U.S. patent application number 13/140774 was filed with the patent office on 2011-10-13 for isoxazole derivatives for use as plant growth regulators.
This patent application is currently assigned to SYNGENTA CROP PROTECTION LLC. Invention is credited to Carla Bobbio, Camilla Corsi, Micah Gliedt, Valeria Grasso, Ulrich Johannes Haas, Jilali Kessabi, Shy-Fuh Lee, Peter Schneiter, Sebastian Volker Wendeborn.
Application Number | 20110251069 13/140774 |
Document ID | / |
Family ID | 40343739 |
Filed Date | 2011-10-13 |
United States Patent
Application |
20110251069 |
Kind Code |
A1 |
Corsi; Camilla ; et
al. |
October 13, 2011 |
ISOXAZOLE DERIVATIVES FOR USE AS PLANT GROWTH REGULATORS
Abstract
The present invention relates to thiophene, furan and pyrrole
compounds of formula (I) having plant growth regulating properties,
to agricultural compositions comprising them, and to the use of
said compounds for regulating plant growth. ##STR00001##
Inventors: |
Corsi; Camilla; (Stein,
CH) ; Wendeborn; Sebastian Volker; (Stein, CH)
; Bobbio; Carla; (Stein, CH) ; Kessabi;
Jilali; (Stein, CH) ; Schneiter; Peter;
(Stein, CH) ; Grasso; Valeria; (Stein, CH)
; Haas; Ulrich Johannes; (Stein, CH) ; Lee;
Shy-Fuh; (Stein, CA) ; Gliedt; Micah;
(Sunnyvale, CA) |
Assignee: |
SYNGENTA CROP PROTECTION
LLC
Greensboro
NC
|
Family ID: |
40343739 |
Appl. No.: |
13/140774 |
Filed: |
December 11, 2009 |
PCT Filed: |
December 11, 2009 |
PCT NO: |
PCT/EP2009/066963 |
371 Date: |
June 17, 2011 |
Current U.S.
Class: |
504/252 ;
504/251; 546/276.4; 546/280.4 |
Current CPC
Class: |
A61P 31/12 20180101;
C07D 413/04 20130101; C07D 413/06 20130101; A61P 17/00 20180101;
A01N 43/80 20130101; A61P 31/10 20180101 |
Class at
Publication: |
504/252 ;
546/280.4; 546/276.4; 504/251 |
International
Class: |
A01N 43/40 20060101
A01N043/40; C07D 401/06 20060101 C07D401/06; A01P 21/00 20060101
A01P021/00; C07D 409/06 20060101 C07D409/06 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 17, 2008 |
GB |
0823002.1 |
Claims
1. (canceled)
2. (canceled)
3. (canceled)
4. (canceled)
5. (canceled)
6. (canceled)
7. (canceled)
8. (canceled)
9. (canceled)
10. (canceled)
11. (canceled)
12. (canceled)
13. A compound having the forumula
2-(2,4-difluorophenyl)-4-(2-chlorophenyl)-3-[(3-pyridyl)hydroxymethyl]thi-
ophene.
14. A compound, which is the (R)-enantiomer of the compound of
formula (I) and salts thereof wherein said compound has the formula
##STR00190## wherein X is S, O, or NR.sub.5; R is H; alkyl;
alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; arylthioalkyl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; aryl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, nitro; heteroaryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or
alkylsilyl; R.sub.1 is alkyl; alkoxyalkyl; haloalkyl; arylalkyl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted
with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,
alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;
arylthioalkyl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; or alkylsilyl; R.sub.2 is alkyl;
alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; heteroaryl, optionally substituted
with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,
alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;
5-pyrimidinyl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; or 2- or 5-thiazolyl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, alkoxy,
alkylthio, haloalkyl, haloalkenyl, haloalkoxy, haloalkylthio,
cyano, or nitro; R.sub.3 is alkyl; alkoxyalkyl; haloalkyl;
arylalkyl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted
with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,
alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;
arylthioalkyl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; or alkylsilyl; R.sub.4 is H; acyl;
haloacyl; alkoxycarbonyl; aryloxycarbonyl; alkylaminocarbonyl; or
dialkylaminocarbonyl; R.sub.5 is H; alkyl; alkenyl; alkynyl;
alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; arylthioalkyl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; aryl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, nitro; heteroaryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or
alkylsilyl;
15. A compound, which is the (S)-enantiomer of a compound of
formula (I) and salts thereof wherein said compound has the formula
##STR00191## wherein X is S, O, or NR.sub.5; R is H; alkyl;
alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; arylthioalkyl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; aryl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, nitro; heteroaryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or
alkylsilyl; R.sub.1 is alkyl; alkoxyalkyl; haloalkyl; arylalkyl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted
with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,
alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;
arylthioalkyl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; or alkylsilyl; R.sub.2 is alkyl;
alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; heteroaryl, optionally substituted
with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,
alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;
5-pyrimidinyl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; or 2- or 5-thiazolyl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, alkoxy,
alkylthio, haloalkyl, haloalkenyl, haloalkoxy, haloalkylthio,
cyano, or nitro; R.sub.3 is alkyl; alkoxyalkyl; haloalkyl;
arylalkyl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted
with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,
alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;
arylthioalkyl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; or alkylsilyl; R.sub.4 is H; acyl;
haloacyl; alkoxycarbonyl; aryloxycarbonyl; alkylaminocarbonyl; or
dialkylaminocarbonyl; R.sub.5 is H; alkyl; alkenyl; alkynyl;
alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; arylthioalkyl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; aryl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, nitro; heteroaryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or
alkylsilyl;
16. A method of regulating plant growth of crops of useful plants,
which comprises applying to said plants, to one or more parts of
said plants, or to the locus thereof or plant propagation material,
a compound of formula (I) having the formula ##STR00192## wherein X
is S, O, or NR.sub.5; R is H; alkyl; alkoxyalkyl; haloalkyl;
arylalkyl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted
with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,
alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;
arylthioalkyl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; or alkylsilyl; R.sub.1 is alkyl;
alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; arylthioalkyl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; aryl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, nitro; heteroaryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or
alkylsilyl; R.sub.2 is alkyl; alkoxyalkyl; haloalkyl; arylalkyl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; heteroaryl,
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; 5-pyrimidinyl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; or 2- or 5-thiazolyl optionally substituted with halogen,
alkyl, alkenyl, alkynyl, alkoxy, alkylthio, haloalkyl, haloalkenyl,
haloalkoxy, haloalkylthio, cyano, or nitro; R.sub.3 is alkyl;
alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; arylthioalkyl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; aryl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, nitro; heteroaryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or
alkylsilyl; R.sub.4 is H; acyl; haloacyl; alkoxycarbonyl;
aryloxycarbonyl; alkylaminocarbonyl; or dialkylaminocarbonyl;
R.sub.5 is H; alkyl; alkenyl; alkynyl; alkoxyalkyl; haloalkyl;
arylalkyl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted
with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,
alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;
arylthioalkyl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; or alkylsilyl;
17. A method according to claim 16, which comprises one or more
applications of one of more compounds of formula (I) alone or in
conjunction with one or more customary plant protection formulating
auxiliaries.
18. A method according to claim 17 wherein two or more applications
are carried out in sequence, and wherein the two or more
applications have the same or different concentration or
combinations of compounds of formula (I) or both.
19. A method according to claim 16 wherein the useful crop plants
are selected from the group consting of cereals, rice, beets,
leguminous plants, oil plants, cucumber plants, fibre plants,
vegetables, plantation crops, ornamentals, vines, bushberries,
caneberries, cranberries, peppermint, rhubarb, spearmint, sugar
cane and turf grasses.
20. A method according to claim 16 wherein the plant growth
regulating effect is an inhibition or a retardation of the plant
growth.
21. An agricultural composition comprising one or more compounds of
formula (I) and one or more customary plant protection auxiliaries
wherein said compound has the formula ##STR00193## wherein X is S,
O, or NR.sub.5; R is H; alkyl; alkoxyalkyl; haloalkyl; arylalkyl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted
with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,
alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;
arylthioalkyl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; or alkylsilyl; R.sub.1 is alkyl;
alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; arylthioalkyl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; aryl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, nitro; heteroaryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or
alkylsilyl; R.sub.2 is alkyl; alkoxyalkyl; haloalkyl; arylalkyl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; heteroaryl,
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; 5-pyrimidinyl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; or 2- or 5-thiazolyl optionally substituted with halogen,
alkyl, alkenyl, alkynyl, alkoxy, alkylthio, haloalkyl, haloalkenyl,
haloalkoxy, haloalkylthio, cyano, or nitro; R.sub.3 is alkyl;
alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; arylthioalkyl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; aryl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, nitro; heteroaryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or
alkylsilyl; R.sub.4 is H; acyl; haloacyl; alkoxycarbonyl;
aryloxycarbonyl; alkylaminocarbonyl; or dialkylaminocarbonyl;
R.sub.5 is H; alkyl; alkenyl; alkynyl; alkoxyalkyl; haloalkyl;
arylalkyl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted
with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,
alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;
arylthioalkyl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl
optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; or alkylsilyl;
Description
[0001] The present invention relates to thiophene, furan and
pyrrole compounds having plant growth regulating properties, to
agricultural compositions comprising them, and to the use of said
compounds for regulating plant growth.
[0002] Plant growth regulators (PGRs) are generally any substances
or mixtures of substances intended to accelerate or retard the rate
of growth or maturation, or otherwise alter the development of
plants or their produce. PGRs affect growth and differentiation of
plants, a process which is commonly and hereinafter referred to as
"plant health". There exists a need for further substances having
PGR activity.
[0003] International patent application WO2007/075487 refers to a
series of thiophene, furan and pyrrole derivatives having
fungicidal properties.
[0004] It has surprisingly been found that the thiophene, furan and
pyrrole compounds of the present invention exhibit plant growth
regulating properties and are therefore suitable for use in
agriculture for the improvement and control of plant health.
[0005] Accordingly, in a first aspect, the present invention
provides for the use of a compound of the formula (I)
##STR00002## [0006] wherein [0007] X is S, O, or NR.sub.5; [0008] R
is H; alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally
substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,
alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally
substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,
alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl
optionally substituted (e.g., 1, 2, 3 or 4 times) with halogen,
alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally
substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,
alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally
substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,
alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl; [0009]
R.sub.1 is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally
substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,
alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally
substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,
alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl
optionally substituted (e.g., 1, 2, 3 or 4 times) with halogen,
alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally
substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,
alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally
substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,
alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl; [0010]
R.sub.2 is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally
substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,
alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally
substituted (e.g. 1, 2, 3 or 4 times) with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; heteroaryl, especially 2-, 3- or
4-pyridyl optionally substituted (e.g. 1, 2, 3 or 4 times) with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;
5-pyrimidinyl optionally substituted (e.g. 1, 2, 3 or 4 times) with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or 2- or
5-thiazolyl optionally substituted (e.g. 1, 2, 3 or 4 times) with
halogen, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, haloalkyl,
haloalkenyl, haloalkoxy, haloalkylthio, cyano, or nitro; [0011]
R.sub.3 is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally
substituted (e.g. 1, 2, 3 or 4 times) with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted
(e.g. 1, 2, 3 or 4 times) with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; arylthioalkyl optionally
substituted (e.g. 1, 2, 3 or 4 times) with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryl optionally substituted (e.g.
1, 2, 3 or 4 times) with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, nitro; heteroaryl optionally substituted
(e.g. 1, 2, 3 or 4 times) with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; or alkylsilyl; [0012] R.sub.4 is H;
acyl (e.g., acetyl, benzoyl, phenylacetyl); haloacyl;
alkoxycarbonyl; aryloxycarbonyl; alkylaminocarbonyl; or
dialkylaminocarbonyl; [0013] R.sub.5 is H; alkyl; alkenyl; alkynyl;
alkoxyalkyl; haloalkyl; arylalkyl optionally substituted (e.g., 1,
2, 3 or 4 times) with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; aryloxyalkyl optionally substituted (e.g., 1, 2, 3 or 4
times) with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; arylthioalkyl optionally substituted (e.g., 1, 2, 3 or 4
times) with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; aryl optionally substituted (e.g., 1, 2, 3 or 4 times)
with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,
alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro;
heteroaryl optionally substituted (e.g., 1, 2, 3 or 4 times) with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or
alkylsilyl; [0014] and salts thereof; as a plant growth
regulator.
[0015] Plant growth regulators can, for example, reduce plant
height, stimulate seed germination, induce flowering, darken leaf
coloring, change the rate of plant growth and modify the timing and
efficiency of fruiting. In addition, PGRs may exhibit pronounced
growth-regulating properties which can result in an increase in the
yield of cultivated plants or harvested crops.
[0016] PGRs may also have a growth inhibiting action which is
dependent on concentration. The growth of both monocots and dicots
may be inhibited. Inhibition of the vegetative growth of many
cultivated plants permits more plants to be sown in a crop area, so
that a higher yield may be obtained per unit of area. Inhibition of
the vegetative growth of monocot plants, e.g. cultivated plants
such as cereals, is sometimes desirable and advantageous. Such a
growth inhibition is of economic interest.
[0017] The use of PGRs for inhibiting the growth in height of
cereals is also important, as shortening the stalks diminishes or
completely eliminates the danger of lodging before harvesting.
Additionally, PGRs are able to bring about a strengthening of the
stalks in crops of cereals and this too counteracts lodging.
[0018] Furthermore, the present invention also provides
compositions comprising the thiophene, furan and pyrrole
derivatives of the present invention that improve plants, a process
which is commonly and hereinafter referred to as "plant
health".
[0019] For example, advantageous properties that may be mentioned
are improved crop characteristics including: emergence, crop yield,
protein content, increased vigour, faster/delayed maturation,
increased speed of seed emergence, improved nutrient utilization
efficiency, improved nitrogen utilization efficiency, improved
water use efficiency, improved oil content and /or quality,
improved digestibility, faster/more even ripening, improved flavor,
improved starch content, more developed root system (improved root
growth), improved stress tolerance (e.g. against drought, heat,
salt, light, UV, water, cold), reduced ethylene (reduced production
and/or inhibition of reception), tillering increase, increase in
plant height, bigger leaf blade, less dead basal leaves, stronger
tillers, greener leaf color, pigment content, photosynthetic
activity, less input needed (such as fertilizers or water), less
seeds needed, more productive tillers, earlier flowering, early
grain maturity, less plant verse (lodging), increased shoot growth,
enhanced plant vigor, increased plant stand and early and better
germination.
[0020] Advantageous properties obtained, especially from treated
seeds, include, for example, improved germination and field
establishment, better vigor and more homogeneous field
establishment.
[0021] Advantageous properties obtained, especially from foliar
and/or in-furrow application include, for example, improved plant
growth and plant development, better growth, more tillers, greener
leafes, largers leaves, more biomass, better roots, improved stress
tolerance of the plants, more grain yield, more biomass harvested,
improved quality of the harvest (content of fatty acids,
metabolites, oil etc), more marketable products (e.g. improved
size), improved process (e.g. longer shelf-life, better extraction
of compounds), improved quality of seeds (for being seeded in the
following seasons for seed production); or any other advantages
familiar to a person skilled in the art.
[0022] It is therefore an object of the present invention to
provide compositions and methods suitable for addressing the
opportunities outlined above.
[0023] The present invention provides plant-protecting active
ingredients that are thiophene, furan and pyrrole compounds of
formula (I) according to the invention, in particular the
individual thiophene, furan and pyrrole compounds described in the
description as being preferred, and mixtures with increased
efficacy and to a method of improving the health of plants by
applying said compounds and mixtures to the plants or the locus
thereof.
[0024] The action of the compounds of formula (I) is separate to
any fungicidal action. The thiophene, furan and pyrrole compounds
of formula (I) according to the invention, in particular the
individual thiophene, furan and pyrrole compounds described in the
above description as being preferred compounds exhibit plant health
properties.
