Note: Descriptions are shown in the official language in which they were submitted.
1~4a9 49
THIS IS A DIVISIONAL APPLICATION OF CANADIAN PATENT APPLICATION
SERIAL DfUMBER 560,436 FILED ON MARCH 3, 1988
1 FIELD OF THE INVENTION
The present invention relates to novel imidazole
compounds and biocidal compositions comprising the same
for controlling harmful organisms.
BACKGROUND OF THE INVENTION
Imidazole type compounds proposed so far are
exemplified below.
Belgian Patient 852313 (published Sept. 12, 1977)
discloses (4,!5)-dichloro-imidazole(2)-carboxylic acid
C1
derivatives having the formula XYZC -~~ wherein CXYZ
N C1
H
represents a (: atom with 3 bonds attached to hetero atoms,
and Japanese Patent Publication No. 15625/85 (published
Apr. 20, 1985) discloses the following reaction scheme,
C1 ,\ C1
CC13
CC12
C1 Ni C1 N C1
while no compound having other substituents than chlorine
atoms at the 4 and 5-positions in the imidazole ring and
having a substituted sulfonyl group in the imidazole ring
is disclosed in both of the above references.
- 1 -
1 3 ~ 09 49
1 Recl. Tr;~v. Chim. Pays-Bas ,1973, 92(3), 449-59
phenyl . ~ phenyl
discloses NC -< ~ , NC -~ ~ , etc. ;
N~ H N phenyl
H H
DT-OS 2317453 (published Oct. 11, 1973) discloses
CN ~ CN
quaternary ammonium salts of NC ~ or N02--
N CN N CN
H H
etc.; J. Org. Chem., Vol. 44, No. 16, 1979, 2902-2906
_. ~ , R
discloses NC -~ ~ (R: H, CH3), etc.; EP 31086
N'
H
X
(published July 1, 1987.) discloses R'--C~~ (R': -CQZR,
N y
H
CN); J. Orct. Chem., Vol. 51, No. 10, 1986, 1891-1894
discloses 2-cyano innidazole, etc.; and Research
Disclosure, June (1986), 323-324 (C. A., 106, 49942e)
phenyl-X
discloses NC-~~'~ , etc.; while no
N phenyl-X'
H
compound having a substituted sulfonyl group in the
imidazole ring is disclosed in any of the above-described
references.
Japanese Patent Application (OPI) No. 4303/80
(published Jan. 12, 1980) (the term "OPI" as used herein
- 2 -
X3409 49
1 means a "publi.shed unexamined patent application")
discloses 1-(N,N-~dimethyl-
S02N(CH3)2
I
N CN
sulfamoylj-4,5-d:icyanoimidazole ~ ~ ; C.A., 95:
N CN
7283q [Japanese Patent Application (OPI) No. 157570/80
(published Dec. 8, 1981))] discloses sulfamoylimidazole
:i OZN ( Cla3 ) 2 S02N ( CH3 ) 2
N CN N CONHZ
derivatives of ~ ~ and ~ ~ ; C.A., 101:
rl CO1NH2 N . CN
7092u (J.Chem. Soc., PE~rkin Trans. 1, 1984, (3), 481-6)
SO,~N ( CH3 ,) 2
N Li
discloses Li~ ~ , etc.; and C.A., 106: 138324x
N'
(Tetrahedron, 19f.6, 42(8), 2351-8) discloses
S02N(CH3)2
I
Li
(Et)3Si~ ~ . etc.; while no compounds having other
N
than a hydrogen atom, a lithium atom, or an -Si(Et)3 group
at the 2-position in i=he imidazole ring as a substituent
are disclosed.
Japanese Patent Application (OPI) No. 142164/87
(published June 25, 1987) discloses 4,5-dichloro-imidazole
C1
compounds having the formula R3 -~~ , while no
N C1
I
S02NR1R2
- 3 -
13449 49
1 compounds having other substituents than chlorine atoms at
the 4 and 5-posit:ions in the imidazole ring are disclosed.
References li~;ted below disclose imidazopyridine
compounds- and/or benz;imidazole compounds in which the
compounds contain a condensed ring of an imidazole ring
with a benzene ring and/or a pyridine ring in their
chemical structures.
U.S. Patent 36179157 (issued Sept. 28, 1971)
U.S. Patent 3681369 (issued Aug. 1, 1972)
. Belgian Patent 830719 (published Dec. 29, 1975)
Belgian Patent 845641 (published Feb. 28, 1977)
U.S. Patent 4536502 (issued Aug. 20, 1985)
U.S. PatE~nt 45;79853 (issued Apr. 1, 1986)
French Patent :?559150 (published Aug. 9, 1985)
Japanese Patent: Application (OPI) No. 103873/86
(published May 22, 1086)
Japanese Patent: Application (OPI) No. 22782/87
(published Jan.. 30, 1987)'
EP 219192 (pubT~ished Apr. 22, 1987)
Japanese Patent: Application (OPI) No. 195379/87
(published Aug. 28, 1987)
EP 239508~ (publ.ished Sept. 30, 1987)
SUMMARY OF THE INVENTION
An object: of the present invention is to provide
imidazole compounds of the following general formula (I)
and biocidal compositions comprising the same for
controlling harmful organisms:
- 4 -
13~09.4~
R2
1 R1 I
N R3
_ i
S0,2R4
wherein:
R1 represents a cyano group or a -CSNHRS group,
wherein R5 represents .a hydrogen atom, a C1-4 alkyl group,
or a -CORE group, wherein R6 represents a Cl_4 alkyl group,
a halogenated C1_4 alkyl group, or a~phenyl group;
R2 and R3 each represents a hydrogen atom; a
halogen atom; a nitro group; a cyano group; a trimeth-
ylsilyl group; a C;;_6 cycloalkyl group; a naphthyl
group; a C1-12 alkyl group which is optionally
substituted with one or more halogen atoms, hydroxyl
groups, acetoxy groups, Cl_4 alkoxy groups, halogenated
C1_4 alkoxy groups, phenyl groups, halogenated phenyl
groups, or C1_4 alkylated phenyl groups; a C2_lo alkenyl
group which is optionally substituted with one or more
halogen atoms; a Cl_6 alkoxy group which is optionally
substituted with one or more halogen atoms; a phenyl
group which is optionally substituted with one or more
halogen atoms, C:1_4 a7Lky1 groups, halogenated Cl_4 alkyl
groups, C1_4 alkoxy groups, halogenated C1_9 alkoxy groups,
C1_q alkylthio groups, halogenated C1_4 alkylthio groups,
nitro groups, cyano groups, or 3,4-methylenedioxy groups;
- 5 -
~~~409 49
1 a furyl group which is optionally substituted with one or
more halogen atoms or C1_q alkyl groups; a thienyl group
which is optionally substituted with one or more halogen
atoms or -C1_q alkyl .groups; a pyridyl group which is
optionally substituted. with one or more halogen atoms or
Cl_q alkyl groups; an -SOnR7 group, wherein R~ represents
a Cl_6 alkyl group, a C2_6 alkenyl group, a phenyl group
which is optionally substituted with one or more halogen
atoms, a benzyl <iroup, a pyridyl group which is optionally
. substituted with one or more halogen atoms, C1_q alkyl
groups, or halogenated Cl_q alkyl groups; or an -NR$R9
group, wherein I~g and R9 each represents a Cl_q alkyl
group, and n is 0, 7., or 2; or a -CO(NH)mRlp group,
wherein Rlp represents a Cl_q alkyl group which is
optionally substituted with one or more halogen atoms, a
Cl_q alkoxy group which is optionally substituted with one
or more halogen atoms, or a phenyl group which is
optionally substituted with one or more halogen atoms;
and m is 0 or 1; and
Rq represents a C1_6 alkyl group which is
optionally substituted with one or more halogen atoms; a
C3_6 cycloalkyl group; a phenyl group; a thienyl group;
or an -NR11R12 group, wlherein R11 and R12 each represents a
hydrogen atom, a~ Cl_q alkyl group which is optionally
substituted with one or more halogen atoms, a C2_q alkenyl
group, or R11 and R;~2 are combined with each other
- 6 -
13409 49
1 together with a nitrogen atom adjacent thereto to form a
pyrrolidinyl grc>up, a piperidinyl group, a morpholino
group, or a thiomorpholino group, provided that R11 and
R12 are not simultaneously a hydrogen atom;
provided that R2 and R3 are not simultaneously a
halogen atom.
Another object: of the present invention is to
provide a process; for preparing the imidazole compounds of
the formula (I) hereinabove.
_ . A further object of the present invention is to
provide intermediate compounds of the following general
formula (II'):
R2
NC (II')
N R3
H
wherein R2 and R.3 each represents a hydrogen atom; a
halogen atom; a nitro group; a cyano group; a trimeth-
ylsilyl group; a Cg._6 cycloalkyl group; a naphthyl
group; a Cl-12 alkyl group which is optionally
substituted with one or more halogen atoms, hydroxyl
groups, acetoxy groups, Cl_q alkoxy groups, halogenated
Cl_4 alkoxy groups, phenyl groups, halogenated phenyl
groups, or Cl_4 aLkylat~ed phenyl groups; a C2_lo alkenyl
group which is optionally substituted with one or more
X3409 49
1 halogen atoms; a Cl_6 alkoxy group which is optionally
substituted with one or more halogen atoms; a phenyl
group which is optionally substituted with one or more
halogen atoms, C:1_4 alkyl groups, halogenated Cl_4 alkyl
groups, C1_4 alkoxy groups, halogenated Cl_4 alkoxy groups,
C1_4 alkylthio groups, halogenated Cl_4 alkylthio groups,
nitro groups, cy~ano groups, or 3,4-methylenedioxy groups;
a furyl group which is optionally substituted with one or
more halogen atoms or C1_4 alkyl groups; a thienyl group
_ which is optionally substituted with one or more halogen
atoms or C1_4 alkyl groups; a pyridyl group which is
optionally substituted with one or more halogen atoms or
Cl_4 alkyl groups; an -SOnR7 group, wherein R~ represents
a Cl_6 alkyl group, a CZ_6 alkenyl group, a phenyl group
which is optionally substituted with one or more halogen
atoms, a benzyl o~roup, a pyridyl group which is optionally
substituted with one or more halogen atoms, Cl_4 alkyl
groups, or halogenated Cl_4 alkyl groups; or an -NR8R9
group, wherein R$ and R9 each represents a C1_4 alkyl
group, and n is 0, l, or 2; or a -CO(NH)mRlp group,
wherein Rlp represents a Cl_4 alkyl group which is
optionally substituted with one or more halogen atoms, a
C1_4 alkoxy group which is optionally substituted with one
or more halogen atoms, or a phenyl group which is
optionally substituted with one or more halogen atoms;
and m is 0 or 1,
_ g _
1 3 4 09 49
provided that compoundls represented by the following
general formula (II"):
R '
v
rIC ~ ' (II")
p- ~R
H 3
wherein RZ' and l~3' are simultaneously a hydrogen atom, an
unsubstituted phenyl group or a phenyl group which substituent
is selected from i=he group consisting of the same or different
C~_2 alkoxy group or C~_2 alkylthio group at the para-position,
an unsubstituted C~_4 a:Lkyl group or a substituted C~_4 alkyl
group which substituent is selected from the group consisting
of one or more halogen atoms, hydroxyl groups, acetoxy groups,
C~_4 alkoxy groups, halogenated C~_4 alkoxy groups, phenyl
groups, halogenat:ed phenyl groups, or C~_4 alkylated phenyl
~> ~ groups, ~ wherein RZ' and R3' are each independently selected
from the group consisting of a halogen atom, a cyano group, or
a nitro group; and wherein one of RZ' and R3' is a hydrogen
atom and the other is a halogen atom, a methyl group or a
phenyl group, are excluded.
Among the imiolazole compounds represented by the
general formula (I), preferred compounds of the present
invention are illustraterd below.
- g _
B
X3409 49
Compounds of the general formula ( I ) wherein R, is
a cyano group;
Compounds of the general formula (I) wherein RZ
and R~ each represents a hydrogen atom; a halogen atom; a
nitro group; a c:yano group; a C1_~Z alkyl group which is
optionally substituted with one or more halogen atoms,
hydroxyl groups, C1_4 alkoxy groups, phenyl groups,
halogenated phenyl groups, or C1_' alkylated phenyl groups;
a CZ_,o alkenyl group which is optionally substituted with
one or more halogen atoms; a phenyl
- 9a -
~3~09 49
1 group which is optionally substituted with one or more
halogen atoms, C1_4 alkyl groups, C1_4 alkoxy groups,
halogenated Cl_q alkoxy groups or vitro groups; an -SOnR~
group, wherein R;. represents a Cl_6 alkyl group, a phenyl
group which is optionally substituted with one or more
halogen atoms; or an -NRgRg group, wherein Rg and Rg each
represents a Cl_q alkyl. group, and n is 0, 1, or 2; or a
-CONHRIO group, wherein Rlo represents a phenyl group
which is optiona:Lly su~.bstituted with one or more halogen
_ atoms, provided that R2 and R3 are not simultaneously a
halogen atom;
Compounds of the general formula (I) wherein R4 is
a Cl_6 alkyl group or an -NR11Ri2 group, wherein R11 and R12
each represents a C1_4 ;alkyl group;
Compounds of the general formula (I) wherein R2 is
a hydrogen atom; a C1_12 alkyl group which is optionally
substituted with one or more halogen atoms, phenyl groups,
or halogenated phenyl groups; a C2_4 alkenyl group; a
phenyl group which is optionally substituted with one or
more halogen atoms, C1_4 alkyl groups, Cl_4 alkoxy groups,
or halogenated C1_.4 alkoxy groups; a Cl_6 alkylthio group;
or a phenylthio group which is optionally substituted with
one or more haloge n atoms;
Compounds of the general formula (I) wherein R3 is
a hydrogen atom, a halogen atom, or a cyano group;
- 10 -
~3~09 49
1 Compound, of the general formula (I) wherein R4 is
an -N(CH3)2 group;
Compounds of the general formula (I) wherein RZ is
a Cl-12 alkyl group which is optionally substituted with
one or more halogen atoms, phenyl groups, or halogenated
phenyl groups; a C2._4 alkenyl group; a phenyl group
which is optionally substituted with one or more halogen
atoms; or a Cl_6 alkylthio group;
Compounds of t:he general formula {I) wherein R3 is
l0 . a halogen atom; and '
Compounds of ithe general formula (I) wherein Rl
represents a cyano group; R2 represents a C1_12 alkyl
group or a phenyl group; R3 represents a chlorine atom;
and R4 represents an -D~(CH3)2 group.
