
C.sub.20H.sub.16Cl.sub.6N.sub.2O.sub.2, 1H), 8.02 (d, J = 2.4
Hz,
521.9343; found, 1H), 7.63 (d, J = 1.7 Hz, 525.9348. 1H), 7.59 (d,
J = 2.4 Hz, 1H), 7.56 (d, J = 1.6 Hz, 2H), 3.63 (d, J = 8.5 Hz,
1H), 3.51 (d, J = 8.5 Hz, 1H), 3.20 (q, J = 6.5 Hz, 2H), 1.52 (h, J
= 7.2 Hz, 2H), 0.92 (t, J = 7.4 Hz, 3H); .sup.13C NMR (126 MHz,
DMSO-d.sub.6) .delta. 165.15, 162.86, 139.66, 138.14, 137.08,
133.97, 131.99, 127.82, 127.63, 122.00, 120.26, 117.36, 61.94,
40.61, 38.36, 36.71, 22.07, 11.30 F96 ESIMS 575 .sup.1H NMR (400
MHz, Acetone- ([M + H].sup.+) d.sub.6) .delta. 10.11 (s, 1H), 8.02
(d, J = 8.0 Hz, 1H), 7.80 (d, J = 2.5 Hz, 1H), 7.74 (dd, J = 8.7,
2.6 Hz, 1H), 7.56-7.45 (m, 5H), 7.39 (d, J = 8.7 Hz, 1H), 7.15-7.04
(m, 2H), 5.28 (p, J = 7.2 Hz, 1H), 3.64 (d, J = 8.3 Hz, 1H), 3.40
(d, J = 8.3 Hz, 1H), 1.56 (d, J = 7.0 Hz, 3H); .sup.19F NMR (376
MHz, Acetone) .delta. -117.60, -117.61, -117.63 F97 ESIMS 589
.sup.1H NMR (400 MHz, Acetone- ([M + H].sup.+) d.sub.6) .delta.
10.10 (s, 1H), 7.87 (s, 1H), 7.81-7.70 (m, 2H), 7.64-7.55 (m, 2H),
7.59-7.46 (m, 3H), 7.39 (d, J = 8.6 Hz, 1H), 7.08 (t, J = 8.8 Hz,
2H), 3.65 (d, J = 8.3 Hz, 1H), 3.41 (d, J = 8.4 Hz, 1H), 1.78 (d, J
= 2.0 Hz, 6H); .sup.19F NMR (376 MHz, Acetone- d.sub.6) .delta.
-119.11 F98 158-163 HRMS-ESI [M+].sup.+ .sup.1H NMR (500 MHz,
DMSO-d.sub.6) calcd for .delta. 10.32 (s, 1H), 8.52 (t, J = 5.5 Hz,
C.sub.19H.sub.14Cl.sub.6N.sub.2O.sub.2, 1H), 7.93 (s, 1H),
511.9186; found, 7.79 (s, 1H), 7.63 (t, J = 1.8 Hz, 511.9187. 1H),
7.52 (d, J = 1.7 Hz, 2H), 3.81 (d, J = 8.6 Hz, 1H), 3.62 (d, J =
8.5 Hz, 1H), 3.24 (p, J = 7.0 Hz, 2H), 1.10 (t, J = 7.2 Hz, 3H);
.sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 164.72, 163.26,
137.15, 136.23, 133.96, 133.59, 129.95, 127.72, 127.61, 126.47,
126.20, 124.21, 62.38, 37.21, 37.07, 33.83, 14.36 F99 140-145
HRMS-ESI [M+].sup.+ .sup.1H NMR (500 MHz, DMSO-d.sub.6) calcd for
.delta. 10.33 (s, 1H), 8.81 (t, J = 5.6 Hz,
C.sub.19H.sub.13Cl.sub.6FN.sub.2O.sub.2, 1H), 7.96 (s, 1H),
529.9092; found, 7.81 (s, 1H), 7.63 (t, J = 1.7 Hz, 529.9092. 1H),
7.52 (d, J = 1.6 Hz, 2H), 4.52 (dt, J = 47.4, 5.0 Hz, 2H), 3.81 (d,
J = 8.6 Hz, 1H), 3.62 (d, J = 8.5 Hz, 1H), 3.53 (dq, J = 27.1, 5.3
Hz, 2H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 165.38,
163.27, 137.15, 135.78, 133.96, 133.61, 130.02, 127.72, 127.61,
126.69, 126.21, 124.25, 82.56, 81.24, 62.38, 37.21, 37.08; .sup.19F
NMR (471 MHz, DMSO-d.sub.6) .delta. 20.05, 19.99, 19.95, 19.93,
19.89, 19.85, 19.83, 19.79, 19.73 F100 175-179 HRMS-ESI [M+].sup.+
.sup.1H NMR (500 MHz, DMSO-d.sub.6) calcd for .delta. 10.36 (s,
1H), 9.27 (t, J = 6.3 Hz,
C.sub.19H.sub.11Cl.sub.6F.sub.3N.sub.2O.sub.2, 1H), 7.99 (s, 1H),
565.8904; found, 7.85 (s, 1H), 7.63 (t, J = 1.7 Hz, 565.8905. 1H),
7.52 (d, J = 1.6 Hz, 2H), 4.08 (m, 2H), 3.82 (d, J = 8.6 Hz, 1H),
3.63 (d, J = 8.5 Hz, 1H); .sup.13C NMR (126 MHz, DMSO-d.sub.6)
.delta. 165.79, 163.34, 137.15, 134.92, 133.96, 133.74, 130.19,
127.81, 127.72, 127.61, 127.04, 126.12, 125.59, 124.09, 123.37,
121.15, 62.39, 37.23, 37.09; .sup.19F NMR (471 MHz, DMSO-d.sub.6)
.delta. -70.38, -70.40, -70.43 F101 186-190 HRMS-ESI [M+].sup.+
.sup.1H NMR (500 MHz, DMSO-d.sub.6) calcd for .delta. 10.32 (s,
1H), 8.52 (t, J = 5.7 Hz, C.sub.20H.sub.16Cl.sub.6N.sub.2O.sub.2,
1H), 7.93 (s, 1H), 525.9343; found, 7.79 (s, 1H), 7.63 (t, J = 1.8
Hz, 525.9348. 1H), 7.52 (d, J = 1.6 Hz, 2H), 3.81 (d, J = 8.6 Hz,
1H), 3.63 (d, J = 8.5 Hz, 1H), 3.18 (q, J = 6.4 Hz, 2H), 1.51 (h, J
= 7.3 Hz, 2H), 0.90 (t, J = 7.4 Hz, 3H); .sup.13C NMR (126 MHz,
DMSO-d.sub.6) .delta.164.95, 163.26, 137.16, 136.34, 133.95,
133.60, 129.93, 127.72, 127.60, 126.41, 126.13, 124.18, 62.39,
