U.S. patent application number 11/634118 was filed with the patent office on 2007-05-10 for tetrazoyloxime derivative and agricultural chemical containing the same as active ingredient.
This patent application is currently assigned to NIPPON SODA CO., LTD. Invention is credited to Kumiko Akiba, Toru Asada, Hiroyuki Hamano, Takeo Kobori, Akihiro Koiso, Hitoshi Kondo, Hidetoshi Nakayama, Akira Ohno, Tsuneyuki Otaguro, Hiroyuki Tsuboi.
Application Number | 20070105926 11/634118 |
Document ID | / |
Family ID | 19078078 |
Filed Date | 2007-05-10 |
United States Patent
Application |
20070105926 |
Kind Code |
A1 |
Kobori; Takeo ; et
al. |
May 10, 2007 |
Tetrazoyloxime derivative and agricultural chemical containing the
same as active ingredient
Abstract
The present invention provides a tetrazoyloxime derivative which
is less likely to cause chemical injury to useful plants and is
also superior in chemical efficacy to a conventional hetero
ring-substituted oxime derivative. A tetrazoyloxime derivative
represented by the general formula (1): ##STR1## X represents a
hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, a
cyano group, a methanesulfonyl group, a nitro group, a
trifluoromethyl group, or an aryl group; A represents a
1-alkyltetrazoyl-5-yl group or a 5-alkyltetrazoyl-1-yl group; and
Het represents a pyridyl group having a substituent or a thiazoyl
group having a substituent, and a plant disease controlling agent
containing the same as an active ingredient are disclosed.
Inventors: |
Kobori; Takeo; (Inba-gun,
JP) ; Kondo; Hitoshi; (Chiba-shi, JP) ;
Tsuboi; Hiroyuki; (Yachiyo-shi, JP) ; Akiba;
Kumiko; (Chiba-shi, JP) ; Koiso; Akihiro;
(Sakura-shi, JP) ; Otaguro; Tsuneyuki;
(Sakura-shi, JP) ; Nakayama; Hidetoshi;
(Chiba-shi, JP) ; Hamano; Hiroyuki; (Sakura-shi,
JP) ; Ohno; Akira; (Chiba-shi, JP) ; Asada;
Toru; (Inba-gun, JP) |
Correspondence
Address: |
ARMSTRONG, KRATZ, QUINTOS, HANSON & BROOKS, LLP
1725 K STREET, NW
SUITE 1000
WASHINGTON
DC
20006
US
|
Assignee: |
NIPPON SODA CO., LTD
Tokyo
JP
|
Family ID: |
19078078 |
Appl. No.: |
11/634118 |
Filed: |
December 6, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10486205 |
Feb 13, 2004 |
7183299 |
|
|
11634118 |
Dec 6, 2006 |
|
|
|
Current U.S.
Class: |
514/381 ;
548/253 |
Current CPC
Class: |
A01N 43/713 20130101;
C07D 417/12 20130101; C07D 401/12 20130101; C07D 257/04 20130101;
A01N 43/82 20130101; A01N 43/78 20130101 |
Class at
Publication: |
514/381 ;
548/253 |
International
Class: |
C07D 257/02 20060101
C07D257/02; A61K 31/41 20060101 A61K031/41 |
Foreign Application Data
Date |
Code |
Application Number |
Aug 20, 2001 |
JP |
2001-249006 |
Claims
1. A tetrazoylhydroxyimino derivative represented by the general
formula (6): ##STR69## wherein X.sup.1 represents a hydrogen atom,
a halogen atom, an alkyl group, or an alkoxy group; and Y.sup.1
represents an alkyl group.
2. A tetrazoylhydroxyimino derivative represented by the general
formula (7): ##STR70## wherein X.sup.2 represents an alkyl group,
an alkoxy group, a cyano group, a methanesulfonyl group, a nitro
group, a trifluoromethyl group, or an aryl group; and Y.sup.2
represents an alkyl group.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application is a division of Ser. No. 10/486,205, filed
Feb. 13, 2004, which is a 35 U.S.C. 371 application of
international application No. PCT/JP98/02153 filed May 15, 1998,
which is based on Japanese Application No. 2001-249006 filed Aug.
20, 2001.
TECHNICAL FIELD
[0002] The present invention relates to a novel tetrazoyloxime
derivative and to an agricultural chemical containing the same as
an active ingredient and, more particularly, to a plant disease
controlling agent.
BACKGROUND ART
[0003] Japanese Unexamined Patent Application, First Publication
No. Hei 11-269176 (WO99/29689, EP-A-1038874) and Japanese
Unexamined Patent Application, First Publication No. 2001-55387
(WO00/75138, EP-A-1184382) according to an invention of the present
inventors disclose that hetero ring-substituted oxime derivatives
act as plant disease controlling agents.
[0004] Specifically, Japanese Unexamined Patent Application, First
Publication No. Hei 11-269176 (WO99/29689, EP-A-1038874) discloses
oxime derivatives represented by the general formula (A): wherein
R.sup.1 represents a hydrogen atom or a lower alkyl group; X
represents a halogen atom, a nitro group, a hydroxy group, a cyano
group, a carboxyl group, an alkoxycarbonyl group, a lower alkyl
group, a lower alkoxy group, a lower alkylthio group, a lower
alkylsulfonyl group, an aryl group, an aryloxy group, or an amino
group; n represents an integer of 0 to 3; Het A represents a
six-membered nitrogen-containing aromatic ring having one or more
nitrogen atoms, which may be substituted with one or more
substituents selected from the group consisting of a halogen atom,
a lower alkyl group, a lower alkylthio group, a lower alkylsulfonyl
group, a lower alkoxy group, a trifluoromethyl group and a cyano
group, or a benzo condensed ring type nitrogen-containing aromatic
ring; and Het B represents a group represented by any one of the
ring structures of the general formula: ##STR2## the general
formula: ##STR3## and the general formula: ##STR4## (wherein Y
represents a hydrogen atom, a halogen atom, or a lower alkyl
group).
[0005] Also Japanese Unexamined Patent Application, First
Publication No. 2001-55387 (WO00/75138, EP-A-1184382) discloses
oxime derivatives represented by the general formula (B): ##STR5##
wherein Het A represents a group represented by any one of the
following three formulas: ##STR6## (wherein Q represents a hydrogen
atom, a halogen atom, or a lower alkyl group; R.sup.1 represents a
hydrogen atom, a lower alkyl group, a cycloalkyl group, a lower
alkenyl group, a lower alkynyl group, an aralkyl group, or an aryl
group; and R.sup.2 represents a hydrogen atom or a lower alkyl
group); Het B represents a group represented by any one of the
following nine formulas: ##STR7## (wherein Y represents a hydrogen
atom or a lower alkyl group; and R.sup.3 represents a hydrogen atom
or a lower alkyl group); and Het C represents a group represented
by any one of the following nine formulas: ##STR8## (wherein
R.sup.4 represents a hydrogen atom or a lower alkyl group; X
represents a hydrogen atom, a halogen atom, a lower alkyl group, a
lower alkoxy group, or a cyano group; Z represents a hydrogen atom,
a halogen atom, or a lower alkyl group, and n represents an integer
of 0 to 3).
[0006] Although the respective compounds described in Japanese
Unexamined Patent Application, First Publication No. Hei 11-269176
(WO99/29689, EP-A-1038874) and Japanese Unexamined Patent
Application, First Publication No. 2001-55387 (WO00/75138,
EP-A-1184382) exhibit considerable control activity, it is
particularly necessary to develop chemicals which exert superior
control activity.
[0007] The document (Bull. Soc. Chim. Belg., Vol. 96, page 675,
1987) discloses only compounds similar to tetrazoylhydroxime
derivatives represented by the general formula (7) described in
claim 9 of the present invention, which are suited for use as an
intermediate for synthesis of tetrazoyloxime derivatives described
in claim 1 of the present invention, for example, compound of the
general formula (7) X.sup.2 is a hydrogen atom and Y.sup.2 is a
methyl group, compound wherein X.sup.2 is a hydrogen atom and
Y.sup.2 is an isopropyl group, and compound wherein X.sup.2 is a
chlorine atom and Y.sup.2 is a methyl group. These three compounds
were synthesized during research for the purpose of elucidation of
a reaction mechanism. The document does not disclose the utility of
these compounds, for example, tetrazoyloxime derivatives
represented by the general formula (1) described in claim 1 of the
present invention can be synthesized by using the compounds and the
compounds are suited for use as an intermediate for preparation of
an agricultural chemical.
DISCLOSURE OF INVENTION
[0008] An object of the present invention to be achieved by the
present invention is to provide tetrazoyloxime derivatives which
are less likely to chemically injure useful plants and are also
superior in chemical efficacy against plant diseases to
conventional hetero ring-substituted oxime derivatives.
[0009] Another object to be achieved by the present invention is to
provide an agricultural chemical containing the tetrazoyloxime
derivatives as an active ingredient, which has sufficient plant
disease controlling activity.
[0010] Still another object to be achieved by the present invention
is to provide tetrazoylhydroxime derivatives suited for use as
intermediates for preparation of the tetrazoyloxime
derivatives.
[0011] To achieve these objects, the present inventors have
synthesized various tetrazoyloxime derivatives and intensively
researched their bioactivity. As a result, they have found that a
tetrazoyloxime derivative represented by the following formula (1)
is less likely to cause chemical injury to useful plants and also
exhibits particularly superior plant disease controlling activity
using small amounts thereof. Thus, the present invention has been
completed.
[0012] To achieve the above object, the present invention provides
a tetrazoyloxime derivative represented by the general formula (1):
##STR9##
[0013] wherein X represents a hydrogen atom, a halogen atom, an
alkyl group, an alkoxy group, a cyano group, a methanesulfonyl
group, a nitro group, a trifluoromethyl group, or an aryl group; A
represents a tetrazoyl group represented by the general formula
(2): ##STR10## TABLE-US-00001 TABLE 35 Compound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (9)-4 Z 1.52(s, 9H), 2.36(s, 3H),
3.95(s, 3H), 5.23(s, 2H), .quadrature.6.92(d, 1H, J=7.2Hz), 7.17(m,
2H), 7.31(brd, 1H), .quadrature.7.39(m, 2H), 7.64(dd, 1H, J=7.2,
8.4Hz), .quadrature.7.86(d, 1H, J=8.4Hz). (9)-5 Z 0.92(t, 3H,
J=7.0Hz), 1.36(m, 4H), 1.68(m, 2H), 2.36(s, 3H), 3.96(s, 3H),
4.17(t, 2H, J=6.7Hz), 5.24(s, 2H), 6.95(d, 1H, J=7.5Hz), 7.17(m,
2H), 7.38(m, 2H), 7.46(brd, 1H), 7.67(dd, 1H, J=7.5, 8.1Hz),
7.89(d, 1H, J=8.1Hz). (9)-6 Z 0.98(t, 3H, J=7.4Hz), 1.71(tq, 2H,
J=6.7, 7.4Hz), 3.99(s, 3H), 4.15(q, 2H, J=6.7Hz), 6.95(d, 1H,
J=7.0H), 7.1-7.25(m, 2H), 7.3-7.45(m, 3H), 7.69(dd, 1H, J=7.0,
8.3Hz), 7.91(d, 1H, J=8.3Hz). (9)-7 Z 0.91(t, 3H, J=7.1Hz), 1.36(m,
4H), 1.73(m, 2H), 2.33(s, 3H), 2.39(q, 2H, J=7.5Hz), 3.96(s, 3H),
5.26(s, 2H), 7.00(d, 1H, J=7.5Hz), 7.27(m, 4H), 7.69(dd, 1H, J=7.5,
8.3Hz), 7.89(brd, 1H), 8.15(d, 1H, J=8.3Hz). (9)-8 Z 1.52(s, 9H),
2.33(s, 3H), 3.96(s, 3H), 5.24(s, 2H), 6.92(d, 1H, J=6.8Hz),
7.2-7.35(m, 5H), 7.65(dd, 1H, J=6.8, 8.3Hz), 7.86(d, 1H, J=8.3Hz).
(9)-9 Z 0.93(t, 3H, J=7.5Hz), 1.49(s, 6H), 1.83(q, 2H, J=7.5Hz),
2.36(s, 3H), 3.96(s, H), 5.23(s, 2H), 6.92(d, 1H, J=7.0Hz), 7.19(m,
3H), 7.39(m, 2H), 7.64(dd, 1H, J=7.0, 8.3Hz), 7.85(d, 1H,
J=8.3Hz).
(wherein Y represents an alkyl group) or a tetrazoyl group
represented by the general formula (3): ##STR11## (wherein Y
represents an alkyl group); and Het represents a pyridyl group
represented by the general formula (4): ##STR12## (wherein R
represents a hydrogen atom or a halogen atom; Z represents a
hydrogen atom, an amino group, the general formula QC(.dbd.O)NH--
(Q represents a hydrogen atom, an alkyl group having 1 to 8 carbon
atoms, an alkyl group having 1 to 6 carbon atoms substituted with a
halogen atom, a cycloalkyl group having 3 to 6 carbon atoms, an
alkoxyl group having 1 to 8 carbon atoms, a cycloalkyloxy group
having 3 to 6 carbon atoms, a benzyloxy group, a 2-phenylethyloxy
group, a thioalkyl group substituted with an alkyl group having 1
to 4 carbon atoms, an alkyl group having 1 to 2 carbon atoms
substituted with an alkoxyl group having 1 to 4 carbon atoms, an
alkyl group having 1 to 6 carbon atoms substituted with an
acylamino group having 1 to 4 carbon atoms, an alkoxy group having
1 to 6 carbon atoms substituted with an acylamino group having 1 to
4 carbon atoms, an alkylamino group having 1 to 8 carbon atoms, an
alkenyl group having 2 to 6 carbon atoms, an aralkyl group, or a
phenyl group)), or a thiazoyl group represented by the general
formula (5): ##STR13## (wherein R and Z are as defined in the
general formula (4).
[0014] To achieve the above object, the present invention provides
a tetrazoylhydroxyimino derivative represented by the general
formula (6): ##STR14## wherein X.sup.1 represents a hydrogen atom,
a halogen atom, an alkyl group, or an alkoxy group; and Y.sup.1
represents an alkyl group, and a tetrazoylhydroxyimino derivative
represented by the general formula (7): ##STR15## wherein X.sup.2
represents an alkyl group, an alkoxy group, a cyano group, a
methanesulfonyl group, a nitro group, a trifluoromethyl group, or
an aryl group; and Y.sup.2 represents an alkyl group, which are
suited for use as an intermediate for synthesis of the
tetrazoyloxime derivative represented by the general formula
(1).
[0015] To achieve the above object, the present invention provides
an agricultural chemical, especially a plant disease controlling
agent, comprising the tetrazoyloxime derivative represented by the
general formula (1) as an active ingredient.
BEST MODE FOR CARRYING OUT THE INVENTION
[0016] In the tetrazoyloxime derivative rented by the general
formula (1), the substitution position of X is not specifically
limited and X represents a hydrogen atom, a halogen atom, an alkyl
group, an alkoxy group, a cyano group, a methanesulfonyl group, a
nitro group, a trifluoromethyl group, or an aryl group.
[0017] Examples of a halogen atom for X include a chlorine atom, a
bromine atom, an iodine atom, and a fluorine atom. Among these
halogen atoms, a chlorine atom or a fluorine atom is particularly
preferable because the resulting compound is less likely to cause
chemical injury and is superior in control activity.
[0018] The alkyl group represented for X is preferably an alkyl
group having 1 to 4 carbon atoms and specific examples thereof
include a methyl group, an ethyl group, an n-propyl group, an
isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl
group, and a tert-butyl group. Among these alkyl groups, a methyl
group or a tert-butyl group is particularly preferable because the
resulting compound is less likely to cause chemical injury and is
superior in control activity.
[0019] The alkoxy group for X is preferably alkoxy group having 1
to 3 carbon atoms and specific examples thereof include a methoxy
group, an ethoxy group, a propoxy group, and an isopropoxy group.
Among these alkoxy groups, a methoxy group or an ethoxy group is
particularly preferable because the resulting compound is less
likely to cause chemical injury and is superior in control
activity.
[0020] Examples of the aryl group for X include a phenyl group, a
4-methylphenyl group, and a 4-chlorophenyl group. Among these aryl
groups, a phenyl group is particularly preferable because the
resulting compound is less likely to cause chemical injury and is
superior in control activity.
[0021] Among these, a hydrogen atom is most preferable.
[0022] In the tetrazoyl group represented by the general formula
(2) or (3), Y represents an alkyl group. Among these alkyl groups,
an alkyl group having 1 to 3 carbon atoms such as a methyl group,
an ethyl group, an n-propyl group, or an isopropyl group is
preferable. Among these alkyl groups, a methyl group or an ethyl
group is particularly preferable because the resulting compound is
less likely to cause chemical injury and is superior in control
activity.
[0023] R in the pyridyl group represented by the general formula
(4) represents a hydrogen atom, or a halogen atom such as a
chlorine atom, a bromine atom, an iodine atom, or a fluorine atom.
Among these, a hydrogen atom or a chlorine atom is particularly
preferable because the resulting compound is less likely to cause
chemical injury and is superior in control activity.
[0024] Het in the tetrazoyloxime derivative represented by the
general formula (1) is either a pyridyl group represented by the
general formula (4), or a thiazoyl group represented by the general
formula (5), while Z in the general formulas (4) and (5) represents
a hydrogen atom, an amino group, or a group represented by the
general formula QC(.dbd.O)NH.
[0025] Q in the group represented by the general formula
QC(.dbd.O)NH represents a hydrogen atom, a lower alkyl group, a
lower alkyl group substituted with a halogen atom, a cycloalkyl
group having 3 to 6 carbon atoms, a benzyloxy group, a
2-phenylethyloxy group, an alkoxy group having 1 to 8 carbon atoms,
a cycloalkyloxy group having 3 to 6 carbon atoms, a lower alkyl
group substituted with an alkoxy group having 1 to 6 carbon atoms,
a thioalkyl group substituted with an alkyl group having 1 to 4
carbon atoms, an alkyl group having 1 to 6 carbon atoms substituted
with an acylamino group having 1 to 4 carbon atoms, an alkoxy group
having 1 to 6 carbon atoms substituted with an acylamino group
having 1 to 4 carbon atoms, an alkylamino group having 1 to 8
carbon atoms, an alkenyl group having 2 to 6 carbon atoms, an
aralkyl group, or a phenyl group.
[0026] The lower alkyl group for Q is preferably an alkyl group
having 1 to 8 carbon atoms and specific examples thereof include a
methyl group, an ethyl group, an n-propyl group, an isopropyl
group, a 1,1-dimethylpropyl group, an n-butyl group, an isobutyl
group, a sec-butyl group, a tert-butyl group, an isoamyl group, a
1-methylbutyl group, a 2-methylbutyl group, an neopentyl group, a
1-ethylpropyl group, an n-pentyl group, a hexyl group, a heptyl
group, and an octyl group.
[0027] The lower alkyl group substituted with the halogen atom for
Q is preferably an alkyl group having 1 to 6 carbon atoms
substituted with a halogen atom and specific examples thereof
include a chloromethyl group, a difluoromethyl group, a
trifluoromethyl group, a difluorochloromethyl group, a
pentafluoroethyl group, a 3,3,3-trifluoro-n-propyl group, and a
1-chlorohexyl group.
[0028] Specific examples of the cycloalkyl group having 3 to 6
carbon atoms for Q include a cyclopropyl group, a cyclobutyl group,
a cyclopentyl group, and a cyclohexyl group.
[0029] Specific examples of the alkoxy group having 1 to 8 carbon
atoms for Q include a methoxy group, an ethoxy group, a propoxy
group, an isopropoxy group, a 1,1-dimethylpropoxy group, a butoxy
group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group,
an isopentyloxy group, a 1-methylbutoxy group, a 2-methylbutoxy
group, an neopentyloxy group, a 1-ethylpropoxy group, an
n-pentyloxy group, a hexyloxy group, a heptyloxy group, and an
octyloxy group.