DETAILED DESCRIPTION OF THE INVENTION
In the general formula (I) described above,
definitions of C~._4 alk:yl group and alkyl moieties of Cl_4
alkoxy group and Cl_4 ,alkylthio group may include methyl,
ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl
and tert-butyl groups. Definition of C1_6 alkyl group may
include n-pentyl and n-hexyl groups in addition to the
exemplified Cl_4 alkyl groups hereinabove. Definition of
Ci_12 alkyl group may include heptyl, octyl, nonyl, and
decyl groups in addition to the exemplified Cl_6 alkyl
groups hereinabove. Definition of C3_6 cycloalkyl group
may include cyclopropyl, cyclobutyl, cyclopentyl, and
- 11 -
X3409 49
cyclohexyl group:. Df~finition of CZ_q alkenyl group may
include an allyl group, etc. Definition of C2_6 alkenyl
group may include a pe~ntenyl group, etc. in addition to
the exemplified C2_4 alkenyl groups hereinabove.
Definition of C2_lo al.kenyl group may include a geranyl
group, etc. in addition to the exemplified C2_6 alkenyl
groups hereinabove. Definition of halogen atom may
include chlorine, bromine, fluorine, and iodine atoms.
- 12 -
1309 49
The novel imidazole compound represented by the
general formula (I) described above can be prepared
specifically by t:he following process:
(A]
R2
Ri / I + Y-SOZR4
N~ ~R
H 3 (III)
(II)
R2
to 150°C
Ri
1 to ~48 hours N
SOZR4
(I)
wherein Ri, R2, R3, and R4 have the same meanings as
described above; and Y is a halogen atom.
In the general formula (I) described above,
compounds wherein Ri is a cyano group can also be prepared
l0 by the following process: .
- 13 -
°
~340~ ~g
[B]
R2 ,
R2
Step-1 NC
NC -
N' Y-S02R4 (III) N
H 10 to 150°C SOZR4
1 to 48 hours
(II 1) (I-1)
Step-2
_ RZ
n-C4H9Li/tetrahydrofuran
NC
R3_.I N R3
-~80 to 30°C
1. to 24 hours S02Ra
(I-2)
In the general formula (I-2) described above
wherein R3 is an -SR.i group, R~SSR~ can also be used
instead of R3-I in Step-2 of the process [B] described
above. In the foregoing formulae, R2, R3, R4, R~, and Y
have the same meanings as described above.
In the ~genera~l formula (I) described above,
compounds wherein R1 is a cyano group, and R3 is a
hydrogen atom, a chlorine atom, or a bromine atom can also
be prepared by the' following process:
- 14 -
~~4~09 ~49~
, 102R4
- / R2n Step-1 R2..
1 NC I _ NC
N ,R ~~ Y-S02Rq ( I I I ) N R n
H 3 10 t0 150°C
1 to 48 hours
(II_2) (I-3)
10284
Step-2
R2
n-C4H9Li/'tetrahydrofuran
NC
R2._y ~ N R n
-80 to~ 30°C
1 to 24 hours
(I-4)
In the general formula (I-4) described above
wherein R2 is a.n -SP:~ group, R~SSR~ can also be used
instead of R2-Y' in Step-2 of the process (C] described
above; and wherein R2 is a -CH(OH)-813 group (wherein 813
is an alkyl group or an optionally substituted phenyl
group), 813-CHO can also be used instead of R2-Y' in Step-
2 of the process [C] described above. In the foregoing
formulae, R2, R4, a,nd R~ have the same meanings as
described above; R~," and R3" are simultaneously a
- 15 -
~3~Or ~~
1 hydrogen atom, a chlorine atom or a bromine atom; and Y'
is a chlorine atom, a bromine atom, or a iodine atom.
In the general formula (I) described above,
compounds- wherein R~, is a -CSNHZ group or a -CSNHCOR6
group can also be prepared by the following process:
[D]
R2 Step-1 R2
_. NC ~ I - NC
_ Y-SOZR4 (IrI)
N R
'R3 10 t0 150°C
1 to 48 hours S02R4
(II 3) (I-5)
Step-2
H2S S R2
H2NIC I
dioxane, triethylamine N R3
t0 70°C S02R4
0.1 t~o 5 hours
(I-6)
- 16 -
Step-3
R6COC1 II II R2
_~ R6CHNC
acetone,, pyridine N ~R3
0 t0 li 0 ° C S02R4
0.5 to 5 hours
(I-7)
wherein R2, R3, R4, RE,, and Y have the same meanings as
described above.
The process [A] and Step-1 of the processes [B]
through [D] described above are carried out, if necessary
and desired, in the presence of a solvent and an acid
acceptor.
Examples of the solvent include aromatic
hydrocarbons such as benzene, toluene, xylene, chloro-
l0 benzene, etc.; cyclic: or acyclic aliphatic hydrocarbons
such as chloro:Eorm, carbon tetrachloride, methylene
chloride, dichloroetlnane, trichloroethane, n-hexane,
cyclohexane, etc.; ethers such as diethyl ether, dioxane,
tetrahydrofuran, etc.; ketones such as acetone, methyl
15 ethyl ketone, methyl isobutyl ketone, etc.; nitriles such
as acetonitrile, propionitrile, etc.; and aprotic polar
solvents such asc dime~thylformamide, N-methylpyrrolidone,
dimethyl sulfoxide, su7.folane, etc.
As the acid acceptor, any of inorganic bases and
20 organic bases can be used. Examples of the inorganic base
- 17 -
134ag ~9
1 include alkali metal lhydroxides such as sodium hydroxide,
potassium hydroxide, e~tc.; alkali metal or alkaline earth
metal carbonates such as anhydrous potassium carbonate,
anhydrous-calcium carbonate, etc.; alkali metal hydrides
such as sodium hydride; alkali metals such as metallic
sodium; etc. Further, as the organic base, metion may be
made of triethylamine, etc.
The reaction described above can be carried out in
the presence of a suitable catalyst. As the catalyst,
l0 _ mention may be made of, for example, a phase transfer
catalyst such as a quaternary ammonium derivative.
As the halogen atom shown by Y in the general
formula (III) described above, mention may be made of a
chlorine atom, a bromine atom, an iodine atom, and a
fluorine atom; of these, preferred is a chlorine atom.
In the reaci:ion scheme described above, the
compounds represented by the general formula (III) are
known compounds, and the compounds represented by the
general formula (II) c:an be prepared by either one of the
following processes.
(1)
R2 R2
C1;i02R4
N R K2C~3. CH3CN N R3
g 3 10 to 150°C
1 to 48 hours S~2R4
- 1$ -
v~409 4~
n-C4H9Li, RSNCS S R2
RSNHC
tetrahydrofuran '
-80 to 30°C N R3
1_ to 24 hours S02Rq
HC1 S R2
RSNHC
50 to 100°C
1 to 12 hours H R3
(2)
R2 n-C,iH Li O R2
dimet~ylformamide
HC
N R tetrahydrofuran N R
-.BO to 30°C
S02R9 1 to 24 hours SO2R4
R2
NH20H~HC1 .
HON=CH
pyridine N R
50 to 150°C
1 to 24 hours S~2Rq
R2
acetic anhydride
NC
pyridine
50 to 1~i0°C H R3
1 to 24 hours
H2S ~) R2
H2NC
triethylamine
pyridine N R3
to 70°C H
0.1 to 5 hours
- 19 -
'~~~09 ~9
(3)
R2 C1CH20CZH4Si(CH3)3 R2
dimethylformamide N R
R3 NaH, 10 to 70°C
1 to 12 hours CH20C2H4Si(CH3)3
C1CN, CH3C;N R2 HC1
--~- NC i
-30 to 70°C ' 50 to 100°C
1 to 12 hours N R3 1 to 12 hours
CH20C2H4Si(CH3)3
»2
Nc
N 'R3
H
(4)
2 -halogenating agent ~ R2
NC I NC
-50 to 100°C
N 1 to 24 hours N
H H
(5)
R
2
R Y-SOZR4
NC ~ I -- NC
to 150°C N
N 1 to 48 hours
H S02R4
- 20 -
~~~09 ~9
n-C4H9Li, R3-I ~ RZ HCl water
NC
tetrahydrofuran 30 to 100°C
-80 to 30°C i R3 0.5 to 2 hours
1 to 24 hours
- S02R4
l~2
NC
N ~R3
H
R
R~Z NH40H ~ 2
NC
:10 to 120°C
N R3 :L to 60 hours ~ R3
H
(7)
/NH
RZ R3 ( CH30 ) ZCHC/~\ ~ HC1
~CH3 CH3 \ R2'
C2H50-C-CH
CH
CH3OH, 0 to 70°C
C2H50 NH:2 1 to 12 hours CH30 / N R3
H
(i) HC1
ii ) NH20H~HC1/pyridine Rz
(iii)acetic anhydride
NC
50 to 150°C N R3
1 to 24 hours H
- 21 -
~3~09 ~9
c8)
O R2 ;NH40H . ~) R2
CH OC
- H2NC
!i0 to 150°C
H 'R3 :L to 100 hours H R3
POC13 R2
I
50 to 110°C
1 to 12 hours H R3
O )Z2 ~R5NH2 ~~ R2
CH30'C ~ I - RSNH ~ I
0 to 150°C
'R3 1 to 50 hours H R3
~) i~S
CH30 -O- P\, / --«OCH3 S R2
S ~S (I
RSNH
toluene N R3
H
(10)
R
R2 NH3/02 ~ 2
CH3 ~ ( - ~- NC I
N N
H H
- 22 -
X3409 49
cll)
R
;R2 - K2S208 : ~ 2
CH I --~ HOCH2
3
-N N
H H
R2
Mn02 ~~ ~ ~'' RZ NH20H ~ HC1
HC - I HON=CH
N ~ N
H H
R2
acetic anhydride
NC
N
H
(12)
R
C12~HC1 w 2 HC1
CH3 ~ I -~ C12C
N N C1
H
R2 NH.40H ~ R2
CC13 ~ I --~ NC
N 'C1 N ~Cl
H H
- 23 -
~34Q9 ~9
(13)
R2 R2 .
NaCN
N - Q ~N electrode reaction
H
R., R
ac5.d or alkali
NC I NC
S2 N N
H
(14)
R2 halogenating agent R2
n-C4H9Li ~ CuCN
Y
S2 N Q N
R2
R2
NC I acid or alkali
NC
N
N
H
- 24 -
°
~~409 ~9
(15)
R2
C1COORa O R2
n-C4H9Li ~~ acid or alkali
RaOC
S2 N S2 ..N
R~' ( i ) SOC12/ ( i i ) NH40H il R2
HOC I H2NC
-- N . N
H ' H
POC13 or SOC1,, R2
~ NC:
N
H
(16)
R2 R2
( CH20 ) n ~ Mn02
~. HOCH2
S2 N Q N
O F;2 RZ
NH20H ~ HC1
HC I _~ HON=C
N Q N
- 25 -
~~~09 ~~
R2 acetic
acid or alkali ~ anhydride
HON=CH
N
H
R2
NC
N
H
(17)
. R2 dimethylformamide ~ I' . R2
n-C9H91Li
HC
N Q N
R
NH20H~HCl 2 acid or alkali
H:ON=CH-
i~ N
acetic R
anhydride
HON=CH ( - ~ NC
N~ N
H H
- 26 -
X3409 49
(la)
R.2 Na/NH3 . R2 Mn02
HOCH2 . I HOCH2
r
Q N N
H
R2 acetic
NH20H~HC1 ~ ~ anhydride
HON=CH-
N
H
R2
NC
N
H
(19)
R2 S R
(i)CS2/(ii) acid or alkali
- HSC
N N
H
R2 acetic
NH20H~HC1 ~ ~ anhydride
HON=CH
N
H
- 27 -
°
3409 49
R2
NC
N
H
(20)
II R2 H2~~2 II / RZ
HSC ~ I -~ HOC
N N
H H
(i) SOC12/(ii) NH4OH O R2
II
H2NC
N
H
POC13 or SOC_L2 R2
NC
N
H
(21)
O
O
2
R Q ~ CIC1 o- CIHN R2
N Na013 ~HN
H II
O
- 28 -
~~~09 4~
trifluoro-
acetic R2 _ R2
anhydride / NHg
CF3 ( ~ NC /
CH30H
N N
H H
(22)
R2
. CF3I / R2 _ NH3
:~ CF3
N by
H N
_. H , .
R2
N~ /
N
H
In the foregoing formulae, R2, R3, R4, R5, and Y
have the same n~eaninc~s as described above; X is a CF3
group or a CC13 group; Ra is an alkyl group; and Q is a
protective group.
As the :protective groups for Q, an -SOZRb group,
wherein Rb is a dialk:ylamino group, an alkyl group, or an
optionally alky7.ated phenyl group; a -CH(Rc)-Rd group,
wherein Rc is a hydrogen atom or a methyl group, and Rd is
an alkoxy group, a phenyl group which is optionally
substituted with, an alkyl group or an alkoxy group, or a
-OC2HQSi(CH3)3, e~tc. are exemplified.
In each of the processes as described above, the
reaction conditions such as reaction temperature, reaction
_ 29 -
~~~409 ~49
time, solvent, acid acceptor, alkali acceptor, etc, can
appropriately be chosen from the conventionally known
reaction conditions.