40.65, 37.21, 37.05, 22.06, 11.30 F102 190-195 HRMS-ESI [M+].sup.+
.sup.1H NMR (500 MHz, DMSO-d.sub.6) calcd for .delta. 10.34 (s,
1H), 8.78 (t, J = 5.7 Hz,
C.sub.20H.sub.13Cl.sub.6F.sub.3N.sub.2O.sub.2, 1H), 7.95 (s, 1H),
579.9060; found, 7.81 (s, 1H), 7.63 (t, J = 1.6 Hz, 579.9060. 1H),
7.52 (d, J = 1.6 Hz, 2H), 3.82 (d, J = 8.6 Hz, 1H), 3.63 (d, J =
8.5 Hz, 1H), 3.46 (q, J = 6.6 Hz, 2H), 2.53 (m, 2H); .sup.13C NMR
(126 MHz, DMSO-d.sub.6) .delta. 165.13, 163.27, 137.15, 135.58,
133.96, 133.65, 130.09, 129.95, 127.74, 127.72, 127.61, 126.84,
126.23, 125.54, 124.24, 123.34, 62.39, 37.20, 37.06, 32.54, 32.51,
32.47, 32.26, 32.04, 31.83; .sup.19F NMR (471 MHz, DMSO-d.sub.6)
.delta. -63.79, -63.82, -63.84 F103 162-165 HRMS-ESI [M+].sup.+
.sup.1H NMR (500 MHz, DMSO-d.sub.6) calcd for .delta. 10.87 (s,
1H), 8.46 (t, J = 5.6 Hz, C.sub.19H.sub.15Cl.sub.4FN.sub.2O.sub.2,
1H), 7.74 (d, J = 2.6 Hz, 461.9872; found, 1H), 7.70 (dd, J = 7.1,
1.9 Hz, 461.9873. 1H), 7.67 (dd, J = 8.8, 2.6 Hz, 1H), 7.46 (m,
3H), 3.57 (d, J = 8.5 Hz, 1H), 3.42 (d, J = 8.5 Hz, 1H), 3.25 (p, J
= 6.6 Hz, 2H), 1.11 (t, J = 7.2 Hz, 3H); .sup.13C NMR (126 MHz,
DMSO-d.sub.6) .delta. 165.60, 162.56, 157.73, 155.76, 137.46,
130.97, 130.93, 130.90, 129.97, 129.72, 129.66, 123.85, 120.75,
119.43, 119.29, 118.89, 116.89, 116.72, 62.20, 38.42, 36.48, 33.74,
14.45; .sup.19F NMR (471 MHz, DMSO-d.sub.6) .delta. -117.27,
-117.28, -117.29, -117.30, -117.31 F104 188-191 HRMS-ESI [M+].sup.+
.sup.1H NMR (500 MHz, DMSO-d.sub.6) calcd for .delta. 10.89 (s,
1H), 8.74 (t, J = 5.6 Hz,
C.sub.19H.sub.14Cl.sub.4F.sub.2N.sub.2O.sub.2, 1H), 7.76 (d, J =
2.6 Hz, 479.9777; found, 1H), 7.69 (m, 2H), 479.9779. 7.47 (m, 3H),
4.53 (dt, J = 47.5, 5.0 Hz, 2H), 3.54 (dd, J = 31.2, 6.4 Hz, 3H),
3.42 (d, J = 8.5 Hz, 1H); .sup.13C NMR (126 MHz, DMSO-d.sub.6)
.delta. 166.26, 162.58, 157.73, 155.76, 137.48, 137.00, 130.97,
130.93, 130.90, 130.03, 129.73, 129.66, 123.86, 120.94, 119.44,
119.29, 118.93, 116.89, 116.72, 82.59, 81.27, 62.20, 38.43, 36.49;
.sup.19F NMR (471 MHz, DMSO-d.sub.6) .delta. 19.95, 19.89, 19.85,
19.83, 19.79, 19.75, 19.73, 19.69, 19.63, -117.27, -117.28,
-117.29, -117.30, -117.31 F105 190-193 HRMS-ESI [M+].sup.+ .sup.1H
NMR (500 MHz, DMSO-d.sub.6) calcd for .delta. 10.93 (s, 1H), 9.22
(t, J = 6.3 Hz, C.sub.19H.sub.12Cl.sub.4F.sub.4N.sub.2O.sub.2, 1H),
7.78 (d, J = 2.6 Hz, 515.9589; found, 1H), 7.74 (dd, J = 8.8, 2.6
Hz, 515.9593. 1H), 7.70 (dd, J = 7.1, 1.8 Hz, 1H), 7.52 (d, J = 8.7
Hz, 1H), 7.46 (m, 2H), 4.09 (m, 2H), 3.58 (d, J = 8.5 Hz, 1H), 3.42
(d, J = 8.5 Hz, 1H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta.
166.63, 162.65, 157.74, 155.78, 137.58, 136.15, 130.98, 130.92,
130.90, 130.20, 129.73, 129.67, 127.89, 125.66, 123.80, 123.44,
121.31, 121.22, 119.45, 119.31, 118.85, 116.90, 116.73, 62.20,
38.46, 36.50; .sup.19F NMR (471 MHz, DMSO-d.sub.6) .delta. -70.43,
-70.45, -70.47, -117.25, -117.27, -117.28, -117.30 F106 171-174
HRMS-ESI [M+].sup.+ .sup.1H NMR (500 MHz, DMSO-d.sub.6) calcd for
.delta. 10.87 (s, 1H), 8.45 (t, J = 5.7 Hz,
C.sub.20H.sub.17Cl.sub.4FN.sub.2O.sub.2, 1H), 7.74 (d, J = 2.6 Hz,
476.0028; found, 1H), 7.69 (m, 2H), 476.0026. 7.46 (m, 3H), 3.58
(d, J = 8.4 Hz, 1H), 3.42 (d, J = 8.5 Hz, 1H), 3.19 (m, 2H), 1.52
(h, J = 7.2 Hz, 2H), 0.92 (t, J = 7.4 Hz, 3H); .sup.13C NMR (126
MHz, DMSO-d.sub.6) .delta. 165.84, 162.56, 157.73, 155.77, 137.59,
137.47, 130.97, 130.93, 130.90, 129.95, 129.73, 129.66, 123.81,
120.72, 119.44, 119.30, 118.89, 116.89, 116.72, 62.20, 40.57,
38.43, 36.48, 22.14, 11.32; .sup.19F NMR (471 MHz, DMSO-d.sub.6)
.delta. -117.26, -117.28, -117.29, -117.31 F107 86-92 HRMS-ESI
[M+].sup.+ .sup.1H NMR (500 MHz, DMSO-d.sub.6) calcd for .delta.