[0030] Specific examples of the cycloalkyloxy group having 3 to 6
carbon atoms for Q include a cyclopropyloxy group, a cyclobutyloxy
group, a cyclopentyloxy group, and a cyclohexyloxy group.
[0031] Examples of the alkyl group having 1 to 2 carbon atoms
substituted with the alkoxy group having 1 to 4 carbon atoms for Q
include a methoxymethyl group, an ethoxymethyl group, an
ethoxyethyl group, and a butoxymethyl group.
[0032] Specific examples of the alkylthio group substituted with
the alkyl group having 1 to 4 carbon atoms for Q include a
methylthiomethyl group, a methylthioethyl group, an ethylthiomethyl
group, and a butylthiomethyl group.
[0033] Specific examples of the alkoxy group having 1 to 6 carbon
atoms substituted with the acylamino group having 1 to 4 carbon
atoms for Q include an acetylaminomethoxy group, a
2-(propionylamino)ethoxy group, a 3-(acetylamino)propoxy group, a
3-(propionylamino)propoxy group, a 3-(isopropionylamino)propoxy
group, a 3-(butyroylamino)propoxy group, a
3-(isobutyroylamino)propoxy group, a 3-(sec-butyroylamino)propoxy
group, a 3-(tert-butyroylamino)propoxy group, a
4-(acetylamino)butoxy group, a 5-(acetylamino)pentyloxy group, and
a 6-(acetylamino)hexyloxy group.
[0034] Specific examples of the alkyl group having 1 to 6 carbon
atoms substituted with the acylamino group having 1 to 4 carbon
atoms for Q include an acetylaminomethyl group, a
2-(propionylamino)ethyl group, a 3-(acetylamino)propyl group, a
3-(propionylamino)propyl group, a 3-(isopropionylamino)propyl
group, a 3-(butyroylamino)propyl group, a
3-(isobutyroylamino)propyl group, a 3-(sec-butyroylamino)propyl
group, 3-(tert-butyroylamino)propyl group, a 4-(acetylamino)butyl
group, a 5-(acetylamino)pentyl group, and a 6-(acetylamino)hexyl
group.
[0035] Specific examples of the alkylamino group having 1 to 8
carbon atoms for Q include a methylamino group, an ethylamino
group, a propylamino group, an isopropylamino group, a butylamino
group, an isobutylamino group, a sec-butylamino group, a
tert-butylamino group, an neopentylamino group, a
1-ethylpropylamino group, an n-pentylamino group, a hexylamino
group, a heptylamino group, and an octylamino group.
[0036] Specific examples of the alkenyl group having 2 to 6 carbon
atoms for Q include an allyl group, an isopropenyl group, a
1-butenyl group, a 2-butenyl group, a 2-pentenyl group, and a
5-hexenyl group.
[0037] Examples of the aralkyl group for Q include a benzyl group
and a phenethyl group.
[0038] X.sup.1 in the tetrazoylhydroxime compound represented by
the general formula (6) represents a hydrogen atom, a halogen atom,
an alkyl group, or an alkoxy group.
[0039] Examples of the halogen atom for X.sup.1 include a chlorine
atom, a bromine atom, an iodine atom, and a fluorine atom. Among
these, chlorine or a fluorine atom is particularly preferable.
[0040] The alkyl group for X.sup.1 is preferably an alkyl group
having 1 to 4 carbon atoms and specific examples thereof include a
methyl group, an ethyl group, an n-propyl group, an isopropyl
group, a 1,1-dimethylpropyl group, an n-butyl group, an isobutyl
group, a sec-butyl group, and a tert-butyl group. Among these
groups, a methyl group is particularly preferable.
[0041] The alkoxy group for X.sup.1 is preferably an alkoxy group
having 1 to 3 carbon atoms and specific examples thereof include a
methoxy group, an ethoxy group, a propoxy group, and an isopropoxy
group. Among these groups, a methoxy group is particularly
preferable.
[0042] Y.sup.1 in the tetrazoylhydroxime compound represented by
the general formula (6) represents an alkyl group. Among alkyl
groups, an alkyl group having 1 to 3 carbon atoms such as a methyl
group, an ethyl group, an n-propyl group, or an isopropyl group is
preferable, and a methyl group is particularly preferable.
[0043] X.sup.2 in the tetrazoylhydroxime compound represented by
the general formula (7) represents an alkyl group, an alkoxy group,
a cyano group, a methanesulfonyl group, a nitro group, a
trifluoromethyl group, or an aryl group.
[0044] The alkyl group for X.sup.2 is preferably an alkyl group
having 1 to 4 carbon atoms, such as a methyl group, an ethyl group,
an n-propyl group, an isopropyl group, a 1,1-dimethylpropyl group,
an n-butyl group, an isobutyl group, a sec-butyl group, or a
tert-butyl group. Among these alkyl groups, a methyl group or a
tert-butyl group is particularly preferable.
[0045] The alkoxy group for X.sup.2 is preferably an alkoxy group
having 1 to 3 carbon atoms, such as a methoxy group, an ethoxy
group, a propoxy group, or an isopropoxy group. Among these alkoxy
groups, a methoxy group is particularly preferable.
[0046] Specific examples of the aryl group for X.sup.2 include a
phenyl group, a 4-methylphenyl group, and a 4-chlorophenyl group.
Among these aryl groups, a phenyl group is particularly
preferable.
[0047] The alkyl group for Y.sup.2 is preferably an alkyl group
having 1 to 3 carbon atoms, such as a methyl group, an ethyl group,
an n-propyl group, or an isopropyl group. Among these alkyl groups,
a methyl group is particularly preferable.
[0048] Among the compounds represented by the general formula (1),
preferred is a tetrazoyloxime derivative wherein Z is a group
represented by the general formula: QC(.dbd.O)NH-- (wherein Q
represents an alkyl group having 1 to 8 carbon atoms, or an alkoxyl
group having 1 to 8 carbon atoms) and Het is a pyridyl group
represented by the general formula (4) or a thiazoyl group
represented by the general formula (5), and particularly preferred
is a tetrazoyloxime derivative wherein X is a hydrogen atom or a
halogen atom.
[0049] The stereostructure of the oxime moiety, which exists in the
tetrazoyloxime derivative represented by the general formula (1)
and the tetrazoylhydroxyimino derivative represented by the general
formula (6) or (7) includes (E) or (Z) isomer, and these
stereoisomers are included in the present invention. The
synthesized product is usually obtained in the form of the (Z)
isomer or a mixture of (E) and (Z) isomers, each of which can be
isolated by separation and purification.
[0050] In the tetrazoyloxime derivative represented by the general
formula (1), the (Z) isomer is particularly superior to the (E)
isomer in plant disease controlling activity. However, both the (E)
isomer and the (Z) isomer exist in a fixed ratio in the form of a
mixture since the (Z) isomer is converted into the (E) isomer by
light in a natural environment. The stable ratios of the (E) and
(Z) isomers vary according to the type of compound.
Method
[0051] The tetrazoyloxime derivative represented by the general
formula (1) can be prepared by the method (A) in the case in which
a tetrazoyl group is a tetrazoyl group represented by the general
formula (2), or can be prepared by the method (B) in the case in
which a tetrazoyl group is a tetrazoyl group represented by the
general formula (3). However, the method of preparing the
tetrazoyloxime derivative of the present invention is not limited
these methods. ##STR16## wherein X, Y and Het are as defined in the
general formula (1), and L represents a chlorine atom, a bromine
atom, or an iodine atom.
[0052] According to the method (A), a tetrazoyloxime derivative
represented by the general formula (1-a) is prepared by reacting a
tetrazoylmethanone derivative represented by the general formula
(a-1) with hydroxylamine to obtain a tetrazoylhydroxyimino
derivative represented by the general formula (6'), and reacting
the tetrazoylhydroxyimino derivative with a compound represented by
the general formula (b) in the presence of a base (for example,
sodium hydride, sodium hydroxide, potassium hydroxide, sodium
carbonate, potassium carbonate, cesium carbonate, triethylamine,
pyridine, or N,N-dimethylaminopyridine).
[0053] The tetrazoylmethanone derivative represented by the general
formula (a-1), as a starting material, can be easily prepared by
reacting 1-alkyltetrazole with esters according to the method
described, for example, in the document (Can. J. Chem., Vol. 49,
page 2139, 1971). ##STR17## wherein X, Y and Het are as defined in
the general formula (1), and L represents a chlorine atom, a
bromine atom, or an iodine atom.
[0054] According to the method (B), a tetrazoyloxime derivative
represented by the general formula (1-b) is prepared by reacting a
tetrazoylhydroxyimino derivative represented by the general
represented by the general formula (7') with a compound represented
by the general formula (b) in the presence of a base (for example,
sodium hydride, sodium hydroxide, potassium hydroxide, sodium
carbonate, potassium carbonate, cesium carbonate, triethylamine,
pyridine, or N,N-dimethylaminopyridine).
[0055] The tetrazoylhydroxyimino compound represented by the
general formula (7'), as a starting material, can be easily
prepared by reacting 5-alkyltetrazole with phenylhydroxyiminoyl
chloride in the presence of triethylamine according to the method
described, for example, in the document (Bull. Soc. Chim. Belg.
Vol. 96, page 675, 1987).
[0056] Specific structures of the tetrazoyloxime derivative
represented by the general formula (1) of the present invention
prepared by the method described above are as shown in Tables 1 to
23. In the tables, X, Y, Z and R are as defined in the general
formula (1), and the abbreviation cyclo denotes a ring structure.
TABLE-US-00002 TABLE 1 ##STR18## Compound No. Z R X Y (1)-1 H H H
CH.sub.3 (1)-2 H.sub.2N H H CH.sub.3 (1)-3 HCONH H H CH.sub.3 (1)-4
CH.sub.3CONH H H CH.sub.3 (1)-5 CH.sub.3CH.sub.2CONH H H CH.sub.3
(1)-6 CH.sub.3CH.sub.2CH.sub.2CONH H H CH.sub.3 (1)-7
(CH.sub.3).sub.2CHCONH H H CH.sub.3 (1)-8
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CONH H H CH.sub.3 (1)-9
(CH.sub.3).sub.2CHCH.sub.2CONH H H CH.sub.3 (1)-10
CH.sub.3CH.sub.2CH(CH.sub.3)CONH H H CH.sub.3 (1)-11
(CH.sub.3).sub.3CCONH H H CH.sub.3 (1)-12
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H CH.sub.3 (1)-13
(CH.sub.3).sub.2CHCH.sub.2CH.sub.2CONH H H CH.sub.3 (1)-14
CH.sub.3CH.sub.2CH(CH.sub.3)CH.sub.2CONH H H CH.sub.3 (1)-15
CH.sub.3CH.sub.2CH.sub.2CH(CH.sub.3)CONH H H CH.sub.3 (1)-16
(CH.sub.3).sub.3CCH.sub.2CONH H H CH.sub.3 (1)-17
(CH.sub.3CH.sub.2).sub.2CHCONH H H CH.sub.3 (1)-18
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H CH.sub.3
(1)-19 CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH
H H CH.sub.3 (1)-20
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CON-
H H H CH.sub.3 (1)-21 cyclo-C.sub.3H.sub.5--CONH H H CH.sub.3
(1)-22 cyclo-C.sub.5H.sub.9--CONH H H CH.sub.3 (1)-23
cyclo-C.sub.6H.sub.11--CONH H H CH.sub.3
[0057] TABLE-US-00003 TABLE 2 ##STR19## Compound No. Z R X Y (2)-1
H H H CH.sub.3 (2)-2 H.sub.2N H H CH.sub.3 (2)-3 HCONH H H CH.sub.3
(2)-4 CH.sub.3CONH H H CH.sub.3 (2)-5 CH.sub.3CH.sub.2CONH H H
CH.sub.3 (2)-6 CH.sub.3CH.sub.2CH.sub.2CONH H H CH.sub.3 (2)-7
(CH.sub.3).sub.2CHCONH H H CH.sub.3 (2)-8
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CONH H H CH.sub.3 (2)-9
(CH.sub.3).sub.2CHCH.sub.2CONH H H CH.sub.3 (2)-10
CH.sub.3CH.sub.2CH(CH.sub.3)CONH H H CH.sub.3 (2)-11
(CH.sub.3).sub.3CCONH H H CH.sub.3 (2)-12
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H CH.sub.3 (2)-13
(CH.sub.3).sub.2CHCH.sub.2CH.sub.2CONH H H CH.sub.3 (2)-14
CH.sub.3CH.sub.2CH(CH.sub.3)CH.sub.2CONH H H CH.sub.3 (2)-15
CH.sub.3CH.sub.2CH.sub.2CH(CH.sub.3)CONH H H CH.sub.3 (2)-16
(CH.sub.3).sub.3CCH.sub.2CONH H H CH.sub.3 (2)-17
(CH.sub.3CH.sub.2).sub.2CHCONH H H CH.sub.3 (2)-18
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H CH.sub.3
(2)-19 CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH
H H CH.sub.3 (2)-20
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CON-
H H H CH.sub.3 (2)-21 cyclo-C.sub.3H.sub.5--CONH H H CH.sub.3
(2)-22 cyclo-C.sub.5H.sub.9--CONH H H CH.sub.3 (2)-23
cyclo-C.sub.6H.sub.11--CONH H H CH.sub.3
[0058] TABLE-US-00004 TABLE 3 ##STR20## Com- pound No. Z R X Y
(3)-1 CH.sub.3OCONH H H CH.sub.3 (3)-2 CH.sub.3CH.sub.2OCONH H H
CH.sub.3 (3)-3 CH.sub.3CH.sub.2CH.sub.2OCONH H H CH.sub.3 (3)-4
(CH.sub.3).sub.2CHOCONH H H CH.sub.3 (3)-5
CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H H CH.sub.3 (3)-6
(CH.sub.3).sub.2CHCH.sub.2OCONH H H CH.sub.3 (3)-7
CH.sub.3CH.sub.2CH(CH.sub.3)OCONH H H CH.sub.3 (3)-8
(CH.sub.3).sub.3COCONH H H CH.sub.3 (3)-9
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H H CH.sub.3 (3)-10
(CH.sub.3).sub.2CHCH.sub.2CH.sub.2OCONH H H CH.sub.3 (3)-11
CH.sub.3CH.sub.2CH(CH.sub.3)CH.sub.2OCONH H H CH.sub.3 (3)-12
CH.sub.3CH.sub.2CH.sub.2CH(CH.sub.3)OCONH H H CH.sub.3 (3)-13
(CH.sub.3).sub.3CCH.sub.2OCONH H H CH.sub.3 (3)-14
(CH.sub.3CH.sub.2).sub.2CHOCONH H H CH.sub.3 (3)-15
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H H CH.sub.3
(3)-16
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H H
CH.sub.3 (3)-17
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCO-
NH H H CH.sub.3 (3)-18 C.sub.6H.sub.5CH.sub.2OCONH H H CH.sub.3
(3)-19 C.sub.6H.sub.5CH.sub.2CH.sub.2OCONH H H CH.sub.3 (3)-20
cyclo-C.sub.3H.sub.5--OCONH H H CH.sub.3 (3)-21
CH.sub.3CH.sub.2C(CH.sub.3).sub.2OCONH H H CH.sub.3 (3)-22
cyclo-C.sub.5H.sub.9--OCONH H H CH.sub.3 (3)-23
cyclo-C.sub.6H.sub.11--OCONH H H CH.sub.3 (3)-24
CH.sub.3CONHCH.sub.2CH.sub.2OCONH H H CH.sub.3 (3)-25
CH.sub.3CONHCH.sub.2CH.sub.2CH.sub.2OCONH H H CH.sub.3
[0059] TABLE-US-00005 TABLE 4 ##STR21## Com- pound No. Z R X Y
(4)-1 CH.sub.3OCONH H H CH.sub.3 (4)-2 CH.sub.3CH.sub.2OCONH H H
CH.sub.3 (4)-3 CH.sub.3CH.sub.2CH.sub.2OCONH H H CH.sub.3 (4)-4
(CH.sub.3).sub.2CHOCONH H H CH.sub.3 (4)-5
CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H H CH.sub.3 (4)-6
(CH.sub.3).sub.2CHCH.sub.2OCONH H H CH.sub.3 (4)-7
CH.sub.3CH.sub.2CH(CH.sub.3)OCONH H H CH.sub.3 (4)-8
(CH.sub.3).sub.3COCONH H H CH.sub.3 (4)-9
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H H CH.sub.3 (4)-10
(CH.sub.3).sub.2CHCH.sub.2CH.sub.2OCONH H H CH.sub.3 (4)-11
CH.sub.3CH.sub.2CH(CH.sub.3)CH.sub.2OCONH H H CH.sub.3 (4)-12
CH.sub.3CH.sub.2CH.sub.2CH(CH.sub.3)OCONH H H CH.sub.3 (4)-13
(CH.sub.3).sub.3CCH.sub.2OCONH H H CH.sub.3 (4)-14
(CH.sub.3CH.sub.2).sub.2CHOCONH H H CH.sub.3 (4)-15
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H H CH.sub.3
(4)-16
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H H
CH.sub.3 (4)-17
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCO-
NH H H CH.sub.3 (4)-18 C.sub.6H.sub.5CH.sub.2OCONH H H CH.sub.3
(4)-19 C.sub.6H.sub.5CH.sub.2CH.sub.2OCONH H H CH.sub.3 (4)-20
cyclo-C.sub.3H.sub.5--OCONH H H CH.sub.3 (4)-21
CH.sub.3CONHCH.sub.2CH.sub.2OCONH H H CH.sub.3 (4)-22
CH.sub.3CONHCH.sub.2CH.sub.2CH.sub.2OCONH H H CH.sub.3
[0060] TABLE-US-00006 TABLE 5 ##STR22## Compound No. Z R X Y (5)-1
CH.sub.3OCH.sub.2CONH H H CH.sub.3 (5)-2
CH.sub.3CH.sub.2OCH.sub.2CONH H H CH.sub.3 (5)-3
CH.sub.3CH.sub.2OCH.sub.2CH.sub.2CONH H H CH.sub.3 (5)-4
CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCH.sub.2CONH H H CH.sub.3 (5)-5
CH.sub.3SCH.sub.2CONH H H CH.sub.3 (5)-6
CH.sub.3SCH.sub.2CH.sub.2CONH H H CH.sub.3 (5)-7
CH.sub.3C(.dbd.CH.sub.2)CONH H H CH.sub.3 (5)-8
CH.sub.3CH.dbd.CHCH.sub.2CH.sub.2CONH H H CH.sub.3 (5)-9
CH.sub.3CH.sub.2CH.dbd.CHCH.sub.2CONH H H CH.sub.3 (5)-10
CH.sub.3CH.sub.2CH.dbd.CHCONH H H CH.sub.3 (5)-11
CH.sub.3CH.sub.2CH.sub.2CH.dbd.CHCONH H H CH.sub.3 (5)-12
C.sub.6H.sub.5CH.sub.2CONH H H CH.sub.3 (5)-13
C.sub.6H.sub.5CH.sub.2CH.sub.2CONH H H CH.sub.3 (5)-14
C.sub.6H.sub.5CONH H H CH.sub.3 (5)-15 ClCH.sub.2CONH H H CH.sub.3
(5)-16 F.sub.2CHCONH H H CH.sub.3 (5)-17 F.sub.3CCONH H H CH.sub.3
(5)-18 F.sub.3CCH.sub.2CONH H H CH.sub.3 (5)-19
CH.sub.3CONHCH.sub.2CH.sub.2CONH H H CH.sub.3 (5)-20
CH.sub.3CONHCH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H
CH.sub.3
[0061] TABLE-US-00007 TABLE 6 ##STR23## Compound No. Z R X Y (6)-1
CH.sub.3OCH.sub.2CONH H H CH.sub.3 (6)-2
CH.sub.3CH.sub.2OCH.sub.2CONH H H CH.sub.3 (6)-3
CH.sub.3CH.sub.2OCH.sub.2CH.sub.2CONH H H CH.sub.3 (6)-4
CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCH.sub.2CONH H H CH.sub.3 (6)-5
CH.sub.3SCH.sub.2CONH H H CH.sub.3 (6)-6
CH.sub.3SCH.sub.2CH.sub.2CONH H H CH.sub.3 (6)-7
CH.sub.3C(.dbd.CH.sub.2)CONH H H CH.sub.3 (6)-8
CH.sub.3CH.dbd.CHCH.sub.2CH.sub.2CONH H H CH.sub.3 (6)-9
CH.sub.3CH.sub.2CH.dbd.CHCH.sub.2CONH H H CH.sub.3 (6)-10
CH.sub.3CH.sub.2CH.dbd.CHCONH H H CH.sub.3 (6)-11
CH.sub.3CH.sub.2CH.sub.2CH.dbd.CHCONH H H CH.sub.3 (6)-12
C.sub.6H.sub.5CH.sub.2CONH H H CH.sub.3 (6)-13
C.sub.6H.sub.5CH.sub.2CH.sub.2CONH H H CH.sub.3 (6)-14
C.sub.6H.sub.5CONH H H CH.sub.3 (6)-15
CH.sub.3CH.sub.2CH.sub.2OCH.sub.2CH.sub.2CONH H H CH.sub.3 (6)-16
CH.sub.30CH.sub.2CH.sub.2OCONH H H CH.sub.3 (6)-17 F.sub.2CHCONH H
H CH.sub.3 (6)-18 F.sub.3CCONH H H CH.sub.3 (6)-19
F.sub.3CCH.sub.2CH.sub.2CONH H H CH.sub.3 (6)-20
CH.sub.3CONHCH.sub.2CH.sub.2CONH H H CH.sub.3 (6)-21
CH.sub.3CONHCH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H
CH.sub.3
[0062] TABLE-US-00008 TABLE 7 ##STR24## Compound No. Z R X Y (7)-1
CH.sub.3CH.sub.2CH.sub.2CONH H 4-Cl CH.sub.3 (7)-2
(CH.sub.3).sub.2CHCONH H 4-Cl CH.sub.3 (7)-3
cyclo-C.sub.3H.sub.5--CONH H 4-Cl CH.sub.3 (7)-4
CH.sub.3CH.sub.2CONH H 3-F CH.sub.3 (7)-5 (CH.sub.3).sub.2CHCONH H
3-F CH.sub.3 (7)-6 cyclo-C.sub.3H.sub.5--CONH H 3-F CH.sub.3 (7)-7
(CH.sub.3).sub.3CCONH H 3-F CH.sub.3 (7)-8 (CH.sub.3).sub.2CHCONH H
4-F CH.sub.3 (7)-9 (CH.sub.3).sub.2CHCONH H 4-CH.sub.3O CH.sub.3
(7)-10 (CH.sub.3).sub.3CCONH H 4-CH.sub.3O CH.sub.3 (7)-11
cyclo-C.sub.3H.sub.5--CONH H 4-CH.sub.3O CH.sub.3 (7)-12
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H 4-CH.sub.3 CH.sub.3
(7)-13 (CH.sub.3).sub.3CCH.sub.2CONH H 4-CH.sub.3 CH.sub.3 (7)-14
(CH.sub.3).sub.2CHCONH Cl H CH.sub.3 (7)-15 (CH.sub.3).sub.2CHCONH
Cl H CH.sub.3CH.sub.2 (7)-16 (CH.sub.3).sub.3CCONH H H
CH.sub.3CH.sub.2 (7)-17 (CH.sub.3).sub.2CHCONH H H CH.sub.3CH.sub.2
(7)-18 H H 4-F CH.sub.3 (7)-19 H H 3-F CH.sub.3 (7)-20 H H 4-Cl
CH.sub.3
[0063] TABLE-US-00009 TABLE 8 ##STR25## Compound No. Z R X Y (8)-1
CH.sub.3CH.sub.2CH.sub.2CONH H 4-Cl CH.sub.3 (8)-2
(CH.sub.3).sub.2CHCONH H 4-Cl CH.sub.3 (8)-3
cyclo-C.sub.3H.sub.5--CONH H 4-Cl CH.sub.3 (8)-4
CH.sub.3CH.sub.2CONH H 3-F CH.sub.3 (8)-5 (CH.sub.3).sub.2CHCONH H
3-F CH.sub.3 (8)-6 cyclo-C.sub.3H.sub.5--CONH H 3-F CH.sub.3 (8)-7
(CH.sub.3).sub.3CCONH H 3-F CH.sub.3 (8)-8 (CH.sub.3).sub.2CHCONH H
4-F CH.sub.3 (8)-9 (CH.sub.3).sub.2CHCONH H 4-CH.sub.3O CH.sub.3
(8)-10 (CH.sub.3).sub.3CCONH H 4-CH.sub.3O CH.sub.3 (8)-11
cyclo-C.sub.3H.sub.5--CONH H 4-CH.sub.3O CH.sub.3 (8)-12
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H 4-CH.sub.3 CH.sub.3
(8)-13 (CH.sub.3).sub.3CCH.sub.2CONH H 4-CH.sub.3 CH.sub.3 (8)-14
(CH.sub.3).sub.2CHCONH Cl H CH.sub.3 (8)-15 (CH.sub.3).sub.2CHCONH
Cl H CH.sub.3CH.sub.2 (8)-16 (CH.sub.3).sub.3CCONH H H
CH.sub.3CH.sub.2 (8)-17 (CH.sub.3).sub.3CCONH H 4-Cl CH.sub.3
[0064] TABLE-US-00010 TABLE 9 ##STR26## Compound No Z R X Y (9)-1
(CH.sub.3).sub.3COCONH H 3-F CH.sub.3 (9)-2 (CH.sub.3).sub.2CHOCONH
H 4-F CH.sub.3 (9)-3 (CH.sub.3).sub.3COCONH H 4-F CH.sub.3 (9)-4
(CH.sub.3).sub.3COCONH H 4-CH.sub.3 CH.sub.3 (9)-5
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H 4-CH.sub.3 CH.sub.3
(9)-6 CH.sub.3CH.sub.2CH.sub.2OCONH H 3-F CH.sub.3 (9)-7
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H 3-CH.sub.3 CH.sub.3
(9)-8 (CH.sub.3).sub.3COCONH H 3-CH.sub.3 CH.sub.3 (9)-9
CH.sub.3CH.sub.2C(CH.sub.3).sub.2OCONH H 4-CH.sub.3 CH.sub.3 (9)-10
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H 2-CH.sub.3 CH.sub.3
(9)-11 CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H 2-CH.sub.3
CH.sub.3
[0065] TABLE-US-00011 TABLE 10 ##STR27## Compound No Z R X Y (10)-1
(CH.sub.3).sub.3COCONH H 3-F CH.sub.3 (10)-2
(CH.sub.3).sub.2CHOCONH H 4-F CH.sub.3 (10)-3
(CH.sub.3).sub.3COCONH H 4-F CH.sub.3 (10)-4 (CH.sub.3).sub.3COCONH
H 4-CH.sub.3 CH.sub.3 (10)-5
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H 4-CH.sub.3
CH.sub.3
[0066] TABLE-US-00012 TABLE 11 ##STR28## Compound No. Z R X Y
(11)-1 H H H CH.sub.3 (11)-2 H.sub.2H H H CH.sub.3 (11)-3 HCONH H H
CH.sub.3 (11)-4 CH.sub.3CONH H H CH.sub.3 (11)-5
CH.sub.3CH.sub.2CONH H H CH.sub.3 (11)-6
CH.sub.3CH.sub.2CH.sub.2CONH H H CH.sub.3 (11)-7
(CH.sub.3).sub.2CHCONH H H CH.sub.3 (11)-8
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CONH H H CH.sub.3 (11)-9
(CH.sub.3).sub.2CHCH.sub.2CONH H H CH.sub.3 (11)-10
CH.sub.3CH.sub.2CH(CH.sub.3)CONH H H CH.sub.3 (11)-11
(CH.sub.3).sub.3CCONH H H CH.sub.3 (11)-12
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H CH.sub.3 (11)-13
(CH.sub.3).sub.2CHCH.sub.2CH.sub.2CONH H H CH.sub.3 (11)-14
CH.sub.3CH.sub.2CH(CH.sub.3)CH.sub.2CONH H H CH.sub.3 (11)-15
CH.sub.3CH.sub.2CH.sub.2CH(CH.sub.3)CONH H H CH.sub.3 (11)-16
(CH.sub.3).sub.3CCH.sub.2CONH H H CH.sub.3 (11)-17
(CH.sub.3CH.sub.2).sub.2CHCONH H H CH.sub.3 (11)-18
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H CH.sub.3
(11)-19
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H
CH.sub.3 (11)-20
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CO-
NH H H CH.sub.3 (11)-21 cyclo-C.sub.3H.sub.5--CONH H H CH.sub.3
(11)-22 cyclo-C.sub.5H.sub.9--CONH H H CH.sub.3 (11)-23
cyclo-C.sub.6H.sub.11--CONH H H CH.sub.3 (11)-24
CH.sub.3CONHCH.sub.2CH.sub.2CONH H H CH.sub.3 (11)-25
CH.sub.3CONHCH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H
CH.sub.3
[0067] TABLE-US-00013 TABLE 12 ##STR29## Compound No. Z R X Y
(12)-1 H H H CH.sub.3 (12)-2 H.sub.2H H H CH.sub.3 (12)-3 HCONH H H
CH.sub.3 (12)-4 CH.sub.3CONH H H CH.sub.3 (12)-5
CH.sub.3CH.sub.2CONH H H CH.sub.3 (12)-6
CH.sub.3CH.sub.2CH.sub.2CONH H H CH.sub.3 (12)-7
(CH.sub.3).sub.3CHCONH H H CH.sub.3 (12)-8
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CONH H H CH.sub.3 (12)-9
(CH.sub.3).sub.2CHCH.sub.2CONH H H CH.sub.3 (12)-10
CH.sub.3CH.sub.2CH(CH.sub.3)CONH H H CH.sub.3 (12)-11
(CH.sub.3).sub.3CCONH H H CH.sub.3 (12)-12
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H CH.sub.3 (12)-13
(CH.sub.3).sub.2CHCH.sub.2CH.sub.2CONH H H CH.sub.3 (12)-14
CH.sub.3CH.sub.2CH(CH.sub.3)CH.sub.2CONH H H CH.sub.3 (12)-15
CH.sub.3CH.sub.2CH.sub.2CH(CH.sub.3)CONH H H CH.sub.3 (12)-16
(CH.sub.3).sub.3CCH.sub.2CONH H H CH.sub.3 (12)-17
(CH.sub.3CH.sub.2).sub.2CHCONH H H CH.sub.3 (12)-18
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H CH.sub.3
(12)-19
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H
CH.sub.3 (12)-20
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CO-
NH H H CH.sub.3 (12)-21 cyclo-C.sub.3H.sub.5--CONH H H CH.sub.3
(12)-22 cyclo-C.sub.5H.sub.9--CONH H H CH.sub.3 (12)-23
cyclo-C.sub.6H.sub.11--CONH H H CH.sub.3 (12)-24
CH.sub.3CONHCH.sub.2CH.sub.2CONH H H CH.sub.3 (12)-25
CH.sub.3CONHCH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H
CH.sub.3
[0068] TABLE-US-00014 TABLE 13 ##STR30## Com- pound No. Z R X Y
(13)-1 CH.sub.3OCONH H H CH.sub.3 (13)-2 CH.sub.3CH.sub.2OCONH H H
CH.sub.3 (13)-3 CH.sub.3CH.sub.2CH.sub.2OCONH H H CH.sub.3 (13)-4
(CH.sub.3).sub.2CHOCONH H H CH.sub.3 (13)-5
CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H H CH.sub.3 (13)-6
(CH.sub.3).sub.2CHCH.sub.2OCONH H H CH.sub.3 (13)-7
CH.sub.3CH.sub.2CH(CH.sub.3)OCONH H H CH.sub.3 (13)-8
(CH.sub.3).sub.3COCONH H H CH.sub.3 (13)-9
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H H CH.sub.3 (13)-10
(CH.sub.3).sub.2CHCH.sub.2CH.sub.2OCONH H H CH.sub.3 (13)-11
CH.sub.3CH.sub.2CH(CH.sub.3)CH.sub.2OCONH H H CH.sub.3 (13)-12
CH.sub.3CH.sub.2CH.sub.2CH(CH.sub.3)OCONH H H CH.sub.3 (13)-13
(CH.sub.3).sub.3CCH.sub.2OCONH H H CH.sub.3 (13)-14
(CH.sub.3CH.sub.2).sub.2CHOCONH H H CH.sub.3 (13)-15
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H H CH.sub.3
(13)-16
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H H
CH.sub.3 (13)-17
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OC-
ONH H H CH.sub.3 (13)-18 C.sub.6H.sub.5CH.sub.2OCONH H H CH.sub.3
(13)-19 C.sub.6H.sub.5CH.sub.2CH.sub.2OCONH H H CH.sub.3 (13)-20
cyclo-C.sub.3H.sub.5--OCONH H H CH.sub.3 (13)-21
cyclo-C.sub.5H.sub.9--OCONH H H CH.sub.3 (13)-22
cyclo-C.sub.6H.sub.11--OCONH H H CH.sub.3 (13)-23
CH.sub.3CONHCH.sub.2CH.sub.2OCONH H H CH.sub.3 (13)-24
CH.sub.3CONHCH.sub.2CH.sub.2CH.sub.2OCONH H H CH.sub.3
[0069] TABLE-US-00015 TABLE 14 ##STR31## Com- pound No. Z R X Y
(14)-1 CH.sub.3OCONH H H CH.sub.3 (14)-2 CH.sub.3CH.sub.2OCONH H H
CH.sub.3 (14)-3 CH.sub.3CH.sub.2CH.sub.2OCONH H H CH.sub.3 (14)-4
(CH.sub.3).sub.2CHOCONH H H CH.sub.3 (14)-5
CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H H CH.sub.3 (14)-6
(CH.sub.3).sub.2CHCH.sub.2OCONH H H CH.sub.3 (14)-7
CH.sub.3CH.sub.2CH(CH.sub.3)OCONH H H CH.sub.3 (14)-8
(CH.sub.3).sub.3COCONH H H CH.sub.3 (14)-9
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H H CH.sub.3 (14)-10
(CH.sub.3).sub.2CHCH.sub.2CH.sub.2OCONH H H CH.sub.3 (14)-11
CH.sub.3CH.sub.2CH(CH.sub.3)CH.sub.2OCONH H H CH.sub.3 (14)-12
CH.sub.3CH.sub.2CH.sub.2CH(CH.sub.3)OCONH H H CH.sub.3 (14)-13
(CH.sub.3).sub.3CCH.sub.2OCONH H H CH.sub.3 (14)-14
(CH.sub.3CH.sub.2).sub.2CHOCONH H H CH.sub.3 (14)-15
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H H CH.sub.3
(14)-16
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H H
CH.sub.3 (14)-17
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OC-
ONH H H CH.sub.3 (14)-18 C.sub.6H.sub.5CH.sub.2OCONH H H CH.sub.3
(14)-19 C.sub.6H.sub.5CH.sub.2CH.sub.2OCONH H H CH.sub.3 (14)-20
cyclo-C.sub.3H.sub.5--OCONH H H CH.sub.3 (14)-21
CH.sub.3CONHCH.sub.2CH.sub.2OCONH H H CH.sub.3 (14)-22
CH.sub.3CONHCH.sub.2CH.sub.2CH.sub.2OCONH H H CH.sub.3
[0070] TABLE-US-00016 TABLE 15 ##STR32## Compound No. Z R X Y
(15)-1 C.sub.6H.sub.5CH.sub.2CONH H H CH.sub.3 (15)-2
C.sub.6H.sub.5CH.sub.2CH.sub.2CONH H H CH.sub.3 (15)-3
C.sub.6H.sub.5CONH H H CH.sub.3 (15)-4 F.sub.2CHCONH H H CH.sub.3
(15)-5 F.sub.3CCONH H H CH.sub.3 (15)-6
F.sub.3CCH.sub.2CH.sub.2CONH H H CH.sub.3
[0071] TABLE-US-00017 TABLE 16 ##STR33## Compound No. Z R X Y
(16)-1 C.sub.6H.sub.5CH.sub.2CONH H H CH.sub.3 (16)-2
C.sub.6H.sub.5CH.sub.2CH.sub.2CONH H H CH.sub.3 (16)-3
C.sub.6H.sub.5CONH H H CH.sub.3 (16)-4 F.sub.2CHCONH H H CH.sub.3
(16)-5 F.sub.3CCONH H H CH.sub.3 (16)-6
F.sub.3CCH.sub.2CH.sub.2CONH H H CH.sub.3
[0072] TABLE-US-00018 TABLE 17 ##STR34## Compound No. Z R X Y
(17)-1 CH.sub.3CH.sub.2CH.sub.2CONH H 4-Cl CH.sub.3 (17)-2
(CH.sub.3).sub.2CHCONH H 4-Cl CH.sub.3 (17)-3
cyclo-C.sub.3H.sub.5--CONH H 4-Cl CH.sub.3 (17)-4
CH.sub.3CH.sub.2CONH H 3-F CH.sub.3 (17)-5 (CH.sub.3).sub.2CHCONH H
3-F CH.sub.3 (17)-6 cyclo-C.sub.3H.sub.5--CONH H 3-F CH.sub.3
(17)-7 (CH.sub.3).sub.3CCONH H 3-F CH.sub.3 (17)-8
(CH.sub.3).sub.2CHCONH H 4-F CH.sub.3 (17)-9 (CH.sub.3).sub.2CHCONH
H 4-CH.sub.3O CH.sub.3 (17)-10 (CH.sub.3).sub.3CCONH H 4-CH.sub.3O
CH.sub.3 (17)-11 cyclo-C.sub.3H.sub.5--CONH H 4-CH.sub.3O CH.sub.3
(17)-12 CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H 4-CH.sub.3
CH.sub.3 (17)-13 (CH.sub.3).sub.3CCH.sub.2CONH H 4-CH.sub.3
CH.sub.3 (17)-14 (CH.sub.3).sub.2CHCONH Cl H CH.sub.3 (17)-15
(CH.sub.3).sub.2CHCONH Cl H CH.sub.3CH.sub.2 (17)-16
(CH.sub.3).sub.3CCONH H H CH.sub.3CH.sub.2 (17)-17
(CH.sub.3).sub.2CHCONH H H CH.sub.3CH.sub.2 (17)-18 H H 4-F
CH.sub.3 (17)-19 H H 3-F CH.sub.3 (17)-20 H H 4-Cl CH.sub.3 (17)-21
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H
CH.sub.3CH.sub.2
[0073] TABLE-US-00019 TABLE 18 ##STR35## Compound No. Z R X Y
(18)-1 CH.sub.3CH.sub.2CH.sub.2CONH H 4-Cl CH.sub.3 (18)-2
(CH.sub.3).sub.2CHCONH H 4-Cl CH.sub.3 (18)-3
cyclo-C.sub.3H.sub.5--CONH H 4-Cl CH.sub.3 (18)-4
CH.sub.3CH.sub.2CONH H 3-F CH.sub.3 (18)-5 (CH.sub.3).sub.2CHCONH H
3-F CH.sub.3 (18)-6 cyclo-C.sub.3H.sub.5--CONH H 3-F CH.sub.3
(18)-7 (CH.sub.3).sub.3CCONH H 3-F CH.sub.3 (18)-8
(CH.sub.3).sub.2CHCONH H 4-F CH.sub.3 (18)-9 (CH.sub.3).sub.2CHCONH
H 4-CH.sub.3O CH.sub.3 (18)-10 (CH.sub.3).sub.3CCONH H 4-CH.sub.3O
CH.sub.3 (18)-11 cyclo-C.sub.3H.sub.5--CONH H 4-CH.sub.3O CH.sub.3
(18)-12 CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H 4-CH.sub.3
CH.sub.3 (18)-13 (CH.sub.3).sub.3CCH.sub.2CONH H 4-CH.sub.3
CH.sub.3 (18)-14 (CH.sub.3).sub.2CHCONH Cl H CH.sub.3 (18)-15
(CH.sub.3).sub.2CHCONH Cl H CH.sub.3CH.sub.2 (18)-16
(CH.sub.3).sub.3CCONH H H CH.sub.3CH.sub.2 (18)-17
(CH.sub.3).sub.2CHCONH H H CH.sub.3 (18)-18
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CONH H 4-Cl CH.sub.3 (18)-19
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H
CH.sub.3CH.sub.2
[0074] TABLE-US-00020 TABLE 19 ##STR36## Compound No Z R X Y (19)-1
(CH.sub.3).sub.3COCONH H 3-F CH.sub.3 (19)-2
(CH.sub.3).sub.2CHOCONH H 4-F CH.sub.3 (19)-3
(CH.sub.3).sub.3COCONH H 4-F CH.sub.3 (19)-4 (CH.sub.3).sub.3COCONH
H 4-CH.sub.3 CH.sub.3 (19)-5 CH.sub.3CH.sub.2CH.sub.2OCONH H 3-F
CH.sub.3 (19)-6 CH.sub.3CH.sub.2CH.sub.2OCONH H 4-F CH.sub.3 (19)-7
CH.sub.3CH.sub.2CH.sub.2OCONH H 3-Cl CH.sub.3 (19)-8
CH.sub.3CH.sub.2CH.sub.2OCONH H 4-Cl CH.sub.3 (19)-9
CH.sub.3CH.sub.2CH.sub.2OCONH H 3-CH.sub.3 CH.sub.3 (19)-10
CH.sub.3CH.sub.2CH.sub.2OCONH H 4-CH.sub.3 CH.sub.3 (19)-11
CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H 3-F CH.sub.3 (19)-12
CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H 4-F CH.sub.3 (19)-13
CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H 3-Cl CH.sub.3 (19)-14
CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H 4-Cl CH.sub.3 (19)-15
CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H 3-CH.sub.3 CH.sub.3 (19)-16
CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H 4-CH.sub.3 CH.sub.3 (19)-17
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H 3-F CH.sub.3
(19)-18 CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H 4-F
CH.sub.3 (19)-19 CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H
3-Cl CH.sub.3 (19)-20 CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH
H 4-Cl CH.sub.3 (19)-21
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H 3-CH.sub.3 CH.sub.3