Further, the compounds of the formula
R2
CH3 ~ I in the reaction schemes of the processes
N
H
( 10 ) , ( 11 ) , and ( 12 ) described above can be prepared by,
for example, the following methods:
(23)
R2 CH3-A2
R 2 A 1 -----
or
A1
O
(24)
R2 i~H3 Aq
NH3
0
(25)
R
NH2 CH -A ~ 2 oxidation
3 g ~ CH3 H
NH2 . H
H
- 30 -
~~~09 ~~
(26)
R2 .
CH3 ~ I - TiCl3
- N
OH
Still further, the compounds of the formula
R2
in the reaction schemes of the processes
N
H . '
(13), (21), and (22) described above can be prepared by,
for example, the following methods:
(27)
R2
R2 A1 A2-H
or
A1
~O
(28)
R2 R;Z Al HCONHZ R2 HCONH2
or
A1
~O O
- 31 -
~~409 49
(29)
R2 ~ ~ R2
R,2 A KSCN / ~ HN03
or 1 ~ HS
Al N
H
(30)
R2 R
R~, A1 guanidine
or g
2
_ A1 . N
' ~0 H
( i ) diazot~zatio;n/( ii ) reduction
(31)
R2
A4-H:
\0 NH3
(32)
R2 H2 A4-H R2
oxidation
H
NH2 N
H H
- 32 -
X3409 49
(33)
R2
Z'iCl3
1
N
OH
In the foregoing formulae, RZ has the same
meanings as described above; Al is a halogen atom, an
amino group, a hydroxyl group, or an alkanoyloxy group;
A2 is a -CONH2 group, a -C(NH)NH2.group, or a -C(NH)-A3
group, wherein A3 is an alkoxy group or an alkylthio
group: and AQ is a fo:rmyl group.
The carbonyl group included in the above described
formulae may bE~ in the latent form of, for example,
acetal, thioacetal, cyclic acetal, cyclic thioacetal, etc.
Further, the formyl group represented by A4 may be in the
latent form of, Eor example, acetal, hemiacetal, etc.
In each of the processes as described above, the
reaction conditions such as reaction temperature, reaction
time, solvent, acid acceptor, alkali acceptor, etc. can
appropriately be chosen from the conventionally known
reaction conditions.
- 33 -
X3409 49
Typical e~xampl~es of the intermediate' compounds
represented by the general formula (II), for the imidazole
compounds of the present invention represented by the
general formula (I) are shown in Table 1.
Table 1
RZ
Ri- ~ I (I=)
R3
H
Intermediate Melting
No. R~ R2 R3 Point
(oC)
2 CN 3-trifluoromethyl- g 160-168
phenyl .
3 " C1 CH3 194-196
4 " 4-me~thoxyphenyl C1 150-155
" phen,~rl CH3 222-225
6 " " Hr 120-125
7 " 4-fluorophenyl H 211-213
" 4-met:hylphenyl " 228-232
9 " " Hr 142-144
" 4-fluorophenyl " 176-178
11 " 3,4-dichlorophenyl H 115-121
12 " 4-met;hylphenyl Cl 124-129
14 " n-C3H~ Cl 107-109
" phenyl " 149-151
- 34 -
C
a
Table 1 (cont'd
Intermediate , Melting
No. R1 R2 R3 Point
- -
C~)
16 CN 3-methylphenyl C1 140-142
17 " 3,4-dimethylphenyl " 150-152
18 ~ " 4-fluorophenyl " 153-155
19 " 4-bromophenyl " 162-167
20 " 4-ethylphenyl " 141-145
21 " " . H 214-217
'22 " 3-methoxyphenyl " 218-220
23 " 4-nitrophenyl " 230-235
24 " 5-chloro-2-thienyl " 202-206
25 " SCH3 "
26 " phenylthio " 166-169
~
27 " phenyl CN 207-215
29 " 2-naphthyl C1 196-149
30 " " H 253-255
31 " 4-nitrophenyl C1 189-191
32 " 4-chlorophenyl 8 215-224
33 " 4-chlorophenyl C1 ~ 178-181
34 " 2-chlorophenyl " 145-152
35 " " Br 152-156
36 " 4-isopropylphenyl Ii 180-184
37 " 4-methylthiophenyl " 217-219
- 35 -
B
~~~o~ ~~
'fable 1 (cont'd
Intermediate ' M
g
No . R:1 R2 R3 point
-- (C)
3g CN 4-(2',2',2'-trifluoro- H 195-198
ethoxy)phenyl
39 ~~ CHa N02 125-130
40 " tert-C4H9 Br 120-127
41 " 2-methylphenyl H
4 2 ~ ~~ ~~ C1
43 " 5-methyl-2-furyl ' H 169-171
44 " 3,4-dimethoxyphenyl " 188-190
45 " 4-~ethoxyphenyl " 218-219
46 " 3-methyl-4-methoxy- " 199-205
phenyl
47 " 2-~thienyl " 195-203
4g " 4-(2',2',2'-trifluro- C1 164-166
et:hoxy ) phenyl
49 " " Br 150-155
50 " 3--methyl-4-methoxy- C1 145-149
phenyl
51 " 3--chloro-4-methyl- Br 190-194
phenyl
52 " CH3 CN 142-145
53 " C~,HS H 127-129
54 " " C1 138-140
55 ~~ n._C3g~ H 52-54
56 " ." I 106-109
57 " n._C4H9 H 83-85
- 36 -
X3409 49
Table 1 ( cont' d )
Intermediate , Melting
No. R1- R2 R3 Point
(oC)
58 CN n-C4H9 C1 107-109
59 " n-C5H11 H 89-92
60 " n-CSH11 C1 109-110
61 " iso-C3H~ H 88-91
62 " " C1 84-87
- 63 " iso-C4H9 . . H
~64 " " C1 142-145
65 " tert-C4H9 H 130-135
66 " " C1 120-124
67 " iso-C5H11 H 144-146
68 ~ " " C1 104-107
69 " cyclopropyl " 170-183
70 " cyclohexyl H 185-190
71 " " C1 130-133
72 " 3-chloropropyl " 117-120
7 3 " CH2(~CH3 "
74 " CH2l7C2H5
75 " ben:zyl " 144-146
76 " phenethyl " 147-152
77 " SCZH5 H 112-115
78 " " C1 128-131
79 " S-w-CQH9 H 97-99
80 " " C1 95-99
- 37 -
X3409 49
T<~ble 1 ( cont' d )
Intermediate , Melting
No. Rl_ R2 Rg Point
(°C)
81 CN 3-fluoropropyl Cl
82 " SOZN(CH3)2 H 175-180
83 " 3-chlorophenyl " 140-143
84 " " C1 124-128
85 " 2,3-dichlorophenyl H 202-206
-- 86 " " C1 198-204
87 " 3-chloro-4-methoxy- " 158-160
phenyl
88 " " Br 161-163
89 " 3-chloro-4-methyl- C1 165-169
phenyl
90 " 4-cyanophenyl H 240-244
91 " " C1 250-255
92 " " Br 239-244
93 " 4-ethoxyphenyl C1 151-153
94 " " Br 140-145
95 " 2-fluorophenyl H 190-195
96 " " C1 155-159
97 " 2-methoxyphenyl H 155-159
98 " " C1 223-230
99 " 3,4-methylenedioxy- H 228-231
. phenyl
100 " " C1 149-152
101 " " Br 166-169
- 38 -
~~~09 49
The following three compounds are reference
compounds and are specifically excluded from the present
invention.
Table 11
R2
R.1 ~ I III)
N ~R3
H
' Intermediate Melting
No. R1_ R2 R3 Point
C°C)
1 CN Br H 196-201
13 " C1 H 150-153
28 " H F
- 38a -
~~409 ~9
In the case that R2 and R3 are different from each
other, the intEarmediate compounds represented by the
general formula (II) described above include tautomers
represented by the general formulae (II-a) and (II-b)
described below:
H
R2 R2
R1 ~ I R1 ~ I
'R3 N 'R3
H
- . (II_a) ~ (II-b)
wherein Rl, R2, a.nd R3 have the same meanings as described
hereinabove. Ac<:ordingly, in the case that the imidazole
compounds of the present invention represented by the
general formula (I) are prepared using the compounds
represented by t:he gE~neral formula ( II ) as a starting
material, the imidazole compounds represented by the
general formulae (I-a) and/or (I-b) described below can be
obtained.
S02Rq
w R2 R2
Rl ~ ( and/or Rl ~ I
i'' ~R3 N ~R3
S02:R4
(I_a) (I_b)
- 39 -
~34a9 4~
1 wherein Rl, R2, R3, and R4 have the same meanings as
described hereinabove. In the case that R2 and R3 are
different from each other, the imidazole compounds
represented by the general formulae (I-a) and (I-b) are
tautomers each other. The same also applies to the
compounds represErnted ~by the general formulae (I-1), (I-
5), (I-6). and (I-7) in. the processes [B] to [D] described
hereinabove, etc.
The imidazole compounds represented by the general
. formula (I-a) or (I-b) described- hereinabove can be
separated concretely, for example, by methods [E-1] to [E
3] described below:
[E-1] Method by means of chromatography:
Each compound can be separated from a mixture of
isomers of the general formulae (I-a) and (I-b) described
above, by means of silica gel column chromatography,
preparative high performance liquid chromatography, flash
chromatography, etc. In the case of silica gel column
chromatography, for example, n-hexane, carbon
tetrachloride, methyle ne chloride, chloroform, ethyl
acetate, or a mixture thereof can be used as a developing
solvent.
[E-2] Method by means of recrystallization:
Each compound c:an be separated from a mixture of
isomers of the general formulae (I-a) and (I-b) described
above, using as a solvent fox recrystallization, for
- 40 -
~3~09 49
1 example, carbon tetrac:hloride, methylene chloride, chloro-
form, 1,2-dichloroeth.ane, ethyl ,acetate, diethyl ether,
tetrahydrofuran, acetone, or a mixture thereof.
[E-3] Method by means of decomposition:
Either compound can be separated from a mixture of
isomers of the c~enera:~l formulae (I-a) and (I-b) described
above, by the selective hydrolysis under conditions of
from 0 to 80°C (preferably from room temperature to 50°C)
for from 1 to 48 hours (preferably from 5 to 24 hours).
_ As the m.ixture~ of isomers used . in the methods [E-
1] to [E-3] described above, it is preferred to use the
mixture having a mixing ratio of both isomers as large as
possible by appropriately choosing reaction conditions
previously in ithe process [A] described above, for
example, kind o1. solvent and acid acceptor and amounts
thereof to be u:>ed, reaction temperature, reaction time,
etc.
Further, in the case of preparing imidazole
compounds wherein R1 is a -CSNHZ group or a -CSNHRS group,
wherein R5 has the sarne meaning as described hereinabove
from compounds wherein R, is a cyano group in the
compounds represented by the general formula (I-b)
separated by the method [E-1], [E-2], or [E-3] described
above, such compounds c:an be obtained, for example, by the
following method:
- 41 -
'134 09 49
[F]
SO,~R4 - S02R4
R2 g g S I R2
1 NC \ H2NC
N ~ R3 dioxane N R3
triethylamine
S02R4
R
R6COC1 O S 2
_. R6CHNC
acei;.one
- pyr:idine N Rg
wherein R2, R3, R4, and R6, have the same meanings as
described hereinabove.
Specific examples of synthesizing the imidazole
compounds of the present invention are described below.
Synthesis Example 1
Synthesis of 2-cya,no-1-dimethylsulfamoylimidazole
(Compound No,. 1)
Thirty grams of 2-cyanoimidazole, 53.4 g of an-
hydrous potassium carbonate and 600 ml of acetonitrile
were mixed at room temperature. After reacting for 2
hours at the ref:luxincf temperature, the reaction mixture
was cooled, and 55.6 g of dimethylsulfamoyl chloride was
added thereto. The mixture was reacted again at the
refluxing tempera~.ture f:or 2 hours.
- 42 -
After completion of the reaction, the reaction
mixture was poured into water. Extraction with methylene
chloride was carried out. After 'washing with water, the
extract was driE~d ovE~r anhydrous sodium sulfate. The
solvent was removed by distillation. The obtained residue
was purified by ~;ilica gel column chromatography (develop-
ing solvent: mE~thylene chloride) to give 28.0 g of 2-
cyano-1-dimethylsulfamoylimidazole (Compound No. 1) having
a melting point of from 74 to 76°C.
-- Synthesis Example 2
'Synthesis of 2-cyano-1-dimethylsulfamoyl-5-
phenylthioimidazoler (Compound No. 10-b)
In a four-necked flask were charged 12.0 g of 2
cyano-1-dimethylsulfamoylimidazole (Compound No. 1) and
240 ml of dry tetrahydrofuran in a nitrogen flow. While
maintaining the mixture at -75°C or below with dry ice-
acetone, 41.3 m:L of a 1.6 M n-butyl lithium hexane
solution (manufac:tured by Aldrich) was gradually added
dropwise to the mixture. After completion of the dropwise
addition, the system was kept at the same temperature for
15 minutes. Then, a solution of 17 g of diphenyl
disulfide in 30 ml of tetrahydrofuran was added dropwise
to the mixture at ~-70°C or below. While stirring
overnight, the temperature was gradually reverted to room
temperature.
After completion of the reaction, the reaction
mixture was poured into water. Extraction with 500 ml of
ethyl acetate was carried out. After washing with water,
- 43 -
'~~409 4~
1 the extract was dried over anhydrous sodium sulfate. The
ethyl acetate wars removed by distillation, and the residue
was purified by silica gel column chromatography (develop-
ing solvent: methylE~ne chloride) to give 4.3 g of 2-
cyano-1-dimethyl:~ulfamoyl-5-phenylthioimidazole (Compound
No. 10-b) having a melting point of from 106 to 107°C.
ythesis Example 3
Synthesis of 4-chloro-2-cyano-1-dimethyl-
sulfamoyl-5-n-prop:ylimidazole (Compound No. 16-b)
-. [1] 4.8 g of 2-cyano-1-dimethylsulfamoyl-5-n-
propylimidazole having a melting point of from 51 to 52°C
(Compound No. 3-b) was synthesized by the reaction of 12.0
g of 2-cyano-1-d:imethylsulfamoylimidazole (Compound No. 1)
and 15.3 g of n-propyl iodide in a manner similar to
Synthesis Example 2 described above.