10.89 (s, 1H), 8.71 (t, J = 5.7 Hz,
C.sub.20H.sub.14Cl.sub.4F.sub.4N.sub.2O.sub.2, 1H), 7.76 (d, J =
2.6 Hz, 529.9749; found, 1H), 7.69 (m, 2H), 529.9746. 7.47 (m, 3H),
3.58 (d, J = 8.5 Hz, 1H), 3.47 (q, J = 6.4 Hz, 2H), 3.42 (d, J =
8.5 Hz, 1H), 2.54 (m, 2H); .sup.19F NMR (471 MHz, DMSO-d.sub.6)
.delta. -63.74, -63.77, -63.79, -117.27, -117.28, -117.30, -117.31
F108 ESIMS 503 .sup.1H NMR (400 MHz, Acetone- ([M + H].sup.+)
d.sub.6) .delta. 10.16 (s, 1H), 8.23 (t, J = 6.5 Hz, 1H), 7.92 (d,
J = 2.6 Hz, 1H), 7.82-7.74 (m, 1H), 7.49-7.36 (m, 2H), 7.40-7.25
(m, 2H), 4.27-4.14 (m, 2H), 3.65-3.58 (m, 1H), 3.33 (d, J = 8.3 Hz,
1H); .sup.19F NMR (376 MHz, Acetone- d.sub.6) .delta. -72.58,
-72.59, -139.57, -139.63, -140.84 F109 ESIMS 580 .sup.1H NMR (400
MHz, Acetone- ([M + H].sup.+) d.sub.6) .delta. 10.14 (s, 1H), 8.24
(t, J = 6.5 Hz, 1H), 7.91 (d, J = 2.6 Hz, 1H), 7.84-7.73 (m, 2H),
7.61 (d, J = 8.3 Hz, 1H), 7.51-7.41 (m, 2H), 4.21 (qd, J = 9.4, 6.5
Hz, 2H), 3.63 (dt, J = 8.2, 0.7 Hz, 1H), 3.37 (d, J = 8.3 Hz, 1H);
.sup.19F NMR (376 MHz, Acetone-
d.sub.6) .delta. -72.54, -72.54, -72.55, -72.55, -72.56 F111 ESIMS
624 .sup.1H NMR (400 MHz, Acetone- ([M + H].sup.+) d.sub.6) .delta.
10.14 (s, 1H), 8.24 (t, J = 6.5 Hz, 1H), 7.91 (d, J = 2.6 Hz, 1H),
7.83-7.72 (m, 3H), 7.50-7.35 (m, 2H), 4.20 (qd, J = 9.5, 6.5 Hz,
2H), 3.61 (dt, J = 8.3, 0.8 Hz, 1H), 3.36 (d, J = 8.3 Hz, 1H);
.sup.19F NMR (376 MHz, Acetone- d.sub.6) .delta. -72.55 F112 ESIMS
552 .sup.1H NMR (400 MHz, Acetone- ([M + H].sup.+) d.sub.6) .delta.
10.21 (s, 1H), 8.24 (t, J = 6.5 Hz, 1H), 7.92 (d, J = 2.6 Hz, 1H),
7.85-7.74 (m, 2H), 7.58-7.48 (m, 2H), 7.45 (d, J = 8.7 Hz, 1H),
4.21 (qd, J = 9.4, 6.5 Hz, 2H), 3.77-3.70 (m, 1H), 3.46 (d, J = 8.3
Hz, 1H); .sup.19F NMR (376 MHz, Acetone- d.sub.6) .delta. -61.78,
-61.79, -61.81, -61.82, -61.82, -72.57, -72.58, -72.58, -72.59,
-72.60, -116.26, -116.30, -116.33, -116.36 F113 ESIMS 563 .sup.1H
NMR (400 MHz, Acetone- ([M + H].sup.+) d.sub.6) .delta. 10.16 (s,
1H), 8.23 (t, J = 6.4 Hz, 1H), 7.92 (d, J = 2.6 Hz, 1H), 7.82-7.74
(m, 1H), 7.71 (dd, J = 8.3, 7.3 Hz, 1H), 7.51-7.35 (m, 2H),
7.30-7.22 (m, 1H), 4.20 (qd, J = 9.4, 6.5 Hz, 2H), 3.62 (dd, J =
8.3, 0.8 Hz, 1H), 3.36 (d, J = 8.3 Hz, 1H); .sup.19F NMR (376 MHz,
Acetone- d.sub.6) .delta. -72.59, -72.60, -108.83 F114 ESIMS 613
.sup.1H NMR (400 MHz, Acetone- ([M + H].sup.+) d.sub.6) .delta.
10.17 (s, 1H), 8.23 (s, 1H), 8.23 (d, J = 13.2 Hz, 0H), 8.01-7.84
(m, 3H), 7.78 (dd, J = 8.7, 2.7 Hz, 1H), 7.68 (ddt, J = 8.2, 1.7,
0.8 Hz, 1H), 7.46 (d, J = 8.7 Hz, 1H), 4.20 (qd, J = 9.5, 6.5 Hz,
2H), 3.73 (d, J = 8.3 Hz, 1H), 3.47 (d, J = 8.4 Hz, 1H); .sup.19F
NMR (376 MHz, Acetone- d.sub.6) .delta. -62.89, -62.90, -72.60,
-72.61 F115 ESIMS 613 .sup.1H NMR (400 MHz, Acetone- ([M +
H].sup.+) d.sub.6) .delta. 10.16 (s, 1H), 8.23 (t, J = 6.5 Hz, 1H),
7.95-7.85 (m, 3H), 7.82-7.72 (m, 1H), 7.67 (dd, J = 8.4, 2.2 Hz,
1H), 7.45 (d, J = 8.7 Hz, 1H), 4.27-4.13 (m, 2H), 3.71 (d, J = 8.3
Hz, 1H), 3.44 (d, J = 8.3 Hz, 1H); .sup.19F NMR (376 MHz, Acetone-
d.sub.6) .delta. -63.00, -63.00, -63.00, -72.60, -72.61 F116 ESIMS
569 .sup.1H NMR (400 MHz, Acetone- ([M + H].sup.+) d.sub.6) .delta.
10.18 (s, 1H), 8.24 (t, J = 6.4 Hz, 1H), 7.96-7.85 (m, 2H),
7.83-7.74 (m, 2H), 7.64 (ddt, J = 8.2, 1.7, 0.9 Hz, 1H), 7.46 (d, J
= 8.8 Hz, 1H), 4.21 (qd, J = 9.5, 6.5 Hz, 2H), 3.73 (d, J = 8.4 Hz,
1H), 3.47 (d, J = 8.4 Hz, 1H); .sup.19F NMR (376 MHz, Acetone-
d.sub.6) .delta. -62.87, -62.88, -62.88, -62.89, -62.89, -62.90,
-62.90, -62.91, -72.60, -72.61, -72.61, -72.63 F117 ESIMS 568
.sup.1H NMR (400 MHz, Acetone- ([M + H].sup.+) d.sub.6) .delta.
10.16 (s, 1H), 8.24 (t, J = 6.5 Hz, 1H), 7.91 (dd, J = 4.1, 2.2 Hz,
2H), 7.83-7.69 (m, 3H), 7.45 (d, J = 8.8 Hz, 1H), 4.21 (qd, J =
9.4, 6.5 Hz, 2H), 3.73 (d, J = 8.3 Hz, 1H), 3.44 (d, J = 8.3 Hz,
1H); .sup.19F NMR (376 MHz, Acetone- d.sub.6) .delta. -63.00,
-72.59 F118 ESIMS 563 .sup.1H NMR (400 MHz, Acetone- ([M +
H].sup.+) d.sub.6) .delta. 10.13 (s, 1H), 8.24 (t, J = 6.5 Hz, 1H),
7.92 (d, J = 2.6 Hz, 1H), 7.81-7.71 (m, 2H), 7.55-7.41 (m, 2H),
7.33 (t, J = 8.6 Hz, 1H), 4.21 (qd, J = 9.5, 6.5 Hz, 2H), 3.62 (dd,
J = 8.3, 0.9 Hz, 1H), 3.34 (d, J = 8.3 Hz, 1H); .sup.19F NMR (376
MHz, Acetone- d.sub.6) .delta. -72.55, -72.57, -110.10 F119 ESIMS
552 .sup.1H NMR (400 MHz, Acetone- ([M + H].sup.+) d.sub.6) .delta.