[0025] The present invention also concerns compositions comprising
or consisting essentially of an active compound as described herein
in combination with a suitable carrier (e.g., an agricultural
carrier).
[0026] The foregoing and other objects and aspects of the present
invention are explained in greater detail below.
[0027] "Alkyl" as used herein refers to a saturated hydrocarbon
radical which may be straight-chain or branched-chain or cyclic
(cycloalkyl) and contains from 1 to 24 carbon atoms. This
definition applies both when the term is used alone and when it is
used as part of a compound term, such as haloalkyl and similar
terms. Preferred straight chain and branched alkyl groups may
contain 1 to 8 carbon atoms, more preferably 1 to 4 carbons, even
more preferably, 1 to 4 carbon atoms. Representative alkyl groups
include, for example, methyl, ethyl, isopropyl, n-propyl, n-butyl,
t-butyl, t-amyl, and 2,5-dimethylhexyl. Preferred cycloalkyl groups
may contain 3 to 12 carbon atoms, more preferably 4 to 10 carbons,
even more preferably, 5 to 8 carbon atoms and most preferably 5 or
6 carbon atoms. Preferred cycloalkyl groups include, for example,
cyclobutyl, cyclopropyl, cyclopentyl and cyclohexyl.
[0028] "Alkenyl" as used herein, refers to a straight or branched
chain hydrocarbon containing from 2 to 24 carbons, more preferably
2 to 8 carbons, yet more preferably, 2 to 6 carbon atoms, even more
preferably 2 to 4 carbon atoms, and containing at least one
carbon-carbon double bond. Representative alkenyl groups include,
for example, ethenyl, 2-propenyl, 2-methyl-2-propenyl, 3-butenyl,
4-pentenyl, 5-hexenyl, 2-heptenyl, 2-methyl-1-heptenyl and
3-decenyl.
[0029] "Alkynyl" as used herein, refers to a straight or branched
chain hydrocarbon group containing from 2 to 24 carbons, more
preferably 2 to 8 carbons, yet more preferably, 2 to 6 carbon
atoms, even more preferably 2 to 4 carbon atoms, and containing at
least one carbon-carbon triple bond. Representative alkynyl groups
include, for example, acetylenyl, 1-propynyl, 2-propynyl,
3-butynyl, 2-pentynyl and 1-butynyl.
[0030] Representative alkoxy groups include, for example, methoxy,
ethoxy and t-butoxy.
[0031] Representative alkylthio groups include, for example,
methylthio, ethylthio, t-butylthio and hexylthio.
[0032] "Aryl" refers to an aromatic substituent which may be a
single ring or multiple rings which are fused together, linked
covalently or linked to a common group such as an ethylene or
methylene moiety. The aromatic rings may each contain heteroatoms
and hence aryl encompasses heteroaryl as used herein. Aryl moieties
may be optionally substituted with 1 to 4 substituents
independently selected from halogen, nitro, alkylcarboxyl, alkoxy
and phenoxy. Representative examples of aryl include phenyl
azulenyl, indanyl, indenyl, naphthyl, tetrahydronaphthyl, biphenyl,
diphenylmethyl, 2,2-diphenyl-1-ethyl, thienyl, pyridyl and
quinoxalyl. Most preferably, aryl is phenyl.
[0033] "Heteroaryl" means a cyclic, aromatic hydrocarbon containing
3 to 10 ring-atoms including 1 to 4 heteroatoms independently
selected from nitrogen, oxygen and sulfur. Preferred heteroaryl
groups are five and six membered rings and contain from one to
three heteroatoms independently selected from nitrogen, oxygen and
sulphur. Heteroaryl moieties may be optionally substituted with 1
to 4 substituents independently selected from halogen, nitro,
alkylcarboxyl, alkoxy and phenoxy. Examples of heteroaryl groups
include furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,
pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl,
thiadiazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyranyl,
pyridazinyl, tetrazolyl, triazinyl.
[0034] In addition, the term heteroaryl includes fused heteroaryl
groups, for example benzimidazolyl, benzoxazolyl, imidazopyridinyl,
benzoxazinyl, benzothiazinyl, oxazolopyridinyl, benzofuranyl,
quinolinyl, quinazolinyl, quinoxalinyl, benzothiazolyl,
phthalimido, benzofuranyl, benzodiazepinyl, indolyl, isoindolyl,
isobenzofuranyl, chromenyl, xanthenyl, indolizinyl, indazolyl,
purinyl, quinolizinyl, isoquinolyl, phthalazinyl, naphthyridinyl
and benzo[b]thienyl.
[0035] "Heterocyclyl", as used herein refers to a saturated or
partially unsaturated cyclic hydrocarbon containing from 3 to 10
ring-atoms up to 4 of which may be hetero-atoms such as nitrogen,
oxygen and sulfur. Examples of heterocyclyl groups are oxiranyl,
azetidinyl, tetrahydrofuranyl, thiolanyl, pyrrolidinyl, pyrrolinyl,
imidazolidinyl, imidazolinyl, sulfolanyl, dioxolanyl,
dihydropyranyl, tetrahydropyranyl, piperidinyl, pyrazolinyl,
pyrazolidinyl, dioxanyl, morpholinyl, dithianyl, thiomorpholinyl,
piperazinyl, azepinyl, oxazepinyl, thiazepinyl, thiazolinyl and
diazapanyl.
[0036] "Acyl" includes any readily hydrolysable acyl groups, and
comprises, for example, C(O)R.sup.6, C(O)OR.sup.6, C(O)NHR.sup.6
and C(O)NR.sup.6R.sup.7, wherein R.sup.6 and R.sup.7 are each
independently selected from alkyl, alkenyl, akynyl, heterocyclyl,
aryl and heteroaryl. Acyl groups may be optionally substituted with
one or more, for example 1, 2, 3 or 4, halo or OR.sup.6 groups.
Preferred acyl groups are acetyl, benzoyl and phenylacetyl.
[0037] "Halo" or "halogen" means fluoro, chloro, bromo and iodo and
is preferably fluoro or chloro.
[0038] "Haloalkyl" includes monohaloalkyl, polyhaloalkyl and
perhaloalkyl, for example, chloromethyl, 2-bromoethyl,
2-fluoroethyl, 2,2,2-trifluoroethyl, chlorodifluoromethyl,
trichloromethyl, trifluoromethyl, pentafluoroethyl and
2-chloro-3-fluoropentyl.
[0039] "Organic base" as used herein includes, for example,
triethylamine, triisobutylamine, triiooctylamine, triisodecylamine,
diethanolamine, triethanolamine, pyridine, morpholine, and mixtures
thereof. A preferred category of organic base is organic
amines.
[0040] "Inorganic base" as used herein includes, for example,
sodium carbonate, sodium bicarbonate, potassium carbonate, and
mixtures thereof.
[0041] "Inert solvent" as used herein includes any suitable inert
solvent including, for example, tetrahydrofuran,
N-methylpyrrolidone, dimethylformamide, toluene, dimethyl ether,
methyl t-butyl ether and dioxane, methylene chloride, chloroform,
1,2-dichloroethane, and mixtures thereof.
[0042] "Protic solvent" as used herein may be any suitable protic
solvent including, for example, methanol, ethanol, isopropanol,
n-butanol, ethylene glycol, methyl Cellosolve, ethyl Cellosolve,
cyclohexanol, glycerol, diethylene glycol, triethanolamine,
polyethylene glycol, sec-butanol, n-propanol and tert-butanol.
[0043] "Optionally substituted" means substituted by one or more
substituents, in particular, one, two, three or four substituents.
In the case where groups may be selected from a number of
alternative groups, the selected groups may be the same or
different.
[0044] "Agriculturally acceptable salt" means a salt the cation of
which is known and accepted in the art for the formation of salts
for agricultural or horticultural use. Preferably the salts are
water-soluble.
[0045] The compounds of formula (I) may exist in different
geometric or optical isomeric forms or in different tautomeric
forms. One or more centres of chirality may be present, in which
case compounds of the formula (I) may be present as pure
enantiomers, mixtures of enantiomers, pure diastereomers or
mixtures of diastereomers. There may be double bonds present in the
molecule, such as C.dbd.C or C.dbd.N bonds, in which case compounds
of formula (I) may exist as single isomers of mixtures of isomers.
Centres of tautomerisation may be present. This invention covers
all such isomers and tautomers and mixtures thereof in all
proportions as well as isotopic forms such as deuterated
compounds.
[0046] Suitable salts of the compounds of formula (I), include acid
addition salts such as those with an inorganic acid such as
hydrochloric, hydrobromic, sulphuric, nitric or phosphoric acid, or
an organic carboxylic acid such as oxalic, tartaric, lactic,
butyric, toluic, hexanoic or phthalic acid, or a sulphonic acid
such as methane, benzene or toluene sulphonic acid. Other examples
of organic carboxylic acids include haloacids such as
trifluoroacetic acid.
[0047] N-oxides are oxidised forms of tertiary amines or oxidised
forms of nitrogen containing heteroaromatic compounds. They are
described in many books for example in "Heterocyclic N-oxides" by
Angelo Albini and Silvio Pietra, CRC Press, Boca Raton, Fla.,
1991.
[0048] In another aspect, the present invention provides a method
of regulating plant growth of crops of useful plants, which
comprises applying to said plants, to one or more parts of said
plants, or to the locus thereof or plant propagation material, a
compound of formula (I) as defined herein.
[0049] The preferred embodiments of the invention as defined below
apply equally to each aspect and preferred aspects thereof of the
invention as defined herein.
[0050] In an embodiment, the present invention relates to the use
of a compound of the formula (I) as defined herein wherein said
compound of formula I is selected from the group consisting of
compounds of formula (Ia), compounds of formula (Ib), and compounds
of formula (Ic):
##STR00003## [0051] wherein [0052] R is H; alkyl; alkoxyalkyl;
haloalkyl; arylalkyl optionally substituted (e.g., 1, 2, 3 or 4
times) with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; aryloxyalkyl optionally substituted (e.g., 1, 2, 3 or 4
times) with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; arylthioalkyl optionally substituted (e.g., 1, 2, 3 or 4
times) with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; aryl optionally substituted (e.g., 1, 2, 3 or 4 times)
with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,
alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro;
heteroaryl optionally substituted (e.g., 1, 2, 3 or 4 times) with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or
alkylsilyl; [0053] R.sub.1 is alkyl; alkoxyalkyl; haloalkyl;
arylalkyl optionally substituted (e.g., 1, 2, 3 or 4 times) with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl
optionally substituted (e.g., 1, 2, 3 or 4 times) with halogen,
alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl
optionally substituted (e.g., 1, 2, 3 or 4 times) with halogen,
alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally
substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,
alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally
substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,
alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl; [0054]
R.sub.2 is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally
substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,
alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally
substituted (e.g. 1, 2, 3 or 4 times) with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; heteroaryl, especially 2-, 3- or
4-pyridyl optionally substituted (e.g. 1, 2, 3 or 4 times) with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;
5-pyrimidinyl optionally substituted (e.g. 1, 2, 3 or 4 times) with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or 2- or
5-thiazolyl optionally substituted (e.g. 1, 2, 3 or 4 times) with
halogen, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, haloalkyl,
haloalkenyl, haloalkoxy, haloalkylthio, cyano, or nitro; [0055]
R.sub.3 is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally
substituted (e.g. 1, 2, 3 or 4 times) with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted
(e.g. 1, 2, 3 or 4 times) with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; arylthioalkyl optionally
substituted (e.g. 1, 2, 3 or 4 times) with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; aryl optionally substituted (e.g.
1, 2, 3 or 4 times) with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, nitro; heteroaryl optionally substituted
(e.g. 1, 2, 3 or 4 times) with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; or alkylsilyl; [0056] R.sub.4 is H;
acyl (e.g., acetyl, benzoyl, phenylacetyl); haloacyl;
alkoxycarbonyl; aryloxycarbonyl; alkylaminocarbonyl; or
dialkylaminocarbonyl; [0057] R.sub.5 is H; alkyl; alkenyl; alkynyl;
alkoxyalkyl; haloalkyl; arylalkyl optionally substituted (e.g., 1,
2, 3 or 4 times) with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; aryloxyalkyl optionally substituted (e.g., 1, 2, 3 or 4
times) with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; arylthioalkyl optionally substituted (e.g., 1, 2, 3 or 4
times) with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; aryl optionally substituted (e.g., 1, 2, 3 or 4 times)
with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,
alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro;
heteroaryl optionally substituted (e.g., 1, 2, 3 or 4 times) with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or
alkylsilyl.
[0058] In a preferred embodiment, R is H or C.sub.1-C.sub.8-alkyl.
More preferably, R is H or C.sub.1-C.sub.4-alkyl. Most preferably,
R is H or methyl.
[0059] In a preferred embodiment, R.sub.1 is aryl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; or heteroaryl optionally substituted with halogen, alkyl,
alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, or nitro.
[0060] Preferably, R.sub.1 is aryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkylthio,
haloalkoxy, phenoxy, cyano, or nitro; or heteroaryl optionally
substituted with halogen.
[0061] More preferably, R.sub.1 is phenyl optionally substituted
with halogen, C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl,
C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-haloalkyl,
C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-alkylthio,
C.sub.1-C.sub.6-haloalkoxy, cyano, or nitro; or furanyl, thienyl,
pyridyl, or benzothienyl, each optionally substituted with
halogen.
[0062] Most preferably, R.sub.1 is 2-chlorophenyl, 4-chlorophenyl,
2,4-dichlorophenyl, 2-fluorophenyl, 2,4-difluorophenyl,
3,5-difluorophenyl, 4-trifluoro-methylphenyl,
4-trifluoromethoxyphenyl, 2-thienyl, 3-thienyl, 5-chloro-2-thienyl
or 5-chloro-2-furyl.
[0063] In another preferred embodiment R.sub.1 is alkyl; or
arylalkyl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro.
[0064] Preferably, R.sub.1 is C.sub.1-C.sub.6-alkyl; or arylalkyl
optionally substituted with halogen or alkyl.
[0065] More preferably, R.sub.1 is C.sub.1-C.sub.6-alkyl; or
phenyl-C.sub.1-C.sub.6-alkyl optionally substituted with halogen or
C.sub.1-C.sub.6-alkyl.
[0066] Most preferably, R.sub.1 is n-pentyl, t-butyl, benzyl or
4-chlorobenzyl.
[0067] In a preferred embodiment, R.sub.2 is heteroaryl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano or
nitro.
[0068] Preferably, R.sub.2 is pyridyl, pyrimidinyl or isoquinolyl,
each optionally substituted with halogen, alkyl, alkenyl, alkynyl,
haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano or nitro.
[0069] More preferably, R.sub.2 is pyridyl, pyrimidinyl or
isoquinolyl, each optionally substituted with halogen,
C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl,
C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-haloalkyl,
C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-alkylthio,
C.sub.1-C.sub.6-haloalkoxy, cyano, or nitro.
[0070] Yet more preferably, R.sub.2 is 2-, 3- or 4-pyridyl or
5-pyrimidinyl, each optionally substituted with halogen,
C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy or
C.sub.1-C.sub.6-alkylthio.
[0071] Most preferably, R.sub.2 is 2-pyridyl, 3-pyridyl, or
5-pyrimidinyl, each optionally substituted with methyl, chloro,
fluoro, methoxy, thiomethoxy or trifluoromethyl.