[2] 4.8 g of 2-cyano-1-dimethylsulfamoyl-5-n-
propylimidazo~e as obtained in [1] above, 40 ml of
pyridine, and 11..4 g of pyridinium chloride were mixed,
and the mixture was stirred at 90°C for 4 hours. After
completion of th,e reaction, the pyridine was removed by
distillation from the reaction mixture, and the residue
was extracted wiith ethyl acetate. The extract was washed
with water and then dried over anhydrous sodium sulfate.
Thereafter, the f:thyl acetate was removed by distillation,
and the residue was purified by silica gel column
chromatography (developing solvent: a mixture of ethyl
acetate and n-he:Kane) and separated to give 2.46 g of 2-
- 44 -
~3~09v9
1 cyano-4(5)-n-propylimidazole (Intermediate No. 55) having
a melting point of from 52 to 54°C,.
[3] 2.3:5 g of 2-cyano-4(5)-n-propylimidazole as
obtained in [2] above, 80 ml of chloroform, and 2.6 g of
N-chlorosuccinimide were mixed, and the mixture was
reacted at the refluxing temperature for 4 hours. After
completion of the reaction, 200 ml of water was added to
the reaction mixture. The resulting organic layer was
washed with watE~r and then dried over anhydrous sodium
_ sulfate. After drying, the chloroform was removed by
distillation, and the residue was purified by silica gel
column chromatography (developing solvent: a 1:1 mixture
of ethyl acetate and n-hexane) and separated to give 2.2 g
of 4(5)-chloro-~2-cyano-5(4)-n-propylimidazole (Inter-
mediate No. 14) having a melting point of from 107 to
109°C
[4] 2.0 g of 4(5)-chloro-2-cyano-5(4)-n-propyl-
imidazole as obtained :in [3] above, 30 ml of acetonitrile,
1.95 g of anhydrous potassium carbonate, and 1.86 g of
dimethylsulfamoyl. chloride were mixed, and after gradually
elevating the temperature, the mixture was reacted at the
refluxing temperature for 1 hours. After completion of
the reaction, the acetonitrile was removed by distillation
from the reaction mixture. After pouring 100 ml of water
into the residue, the :resulting mixture was extracted with
50 ml of methylene chloride. The extract was washed with
- 45 -
X3409 49
1 water and dried over anhydrous sodium sulfate. There-
after, the methylene chloride was removed by distillation.
The residue was allowed to stand overnight, and the
analysis thereof revea:Led that one of the two isomers in
the mixture decomposed and returned to the starting 4(5)-
chloro-2-cyano-5(4)-n--propylimidazole. The residue
containing the other isomer was purified by silica gel
column chromatography (developing solvent: methylene
chloride) and sep~aratecl to give 1.1 g of 4-chloro-2-cyano-
_ 1-dimethylsulfamoyl-5-n-propylimidazble (Compound No. 16-
b) having a melting point of from 64 to 66°C.
Synthesis Example 4
Synthesis oi= 2-c,yano-1-dimethylsulfamoyl-4(5)-
phenylimidazo~le (Cc>mpound No. 4)
I11 In 320 ml of acetone was dissolved 23.04 g of
4(5)-phenylimidazole, and 12.14 g of anhydrous potassium
carbonate was added to the solution. The mixture was
heated at the re~fluxirig temperature for 2 hours. After
cooling, 45 ml of an acetone solution containing 25.25 g
of dimethylsulfarnoyl chloride was added dropwise to the
mixture. After completion of the dropwise addition, the
mixture was heated at the refluxing temperature for 4.5
hours to complete the reaction.
After completion of the reaction, the reaction
mixture was cooled, and solid substances were removed by
filtration. After the solvent was removed by distillation
under reduced pressure, the residue was purified b~~ s~lica
- 46 -
X34 Q9 49
1 gel column chromatography (developing solvent: methylene
chloride) to gave 1'7.8 g of 1-dimethylsulfamoyl-4(5)-
phenylimidazole having a melting point of from 96 to
100°C.
[2] In 290 ml. of tetrahydrofuran was dissolved 17
g of 1-dimethylsulfamoyl-4(5)-phenylimidazole as obtained
in [1] above. The solution was cooled to -70°C in a
nitrogen flow, and 51 ml of a 1.6 M n-butyl lithium hexane
solution was added dropwise to the mixture over 30
_ minutes. After completion of the dropwise addition, the
reaction mixturE~ was stirred at -70°C for 30 minutes.
Then, 12 ml of .a tetrahydrofuran solution containing 6 g
of N,N-dimethylformamide was added dropwise to the
mixture. After completion of the dropwise addition, the
reaction mixture was reacted for 15 hours with stirring
while slowly elevating the temperature to room
temperature.
After completion of the reaction, the reaction
mixture was poured into ice water and extracted with ethyl
acetate. After washing the extracted layer with water,
the extracted :Layer was dried over anhydrous sodium
sulfate. The aolvent was distilled off under reduced
pressure, and t:he residue was purified by silica gel
column chromatography (developing solvent: a 1:2 mixture
of ethyl acetate anf, n-hexane) to give 12.8 g of 1-
- 47 -
1~4~09 49
1 dimethylsulfamoyl-2-formyl-4(5)-phenylimidazole having a
melting point of from 86 to 89°C.:
[3] In 120 ml of pyridine were dissolved 11.16 g
of 1-dimethylsulfamoyl-2-formyl-4(5)-phenylimidazole as
obtained in [2] above and 5.56 g of hydroxylamine
hydrochloride, and 24 ml of acetic anhydride was added
dropwise to the solution at room temperature. After
completion of t:he dropwise addition, the temperature was
gradually raised, and the mixture was reacted at 100°C for
. 12 hours.
After completion of the reaction, the solvent in
the reaction mixture was removed by distillation under
reduced pressure. Then, 125 ml of water was added to the
residue, and the precipitated solid was separated by
filtration. The crude product was dissolved in ethyl
acetate and purified by silica gel column chromatography
(developing sol~~ent: ethyl acetate) to give 5.55 g of 2-
cyano-4(5)-phenylimidazole having a melting point of from
203 to 205°C.
[4] In 88 ml of acetone was dissolved 1.7 g of 2-
cyano-4(5)-phenylimidazole as obtained in [3] above, and
1.7 g of anhydrous potassium carbonate was added to the
solution. The mixture was heated at the refluxing
temperature for 2 hours.
After cooling, 6 ml of an acetone solution
containing 1.7 c3 of dimethylsulfamoyl chloride was added
- 48 -
'~ 3 4~ ~ 9 ~ ~
1 dropwise to the mixture. After completion of the dropwise
addition, the mixture was heated at the refluxing
temperature for 2 hours to complete the reaction.
After c:omplet:ion of the reaction, the reaction
mixture was cooled, and solid substances were removed by
filtration. After the solvent was removed by distillation
under reduced pressure, the residue was extracted with
ethyl acetate. The extract was washed with water and
dried over anhydrous sodium sulfate. The solvent was
_ removed by distillation under reduced pressure to give 2 g
of 2-cyano-1-dimethylsulfamoyl-4(5)-phenylimidazole
(Compound No. ~E) having a melting point of from 101 to
102°C.
S'tnthesis Example 5
Synthesis of 4(5)-ch7.oro-2-cyano-1-dimethylsulfamoyl-5(4)-
phenylimidazole (Compound No. 17) and 4-chloro-2-cyano-1-
dimethylsulfamo:yl-5-phenylimidazole (Compound No. 17-b)
[1] In 100 ml of chloroform was dissolved 1.352 g
of 2-cyano-4(5)-phenylimidazole, and 1.175 g of N-chloro
succinimide was added to the solution. The mixture was
reacted upon heating at the refluxing temperature for 4
hours.
After completion of the reaction, the reaction
mixture was poured into water and extracted with chloro-
form. After washing with water, the extracted layer was
dried over anhydrous sodium sulfate. The solvent was
distilled off under reduced pressure, and the residue was
- ~9 -
'3409 49
1 purified by silica gel column chromatography (developing
solvent: methylene chloride) to_. give 1.28 g of 4(5)-
chloro-2-cyano-5(4)-phenylimidazole (Intermediate No. 15)
having a melting point: of from 149 to 151°C.
[2] In 6 ml of acetone was dissolved 0.43 g of
4(5)-chloro-2-cyano-5I;4)-phenylimidazole as obtained in
[1] above, and 0.29 g of anhydrous potassium carbonate and
0.36 g of dimethylsulfamoyl chloride were added to the
solution. ' The mixture was reacted upon heating at the
. refluxing temperature for 30 minutes.
After c:omple~:.ion of the reaction, the reaction
mixture was poured into water and extracted with ethyl
acetate. After washing with water, the extracted layer
was dried over anhydrous sodium sulfate. The solvent was
distilled off under reduced pressure, and the residue was
then purified by silica gel column chromatography
( developing solvent : methylene chloride ) to give 0 . 5 g of
4(5)-chloro-2-cyano-1-dimethylsulfamoyl-5(4)
phenylimidazole (Compound No. 17) having a melting point
of from 106 to :109°C.
As a result of analysis by means of NMR spectra,
the compound dE~scribE~d above was an isomer mixture of 4-
chloro-2-cyano-1-dimE:thylsulfamoyl-5-phenylimidazole and
5-chloro-2-cyan~o-1-dimethylsulfamoyl-4-phenylimidazole in
almost equal ratios.
- 50 -
'3409 49
1 ~ [3] After allowing to stand for 24 hours at room
temperature, 2.9~ g of the mixture of these isomers as
obtained in a manner :similar to [ 2 ] above was purified by
silica gel column chromatography (developing solvent:
methylene chloride) to give 1.15 g of 4-chloro-2-cyano-1
dimethylsulfamoy:l-5-ph~enylimidazole (Compound No. 17-b)
having a melting point of from 109 to 112°C. Further, by
purification of ;end isolation from this compound, 0.7 g of
4(5)-chloro-2-cyano-5(4)-phenylimidazole (Intermediate No.
. 15) was also obtained.
~zthesis Example 6
Synthesis of 4(5)-c:hloro-2-cyano-1-dimethylsulfamoyl-
5(4)-(4-methylphenyl)imidazole (Compound No. 18) and 4-
chloro-2-cyano--1-dimethylsulfamoyl-5-(4-methylphenyl)-
imidazole (Compound No. 18-b)
An isomer mixture (Compound No. 18), having a
melting point of from 101 to 108°C, of 4-chloro-2-cyano-1-
dimethylsulfamoyl-5-(4-methylphenyl)imidazole and 5-
chloro-2-cyano-1~-dimet~hylsulfamoyl-4-(4-methylphenyl)imid-
azole was obtair~ed~from 4(5)-(4-methylphenyl)imidazole in
a ratio of 6:4 i:n a manner similar to Synthesis Examples 4
and 5 described above. After 0.75 g of the isomer mixture
was reacted at 40°C for 8 hours, the reaction mixture was
purified by silica gel column chromatography (developing
solvent: methylene chloride) to give 0.45 g of 4-chloro-2-
cyano-1-dimethylsulf,amoyl-5~(4-methylphenyl)imidazole
(Compound No. 18-b) having a melting point of from 133 to
134°C. Further, by purification of and isolation from
- 51 -
X3409 49
1 this compound, 0.15 g of 4(5)-chloro-2-cyano-5(4)-(4-
methylphenyl)imidazole (Intermediate No. 12) having a
melting point of from 124 to 129°C was also obtained.
~zthesis Example 7
Synthesis of 4(5)-chloro-5(4)-(4-chlorophenyl)-2-
cyano-1-dimethylsulfamoylimidazole (Compound No. 23),
4-chloro-5-(~4-chlorophenyl)-2-cyano-1-dimethyl-
sulfamoylimidazole (Compound No. 23-b) and 5-chloro-
4-(4-chlorophE~nyl)-2-cyano-1-dimethylsulfamoylimid-
azole (Compound No. 23-a)
In a manner similar to Synthesis Examples 4 and 5
described above, 0.80 g of an isomer mixture (Compound No.
23)~, having a melting point of 108°C, of 4-chloro-5-(4-
chlorophenyl)-2-c:yano-:1-dimethylsulfamoylimidazole and 5-
chloro-4-(4-chlorophen.yl)-2-cyano-1-dimethylsulfamoylimid-
azole was obtained from 4(5)-(4-chlorophenyl)imidazole.
The isomer mixture was purified by silica gel column
chromatography (developing solvent: methylene chloride).
The eluate of the second fraction was concentrated and
recrystallized from me~thylene chloride to give 0.16 g of
4-chloro-5-(4--chlorophenyl)-2-cyano-1-dimethyl-
sulfamoylimidazol.e (Compound No. 23-b) having a melting
point of from 11.7 to 120°C. Further, the eluate of the
first fraction was likewise concentrated and recrystalliz-
ed from methylene chloride to give 0.50 g of 5-chloro-4-
(4-chlorophenyl)-2-cyano-1-dimethylsulfamoylimidazole
(Compound No. 23--a) having a melting point of from 133 to
138°C.
w
- 52 -
1~3~09 49
1 ~nthesis Example 8
Synthesis of 1-~dimethylsulfamoyl-4(5)-phenyl-
imidazole-2-carbothioamide (Compound No. 49)
In 30 ml of dioxane was dissolved 1.0 g of 2
cyano-1-dimethylsulfamoyl-4(5)-phenylimidazole (Compound
No. 4), and 0.:36 g of triethylamine was added to the
solution. The mixture was heated to 40 to 50°C while
stirring, and .a hydrogen sulfide gas was introduced
thereinto for one hour and 25 minutes. Thereafter, the
m-fixture was reacted at 40 to 50°C for an additional 50
minutes.