10.17 (s, 1H), 8.25 (t, J = 6.5 Hz, 1H), 7.92 (d, J = 2.5 Hz, 1H),
7.87-7.74 (m, 3H), 7.53-7.41 (m, 2H), 4.28-4.14 (m, 2H), 3.75-3.68
(m, 1H), 3.43 (d, J = 8.3 Hz, 1H); .sup.19F NMR (376 MHz, Acetone-
d.sub.6) .delta. -61.84, -61.87, -61.87, -72.58, -117.54, -117.58
F120 ESIMS 519 .sup.1H NMR (400 MHz, Acetone- ([M + H].sup.+)
d.sub.6) .delta. 10.15 (s, 1H), 8.23 (t, J = 6.5 Hz, 1H), 7.92 (d,
J = 2.6 Hz, 1H), 7.81-7.73 (m, 1H), 7.57 (t, J = 8.0 Hz, 1H),
7.51-7.38 (m, 2H), 7.31 (ddt, J = 8.3, 1.9, 0.8 Hz, 1H), 4.20 (qd,
J = 9.4, 6.5 Hz, 2H), 3.63 (dd, J = 8.3, 0.8 Hz, 1H), 3.35 (d, J =
8.3 Hz, 1H); .sup.19F NMR (376 MHz, Acetone- d.sub.6) .delta.
-72.57, -72.57, -72.58, -72.58, -116.92, -116.93 F121 ESIMS 502
.sup.1H NMR (400 MHz, Acetone- ([M + H].sup.+) d.sub.6) .delta.
10.16 (s, 1H), 8.23 (t, J = 6.5 Hz, 1H), 7.92 (d, J = 2.6 Hz, 1H),
7.78 (dd, J = 8.8, 2.6 Hz, 1H), 7.45 (d, J = 8.7 Hz, 1H), 7.20-7.09
(m, 2H), 7.05 (tt, J = 9.1, 2.4 Hz, 1H), 4.27-4.13 (m, 2H), 3.65
(d, J = 8.3 Hz, 1H), 3.38 (d, J = 8.4 Hz, 1H); .sup.19F NMR (376
MHz, Acetone- d.sub.6) .delta. -72.58, -72.59, -72.59, -72.60,
-110.72, -110.98, -110.98, -110.99 F122 ESIMS 552 .sup.1H NMR (400
MHz, Acetone- ([M + H].sup.+) d.sub.6) .delta. 10.15 (s, 1H), 8.24
(t, J = 6.4 Hz, 1H), 7.92 (d, J = 2.6 Hz, 1H), 7.78 (dd, J = 8.8,
2.7 Hz, 1H), 7.69 (dt, J = 1.8, 1.0 Hz, 1H), 7.58 (ddt, J = 24.9,
8.6, 2.0 Hz, 2H), 7.45 (d, J = 8.7 Hz, 1H), 4.21 (qd, J = 9.5, 6.5
Hz, 2H), 3.77 (d, J = 8.3 Hz, 1H), 3.49 (d, J = 8.3 Hz, 1H);
.sup.19F NMR (376 MHz, Acetone- d.sub.6) .delta. -63.21, -72.60,
-72.60, -111.80 F123 ESIMS 563 .sup.1H NMR (400 MHz, Acetone- ([M +
H].sup.+) d.sub.6) .delta. 10.13 (s, 1H), 8.24 (t, J = 6.5 Hz, 1H),
7.91 (d, J = 2.6 Hz, 1H), 7.77 (dd, J = 8.7, 2.6 Hz, 1H), 7.51 (s,
1H), 7.50-7.37 (m, 2H), 7.30 (dt, J = 9.5, 1.9 Hz, 1H), 4.21 (qd, J
= 9.5, 6.5 Hz, 2H), 3.66 (d, J = 8.3 Hz, 1H), 3.40 (d, J = 8.4 Hz,
1H); .sup.19F NMR (376 MHz, Acetone- d.sub.6) .delta. -72.54,
-72.56, -111.81 F124 ESIMS 613 .sup.1H NMR (400 MHz, Acetone- ([M +
H].sup.+) d.sub.6) .delta. 10.13 (s, 1H), 8.23 (t, J = 6.5 Hz, 1H),
8.01-7.88 (m, 3H), 7.84 (s, 1H), 7.78 (dd, J = 8.7, 2.6 Hz, 1H),
7.45 (d, J = 8.7 Hz, 1H), 4.21 (qd, J = 9.5, 6.5 Hz, 2H), 3.77 (d,
J = 8.3 Hz, 1H), 3.51 (d, J = 8.3 Hz, 1H); .sup.19F NMR (376 MHz,
Acetone- d.sub.6) .delta. -63.23, -63.24, -72.60, -72.61 F125 ESIMS
532 .sup.1H NMR (400 MHz, Acetone- ([M + H].sup.+) d.sub.6) .delta.
10.13 (s, 1H), 8.22 (t, J = 6.5 Hz, 1H), 7.91 (d, J = 2.6 Hz, 1H),
7.77 (dd, J = 8.8, 2.6 Hz, 1H), 7.45 (d, J = 8.8 Hz, 1H), 7.30-7.02
(m, 2H), 4.20 (qd, J = 9.5, 6.5 Hz, 2H), 3.99 (d, J = 1.1 Hz, 3H),
3.58 (d, J = 8.3 Hz, 1H), 3.31 (d, J = 8.3 Hz, 1H); .sup.19F NMR
(376 MHz, Acetone- d.sub.6) .delta. -72.61, -129.67 F126 ESIMS 520
.sup.1H NMR (400 MHz, Acetone- ([M + H].sup.+) d.sub.6) .delta.
10.16 (s, 1H), 8.23 (t, J = 6.5 Hz, 1H), 7.91 (d, J = 2.6 Hz, 1H),
7.77 (dd, J = 8.8, 2.6 Hz, 1H), 7.45 (d, J = 8.7 Hz, 1H), 7.41-7.27
(m, 2H), 4.20 (qd, J = 9.5, 6.5 Hz, 2H), 3.74-3.48 (m, 1H), 3.37
(d, J = 8.3 Hz, 1H); .sup.19F NMR (376 MHz, Acetone- d.sub.6)
.delta. -72.61, -136.27, -163.62 F127 ESIMS m/z 520 .sup.1H NMR
(400 MHz, Acetone- ([M + H]+) d.sub.6) .delta. 10.05 (s, 1H),
8.43-8.04 (m, 1H), 7.79 (d, J = 2.6 Hz, 1H), 7.68 (dd, J = 8.8, 2.7
Hz, 1H), 7.41 (d, J = 8.8 Hz, 1H), 7.36-7.22 (m, 2H), 4.35-4.11 (m,
2H), 3.54 (d, J = 11.3 Hz, 1H), 3.25 (d, J = 11.3 Hz, 1H); .sup.19F
NMR (376 MHz, Acetone- d.sub.6) .delta. -72.51, -137.68, -164.86
F128 HRMS-ESI .sup.1H NMR (500 MHz, Acetone- [M + H].sup.+ calcd
for d.sub.6) .delta. 10.15 (s, 1H), 8.23 (t, J = 6.5 Hz,
C.sub.20H.sub.14Cl.sub.4F.sub.5N.sub.2O.sub.2, 1H), 7.92 (dd, J =
2.6, 548.9724; found, 1.2 Hz, 1H), 7.77 (ddd, J = 8.8, 548.9720.