(19)-22 CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H 4-CH.sub.3
CH.sub.3 (19)-23 CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H
4-CH.sub.3O CH.sub.3 (19)-24
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H 4-CH.sub.3O
CH.sub.3
[0075] TABLE-US-00021 TABLE 20 Compound No. Z R X Y (19)-25
CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H 4-CN CH.sub.3 (19)-26
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H 4-CN CH.sub.3
(19)-27 CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H 4-CH.sub.3SO.sub.2
CH.sub.3 (19)-28 CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H
4-CH.sub.3SO.sub.2 CH.sub.3 (19)-29
CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H 4-NO.sub.2 CH.sub.3 (19)-30
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H 4-NO.sub.2 CH.sub.3
(19)-31 CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H 4-CF.sub.3 CH.sub.3
(19)-32 CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H 4-CF.sub.3
CH.sub.3 (19)-33 CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H H CH.sub.3
(19)-34 CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H 4-CH.sub.3CH.sub.2
CH.sub.3 (19)-35 CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H
4-(CH.sub.3).sub.3C CH.sub.3 (19)-36
CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H 4-C.sub.6H.sub.5 CH.sub.3
(19)-37 CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H 2-Cl CH.sub.3
(19)-38 CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH H 2-CH.sub.3
CH.sub.3
[0076] TABLE-US-00022 TABLE 21 ##STR37## Compound No Z R X Y (20)-1
(CH.sub.3).sub.3COCONH H 3-F CH.sub.3 (20)-2
(CH.sub.3).sub.2CHOCONH H 4-F CH.sub.3 (20)-3
(CH.sub.3).sub.3COCONH H 4-F CH.sub.3 (20)-4 (CH.sub.3).sub.3COCONH
H 4-CH.sub.3 CH.sub.3 (20)-5 CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCONH
H 4-CH.sub.3 CH.sub.3 (20)-6
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCONH H H
CH.sub.3CH.sub.2
[0077] TABLE-US-00023 TABLE 22 ##STR38## Compound No. Z R X Y
(21)-1 CH.sub.3NHCONH H H CH.sub.3 (21)-2 CH.sub.3CH.sub.2NHCONH H
H CH.sub.3 (21)-3 CH.sub.3CH.sub.2CH.sub.2NHCONH H H CH.sub.3
(21)-4 (CH.sub.3).sub.2CHNHCONH H H CH.sub.3 (21)-5
CH.sub.3CH.sub.2CH.sub.2CH.sub.2NHCONH H H CH.sub.3 (21)-6
(CH.sub.3).sub.2CHCH.sub.2NHCONH H H CH.sub.3 (21)-7
CH.sub.3CH.sub.2CH(CH.sub.3)NHCONH H H CH.sub.3 (21)-8
(CH.sub.3).sub.3CNHCONH H H CH.sub.3 (21)-9
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H CH.sub.3 (21)-10
(CH.sub.3).sub.2CHCH.sub.2CH.sub.2NHCONH H H CH.sub.3 (21)-11
CH.sub.3CH.sub.2CH(CH.sub.3)CH.sub.2CONH H H CH.sub.3 (21)-12
CH.sub.3CH.sub.2CH.sub.2CH(CH.sub.3)CONH H H CH.sub.3 (21)-13
(CH.sub.3).sub.3CCH.sub.2NHCONH H H CH.sub.3 (21)-14
(CH.sub.3CH.sub.2).sub.2CHNHCONH H H CH.sub.3 (21)-15
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H CH.sub.3
(21)-16
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CONH H H
CH.sub.3 (21)-17
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CO-
NH H H CH.sub.3
[0078] TABLE-US-00024 TABLE 23 ##STR39## Com- pound No. Z R X Y
(22)-1 CH.sub.3NHCONH H H CH.sub.3 (22)-2 CH.sub.3CH.sub.2NHCONH H
H CH.sub.3 (22)-3 CH.sub.3CH.sub.2CH.sub.2NHCONH H H CH.sub.3
(22)-4 (CH.sub.3).sub.2CHNHCONH H H CH.sub.3 (22)-5
CH.sub.3CH.sub.2CH.sub.2CH.sub.2NHCONH H H CH.sub.3 (22)-6
(CH.sub.3).sub.2CHCH.sub.2NHCONH H H CH.sub.3 (22)-7
CH.sub.3CH.sub.2CH(CH.sub.3)NHCONH H H CH.sub.3 (22)-8
(CH.sub.3).sub.3CNHCONH H H CH.sub.3 (22)-9
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2NHNHCONH H H CH.sub.3
(22)-10 (CH.sub.3).sub.2CHCH.sub.2CH.sub.2NHCONH H H CH.sub.3
(22)-11 CH.sub.3CH.sub.2CH(CH.sub.3)CH.sub.2NHCONH H H CH.sub.3
(22)-12 CH.sub.3CH.sub.2CH.sub.2CH(CH.sub.3)NHCONH H H CH.sub.3
(22)-13 (CH.sub.3).sub.3CCH.sub.2NHCONH H H CH.sub.3 (22)-14
(CH.sub.3CH.sub.2).sub.2CHNHCONH H H CH.sub.3 (22)-15
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2NHCONH H H CH.sub.3
(22)-16
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2NHCONH H H
CH.sub.3 (22)-17
CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH-
CONH H H CH.sub.3
[0079] The tetrazoyloxime derivative of the present invention has
high activity against various plant pathogens and exhibits high
control effects for prevention and treatment of plant diseases
caused by plant pathogens. The tetrazoyloxime derivative of the
present invention is particularly effective for various plant
diseases caused by filamentous fungi among plant pathogens, and is
used particularly preferably to control various plant diseases
caused by oomycetes, zygomycetes, ascomycetes, basidiomycetes, and
deuteromycetes. Examples of plant pathogens include, but are not
limited to, the following.
[0080] Examples of oomycetes include fungi belonging to the genus
Pythium, such as damping-off (Pythium ultimum) on various crops;
fungi belonging to the genus Phytophthora, such as late blight
(Phytophthora infestans) on potato and phytophthora rot
(Phytophthora capsici) on tomato; fungi belonging to the genus
Pseudoperonospora, such as downy mildew (Pseudoperonospora
cubensis) on cucumber and downy mildew (Pseudoperonospora humuli)
on hops; fungi belonging to the genus Plasmopara, such as downy
mildew (Plasmopara viticola) on grape; and fungi belonging to the
genus Peronospora, such as downy mildew (Peronospora brassicae) on
vegetables belonging to the family Cruciferae, downy mildew
(Peronospora destructor) on leeks, and downy mildew (Peronospora
spinaciae) on spinach.
[0081] Examples of ascomycetes include fungi belonging to the genus
Erysiphe, such as powdery mildew (Erysiphe graminis) on wheat;
fungi belonging to the genus Sphaerotheca, such as powdery mildew
(Sphaerotheca fuliginea) on vegetables; fungi belonging to the
genus Venturia, such as black spot (Venturia inaequalis) on apple
and black spot (Venturia nashicola) on pear; fungi belonging to the
genus Pyrenophora, such as net blotch (Pyrenophora teres) on
barley; fungi belonging to the genus Cochliobolus, such as leaf
spot (Cochliobolus sativus) on wheat; and fungi belonging to the
genus Sclerotinia, such as sclerotal disease (Sclerotinia
sclerotiorum) on vegetables.
[0082] Examples of basidiomycetes include fungi belonging to the
genus Puccinia, such as leaf rust (Puccinia recondita) on wheat;
fungi belonging to the genus Tilletia, such as bunt (Tilletia
caries) on wheat; and fungi belonging to the genus Ustilago, such
as head smut (Ustilago nuda) on barley.
[0083] Examples of deuteromycetes include fungi belonging to the
genus Phoma, such as stem blight (Phoma asparagi) on asparagus;
fungi belonging to the genus Septoria, such as glume blotch
(Septoria nodorum) on wheat; fungi belonging to the genus
Colletotrichum, such as anthracnose (Colletotrichum lagenarium) on
gourds; fungi belonging to the genus Pyricularia, such as blast
(Pyricularia oryzae) on rice; fungi belonging to the genus
Botrytis, such as gray mold (Botrytis cinerea) on vegetables; fungi
belonging to the genus Alternaria, such as alternaria blotch
(Alternaria mali) on apple and ring spot (Alternaria solani) on
tomato; fungi belonging to the genus Cercospora, such as brown
spots (Cercospora beticola) on sugar beet; fungi belonging to the
genus Cladosporium, such as black spot (Cladosporium carpophilum)
on peach; and fungi belonging to the genus Rhizoctonia, such as
sheath blight (Rhizoctonia solani) on rice.
[0084] Although the tetrazoyloxime derivative of the present
invention can be used alone as an agricultural chemical, the
tetrazoyloxime derivative, as an active ingredient, is usually
mixed with conventional solid and liquid carriers used in the
formulation of the agricultural chemical, and auxiliaries such as
dispersants, diluents, emulsifiers, spreaders, and thickeners to
give formulations in the form of wettable powders, liquid
formulations, oil solutions, dusts, granules, and sols
(flowables).
[0085] Examples of the solid and liquid carriers include talc,
clay, bentonite, kaolin, diatomaceous earth, montmorillonite, mica,
vermiculite, gypsum, calcium carbonate, white carbon, wood flour,
starch, alumina, silicate, dextrin, waxes, alcohols (e.g., methyl
alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol,
n-butyl alcohol, ethylene glycol, etc.), petroleum fractions (e.g.,
petroleum ether, kerosine, solvent naphtha, etc.), aliphatic or
alicyclic hydrocarbons (e.g., n-hexane, cyclohexane, etc.),
aromatic hydrocarbons (e.g., benzene, toluene, xylene,
ethylbenzene, chlorobenzene, cumene, methylnaphthalene, etc.),
halogenated hydrocarbons (e.g., chloroform, dichloromethane, etc.),
ethers (e.g., isopropyl ether, ethylene oxide, tetrahydrofuran,
etc.), ketones (e.g., acetone, methyl ethyl ketone, cyclohexanone,
methyl isobutyl ketone, etc.), esters (e.g., ethyl acetate, butyl
acetate, ethylene glycol acetate, amyl acetate, etc.), acid amides
(e.g., dimethylformamide, diethylacetanilide, etc.), nitriles
(e.g., acetonitrile, propionitrile, acrylonitrile, etc.),
sulfoxides (e.g., dimethyl sulfoxide, etc.), and alcohol ethers
(e.g., ethylene glycol monomethyl ether, ethylene glycol monoethyl
ether, etc.).
[0086] Examples of the auxiliary include nonionic surfactants
(e.g., polyoxyethylene alkyl ether, polyoxyethylene alkyl ester,
polyoxyethylene alkyl phenyl ether, polyoxyethylene sorbitan alkyl
ester, sorbitan alkyl ester, etc.), anionic surfactants (e.g.,
alkylbenzene sulfonate, alkyl sulfosuccinate, polyoxyethylene alkyl
sulfonate, aryl sulfonate, etc.), cationic surfactants (e.g.,
alkylamines, polyoxyethylene alkylamines, quaternary ammonium
salts, etc.), amphoteric surfactants (e.g., alkylaminoethylglycine,
alkyldimethylbetaine, etc.), polyvinyl alcohol,
hydroxypropylcellulose, carboxymethylcellulose, gum arabic,
tragacanth gum, xanthan gum, polyvinyl acetate, gelatin, casein,
and sodium alginate.
[0087] The tetrazoyloxime derivative of the present invention can
be mixed with agricultural chemicals such as publicly known
conventional fungicides, herbicides, plant growth regulators,
insecticides and acaricides, and fertilizers. The content of
tetrazoyloxime derivative of the present invention varies according
to the type of the formulation, the method of application, and
other conditions, but is usually within a range from 0.5 to 95% by
weight, and preferably from 2 to 70% by weight.
[0088] The method of applying the agricultural chemical of the
present invention includes, for example, application to plants
(stem and leaf application), application to growing soil of plants
(soil application), application to the surface of the water in a
paddy field (water surface application), and application to seeds
(seed treatment).
[0089] The amount of the agricultural chemical of the present
invention to be applied varies according to the kind of plant and
the type of damage. In the case of the stem and leaf application, a
solution containing an active ingredient in a concentration within
a range of 1 to 10000 ppm, preferably from 10 to 1000 ppm, is
preferably applied in an amount within a range from 50 to 300
liters per 10 ares. In the case of the soil application and water
surface application, the active ingredient is preferably applied in
an amount within a range from 0.1 to 1000 g, and particularly
preferably from 10 to 100 g, per 10 ares. In the case of the seed
treatment, the active ingredient is preferably applied in an amount
within a range from 0.001 to 50 g per 1 kg of seeds.
EXAMPLES
[0090] The following Preparation Examples, Formulation Examples and
Test Examples further illustrate the present invention, although
the present invention is not limited to these Examples.
[0091] First, Preparation Examples of the tetrazoylhydroxyimino
derivative are described.
Preparation Example 1
[0092] (1-methyltetrazol-5-yl)phenylmethanone (11.1 g, 59.1 mmol)
and hydroxylammonium chloride (10.3 g, 148 mmol) were added to 100
ml of pyridine, followed by stirring at 45.degree. C. for 24 hours.
After the completion of the reaction, the reaction solution was
concentrated under reduced pressure and water and ethyl acetate
were added to the resulting residue, and then the reaction product
was extracted. The organic layer was washed in turn with dilute
hydrochloric acid, water and an aqueous sodium hydrogencarbonate,
and the organic layer was dried over anhydrous magnesium sulfate.
The solvent was distilled off from the organic layer to obtain
(1-methyltetrazol-5-yl)phenylmethanoneoxime (12.0 g, yield: 100%)
represented by the formula: ##STR40##
[0093] .sup.1H-NMR(CDCl.sub.3, .delta.): 4.03(s, 3H), 7.3-7.55(m,
5H), 9.0(brd, 1H).
Preparation Example 2
[0094] In the same manner as in Preparation Example 1, except that
(1-methyltetrazol-5-yl)4-chlorophenylmethanone (560 mg, 2.52 mmol)
was used in place of (1-methyltetrazol-5-yl)phenylmethanone in
Preparation Example 1, 600 mg of
(1-methyltetrazol-5-yl)4-chlorophenylmethanoneoxime represented by
the formula: ##STR41## was obtained.
[0095] .sup.1H-NMR(CDCl.sub.3, .delta.): 4.04(s, 3H), 7.36(m, 2H),
7.46(m, 2H), 9.00(brd, 1H).
Preparation Example 3
[0096] In the same manner as in Preparation Example 1, except that
(1-methyltetrazol-5-yl)3-fluorophenylmethanone (964 mg, 4.68 mmol)
was used in place of (1-methyltetrazol-5-yl)phenylmethanone in
Preparation Example 1, 999 mg of
(1-methyltetrazol-5-yl)3-fluorophenylmethanoneoxime represented by
the formula: ##STR42## was obtained.
[0097] .sup.1H-NMR(CDCl.sub.3, .delta.): 4.04(s, 3H), 7.11(m, 1H),
7.2-7.5(m, 3H), 12.31(brd, 1H).
Preparation Example 4
[0098] In the same manner as in Preparation Example 1, except that
(1-methyltetrazol-5-yl)4-fluorophenylmethanone (850 mg, 4.14 mmol)
was used in place of (1-methyltetrazol-5-yl)phenylmethanone in
Preparation Example 1, 930 mg of
(1-methyltetrazol-5-yl)4-fluorophenylmethanoneoxime represented by
the formula: ##STR43## was obtained.
[0099] .sup.1H-NMR(CDCl.sub.3, .delta.): 4.05(s, 3H), 7.08(dd, 1H,
J=8.6, 8.6 Hz), 7.53(m, 2H), 8.68(brd, 1H).
Preparation Example 5
[0100] In the same manner as in Preparation Example 1, except that
(1-methyltetrazol-5-yl)4-methoxyphenylmethanone (386 mg, 1.77 mmol)
was used in place of (1-methyltetrazol-5-yl)phenylmethanone in
Preparation Example 1, 410 mg of
(1-methyltetrazol-5-yl)4-methoxyphenylmethanoneoxime represented by
the formula: ##STR44## was obtained.
[0101] .sup.1H-NMR(CDCl.sub.3, .delta.): 3.83(s, 3H), 4.03(s, 3H),
6.89(m, 2H), 7.45(m, 2H), 8.36(brd, 1H).
Preparation Example 6
[0102] In the same manner as in Preparation Example 1, except that
(1-methyltetrazol-5-yl)3-methylphenylmethanone (1.36 g, 6.78 mmol)
was used in place of (1-methyltetrazol-5-yl)phenylmethanone in
Preparation Example 1, 1.31 g of
1-methyltetrazol-5-yl)3-methylphenylmethanoneoxime represented by
the formula: ##STR45## was obtained.
[0103] .sup.1H-NMR(CDCl.sub.3, .delta.): 2.31(s, 3H), 3.99(s, 3H),
7.2-7.3(m, 5H), 9.92(brd, 1H).