After completion of the reaction, the reaction
mixture was cooled, poured into water, and extracted with
ethyl acetate. After washing with water, the extracted
layer was dried over anhydrous sodium sulfate. The
solvent was distilled off under reduced pressure, and the
residue was purified by silica gel column chromatography
(developing solvent: a. 1:3 mixture of ethyl acetate and n-
hexane) to give 0.8 g of 1-dimethylsulfamoyl-4(5)-phenyl-
imidazole-2-carbothioamide (Compound No. 49) having a
melting point o:E from 155 to 175°C. Crystals of 4(5)-
phenylimidazole-2-carbothioamide were also obtained in a
small quantity.
~nthesis Example 9
Synthesis of 2-cyano-1-isopropylsulfonyl-4(5)-
phenylimidazole (C:ompound No. 101)
- 53 -
~3~09 49~
1 One gram of 2-cyano-4(5)-phenylimidazole, 0.98 g
of anhydrous potassium carbonate, and 30 ml of aceto-
nitrile were mi:Ked at: room temperature. After reacting
for 2 hours at the refluxing temperature, the reaction
mixture was cooled, and a solution of 1.0 g of
isopropylsulfonyl chloride in 5 ml of acetonitrile was
added thereto. The mixture was reacted again at the
refluxing temperature for 1.5 hours.
After completion of the reaction, the reaction
. mixture was poured invto water. Extraction with methylene
chloride was carried out. After washing with water, the
extract was dried over anhydrous sodium sulfate. The
solvent was removed by distillation under reduced
pressure, and t:he rE~sidue was purified by silica gel
column chromatography (developing solvent: methylene
chloride) to give 1.4 g of 2-cyano-1-isopropylsulfonyl-
4(5)-phenylimidazole (Compound No. 101) having a melting
point of from 80 to 83°C.
S~~thesis Example 10
Synthesis of 9E(5)-(2-thienyl)-2-cyano-1-di-
methylsult:amoyl:imidazole (Compound No. 6)
[ 1 ] To 150 ml of formamide was added 25 g of 2-
(bromoacetyl)thiophene. The mixture was reacted at 180 to
190°C for 2 hours.
After completion of the reaction, the reaction
mixture was poured into water, and concentrated
hydrochloric acid was added thereto to render the system
- 54 -
1 3 ~4 ~9 49
acidic. Then, washing with methylene chloride was carried
out. After neut:raliz:ing with ammonia water, the aqueous
phase was extracted with methylene chloride. After
washing with water, the extract was dried over anhydrous
sodium sulfate. The solvent was removed by distillation
under reduced pressures to give 11 g of 4(5)-(2-thienyl)-
imidazole.
[2] To 200 ml. of acetonitrile were added 11.6 g
of dimethylsulf.amoyl chloride, 11.1 g of anhydrous
_ potassium carbonate, and 11 g of 4(5)-(2-thienyl)imidazole
as obtained in [1] above. The mixture was reacted for 2
hours while stirring.
After completion of the reaction, the reaction
mixture was poured into water. Extraction with ethyl
acetate was carried Out. After washing with water, the
extract was driE~d ovE:r anhydrous sodium sulfate. The
solvent was removed by distillation under reduced pressure
to give 14.5 g of 4(5)-(2-thienyl)-1-dimethylsulfamoyl-
imidazole.
[3] In 120 m:L of anhydrous tetrahydrofuran was
dissolved 9.5 g of 4(5)-(2-thienyl)-1-dimethylsulfamoyl-
imidazole as obtained in [2] above. In a nitrogen flow,
26.2 ml of a 1.6 M n-butyl lithium hexane solution was
added dropwise to the solution at -78°C, and the mixture
was stirred at the same' temperature for 15 minutes. Then,
20 ml of a tetrahydrofuran solution having dissolved
- 55 -
~3~09 49
therein 5.4 g of N,N-dimethylformamide was added dropwise
to the mixture. After completion of the dropwise
addition, the te~mperat:ure was gradually reverted to room
temperature to complete the reaction.
After completion of the reaction, the reaction
mixture was poured into water. Extraction with ethyl
acetate was carried out. After washing with water, the
extract was dried over anhydrous sodium sulfate. The
solvent was removed by distillation under reduced pressure
_ to give 5.4 g of 4(5)-(2-thienyl)-2-formyl-1-dimethyl-
sulfamoylimidazole.
[ 4 ] In '54 ml of pyridine were dissolved 2. 6 g of
hydroxylamine hydrochloride and 5.4 g of 4(5)-(2-thienyl)-
2-formyl-1-dimethylsulfamoylimiazole as obtained in [3]
above. The solution was stirred at room temperature for
15 minutes. Then, 10 ml of acetic anhydride was gradually
added to the solution, followed by reacting at 60 to 70°C
for 2 hours.
After completion of the reaction, the reaction
mixture was poured into water. Extraction with ethyl
acetate was carried out. After washing with water, the
extract was dried ovE~r anhydrous sodium sulfate. The
solvent was removed by distillation under reduced
pressure, and the residue was purified by silica gel
column chromatography (developing solvent: a 2:1 mixture
of ethyl acetate and n-hexane) to give 1.2 g of 4(5)-(2-
- 56 -
1409 49
1 thienyl)-2-cyanoimiazole (Intermediate No. 47) having a
melting point of from 195 to 203°C.
[5j To 50 ml of acetonitrile were added 1.1 g of
dimethylsulfamoyl chloride, 1.0 g of anhydrous potassium
carbonate, and ?L.2 g of 4(5)-(2-thienyl)-2-cyanoimidazole
as obtained in [4] above. The mixture was reacted at the
refluxing temperature for 2 hours.
After completion of the reaction, the reaction
mixture was poured into water and extracted with ethyl
. acetate. After drying the extract' over anhydrous sodium
sulfate, the solvent was distilled off under reduced
pressure, and t:he residue was purified by silica gel
column chromatography (developing solvent: methylene
chloride) to give 1.3 g of 4(5)-(2-thienyl)-2-cyano-1-
dimethylsulfamoylimidazole (Compound No. 6) having a
melting point of from 145 to 15d°C
ythesis Example 11
Synthesis of 4(5)-chloro-2-cyano-1-dimethyl-
sulfamoyl-5(4)-iso~propylimidazole (Compound No.
125) and 4--chloro-2-cyano-1-dimethylsulfamoyl-5
isopropylimidazole (Compound No. 125-b)
[lj 360 g of formamide was heated to 180°C, and
102 g of 1-hydroxy-3-methyl-2-butanone (prepared in a
manner as described in Lipshutz and Morey, J. Orq. Chem.,
48, 3745 (1983)) ways added dropwise thereto over 30
minutes. After completion of the dropwise addition, the
mixture was reacted at 180°C for one hour.
- 57 -
~~4 09 49
1 After completion of the reaction, the reaction
mixture was cooled ;end poured =into ice water. The
resulting mixture ways adjusted at a pH of 1 with
hydrochloric acid and washed with methylene chloride. The
aqueous layer was adjusted at a pH of 4 to 5 with
ammonia water. 5 g of activated charcoal was added
thereto, and the mixture was stirred for one hour. The
activated charcoal wa.s removed by filtration, and the
filtrate was adjusted at a pH of 8 with ammonia water.
. Then, extraction with methylene chloride was carried out,
and the extract was dried over anhydrous sodium sulfate.
The solvent was distilled off under reduced pressure to
give 13 g of 4(5)-isopropylimidazole.
[ 2 J In :300 ml of acetonitrile was dissolved 11. 8
g of 4(5)-isopropylimiiiazole as obtained in [1) above, and
18 g of anhydrous potassium carbonate was added to the
solution. The rnixture~ was refluxed for 30 minutes, and
after cooling, :L7 g of dimethylsulfamoyl chloride was
added dropwise thereto. After completion of the dropwise
addition, the mixture was refluxed to complete the
reaction.
After completion of the reaction, the reaction
mixture was cooled, poured into water, and then extracted
with ethyl acetat:e. T'he extracted layer was washed with
water and dried over anhydrous sodium sulfate. The
solvent was distilled off under reduced pressure, and the
- 58 -
~3~~9 ~~
1 residue was purified by silica gel column chromatography
(developing solvent: methylene chloride) to give 13 g of
1-dimethylsulfamoyl-4(5)-isopropylimidazole.
[3] In 200 ml. of tetrahydrofuran was dissolved 13
g of 1-dimeth;ylsulf'amoyl-4(5)-isopropylimidazole as
obtained in [2] above. The solution was cooled to -70°C
in a nitrogen flow, and 38 ml of a 1.6 M n-butyl lithium
hexane solution was added dropwise thereto over 15
minutes. After completion of the dropwise addition, the
. mixture was stirred at -70°C for 30 minutes. After
dropwise addition of 5.6 g of N,N-dimethylformamide, the
mixture was reacted with stirring for 15 hours while
slowly elevating the temperature to room temperature.
After completion of the reaction, the reaction
mixture was poured into ice water and extracted with ethyl
acetate. The extracted layer was washed with water and
dried over anhydrous sodium sulfate. The solvent was
distilled off uncter reduced pressure to obtain 8.6 g of 1
dimethylsulfamoyl.-2-formyl-4(5)-isopropylimidazole.
[4] In 7L00 ml of pyridine were dissolved 8.5 g of
1-dimethylsulfamoyl-2-formyl-4(5)-isopropylimidazole as
obtained in [3] above and 4.8 g of hydroxylamine
hydrochloride, and 10 ml of acetic anhydride was added
dropwise to the solution at room temperature. After
completion of the dropwise addition, the temperature was
- 59 -
~~~409 49
1 gradually elevated, and the mixture was reacted at 80 to
90°C for 5 hours.
After cc>mplet~~.on of the reaction, the solvent in
the reaction mixture was distilled off under reduced
pressure. To the residue was added water, and the mixture
was extracted with ethyl acetate. The extracted layer was
washed with dilute hydrochloric acid and then with water
and dried over anhydrous sodium sulfate. The solvent was
distilled off under reduced pressure to give 2.35 g of 2-
, cyano-4(5)-isopropylim:idazole (Intermediate No. 61) having
a melting point of from 88 to 91°C.
[ 5 ) In .BO ml of methanol was dissolved 2 g of 2-
cyano-4(5)-isopropylimidazole as obtained in [4] above,
and 2.1 g of N-chlorosuccinimide was added to the
solution. The m~.xture was stirred at room temperature for
hours and then reacted at 40°C for 8 hours.
After completion of the reaction, the methanol in
the reaction mixture was distilled off under reduced
pressure. To the residue was added water, and the mixture
20 was extracted with ethyl acetate. The extracted layer was
washed with water and dried over anhydrous sodium sulfate.
The solvent was distilled off under reduced pressure, and
the residue w,as purified by silica gel column
chromatography (developing solvent: methylene chloride) to
give 1.67 g of 4(5)-ch:loro-2-cyano-5(4)-isopropylimidazole
- 60 -
~~~09 ~9
1 (Intermediate No. 62) having a melting point of from 84 to
87°C.
[ 6 ] In 30 ml of acetonitrile was dissolved 1.6 g
of 4(5)-chloro-2-cyano-5(4)-isopropylimidazole as obtained
in [5] above, and l.SEi g of anhydrous potassium carbonate
was added to the solution. The mixture was refluxed for
30 minutes. After cooling, 1.49 g of dimethylsulfamoyl
chloride was added dropwise thereto. After completion of
the dropwise addition, the mixture was refluxed for 15
_ minutes to complete the reaction.
After completion of the reaction, the reaction
mixture was cooled, poured into water, and then extracted
with ethyl acetate. The extracted layer was washed with
water and dried over anhydrous sodium sulfate. The
solvent was distilled off under reduced pressure, and the
residue was purified by silica gel column chromatography
(developing solvent: methylene chloride) to give 2.1 g of
4(5)-chloro-2-cyano-1--dimethylsulfamoyl-5(4)-isopropyl-
imidazole (Compound No. 125).
As a result of analysis by means of NMR spectra,
the compound described above 'was an isomer mixture of 4-
chloro-2-cyano-1-dimet:hylsulfamoyl-5-isopropylimidazole
and 5-chloro-2-c.yano-1-dimethylsulfamoyl-4-isopropylimid-
azole in a proportion of about 2:1.
[7] After allowing to stand for 5 days at room
temperature, 2.1 g of the isomer mixture as obtained in
- 61 -
'l 3 ~ 09 49
1 [6] above was purified by silica gel column chromatography
(developing solvent: methylene chloride) to give 1 g of 4-
chloro-2-cyano-:L-dimethylsulfamoyl-5-isopropylimidazole
(Compound-No. 125-b) having a melting point of from 75 to
82°C (decomposed). Further, by purification of and
isolation from this compound, 4(5)-chloro-2-cyano-5(4)-
isopropylimidazole (Intermediate No. 62) was also
obtained.
Synithesis Example 12
. Synthesis of ~E-chloro-1-dimethylsulfamoyl-5-n-propyl-
imidazole-2-ca:rbothi~oamide (Compound No. 185-b)
[lJ In a four-necked flask were charged 6.0 g of
2-cyano-4,5-dichloro-1-~dimethylsulfamoylimidazole having a
melting point of from 100 to 103°C and 180 ml of dry
tetrahydrofuran in a nitrogen flow. While maintaining the
mixture at -75°C or below with dry ice-acetone, 15.3 ml of
a 1.6 M n-butyl lithium hexane solution (manufactured by
Aldrich) was gradually added dropwise to the mixture.
After completion of thEa dropwise addition, the system was
kept at the same' temperature for 15 minutes. Then, a
solution of 5.7 g of n-propyl iodide in 15 ml of
tetrahydrofuran w.as added dropwise to the mixture at -70°C
or below. While stirring overnight, the temperature was
gradually reverted to room temperature.