[0072] In a preferred embodiment, R.sub.3 is alkyl; alkoxyalkyl;
haloalkyl; arylalkyl optionally substituted with halogen;
aryloxyalkyl optionally substituted with halogen; aryl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
alkoxy, alkylthio, haloalkoxy, alkoxyalkynyl, cyano or nitro;
heteroaryl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, alkoxy, alkylthio, haloalkoxy, cyano, or nitro;
or alkylsilyl;
[0073] Preferably, R.sub.3 is alkyl; aryl optionally substituted
with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,
alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;
heteroaryl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, nitro; or alkylsilyl
[0074] More preferably, R.sub.3 is C.sub.1-C.sub.6-alkyl; phenyl
optionally substituted with halogen, C.sub.1-C.sub.6-alkyl,
C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy,
C.sub.1-C.sub.6-alkylthio, cyano or nitro; furanyl, thienyl or
pyridyl, each optionally substituted with halogen,
C.sub.1-C.sub.6-alkyl or C.sub.1-C.sub.6-alkoxy; or
C.sub.1-C.sub.6-alkylsilyl.
[0075] Most preferably, R.sub.3 is phenyl, 3-chlorophenyl,
4-chlorophenyl, 4-fluorophenyl, 2,4-difluorophenyl,
3,5-difluorophenyl, 4-methylphenyl, 2-thienyl, 5-chloro-2-thienyl,
5-methyl-2-thienyl, 3-thienyl, t-butyl or trimethylsilyl.
[0076] In a preferred embodiment, R.sub.4 is H, acetyl, benzoyl or
phenylacetyl. Most preferably, R.sub.4 is H.
[0077] In a preferred embodiment R.sub.5 is H, alkyl or haloalkyl.
Preferably, R.sub.5 is C.sub.1-C.sub.6-alkyl, or
C.sub.1-C.sub.6-haloalkyl. Yet more preferably, R.sub.5 is
C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4-haloalkyl. Most
preferably, R.sub.5 is methyl.
[0078] In one preferred aspect of the present invention: [0079] R
is H or alkyl; [0080] R.sub.1 is alkyl; or arylalkyl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; aryl optionally substituted with halogen, alkyl, alkenyl,
alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,
haloalkylthio, cyano, or nitro; or heteroaryl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
or nitro; [0081] R.sub.2 is heteroaryl optionally substituted with
halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,
alkylthio, haloalkoxy, haloalkylthio, cyano or nitro; [0082]
R.sub.3 is alkyl; aryl optionally substituted with halogen, alkyl,
alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,
haloalkoxy, haloalkylthio, cyano, or nitro; heteroaryl optionally
substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl,
haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano,
nitro; or alkylsilyl; and [0083] R.sub.4 is H, acetyl, benzoyl or
phenylacetyl; and [0084] R.sub.5 is C.sub.1-C.sub.6-alkyl, or
C.sub.1-C.sub.6-haloalkyl; or a salt thereof.
[0085] In a more preferred aspect of the present invention: [0086]
R is H or C.sub.1-C.sub.4-alkyl; [0087] R.sub.1 is
C.sub.1-C.sub.6-alkyl; or phenyl-C.sub.1-C.sub.6-alkyl optionally
substituted with halogen or C.sub.1-C.sub.6-alkyl; phenyl
optionally substituted with halogen, C.sub.1-C.sub.6-alkyl,
C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl,
C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy,
C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-haloalkoxy, cyano, or
nitro; or furanyl, thienyl, pyridyl, or benzothienyl, each
optionally substituted with halogen; [0088] R.sub.2 is pyridyl,
pyrimidinyl or isoquinolyl, each optionally substituted with
halogen, C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl,
C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-haloalkyl,
C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-alkylthio,
C.sub.1-C.sub.6-haloalkoxy, cyano, or nitro; [0089] R.sub.3 is
C.sub.1-C.sub.6-alkyl; phenyl optionally substituted with halogen,
C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl,
C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-alkylthio, cyano or nitro;
furanyl, thienyl or pyridyl, each optionally substituted with
halogen, C.sub.1-C.sub.6-alkyl or C.sub.1-C.sub.6-alkoxy; or
C.sub.1-C.sub.6-alkylsilyl; [0090] R.sub.4 is H; and [0091] R.sub.5
is C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4-haloalkyl; or a salt
thereof.
[0092] In a yet more preferred aspect of the present invention:
[0093] R is H or methyl; [0094] R.sub.1 is n-pentyl, t-butyl,
benzyl or 4-chlorobenzyl; 2-chlorophenyl, 4-chlorophenyl,
2,4-dichlorophenyl, 2-fluorophenyl, 2,4-difluorophenyl,
3,5-difluorophenyl, 4-trifluoro-methylphenyl,
4-trifluoromethoxyphenyl, 2-thienyl, 3-thienyl, 5-chloro-2-thienyl
or 5-chloro-2-furyl; [0095] R.sub.2 is 2-, 3- or 4-pyridyl or
5-pyrimidinyl, each optionally substituted with halogen,
C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy or
C.sub.1-C.sub.6-alkylthio; [0096] R.sub.3 is phenyl,
3-chlorophenyl, 4-chlorophenyl, 4-fluorophenyl, 2,4-difluorophenyl,
3,5-difluorophenyl, 4-methylphenyl, 2-thienyl, 5-chloro-2-thienyl,
5-methyl-2-thienyl, 3-thienyl, t-butyl or trimethylsilyl; [0097]
R.sub.4 is H; and [0098] R.sub.5 is methyl; or a salt thereof.
[0099] Preferred compounds of formula (I) for use according to the
methods of the present invention are selected from:
[0100]
2,4-Bis-(3-chlorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene
(compound 1);
[0101]
4-(3-Chlorophenyl)-2-(5-chloro-2-thienyl)-3-[(3pyridyl)hydroxymethy-
l]thiophene (cpd. 2);
[0102]
4-(3-Chlorophenyl)-2-(3,5-difluorophenyl)-3-[(3-pyridyl)hydroxymeth-
yl]thiophene (cpd. 3);
[0103]
4-(4-Chlorophenyl)-2-(5-chloro-2-thienyl)-3-[(3-pyridyl)hydroxymeth-
yl]thiophene (cpd. 4);
[0104]
4-(4-Chlorophenyl)-2-(3,5-difluorophenyl)-3-[(3-pyridyl)hydroxymeth-
yl]thiophene (cpd. 5);
[0105]
2-(4-Chlorophenyl)-4-(2,4-difluorophenyl)-3-[(3-pyridyl)phydroxymet-
hyl]thiophene (cpd. 6);
[0106]
4-(2,4-Difluorophenyl)-2-(1,1-dimethylethyl)-3-[(3-pyridyl)phydroxy-
methyl]thiophene (cpd. 7);
[0107]
2,4-Bis-(4-chlorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene
(cpd. 8);
[0108]
4-(4-Chlorophenyl)-3-[(3-pyridyphydroxymethyl]-2-(2-thienyl)thiophe-
ne (cpd. 9);
[0109]
2-(4-Chlorophenyl)-4-(5-chloro-2-thienyl)-3-[(3-pyridyl)phydroxymet-
hyl]thiophene (cpd. 10);
[0110]
4-(5-Chloro-2-thienyl)-2-(2,4-difluorophenyl)--3-[(3-pyridyl)phydro-
xymethyl]thiophene (cpd. 11);
[0111]
2-(4-Chlorophenyl)-3-[(3-pyridyphydroxymethyl]-4-(2-thienyl)thiophe-
ne (cpd. 12);
[0112]
2-(2,4-Difluorophenyl)-3-[(3-pyridyphydroxymethyl]-4-(2-thienyl)thi-
ophene (cpd. 13);
[0113]
2-(2,4-Difluorophenyl)-3-[(3-pyridyphydroxymethyl]-4-(2-thienyl)thi-
ophene (cpd. 14);
[0114]
2-(4-Butylphenyl)-4-(5-methyl-2-thienyl)-3-[(3-pyridyl)phydroxymeth-
yl]thiophene (cpd. 15);
[0115]
2,4-Bis-(2,4-Difluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene
(cpd. 16);
[0116]
4-(4-Chlorophenyl)-2-(2,4-difluorophenyl)-3-[(3-pyridyl)phydroxymet-
hyl]thiophene (cpd. 17);
[0117]
2,4-Bis-(2-trifluoromethylphenyl)-3-[(3-pyridyl)phydroxymethyl]thio-
phene (cpd. 18);
2,4-Bis-(3-trifluoromethylphenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene
(cpd. 19);
[0118]
2,4-Bis-(4-trifluoromethylphenyl)-3-[(3-pyridyl)phydroxymethyl]thio-
phene (cpd. 20);
[0119]
4-(4-Chlorophenyl)-3-[(3-pyridyphydroxymethyl]-2-(3-thienyl)thiophe-
ne (cpd. 21);
[0120]
2-(5-Bromo-2-thienyl)-4-(4-chlorophenyl)-3-[(3-pyridylphydroxymethy-
l]thiophene (cpd. 22)
[0121]
4-(4-Chlorophenyl)-2-(5-methyl-2-thienyl)-3-[(3-pyridyl)phydroxymet-
hyl]thiophene (cpd. 23);
[0122]
2-(3,5-Difluorophenyl)-3-[(3-pyridyphydroxymethyl]-4-(3-thienyl)thi-
ophene (cpd. 24);
[0123]
2-(2,4-Difluorophenyl)-3-[(3-pyridyphydroxymethyl]-4-(3-thienyl)thi-
ophene (cpd. 25);
[0124]
2-(3,5-Difluorophenyl)-4-(4-fluorophenyl)-3-[(3-pyridyl)phydroxymet-
hyl]thiophene (cpd. 26);
[0125]
2-(2,4-Difluorophenyl)-4-(4-fluorophenyl)-3-[(3-pyridyl)phydroxymet-
hyl]thiophene (cpd. 27);
[0126]
2-(4-Chlorophenyl)-3-[(3-pyridyphydroxymethyl]-4-(3-thienyl)thiophe-
ne (cpd. 28);
[0127]
3-[(3-Pyridyl)phydroxymethyl]-2-(2-tetrahydropyranyloxymethyl)-4-(3-
-thienyl)thiophene (cpd. 29);
[0128]
4-(2,4-Difluorophenyl)-3-[(3-pyridyphydroxymethyl]-2-(3-thienyl)thi-
ophene (cpd. 32);
[0129]
4-(2,4-Difluorophenyl)-3-[(3-pyridyphydroxymethyl]-2-(2-thienyl)thi-
ophene (cpd. 39);
[0130]
2-(2,4-Difluorophenyl)-4-(2-fluorophenyl)-3-[(3-pyridyl)phydroxymet-
hyl]thiophene (cpd. 45);
[0131]
2,4-Bis-(2-Chlorophenyl)-3-[(3-pyridyl)hydroxymethyl]-thiophene
(cpd. 49);
[0132]
2,4-Bis-(3-Chlorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene
(cpd. 50);
[0133] 2,4-Bis-(Phenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd.
51);
[0134]
2,4-Bis-(2,4-Dichlorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene
(cpd. 52);
[0135]
2,4-Bis-(2-Fluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene
(cpd. 53);
[0136]
2,4-Bis-(3-Fluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene
(cpd. 54);
[0137]
2-(3-Chlorophenyl)-4,5-dimethyl-3-[(3-pyridyl)hydroxymethyl]thiophe-
ne (cpd. 55);
[0138]
4-(5-Chloro-2-furanyl)-2-(4-chlorophenyl)-3-[(3-pyridyl)hydroxymeth-
yl]thiophene (cpd. 56);
[0139]
4-(5-Chloro-2-furanyl)-2-(2,4-difluorophenyl)-3-[(3-pyridyl)phydrox-
ymethyl]thiophene (cpd. 57);
[0140] 2,4-Bis-(2-thienyl)-3-[(3-pyridyl)hydroxymethyl]thiophene
(cpd. 58);
[0141]
2,4-Bis-(4-Fluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene
(cpd. 59);
[0142]
2-(3-Chlorophenyl)-4-phenyl-3-[(3-pyridyl)hydroxymethyl]thiophene
(cpd. 60);
[0143]
2,4-Bis-(3-chloro-5-trifluoromethylphenyl)-3-[(3-pyridyl)hydroxymet-
hyl]-thiophene (cpd. 61);
[0144]
2,4-Bis-(2,5-difluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene
(cpd. 62);
[0145]
2,4-Bis-(4-chloro-3-fluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiop-
hene (cpd. 63);
[0146]
2,4-Bis-(3-Methoxyphenyl)-3-[(3-pyridyl)hydroxymethyl]-thiophene
(cpd. 64);
[0147]
4-(2-Fluorophenyl)-3-[(3-pyridyl)hydroxymethyl]-2-(2-thienyl)thioph-
ene (cpd. 65);
[0148]
2,4-Bis-(2-chloro-4-trifluoromethylphenyl)-3-[(3-pyridyl)hydroxymet-
hyl]thiophene (cpd. 66);
[0149]
2,4-Bis-(4-Methoxyphenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene
(cpd. 67);
[0150]
2-(3-Chlorophenyl)-4-(2,4-difluorophenyl)-3-[(3-pyridyl)hydroxymeth-
yl]-thiophene (cpd. 68);
[0151]
2-(5-Bromo-2-thienyl)-4-(2,4-difluorophenyl)-3-[(3-pyridyl)hydroxym-
ethyl]thiophene (cpd. 69);
[0152]
2-(5-Chloro-2-thienyl)-4-(2,4-difluorophenyl)-3-[(3-pyridyl)hydroxy-
methyl]thiophene (cpd. 70);
[0153]
5-Chloro-2-(5-chloro-2-thienyl)-4-(2,4-difluorophenyl)-3-[(3-pyridy-
l)hydroxymethyl]thio (cpd. 71);
[0154]
4-(4-Chlorophenyl)-2-(2-fluorophenyl)-3-[(3-pyridyl)hydroxymethyl]t-
hiophene (cpd. 72);
[0155]
4-(4-Chlorophenyl)-2-(3-fluorophenyl)-3-[(3-pyridyl)phydroxymethyl]-
thiophene (cpd. 73);
[0156]
2-(2-Chlorophenyl)-4-(2,4-difluorophenyl)-3-[(3-pyridyl)phydroxymet-
hyl]thiophene (cpd. 74);
[0157]
4-(2,4-Difluorophenyl)-2-(2-fluorophenyl)-3-[(3-pyridyl)phydroxymet-
hyl]thiophene (cpd. 75);
[0158]
2-(4-Chlorophenyl)-4-(4-chloro-2-fluorophenyl)-3-[(3-pyridyl)phydro-
xymethyl]thiophene (cpd. 76);
[0159]
2-(3-Chlorophenyl)-4-(4-chloro-2-fluorophenyl)-3-[(3-pyridyl)phydro-
xymethyl]thiophene (cpd. 77);
[0160]
4-(2,4-Difluorophenyl)-2-(4-fluorophenyl)-3-[(3-pyridyl)phydroxymet-
hyl]thiophene (cpd. 78);
[0161]
2-(2,4-Difluorophenyl)-4-(2-chlorophenyl)-3-[(3-pyridyl)phydroxymet-
hyl]-thiophene (cpd. 175);
and salts thereof.
[0162] In a further aspect, the following preferred compounds of
for use according to the methods of the present invention are
selected from:
[0163]
4-(3-Chlorophenyl)-2-(3,5-difluorophenyl)-3-[(3-pyridyl)phydroxymet-
hyl]thiophene (cpd. 3);
[0164]
4-(4-Chlorophenyl)-2-(3,5-difluorophenyl)-3-[(3-pyridyl)phydroxymet-
hyl]thiophene (cpd. 5);
[0165]
2-(4-Chlorophenyl)-4-(2,4-difluorophenyl)-3-[(3-pyridyl)phydroxymet-
hyl]thiophene (cpd. 6);
[0166]
4-(4-Chlorophenyl)-2-(2,4-difluorophenyl)-3-[(3-pyridyl)phydroxymet-
hyl]thiophene (cpd. 17);
[0167]
2-(2,4-Difluorophenyl)-4-(4-fluorophenyl)-3-[(3-pyridyl)phydroxymet-
hyl]thiophene (cpd. 27);
[0168]
2-(2,4-Difluorophenyl)-4-(2-chlorophenyl)-3-[(3-pyridyl)phydroxymet-
hyl]-thiophene (cpd. 175);
and salts thereof.