Preparation Example 7
[0104] In the same manner as in Preparation Example 1, except that
(1-methyltetrazol-5-yl)4-methylphenylmethanone (1.65 g, 8.16 mmol)
was used in place of (1-methyltetrazol-5-yl)phenylmethanone in
Preparation Example 1, 1.67 g of
(1-methyltetrazol-5-yl)4-methylphenylmethanoneoxime represented by
the formula: ##STR46## was obtained.
[0105] .sup.1H-NMR(CDCl.sub.3, .delta.): 2.37(s, 3H), 4.01(s, 3H),
7.18(m, 2H), 7.37(m, 2H), 9.02(brd, 1H).
Preparation Example 8
[0106] In the same manner as in Preparation Example 1, except that
(1-methyltetrazol-5-yl)2-methylphenylmethanone (1.90 g, 9.40 mmol)
was used in place of (1-methyltetrazol-5-yl)phenylmethanone in
Preparation Example 1, 1.93 g of
(1-methyltetrazol-5-yl)2-methylphenylmethanoneoxime represented by
the formula: ##STR47## was obtained.
[0107] .sup.1H-NMR(CDCl.sub.3, .delta.): Z isomer: 2.22(s, 3H),
4.06(s, 3H), 7.2-7.4(m, 4H), 9.05(brd, 1H). E isomer: 2.21(s, 3H),
4.31(s, 3H), 7.15-7.45(m, 4H), 8.43(brd, 1H).
Preparation Example 9
[0108] In the same manner as in Preparation Example 1, except that
(1-ethyltetrazol-5-yl)phenylmethanone (1.00 g, 4.95 mmol) was used
in place of (1-methyltetrazol-5-yl)phenylmethanone in Preparation
Example 1, 1.00 g of (1-ethyltetrazol-5-yl)phenylmethanoneoxime
represented by the formula: ##STR48## was obtained.
[0109] .sup.1H-NMR(CDCl.sub.3, .delta.): 1.51(t, J=7.3 Hz, 3H),
4.35(q, J=7.3 Hz, 2H), 7.33-7.55 (m, 5H), 10.45(brd, 1H).
Preparation Example 10
[0110] To a solution prepared by dissolving 3-fluorobenzoaldoxime
(2.78 g, 20 mmol) in 25 ml of N,N-dimethylformamide, imide
N-chlorosuccinate (2.80 g, 21 mmol) was added while maintaining a
liquid temperature at 45.degree. C. or lower. After stirring at
room temperature for one hour, the reaction solution was poured
into saturated ammonium chloride water and then extracted with
ethyl acetate. The organic layer was washed in turn with water and
saturated saline solution, and the organic layer was dried over
anhydrous sodium sulfate. The solvent was distilled off from the
organic layer, and 5-methyltetrazole (1.70 g, 20 mmol) and 25 ml of
dichloromethane were added to the resulting residue. To the
solution, triethylamine (3.6 ml, 1.26 mmol) was added dropwise at
room temperature. After stirring at room temperature for 6 hours,
the reaction solution was poured into saturated ammonium chloride
water and then extracted with ethyl acetate. The organic layer was
washed in turn with water and saturated saline solution and then
dried over anhydrous sodium sulfate. The solvent was distilled off
and the resulting residue was purified by silica gel chromatography
to obtain 1.40 g of
(5-methyltetrazol-1-yl)-3-fluorophenylmethanoneoxime represented by
the formula: ##STR49##
[0111] .sup.1H-NMR(CDCl.sub.3, .delta.): 2.57 (s, 3H), 7.06-7.09(m,
1H), 7.18-7.27(m, 2H), 7.36-7.43(m, 1H), 8.67(s, 1H).
Preparation Example 11
[0112] In the same manner as in Preparation Example 10, except that
4-fluorobenzoaldoxime (2.78 g, 20 mmol) was used in place of
3-fluorobenzoaldoxime in Preparation Example 10, 1.00 g of
(5-methyltetrazol-1-yl)-4-fluorophenylmethanoneoxime represented by
the formula: ##STR50## was obtained.
[0113] .sup.1H-NMR(CDCl.sub.3, .delta.): 2.53 (s, 3H), 7.06-7.12(m,
2H), 7.38-7.45(m, 2H), 12.11(s, 1H).
Preparation Example 12
[0114] In the same manner as in Preparation Example 10, except that
3-chlorobenzoaldoxime (3.11 g, 20 mmol) was used in place of
3-fluorobenzoaldoxime in Preparation Example 10, 2.05 g of
(5-methyltetrazol-1-yl)-3-chlorophenylmethanoneoxime represented by
the formula: ##STR51## was obtained.
[0115] .sup.1H-NMR(CDCl.sub.3, .delta.): 2.58 (s, 3H), 7.20-7.23(m,
1H), 7.33-7.38(m, 2H), 7.46-7.51(m,1H), 9.22(s, 1H).
Preparation Example 13
[0116] In the same manner as in Preparation Example 10, except that
4-chlorobenzoaldoxime (3.11 g, 20 mmol) was used in place of
3-fluorobenzoaldoxime in Preparation Example 10, 2.17 g of
(5-methyltetrazol-1-yl)-4-chlorophenylmethanoneoxime represented by
the formula: ##STR52## was obtained.
[0117] .sup.1H-NMR(CDCl.sub.3, .delta.): 2.53 (s, 3H), 7.33-7.39(m,
4H), 12.07 (s, 1H).
Preparation Example 14
[0118] In the same manner as in Preparation Example 10, except that
4-methylbenzoaldoxime (2.70 g, 20 mmol) was used in place of
3-fluorobenzoaldoxime in Preparation Example 10, 2.50 g of
(5-methyltetrazol-1-yl)-4-methylphenylmethanoneoxime represented by
the formula: ##STR53## was obtained.
[0119] .sup.1H-NMR(CDCl.sub.3, .delta.): 2.39 (s, 3H), 2.56 (s,
3H), 7.20-7.30(m, 4H), 8.69(s, 1H).
Preparation Example 15
[0120] In the same manner as in Preparation Example 10, except that
4-methoxybenzoaldoxime (3.20 g, 20 mmol) was used in place of
3-fluorobenzoaldoxime in Preparation Example 10, 1.96 g of
(5-methyltetrazol-1-yl)-4-methoxyphenylmethanoneoxime represented
by the formula: ##STR54## was obtained.
[0121] .sup.1H-NMR(CDCl.sub.3, .delta.): 2.55 (s, 3H), 3.84 (s,
3H), 6.89-6.94(m, 2H), 7.30-7.35(m, 2H), 8.13(s, 1H).
Preparation Example 16
[0122] In the same manner as in Preparation Example 10, except that
4-cyanobenzoaldoxime (2.92 g, 20 mmol) was used in place of
3-fluorobenzoaldoxime in Preparation Example 10, 1.70 g of
5-methyltetrazol-1-yl)-4-cyanophenylmethanoneoxime represented by
the formula: ##STR55## was obtained.
[0123] .sup.1H-NMR(CDCl.sub.3, .delta.): 2.54 (s, 3H), 7.53-7.56(m,
2H), 7.68-7.71(m, 2H), 12.71(s, 1H).
Preparation Example 17
[0124] In the same manner as in Preparation Example 10, except that
4-methylsulfonylbenzoaldoxime (1.30 g, 6.5 mmol) was used in place
of 3-fluorobenzoaldoxime in Preparation Example 10, 1.20 g of
(5-methyltetrazol-1-yl)-4-methylsulfonylphenylmethanoneoxime
represented by the formula: ##STR56## was obtained.
[0125] .sup.1H-NMR(CDCl.sub.3, .delta.): 2.55 (s, 3H), 3.08 (s,
3H), 7.62-7.65(m, 2H), 7.95-7.98(m, 2H), 12.68(s, 1H).
Preparation Example 18
[0126] In the same manner as in Preparation Example 10, except that
4-nitrobenzoaldoxime (3.32 g, 20 mmol) was used in place of
3-fluorobenzoaldoxime in Preparation Example 10, 1.00 g of
(5-methyltetrazol-1-yl)-4-nitrophenylmethanoneoxime represented by
the formula: ##STR57## was obtained.
[0127] .sup.1H-NMR(CDCl.sub.3, .delta.): 2.55 (s, 3H), 7.61-7.64(m,
2H), 8.24-8.26(m, 2H), 12.72(s, 1H).
Preparation Example 19
[0128] In the same manner as in Preparation Example 10, except that
4-trifluoromethylbenzoaldoxime (3.78 g, 20 mmol) was used in place
of 3-fluorobenzoaldoxime in Preparation Example 10, 0.78 g of
(5-methyltetrazol-1-yl)-4-trifluoromethylphenylmethanoneoxime
represented by the formula: ##STR58## was obtained.
[0129] .sup.1HNMR(CDCl.sub.3, .delta.): 2.54(s,3H), 7.55(d, 2H,
J=8.41 Hz), 7.66(d, 2H, J=8.41 Hz), 12.26(s, 1H).
Preparation Example 20
[0130] In the same manner as in Preparation Example 10, except that
4-ethylbenzoaldoxime (1.49 g, 10 mmol) was used in place of
3-fluorobenzoaldoxime in Preparation Example 10, 1.35 g of
(5-methyltetrazol-1-yl)-4-ethylphenylmethanoneoxime represented by
the formula: ##STR59## was obtained.
[0131] .sup.1H-NMR(CDCl.sub.3, .delta.): 1.34(t, 3H, J=7.51 Hz),
2.56 (s, 3H), 2.69 (q, 2H, J=7.69H), 7.22-7.32(4H, m), 8.69(s,
1H).
Preparation Example 21
[0132] In the same manner as in Preparation Example 10, except that
4-tert-butylbenzoaldoxime (1.77 g, 10 mmol) was used in place of
3-fluorobenzoaldoxime in Preparation Example 10, 1.35 g of
(5-methyltetrazol-1-yl)-4-tert-butylphenylmethanoneoxime
represented by the formula: ##STR60## was obtained.
[0133] .sup.1H-NMR(CDCl.sub.3, .delta.):1.33(s, 9H), 2.55 (s, 3H),
7.32(d, 2H, J=8.62 Hz), 7.44(d, 2H, J=8.62 Hz), 7.99(s, 1H).
Preparation Example 22
[0134] In the same manner as in Preparation Example 10, except that
4-biphenylaldoxime (1.97 g, 20 mmol) was used in place of
3-fluorobenzoaldoxime in Preparation Example 10, 1.20 g of
5-methyltetrazol-1-yl)-4-biphenylmethanoneoxime represented by the
formula: ##STR61## was obtained.
[0135] .sup.1H-NMR(CDCl.sub.3, .delta.): 2.56 (s, 3H), 7.29-7.49(m,
5H), 7.58-7.63(m, 4H), 12.05(s, 1H).
Preparation Example 23
[0136] In the same manner as in Preparation Example 10, except that
5-ethyltetrazole (2.00 g, 20.4 mmol) was used in place of
5-methyltetrazole and benzaldoxime (2.70 g, 22 mmol) was used in
place of 3-fluorobenzoaldoxime in Preparation Example 10, 1.93 g of
(5-ethyltetrazol-1-yl)phenylmethanoneoxime represented by the
formula: ##STR62## was obtained.
[0137] .sup.1H-NMR(CDCl.sub.3, .delta.): 1.37(t, J=7.6 Hz, 3H),
2.88(q, J=7.6 Hz, 2H), 7.35-7.55(m, 5H), 9.42(s, 1H).
[0138] Preparation Examples of a tetrazoyloxime derivative are
described below.
Preparation Example 24
[0139] After sodium hydride (1.40 g, 60% in oil) was suspended in
30 ml of dry N,N-dimethylformamide, a solution of
(1-methyltetrazol-5-yl)phenylmethanoneoxime (2.6 g, 12.6 mmol)
obtained in Preparation Example 1 and 15 ml of dry
N,N-dimethylformamide was added dropwise while cooling in an ice
bath. After continuously stirring for 10 minutes, a solution
prepared by dissolving 2-bromomethyl-6-(hexanoylamino)pyridine (4.0
g, 14 mmol) in 15 ml of dry N,N-dimethylformamide was added
dropwise. After the completion of dropwise addition, the ice bath
was removed and the mixture was continuously stirred for 1.5 hours.
The reaction solution was poured into saturated ammonium chloride
water, and the reaction product was extracted with ethyl acetate.
The organic layer was washed in turn with water and saturated
saline solution, and the organic layer was dried over anhydrous
sodium sulfate. The solvent was distilled off from the organic
layer and the resulting residue was purified by silica gel
chromatography to obtain 3.55 g of
(Z)-(1-methyltetrazol-5-yl)phenylmethanoneoxime
0-(6-(hexanoylamino)pyridin-2-yl)methyloxime (compound No. (1)-12)
represented by the formula: ##STR63##
[0140] .sup.1H-NMR(CDCl.sub.3, .delta.): 0.91(t, 3H, J=7.2 Hz),
1.37(m, 4H), 1.74(m, 2H), 2.39(t, 2H, J=7.7 Hz), 3.97(s, 3H),
5.26(s, 2H), 7.00(d, 1H, J=7.3 Hz), 7.3-7.55(m, 5H), 7.70(dd, 1H,
J=7.3, 8.1 Hz), 7.86(brd, 1H), 8.15(d, 1H, J=8.1 Hz).
Preparation Example 25
[0141] (1-methyltetrazol-5-yl)phenylmethanoneoxime (60 mg, 0.30
mmol) obtained in Preparation Example 1 and
4-chloromethyl-2-(n-pentyloxycarbonylamino)thiazole (85 mg, 0.32
mmol) were dissolved in 4 ml of dry N,N-dimethylformamide, and
sodium hydride (40 mg, 60% in oil) was added to the solution while
cooling in an ice bath. After the ice bath was removed and the
mixture was continuously stirred for 3 hours, the reaction solution
was poured into saturated ammonium chloride water and the reaction
product was extracted with ethyl acetate. The organic layer was
washed in turn with water and saturated saline solution, and then
the organic layer was dried over anhydrous magnesium sulfate. The
solvent was distilled off from the organic layer, and the resulting
residue was purified by silica gel chromatography to obtain 120 mg
of (Z)-(1-methyltetrazol-5-yl)phenylmethanoneoxime
0-(2-(n-pentyloxycarbonylamino)thiazol-4-yl)methyloxime (compound
No. (4)-9) represented by the formula: ##STR64##
[0142] .sup.1H-NMR(CDCl.sub.3): 0.89(t, 3H, J=7.0 Hz), 1.34(m, 4H),
1.68(m, 2H), 3.87(s, 3H), 4.23(t, 2H, J=6.9 Hz), 5.30(s, 2H),
6.89(s, 1H), 7.30-7.55(m, 5H), 10.21(brd, 1H).
Preparation Example 26
[0143] Sodium hydride (1.79 g, 60% oily product) was suspended in
60 ml of dry N,N-dimethylformamide and a solution of
(Z)-(5-methyltetrazol-1-yl)phenylmethanoneoxime (8.24 g, 40.6 mmol)
and 30 ml of dry N,N -dimethylformamide was added dropwise to the
suspension while cooling in an ice bath. After stirring
continuously for 10 minutes, a solution of
2-bromomethyl-6-(hexanoylamino)pyridine (12.7 g, 44.5 mmol) and 40
ml of dry N,N-dimethylformamide was added dropwise. After the
completion of dropwise addition, the ice bath was removed and the
mixture was continuously stirred for 2 hours. The reaction solution
was poured into saturated ammonium chloride water and the reaction
product was extracted with ethyl acetate. The organic layer was
washed in turn with water and saturated saline solution, and then
the organic layer was dried over anhydrous sodium sulfate. The
solvent was distilled off from the organic layer, and the resulting
residue was purified by silica gel chromatography to obtain 10.5 g
of (Z)-(5-methyltetrazol-1-yl)phenylmethanoneoxime
0-(6-(hexanoylamino)pyridin-2-yl)methyloxime (compound No. (11)-12)
represented by the formula: ##STR65##
[0144] .sup.1H-NMR(CDCl.sub.3, .delta.): 0.91(t, 3H, J=7.1 Hz),
1.31-1.38(m, 4H), 1.70-1.77(m, 2H), 2.45(t, 2H, J=7.5 Hz), 2.46(s,
3H), 5.23(s, 2H), 6.92(s, 1H), 7.34-7.53(m, 5H), 9.10(brd, 1H).
Preparation Example 27
[0145] (Z)-(5-methyltetrazol-1-yl)phenylmethanoneoxime (100 mg,
0.42 mmol) and 4-chloromethyl-2-(n-hexanoylamino)thiazole (120 mg,
0.51 mmol) were dissolved in 2 ml of dry N,N-dimethylformamide, and
sodium hydride (40 mg, 60% in oil) was added to the solution while
cooling in an ice bath. After removing the ice bath, the mixture
was continuously stirred for 3 hours. The reaction solution was
poured into saturated ammonium chloride water and the reaction
product was extracted with ethyl acetate. The organic layer was
washed in turn with water and saturated saline solution, and then
the organic layer was dried over anhydrous magnesium sulfate. The
solvent was distilled off from the organic layer and the resulting
residue was purified by silica gel chromatography to obtain 117 mg
of (Z)-(5-methyltetrazol-1-yl)phenylmethanoneoxime
0-(2-(n-hexanoylamino)thiazol-4-yl)methyloxime (Compound No.
(12)-12) represented by the formula: ##STR66##
[0146] .sup.1H-NMR(CDCl.sub.3): 0.91(t, 3H, J=7.1 Hz), 1.31-1.38(m,
4H), 1.70-1.77(m, 2H), 2.45(t, J=7.5 Hz,2H), 2.46(s,3H), 5.23(s,
2H), 6.92(s, 1H), 7.34-7.53(m, 5H), 9.10(brd, 1H).
[0147] .sup.1NMR spectrum data of tetrazoyloxime derivatives
prepared in the same manner as in these Preparation Examples are
summarized in Tables 24 to 45. Regarding the indication of the
compounds in the tables, for example, the compound (1)-1 represents
a compound No. 1 in Table 1. "Z/E" in the column represents a (Z)
isomer or an (E) isomer. TABLE-US-00025 TABLE 24 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (1)-1 Z 4.00(s, 3H), 5.41(s, 1H),
7.22-7.28(m, 2H), 7.3-7.47(m, 3H), 7.51-7.55(m, 2H), 7.67(t, d,
J=7.7Hz, J=1.7Hz, 1H), 8.58(d, d, J=7.5Hz, J=1, 7Hz, 1H). (1)-2 Z
3.4(s, 3H), 5.25(s, 2H), 7.15(d, J=7.1Hz, 1H), 7.35-7.53(m, 5H),
7.80(d, d, J=7.1Hz, J=8.0Hz, 1H), 8.10(d, J=8.0Hz, 1H). (1)-5 Z
1.26(t, J=7.5Hz, 3H), 2.44(q, J=7.5Hz, 2H), 4.10(s, 3H), 5.27(s,
2H), 7.00(d, J=7.5Hz, 1H), 7.35-7.52(m, 5H), 7.70(d, J=7.5Hz,
J=8.1Hz, 1H), 8.14(d, J=8.1Hz, 1H). (1)-7 Z 1.27(d, 6H, J=7.0Hz),
2.55(seq, 1H, J=7.0Hz), 3.97(s, 3H), 5.27(s, 2H), 6.99(d, 1H,
J=7.5Hz), 7.3-7.55(m, 5H), 7.70(dd, 1H, J=7.5, 8.4Hz), 7.85(brd,
1H), 8.17(d, 1H, J=8.4Hz). (1)-8 Z 0.93(t, J=7.3Hz, 3H), 1.40(sept,
J=7.3Hz, 2H), 1.72(sept, 7.3Hz, 2H), 2.41(t, J=7.3Hz, 2H), 3.97(s,
3H), 5.26(s, 2H), 7.00(d, J=7.5Hz, 1H), 7.35-7.52(m, 5H), 7.70(d,
d, J=7.5Hz, J=8.2Hz, 1H), 8.16(d, J=8.2Hz, 1H). (1)-11 Z 1.34(s,
9H), 3.98(s, 3H), 5.27(s, 2H), 7.00(d, J=6.8Hz, 1H), 7.35-7.53(m,
5H), 7.72(d, d, J=6.8Hz, J=8.2Hz, 1H), 8.18(d, J=8.2Hz, 1H).