After completion of the reaction, the reaction
mixture was poured into water. Extraction with 500 ml of
methylene chloride was carried out. After washing with
- 62 -
°
~3~09 49
1 water, the extract was dried over anhydrous sodium
sulfate. The methylene chloride was removed by
distillation, and the residue was purified by silica gel
column chromatc>graph:y (developing solvent: methylene
chloride) and then again purified by silica gel column
chromatography (developing solvent: a mixture of ethyl
acetate and n-hexane) to give 2.8 g of 4-chloro-2-cyano-1-
dimethylsulfamoy:l-5-n-propylimidazole (Compound No. 16-b)
having a melting point of from 66 to 68°C.
. [ 2 ] In a four-necked flask were charged 2 . 7 g of
4-chloro-2-cyano-1-dimethylsulfamoyl-5-n-propylimidazole
as obtained in [1] above, 40 ml of dioxane, 1.0 g of
triethylamine, and 0.8 g of pyridine. Into this mixture
was introduced a hydrogen sulfide gas at 20 to 25°C for
about 30 minutes until the starting materials had
disappeared.
After completion of the reaction, the reaction
mixture was poured into water, and precipitated crystals
were filtered by means of a Nutsche and dried. The
resulting crystals wE~re purified by silica gel column
chromatography (;developing solvent: methylene chloride)
and separated to give 2.3 g of 4-chloro-1-di
methylsulfamoyl.-5-n-propylimidazole-2-carbothioamide
(Compound No. 18!5-b) having a melting point of from 160 to
162°C.
- 63 -
X3409 4~
1 Synthesis Example 13
Synthesis of N-~propionyl-4-chloro-1-dimethylsulfamoyl-5-
n-propylimidazole-2-carbothioamide (Compound No. 187-b)
Into a four-necked flask were charged 2.0 g of 4-
_5 chloro-1-dimethylsu,lfamoyl-5-n-propylimidazole-2-
carbothioamide (C:ompound No. 185-b), 24 ml of acetone, and
1.12 g of pyridine. 1.19 g of propionyl chloride was
added dropwise to the mixture at 0 to 5°C. After
completion of t:he dropwise addition, the reaction was
carried out at 30 to 35°C for one hour and at the
refluxing temperature for an additional 30 minutes with
stirring.
After completion of the reaction, the reaction
mixture was poured into water and extracted with ethyl
acetate. The ex:tractE~d layer was washed with water and
dried over anhydrous sodium sulfate. Thereafter, the
ethyl acetate was removed by distillation, and the residue
was purified by silica gel column chromatography
(developing solvent: methylene chloride) and separated to
give 1.02 g of N--propionyl-4-chloro-1-dimethylsulfamoyl-5-
n-propylimidazole-2-carbothioamide (Compound. No. 187-b)
having a melting point of from 150 to 152°C.
Synt=hesis Example 14
Synthesis of 2-cyano-1-dimethylsulfamoyl-4,5-diphenyl-
thioimidazole (Compound No. 141)
[1] 8.0 g of 2-cyano-1-dimethylsulfamoyl-5-
phenylthioimidazole (Compound No. 10-b) as obtained in a
- 64 -
~~09 49
1 similar manner to Synthesis Example 2 described above, 60
ml of methanol, and 60 ml of ,a 7% hydrochloric acid
aqueous solution were charged, and the mixture was reacted
with stirring at 40 to 50°C for 2 hours. After completion
of the reaction, the reaction mixture was rendered weakly
alkaline with ammonia, and precipitated crystals were
separated by filtration and dried to give 4.2 g of 2-
cyano-4(5)-phenylthioimidazole (Intermediate No. 26)
having a melting point of from 166 to 169°C.
l0 - [2] To a mixture of 4.2 g of 2-cyano-4(5)-
phenylthioimidazole as, obtained in [1) above, 80 ml of
acetonitrile, and 3.1 g of anhydrous potassium carbonate,
was added 3.4 g of dimethylsulfamoyl chloride. The
resulting mixture' was reacted at the refluxing temperature
for one hour. After completion of the reaction, the
reaction mixture was cooled, and solid substances were
filtered. The solvent in the filtrate was removed by
distillation, and the residue was purified by silica gel
column chromatography (developing solvent: methylene
chloride) and separated to give 5.8 g of 2-cyano-1-
dimethylsulfamoyl.-4(5)--phenylthioimidazole (Compound No.
10).
[3] In a four-necked flask were charged 5.8 g of
2-cyano-1-dimeth;ylsulfamoyl-4(5)-phenylthioimidazole as
obtained in [2] above and 150 ml of dry tetrahydrofuran in
a nitrogen atmo:;phere,, and 12.9 ml of a 1.6 M n-butyl
- 65 -
1 lithium hexane solution (manufactured by Kanto Kagaku) was
added dropwise to the mixture; while maintaining the
temperature at -75°C or below with dry ice-acetone. After
completion of the dropwise addition, the mixture was kept
at the same temperature for 15 minutes, and 20 ml of a
solution of 5.2 ~g of diphenyl disulfide in tetrahydrofuran
was added dropwise thereto at -70°C or below. Thereafter,
the mixture was returned to room temperature. After
completion of t:he rE~action, the reaction mixture was
_ extracted with ei:hyl acetate. The extract was washed with
water and dried over anhydrous sodium sulfate. The
solvent was removed by distillation, and the residue was
purified by silica ge:l column chromatography (developing
solvent: methylene chloride) and separated to give 1.7 g
of 2-cyano-1-dirnethyl;sulfamoyl-4,5-diphenylthioimidazole
(Compound No. 141) having a melting point of from 98 to
101°C.
Synthesis Example 15
Synthesis of 9:-bromo-2-cyano-1-dimethylsulfamoyl-5-n-
propylimidazole (Compound No. 157-b)
[1] 2 - C y a n o - 4 , 5 - d i b r o m o - 1 -
dimethylsulfamoylimidazole having a melting point of from
118 to 120°C wa.s synthesized from 2-cyano-4,5-dibromo-
imidazole having a melting point of from 200 to 203°C in a
similar manner to Synthesis Example 1 described above.
[2] In a, 200 ml four-necked flask were charged 5
g of 2-cyano-4,5-dibromo-1-dimethylsulfamoylimidazole as
- 66 -
~ 3.4 49 49
1 obtained in [1) above and 120 ml of dry tetrahydrofuran in
a nitrogen flow. While maintain~.ng the mixture at -75°C
or below with dry ice-acetone, 9.6 ml of a 1.6 M n-butyl
lithium hexane solution (manufactured by Aldrich) was
gradually added dropwise to the mixture. After completion
of the dropwise addition, the system was kept at the same
temperature for 15 minutes. Then, a solution of 3.6 g of
n-propyl iodide in 1:5 ml of tetrahydrofuran was added
dropwise to the mixture at -75°C or below. While
_ stirring, the temperature was gradually reverted to room
temperature.
After completion of the reaction, the reaction
mixture was extracted with ethyl acetate. After washing
with water, the extract was dried over anhydrous sodium
sulfate. The ethyl acetate was removed by distillation,
and the residue' was purified by silica gel column
chromatography (developing solvent: methylene chloride) to
give 2.1 g of 4-bromo-2-cyano-1-dimethylsulfamoyl-5-n
propylimidazole (Compound No. 157-b) having a melting
point of from 93 to 94°'C.
- 67 -
13 4 09 49
Typical examples of the imidazole compounds
(general formula (I)) of the present invention are shown
in Table 2.
Table 2
R2
R1 I (I)
N R3
S02R4
Compound Melting
No. Rl _ RZ R3 R4 Point
(C)
1 CN H H -N(CH3)2 74-76
2 " CH3 " " 78-83
3 " n-C H " "
3 7
4 " phenyl " " 101-102
" 4-chlorophenyl " " 148-149
6 " 2-thienyl " " 145-150
7 " 5-chloro-2- " " 145-148
thienyl
8 " 5-bromo-2- " " 138-140
thienyl
9 " SCH " "
3
" phe:nylthio " "
11 " 2-c'.hlorophenyl " " 118-121
12 " 4-nitrophenyl " " 107-108
13 " 4-trifluoro- " "
me tlhylphenyl
14 " H C1 "
- 68 -
13409 49
Table 2 ( cont' d )
Compound Melting
No. R1 _ RZ R3 Rg Point
(°C)
15 CN CH3 C1 -N(CH3)2
16 " n-C H " "
3 7
17 " phenyl " " 106-109
18 " 4-methylphenyl " " 101-108
19 " 3-methylphenyl " " 90-95
20 " 2-methylphenyl " "
21 " 3,4-dimethyl- " " 95-105
phenyl
22 " 4-methoxyphenyl " " 102-107
23 " 4-chlorophenyl " " 108
24 " 2-c:hlorophenyl " "
25 " 3,4-dichloro- " " 99-105
phenyl
26 " 4-f.luorophenyl " " 105-107
2 " SCH. " "
7 .3
28 " phenylthio " "
29 " H Br "
30 " CH " "
3
31 " ter't-C4H9 " " 88-90
32 " phenyl " "
33 " 4-methylphenyl " " 106-108
34 " 4-tort-butyl- " " 105-110
phenyl
35 " 4-methoxyphenyl " " 96-99
- 69 -
13409 49
Table 2 (co nt'd)
Compound Melting
No. Rl _ R2 R3 R4 Point
(C)
36 CN 4-f~luorophenyl Br -N(CH3)2 87-93
37 " 4-c:hlorophenyl " "
38 " 1,2-dibromo- C1 "
ethyl
39 " C2H5 Br "
40 " -CH2CH=CH2 " "
41 " 4-b~romophenyl C1 " 110-116
42 " 4-isopropyl- " "
phenyl
43 " 2-naphthyl " 124-126
44 " CH3 CH3 " 52-54
45 " phenyl " " 101-105
46 " " SCH "
3
47 " " phenyl" 148-149
48 " " CN " 124-129
49 phenyl H " 155-175
-CSNH:Z
50 " 4-chlorophenyl " " 197-201
51 " phenyl C1 " 110-130
52 " H Br " 140-144
53 " phenyl " "
54 CN 3,4-dimethoxy- H "
phenyl
55 " 3-methyl-4- C1 "
met:hoxyphenyl
- 70 -
~~409 49
Table 2 (cont'd)
Compound Melting
No. R1 _ RZ R3 Rg Point
(°C)
56 CN 4-ethylphenyl C1 -N(CH3)2
57 " phenylthio Br "
58 " benzyl " "
59 " 3-chloropropyl H "
60 " -SO C H " "
2 2 5
61 " 3-fluoropropyl C1 "
62 " 4-methylthio- H "
phenyl
63 " vinyl C1 "
64 " 5-methyl-2- H "
thienyl
65 " 2-chlorophenyl Br "
66 " 3,4-dichloro- H " 139-142
phenyl
67 " 4-(2',2',2'- C1 "
trifluoroethoxy )-
phenyl
68 ~~ ~~ Br
69 " -CH20H H "
70 " 3-chlorophenyl C1 "
71 " 3-fluorophenyl " "
72 " 2-fluorophenyl " " 96-101
7 " -SC:HZCH=CH2 H "
3
74 " CH3 N02 " 110-117
- 71 -
~34~9 49
Table 2 (cont'd)
Compound Melting
No. R1 _ R2 R3 Rg Point
(°C)
CH2
75 CN I ~ H -N(CH3)2
-(:H -
(1,2-diphenylethyl)
OH
7 6 " -CH -O
(a-hydroxybenzyl)
OH
77 " -CH-~ C1 " "
(4-chloro-a-
hydroxybenzyl)
O
7 8 " -CI'.-~- C l
(4-chlorobenzoyl)
79 " acetyl " "
S O
80 -CI NHICCH3 phenyl " "
(N-acetylthio-
carbamoyl)
S O
81 -CI NHICCH2CH2C1 " " "
(N-(3-chloro-
propionyl)-
thiocarbamoyl]
_ 72 -
'3409 49
Table 2 (cont'd)
Compound Melting
No. R1 _ R2 R3 R4 Point
(°C)
82 N-acetyl-- CH3 H -N(CH3)2
thiocarba-
moyl
S O
8 -yNHC -C
3
(N-benzoyl thio-
carbamoyl)
84 CN 5-methyl-2- " " 120-124
furyl
85 " C2H;5 C1 1-piperid-
inyl
86 " " " phenyl
87 " 4-(chloro- H -N(CH3)2 142-146
methylthio)-
phenyl
88 " CH3 CN " 80-84
89 " cyclohexyl H "
9 " -S0 CH " "
0 2 3
91 " 4-clhloro- " "
ben:zenesulfonyl