2.7, 1.2 Hz, 1H), 7.68 (tt, J = 1.9, 0.9 Hz, 1H), 7.63 (p, J = 1.4
Hz, 2H), 7.45 (d, J = 8.7 Hz, 1H), 6.96 (t, J = 55.8 Hz, 1H),
4.27-4.09 (m, 2H), 3.71 (d, J = 8.3 Hz, 1H), 3.45 (d, J = 8.3 Hz,
1H); .sup.19F NMR (471 MHz, Acetone- d.sub.6) .delta. -72.57 (t, J
= 9.6 Hz), -112.20 (dd, J = 55.8, 14.2 Hz) F129 HRMS-ESI .sup.1H
NMR (500 MHz, Acetone- [M + H].sup.+ calcd for d.sub.6) .delta.
10.15 (s, 1H), 8.22 (t, J = 6.4 Hz,
C.sub.20H.sub.14Cl.sub.4F.sub.5N.sub.2O.sub.2, 1H), 7.92 (dd, J =
2.7, 548.9724; found, 1.2 Hz, 1H), 7.77 (ddd, J = 8.7, 548.9719.
2.6, 1.1 Hz, 1H), 7.76-7.73 (m, 1H), 7.66-7.57 (m, 2H), 7.45 (d, J
= 8.7 Hz, 1H), 7.14 (t, J = 54.5 Hz, 1H), 4.25-4.14 (m, 2H), 3.69
(d, J = 8.3 Hz, 1H), 3.41 (d, J = 8.3 Hz, 1H); .sup.19F NMR (471
MHz, Acetone- d.sub.6) .delta. -116.25 (d, J = 54.7 Hz) F130
HRMS-ESI .sup.1H NMR (500 MHz, Acetone- [M + H].sup.+ calcd for
d.sub.6) .delta. 10.16 (s, 1H), 8.23 (t, J = 6.5 Hz,
C.sub.20H.sub.14Cl.sub.3F.sub.6N.sub.2O.sub.2, 1H), 7.92 (dd, J =
2.6, 533.0020; found, 1.2 Hz, 1H), 7.78 (ddd, J = 8.8, 533.0013.
2.7, 1.2 Hz, 1H), 7.53 (q, J = 1.1 Hz, 1H), 7.45 (d, J = 8.7 Hz,
1H), 7.47-7.41 (m, 1H), 7.38 (ddd, J = 8.9, 2.6, 1.3 Hz, 1H), 6.97
(t, J = 55.8 Hz, 1H), 4.25-4.14 (m, 2H), 3.71 (d, J = 8.3 Hz, 1H),
3.43 (d, J = 8.4 Hz, 1H); .sup.19F NMR (471 MHz, Acetone- d.sub.6)
.delta. -72.59 (t, J = 9.4 Hz), -112.06 (dd, J = 55.8, 14.3 Hz),
-112.93 (t, J = 9.1 Hz)
F131 HRMS-ESI .sup.1H NMR (500 MHz, Acetone- [M + H].sup.+ calcd
for d.sub.6) .delta. 10.15 (s, 1H), 8.23 (t, J = 6.5 Hz,
C.sub.20H.sub.14Cl.sub.3F.sub.6N.sub.2O.sub.2, 1H), 7.92 (dd, J =
2.6, 533.0020; found, 1.2 Hz, 1H), 7.78 (ddd, J = 8.8, 533.0016.
2.7, 1.1 Hz, 1H), 7.68 (ddt, J = 9.6, 6.1, 1.7 Hz, 2H), 7.45 (d, J
= 8.7 Hz, 1H), 7.39-7.31 (m, 1H), 7.12 (t, J = 54.6 Hz, 1H),
4.28-4.14 (m, 2H), 3.67 (d, J = 8.3 Hz, 1H), 3.37 (d, J = 8.3 Hz,
1H); .sup.19F NMR (471 MHz, Acetone- d.sub.6) .delta. -72.58 (t, J
= 9.5 Hz), -114.91 (dd, J = 54.7, 3.6 Hz), -119.78--122.55 (m) F132
HRMS-ESI .sup.1H NMR (500 MHz, Acetone- [M + H].sup.+ calcd for
d.sub.6) .delta. 10.16 (s, 1H), 8.23 (t, J = 6.5 Hz,
C.sub.20H.sub.14Cl.sub.4F.sub.5N.sub.2O.sub.2, 1H), 7.92 (dd, J =
2.6, 548.9724; found, 1.2 Hz, 1H), 548.9723. 7.80-7.72 (m, 2H),
7.65 (dd, J = 1.9, 1.0 Hz, 1H), 7.58 (dd, J = 8.1, 1.6 Hz, 1H),
7.45 (d, J = 8.7 Hz, 1H), 7.13 (t, J = 54.6 Hz, 1H), 4.30-4.12 (m,
2H), 3.72-3.65 (m, 1H), 3.43 (d, J = 8.3 Hz, 1H); .sup.19F NMR (471
MHz, Acetone- d.sub.6) .delta. -72.56 (t, J = 9.5 Hz), -116.13 (d,
J = 54.6 Hz) F133 HRMS-ESI .sup.1H NMR (500 MHz, Acetone- [M +
H].sup.+ calcd for d.sub.6) .delta. 10.18 (s, 1H), 8.23 (t, J = 6.5
Hz, C.sub.20H.sub.14Cl.sub.3F.sub.6N.sub.2O.sub.2, 1H), 7.92 (dd, J
= 2.6, 533.0020; found, 1.1 Hz, 1H), 7.78 (ddd, J = 8.8, 533.0011.
2.7, 1.1 Hz, 1H), 7.70 (t, J = 7.7 Hz, 1H), 7.45 (d, J = 8.8 Hz,
1H), 7.44 (dd, J = 8.2, 1.5 Hz, 1H), 7.42-7.38 (m, 1H), 7.11 (t, J
= 54.7 Hz, 1H), 4.29-4.11 (m, 2H), 3.69 (d, J = 8.3 Hz, 1H), 3.41
(d, J = 8.3 Hz, 1H); .sup.19F NMR (471 MHz, Acetone- d.sub.6)
.delta. -72.58 (t, J = 9.4 Hz), -114.82 (dd, J = 54.7, 3.7 Hz),
-119.99 (ddt, J = 11.4, 7.5, 3.6 Hz) F134 HRMS-ESI .sup.1H NMR (500
MHz, Acetone- [M + H].sup.+ calcd for d.sub.6) .delta. 10.16 (s,
1H), 8.23 (t, J = 6.6 Hz,
C.sub.20H.sub.15Cl.sub.3F.sub.5N.sub.2O.sub.2, 1H), 7.93 (d, J =
2.6 Hz, 515.0114; found, 1H), 7.78 (dd, J = 8.7, 515.0108. 2.6 Hz,
1H), 7.65-7.56 (m, 4H), 7.45 (d, J = 8.7 Hz, 1H), 6.93 (t, J = 56.1
Hz, 1H), 4.25-4.15 (m, 2H), 3.68 (d, J = 8.3 Hz, 1H), 3.38 (d, J =
8.4 Hz, 1H); .sup.19F NMR (471 MHz, Acetone- d.sub.6) .delta.
-72.57 (t, J = 9.5 Hz), -111.22 (dd, J = 56.0, 14.1 Hz) F135
HRMS-ESI .sup.1H NMR (500 MHz, Acetone- [M + H].sup.+ calcd for
d.sub.6) .delta. 10.17 (s, 1H), 8.23 (t, J = 6.4 Hz,
C.sub.20H.sub.15Cl.sub.3F.sub.5N.sub.2O.sub.2, 1H), 7.93 (dd, J =
2.6, 515.0114; found, 1.2 Hz, 1H), 7.78 (ddd, J = 8.7, 515.0108.