[0169] In a further aspect, the following preferred compound of for
use according to the methods of the present invention is:
[0170]
2-(2,4-Difluorophenyl)-4-(2-chlorophenyl)-3-[(3-pyridyl)phydroxymet-
hyl]-thiophene (cpd. 175);
and salts thereof.
[0171] In a further aspect, the present invention provides a method
of regulating plant growth of crops of useful plants, which
comprises applying to said plants, to one or more parts of said
plants, or to the locus thereof or plant propagation material, a
compound of formula (I) as defined herein
[0172] In an embodiment, the present invention provides a method of
regulating plant growth of crops of useful plants, which comprises
one or more applications of one of more compounds of formula (I)
alone or in conjunction with one or more customary plant protection
formulating auxiliaries.
[0173] In another embodiment, the present invention provides a
method of regulating plant growth of crops of useful plants, which
comprises applying to said plants, to one or more parts of said
plants, or to the locus thereof or plant propagation material, a
compound of formula (I) as defined herein, wherein two or more
applications are carried out in sequence, and wherein the two or
more applications have the same or different concentration or
combinations of compounds as defined herein or both.
[0174] In a further embodiment, the present invention provides a
method of regulating plant growth of crops of useful plants,
wherein the crops of useful plants are selected from cereals, rice,
beets, leguminous plants, oil plants, cucumber plants, fibre
plants, vegetables, plantation crops, ornamentals, vines,
bushberries, caneberries, cranberries, peppermint, rhubarb,
spearmint, sugar cane and turf grasses.
[0175] In a preferred embodiment of the invention, the plant growth
regulating effect is an inhibition or a retardation of the plant
growth.
[0176] In an especially preferred embodiment, the present invention
provides an agricultural composition comprising one or more
compounds of formula (I) as defined herein and one or more
customary plant protection auxiliaries.
[0177] In a further aspect, the present invention is directed to
the (R)-enantiomers of the compounds of formula (I), designated
(R)-(I), wherein X, R, R.sub.1, R.sub.2, R.sub.3, R.sub.4 and
R.sub.5 are as defined herein; and salts thereof.
[0178] Preferred compounds of formula (R)-(I) include the
(R)-enantiomers of compounds 1 to 175 of Table 1 herein.
[0179] The present invention provides the compound of formula
(R)-(I) as a single enantiomer having an enantiomeric excess (e.e.)
of at least 40%, for example, at least 50%, 60%, 70% or 80%,
preferably at least 90%, more preferably at least 95%, yet more
preferably at least 98% and most preferably at least 99%.
[0180] In a further aspect, the present invention is directed to
the (S)-enantiomers of the compounds of formula (I), designated
(S)-(I), wherein X, R, R.sub.1, R.sub.2, R.sub.3, R.sub.4 and
R.sub.5 are as defined herein; and salts thereof.
[0181] The present invention provides the compound of formula
(S)-(I) as a single enantiomer having an enantiomeric excess (e.e.)
of at least 40%, for example, at least 50%, 60%, 70% or 80%,
preferably at least 90%, more preferably at least 95%, yet more
preferably at least 98% and most preferably at least 99%.
[0182] Preferred compounds of formula (S)-(I) include the
(S)-enantiomers of compounds 1 to 175 of Table 1 herein.
[0183] In a further aspect, the present invention is is directed to
the (R)-enantiomers of the compounds of formula (la), designated
(R)-(Ia), wherein R, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as
defined herein; and salts thereof.
[0184] Preferred compounds of formula (R)-(Ia) include the
(R)-enantiomers of compounds 1 to 82 and 175 of Table 1 herein.
[0185] The present invention provides the compound of formula
(R)-(la) as a single enantiomer having an enantiomeric excess
(e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%,
preferably at least 90%, more preferably at least 95%, yet more
preferably at least 98% and most preferably at least 99%.
[0186] In a further aspect, the present invention is is directed to
the (R)-enantiomers of the compounds of formula (Ib), designated
(R)-(lb), wherein R, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as
defined herein; and salts thereof.
[0187] Preferred compounds of formula (R)-(Ib) include the
(R)-enantiomers of compounds 83 to 128 of Table 1 herein.
[0188] The present invention provides the compound of formula
(R)-(Ib) as a single enantiomer having an enantiomeric excess
(e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%,
preferably at least 90%, more preferably at least 95%, yet more
preferably at least 98% and most preferably at least 99%.
[0189] In a further aspect, the present invention is is directed to
the (R)-enantiomers of the compounds of formula (lc), designated
(R)-(lc), wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5
are as defined herein; and salts thereof.
[0190] Preferred compounds of formula (R)-(lc) include the
(R)-enantiomers of compounds 129 to 174 of Table 1 herein.
[0191] The present invention provides the compound of formula
(R)-(lc) as a single enantiomer having an enantiomeric excess
(e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%,
preferably at least 90%, more preferably at least 95%, yet more
preferably at least 98% and most preferably at least 99%.
[0192] In a further aspect, the present invention is is directed to
the (S)-enantiomers of the compounds of formula (Ia), designated
(S)-(Ia), wherein R, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as
defined herein; and salts thereof.
[0193] Preferred compounds of formula (S)-(Ia) include the
(S)-enantiomers of compounds 1 to 82 and 175 of Table 1 herein.
[0194] The present invention provides the compound of formula
(S)-(Ia) as a single enantiomer having an enantiomeric excess
(e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%,
preferably at least 90%, more preferably at least 95%, yet more
preferably at least 98% and most preferably at least 99%.
[0195] In a further aspect, the present invention is is directed to
the (S)-enantiomers of the compounds of formula (Ib), designated
(S)-(Ib), wherein R, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as
defined herein; and salts thereof.
[0196] Preferred compounds of formula (S)-(Ib) include the
(S)-enantiomers of compounds 83 to 128 of Table 1 herein.
[0197] The present invention provides the compound of formula
(S)-(Ib) as a single enantiomer having an enantiomeric excess
(e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%,
preferably at least 90%, more preferably at least 95%, yet more
preferably at least 98% and most preferably at least 99%.
[0198] In a further aspect, the present invention is is directed to
the (S)-enantiomers of the compounds of formula (Ic), designated
(S)-(Ic), wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5
are as defined herein; and salts thereof.
[0199] Preferred compounds of formula (S)-(Ic) include the
(S)-enantiomers of compounds 129 to 174 of Table 1 herein.
[0200] The present invention provides the compound of formula
(S)-(Ic) as a single enantiomer having an enantiomeric excess
(e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%,
preferably at least 90%, more preferably at least 95%, yet more
preferably at least 98% and most preferably at least 99%.
[0201] "Plant propagation material" means the generative parts of a
plant including seeds of all kinds (fruit, tubers, bulbs, grains
etc), roots, rhizomes, cuttings, cut shoots and the like. Plant
propagation material may also include plants and young plants which
are to be transplanted after germination or after emergence from
the soil.
[0202] "Locus" means the fields on which the plants to be treated
are growing, or where the seeds of cultivated plants are sown, or
the place where the seed will be placed into the soil.
[0203] The crops of useful plants to be protected typically
comprise, for example, the following species of plants: cereals
(wheat, barley, rye, oats, maize (including field corn, pop corn
and sweet corn), rice, sorghum and related crops); beet (sugar beet
and fodder beet); leguminous plants (beans, lentils, peas,
soybeans); oil plants (rape, mustard, sunflowers); cucumber plants
(marrows, cucumbers, melons); fibre plants (cotton, flax, hemp,
jute); vegetables (spinach, lettuce, asparagus, cabbages, carrots,
eggplants, onions, pepper, tomatoes, potatoes, paprika, okra);
plantation crops (bananas, fruit trees, rubber trees, tree
nurseries), ornamentals (flowers, shrubs, broad-leaved trees and
evergreens, such as conifers); as well as other plants such as
vines, bushberries (such as blueberries), caneberries, cranberries,
peppermint, rhubarb, spearmint, sugar cane and turf grasses
including, for example, cool-season turf grasses (for example,
bluegrasses (Poa L.), such as Kentucky bluegrass (Poa pratensis
L.), rough bluegrass (Poa trivialis L.), Canada bluegrass (Poa
compressa L.) and annual bluegrass (Poa annua L.); bentgrasses
(Agrostis L.), such as creeping bentgrass (Agrostis palustris
Huds.), colonial bentgrass (Agrostis tenius Sibth.), velvet
bentgrass (Agrostis canina L.) and redtop (Agrostis alba L.);
fescues (Festuca L.), such as tall fescue (Festuca arundinacea
Schreb.), meadow fescue (Festuca elatior L.) and fine fescues such
as creeping red fescue (Festuca rubra L.), chewings fescue (Festuca
rubra var. commutate Gaud.), sheep fescue (Festuca ovina L.) and
hard fescue (Festuca longifolia); and ryegrasses (Lolium L.), such
as perennial ryegrass (Lolium perenne L.) and annual (Italian)
ryegrass (Lolium multiflorum Lam.)) and warm-season turf grasses
(for example, Bermudagrasses (Cynodon L. C. Rich), including hybrid
and common Bermudagrass; Zoysiagrasses (Zoysia Willd.), St.
Augustinegrass (Stenotaphrum secundatum (Walt.) Kuntze); and
centipedegrass (Eremochloa ophiuroides (Munro.) Hack.)).
[0204] The term "useful plants" also includes useful plants that
have been rendered tolerant to herbicides like bromoxynil or
classes of herbicides (such as HPPD inhibitors, ALS inhibitors; for
example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS
(5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS
(glutamine synthetase) inhibitors or PPO
(protoporphyrinogen-oxidase) inhibitors) as a result of
conventional methods of breeding or genetic engineering. An example
of a crop that has been rendered tolerant to imidazolinones (e.g.
imazamox) by conventional methods of breeding (mutagenesis) is
Clearfield.RTM. summer rape (Canola). Examples of crops that have
been rendered tolerant to herbicides or classes of herbicides by
genetic engineering methods include glyphosate- and
glufosinate-resistant maize varieties commercially available under
the trade names RoundupReady.RTM., Herculex I.RTM. and
LibertyLink.RTM..
[0205] The term "useful plants" also includes useful plants which
have been so transformed by the use of recombinant DNA techniques
that they are capable of synthesising one or more selectively
acting toxins, such as are known from toxin-producing bacteria,
especially those of the genus Bacillus.
[0206] The term "useful plants" also includes useful plants which
have been so transformed by the use of recombinant DNA techniques
that they are capable of synthesising antipathogenic substances
having a selective action, such as the so-called
"pathogenesis-related proteins" (PRPs, see e.g. European patent
application EP 0,392,225). Examples of such antipathogenic
substances and transgenic plants capable of synthesising such
antipathogenic substances are known, for example, from European
patent applications EP 0,392,225 and EP 0,353,191, and
International patent application WO 95/33818. The methods of
producing such transgenic plants are generally known to the person
skilled in the art and are described, for example, in the
publications mentioned above.
[0207] The agrochemical compositions of the present invention will
usually contain from 0.1 to 99% by weight, preferably from 0.1 to
95% by weight, of the compound of formula (I), 99.9 to 1% by
weight, preferably 99.8 to 5% by weight, of a solid or liquid
adjuvant, and from 0 to 25% by weight, preferably from 0.1 to 25%
by weight, of a surfactant.
[0208] Suitably, the agrochemical compositions of the present
invention are applied prior to disease development. Rates and
frequency of use of the formulations are those conventionally used
in the art and will depend on factors such as the developmental
stage of the plant and on the location, timing and application
method. Advantageous rates of application are normally from 5 g to
2 kg of active ingredient (a.i.) per hectare (ha), preferably from
10 g to 1 kg a.i./ha, most preferably from 20 g to 600 g a.i./ha.
When used as seed drenching agent, convenient rates of application
are from 10 mg to 1 g of active substance per kg of seeds.
[0209] In practice, as indicated above, the agrochemical
compositions comprising a compound of formula (I) are applied as a
formulation containing the various adjuvants and carriers known to
or used in the industry. They may therefore be formulated as
granules, wettable or soluble powders, emulsifiable concentrates,
coatable pastes, dusts, flowables, solutions, suspensions or
emulsions, or as controlled release forms such as microcapsules.
These formulations are described in more detail below and may
contain from 0.5% to 95% or more by weight of the active
ingredient. The optimum amount will depend on formulation,
application equipment and nature of the plant to be treated.
[0210] Suspension concentrates are aqueous formulations in which
finely divided solid particles of the active compound are
suspended. Such formulations include anti-settling agents and
dispersing agents and may further include a wetting agent to
enhance activity as well an anti-foam and a crystal growth
inhibitor. In use, these concentrates are diluted in water and
normally applied as a spray to the area to be treated. The amount
of active ingredient may range from 0.5% to 95% of the
concentrate.
[0211] Wettable powders are in the form of finely divided particles
which disperse readily in water or other liquid carriers. The
particles contain the active ingredient retained in a solid matrix.
Typical solid matrices include fuller's earth, kaolin clays,
silicas and other readily wet organic or inorganic solids. Wettable
powders normally contain from 5% to 95% of the active ingredient
plus a small amount of wetting, dispersing or emulsifying
agent.
[0212] Emulsifiable concentrates are homogeneous liquid
compositions dispersible in water or other liquid and may consist
entirely of the active compound with a liquid or solid emulsifying
agent, or may also contain a liquid carrier, such as xylene, heavy
aromatic naphthas, isophorone and other non-volatile organic
solvents. In use, these concentrates are dispersed in water or
other liquid and normally applied as a spray to the area to be
treated. The amount of active ingredient may range from 0.5% to 95%
of the concentrate.
[0213] Granular formulations include both extrudates and relatively
coarse particles and are usually applied without dilution to the
area in treatment is required. Typical carriers for granular
formulations include sand, fuller's earth, attapulgite clay,
bentonite clays, montmorillonite clay, vermiculite, perlite,
calcium carbonate, brick, pumice, pyrophyllite, kaolin, dolomite,
plaster, wood flour, ground corn cobs, ground peanut hulls, sugars,
sodium chloride, sodium sulphate, sodium silicate, sodium borate,
magnesia, mica, iron oxide, zinc oxide, titanium oxide, antimony
oxide, cryolite, gypsum, diatomaceous earth, calcium sulphate and
other organic or inorganic materials which absorb or which can be
coated with the active compound. Granular formulations normally
contain 5% to 25% of active ingredients which may include
surface-active agents such as heavy aromatic naphthas, kerosene and
other petroleum fractions, or vegetable oils; and/or stickers such
as dextrins, glue or synthetic resins.
[0214] Dusts are free-flowing admixtures of the active ingredient
with finely divided solids such as talc, clays, flours and other
organic and inorganic solids which act as dispersants and
carriers.
[0215] Microcapsules are typically droplets or granules of the
active ingredient enclosed in an inert porous shell which allows
escape of the enclosed material to the surroundings at controlled
rates. Encapsulated droplets are typically 1 to 50 microns in
diameter. The enclosed liquid typically constitutes 50 to 95% of
the weight of the capsule and may include solvent in addition to
the active compound. Encapsulated granules are generally porous
granules with porous membranes sealing the granule pore openings,
retaining the active species in liquid form inside the granule
pores. Granules typically range from 1 millimetre to 1 centimetre
and preferably 1 to 2 millimetres in diameter. Granules are formed
by extrusion, agglomeration or prilling, or are naturally
occurring. Examples of such materials are vermiculite, sintered
clay, kaolin, attapulgite clay, sawdust and granular carbon. Shell
or membrane materials include natural and synthetic rubbers,
cellulosic materials, styrene-butadiene copolymers,
polyacrylonitriles, polyacrylates, polyesters, polyamides,
polyureas, polyurethanes and starch xanthates.