[0148] TABLE-US-00026 TABLE 25 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (1)-12 Z 0.91(t, J=6.9Hz, 3H),
1.33-1.41(m, 3H), 1.69-1.79(m, 3H), 2.3(t, J=7.2Hz, 2H), 3.98(s,
3H), 5.26(s, 2H), 7.00(d, J=7.0Hz, 1H), 7.35-7.52(m, 5H), 7.69(d,
d, J=7.0Hz, J=8.3Hz, 1H), 8.15(d, J=8.3Hz, 1H). (1)-16 Z 1.11(s,
9H), 2.26(s, 2H), 3.97(s, 3H), 5.26(s, 2H), 7.00(d, 1H, J=7.5Hz),
7.3-7.55(m, 5H), 7.69(dd, 1H, J=7.5, 8.2Hz), 7.80(brd, 1H), 8.16(d,
1H, J=8.2Hz). (1)-18 Z 0.89(t, 3H, J=6.8Hz), 1.25-1.5(m, 6H),
1.73(m, 2H), 2.40(t, 2H, J=7.6Hz), 3.97(s, 3H), 5.26(s, 2H),
7.00(d, 1H, J=7.0Hz), 7.3-7.55(m, 5H), 7.70(dd, 1H, J=7.0, 8.2Hz),
7.86(brd, 1H), 8.15(d, 1H, J=8.2Hz). (1)-21 Z 0.87-0.93(m, 2H),
1.08-1.13(m, 2H), 1.52-1.55(m, 1H), 3.97(s, 3H), 5.27(s, 2H),
7.00(d, J=7.5Hz, 1H), 7.35-7.53(m, 5H), 7.68(d, d, J=7.5Hz,
J=8.0Hz, 1H), 8.11(d, J=8.0Hz, 1H). (1)-23 Z 1.31-2.05(m, 10H),
2.262.31(m, 1H), 3.97(s, 3H), 5.26(s, 2H), 6.99(d, J=7.5Hz, 1H),
7.35-7.52(m, 5H), 7.72(d, d, J=7.5Hz, J=8.3Hz, 1H), 8.15(d,
J=8.3Hz, 1H).
[0149] TABLE-US-00027 TABLE 26 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (2)-7 Z 1.29(d, 6H, J=6.8Hz),
2.63(seq, 1H, J=6.8Hz), 3.95(s, 3H), 5.25(s, 2H), 6.92(s, 1H),
7.3-7.5(m, 3H), 7.52(m, 2H), 8.78(brd, 1H). (2)-11 Z 1.33(s, 9H),
3.95(s, 3H), 5.27(s, 2H), 6.92(s, 1H), 7.3-7.5(m, 3H), 7.52(m, 2H),
8.89(brd, 1H). (2)-12 Z 0.90(t, 3H, J=7.1Hz), 1.2-1.4(m, 4H),
1.73(m, 2H), 2.44(t, 2H, J=7.5Hz), 3.93(s, 3H), 5.24(s, 2H),
6.91(s, 1H), 7.3-7.55(m, 5H), 9.17(brd, 1H). (2)-18 Z 0.87(t, 3H,
J=6.8Hz), 1.30(m, 6H), 1.72(m, 4H), 2.44(t, 2H, J=7.5Hz), 3.92(s,
3H), 5.24(s, 2H), 6.91(s, 1H), 7.3-7.55(m, 5H), 9.35(brd, 1H).
(2)-19 Z 0.87(t, 1H, J=6.8Hz), 1.2-1.4(m, 8H), 1.71(m, 2H), 2.44(t,
2H, J=7.5Hz), 3.92(s, 3H), 5.23(s, 2H), 6.91(s, 1H), 7.3-7.55(m,
5H), 9.48(brd, 1H).
[0150] TABLE-US-00028 TABLE 27 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (3)-2 Z 1.26(t, J=7.2Hz, 3H),
3.98(s, 3H), 4.12(q, J=7.2Hz, 2H), 5.26(s, 2H), 6.95(d, J=7.7Hz,
1H), 7.26-7.52(m, 5H), 7.68(d, d, J=7.7Hz, J=8.2Hz, 1H), 7.90(d,
J=8.2Hz, 1H). (3)-2 E 1.33(t, J=7.2Hz, 3H), 4.00(s, 3H), 5.13(s,
2H), 7.15(d, J=7.3Hz, 1H), 7.26-7.52(m, 5H), 7.80(d, d, J=7.3Hz,
J=8.1Hz, 1H), 8.10(d, J=8.1Hz, 1H). (3)-3 Z 0.97(t, 3H, J=7.4Hz),
1.70(tq, 2H, J=6.7, 7.4Hz), 3.97(s, 3H), 4.14(t, 2H, J=6.7Hz),
5.26(s, 2H), 6.96(d, 1H, J=7.0Hz), 7.3-7.55(m, 6H), 7.68(dd, 1H,
J=7.0, 8.4Hz), 7.90(d, 1H, J=8.4Hz). (3)-4 Z 1.30(d, 6H, J=6.2Hz),
3.98(s, 3H), 5.03(seq, 1H, J=6.2Hz), 5.26(s, 2H), 6.95(d, 1H,
J=7.0Hz), 7.3-7.55(m, 6H), 7.67(dd, 1H, J=7.0, 8.3Hz), 7.89(d, 1H,
J=8.3Hz). (3)-5 Z 0.95(t, 3H, J=7.3Hz), 1.40(tq, 2H, J=7.3, 7.3Hz),
1.66(tt, 2H, J=6.6, 7.3Hz), 3.97(s, 3H), 4.18(t, 2H, J=6.6Hz),
5.26(s, 2H), 6.95(d, 1H, J=7.3Hz), 7.25-7.6(m, 6H), 7.68(dd, 1H,
J=7.3, 8.3Hz), 7.90(d, 1H, J=8.3Hz). (3)-8 Z 1.5(s, 9H), 3.97(s,
3H), 5.25(s, 2H), 6.92(d, J=7.5Hz, 1H), 7.34-7.53(m, 5H), 7.64(d,
d, J=7.5Hz, J=8.2Hz, 1H), 7.86(d, J=8.2Hz, 1H).
[0151] TABLE-US-00029 TABLE 28 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (3)-9 Z 0.91(t, 3H, J=7.1Hz),
1.35(m, 4H), 1.68(m, 2H), 3.98(s, 3H), 4.18(t, 2H, J=6.7Hz),
5.26(s, 2H), 6.95(d, 1H, J=6.8Hz), 7.3-7.55(m, 6H), 7.68(dd, 1H,
J=6.8, 8.3Hz), 7.90(d, 1H, J=8.3Hz). (3)-15 Z 0.90(t, 3H, J=7.0Hz),
1.25-1.45(m, 6H), 1.68(m, 2H), 3.98(s, 3H), 4.18(t, 2H, J=6.8Hz),
5.26(s, 2H), 6.95(d, 1H, J=7.7Hz), 7.3-7.55(m, 6H), 7.68(dd, 1H,
J=7.7, 8.4Hz), 7.90(d, 1H, J=8.4Hz). (3)-16 Z 0.89(t, 3H, J=6.8Hz),
1.2-1.4(m, 8H), 1.68(m, 2H), 3.97(s, 3H), 4.18(t, J=6.8Hz, 2H),
5.26(s, 2H), 6.95(s, 1H), 7.3-7.55(m, 6H), 7.68(dd, 1H,
J=7.3.7.9Hz), 7.90(d, J=7.9Hz, 1H). (3)-18 Z 3.96(s, 3H), 5.22(s,
2H), 5.24(s, 2H), 6.95(d, 1H, J=7.3Hz), 7.3-7.55(m, 5H), 7.68(dd,
1H, J=7.3, 8.2Hz), 7.91(d, 1H, J=8.2Hz). (3)-21 Z 0.92(t, 3H,
J=7.5Hz), 1.49(s, 6H), 1.83(q, 2H, J=7.5Hz), 3.97(s, 3H), 5.25(s,
2H), 6.93(d, 1H, J=7.0Hz), 7.2-7.55(m, 6H), 7.65(dd, 1H, J=7.0,
8.2Hz), 7.86(d, 1H, J=8.2Hz). (3)-22 Z 1.21.6(m, 6H), 1.75(m, 2H),
1.89(m, 2H), 3.97(s, 3H), 4.77(m, 1H), 5.26(s, 2H), 6.95(d, 1H,
J=6.8Hz), 7.3-7.55(m, 6H), 7.67(dd, 1H, J=6.8, 8.3Hz), 7.59(d, 1H,
J=8.3Hz).
[0152] TABLE-US-00030 TABLE 29 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (4)-3 Z 3.36(s, 3H), 3.61(t,
J=4.6Hz, 2H), 3.87(s, 3H), 4.37(t, J=4.6Hz, 2H), 5.31(s, 2H),
6.91(s, 1H), 7.31-7.51(m, 5H). (4)-5 Z 0.93(t, J=7.3Hz, 3H),
1.32-1.45(m, 2H), 1.63-1.73(m, 2H), 3.87(s, 3H), 4.27(t, J=6.8Hz,
2H), 5.29(s, 2H), 6.89(s, 1H), 7.32-7.61(m, 5H), 10.18(brd, 1H).
(4)-9 Z 0.89(t, 3H, J=7.0Hz), 1.34(m, 4H), 1.68(m, 2H), 3.87(s,
3H), 4.23(t, 2H, J=6.9Hz), 5.30(s, 2H), 6.89(s, 1H), 7.3-7.55(m,
5H), 10.21(brd, 1H). (4)-15 Z 0.87(t, 3H, J=6.7Hz), 1.2-1.45(m,
6H), 1.69(m, 2H), 3.86(s, 3H), 4.22(t, 2H, J=6.9Hz), 5.31(s, 2H),
6.89(s, 1H), 7.25-7.55(m, 5H), 10.50(brd, 1H). (4)-16 Z 0.87(t,
J=6.9Hz, 3H), 1.24-1.31(m, 7H), 1.64-1.72(m, 3H), 3.88(s, 3H),
4.23(t, J=6.8Hz, 2H), 5.29(s, 2H), 6.89(s, 1H), 7.31-7.52(m, 5H),
9.94(brd, 1H) (4)-18 Z 3.79(s, 3H), 5.10(s, 2H), 5.22(s, 2H),
6.85(s, 1H), 7.2-7.55(m, 10H), 10.89(brd, 1H). (5)-1 Z 3.52(s, 3H),
3.99(s, 3H), 4.04(s, 2H), 5.29(s, 2H), 7.04(d, J=7.1Hz),
7.34-7.53(m, 4H), 7.72(dd, J=7.9Hz, J=7.9Hz, 1H), 8.18(d, J=8.3Hz),
8.81(brd, 1H). (5)-2 Z 1.32(t, J=7.0Hz), 3.67(q, J=7.0Hz, 2H),
4.00(s, 3H), 4.07(s, 2H), 5.30(s, 2H), 7.04(d, J=7.5Hz, 1H),
7.34-7.55(m, 4H), 7.72(dd, J=7.9, J=7.9Hz, 1H), 8.18(d, J=8.3Hz),
8.85(brd, 1H).
[0153] TABLE-US-00031 TABLE 30 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (5)-10 Z 1.08(t, J=7.3Hz, 3H),
2.24-2.31(m, 2H), 3.96(s, 3H), 5.26(s, 2H), 5.95(d, J=15.2Hz, 1H),
7.01(d, J=7.3Hz, 1H), 7.10(t, J=6.4Hz, 1H), 7.33-7.51(m, 5H),
7.69(d, d, J=7.3Hz, J=8.2Hz, 1H), 8.22(d, J=8.2Hz, 1H). (5)-12 Z
3.76(s, 2H), 3.89(s, 3H), 5.20(s, 2H), 6.99(d, 1H, J=7.0Hz),
7.25-7.55(m, 10H), 7.68(dd, 1H, J=7.0, J=8.3Hz), 7.82(brd, 1H),
8.15(d, 1H, J=8.3Hz). (6)-1 Z 3.51(s, 3H), 3.95(s, 3H), 4.12(s,
2H), 5.27(s, 2H), 6.95(s, 1H), 7.35-7.55(m, 5H), 9.65(brd, 1H).
(6)-2 Z 1.29(t, J=7.1Hz, 3H), 3.66(q, J=7.0Hz, 2H), 3.95(s, 3H),
4.17(s, 2H), 5.28(s, 2H), 6.93(s, 1H), 7.35-7.54(m, 5H), 9.65(brd,
1H). (6)-3 Z 1.27(t, J=6.7Hz, 3H), 2.73(t, J=5.6Hz, 2H), 3.62(q,
J=7.0Hz), 3.77(t, J=5.6Hz, 2H), 3.96(s, 2H), 6.91(s, 1H),
7.34-7.61(m, 5H). (6)-6 Z 2.15(s, 3H), 2.76(t, J=6.7Hz, 2H),
2.89(t, J=7.1Hz, 2H), 3.93(s, 3H), 5.24(s, 2H), 6.93(s, 1H),
7.33-7.53(m, 5H), 9.70(brd, 1H). (6)-7 Z 2.06(s, 3H), 3.91(s, 3H),
5.24(s, 2H), 5.58(s, 1H), 5.93(s, 1H), 6.94(s, 1H), 7.33-7.52(m,
5H).
[0154] TABLE-US-00032 TABLE 31 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (7)-1 Z 1.01(t, 3H, J=7.3Hz),
1.76(qt, 2H, J=7.3, 7.4Hz), 2.37(t, 2H, J=7.4Hz), 3.97(s, 3H),
5.26(s, 2H), 6.99(d, 1H, J=7.5Hz), 7.35(m, 2H), 7.47(m, 2H),
7.70(dd, 1H, J=7.5, 8.4Hz), 7.86(brd, 1H), 8.17(d, 1H, J=8.4Hz).
(7)-2 Z 1.27(d, 2H, J=7.0Hz), 2.56(seq, 1H, J=7.0Hz), 3.98(s, 3H),
5.27(s, 2H), 6.98(d, 1H, J=7.0Hz), 7.35(m, 2H), 7.47(m, 2H),
7.70(dd, 1H, J=7.0, 8.1Hz), 7.8(brd, 1H), 8.17(d, 1H, J=8.1Hz).
(7)-3 Z 0.90(m, 2H), 1.11(m, 2H), 1.55(m, 1H), 3.98(s, 3H), 5.27(s,
2H), 6.98(d, 1H, J=6.6Hz), 7.36(m, 2H), 7.47(m, 2H), 7.69(dd, 1H,
J=6.6, 8.1Hz), 8.05(brd, 1H), 8.12(d, 1H, J=8.1Hz). (7)-4 Z 1.26(t,
3H, J=7.5Hz), 2.44(q, 2H, J=7.5Hz), 3.98(s, 3H), 5.27(s, 2H),
7.00(d, 1H, J=7.3Hz), 7.1-7.25(m, 2H), 7.3-7.4(m, 2H), 7.71(dd, 1H,
J=7.3, 8.4Hz), 7.85(brd, 1H), 8.16(d, 1H, J=8.4Hz). (7)-5 Z 1.27(d,
6H, J=7.0Hz), 2.56(seq, 1H, J=7.0Hz), 3.98(s, 3H), 5.28(s, 2H),
7.00(d, 1H, J=7.5Hz), 7.1-7.25(m, 2H), 7.3-7.4(m, 2H), 7.70(dd, 1H,
J=7.5, 8.1Hz), 7.87(brd, 1H), 8.18(d, 1H, J=8.1Hz). (7)-6 Z 1.92(m,
2H), 1.11(m, 2H), 1.56(m, 1H), 3.98(s, 3H), 5.28(s, 2H), 6.99(d,
1H, J=6.6Hz), 7.1-7.25(m, 2H), 7.25-7.45(m, 2H), 7.69(dd, 1H,
J=6.6, 8.1Hz), 8.13(d, 1H, J=8.1Hz), 8.1(brd, 1H).
[0155] TABLE-US-00033 TABLE 32 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (7)-8 Z 1.26(d, 6H, J=7.0Hz),
2.55(seq, 1H, J=7.0Hz), 3.98(s, 3H), 5.26(s, 2H), 7.00(d, 1H,
J=7.7Hz), 7.07(m, 2H), 7.52(m, 2H), 7.70(dd, 1H, J=7.7, 8.4Hz),
7.91(brd, 1H), 8.18(d, 1H, J=8.4Hz). (7)-9 Z 1.27(d, 6H, J=7.0Hz),
2.56(seq, 1H, J=7.0Hz), 3.82(s, 3H), 3.97(s, 3H), 5.23(s, 2H),
6.90(m, 2H), 6.99(d, 1H, J=6.8Hz), 7.44(m, 2H), 7.69(dd, 1H, J=6.8,
J=7.9Hz), 7.86(brd, 1H), 8.15(d, 1H, J=7.9Hz). (7)-11 Z 1.90(m,
2H), 1.18(m, 2H), 1.56(m, 1H), 3.82(s, 3H), 3.97(s, 3H), 5.23(s,
2H), 6.88(m, 2H), 6.98(d, 1H, J=6.8Hz), 7.44(m, 2H), 7.67(dd, 1H,
J=6.8, 7.9Hz), 8.10(d, 1H, J=7.9Hz), 8.14(brd, 1H). (7)-12 Z
1.91(t, 3H, J=7.0Hz), 1.35(m, 4H), 1.73(m, 2H), 2.37(s, 3H),
2.39(t, 2H, J=7.5Hz), 3.96(s, 3H), 5.24(s, 2H), 6.99(d, 1H,
J=7.3Hz), 7.17(m, 2H), 7.38(m, 2H), 7.69(dd, 1H, J=7.3, 8.4Hz),
7.89(brd, 1H), 8.14(d, 1H, J=8.4Hz). (7)-13 Z 1.11(s, 9H), 2.26(s,
2H), 2.37(s, 3H), 3.96(s, 3H), 5.24(s, 2H), 7.00(d, 1H, J=7.0Hz),
7.17(m, 2H), 7.38(m, 2H), 7.68(dd, 1H, J=7.0, 8.2Hz), 7.85(brd,
1H), 8.16(d, 1H, J=8.2H).
[0156] TABLE-US-00034 TABLE 33 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (7)-14 Z 1.28(d, 6H, J=7.0Hz),
2.64(seq, 1H, J=7.0Hz), 4.04(s, 3H) 5.40(s, 2H), 7.3-7.5(m, 3H),
7.55(m, 2H), 7.78(d, 1H, J=86Hz), 8.07(d, 1H, J=8.6Hz), 8.38(brd,
1H). (7)-17 Z 1.27(d, 6H, J=6.8Hz), 1.45(t, 3H, J=7.3Hz), 2.56(seq,
1H, J=6.8Hz), 4.28(q, 2H, J=7.3Hz), 5.25(s, 2H), 7.69(dd, 1H,
J=6.8, 8.0Hz), 7.88(brd, 1H), 8.16(d, 1H, J=8.0Hz). (7)-18 Z
4.02(s, 3H), 5.41(s, 2H), 7.07(m, 2H), 7.25(m, 2H), 7.54(m, 2H),
7.70(ddd, 1H, J=2.0, 7.7Hz, 7.7Hz), 8.59(d, 1H, J=4.8Hz). (7)-19 Z
4.02(s, 3H), 5.42(s, 2H), 7.14(dddd, 1H, J=1.0Hz, 2.6Hz, 7.7Hz,
7.7Hz), 7.18-7.4(m, 5H), 7.70(ddd, 1H, J=1.8Hz, 7.7Hz, 7.7Hz),
8.59(m, 1H). (7)-20 Z 4.01(s, 3H), 5.41(s, 2H), 7.24(m, 2H),
7.35(m, 2H), 7.48(m, 2H), 7.70(ddd, 1H, J=1.8Hz, 7.7Hz, 7.7Hz),
8.59(ddd, 1H, J=1.5Hz, 1.8Hz, 4.4Hz). (8)-2 Z 1.27(d, 6H, J=7.0Hz),
2.64(seq, 1H, J=7.0Hz), 3.92(s, 3H), 5.24(s, 2H), 6.93(s, 1H),
7.34(m, 2H), 7.47(m, 2H), 9.20(brd, 1H).