92 " phenyl C1 C2H5
93 " " " cyclo-
hexyl
94 " " " CF
3
95 " " " 2-thienyl
~H3
96 ~~ ~~ ~~ _N
C2H5
- 73 -
~ 3 4 09 49
Table 2 (cont'd)
Compound Melting
No. R1 _ R2 R3 Rg Point
(°C)
H3
97 CN phenyl C1 -N
CH2CF3
~H3
9 8 ~~ ~~ ~~ -N
CH2CH=CH2
99 " " " 1-pyrrol-
idinyl
100 " 4-methylphenyl " morpholino
101 " phenyl H isopropyl 80-83
102 " " C1 "
103 " " " -N(C2H5)2 70-80
104 " " Br " 55-76
105 " " C1 morpho- 106-110
lino
106 " " Br " 70-83
107 " " C1 thio-
morpholino
108 " 4-(2'-chloro- " -N(CH3)2
ethyl)phenyl
109 " 4-chlorobenzyl Br "
110 " benzyl H "
111 " 4-chloro- C1 "
phenylthio
112 " 3-chloropropyl " "
113 " C H " "
2 5
114 " 2-furyl 2-furyl
" 118-123
115 " 4-pyridyl H " 138-142
- 74 -
13409 49
Table 2 (cont'd)
Compound Melting
No. R1 _ R2 R3 Rg Point
(oC)
116 CN 2-thienyl C1 -N(CH3)2
117 " 4-fluoro-n-butyl " "
118 " 5-fluoropentyl " "
119 " n-C4H9 "
120 "
n-C5H11 n n
121 "
n-C6H13
122 " n-C~HiS " "
123 "
n-C$Hl~
124 "
n-C12H25
125 " iso-C3H~ "
126 " iso-CQH9 " "
127 " tert-CqH9
128 " cyclopropyl
129 " cyclohexyl " "
130 " -CH:2CH=CH2 " "
131 " geranyl (CloHl~)
"
132 " gC2H5 " "
133 " g-n,-C3H~ "
134 " S-n~-CqH9 " " 36-38
135 " benzylthio " "
136 " 3-t.rifluoro- " "
methyl-2-
pyridylthio
137 " " H
_ 75 _
X3409 49
gable 2 (cont'd)
Compound Melting
No. R1 _ R2 R3 Rg Point
(oC)
138 CN 4-clhlorophenyl- H -N(CH3)2
thio
139 ~~ g_n._C3H~
140 " SCZH5
141 " phe:nylthio phenylthio
" 98-101
142 " "
C2H5
143 " benzene- H "
sulfonyl
144 " 2-fluoro- " "
benzenesulfon-
yl
145 " 4-c:hlorobutyl C1 "
146 " 5-c:hloropentyl " "
147 " CH2(~CH3 "
148 " CH2QC2H5 " "
149 " 1-h;ydroxypropyl " "
150 " 1-h:ydroxybutyl " "
151 " benzyl " " 94-97
152 " 4-m~ethylbenzyl " "
153 " 3-methylbenzyl " "
154 " 2-methylbenzyl " "
155 " 2-fluorobenzyl " "
156 " phenethyl " "
157 " n-C3H~ gr
158 " n-C4H9
- 76 -
13409 ~9
Table 2 (cont'd)
Compound Melting
No. R1 _ R2 R3 RQ Point
(°C)
159 CN n-C:5H11 Br -N(CH3)2
160 " n-C: H " "
6 13
161 " iso-C3H~ " "
162 " isc>-C4H9 " "
163 " cyclopropyl " "
164 " cyclohexyl " "
165 " 4-c:hloro- " "
phenylthio
166 " OCH2CF3 " " 77-79
167 " S-n-C3H~
168 " S-n-C4H9
169 " S-i.so-C4H9 " "
170 " CH2,OCH3 "
171 " CH2,OC2H5 " "
172 " me t:hoxycarbonyl" "
173 " N-(4-chloro- " "
phenyl)carbamoyl
174 " N-phenyl- " "
ca r bamoyl
175 " N-ethyl- " "
ca r' bamoyl
176 -CSNH2 C2H5 C1 "
177 N-acety l- " "
thiocarba-
moyl
178 -CSNH2 n-C:4H9 "
_ 77 _
13 4 09 49
Table 2 (cont'd)
Compound Melting
No. R1 _ RZ R3 Rg Point
(°C)
179 N-acetyl- n-C4H9 C1 -N(CH3)2
thiocarba-
moyl
180 CN H I " 101-105
181 n n-C H n n
3 7
182 " " -COCF3 "
183 -CSNH2 " Br "
184 N-acetyl- " " "
thio-
carbamoyl
185 -CSNHZ " C1 "
186 N-acetyl- " " "
thiocarba-
moyl
187 N-propion- " " "
ylthio-
carbamoyl
188 N-methyl- phenyl " "
thio-
carbamoyl
189 N-acetyl- " "
thio-
carbamoyl
190 CN -S02N(CH3)2 H " 142-149
191 " -Si(CH3)3 C1 "
192
n-CloH2i
193 " C2H5 H
194 " n-CqH9
195 " g-n-C4H9 n n
_ 78 _
13409 ~9
Table 2 (cont'd)
Compound Melting
No. R1 _ R2 R3 R4 Point
(°C)
196 CN 1-hydroxy-3- C1 -N(CH3)2
phe~nylpropyl
197 " 1-hydroxypropyl H "
198 " a-hydroxybenzyl C1 "
199 " a-a,cetoxybenzyl " "
200 " 1-hydroxy-3- " "
met.hylbutyl
201 " 4-methyl-3- " "
chl.orophenyl
202 " " Br
203 " 4-methoxy-3- C1
chl.orophenyl
204 " " Br
205 " 2,?.-dichloro- C1 "
phenyl
206 " 4-e~thoxyphenyl " "
207 " '~ . Br
208 " 3.9:-methylene- C1 "
dioxyphenyl
209 " ~~ Br
210 " 4-c:yanophenyl Cl "
211 " " Br
212 " 4-nitrophenyl C1 " 140-145
213 " 2-t>utenyl " "
214 " iso-CSHli '~ "
_ 79 _
13409 49
Table 2 (cont'd)
Compound Melting
No. Ri _ R2 R3 Rg Point
(°C)
215 -CSNH2 H Cl -N(CH3)2
216 " CH3
217 '~ C5H11 "
218 " benzyl " "
219 N-acetylthio- H "
carbamoy7_
220 " CH3
221 " C5
H11
222 " benzyl " "
223 N-propionyl- "
thiocabamoyl
224 -CSNH2 C2H5 Br "
225 N-acetylth_LO-"
carbamoyl
226 N-propionyl- " "
thiocarbamoyl
227 CN 3-chlorobutyl C1 "
228 " -CF2CF=CF2 H "
229 " sec-CqH9 C1 "
230 " -CH2CH=C(CH3)2 " "
- 80 -
13 4 09 49
Table 2 (cont'd)
Compound Melting
No. R1 _ R2 R3 Rg Point
(oC)
3-b CN n-C3H~ H -N(CH3)2 51-52
9-b " SCH.3 " " 114-115
10-b " phenylthio " " 106-107
14-b " H C1 " 111-114
15-b " CH3 " " 90-95
16-b " n-C3H~ " " 64-66
17-b " phenyl " " 109-112
18-b " 4-m.ethylphenyl " " 133-134
19-b " 3-m.ethylphenyl " "
20-b " 2-m.ethylphenyl " " 93-96
21-b " 3,4-dimethyl- " "
phenyl
22-b " 4-m.ethoxyphenyl " "
23-a " 4-chlorophenyl " " 133-138
23-b " " " " 117-120
24-b " 2-chlorophenyl " " 113-117
25-b " 3,4-dichloro- " "
phenyl
26-b " 4-fluorophenyl " " 120-122
27-b " SCH:3 " " 101-103
28-b " phenylthio " " 107-108
29-b " H Br " 100-103
30-b " CH3 " " 107-110
31-b " tert-C4H9 " "
- 81 -
~340g 4~9
Table 2 (cont'd
Compound Melting
R2 Rg Rg Point
No. R1
- (oC)
32-b CN phenyl Br -N(CH3)2 122-124
33-b " 4-methylphenyl " " 136-137
34-b " 4-t.ert-butyl- "
phenyl
35-b " 4-methoxyphenyl " "
36-b " 4-f~luorophenyl " "
37-b " 4-c:hlorophenyl " "
C ~~ ~~ " 112-115
39-b " 2 s
40-b " -CFi2CH=CH2 " " 92-94
41-b " 4-bromophenyl C1 "
42-a " 4-isopropyl- " " 110-114
phf_nyl
42-b " " " " 135-138
43-b " 2-naphthyl "
46-b " phenyl SCH3 " 99-101
49-b -CSNH2 " H
50-b " 4-chlorophenyl " "
51-b " phenyl C1 " 115-128
52-b
.. H Br "
hen 1 " " 110-118
53-b " P y
55-b CN 3-methyl-4- C1 " 115-118
methoxyphenyl
56-b " 4-ethylphenyl " " 110-112
57-b " phenylthio Br " 94-97
_ 82 -
13409 49
Table 2 (cont'd
Compound Melting
No. R1 R2 R3 R4 Point
(°C)
58-b CN benzyl Br -N(CH3)2 87-89
59-b " 3-c:hloropropyl H "
-SC> C H " " 121-12
60-b " 2 2 5 4
61-b " 3-fluoropropyl C1 " 75-79
65-b " 2-c:hlorophenyl Br " 119-123
67-b " 4-(2',2',2'- C1 " 111-113
trifluoro-
ethoxy ) phenyl
68-b " " Br " 115-118
69-b " -CH20H H " 106-107
70-b " 3-chlorophenyl Cl " 96-99
71-b " 3-~Eluorophenyl "
72-b " 2-:Eluorophenyl "
73-b " -S~~H2CH=CH2 H " 20-30
75-b " 1,2-diphenyl- " " 101-103
ethyl
76-b " a-:hydroxybenzyl " " 98-100
103-b " phenyl C1 -N(C2H5)2 99-101
104-b " " Hr "
105-b " " C1 morpholino
106-b " " Br " 126-130
111-b " 4-chlorophenyl- C1 -N(CH3)2 92-94
thio
112-b " 3-chloropropyl " " 102-105
95-97
113-b " C2H5
119-b " n-~C4H9
48-49
- 83 -
13 ~ 09 49
Table 2 lcont'd
Compound Melting
No. R1 _ R2 R3 Rg Point
(C)
120-b CN n-C5H11 C1 -N(CH 3)2 37-39
121-b " n-C~~H13 " " nD 3. 51.
5002
122-b " n-C.~H15 " " nD 3.51.
5019
123-b " n-C~gHl~ " " nD3.61.4981
124-b " n-Ca2H25 " " 34-36
125-b " iso-C3H~ " " 75-82
(decomposed)
126-b " iso-CqH9 " " 73-76
127-b " tert-C9H9 " " 74-80
128-b " cyc:lopropyl " " 76-79
129-b " cyc:lohexyl " " 107-111
130-b " -CH,,CH=CH2 " " 67-72
131-b " geranyl ( CloHl~ "
)
132-b " SC2H5 " " 107-110
133-b " S-n--C3H~ " " 70-74
134-b " S-n--C4H9 " "
135-b " benrylthio " " 149-152
136-b " 3-trifluoro- " " 126-127
methyl-2-
pyridylthio
137-b " " H " 109-111
138-b " 4-chlorophenyl- " " 110-112
thic>
140-a " SC2H5 " " 36-40
- 84 -
13409 49
Table 2 lcont'd
Compound Melting
No. R1 _ R2 R3 R4 Point
CC)
140-b CN SC.,HS H -N
(
CH3
)
2
41-45
142-a " phE~nylthio C2H5 " 86-89
145-b " 4-c:hlorobutyl C1 " nD2.i 1,5382
146-b " 5-c:hloropentyl " " nD4.81.5328
147-b " CH~,OCH3 " " 64-66
148-b " CH~,OC2H5 " " 82-84
149-b " 1-hydroxypropyl " " 70-73
24.2
150-b " 1-hydroxybutyl " " nD 1.5097
151-b " benzyl " " 92-100
152-b " 4-methylbenzyl " " 125-129
153-b " 3-methylbenzyl " " 93-96
154-b " 2-methylbenzyl " " 119-123
155-b " 2-fluorobenzyl " " 105-109
156-b " phe~nethyl " " 106-110
157-b " n-C'.3H~ Br " 93-94
158-b " n-C'.4H9 " "
159-b " n-C'5Hii ' "
160-b " n-G6H13 " " 99-101
161-b " iso-C3H~ " "
162-b " iso-C4H9 " "
163-b " cyclopropyl " "
164-b " cyclohexyl " "
- 85 -
13409 49
Table 2 (cont'd)
Compound Melting
No. R1 - R2 R3 Rg Point
(oC)
165-b CN 4-c:hlorophenyl- Br -N(CH3)2 94-95
thio
167-b " S-n-C3H~ " " 76-78
168-b " S-n-C4H9 " " 48-50
169-b " S-iso-C4H9 " " 77-79
170-b " CH2,OCH3 " " 65-67
171-b " CH2OC2H5 " " 100-101
172-b " met:hoxycarbonyl " " 98-101
173-b " N-(4-chloro- " " 106-109
phe~nyl)carbamoyl
174-b " N-phenyl- " " 105-107
carbamoyl
175-b " N-ethyl- " " 98-101
carbamoyl
181-a " n-C3H~ I " 76-79
181-b " " " " 99-103
182-a " " -COCF3 " 90-92
185-b -CSNH2 " C1 " 160-162
186-b N-acetyl- " " " 119-123
thio-
carbamoyl
187-b N-propion- " " " 150-152
ylthio-
carbamoyl
188-b N-methyl- phenyl " " 67-72
thio-
carbamoyl
- 86 -
X3409 49
Table 2 (cont'd
Compound Melting
No. R1 _ R2 Rg Rg Point
(C)
189-b N-acetyl-- phenyl C1 -N
(
CH3
)
2
110-114
thio-
carbamoy7_
191-b CN -Si(CH3)3 " " 116-119
192-b " n-C1pH21 " " nD3 ~ 6 1.
4994
193-b " C2H5 H " 69-71
194-b " n-C'qH9 " " 52-53
195-b " S-n-CQH9 " " 50-51
196-b " 1-:hydroxy-3- C1 " nDq'~ 1.5512
ph~enylpropyl
197-b " 1-hydroxypropyl H " 94-97
198-b " a-hydroxybenzyl C1 " 102-104
199-b " a-acetoxybenzyl " " 82-86
200-b " 1-hydroxy-3- " " 71-74
methylbutyl
201-b " 4-methyl-3- " " 99-103
chlorophenyl
202-b " " Br " 103-106
203-b " 4-methoxy-3- C1 " 97-101
chlorophenyl
204-b " " Br " 105-110
205-b " 2,3-dichloro- C1 " 103-107
phenyl
206-b " 4-ethoxyphenyl " " 122-124
207-b " " Br " 110-113
208-b " 3,4-methylene- C1 " 150-153
dio.xyphenyl
_ 87 _
~3~09 4~9
Table 2 (cont'd
Compound Melting
No. R1 _ R2 R3 Rg Point
(C)
209-b CN 3,4-methylene- Br -N(CH3)2 95-98
dioxyphenyl
210-b " 4-cyanophenyl C1 " 182-185
211-b " " Br " 175-178
212-b " 4-nitrophenyl C1 " ~ 144-146
213-b " 2-butenyl " " 87-90
214-b " iso-C5H11 " " 45-47
218-b -CSNH2 benzyl " " 118-121
222-b N-acetyl-- " " " 163-165
thiocarbamoyl
223-b N-propionyl- " " " 149-152
thiocarbamoyl
227-b CN 3-clalorobutyl " " 54-57
230-b " -CH;ZCH=C(CH3)2" " 75-78
1 Among the imidazole compounds of the present
invention describe=_d in Table 2 above, the compounds having
a mark "a" in their compound numbers are ones falling
within the general formula (I-a) in the general formula
(I) described hereinabove and the compounds having a
mark "b" in their compound numbers are ones falling within
the general formula (I-b) in the general formula (I)
described hereinabove.