[0216] Other useful formulations for agrochemical applications
include simple solutions of the active ingredient in a solvent in
which it is completely soluble at the desired concentration, such
as acetone, alkylated naphthalenes, xylene and other organic
solvents. Pressurised sprayers, wherein the active ingredient is
dispersed in finely-divided form as a result of vaporisation of a
low boiling dispersant solvent carrier, may also be used.
[0217] Suitable agricultural adjuvants and carriers that are useful
in formulating the compositions of the invention in the formulation
types described above are well known to those skilled in the
art.
[0218] Liquid carriers that can be employed include, for example,
water, toluene, xylene, petroleum naphtha, crop oil, acetone,
methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile,
acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane,
cyclohexanol, alkyl acetates, diacetonalcohol, 1,2-dichloropropane,
diethanolamine, p-diethylbenzene, diethylene glycol, diethylene
glycol abietate, diethylene glycol butyl ether, diethylene glycol
ethyl ether, diethylene glycol methyl ether, N,N-dimethyl
formamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol,
dipropylene glycol methyl ether, dipropylene glycol dibenzoate,
diproxitol, alkyl pyrrolidinone, ethyl acetate, 2-ethyl hexanol,
ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, alpha
pinene, d-limonene, ethylene glycol, ethylene glycol butyl ether,
ethylene glycol methyl ether, gamma-butyrolactone, glycerol,
glycerol diacetate, glycerol monoacetate, glycerol triacetate,
hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate,
isooctane, isophorone, isopropyl benzene, isopropyl myristate,
lactic acid, laurylamine, mesityl oxide, methoxy-propanol, methyl
isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl
octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane,
n-octylamine, octadecanoic acid, octyl amine acetate, oleic acid,
oleylamine, o-xylene, phenol, polyethylene glycol (PEG400),
propionic acid, propylene glycol, propylene glycol monomethyl
ether, p-xylene, toluene, triethyl phosphate, triethylene glycol,
xylene sulfonic acid, paraffin, mineral oil, trichloroethylene,
perchloroethylene, ethyl acetate, amyl acetate, butyl acetate,
methanol, ethanol, isopropanol, and higher molecular weight
alcohols such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol,
octanol, etc., ethylene glycol, propylene glycol, glycerine and
N-methyl-2-pyrrolidinone. Water is generally the carrier of choice
for the dilution of concentrates.
[0219] Suitable solid carriers include, for example, talc, titanium
dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr,
chalk, diatomaxeous earth, lime, calcium carbonate, bentonite clay,
fuller's earth, cotton seed hulls, wheat flour, soybean flour,
pumice, wood flour, walnut shell flour and lignin.
[0220] A broad range of surface-active agents are advantageously
employed in both said liquid and solid compositions, especially
those designed to be diluted with carrier before application. These
agents, when used, normally comprise from 0.1% to 15% by weight of
the formulation. They can be anionic, cationic, non-ionic or
polymeric in character and can be employed as emulsifying agents,
wetting agents, suspending agents or for other purposes. Typical
surface active agents include salts of alkyl sulfates, such as
diethanolammonium lauryl sulphate; alkylarylsulfonate salts, such
as calcium dodecylbenzenesulfonate; alkylphenol-alkylene oxide
addition products, such as nonylphenol-C.sub. 18 ethoxylate;
alcohol-alkylene oxide addition products, such as tridecyl
alcohol-C.sub. 16 ethoxylate; soaps, such as sodium stearate;
alkylnaphthalenesulfonate salts, such as sodium
dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate
salts, such as sodium di(2-ethylhexyl) sulfosuccinate; sorbitol
esters, such as sorbitol oleate; quaternary amines, such as lauryl
trimethylammonium chloride; polyethylene glycol esters of fatty
acids, such as polyethylene glycol stearate; block copolymers of
ethylene oxide and propylene oxide; and salts of mono and dialkyl
phosphate esters.
[0221] Other adjuvants commonly utilized in agricultural
compositions include crystallisation inhibitors, viscosity
modifiers, suspending agents, spray droplet modifiers, pigments,
antioxidants, foaming agents, anti-foaming agents, light-blocking
agents, compatibilizing agents, antifoam agents, sequestering
agents, neutralising agents and buffers, corrosion inhibitors,
dyes, odorants, spreading agents, penetration aids, micronutrients,
emollients, lubricants and sticking agents.
[0222] In addition, further, other biocidally active ingredients or
compositions may be combined with the compound of formula (I) and
used in the methods of the invention and applied simultaneously or
sequentially with the compound of formula (I). When applied
simultaneously, these further active ingredients may be formulated
together with the compound of formula (I) or mixed in, for example,
the spray tank. These further biocidally active ingredients may be
fungicides, herbicides, insecticides, bactericides, acaricides,
nematicides and/or plant growth regulators.
[0223] Accordingly, in one aspect, the present invention provides a
composition comprising a compound of formula (I), which is compound
175 of Table 1, and (i) a fungicide, (ii) a herbicide, (iii) an
insecticide, (iv) a bactericide, (v) an acaricide, (vi) a
nematicide and/or (vii) a plant growth regulator.
[0224] Additionally, the present invention provides for the use of
a composition in the methods of the present invention, said
composition comprising a compound of formula (I), which is compound
175 of Table 1, and (i) a fungicide, (ii) a herbicide, (iii) an
insecticide, (iv) a bactericide, (v) an acaricide, (vi) a
nematicide and/or (vii) a plant growth regulator.
[0225] In a further aspect, the present invention provides a
composition comprising a compound of formula (I), which is the
(R)-enantiomer of formula (R)-(I) and (i) a fungicide, (ii) a
herbicide, (iii) an insecticide, (iv) a bactericide, (v) an
acaricide, (vi) a nematicide and/or (vii) a plant growth
regulator.
[0226] Additionally, the present invention provides for the use of
a composition in the methods of the present invention, said
composition comprising a compound of formula (I), which is the
(R)-enantiomer of formula (R)-(I), and (i) a fungicide, (ii) a
herbicide, (iii) an insecticide, (iv) a bactericide, (v) an
acaricide, (vi) a nematicide and/or (vii) a plant growth
regulator.
[0227] In a further aspect, the present invention provides a
composition comprising a compound of formula (I), which is the
(S)-enantiomer of formula (S)-(I) and (i) a fungicide, (ii) a
herbicide, (iii) an insecticide, (iv) a bactericide, (v) an
acaricide, (vi) a nematicide and/or (vii) a plant growth
regulator.
[0228] Additionally, the present invention provides for the use of
a composition in the methods of the present invention, said
composition comprising a compound of formula (I), which is the
(S)-enantiomer of formula (S)-(I), and (i) a fungicide, (ii) a
herbicide, (iii) an insecticide, (iv) a bactericide, (v) an
acaricide, (vi) a nematicide and/or (vii) a plant growth
regulator.
[0229] In addition, the compounds of the invention may also be
applied with one or more systemically acquired resistance inducers
("SAR" inducer). SAR inducers are known and described in, for
example, U.S. Pat. No. 6,919,298 and include, for example,
salicylates and the commercial SAR inducer
acibenzolar-S-methyl.
[0230] In particular, compositions encompassed by the present
invention include, for example, compositions comprising a compound
of formula (I) and acibenzolar (CGA245704), a compound of formula
(I) and ancymidol, a compound of formula (I) and alanycarb, a
compound of formula (I) and aldimorph, a compound of formula (I)
and amisulbrom, a compound of formula (I) and anilazine, a compound
of formula (I) and azaconazole, a compound of formula (I) and
azoxystrobin, a compound of formula (I) and benalaxyl, a compound
of formula (I) and benthiavalicarb, a compound of formula (I) and
benomyl, a compound of formula (I) and biloxazol, a compound of
formula (I) and bitertanol, a compound of formula (I) and bixafen,
a compound of formula (I) and blasticidin S, a compound of formula
(I) and boscalid, a compound of formula (I) and bromuconazole, a
compound of formula (I) and bupirimate, a compound of formula (I)
and captafol, a compound of formula (I) and captan, a compound of
formula (I) and carbendazim, a compound of formula (I) and
carbendazim, a compound of formula (I) and chlorhydrate, a compound
of formula (I) and carboxin, a compound of formula (I) and
carpropamid, a compound of formula (I) and carvone, a compound of
formula (I) and CGA41396, a compound of formula (I) and CGA41397, a
compound of formula (I) and chinomethionate, a compound of formula
(I) and chloroneb, a compound of formula (I) and chlorothalonil, a
compound of formula (I) and chlorozolinate, a compound of formula
(I) and clozylacon, a compound of formula (I) and copper containing
compounds such as copper oxychloride, copper oxyquinolate, copper
sulphate, copper tallate and Bordeaux mixture, a compound of
formula (I) and cyflufenamid, a compound of formula (I) and
cymoxanil, a compound of formula (I) and cyproconazole, a compound
of formula (I) and cyprodinil, a compound of formula (I) and
debacarb, a compound of formula (I) and di-2-pyridyl disulphide
1,1'-dioxide, a compound of formula (I) and dichlofluanid, a
compound of formula (I) and diclomezine, a compound of formula (I)
and dichlozoline, a compound of formula (I) and dichlone, a
compound of formula (I) and dicloran, a compound of formula (I) and
diclocymet, a compound of formula (I) and diethofencarb, a compound
of formula (I) and difenoconazole, a compound of formula (I) and
difenzoquat, a compound of formula (I) and diflumetorim, a compound
of formula (I) and O,O-di-iso-propyl-S-benzyl thiophosphate, a
compound of formula (I) and dimefluazole, a compound of formula (I)
and dimetconazole, a compound of formula (I) and dimethomorph, a
compound of formula (I) and dimethirimol, a compound of formula (I)
and dimoxystrobin, a compound of formula (I) and diniconazole, a
compound of formula (I) and dinocap, a compound of formula (I) and
dithianon, a compound of formula (I) and dodecyl dimethyl ammonium
chloride, a compound of formula (I) and dodemorph, a compound of
formula (I) and dodine, a compound of formula (I) and doguadine, a
compound of formula (I) and edifenphos, a compound of formula (I)
and enestrobin, a compound of formula (I) and epoxiconazole, a
compound of formula (I) and ethaboxam, a compound of formula (I)
and ethirimol, a compound of formula (I) and etridiazole, a
compound of formula (I) and famoxadone, a compound of formula (I)
and fenamidone (RPA407213), a compound of formula (I) and
fenarimol, a compound of formula (I) and fenbuconazole, a compound
of formula (I) and fenfuram, a compound of formula (I) and
fenhexamid (KBR2738), a compound of formula (I) and fenoxanil, a
compound of formula (I) and fenpiclonil, a compound of formula (I)
and fenpropidin, a compound of formula (I) and fenpropimorph, a
compound of formula (I) and fentin acetate, a compound of formula
(I) and fentin hydroxide, a compound of formula (I) and ferbam, a
compound of formula (I) and ferimzone, a compound of formula (I)
and fluazinam, a compound of formula (I) and fluopicolide, a
compound of formula (I) and fludioxonil, a compound of formula (I)
and fluoxastrobin, a compound of formula (I) and flumetover, a
compound of formula (I) and SYP-L190 (flumorph), a compound of
formula (I) and fluopyram, a compound of formula (I) and
fluoroimide, a compound of formula (I) and fluquinconazole, a
compound of formula (I) and flusilazole, a compound of formula (I)
and flusulfamide, a compound of formula (I) and flutolanil, a
compound of formula (I) and flutriafol, a compound of formula (I)
and folpet, a compound of formula (I) and fosetyl-aluminium, a
compound of formula (I) and fuberidazole, a compound of formula (I)
and furalaxyl, a compound of formula (I) and furametpyr, a compound
of formula (I) and guazatine, a compound of formula (I) and
hexaconazole, a compound of formula (I) and hydroxyisoxazole, a
compound of formula (I) and hymexazole, a compound of formula (I)
and IKF-916 (cyazofamid), a compound of formula (I) and imazalil, a
compound of formula (I) and imibenconazole, a compound of formula
(I) and iminoctadine, a compound of formula (I) and iminoctadine
triacetate, a compound of formula (I) and ipconazole, a compound of
formula (I) and iprobenfos, a compound of formula (I) and
iprodione, a compound of formula (I) and iprovalicarb (SZX0722), a
compound of formula (I) and isopropanyl butyl carbamate, a compound
of formula (I) and isoprothiolane, a compound of formula (I) and
kasugamycin, a compound of formula (I) and kresoxim-methyl, a
compound of formula (I) and LY186054, a compound of formula (I) and
LY211795, a compound of formula (I) and LY248908, a compound of
formula (I) and maneb, a compound of formula (I) and mancopper, a
compound of formula (I) and man-cozeb, a compound of formula (I)
and mandipropamid, a compound of formula (I) and mefenoxam, a
compound of formula (I) and mepanipyrim, a compound of formula (I)
and mepronil, a compound of formula (I) and metalaxyl, a compound
of formula (I) and metconazole, a compound of formula (I) and
methasulfocarb, a compound of formula (I) and metiram, a compound
of formula (I) and metiram-zinc, a compound of formula (I) and
metominostrobin, a compound of formula (I) and metrafenone, a
compound of formula (I) and myclobutanil, a compound of formula (I)
and myclozoline, a compound of formula (I) and neoasozin, a
compound of formula (I) and nickel dimethyldithiocarbamate, a
compound of formula (I) and nitrothal-isopropyl, a compound of
formula (I) and nuarimol, a compound of formula (I) and ofurace, a
compound of formula (I) and organomercury compounds, a compound of
formula (I) and orysastrobin, a compound of formula (I) and
oxadixyl, a compound of formula (I) and oxasulfuron, a compound of
formula (I) and oxine-copper, a compound of formula (I) and
oxolinic acid, a compound of formula (I) and oxpoconazole, a
compound of formula (I) and oxycarboxin, a compound of formula (I)
and pefurazoate, a compound of formula (I) and penconazole, a
compound of formula (I) and pencycuron, a compound of formula (I)
and penthiopyrad, a compound of formula (I) and phenazin oxide, a
compound of formula (I) and phosdiphen, a compound of formula (I)
and phosphorus acids, a compound of formula (I) and phthalide, a
compound of formula (I) and picoxystrobin (ZA1963), a compound of
formula (I) and polyoxin D, a compound of formula (I) and polyram,
a compound of formula (I) and probenazole, a compound of formula
(I) and prochloraz, a compound of formula (I) and procymidone, a
compound of formula (I) and propamocarb, a compound of formula (I)
and propiconazole, a compound of formula (I) and propineb, a
compound of formula (I) and propionic acid, a compound of formula
(I) and proquinazid, a compound of formula (I) and prothioconazole,
a compound of formula (I) and pyraclostrobin, a compound of formula
(I) and pyrazophos, a compound of formula (I) and pyribencarb, a
compound of formula (I) and pyrifenox, a compound of formula (I)
and pyrimethanil, a compound of formula (I) and pyroquilon, a
compound of formula (I) and pyroxyfur, a compound of formula (I)
and pyrrolnitrin, a compound of formula (I) and quaternary ammonium
compounds, a compound of formula (I) and quinomethionate, a
compound of formula (I) and quinoxyfen, a compound of formula (I)
and quintozene, a compound of formula (I) and silthiofam, a
compound of formula (I) and simeconazole, a compound of formula (I)
and sipconazole (F-155), a compound of formula (I) and sodium
pentachlorophenate, a compound of formula (I) and spiroxamine, a
compound of formula (I) and streptomycin, a compound of formula (I)
and sulphur, a compound of formula (I) and tebuconazole, a compound
of formula (I) and tecloftalam, a compound of formula (I) and
tecnazene, a compound of formula (I) and tetraconazole, a compound
of formula (I) and thiabendazole, a compound of formula (I) and
thifluzamid, a compound of formula (I) and
2-(thiocyanomethylthio)benzothiazole, a compound of formula (I) and
thiophanate-methyl, a compound of formula (I) and thiram, a
compound of formula (I) and tiadinil, a compound of formula (I) and
timibenconazole, a compound of formula (I) and tolclofos-methyl, a
compound of formula (I) and tolylfluanid, a compound of formula (I)
and triadimefon, a compound of formula (I) and triadimenol, a
compound of formula (I) and triazbutil, a compound of formula (I)
and triazoxide, a compound of formula (I) and tricyclazole, a
compound of formula (I) and tridemorph, a compound of formula (I)
and trifloxystrobin (CGA279202), a compound of formula (I) and
triforine, a compound of formula (I) and triflumizole, a compound
of formula (I) and triticonazole, a compound of formula (I) and
validamycin A, a compound of formula (I) and vapam, a compound of
formula (I) and valiphenal a compound of formula (I) and
vinclozolin, a compound of formula (I) and zineb, a compound of
formula (I) and ziram, a compound of formula (I) and zoxamide, a
compound of formula (I) and
3-[5-(4-chlorophenyl)-2,3-dimethylisoxazolidin-3-yl]pyridine, a
compound of formula (I) and
5-chloro-7-(4-methylpiperidine-1-yl)-6-(2,4,6-trifluorophenyl)[1,2,4]tria-
zolo[1,5-a]pyrimidine and a compound of formula (I) and
N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methyl-benzsulfonamide.