[0157] TABLE-US-00035 TABLE 34 Compound No. Z/E .sup.1H-NMR
(CDCl.sub.3) .delta. (8)-7 Z 1.33(s, 9H), 3.96(s, 3H), 5.27(s, 2H),
6.93(s, 1H), 7.1-7.43(m, 4H), 8.95(brd, 1H). (8)-9 Z 1.29(d, 6H,
J=7.0Hz), 2.63(seq, 1H, J=7.0Hz), 3.83(s, 3H), 3.94(s, 3H), 5.22(s,
2H), 6.88(m, 3H), 7.46(m, 2H), 8.87(brd, 1H) (8)-10 Z 1.33(s, 9H),
3.83(s, 3H), 3.94(s, 3H), 5.22(s, 2H), 6.89(m, 3H), 7.46(m, 2H),
8.99(brd, 1H). (8)-12 Z 0.91(t, J=7.1Hz, 3H), 1.31-1.38(m, 4H),
1.70-1.77(m, 2H), 5.23(s, 2H), 6.92(s, 1H), 7.34-7.53(m, 5H),
9.l0(brd, 1H) (8)-15 Z 1.26(d, 6H, 1=7.0Hz), 1.42(t, 3H, J=7.3Hz),
2.65(seq, 1H, J=7.0Hz), 4.26(q, 2H, J=7.3Hz), 5.19(s, 2H),
7.3-7.5(m, 5H), 9.12(brd, 1H). (9)-1 Z 1.52(s, 9H), 3.98(s, 3H),
5.26(s, 2H), 6.92(d, 1H, J=7.7Hz), 7.17.4(m, 5H), 7.66(dd, 1H,
J=7.7, 8.4Hz), 7.88(d, 1H, J=8.4Hz). (9)-2 Z 1.31(d, 6H, J=6.4Hz),
3.99(s, 3H), 5.03(seq, 1H, J=6.4Hz), 5.25(s, 2H), 6.93(4, 1H,
J=7.2Hz), 7.07(m, 2H), 7.28(brd, 1H), 7.53(m, 2H), 7.68(d, 1H,
J=7.2, 8.4Hz), 7.90(d, 1H, J=8.4Hz). 1.52(s, 9H), 3.98(s, 3H),
5.24(s. 2H), 6.91(4, 1H, J=7.3Hz), 7.07(m, 2H), 7.19(brd, 1H),
7.53(m, 2H), 7.65(dd, 1H, J=7.3, 8.4Hz), 7.87(d, 1H, J=8.4Hz).
[0158] TABLE-US-00036 TABLE 36 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (11)-4 Z 2.21(s, 3H), 2.49(s, 3H),
5.24(s, 2H), 7.00(d, J=7.5Hz, 1H), 7.34-7.53(m, 5H), 7.71(dd,
J=7.9Hz, 1H), 7.90(brd, 1H), 8.13(d, J=8.3Hz, 1H). (11)-5 Z 1.26(t,
J=7.5Hz, 3H), 2.44(q, J=7.5Hz, 2H), 2.49(s, 3H), 5.24(s, 2H),
6.99(d, J=7.5Hz, 1H), 7.34-7.50(m, 5H), 7.71(dd, J=7.8Hz, 1H),
7.79(brd, 1H), 8.16(d, J=8.2Hz, 1H). (11)-6 Z 1.02(t, J=7.3Hz,
7.5Hz, 3H), 1.78(m, 2H), 2.38(t, J=7.3Hz, 7.5Hz, 2H), 2.49(s, 3H),
5.24(s, 2H), 6.99(d, J=6.8Hz, 1H), 7.34-7.52(m, 5H), 7.70(dd,
J=7.7Hz, 8.0Hz, 1H), 7.77(brd, 1H), 8.16(d, J=8.4Hz, 1H). (11)-7 Z
1.27(d, J=7.0Hz, 6H), 2.49(s, 3H), 2.51(qq, J=6.8Hz, 1H), 5.24(s,
2H), 6.99(d, J=7.5Hz, 1H), 7.35-7.55(m, 5H), 7.70(dd, J=7.7Hz,
8.3Hz, 1H), 7.80(brd, 1H), 8.17(d, J=8.4Hz, 1H). (11)-8 Z 0.95(t,
J=7.3Hz, 3H), 1.42(m, 2H), 1.2(m, 2H), 2.40(t, J=7.3Hz, 2H),
2.49(s, 3H), 5.24(s, 2H), 6.99(d, J=7.5Hz, 2H), 7.34-7.53(m, 5H),
7.70(dd, J=7.9Hz, 1H), 7.80(brd, 1H), 8.16(d, J=8.3Hz, 1H). (11)-11
Z 1.33(s, 9H), 2.50(s, 3H), 5.25(s, 2H), 6.99(d, J=7.5Hz, 1H),
7.35-7.53(m, 5H), 7.70(dd, J=7.7Hz, 8.0Hz, 1H), 7.97(brd, 1H),
8.19(d, J=8.3Hz, 1H).
[0159] TABLE-US-00037 TABLE 37 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (11)-18 Z 0.89(t, J=6.6Hz, 7.1Hz,
3H), 1.26-1.42(m, 6H), 1.68-1.75(m, 2H), 2.40(t, J=7.4Hz, 7.7Hz,
2H), 2.49(s, 3H), 5.24(s, 2H), 6.99(d, J=7.5Hz, 1H), 7.34-7.52(m,
5H), 7.70(dd, J=7.9Hz, 8.1Hz, 1H), 7.86(brd, 1H), 8.16(d, J=8.2Hz,
1H). (11)-19 Z 0.88(t, J=7.00, 3H), 1.23-1.36(m, 8H), 1.68-1.78(m,
2H), 2.42(t, J=7.5Hz, 2H), 2.49(s, 3H), 5.24(s, 2H), 6.98(d,
J=7.5Hz, 1H), 7.37-7.52(m, 5H), 7.70(dd, J=7.5Hz, J=8.2Hz, 1H),
7.79(brd, 1H), 8.15(d, J=8.2Hz, 1H). (11)-21 Z 0.87-0.93(m, 2H),
1.09-1.14(m, 2H), 1.51-1.62(m, 1H), 2.49(s, 3H), 5.25(s, 2H),
6.98(d, J=7.5Hz, 1H), 7.35-7.52(m, 5H), 7.69(dd, J=7.8Hz, 7.9Hz,
1H), 8.03(brd, 1H), 8.12(d, J=8.6Hz, 1H). (11)-22 Z 1.62-2.16(m,
8H), 2.49(s, 3H), 2.73(tt, J=7.7Hz, 8.0Hz, 1H), 5.24(s, 2H),
6.99(d, J=6.7Hz), 7.34-7.53(m, 5H), 7.70(dd, J=7.7Hz, 8.0Hz, 1H),
7.81(brd, 1H), 8.17(d, J=8.4Hz, 1H). (11)-23 Z 1.22-1.99(m, 10H),
2.27(tt, J=3.5Hz, 11.6Hz, 1H), 2.49(s, 3H), 5.24(s, 2H), 6.98(d,
J=7.4Hz, 1H), 7.34-7.53(m, 5H), 7.69(dd, J=7.9Hz, 1H), 7.83(brd,
1H), 8.17(d, J=7.9Hz, 1H). (12)-3 Z 2.43(s, 3H), 5.25(s, 2H),
7.02(s, 1H)7.32-7.52(m, 5H), 8.54(s, 1H), 11.50(brd, 1H).
[0160] TABLE-US-00038 TABLE 38 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (12)-7 Z 1.25-1.28(m, 6H), 2.46(s,
3H), 2.58-2.73(m, 1H), 5.23(s, 2H), 6.93(s, 1H), 7.20-7.54(m, 5H),
9.43(brd, 1H). (12)-8 Z 0.95(t, 3H, J=7.33Hz), 1.35-1.47(m, 2H),
1.68-1.78(m, 2H), 2.43-2.48(m, 5H), 5.23(s, 1H), 6.91(s, 1H),
7.35-7.52(m, 5H), 8.74(brd, 1H). (12)-9 Z 1.62(d, 6H, J=6.43Hz),
2.20-2.30(m, 1H), 2.32(d, 2H, J=6.58Hz), 2.47(s, 3H), 5.23(s, 2H),
6.91(s, 1H), 7.38-7.50(m, 5H), 8.62(brd, 1H). (12)-16 Z 1.10(s,
9H), 2.31(s, 2H), 2.47(s, 3H), 5.23((s, 2H), 6.91(s, 1H),
7.36-7.61(m, 5H), 8.60(brd, 1H). (12)-18 Z 0.84-0.88(m, 3H),
1.23-1.40(m, 6H), 1.67-1.77(m, 2H), 2.45-2.55(m, 5H), 5.23(s, 2H),
6.93(s, 1H), 7.33-7.73(m, 5H), 9.80(brd, 1H). (12)-19 Z
0.85-0.90(m, 3H), 1.23-1.39(m, 8H), 1.66-1.78(m, 2H), 2.24-2.48(m,
5H), 5.23(s, 2H), 6.91(s, 1H), 7.34-7.52(m, 5H), 8.95(brd, 1H).
(13)-1 Z 2.50(s, 3H), 3.80(s, 3H), , 5.24(s, 2H), 6.94(d, J=7.0Hz,
1H), 7.34-7.43(m, 5H), 7.72(dd, J=7.0Hz, J=8.6Hz, 1H), 7.93(d,
J=8.6Hz, 1H). (13)-2 Z 1.32(t, J=7.0Hz, 3H), 2.50(s, 3H), 4.31(q,
J=7.0Hz, 2H), 5.24(s, 2H), 6.96(d, J=7.1Hz, 1H), 7.33-7.45(m, 5H),
7.74(dd, J=7.1Hz, J=8.6Hz, 1H), 7.96(d, J=8.6Hz, 1H).
[0161] TABLE-US-00039 TABLE 39 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (13)-3 Z 0.93(t, J=6.8Hz, 3H),
1.72(tq.J=6.7Hz, J=6.81Hz, 2H), 2.49(s, 3H), 4.14(t, J=6.7Hz, 2H),
5.25(s, 2H), 6.94(d, J=6.8Hz, 1H), 7.34-7.53(m, 5H), 7.69(dd,
J=6.8Hz, J=8.4Hz, 1H), 7.90(d, J=8.4Hz, 1H). (13)-5 Z 0.95(t,
J=7.3Hz, 3H), 1.43-1.72(m, 4H), 2.49(s, 3H), 4.19(t, J=6.6Hz, 2H),
5.23(s, 2H), 6.93(d, 7.5Hz, 1H), 7.35-7.52(m, 5H), 7.68(dd,
J=7.5Hz, J=8.2Hz, 1H), 7.90(d, J=8.2Hz, 1H). (13)-6 Z 0.96(d,
J=6.8Hz, 6H), 1.98(sept, J=6.8Hz, 1H), 2.49(s, 3H), 3.95(d,
J=6.6Hz, 2H), 5.24(s, 1H), 6.94(d, J=8.0Hz, 1H), 7.32-7.52(m, 5H),
7.68(dd, J=8.0Hz, J=8.2Hz, 1H), 7.90(d, J=8.2Hz, 1H). (13)-6 E
0.96(d, J=6.8Hz, 6H), 1.98(sept, J=6.8Hz, 1H), 2.49(s, 3H), 3.95(d,
J=6.6Hz, 2H), 5.22(s, 1H), 6.92(d, J=8.0Hz, 1H), 7.32-7.52(m, 5H),
7.66(dd, J=8.0Hz, J=8.2Hz, 1H), 7.78(d, J=8.2Hz, 1H). (13)-15 Z
0.90(t, J=6.6Hz, 3H), 1.33-1.43(m, 6H), 1.63-1.72(m, 2H), 2.50(s,
3H), 4.18(t, J=6.6Hz, 2H), 5.24(s, 2H), 6.93(d, J=7.0Hz, J=8.2Hz,
1H), 7.90(d, J=8.2Hz, 1H). (13)-21 Z 1.61-1.95(m, 8H), 2.49(s, 3H),
5.20(m, 1H), 5.23(s, 2H), 6.92(d, J=7.0Hz, 1H), 7.357.52(m, 5H),
7.68(dd, J=7.0Hz, J=8.3Hz, 1H), 7.89(d, J=8.3Hz, 1H).
[0162] TABLE-US-00040 TABLE 40 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (13)-22 Z 1.23-1.94(m, 10H), 2.50(,
s, 3H), 4.73-4.81(m, 1H), 5.24(s, 2H), 6.93(d, J=7.0Hz, 1H),
7.35-7.52(m, 5H), 7.65(dd, J=7.7Hz, 8.1Hz, 1H), 7.90(d, J=8.3Hz,
1H). (14)-3 Z 0.94(t, 3H, J=7.5Hz), 1.73(m, 2H), 2.34(s, 3H),
4.15(m, 2H), 5.33(s, 2H), 6.94(s, 1H), 7.29-7.49(m, 5H), 11.28(brs,
1H). (14)-5 Z 0.94(t, 3H, J=7.33Hz), 1.33-1.46(m, 2H), 1.591.73(m,
2H), 2.42(s, 3H), 4.25(t, 2H, J=6.76Hz), 5.25(s, 2H), 6.88(s, 1H),
7.33-7.50(m, 5H), 9.40(brd, 1H). (14)-9 Z 0.90(t, J=6.8Hz3H),
1.32-1.38(m, 4H), 1.65-1.72(m, 2H), 2.38(s, 3H), 4.26(q, J=7.0Hz,
2H), 5.39(s, 2H), 6.93(s, 1H), 7.31-7.61(m, 5H). (14)-15 Z 0.88(t,
3H, J=6.61Hz), 1.24-1.32(m, 6H), 1.65-1.72(m, 2H), 2.44(s, 1H),
4.24(t, 2H, J=6.79Hz), 5.25(s, 2H), 6.88(s, 1H), 7.34-7.50(m, 5H),
9.05(brd, 1H). (16)-3 Z 2.46(s, 3H), 5.25(s, 2H), 6.99(s, 1H),
7.36-7.65(m, 8H), 7.91-7.94(m, 2H), 9.36(brd, 1H). (17)-21 Z
0.91(t, J=7.1Hz, 3H), 1.32(t, J=7.6Hz, 3H), 1.34(m, 4H), 1.74(m,
2H), 2.39(t, J=7.5Hz, 2H), 2.79(q, J=7.6Hz, 2H), 5.23(s, 2H),
6.99(d, J=7.5Hz, 1H), 7.2-7.6(m, 5H), 7.70(dd, J=7.5Hz, J=8.4Hz,
1H), 7.81(brd, 1H), 8.16(d, J=8.4Hz, 1H).
[0163] TABLE-US-00041 TABLE 41 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (18)-19 Z 0.89(t, J=7.0Hz, 3H),
1.27(t, J=7.7Hz, 3H), 1.2-1.4(m, 4H), 1.73(m, 2H), 2.46(t, J=7.3Hz,
2H), 2.76(q, J=7.7Hz, 2H), 5.22(s, 2H), 6.91(s, 1H), 7.2-7.55(m,
5H), 9.47(brd, 1H). (19)-11 Z 0.96(t, 3H, J=7.33Hz), 1.361.48(m,
2H), 1.63-1.72(m, 2H), 2.50(s, 3H), 4.19(t, 2H, J=6.61Hz), 5.23(s,
2H), 6.93(d, 1H, J=7.33Hz), 7.02-7.05(m, 1H), 7.16-7.26(m, 3H),
7.33-7.41(m, 1H), 7.69(t, 1H, J=7.69Hz), 7.92(d, 1H, J=8.44Hz).
(19)-12 Z 0.95(t, 3H, J=7.33Hz), 1.35-1.48(m, 2H), 1.64-1.72(m,
2H), 2.50(s, 3H), 4.19(t, 2H, J=6.79Hz), 5.23(s, 2H), 6.92(d, 1H,
J=6.79Hz), 7.05-7.13(m, 2H), 7.32(brd, 1H), 7.35-7.41(m, 2H),
7.68(t, 1H, J=6.34Hz), 7.91(d, 1H, J=8.26Hz). (19)-13 Z 0.96(t, 3H,
J=7.33Hz), 1.36-1.48(m, 2H), 1.62-1.72(m, 2H), 2.50(s, 3H), 4.19(t,
2H, J=6.58Hz), 5.25(s, 2H), 6.92(d, 1H, J=7.51Hz), 7.15-7.18(m,
1H), 7.26-7.36(m, 2H), 7.44-7.49(m, 1H), 7.69(t, 1H, J=8.05Hz),
7.92(d, 1H, J=8.23Hz). (19)-14 Z 0.96(t, 3H, J=7.33Hz),
1.36-1.48(m, 2H), 1.62-1.72(m, 2H), 2.49(s, 3H), 4.19(t, 2H,
J=6.61Hz), 5.23(s, 2H), 6.92(d, 1H, J=7.51Hz), 7.30-7.40(m, 4H),
7.68(t, 1H, J=7.51Hz), 7.91(d, 1H, J=8.26Hz).
[0164] TABLE-US-00042 TABLE 42 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (19)-16 Z 0.95(t, 3H, J=7.15Hz),
1.35-1.48(m, 2H), 1.62-1.71(m, 2H), 2.38(s, 3H), 2.48(s, 3H),
4.19(t, 2H, J=6.58Hz), 5.22(s, 2H), 6.93(d, 1H, J=7.33Hz),
7.20-7.30(m, 5H), 7.68(t, 1H, J=7.90Hz), 7.89(d, 1H, J=8.41Hz).
(19)-23 Z 0.96(t, 3H, J=7.48Hz), 1.36-1.48(m, 2H), 1.62-1.72(m,
2H), 2.49(s, 3H), 3.83(s, 3H), 4.19(t, 2H, J=6.79Hz), 5.20(s, 2H),
6.88-6.94(m, 3H), 7.26-7.31(m, 3H), 7.68(t, 1H, J=7.87Hz), 7.92(d,
1H, J=8.23Hz). (19)-25 Z 0.96(t, 3H, J=7.33Hz), 1.36-1.48(m, 2H),
1.63-1.72(m, 2H), 2.51(s, 3H), 4.19(t, 2H, J=6.61Hz), 5.28(s, 2H),
6.92(d, 1H, J=7.15Hz), 7.49-7.53(m, 2H), 7.67-7.72(m, 3H), 7.93(d,
1H, J=8.26Hz). (19)-28 Z 0.90-0.94(m, 3H), 1.34-1.40(m, 4H),
1.65-1.69(m, 2H), 2.52(s, 3H), 3.07(s, 3H), 4.18(t, 2H, J=6.79Hz),
5.29(s, 2H), 6.93(d, 1H, J=7.51Hz), 7.58-7.62(m, 2H), 7.70(t, 1H,
J=7.90Hz), 7.92-8.00(m, 3H). (19)-29 Z 0.96(t, 3H, J=7.33Hz),
1.36-1.48(m, 2H), 1.63-1.72(m, 2H), 2.52(s, 3H), 4.20(t, 2H,
J=6.61Hz), 5.30(s, 2H), 6.93(d, 1H, J=6.97Hz), 7.56-7.61(m, 2H),
7.70(t, 1H, J=7.69Hz), 7.94(d, 1H, J=8.23Hz), 8.24-8.27(m, 2H).