2.6, 1.1 Hz, 1H), 7.64 (dt, J = 8.3, 1.2 Hz, 2H), 7.57 (dt, J =
8.0, 0.9 Hz, 2H), 7.45 (d, J = 8.7 Hz, 1H), 6.93 (t, J = 56.1 Hz,
1H), 4.20 (ttd, J = 9.5, 6.5, 3.2 Hz, 2H), 3.66 (d, J = 8.4 Hz,
1H), 3.36 (d, J = 8.3 Hz, 1H); .sup.19F NMR (471 MHz, Acetone-
d.sub.6) .delta. -72.57 (t, J = 9.4 Hz), -111.22 (d, J = 56.2 Hz)
PF1 ESIMS 622 .sup.1H NMR (400 MHz, Acetone- ([M - H]-) d.sub.6)
.delta. 10.15 (s, 1H), 8.22 (t, J = 6.4 Hz, 1H), 7.92 (d, J = 2.6
Hz, 1H), 7.78 (dd, J = 8.8, 2.6 Hz, 1H), 7.53-7.42 (m, 4H), 4.20
(qd, J = 9.5, 6.5 Hz, 2H), 3.59 (d, J = 8.3 Hz, 1H), 3.41 (d, J =
8.2 Hz, 1H), 2.88 (d, J = 13.0 Hz, 1H); .sup.19F NMR (376 MHz,
Acetone- d.sub.6) .delta. -72.58 PF2 87-93 HRMS-ESI [M+].sup.+
.sup.1H NMR (500 MHz, DMSO-d.sub.6) calcd for .delta. 10.86 (s,
1H), 8.48 (d, J = 8.1 Hz,
C.sub.23H.sub.20Cl.sub.5F.sub.3N.sub.2O.sub.2S, 1H), 7.72 (m, 2H),
619.9640; found, 7.62 (s, 1H), 7.54 (m, 2H), 619.9644. 7.47 (d, J =
8.7 Hz, 1H), 4.08 (dt, J = 14.2, 6.9 Hz, 1H), 3.61 (d, J = 8.5 Hz,
1H), 3.50 (d, J = 8.5 Hz, 1H), 2.75 (dt, J = 10.0, 4.7 Hz, 2H),
2.70 (d, J = 6.9 Hz, 2H), 2.59 (m, 2H), 1.21 (d, J = 6.6 Hz, 3H);
.sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 165.97, 163.01,
138.01, 137.93, 137.77, 134.54, 130.54, 130.46, 128.37, 128.25,
128.17, 126.04, 124.48, 123.84, 121.40, 119.48, 62.62, 45.10,
38.88, 37.60, 37.25, 34.32, 34.11, 33.89, 33.67, 23.92, 20.00;
.sup.19F NMR (471 MHz, DMSO-d.sub.6) .delta. -64.53, -64.56, -64.58
PF3 90-95 HRMS-ESI (m/z) .sup.1H NMR (500 MHz, DMSO-d.sub.6)
[M+].sup.+ calcd for .delta. 10.86 (s, 1H), 8.51 (d, J = 8.2 Hz,
C.sub.22H.sub.18Cl.sub.5F.sub.3N.sub.2O.sub.2S, 1H), 7.72 (m, 2H),
605.9484; found, 7.62 (d, J = 1.7 Hz, 1H), 605.9485. 7.55 (d, J =
1.5 Hz, 2H), 7.48 (d, J = 8.8 Hz, 1H), 4.12 (hept, J = 6.7 Hz, 1H),
3.62 (d, J = 8.5 Hz, 1H), 3.53 (m, 3H), 2.80 (m, 2H), 1.21 (d, J =
6.6 Hz, 3H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 165.41,
162.44, 137.46, 137.30, 137.20, 133.96, 129.98, 129.80, 127.80,
127.60, 125.41, 123.88, 123.22, 120.84, 118.85, 62.05, 44.73,
38.31, 38.09, 36.67, 33.33, 33.08, 32.83, 32.58, 19.40; .sup.19F
NMR (471 MHz, DMSO-d.sub.6) .delta. -65.06, -65.08, -65.08, -65.10,
-65.11, -65.12 PF4 113-118 HRMS-ESI (m/z) .sup.1H NMR (500 MHz,
DMSO-d.sub.6) [M + H].sup.+ calcd for .delta. 10.87 (s, 1H), 8.69
(dd, J = 8.2, C.sub.23H.sub.21Cl.sub.5F.sub.3N.sub.2O.sub.4S, 2.7
Hz, 1H), 7.73 (dd, J = 5.5, 652.9611; found, 3.2 Hz, 2H), 7.62 (s,
1H), 652.9620. 7.54 (d, J = 1.4 Hz, 2H), 7.48 (d, J = 9.0 Hz, 1H),
4.52 (dt, J = 13.8, 6.9 Hz, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.48 (m,
5H), 2.78 (m, 2H), 1.31 (d, J = 6.1 Hz, 3H); .sup.13C NMR (126 MHz,
DMSO-d.sub.6) .delta. 165.68, 163.03, 163.01, 138.04, 137.77,
137.51, 134.54, 130.55, 128.36, 128.17, 127.88, 125.68, 124.48,
121.66, 119.49, 62.63, 57.20, 46.16, 38.83, 37.25, 34.66, 26.89,
26.65, 26.41, 26.17, 25.25, 22.54, 21.09, 14.44, 11.73; .sup.19F
NMR (471 MHz, DMSO-d.sub.6) .delta. -64.28, -64.30, -64.32 PF5
121-126 HRMS-ESI [M + H].sup.+ calcd for
C.sub.23H.sub.21Cl.sub.5F.sub.3N.sub.2O.sub.3S, 636.9662; found,
636.9665. PF6 102-107 HRMS-ESI .sup.1H NMR (500 MHz, DMSO-d.sub.6)
[M + H].sup.+ calcd for .delta. 10.88 (s, 1H), 8.75 (d, J = 8.1 Hz,
C.sub.22H.sub.19Cl.sub.5F.sub.3N.sub.2O.sub.4S, 1H), 7.73 (m, 2H),
638.9455; found, 7.62 (s, 1H), 7.54 (d, J = 1.3 Hz, 638.9465. 2H),
7.49 (d, J = 8.6 Hz, 1H), 4.75 (q, J = 10.2 Hz, 2H), 4.55 (dq, J =
13.3, 6.6 Hz, 1H), 3.58 (m, 2H), 3.49 (m, 2H), 1.33 (d, J = 6.7 Hz,
3H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 165.08, 162.47,
137.50, 137.20, 136.85, 133.96, 130.01, 127.79, 127.59, 125.53,
123.89, 123.32, 121.11, 118.84, 62.06, 58.66, 54.73, 54.50, 54.27,
54.06, 38.27, 36.67, 34.09, 30.85, 24.68, 21.96, 20.40, 13.86;