[0231] Compounds of formula (I) may be prepared using the methods
below.
[0232] Compositions of generic structure Ia wherein R and
R.sub.4.dbd.H may be prepared by the [3+2]-cycloaddition of an
acetylenethiolate anion II and an acetylenic ketone III to give
thiophene ketone IV which upon reduction provides the corresponding
thiophene alcohol Ia (see L. S. Rodinova, M. L. Petrov, and A. A.
Petrov, Zhurnal Organicheskoi Khimii 1981, 17(10), 2071-2075 for a
related thiophene synthesis):
##STR00004##
[0233] The [3+2]-cycloaddition reaction is carried out by
preforming the acetylenethiolate in an inert solvent such as THF
(tetrahydrofuran) at low temperature, preferably -78 .degree., and
then adding it to a solution of the acetylenic ketone III in an
inert solvent or solvent mixture, such as THF and acetonitrile, at
temperatures ranging from 0.degree. C. to -20.degree. C. The
acetylenethiolate II is prepared from the reaction of sulfur with a
lithium salt (VI) of a terminal acetylene V (H. G. Raubenheimer, G.
J. Kruger, C. F. Marais, R. Otte, and J. T. Z. Hattingh,
Organometallics 1988, 7, 1853-1858) :
##STR00005##
[0234] Lithium acetylide VI is formed by the treatment of terminal
acetylene V with a strong base such as n-butyllithium in an inert
solvent such as THF at low temperature, preferably from -40.degree.
C. to -78.degree. C. Addition of sulfur to acetylide VI at low
temperature (-40.degree. C. to -78.degree. C.) and reaction for
1.5-3 hr gives the acetylenethiolate II. Reduction of thiophene
ketone IV is effected with a reducing agent such as LiAlH.sub.4 in
an inert solvent such as ether or THF, or NaBH.sub.4 in a solvent
such as ethanol at temperatures in the range of 0.degree. C. to
20.degree. C.
[0235] Alternatively, the Heck reaction may be employed to arylate
activated thiophenes that are intermediates in the synthesis of la
when R.sub.1 and R.sub.3 are aryl (L. Lavenot, C. Gozzi, K. IIg, I
Orlova, V. Penalva, and M. Lemaire, Journal of Organometallic Chem.
1998, 567, 49-55).
[0236] Thus, thiophene-3-carboxaldehyde VII may be selectively
arylated with aryl iodide R.sub.3I in the presence of a transition
metal catalyst such as a palladium(II) catalyst to give a
2-arylated intermediate VIII. A second palladium-catalyzed
arylation with another aryl iodode R.sub.1I then gives the
2,4-diarylthiophen-3-carboxaldehyde IX. Treatment of IX with
##STR00006##
an organometallic reagent R.sub.2M produces the compositions of
generic structure Ia (R and R.sub.4.dbd.H).
##STR00007##
[0237] The Heck reaction is typically carried out in solvents such
as acetonitrile or water, or in mixtures of the two, at
temperatures in the range of 20-80.degree. C. for 4-72 hrs. The
typical palladium catalysts are palladium chloride, usually used in
association with lithium chloride, or palladium acetate used with
tetra-n-butylammonium bromide with or without a phosphine such as
triphenylphosphine. The addition of the organometallic reagent
R.sub.2M is typically conducted in an inert solvent such as ether
or THF under N.sub.2 atmosphere at 0-20.degree. C. for 1-5 hrs. The
organometallic reagent may be an organolithium reagent, or
preferably an organomagnesium reagent.
[0238] Compositions of generic structure Ia wherein R.sub.4.dbd.H
may also be prepared by the Michael addition of a substituted
.alpha.-mercaptoketone X (R'.dbd.H) to acetylenic ketone III to
give the dihydrothienyl intermediate XI. Dehydration of XI to
thiophene XII and subsequent reduction of XII provides the
composition Ia (R.sub.4.dbd.H).
##STR00008##
[0239] The Michael addition is carried out by reaction of the
.alpha.-mercaptoketone X (R'.dbd.H) and the acetylenic ketone III
in the presence of a base, preferably an organic base such as
morpholine, and an inert solvent such as diethoxymethane at
elevated temperatures such as reflux temperature for 1-8hrs.
Alternatively, .alpha.-acetylthioketone X (R'.dbd.COCH.sub.3) may
be used in the Michael addition wherein the base such as morpholine
cleaves the thioester to the requisite .alpha.-mercaptoketone X
(R'.dbd.H) in situ.
[0240] Intermediate XI is efficiently dehydrated by treatment with
p-toluenesulfonic acid or acetic anhydride in toluene at elevated
temperatures (80-100.degree. C.) for 12-48 hrs. to produce the
thienyl ketone XII, reduction of which is accomplished as above
with a reducing agent such as LiAlH.sub.4 in an inert solvent such
as ether or THF, or NaBH.sub.4 in a solvent such as ethanol at
temperatures in the range of 0.degree. C. to 20.degree. C.
[0241] The .alpha.-acetylthioketones X (R'.dbd.COCH.sub.3) and
.alpha.-mercaptoketones X (R'.dbd.H) are readily available by
treating the corresponding .alpha.-bromoketones XIII with
thioacetic acid in a basic medium to give X (R'.dbd.COCH.sub.3),
which upon treatment with aqueous base (e.g., aqueous NaOH)
produces X (R'.dbd.H).
##STR00009##
[0242] The compositions lb may be prepared from XIII (R.dbd.H) or
its chloro analog by reaction with the .beta.-ketoester XIV under
base catalyzed conditions to give the dihydrofuran XV (see F.
Feist, Chem, Ber. 1902, 35, 1537-44), dehydration of which produces
the furan XVI. This dehydration is efficiently effected by
treatment of XV with p-toluenesulfonic acid or acetic anhydride in
toluene at elevated temperatures (80-100.degree. C.) for 12-48 hrs.
Reduction of furyl ester XVI to furyl alcohol XVII and subsequent
oxidation to furylcarboxaldehyde XVIII followed by addition of
organometallic reagent R.sub.2Li or R.sub.2MgX' gives compound Ib
(R.sub.4.dbd.H) The reduction of XVI to alcohol XVII is
accomplished using a hydride reagent such as LiAlH.sub.4 or
diisobutylaluminum hydride (DIBAL) in an inert solvent such as
ether of THF. Oxidation of XVII to aldehyde my be effected with
reagents including activated MnO.sub.2, o-iodosobenzoic acid (IBX)
in DMSO, or CrO.sub.3/pyr in inert solvents such as
dichloromethane. The addition of the organometallic reagent to
aldehyde XVIII is typically conducted in an inert solvent such as
ether or THF under N.sub.2 atmosphere at 0-20.degree. C. for 1-5
hrs. The organometallic reagent may be an organolithium reagent, or
preferably an organomagnesium reagent.
##STR00010##
[0243] Alternatively, furyl ester XVI may be hydrolyzed to furoic
acid XIX under aqueous basic conditions such as aqueous NaOH or
LiOH. Conversion of the acid XIX to the Weinreb amide XX may be
accomplished by coupling XIX and N,O-hydroxylamine hydrochloride
using 1-hydroxybenzotriazole (HOBT) and diisopropylcarbodiimide
(DIC) in the presence of diisopropylethylamine (DIEA) in an inert
solvent such as dichloromethane (DCM). Addition of organometallic
agent R.sub.2MgX' to XX in an inert solvent such as ether or THF
under N.sub.2 atmosphere at 0-20.degree. C. for 1-5 hrs gives the
ketone XXI, reduction of which is accomplished as above with a
reducing agent such as LiAlH.sub.4 in an inert solvent such as
ether or THF, or NaBH.sub.4 in a solvent such as ethanol at
temperatures in the range of 0.degree. C. to 20.degree. C. to
produce compound Ib (R.sub.4.dbd.H).
##STR00011##
[0244] The compositions Ic may be prepared using an approach
similar to that employed for the thiophenes Ia, i.e., but adding
.alpha.-aminoketones XXII to the alkynylketone III in the Michael
addition. Dehydration of dihydropyrrole XXIII to yield pyrrolyl
ketone XXIV and subsequent reduction with LiAlH.sub.4 or NaBH.sub.4
gives Ic (R.sub.4.dbd.H). Reaction conditions similar to those used
to prepare the aforementioned furans lb may be employed.
##STR00012##
[0245] Alternatively, condensation of .alpha.-aminoketone XXII and
.beta.-ketoester XIV under basic conditions gives the
dihydropyrrole XXV (see L. Knorr, Chem. Ber. 1884, 17, 1635; A. H.
Corwin, Heterocyclic Compounds, 1950, 1, 287), dehydration of which
produces the pyrrolyl ester XXVI. Alkylation of XXVI with R.sub.5I
yields the N-substituted pyrrolyl ester XXVVII. In reactions
similar to those described for the furan system, ester XXVII is
converted to compound Ic (R.sub.4.dbd.H).
##STR00013##
[0246] Ester XXVII may also be hydrolyzed to its corresponding acid
XXX and converted to its Weinreb amide XXXI as above. Addition of
organometallic agent R.sub.2MgX' gives the ketone XXXII, reduction
of which produces compound Ic (R.sub.4.dbd.H).
##STR00014##
[0247] The invention is illustrated by the following Examples.
EXAMPLE 1
2,4-Bis-(3-chlorophenyl)-3-[(3-pyridyl)hydroxymethyll thiophene
(Compound 1)
[0248] To a solution of 273 mg (2.0 mmol) of
3-chlorophenylacetylene in 4 mL of anhydrous THF under a N.sub.2
atmosphere at -78.degree. C. was added 1.25 mL (2.0 mmol) of a 1.6M
solution of n-butyllithium in hexane. The solution was stirred for
1.5 hr, and then 64 mg (2.0 mmol) of sulfur was added. After an
additional 1.5 hr at -78.degree. C., the red solution was warmed to
room temperature and added to a solution of 400 mg (1.66 mmol) of
3-(3-chlorophenyI)-1-(3-pyridyl)-2-propyn-1-one in 4 mL of THF and
1 mL of acetonitrile. The reaction solution was stirred for 2 hr at
room temperature, and was then poured into water. The aqueous layer
was extracted several times with ether. The combined ether extracts
were washed with saturated sodium chloride and dried over magnesium
sulfate. The drying agent was filtered off, and the ether was
removed by rotoevaporation. The crude product was purified by flash
column chromatography on silica gel to give 185 mg (0.45 mmol) of
2,4-bis-(3-chlorophenyl)-3-[(3-pyridyl)carbonyl]thiophene.
[0249] .sup.1H NMR (CDCl.sub.3): 7.95 (d of q, 1), 8.56 (d of d,
1), and 8.73 ppm (d, 1). MS m/z 410.0 (M+H).
[0250] To a solution of 32 mg (0.08 mmol) of
2,4-bis-(3-chlorophenyl)-3-[(3-pyridyl)carbonyl]thiophene in 2 mL
of anhydrous THF was added 10 mg (0.26 mmol) of lithium aluminum
hydride. The mixture was stirred at 0.degree. C. for 0.5 hr and was
then diluted with ethyl acetate. The ethyl acetate solution was
washed with water and dried over magnesium sulfate. The drying
agent was filtered off, and the solvent was removed by
rotoevaporation. The crude product was purified by preparative thin
layer chromatography (prep TLC) to give 30 mg (0.073 mmol)
2,4-bis-(3-chlorophenyl)-3-[(3-pyridyl)hydroxy-methyl]thiophene
(Compound 1) in 91% yield. .sup.1H NMR (CDCl.sub.3): 5.98 (br s,
1), 7.44 (br d, 1), 8.08 (br s, 1), and 8.21 ppm (br d, 1).
[0251] MS m/z 412.0 (M+H).
EXAMPLE 2
4-(4-Chlorophenyl)-2-(5-chloro-2-thienyl)-3-[(3-pyridyl)hydroxymethyl]thio-
phene (Compound 4)
[0252] To a solution of 137 mg (1.0 mmol) of
4-chlorophenylacetylene in 2 mL of anhydrous THF under a N.sub.2
atmosphere at -78.degree. C. was added 0.063 mL (1.0 mmol) of a
1.6M solution of n-butyllithium in hexane. The solution was stirred
for 1.5 hr, and then 32 mg (1.0 mmol) of sulfur was added. After an
additional 1.5 hr at -78.degree. C., the red solution was warmed to
-10.degree. C. One half of the solution was added to a solution of
99 mg (0.39 mmol) of
3-(5-chloro-2-thienyl)-1-(3-pyridyl)-2-propyn-1-one in 2 mL of THF
and 0.5 mL of acetonitrile. After an additional 0.5 hr, the
reaction was diluted with ethyl acetate. The ethyl acetate solution
was washed with saturated sodium chloride and dried over magnesium
sulfate. The drying agent was filtered off, and the solvent was
removed by rotoevaporation. The crude product was purified by flash
column chromatography on silica gel to give 70 mg (0.17 mmol) of
4-(4-chlorophenyl)-2-(5-chloro-2-thienyl)-3-[(3-pyridyl)carbonyl]-thiophe-
ne. .sup.1H NMR (CDCl.sub.3): 6.76 (d, 1), 6.95 (d, 1), 7.96 (br d,
1), 8.59 (br d, 1), and 8.73ppm (br s, 1). MS m/z 415.9 (M+H).
[0253] To a solution of 70 mg (0.17 mmol) of
4-(4-chlorophenyl)-2-(5-chloro-2-thienyl)-3-[(3-pyridyl)carbonyl]thiophen-
e in 3 mL of anhydrous THF was added 13 mg (0.34 mmol) of lithium
aluminum hydride. The mixture was stirred at 0.degree. C. for 0.5
hr and was then diluted with ethyl acetate and a minimum amount of
water to decompose the LiAlH.sub.4. The ethyl acetate solution was
decanted off and evaporated to dryness. The crude product was
purified by preparative thin layer chromatography (prep TLC) to
give 60 mg (0.14 mmol)
4-(4-chlorophenyl)-2-(5-chloro-2-thienyl)-3-[(3-pyridyl)hydroxymethyl]thi-
ophene (Compound 4) in 84% yield. .sup.1H NMR (CDCl.sub.3): 6.08
(br s, 1), 6.81 (d, 1), 6.87 (d, 1), 7.39 (br d, 1), 8.18 (br s,
1), and 8.30 ppm (br d, 1). MS m/z 417.9 (M+H).