[0165] TABLE-US-00043 TABLE 43 Com- pound No. Z/E
.sup.1H-NMR(CDCl.sub.3) .delta. (19)-31 Z 0.96(t, 3H, J=7.33Hz),
1.34-1.48(m, 2H), 1.63-1.72(m, 2H), 2.51(s, 3H), 4.19(t, 2H,
J=6.61Hz), 5.27(s, 2H), 6.93(d, 1H, J=7.33Hz), 7.28(brd, 1H),
7.93(d, 1H, J=8.26Hz). (19)-33 Z 0.95(t, J=7.3Hz, 3H), 1.32(t,
J=7.6Hz, 3H), 1.41(m, 2H), 2.80(q, J=7.6Hz, 2H), 4.19(t, J=6.6Hz,
2H), 5.24(s, 2H), 6.93(d, J=7.0Hz, 1H), 7.2-7.6(m, 6H), 7.68(dd,
J=7.0Hz, 8.3Hz, 1H), 7.90(d, J=8.3Hz, 1H). (19)-34 Z 0.96(t, 3H,
J=7.33Hz), 1.23(t, 3H, J=7.51), 1.35-1.48(m, 2H), 1.67-1.72(m, 2H),
2.49(s, 3H), 2.68(q, 2H, J=7.51), 4.19(t, 2H, J=6.58Hz), 5.21(s,
2H), 6.92(d, 1H, J=7.33Hz), 7.20-7.29(m, 5H), 7.67(t, 1H,
J=7.51Hz), 7.89(d, 1H, J=8.26Hz). (19)-36 Z 0.96(t, 3H, J=7.33Hz),
1.36-1.48(m, 2H), 1.62-1.72(m, 2H), 2.52(s, 3H), 4.19(t, 2H,
J=6.61Hz), 5.25(s, 2H), 6.95(d, 1H, J=7.54Hz), 7.37-7.48(m, 6H),
7.57-7.63(m, 4H), 7.69(t, 1H, J=8.05Hz), 7.91(d, 1H, J=8.26Hz).
(19)-37 Z 0.94(t, 3H, J=7.33Hz), 1.36-1.46(m, 2H), 1.61-1.71(m,
2H), 2.64(s, 3H), 4.19(t, 2H), J=6.79Hz), 5.29(s, 2H), 6.98(d, 1H,
J=7.33Hz).7.34-7.48(m, 3H), 7.59(brd, 1H), 7.64-7.71(m, 2H),
7.95(d, 1H, J=8.08Hz).
[0166] TABLE-US-00044 TABLE 44 Compound No. Z/E .sup.1H-NMR
(CDCl.sub.3) .delta. (19)-38 Z 0.94(t, 3H, J=7.33Hz), 1.34-1.46(m,
2H), 1.61-1.68(m, 2H), 2.59(s, 3H), 3.50(s, 3H), 4.18(t, 2H,
J=6.79Hz), 5.25(s, 2H), 6.84(d, 1H, J=8.05Hz), 6.90-7.11(m, 2H),
7.38-7.48(m, 1H), 7.62-7.73(m, 3H), 7.93(d, 1H, J=8.27Hz). (20)-6 Z
0.87(t, J=7.0Hz, 3H), 1.23(t, J=7.7Hz, 3H), 1.2-1.4(m, 6H), 1.69(m,
2H), 2.71(q, J=7.7Hz, 2H), 4.24(t, J=7.0Hz, 2H), 5.30(s, 2H),
6.87(s, 1H), 7.2-7.5(m, 5H), 10.53(brd, 1H). (21)-5 Z 0.94(t,
J=7.3Hz, 3H), 1.40(m, 2H), 1.56(m, 2H), 3.35(dt, J=6.3, 6.3Hz, 2H),
3.93(s, 3H), 5.27(s, 2H), 6.77(d, J=7.5Hz, 1H), 6.83(d, J=7.5Hz,
1H), 7.3-7.6(m, 5H), 7.58(dd, J=7.5, 8.3Hz, 1H), 8.72(brd, 1H),
9.31(brd, 1H). (21)-15 Z 0.88(t, J=6.8Hz, 3H), 1.2-1.4(m, 6H),
1.56(m, 2H), 3.35(dt, J=6.6, 6.6Hz, 2H), 3.93(s, 3H), 5.27(s, 2H),
6.78(d, J=8.3Hz, 1H), 6.82(d, J=7.5Hz, 1H), 7.3-7.6(m, 5H),
7.57(dd, J=7.5, 8.3Hz, 1H), 8.82(brd, 1H), 9.31(brd, 1H). (22)-15 Z
0.88(t, J=6.9Hz, 3H), 1.2-1.4(m, 6H), 1.57(m, 2H), 2.46(s, 3H),
3.36(td, J=6.5, 6.5Hz, 2H), 5.25(s, 2H), 6.81(d, J=7.5Hz, 1H),
6.84(d, J=8.6Hz, 1H), 7.3-7.6(m, 5H), 7.58(dd, J=7.5, 8.6Hz, 1H),
9.28(brd, 1H), 9.34(brd, 1H).
[0167] TABLE-US-00045 TABLE 45 Compound No. Z/E .sup.1H-NMR
(CDCl.sub.3) .delta. (3)-25 Z 1.64(m, 2H), 2.00(s, 3H), 3.64(q,
J=6.2Hz, 2H), 3.99(s, 3H), 4.18(t, J=6.7Hz, 2H), 5.22(s, 2H),
6.94(d, J=7.0Hz, 1H), 7.3-7.55(m, 6H), 7.65(dd, J=7.0, 8.4Hz, 1H),
7.88(d, J=8.4Hz, 1H). (5)-19 Z 2.03(s, 3H), 2.25(q, J=6.0Hz, 2H),
3.45(q, J=6.0Hz, 1H), 4.13(s, 3H), 5.25(s, 2H), 7.04(d, J=7.3Hz,
1H), 7.31-7.51(m, 5H), 7.76(dd, J=7.5Hz, 8.0Hz, 1H), 8.16(d,
J=8.0Hz, 1H). (11)-24 Z 2.01(s, 3H), 2.22(q, J=6.0Hz, 2H), 2.51(s,
3H), 3.47(q, J=6.0Hz, 2H), 5.27(s, 2H), 6.92(d, J=7.3Hz, 1H),
7.35-7.52(m, 5H), 7.75(dd, J=7.6, 8.2Hz, 1H), 7.76(brd, 1H),
8.19(J=8.1Hz, 1H). (13)-24 Z 1.62(m, 2H), 2.02(s, 3H), 2.51(s, 3H),
3.62(q, J=6.1Hz, 2H), 4.17(t, J=6.7Hz, 2H), 5.23(s, 3H), 6.91(d,
J=6.8Hz, 1H), 7.37-7.59(m, 5H), 7.63(dd, J=6.8, 8.4Hz, 1H), 7.86(d,
J=8.4Hz, 1H).
[0168] Formulation Examples using the compound of the present
invention will now be described. The compounds used in the
Formulation Examples and control tests are mixtures of (Z) and (E)
isomers unless otherwise specified.
Formulation Example 1
Wettable Powders
[0169] 20 parts by weight of each of the tetrazoyloxime derivatives
shown in Tables 1 to 23 was adsorbed to 30 parts by weight of white
carbon. Each tetrazoyloxime derivative adsorbed on white carbon was
mixed with 3 parts by weight of sodium polyoxyethylene lauryl
sulfate, 8 parts by weight of 50 wt % polyoxyethylene alkyl phenyl
ether sulfate ammonium powder, 1 part by weight of sodium
ligninsulfonate and 38 parts by weight of clay, and each mixture
was ground using a jet mill to obtain wettable powders.
Formulation Example 2
Powders
[0170] 2 parts by weight of each of the tetrazoyloxime derivatives
shown in Tables 1 to 23 was mixed with 98 parts by weight of clay,
and each mixture was ground to obtain powders.
Formulation Example 3
Granules
[0171] 5 parts by weight of each of the tetrazoyloxime derivatives
shown in Tables 1 to 23 was mixed with 90 parts by weight of a
mixture of bentonite and talc in a mixing ratio of 1:1 and 5 parts
of sodium alkylbenzenesulfonate, and each mixture was molded to
yield granules.
[0172] The following Test Examples show that the compounds of the
present invention are suited for use as active ingredients of
various plant disease controlling agents. The pathopoiesis state of
the test plant was examined by disease severity using a
pathopoiesis index, and disease severity and control value were
determined by the following equations. The results are shown in
Tables 47 to 56.
Pathopoiesis Index
[0173] Samples where neither colonies nor lesions were observed are
rated "0", samples where colonies and lesions were observed at
about 25% are rated "1", samples where colonies and lesions were
observed at about 25 to 50% are rated "2", and samples where
colonies and lesions were observed at about 50% or more are rated
"3", respectively. Disease severity(%)=[.SIGMA.(number of leaves by
disease severity.times.index/(number of leaves
examined.times.3(maximum value of disease severity
index))].times.100 Control value(%)=(disease severity of
non-treated section-disease severity of treated section)/(disease
severity of non-treated section).times.100
[0174] The following compounds were used as control agents. [0175]
Control agent 1: Manzeb wettable powders (commonly used downy
mildew control agent) [0176] Control agent 2: Typical compound A
described in Japanese Unexamined Patent Application, First
Publication No. Hei 11-269176 (WO99/29689, EP-A-1038874) [0177]
Control agents 3 and 4: Typical compounds B and C described in
Japanese Unexamined Patent Application, First Publication No.
2001-55387 (WO00/75138, EP-A-1184382)
[0178] An active ingredient of manzeb wettable powders used as the
control agent 1 is an agricultural fungicide which was developed by
Rohm and Haas Agricultural Chemicals in USA and register on 1969,
and is zinc-coordinated ethylenebisdithiocarbamate represented by
the formula: ##STR67##
[0179] The control agents 2, 3 and 4 are compounds specified by the
following general formula and the following table. TABLE-US-00046
TABLE 46 ##STR68## R X Y Z Q Control agent 2 H CH S CH H Control
agent 3 Cl N S CH H Control agent 4 H CH CH N Cl
[0180] The control effect against downy mildew on grape and late
blight on tomato mainly includes a protecting effect and a
therapeutic effect. The protecting effect is an effect obtained by
spraying a test substance on young test plants in pots, drying in
air, spray-inoculating a dispersion of spores of the objective
plant pathogens, standing the young test plants in pots under high
humidity conditions, thereby to allow disease to develop, and
growing the young test plants in pots in a greenhouse for a fixed
period. The therapeutic effect is an effect obtained by inoculating
a dispersion of spores of the objective plant pathogens on a young
test plants in pots, standing the young test plants in pots under
high humidity conditions, thereby to allow disease to develop,
spraying a test substance on the young test plants in pots, drying
in air, and growing the young test plants in pots in a greenhouse
for a fixed period.
[0181] The test with regard to the protecting effect to the
compound of the present invention was carried out against downy
mildew on grape and late blight on tomato, together with control
agents 1, 2, 3 and 4. All compounds of the present invention
exhibited effects superior to those of the control agent 1 and also
exhibited effects which were the same as or superior to those of
the control agents 2, 3 and 4. The test with regard to the
therapeutic effect was carried out according to the following grape
downy mildew control test (Test Example 1) and tomato late blight
control test (Test Example 2).
Test Example 1
Grape Downy Mildew Control Test (Therapeutic Effect)
[0182] A dispersion of spores of downy mildew (Plasmopara viticola)
on grape was spray-inoculated on grape plants (variety: Neomuscat,
5- to 6-leaf stage) cultivated in 1/10,000 ares Wagner pots and
inoculated pots were placed in a wet room maintained at 25.degree.
C. for 18 hours. After drying leaves in air, wettable powders
prepared according to the method of Preparation Example 1 were
diluted with water to prepare a chemical solution having an active
ingredient concentration of 100 ppm. The chemical solution was
sprayed enough to drip from leaf surfaces and were then transferred
to a greenhouse to allow disease to develop. After 10 days had
passed since inoculation, disease severity was determined. The
results are shown in Tables 47 to 56. TABLE-US-00047 TABLE 47
Compound No. Concentration (ppm) Control value (%) (1)-6 100 70
(1)-7 100 100 (1)-8 100 70 (1)-12 100 100 (1)-16 100 70 (1)-18 100
100 (1)-21 100 70 (2)-7 100 90 (2)-11 100 100 (2)-12 100 90 (2)-16
100 90 (3)-2 100 70 (3)-3 100 90 (3)-4 100 90 (3)-5 100 100 (3)-8
100 100 (3)-9 100 100 (3)-15 100 100 (3)-16 100 100 (3)-18 100 100
(3)-21 100 70 (3)-22 100 100 (3)-23 100 80
[0183] TABLE-US-00048 TABLE 48 Compound No. Concentration (ppm)
Control value (%) (4)-9 100 80 (4)-15 100 70 (4)-18 100 70 (5)-12
100 100 (5)-14 100 90 (6)-2 100 70 (6)-6 100 70 (6)-7 100 100
(6)-15 100 70 (7)-1 100 70 (7)-3 100 80 (7)-11 100 70 (7)-12 100
100 (8)-2 100 70 (8)-7 100 70 (8)-10 100 70 (8)-17 100 90
[0184] TABLE-US-00049 TABLE 49 Compound No. Concentration (ppm)
Control value (%) (9)-1 100 100 (9)-2 100 70 (9)-3 100 70 (9)-4 100
100 (9)-5 100 100 (9)-6 100 70 (9)-7 100 100 (9)-9 100 100 (9)-10
100 100 (9)-11 100 100 (11)-4 100 70 (11)-5 100 70 (11)-6 100 70
(11)-7 100 100 (11)-8 100 100 (11)-11 100 70 (11)-12 100 100
(11)-21 100 70 (12)-6 100 80 (12)-7 100 90 (12)-12 100 90 (12)-18
100 90
[0185] TABLE-US-00050 TABLE 50 Compound No. Concentration (ppm)
Control value (%) (13)-5 100 70 (13)-8 100 90 (13)-9 100 100
(13)-15 100 80 (13)-21 100 80 (13)-22 100 100 (14)-5 100 70 (16)-3
100 70 (17)-1 100 100 (18)-1 100 100
[0186] TABLE-US-00051 TABLE 51 Compound No. Concentration (ppm)
Control value (%) (19)-1 100 100 (19)-11 100 80 (19)-12 100 90
(19)-13 100 100 (19)-14 100 80 (19)-16 100 100 (19)-23 100 70
(19)-25 100 90 (19)-28 100 100 (19)-29 100 80 (19)-31 100 90
(19)-33 100 100 (19)-34 100 80 (19)-35 100 70 (20)-1 100 70 (22)-2
100 70 (22)-5 100 100 (22)-15 100 100 Control agent 1 750 0 Control
agent 2 100 50 Control agent 3 100 30 Control agent 4 100 20
Test Example 2
Tomato Late Blight Control Test (Therapeutic Effect)
[0187] A dispersion of spores of late blight (Plasmopara viticola)
on tomato was spray-inoculated on tomato plants (variety: Hofuku,
4-leaf stage) cultivated in plastic pots having a diameter of 9 cm
and inoculated pots were placed in a wet room maintained at
20.degree. C. for 18 hours. After drying leaves in air, wettable
powders prepared according to the method of Preparation Example 1
were diluted with water to prepare a chemical solution having an
active ingredient concentration of 100 ppm. The chemical solution
was sprayed enough to drip from leaf surfaces and were then
transferred to a greenhouse to allow disease to develop. After 7
days bad passed since inoculation, disease severity was determined.
The results are shown in Tables 52 to 56. TABLE-US-00052 TABLE 52
Compound No. Concentration (ppm) Control value (%) (1)-6 100 90
(1)-7 100 100 (1)-8 100 90 (1)-12 100 100 (1)-16 100 100 (1)-18 100
100 (1)-21 100 90 (2)-7 100 100 (2)-11 100 100 (2)-12 100 100
(2)-16 100 100 (3)-2 100 90 (3)-3 100 100 (3)-4 100 100 (3)-5 100
100 (3)-8 100 100 (3)-9 100 100 (3)-15 100 100 (3)-16 100 100
(3)-18 100 100 (3)-21 100 100 (3)-22 100 100 (3)-23 100 100
[0188] TABLE-US-00053 TABLE 53 Compound No. Concentration (ppm)
Control value (%) (4)-9 100 100 (4)-15 100 80 (4)-18 100 90 (5)-12
100 100 (5)-14 100 100 (6)-2 100 80 (6)-6 100 80 (6)-7 100 100
(6)-15 100 90 (7)-1 100 80 (7)-3 100 80 (7)-11 100 80 (7)-12 100
100 (8)-2 100 90 (8)-7 100 80 (8)-10 100 90 (8)-17 100 80
[0189] TABLE-US-00054 TABLE 54 Compound No. Concentration (ppm)
Control value (%) (9)-1 100 100 (9)-2 100 80 (9)-3 100 90 (9)-4 100
100 (9)-5 100 100 (9)-6 100 100 (9)-7 100 100 (9)-9 100 100 (9)-10
100 100 (9)-11 100 100 (11)-4 100 80 (11)-5 100 80 (11)-6 100 80
(11)-7 100 100 (11)-8 100 100 (11)-11 100 80 (11)-12 100 100
(11)-21 100 90 (12)-6 100 100 (12)-7 100 100 (12)-12 100 100
(12)-18 100 100
[0190] TABLE-US-00055 TABLE 55 Compound No. Concentration (ppm)
Control value (%) (13)-5 100 90 (13)-8 100 100 (13)-9 100 100
(13)-15 100 90 (13)-21 100 100 (13)-22 100 100 (14)-5 100 80 (16)-3
100 80 (17)-1 100 100 (18)-1 100 100
[0191] TABLE-US-00056 TABLE 56 Compound No. Concentration (ppm)
Control value (%) (19)-1 100 100 (19)-11 100 90 (19)-12 100 100
(19)-13 100 100 (19)-14 100 100 (19)-16 100 100 (19)-23 100 80
(19)-25 100 90 (19)-28 100 100 (19)-29 100 100 (19)-31 100 100
(19)-33 100 100 (19)-34 100 100 (19)-35 100 80 (20)-1 100 80 (22)-2
100 90 (22)-5 100 100 (22)-15 100 100 Control agent 1 750 10
Control agent 2 100 60 Control agent 3 100 40 Control agent 4 100
30
[0192] As is apparent from the results shown in the tables
described above, the tetrazoyloxime derivative of the present
invention is superior, in therapeutic effect, to a conventional
hetero ring-substituted oxime derivative and a commonly used plant
disease controlling agent. Since a plant disease controlling agent
containing the tetrazoyloxime derivative of the present invention,
which is superior in therapeutic effect, has sufficient plant
disease controlling activity even when it is sprayed after
confirming pathopoiesis of plant pathogens, it is made possible to
reduce the number of applications of an agricultural chemical, and
thus the plant disease controlling agent is excellent in view of
saving of labor and cost.
INDUSTRIAL APPLICABILITY
[0193] The tetrazoyloxime derivative represented by the general
formula (1) of the present invention is less likely to cause
chemical injury to useful plants and is also suited for use as an
agricultural chemical, especially a plant disease controlling
agent. The agricultural chemical containing the tetrazoyloxime
derivative as an active ingredient of the present invention is
superior in therapeutic effect against plant diseases to a
conventional hetero ring-substituted oxime derivative, and is
therefore suited for use as a plant disease controlling agent.
Furthermore, tetrahydroxyimino derivatives represented by the
general formulas (6) and (7) according to the present invention are
suited for use as an intermediate of the tetrazoyloxime derivative
represented by the general formula (1) of the present
invention.
* * * * *