.sup.19F NMR (471 MHz, DMSO-d.sub.6) .delta. -59.40, -59.42, -59.44
PF7 123-128 HRMS-ESI (m/z) .sup.1H NMR (500 MHz, DMSO-d.sub.6) [M +
H].sup.+ calcd for .delta. 10.87 (d, J = 2.5 Hz, 1H),
C.sub.22H.sub.19Cl.sub.5F.sub.3N.sub.2O.sub.3S, 8.81 (dd, J = 8.2,
2.0 Hz, 622.9506; found, 0.5H), 8.69 (d, J = 8.1 Hz, 622.9508.
0.5H), 7.72 (td, J = 6.4, 2.4 Hz, 2H), 7.62 (s, 1H), 7.55 (s, 2H),
7.49 (d, J = 8.8 Hz, 1H), 4.39 (dt, J = 13.8, 6.7 Hz, 1H), 4.07 (m,
2H), 3.62 (d, J = 8.5 Hz, 1H), 3.50 (d, J = 8.5 Hz, 1H), 3.14 (m,
2H), 1.31 (m, 3H); .sup.19F NMR (471 MHz, DMSO-d.sub.6) .delta.
-59.52, -59.53, -59.54, -59.55, -59.56, -59.58, -59.63, -59.65,
-59.67, -59.69 PF9 73-79 HRMS-ESI (m/z) .sup.1H NMR (500 MHz,
DMSO-d.sub.6) [M+].sup.+ calcd for .delta. 10.88 (s, 1H), 8.62 (t,
J = 5.7 Hz, C.sub.24H.sub.19Cl.sub.5N.sub.2O.sub.3S, 1H), 7.75 (d,
J = 2.6 Hz, 589.9559; found, 1H), 7.70 (dd, J = 8.8, 2.6 Hz,
589.9564. 1H), 7.62 (t, J = 1.8 Hz, 1H), 7.59 (dd, J = 1.8, 0.8 Hz,
1H), 7.55 (d, J = 1.5 Hz, 2H), 7.48 (d, J = 8.7 Hz, 1H), 6.40 (dd,
J = 3.1, 1.9 Hz, 1H), 6.32 (m, 1H), 3.84 (s, 2H), 3.61 (d, J = 8.5
Hz, 1H), 3.51 (d, J = 8.5 Hz, 1H), 3.40 (q, J = 6.3 Hz, 2H), 2.63
(t, J = 7.1 Hz, 2H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta.
166.52, 163.03, 151.84, 142.95, 138.04, 137.78, 137.71, 134.54,
130.60, 128.38, 128.17, 124.45, 121.50, 119.52, 111.05, 108.21,
62.64, 38.88, 38.85, 37.25, 30.63, 27.36 PF10 93-99 HRMS-ESI
[M].sup.+ .sup.1H NMR (500 MHz, DMSO-d.sub.6) calcd for .delta.
10.88 (d, J = 6.5 Hz, 1H), C.sub.23H.sub.21Cl.sub.5N.sub.2O.sub.4S,
8.95 (d, J = 7.6 Hz, 1H), 595.9665; found, 7.75 (ddd, J = 18.2,
8.1, 2.6 Hz, 595.9668. 2H), 7.63 (t, J = 1.8 Hz, 1H), 7.55 (m, 2H),
7.49 (d, J = 8.7 Hz, 1H), 4.58 (ddt, J = 7.5, 5.2, 2.4 Hz, 1H),
3.69 (s, 3H), 3.63 (d, J = 8.5 Hz, 1H), 3.50 (dd, J = 8.5, 3.0 Hz,
1H), 2.59 (m, 2H), 2.07 (s, 3H), 2.00 (m, 2H); .sup.13C NMR (126
MHz, DMSO-d.sub.6) .delta. 171.82, 166.25, 162.46, 137.48, 137.19,
136.63, 136.61, 133.95, 130.04, 127.80, 127.59, 123.88, 121.03,
119.06, 62.04, 51.96, 51.16, 51.13, 38.32, 36.65, 30.05, 29.52,
14.46, 14.45 PF11 129-135 HRMS-ESI [M+].sup.+ .sup.1H NMR (500 MHz,
DMSO-d.sub.6) calcd for .delta. 10.86 (s, 1H), 9.28 (s, 1H),
C.sub.26H.sub.18Cl.sub.5N.sub.5O.sub.2, 9.11 (t, J = 6.0 Hz, 1H),
606.9903; found, 8.24 (s, 1H), 7.85 (m, 2H), 7.80 (d, 606.9916. J =
2.6 Hz, 1H), 7.71 (dd, J = 8.8, 2.6 Hz, 1H), 7.62 (t, J = 1.8 Hz,
1H), 7.54 (m, 4H), 7.51 (d, J = 8.7 Hz, 1H),
4.51 (d, J = 6.4 Hz, 2H), 3.62 (d, J = 8.5 Hz, 1H), 3.50 (d, J =
8.5 Hz, 1H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 166.07,
162.47, 152.24, 142.12, 138.76, 137.53, 137.18, 137.03, 135.49,
133.95, 130.10, 128.45, 127.80, 127.59, 123.86, 120.98, 119.28,
118.91, 62.03, 41.86, 38.31, 36.66 PF12 94-99 HRMS-ESI [M].sup.+
.sup.1H NMR (500 MHz, DMSO-d.sub.6) calcd for .delta. 10.85 (s,
1H), 8.66 (t, J = 5.7 Hz, C.sub.22H.sub.16Cl.sub.5N.sub.3O.sub.2S,
1H), 7.76 (dd, J = 11.8, 560.9406; found, 3.0 Hz, 2H), 7.67 (dd, J
= 8.8, 560.9399. 2.6 Hz, 1H), 7.63 (t, J = 1.8 Hz, 1H), 7.61 (d, J
= 3.3 Hz, 1H), 7.55 (d, J = 1.5 Hz, 2H), 7.47 (d, J = 8.7 Hz, 1H),
3.62 (m, 3H), 3.50 (d, J = 8.5 Hz, 1H), 3.24 (t, J = 7.1 Hz, 2H)
.sup.13C NMR (126 MHz, DMSO-d.sub.6) .delta. 166.90, 165.95,
162.42, 142.21, 137.43, 137.19, 137.11, 133.95, 129.99, 127.80,
127.59, 123.89, 120.95, 119.49, 118.97, 62.06, 38.28, 36.66, 32.15
PF13 187-189 HRMS-ESI [M].sup.+ .sup.1H NMR (500 MHz, DMSO-d.sub.6)
calcd for .delta. 10.84 (s, 1H), 8.60 (t, J = 5.6 Hz,
C.sub.22H.sub.17Cl.sub.5N.sub.4O.sub.2, 1H), 7.74 (dd, J = 8.8,
543.9794; found, 2.3 Hz, 2H), 7.66 (dd, J = 8.8, 543.9800. 2.6 Hz,
1H), 7.63 (t, J = 1.8 Hz, 1H), 7.55 (d, J = 1.6 Hz, 2H), 7.47 (m,
2H), 6.24 (t, J = 2.0 Hz, 1H), 4.29 (t, J = 6.3 Hz, 2H), 3.62 (q, J
= 5.6 Hz, 3H), 3.50 (d, J = 8.5 Hz, 1H); .sup.13C NMR (126 MHz,
DMSO-d.sub.6) .delta. 166.11, 162.43, 138.77, 137.42, 137.19,
137.00, 133.96, 130.04, 129.98, 127.81, 127.59, 123.87, 121.02,
119.01, 104.93, 62.06, 49.94, 38.26, 36.67 PF14 150-155 ESIMS 596
.sup.1H NMR (500 MHz, DMSO-d.sub.6) ([M - H + Na].sup.-) .delta.