EXAMPLE 3
3-(3-Chlorophenyl)-1-(3-pyridyl)-2-propyn-1-one
[0254] To a solution of 5.0 gm (36.6 mmol) of
3-chlorophenylacetylene in 30 mL of anhydrous THF under a N.sub.2
atmosphere at -78.degree. C. was added 23 mL (36.6 mmol) of a 1.6M
solution of n-butyllithium in hexane. The solution was stirred for
2 hr, and then a solution of 3.9 gm (36.6 mmol) of
pyridine-3-carboxaldehyde in 5 mL of THF was added. The reaction
mixture was stirred at -78.degree. C. for 2 hr and then was poured
into ice water. The solution was extracted several times with
ether. The combined ether extracts were washed twice with aqueous
sodium bisulfite solution to remove any remaining aldehyde, then
with water, and finally with saturated sodium chloride solution.
The ether layer was dried over magnesium sulfate. The drying agent
was filtered off, and the ether was removed by rotoevaporation to
give 8.5 gm (34.7 mmol) of oily product,
3-(3-chlorophenyl)-1-(3-pyridyl)-2-propyn-1-ol.
[0255] The 8.5 gm of 3-(3-chlorophenyl)-1-(3-pyridyl)-2-propyn-1-ol
in 50 mL of DMSO was added 10.7 gm (38 mmol) of o-iodosobenzoic
acid (IBX) in portions. The resulting mixture was stirred for 2 hr
at room temperature, and then was diluted with ethyl acetate and
water. The solution was filtered and the filtrate was extracted
with ethyl acetate. The combined ethyl acetate extracts were washed
consecutively with water and saturated sodium chloride solution.
The ethyl acetate layer was dried over magnesium sulfate, the
drying agent was filtered off, and the solvent was removed by
rotoevaporation to give 6.84 gm (28.3 mmol) of brown solid
3-(3-chlorophenyl)-1-(3-pyridyl)-2-propyn-1-one in an overall 77%
crude yield. 1H NMR (CDCl.sub.3): 8.40 (d of m, 1), 8.84 (d of d,
1), and 9.40 ppm (d, 1). MS m/z 242.0 (M+H).
EXAMPLE 4
2,4-Bis-(2,4-difluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene
[0256] To a suspension of 1.54 gm (11.1 mmol) of potassium
carbonate, 1.44 gm (4.46 mmol) of tetrabutylammonium bromide, and
0.05 gm (0.22 mmol) of palladium(II) diacetate in 1.1 mL of
acetonitrile/H.sub.2O (9:1) under a N.sub.2 atmosphere was added
1.83 gm (6.69 mmol) of 2,4-difluoro-1-iodobenzene and 0.50 gm (4.46
mmol) of thiophene-3-carboxaldehyde. The mixture was heated at
80.degree. C. for 3 days, and then diluted with ethyl acetate. The
ethyl acetate solution was washed with water and dried over
magnesium sulfate. The drying agent was filtered off, and the
solvent was removed by rotoevaporation to give a red-brown solid
which was purified by flash column chromatography on silica gel to
give a mixture of 2-(2,4-difluorophenyl)thiophene-3-carboxaldehyde
and 2,4-bis-(2,4-difluorophenyl)thiophene-3-carboxaldehyde which
was used in the next reaction.
[0257] To a solution of 0.41 gm (2.6 mmol) of 3-bromopyridine in
1.7 mL of anhydrous THF under a N.sub.2 atmosphere was added 1.3 mL
(2.6 mmol) of 2M i-propylmagnesium chloride in THF. After 2 hr of
stirring, 0.39 gm of the above mixture of aldehydes in 2 mL of THF
was added. After another 2 hrs, the reaction was diluted with
water, and ethyl acetate was added to extract the products. The
ethyl acetate extract was washed with saturated sodium chloride and
dried over magnesium sulfate. The drying agent was filtered off,
and the solvent was removed by rotoevaporation to give a mixture of
products that were purified by preparative HPLC. From this
reaction, 167 mg of
2-(2,4-difluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene and 96
mg of the desired
2,4-bis-(2,4-difluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene
were isolated. For the latter, .sup.1H NMR (CDCl.sub.3): 7.67 (br d
of t, 1), 8.55 (d of d, 1), and 8.49 ppm (br d, 1). MS m/z 416.0
(M+H).
EXAMPLE 5
2-(3-Chlorophenyl)-4,5-dimethyl-4-hydroxy-3-[(3-pyridyl)carbonyl]-4,5-dihy-
drothiophene
[0258] A solution of 0.20 gm (0.83 mmol) of
3-(3-chlorophenyl)-1-(3-pyridyl)-2-propyn-1-one, 0.10 gm (0.99
mmol) of 3-mercapto-2-butanone, and 0.072 mL (0.83 mmol) of
morpholine in 3 mL of diethoxymethane was heated to reflux under a
N.sub.2 atmosphere for 8 hrs. The reaction mixture was diluted with
ethyl acetate, and the organic solution was washed with saturated
sodium chloride solution. The ethyl acetate layer was dried over
magnesium sulfate, the drying agent was filtered off, and the
solvent was removed by rotoevaporation. The crude product was
purified by silica gel column chromatography to yield 0.18 gm (0.53
mmol) of
2-(3-chlorophenyl)-4,5-dimethyl-4-hydroxy-3-[(3-pyridyl)carbonyl]-4,5-dih-
ydrothiophene as a mixture of two isomers. .sup.1H NMR
(CDCl.sub.3): 1.56 (d,3), 1.64 (s, 3), 3.80 (t, 1), 7.82 (d of m,
1), 8.45 (d of d, 1), and 8.64 ppm (d, 1). MS m/z 346.0 (M+H).
EXAMPLE 6
2-(3-Chlorophenyl)-4,5-dimethyl-3-[(3-pyridyl)hydroxymethyl]thiophene
(Compound 55)
[0259] A mixture of 0.050 gm (0.14 mmol) of
2-(3-chlorophenyl)-4,5-dimethyl-4-hydroxy-3-[(3-pyridyl)carbonyl]-4,5-dih-
ydrothiophene as a mixture of two isomers and 0.024 mL of acetic
anhydride in 1.0 mL of toluene was placed in a sealed vial and
heated to 100.degree. C. in a sand bath for 48 hrs. The crude
reaction product was purified by preparative thin layer
chromatography (prep TLC) to give 0.037 gm (0.11 mmol) of
2-(3-chlorophenyl)-4,5-dimethyl-3-[3-pyridylcarbonyl]thiophene.
.sup.1H NMR (CDCl.sub.3): 2.09 (s, 3), 2.43 (s, 3), 8.00 (d of m,
1), 8.58 (d of d, 1), and 8.78 ppm (d, 1). MS m/z 328.0 (M+H).
[0260] To a solution of 0.037 gm (0.11 mmol) of the preceding
ketone,
2-(3-chlorophenyI)-4,5-dimethyl-3-[3-pyridylcarbonyl]thiophene, in
3 mL of diethyl ether was added 0.020 gm (0.45 mmol) of lithium
aluminum hydride. The mixture was stirred at 0.degree. C. for 0.5
hr and was then diluted with ethyl acetate and a minimum amount of
water to decompose the LiAlH.sub.4. The ethyl acetate solution was
decanted off and evaporated to dryness. The crude product was
purified by preparative thin layer chromatography (prep TLC) to
give 0.032 gm (0.10 mmol) of
2-(3-chlorophenyl)-4,5-dimethyl-3-[(3-pyridyl)hydroxymethyl]thiophene
(Compound 55). .sup.1H NMR (CDCl.sub.3): 1.82 (s, 3), 2.31 (s, 3),
7.64 (d of m, 1), 8.41 (d, of d, 1), and 8.46ppm (br s, 1). MS m/z
330.0.0 (M+H).
[0261] The compounds of formula (I) in Table 1 may be prepared by
analogous methods.
TABLE-US-00001 TABLE 1 Compound No. Structure Chemical Name 1
##STR00015## 2,4-Bis-(3-chlorophenyl)-3-
[(3-pyridyl)hydroxymethyl]- thiophene 2 ##STR00016##
4-(3-Chlorophenyl)-2-(5- chloro-2-thienyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 3 ##STR00017##
4-(3-Chlorophenyl)-2- (3,5-difluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 4 ##STR00018##
4-(4-Chlorophenyl)-2-(5- chloro-2-thienyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 5 ##STR00019##
4-(4-Chlorophenyl)-2- (3,5-difluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 6 ##STR00020##
2-(4-Chlorophenyl)-4- (2,4-difluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 7 ##STR00021##
4-(2,4-Difluorophenyl)-2- (1,1-dimethylethyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 8 ##STR00022##
2,4-Bis-(4-chlorophenyl)-3- [(3-pyridyl)hydroxymethyl]- thiophene 9
##STR00023## 4-(4-Chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]-
2-(2-thienyl)thiophene 10 ##STR00024## 2-(4-Chlorophenyl)-4-(5-
chloro-2-thienyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 11
##STR00025## 4-(5-Chloro-2-thienyl)- 2-(2,4-difluorophenyl)--
3-[(3-pyridyl) hydroxymethyl]-thiophene 12 ##STR00026##
2-(4-Chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]-
4-(2-thienyl)thiophene 13 ##STR00027## 2-(2,4-Difluorophenyl)-3-
[(3-pyridyl)hydroxymethyl]- 4-(2-thienyl)thiophene 14 ##STR00028##
2-(2,4-Difluorophenyl)-4- (5-methyl-2-thienyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 15 ##STR00029##
2-(4-Butylphenyl)-4-(5- methyl-2-thienyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 16 ##STR00030##
2,4-Bis-(2,4-Difluorophenyl)- 3-[(3-pyridyl)hydroxymethyl]-
thiophene 17 ##STR00031## 4-(4-Chlorophenyl)-2-
(2,4-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 18
##STR00032## 2,4-Bis-(2-trifluoro- methylphenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 19 ##STR00033##
2,4-Bis-(3-trifluoro- methylphenyl)-3-[(3- pyridyl)hydroxymethyl]-
thiophene 20 ##STR00034## 2,4-Bis-(4-trifluoro-
methylphenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 21
##STR00035## 4-(4-Chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]-
2-(3-thienyl)thiophene 22 ##STR00036## 2-(5-Bromo-2-thienyl)-4-
(4-chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 23
##STR00037## 4-(4-Chlorophenyl)-2-(5- methyl-2-thienyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 24 ##STR00038##
2-(3,5-Difluorophenyl)-3- [(3-pyridyl)hydroxymethyl]-
4-(3-thienyl)thiophene 25 ##STR00039## 2-(2,4-Difluorophenyl)-3-
[(3-pyridyl)hydroxymethyl]- 4-(3-thienyl)thiophene 26 ##STR00040##
2-(3,5-Difluorophenyl)-4-(4- fluorophenyl)-3-[(3-pyridyl)
hydroxymethyl]-thiophene 27 ##STR00041##
2-(2,4-Difluorophenyl)-4-(4- fluorophenyl)-3-[(3-pyridyl)
hydroxymethyl]-thiophene 28 ##STR00042## 2-(4-Chlorophenyl)-3-[(3-
pyridyl)hydroxymethyl]-4- (3-thienyl)thiophene 29 ##STR00043##
3-[(3-Pyridyl)hydroxymethyl]- 2-(2-tetrahydropyranyloxy-
methyl)-4-(3-thienyl)thiophene 30 ##STR00044##
4-(5-Chloro-2-thienyl)-3- [(3-pyridyl)hydroxymethyl]-
2-(2-thienyl)thiophene 31 ##STR00045## 4-(5-Chloro-2-thienyl)-3-
[(3-pyridyl)hydroxymethyl]- 2-(3-thienyl)thiophene 32 ##STR00046##
4-(2,4-Difluorophenyl)-3- [(3-pyridyl)hydroxymethyl]-
2-(3-thienyl)thiophene 33 ##STR00047## 2-(2,4-Difluorophenyl)-3-
[(3-pyridyl)hydroxymethyl]- 4-(2-thienyl)thiophene 34 ##STR00048##
2-(4-Chlorophenoxymethyl)-3- [(3-pyridyl)hydroxymethyl]-
4-(2-thienyl)thiophene 35 ##STR00049## 2-(4-Chlorophenoxymethyl)-
3-[(3-pyridyl)hydroxymethyl]- 4-(3-thienyl)thiophene 36
##STR00050## 2-(4-Chlorophenylethyl)-3- [(3-pyridyl)hydroxymethyl]-
4-(2-thienyl)thiophene 37 ##STR00051## 2-(4-Chlorophenylethyl)-3-
[(3-pyridyl)hydroxymethyl]- 4-(3-thienyl)thiophene 38 ##STR00052##
4-(4-Fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]-
2-(2-thienyl)thiophene 39 ##STR00053## 4-(2,4-Difluorophenyl)-3-
[(3-pyridyl)hydroxymethyl]- 2-(2-thienyl)thiophene 40 ##STR00054##
4-(2,4-Difluorophenyl)-3- [(3-pyridyl)hydroxymethyl]-
2-(trimethylsilyl)thiophene 41 ##STR00055##
4-(4-Chlorophenyl)-2-(4- chlorophenylethyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 42 ##STR00056##
2-(4-Chlorophenylethyl)-4- (2,4-difluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 43 ##STR00057##
2-(4-Chlorophenoxymethyl)- 4-(4-chlorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 44 ##STR00058##
2-(4-Chlorophenoxymethyl)- 4-(2,4-difluorophenyl)-3-
[(3-pyridyl)hydroxymethyl]- thiophene 45 ##STR00059##
2-(2,4-Difluorophenyl)- 4-(2-fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 46 ##STR00060##
2-(4-Chlorophenyl)-4- (2-fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 47 ##STR00061##
2-(4-Chlorophenyl)-4- (3-fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 48 ##STR00062##
4-(3-Fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]-
2-(2-thienyl)thiophene 49 ##STR00063## 2,4-Bis-(2-Chlorophenyl)-3-
[(3-pyridyl)hydroxymethyl]- thiophene 50 ##STR00064##
2,4-Bis-(3-Chlorophenyl)-3- [(3-pyridyl)hydroxymethyl]- thiophene
51 ##STR00065## 2,4-Bis-(Phenyl)-3-[(3- pyridyl)hydroxymethyl]-
thiophene 52 ##STR00066## 2,4-Bis-(2,4-Dichlorophenyl)-
3-[(3-pyridyl)hydroxymethyl]- thiophene 53 ##STR00067##
2,4-Bis-(2-Fluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- thiophene
54 ##STR00068## 2,4-Bis-(3-Fluorophenyl)-3-
[(3-pyridyl)hydroxymethyl]- thiophene 55 ##STR00069##
2-(3-Chlorophenyl)-4,5- dimethyl-3-[(3-pyridyl)
hydroxymethyl]-thiophene 56 ##STR00070## 4-(5-Chloro-2-furanyl)-2-
(4-chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 57
##STR00071## 4-(5-Chloro-2-furanyl)-2- (2,4-difluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 58 ##STR00072##
2,4-Bis-(2-thienyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 59
##STR00073## 2,4-Bis-(4-fluorophenyl)-3-
[(3-pyridyl)hydroxymethyl]- thiophene 60 ##STR00074##
2-(3-Chlorophenyl)-4- phenyl-3-[(3-pyridyl) hydroxymethyl]-
thiophene 61 ##STR00075## 2,4-Bis-(3-chloro-5-
trifluoromethylphenyl)-3- [(3-pyridyl)hydroxymethyl]- thiophene 62
##STR00076## 2,4-Bis-(2,5-difluorophenyl)-
3-[(3-pyridyl)hydroxymethyl]- thiophene 63 ##STR00077##
2,4-Bis-(4-chloro-3- fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]-
thiophene 64 ##STR00078## 2,4-Bis-(3-Methoxyphenyl)-
3-[(3-pyridyl)hydroxymethyl]- thiophene 65 ##STR00079##