10.72 (s, 1H), 7.74 (d, J = 2.6 Hz, 1H), 7.61 (m, 3H), 7.55 (d, J =
1.5 Hz, 2H), 7.30 (d, J = 8.7 Hz, 1H), 3.60 (d, J = 8.5 Hz, 1H),
3.46 (m, 3H), 3.12 (m, 2H), 1.90 (p, J = 7.1 Hz, 2H); .sup.13C NMR
(126 MHz, DMSO-d.sub.6) .delta. 171.09, 162.70, 142.03, 137.90,
137.43, 134.50, 130.20, 128.39, 128.10, 124.76, 120.37, 119.81,
62.68, 50.22, 49.01, 38.90, 37.21, 24.24 PF15 115-119 HRMS-ESI
[M+].sup.+ .sup.1H NMR (500 MHz, DMSO-d.sub.6) calcd for .delta.
10.84 (s, 1H), 8.68 (t, J = 5.7 Hz,
C.sub.27H.sub.19Cl.sub.5N.sub.2O.sub.2S, 1H), 7.95 (dd, J = 37.3,
609.9610; found, 7.9 Hz, 2H), 7.78 (d, J = 2.6 Hz, 609.9618. 1H),
7.66 (dd, J = 8.8, 2.6 Hz, 1H), 7.63 (t, J = 1.8 Hz, 1H), 7.55 (d,
J = 1.7 Hz, 2H), 7.53 (s, 1H), 7.48 (d, J = 8.7 Hz, 1H), 7.44 (m,
1H), 7.38 (t, J = 7.1 Hz, 1H), 3.61 (m, 3H), 3.50 (d, J = 8.5 Hz,
1H), 3.09 (t, J = 7.2 Hz, 2H); .sup.13C NMR (126 MHz, DMSO-d.sub.6)
.delta. 165.96, 162.44, 139.56, 138.61, 137.44, 137.25, 137.19,
133.96, 133.39, 130.02, 127.80, 127.59, 124.19, 124.00, 123.92,
122.82, 122.74, 121.55, 120.92, 119.00, 62.05, 38.62, 38.28, 36.67,
27.86 PF16 108-112 HRMS-ESI [M+].sup.+ .sup.1H NMR (500 MHz,
DMSO-d.sub.6) calcd for .delta. 10.86 (s, 1H), 8.73 (t, J = 5.6 Hz,
C.sub.20H.sub.14Cl.sub.5F.sub.3N.sub.2O.sub.3, 1H), 7.78 (m, 1H),
561.9399; found, 7.68 (m, 1H), 7.63 (t, J = 1.8 Hz, 561.9402. 1H),
7.55 (d, J = 1.7 Hz, 2H), 7.48 (d, J = 8.7 Hz, 1H), 6.53 (dd, J =
6.5, 2.2 Hz, 1H), 4.17 (m, 1H), 3.61 (d, J = 8.5 Hz, 1H), 3.57 (m,
1H), 3.50 (d, J = 8.5 Hz, 1H), 3.30 (m, 1H); .sup.19F NMR (471 MHz,
DMSO-d.sub.6) .delta. -76.93, -76.95
TABLE-US-00008 BAW & CL Rating Table % Control (or Mortality)
Rating 50-100 A More than 0-Less than 50 B Not Tested C No activity
noticed in this bioassay D
TABLE-US-00009 GPA & YFM Rating Table % Control (or Mortality)
Rating 80-100 A More than 0-Less than 80 B Not Tested C No activity
noticed in this bioassay D
TABLE-US-00010 TABLE ABC Biological Results Species No. BAW CL GPA
YFM F1 A A C A F2 A A B A F3 A A C A F4 A A A A F5 A A C C F6 A A B
A F7 A A C A F8 A A C C F9 A A C C F10 A A C C F11 A A C C F12 A A
B A F13 A A B A F14 A A B A F15 A A A A F16 A A B A F17 A A B A F18
A A B C F19 A A B A F20 A A B A F21 A A B B F22 A A A B F23 A A A B
F24 A A C A F25 A A C A F26 A A C A F27 A A B A F28 A A A A F29 D D
B A F30 A A A A F31 A A B B F32 A A B A F33 A A B A F34 A A D A F35
A A A A F36 D D D B F37 A A B A F38 A A A A F39 A A A A F40 A A A A
F41 A A D A F42 A A B A F43 A A A C F44 A A A A F45 A A A A F46 A A
A A F47 A A A A F48 A A A B F49 A A A A F50 D A C C F51 A A C B F52
A A C B F53 A A C B F54 A A C B F55 A A A B F56 A A A A F57 A A C D
F58 A A C A F59 A A B A F60 A A C D F61 A A C D F62 A A C D F63 A A
C D F64 A A C D F65 A A C C F66 A A C C F67 A A C D F68 A A C D F69
A A C D F70 A A C D F71 A A C D F72 A A C A F73 A A C A F74 A A C C
F75 A A A A F78 A A C A F79 A A C A F84 A A C D F85 A A C B F86 A A
C B F87 A A C B F88 A A C B F91 A A C A F92 A A C A F93 A A C C F94
A A C A F95 A A C A F96 A A C A F97 A A C A F98 B D C A F99 A A C A
F100 A D C A F101 D D C D F102 B D C A F103 A A C A F104 A A C A
F105 A A C A F106 A A C A F107 A A C B F108 A A C A F109 A A C A
F111 A A C A F112 A A C A F113 A A C A F114 A A C A F115 A A C A
F116 A A C A F117 A A C A F118 A A C A F119 A A C A F120 A A C A
F121 A A C A F122 A A C A F123 A A C A F124 A A C A F125 A A C A
F126 A A C A F127 A A C A F128 A A C A F129 A A C A F130 A A C A
F131 A A C A F132 A A C A F133 A A C A F134 A A C A F135 D A C A
PF1 A A C D PF2 A A C A PF3 A A A B PF4 A A C A PF5 A A C A PF6 A A
B A PF7 A A C A PF9 A A C A PF10 A A C B PF11 A A C A PF12 A A C A
PF13 A A C A PF14 B A C D PF15 A A C A PF16 A A A A
* * * * *