4-(2-Fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]-
2-(2-thienyl)thiophene 66 ##STR00080## 2,4-Bis-(2-chloro-4-
trifluoromethylphenyl)-3- [(3-pyridyl)hydroxymethyl]- thiophene 67
##STR00081## 2,4-Bis-(4-Methoxyphenyl)-
3-[(3-pyridyl)hydroxymethyl]- thiophene 68 ##STR00082##
2-(3-Chlorophenyl)-4- (2,4-difluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 69 ##STR00083##
2-(5-Bromo-2-thienyl)-4- (2,4-difluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 70 ##STR00084##
2-(5-Chloro-2-thienyl)-4- (2,4-difluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 71 ##STR00085##
5-Chloro-2-(5-chloro-2- thienyl)-4-(2,4- difluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 72 ##STR00086##
4-(4-Chlorophenyl)-2- (2-fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 73 ##STR00087##
4-(4-Chlorophenyl)-2- (3-fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 74 ##STR00088##
2-(2-Chlorophenyl)-4- (2,4-difluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 75 ##STR00089##
4-(2,4-Difluorophenyl)- 2-(2-fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 76 ##STR00090##
2-(4-Chlorophenyl)-4-(4- chloro-2-fluorophenyl)-3-
[(3-pyridyl)hydroxymethyl]- thiophene 77 ##STR00091##
2-(3-Chlorophenyl)-4-(4- chloro-2-fluorophenyl)-3-
[(3-pyridyl)hydroxymethyl]- thiophene 78 ##STR00092##
4-(2,4-Difluorophenyl)-2- (4-fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene 79 ##STR00093##
4-(2,4-Dichlorophenyl)-3- [(3-pyridyl)hydroxymethyl]-
2-(3-thienyl)thiophene 80 ##STR00094## 4-(4-Fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- 2-(3-thienyl)thiophene 81 ##STR00095##
4-(4-Chloro-2-fluorophenyl)- 3-[(3-pyridyl)hydroxymethyl]-
2-(3-thienyl)thiophene 82 ##STR00096## 4-(2-Chlorophenyl)-3-[(3-
pyridyl)hydroxymethyl]-
2-(3-thienyl)thiophene 83 ##STR00097## 4-(4-Chlorophenyl)-2-(5-
chloro-2-thienyl)-3-[(3- pyridyl)hydroxymethyl] furan 84
##STR00098## 4-(4-Chlorophenyl)-2- (3,5-difluorophenyl)-3-[(3-
pyridyl)hydroxymethyl] furan 85 ##STR00099## 4-(4-Chlorophenyl)-2-
(2,4-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 86
##STR00100## 4-(4-Chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]-
2-(2-thienyl)furan 87 ##STR00101## 2,4-Bis-(4-chlorophenyl)-3-
[(3-pyridyl)hydroxymethyl] furan 88 ##STR00102##
4-(4-Chlorophenyl)-2-(4- chloro-2-fluorophenyl)-3-
[(3-pyridyl)hydroxymethyl] furan 89 ##STR00103##
2-(4-Chlorophenyl)-4- (2,4-difluorophenyl)-3-[(3-
pyridyl)hydroxymethyl] furan 90 ##STR00104##
4-(2,4-Difluorophenyl)-2- (4-fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl] furan 91 ##STR00105##
4-(2,4-Difluorophenyl)-3- [(3-pyridyl)hydroxymethyl]-
2-(3-thienyl)furan 92 ##STR00106## 4-(2,4-Difluorophenyl)-3-
[(3-pyridyl)hydroxymethyl]- 2-(2-thienyl)furan 93 ##STR00107##
2-(5-Chloro-2-thienyl)-4- (2,4-difluorophenyl)-3-[(3-
pyridyl)hydroxymethyl] furan 94 ##STR00108## 2-(3-Chlorophenyl)-4-
(2,4-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 95
##STR00109## 2-(4-Chlorophenyl)-4-(4- chloro-2-fluorophenyl)-3-
[(3-pyridyl)hydroxymethyl] furan 96 ##STR00110##
2-(3-Chlorophenyl)-4-(4- chloro-2-fluorophenyl)-3-
[(3-pyridyl)hydroxymethyl] furan 97 ##STR00111##
2-(2-Chlorophenyl)-4-(4- chloro-2-fluorophenyl)-3-
[(3-pyridyl)hydroxymethyl] furan 98 ##STR00112##
4-(4-Chloro-2-fluorophenyl)- 2-(4-fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl] furan 99 ##STR00113##
4-(4-Chloro-2-fluorophenyl)- 2-(3-fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl] furan 100 ##STR00114##
4-(4-Chloro-2-fluorophenyl)- 2-(2-fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl] furan 101 ##STR00115##
4-(4-Chloro-2-fluorophenyl)- 3-[(3-pyridyl)hydroxymethyl]-
2-(3-thienyl)furan 102 ##STR00116## 4-(4-Chloro-2-fluorophenyl)-
3-[(3-pyridyl)hydroxymethyl]- 2-(2-thienyl)furan 103 ##STR00117##
4-(4-Chloro-2-fluorophenyl)- 2-(5-chloro-2-thienyl)--3-[(3-
pyridyl)hydroxymethyl]furan 104 ##STR00118## 2-(4-Chlorophenyl)-4-
(2,4-dichlorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 105
##STR00119## 2-(3-Chlorophenyl)-4- (2,4-dichlorophenyl)-3-[(3-
pyridyl)hydroxymethyl] furan 106 ##STR00120## 2-(2-Chlorophenyl)-4-
(2,4-dichlorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 107
##STR00121## 4-(2,4-Dichlorophenyl)- 2-(4-fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl] furan 108 ##STR00122##
4-(2,4-Dichlorophenyl)-2- (3-fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl] furan 109 ##STR00123##
2-(2,4-Difluorophenyl)-3- [(3-pyridyl)hydroxymethyl]-
4-(2-thienyl)furan 110 ##STR00124## 2-(2,4-Dichlorophenyl)-3-
[(3-pyridyl)hydroxymethyl]- 4-(2-thienyl)furan 111 ##STR00125##
2-(4-Chloro-2-fluorophenyl)- 3-[(3-pyridyl)hydroxymethyl]-
4-(2-thienyl)furan 112 ##STR00126## 2-(4-Chlorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- 4-(2-thienyl)furan 113 ##STR00127##
2-(3-Chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]-
4-(2-thienyl)furan 114 ##STR00128## 2-(2-Chlorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- 4-(2-thienyl)furan 115 ##STR00129##
2-(4-Fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]-
4-(2-thienyl)furan 116 ##STR00130## 2-(3-Fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- 4-(2-thienyl)furan 117 ##STR00131##
2-(2-Fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]-
4-(2-thienyl)furan 118 ##STR00132## 2-(3,5-Difluorophenyl)-3-
[(3-pyridyl)hydroxymethyl]- 4-(2-thienyl)furan 119 ##STR00133##
4-(5-Chloro-2-thienyl)-2- (2,4-difluorophenyl)-3-[(3-
pyridyl)hydroxymethyl] furan 120 ##STR00134##
4-(5-Chloro-2-thienyl)-2- (2,4-dichlorophenyl)-3-[(3-
pyridyl)hydroxymethyl] furan 121 ##STR00135##
2-(4-Chloro-2-fluorophenyl)- 4-(5-chloro-2-thienyl)-3-[(3-
pyridyl)hydroxymethyl] furan 122 ##STR00136##
2-(4-Chlorophenyl)-4-(5- chloro-2-thienyl)-3-[(3-
pyridyl)hydroxymethyl] furan 123 ##STR00137##
2-(3-Chlorophenyl)-4-(5- chloro-2-thienyl)-3-[(3-
pyridyl)hydroxymethyl] furan 124 ##STR00138##
2-(2-Chlorophenyl)-4-(5- chloro-2-thienyl)-3-[(3-
pyridyl)hydroxymethyl] furan 125 ##STR00139##
4-(5-Chloro-2-thienyl)-2- (4-fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl] furan 126 ##STR00140##
4-(5-Chloro-2-thienyl)-2- (3-fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl] furan 127 ##STR00141##
4-(5-Chloro-2-thienyl)-2- (2-fluorophenyl)-3-[(3-
pyridyl)hydroxymethyl] furan 128 ##STR00142##
4-(5-Chloro-2-thienyl)-2- (3,5-difluorophenyl)-3-[(3-
pyridyl)hydroxymethyl] furan 129 ##STR00143##
4-(4-Chlorophenyl)-2-(5- chloro-2-thienyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 130 ##STR00144##
4-(4-Chlorophenyl)-2- (3,5-difluorophenyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 131 ##STR00145##
4-(4-Chlorophenyl)-2- (2,4-difluorophenyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 132 ##STR00146##
4-(4-Chlorophenyl)-1-(N- methyl)-3-[(3-pyridyl)
hydroxymethyl]-2-(2- thienyl)pyrrole 133 ##STR00147##
2,4-Bis-(4-chlorophenyl)-1- (N-methyl)-3-[(3-pyridyl)
hydroxymethyl]pyrrole 134 ##STR00148## 4-(4-Chlorophenyl)-2-(4-
chloro-2-fluorophenyl)-3- [(3-pyridyl)hydroxymethyl] pyrrole 135
##STR00149## 2-(4-Chlorophenyl)-4- (2,4-difluorophenyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 136 ##STR00150##
4-(2,4-Difluorophenyl)-2- (4-fluorophenyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 137 ##STR00151##
4-(2,4-Difluorophenyl)-1- (N-methyl)-3-[(3-pyridyl)
hydroxymethyl]-2-(3- thienyl)pyrrole 138 ##STR00152##
4-(2,4-Difluorophenyl)-1- (N-methyl)-3-[(3-pyridyl)
hydroxymethyl]-2-(2- thienyl)pyrrole 139 ##STR00153##
2-(5-Chloro-2-thienyl)- 4-(2,4-difluorophenyl)- 1-(N-methyl)-3-[(3-
pyridyl)hydroxymethyl] pyrrole 140 ##STR00154##
2-(3-Chlorophenyl)-4- (2,4-difluorophenyl)- 1-(N-methyl)-3-[(3-
pyridyl)hydroxymethyl] pyrrole 141 ##STR00155##
2-(4-Chlorophenyl)-4-(4- chloro-2-fluorophenyl)-1-
(N-methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 142 ##STR00156##
2-(3-Chlorophenyl)-4-(4- chloro-2-fluorophenyl)-1-
(N-methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 143 ##STR00157##
2-(2-Chlorophenyl)-4-(4- chloro-2-fluorophenyl)-1-
(N-methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 144 ##STR00158##
4-(4-Chloro-2-fluorophenyl)- 2-(4-fluorophenyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 145 ##STR00159##
4-(4-Chloro-2-fluorophenyl)- 2-(3-fluorophenyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 146 ##STR00160##
4-(4-Chloro-2-fluorophenyl)- 2-(2-fluorophenyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 147 ##STR00161##
4-(4-Chloro-2-fluorophenyl)- 1-(N-methyl)-3-[(3-pyridyl)
hydroxymethyl]-2-(3- thienyl)pyrrole 148 ##STR00162##
4-(4-Chloro-2-fluorophenyl)- 1-(N-methyl)-3-[(3-pyridyl)
hydroxymethyl]-2-(2-thienyl) pyrrole 149 ##STR00163##
4-(4-Chloro-2-fluorophenyl)- 2-(5-chloro-2-thienyl)-1-
(N-methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 150 ##STR00164##
2-(4-Chlorophenyl)-4- (2,4-dichlorophenyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 151 ##STR00165##
2-(3-Chlorophenyl)-4- (2,4-dichlorophenyl)- 1-(N-methyl)-3-[(3-
pyridyl)hydroxymethyl] pyrrole 152 ##STR00166##
2-(2-Chlorophenyl)-4- (2,4-dichlorophenyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 153 ##STR00167##
4-(2,4-Dichlorophenyl)- 2-(4-fluorophenyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 154 ##STR00168##
4-(2,4-Dichlorophenyl)- 2-(3-fluorophenyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 155 ##STR00169##
2-(2,4-Difluorophenyl)- 1-(N-methyl)-3-[(3- pyridyl)hydroxymethyl]-
4-(2-thienyl)pyrrole 156 ##STR00170## 2-(2,4-Dichlorophenyl)-
1-(N-methyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)pyrrole
157 ##STR00171## 2-(4-Chloro-2-fluorophenyl)-
1-(N-methyl)-3-[(3-pyridyl) hydroxymethyl]-4-(2-thienyl) pyrrole
158 ##STR00172## 2-(4-Chlorophenyl)-1- (N-methyl)-3-[(3-
pyridyl)hydroxymethyl]- 4-(2-thienyl)pyrrole 159 ##STR00173##
2-(3-Chlorophenyl)-1- (N-methyl)-3-[(3- pyridyl)hydroxymethyl]-
4-(2-thienyl)pyrrole 160 ##STR00174## 2-(2-Chlorophenyl)-1-
(N-methyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)pyrrole 161
##STR00175## 2-(4-Fluorophenyl)- 1-(N-methyl)-3-[(3-
pyridyl)hydroxymethyl]- 4-(2-thienyl)pyrrole 162 ##STR00176##
2-(3-Fluorophenyl)-1- (N-methyl)-3-[(3- pyridyl)hydroxymethyl]-
4-(2-thienyl)pyrrole 163 ##STR00177## 2-(2-Fluorophenyl)-1-
(N-methyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)pyrrole 164
##STR00178## 2-(3,5-Difluorophenyl)- 1-(N-methyl)-3-[(3-
pyridyl)hydroxymethyl]- 4-(2-thienyl)pyrrole 165 ##STR00179##
4-(5-Chloro-2-thienyl)- 2-(2,4-difluorophenyl)-1-
(N-methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole
166 ##STR00180## 4-(5-Chloro-2-thienyl)- 2-(2,4-dichlorophenyl)-1-
(N-methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 167 ##STR00181##
2-(4-Chloro-2-fluorophenyl)- 4-(5-chloro-2-thienyl)-1-
(N-methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 168 ##STR00182##
2-(4-Chlorophenyl)-4- (5-chloro-2-thienyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 169 ##STR00183##
2-(3-Chlorophenyl)-4- (5-chloro-2-thienyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 170 ##STR00184##
2-(2-Chlorophenyl)-4-(5- chloro-2-thienyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 171 ##STR00185##
4-(5-Chloro-2-thienyl)- 2-(4-fluorophenyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 172 ##STR00186##
4-(5-Chloro-2-thienyl)- 2-(3-fluorophenyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 173 ##STR00187##
4-(5-Chloro-2-thienyl)- 2-(2-fluorophenyl)-1-(N-
methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 174 ##STR00188##
4-(5-Chloro-2-thienyl)-2- (3,5-difluorophenyl)-1-
(N-methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 175 ##STR00189##
2-(2,4-Difluorophenyl)- 4-(2-chlorophenyl)-3-[(3-
pyridyl)hydroxymethyl]- thiophene
[0262] Compounds 1 to 175 all contain one asymmetrical carbon atom
which is the carbon atom linked to one single hydroxy substituent
(OH).
[0263] Biological Evaluation
EXAMPLE 7
Biological Evaluation of Plant Growth Regulation Effects on
Grape
[0264] 5 weeks old grape seedlings cultivar (cv.) Gutedel are
treated with the formulated test compound in a spray chamber. After
an incubation period of 8 days at 22.degree. C. and 80% relative
humidity (r. h.) in a greenhouse, the plant growth regulating
effects are assessed.
EXAMPLE 8
Biological Evaluation of Plant Growth Regulation Effects on
Wheat
[0265] 2 weeks old wheat plants cultivar (cv.). Riband were treated
with the formulated test compound in a spray chamber. After an
incubation period of 8 days at 22.degree. C. and 80% relative
humidity (r. h.) in a greenhouse, the plant growth regulating
effects were assessed.
[0266] Compound 175 showed plant height decrease at 200 ppm.
* * * * *