The imidazole compounds of the present invention
are useful as biocides for controlling harmful organisms
in the agricultural and horticultural areas.
_ 88 _
13 ~ 09 49
1 As agricultural and horticultural fungicides, the
compounds exhibit an excellent effect of controlling
diseases of crop plants such as rice blast caused by
Pyricularia ory~zae, rice sheath blight caused by
Rhizoctonia solani, oat crown rust caused by Puccinia
coronata, cucumber anthracnose caused by Colletotrichum
lagenarium, cucumber powdery mildew caused by Sphaerotheca
fuliginea, cucumber downy mildew caused by
Pseudoperonospora. cubensis, tomato late blight caused by
Phytophthora infestane;, tomato early blight caused by
Alternaria solani, citrus melanose caused by Diaporthe
citri, citrus common green mold caused by Penicillium
digitatum, pear scab caused by Venturia nashicola, apple
alternaria blotch caused by Alternaria mali, grape downy
mildew caused by Pla~~mopara viticola, and further gray
mold caused by Bo_ trytis cinerea and sclerotinia rot
caused by Sclerotinia sclerotiorum of various crops, etc.;
or soil diseases caused by phytopathogenic fungi such as
Fusarium, Pythium, Rhizoctonia, Verticillium,
Plasmodiophora, A. hp anoniyces, etc.
In particular, the compounds exhibit an excellent
effect of preventing deseases such as potato or tomato
late blight caused by Phytophthora infestans, cucumber
downy mildew caused b;~ Pseudoperonospora cubensis, grape
downy mildew caused b:y Plasmopara viticola, and tobacco
blue mold caused by Peronospora tabacina; and soil
_ 89 _
1309 ~9
1 diseases caused by phycomycetes such as Plasmodiophora,
Aphanomyces, Pyth:ium, etc.
The compounds of the present invention have a
prolonged residual ei°fect so that they exhibit an
excellent preventing effect, and further exhibit an
excellent curative effect as well. Therefore, it is
possible to control deseases by treatment after infection.
The compounds of the present invention are appropriate to
be applied to crop plaints by foliar treatment. Further,
the compounds po~.sess a systemic activity so that it is
also possible to control deseases of the stem and leaf by
soil treatment. :fin addition, the compounds of the present
invention show an excellent controlling effect against
agriculturally and horticulturally harmful insects such as
various planthoppers, diamondback moth (Plutella
xylostella), green rice leafhopper (Nephotettix
cincticeps), a~izuki bean weevil (Callosobruchus
.chinensis), common cui~worm (Spodoptera litura), green
peach aphid (MVzus pe~~sicae), etc.; mites such as two-
spotted spider mite (Tetranychus urticae), carmine spider
mite (Tetranychus c:innabarinus), citrus red mite
(Panonychus citri), etc.; and nematodes such as southern
root-knot nematodes (Meloidogyne incognita), etc.
Upon use, the .compounds of the present invention
can be prepared into a variety of forms of biocidal
compositions such as emulsifiable concentrates, suspension
- 90 -
13 4 09 49
concentrates, dusts, wettable powders. aqueous solutions,
granules, etc., together with adjuvants, as in
conventional formulations. Upon actual use of these
formulations, they can be used as such or by diluting with
a diluent such ass water or the like to a predetermined
concentration.
As the agriculturally acceptable adjuvants used
herein, mention may be made of carriers, emulsifying
agents, suspending agents, dispersing agents, spreaders,
penetrating agents, wetting agents, thickeners,
stabilizers, etc.
The carriers are classified into solid carriers
and liquid carrif~rs. As the solid carriers, mention may
be made of animal and vegetable powders such as starch,
sugar, cellulo=>e powders, cyclodextrin, activated
charcoal, soybean powders, wheat powders, chaff powders,
wood powders, fish powders, powdery milk, etc.; and
mineral powders such as talc, kaolin, bentonite, bento-
nite-alkylamine comp7Lex, calcium carbonate, calcium
sulfate, sodium bicarbonate, zealite, diatomaceous earth,
white carbon, clay, al~umina, silica, sulfur powders, etc.
As the liquid c<~rriers, mention may be made of water;
animal and vegetable oils such as corn oil, soybean oil,
cotton seed oil, etc.; alcohols such as ethyl alcohol,
ethylene glycol, etc.; ketones such as acetone, methyl
ethyl ketone, etc.; ethers such as dioxane, tetrahydro-
- 91 -
13409 49
1 furan, etc.; aliphatic hydrocarbons such as kerosene,
lamp oil, liquid paraffin, etc.; aromatic hydrocarbons
such as xylene, trimethylbenzene, tetramethylbenzene,
cyclohexane, solvent naphtha, etc.; halogenated hydro-
carbons such as chloroform, chlorobenzene, etc.; acid
amides such as dimethylformamide, etc.; esters such as
ethyl acetate, fatty acid glycerine esters, ete.;
nitriles such as. acetonitrile, etc.; sulfur-containing
compounds such ass dime~thyl sulfoxide, etc.; and N-methyl
pyrrolidone, etc.
The adjuvants other than the carriers described
hereinabove, such as emulsifying agents, suspending
agents, dispersing agents, spreaders, penetrating agents,
wetting agents, thickeners, stabilizers, etc. are
exemplified more specifically as following surfactants.
PolyoxyethylenE~ alkylarylether, polyoxyethylene
glycol nonyl phenylether, polyoxyethylene laurylether,
polyoxyethylene caster- oil, polyoxyethylene alkylaryl
sulfate (polyoxyethyle ne alkylphenyl ether sulfate),
polyoxyethylene fatty acid ester (polyoxyethylene
stearate), polyoxyethylene sorbitan fatty acid ester,
lower alcohol phosphate, sodium alkylsulfate, sodium
lignin sulfonate, calcium lignin sulfonate, alkylaryl
sulfonate, sodium alltylbenzene sulfonate, sodium
naphthalene sulfonate-formaldehyde condensate, dialkyl-
sulfosuccinate.
- 92 -
1309 ~9
1 The compound~of the present invention is uniformly
mixed with at least one kind of adjuvants described
hereinabove to form a biocidal composition.
A weight ratio of the compound of the present
invention to the adjuvants to be formulated is generally
from 0.05:99.95 to 90:10, preferably from 0.2:99.8 to
80:20.
Since a concentration of the compound of the
present invention to be applied may vary depending upon
crop to be applied, method for application, preparation
form, dose to be applied, etc., it is difficult to define
a specific concentration range. However, if it is forced
to define specifically,, the concentration of the compound
is generally from 0.1 to 10,000 ppm, desirably from 1 to
2,000 ppm in the case of foliar treatment, and is
generally from 10 to 1.00, 000 g/ha, desirably from 200 to
20,000 g/ha in the cases of soil treatment.
Further, if necessary and desired, the compound of
the present inver.,tion can be used as admixture with or in
combination with other agricultural chemicals, for
example, insecticides, acaricides, nematocides, fungi-
cides, antiviral ageni~s, attractants, herbicides, plant
growth regulators, etc. In this case, more excellent
effects can sometimes be exhibited.
As the insecticides, acaricides or nematocides,
mention may be made of, for example, organic phosphrous
- 93 -
l~~~g ~9
1 compounds, car:bamate compounds, organic chlorine
compounds, organic metal compounds, pyrethroid compounds,
benzoyl urea compounds, juvenile hormone-like compounds,
dinitro compounds, organic sulfur compounds, urea
compounds, triazi.ne compounds, etc. The compound of the
present invention can also be used as admixture with or in
combination with biological pesticides such as BT agents,
insect pathogenic viral. agents, etc.
As the fungicides, mention may be made of, for
example, organic phosphorus compounds, organic chlorine
compounds, dithiocarbamate compounds, N-halogenothioalkyl
compounds, dicarbox:Lmide compounds, benzimidazole
compounds, azole compounds, carbinol compounds, benz
anilide compounds, acylalanine compounds, pyridinamine
compounds, piperazine compounds, morpholine compounds,
anthraquinone cornpound;s, quinoxaline compounds, crotonic
acid compounds, sulfenic acid compounds, urea compounds,
antibiotics, etc.
Hereafter, test:. examples of the biocidal composi
tions for controlling harmful organisms in the agri
cultural and horticultural areas in accordance with the
present invention are dlescribed below.
Standards. for evaluation of the agricultural and
horticultural fungicides follow the following criteria for
evaluation, unless otherwise indicated.
- 94 -
~~4~09 49
1 Standards for Evaluation
The controlling effect was determined by visually
observing a degree of desease of a test plant and
expressed by thE~ fol7.owing 5 grades of th e index of
control.
[Index of Control] [D<~gree of Desease]
5: No lesion is noted at all.
4: ArEea, number or length of lesions is
less than 10~ as compared to the non-
trE~ated plot.
3: Area, number or length of lesions is
leas than 40~ as compared to the non-
trE~ated plot.
2: Area, number or length of lesions is
less than 70~ as compared to the non-
tre~ated plot.
1: Area, number or length of lesions is
more than 70% as compared to the non-
treated plot.
Test Example 1
Test on preventive effect against cucumber powdery
mildew
Cucumber (cult:ivars: Suyo) was culti vated in
a
polyethylene pot having a diameter of 7.5 cm. When
cucumber reached the one-leaf stage, 10 ml of a solution
obtained from each o1. test compounds adju sted to a
predetermined concentration was sprayed ove r cucumber
- 95 -
~~409 49
1 using a spray gun. After keeping the pots in a constant
temperature chamber of 22 to 24°C over one day and one
night, conidia o:E fungi of powdery mildew (Sphaerotheca
fuliginea) were inoculated. Ten days after the
inoculation, an area of lesion on the first leaf was
investigated; and an index of control was determined by
the standards for evaluation described above. The results
shown in Table 3 were obtained.
Table 3
Index of Control
Compound No. 500 ppm
15-b 4
23-a 4
59-b 4
106~-b 3
13 3'.-b 4
167-b 3
169-b 3
171-b 5
Test Example 2
Test on preventive ef:Eect against cucumber anthracnose
Cucumber (culti.vars: Suyo) was cultivated in a
polyethylene pot having a diameter of 7.5 cm. When
cucumber reached 'the two-leaf stage, 10 ml of a solution
obtained from each of: test compounds adjusted to a
predetermined concentration was sprayed over cucumber
using a spray gun. After keeping the pots in a constant
- 96 -
13 4 09 49
temperature chamber of 22 to 24°C over one day and one
night, a spore suspension of fungi of anthracnose
(Colletotrichum 1_aqena.rium) was inoculated. Seven days
after the inoculation, an area of lesion on the first leaf
was investigated, and an index of control was determined
by the standards for evaluation described above. The
results shown in Table 4 were obtained.
Table 4
Index of Control
Co_ mpound No. 500 ppm
3-lb 3
17-lb 3
26 5
28-lb 3
51 3
51-lb 3
59-lb 3
69-lb 3
70-lb 4
73-lb 3
75-ib 3
101 4
105 4
106 3
Test Example 3
Test on preventive effect against cucumber downy mildew
_ 97 _
13 4 09 49
1 Cucumber (cultivars: Suyo) was cultivated in a
polyethylene pot having a diameter of 7.5 cm. When
cucumber reached the two-leaf stage, 10 ml of a solution
obtained from each of test compounds adjusted to a
predetermined concentration was sprayed over cucumber
using a spray gun. After keeping the pots in a constant
temperature chamber of 22 to 24°C over one day and one
night, a spore suspension of fungi of downy mildew
(Pseudoperonospor.a cubensis) was inoculated. Six days
after the inoculation, an area of lesion on the first leaf
was investigated, and an index of control was determined
by the standards. for evaluation described above. The
results shown in Table 5 were obtained.
Table 5
Index of Control Index of Control
Compound No. 125 perm 31 ppm Compound No. 125 ppm 31 ppm
4 'S 5 29-b 5 5
5 5 5 30-b 5 5
'S 4 31 4 3
7 '5 5 32-b 5 5
g 5 3 33 - 5
14-b 5 3 34 5 5
15-b 5 5 36 - 5
16-b ~- 5 37 5 5
17 5 5 45 5 5
17-b ~- 5 47 5 5
23 5 5 48 5 5
- 98 -
13409 49
Table 5 (cont'd)
Index: of Control Index of Control
Compound No. 125 1?~ 3:L ppm Compound No. 125 ppm 31 ppm
49 'i 4 101 5 4
50 5 5 103 5 5
52 'i 5 105 4 -
53-b 5 5 106 5 5
Test Example 4
1 Test on curative effE~ct against cucumber downy mildew
Cucumber (cultivars: Suyo) was cultivated in a
polyethylene pot having a diameter of 7.5 cm. When
cucumber reached the two-leaf stage, a spore suspension of
fungi of downy mildew (Pseudoperonospora cubensis) was
inoculated. Six hours after the inoculation, 10 ml of a
solution obtained from each of test compounds adjusted to
a predetermined concentration was sprayed over cucumber
using a spray gun. After keeping the pots in a constant
temperature chamber of 22 to 24°C for 6 days. an area of
lesion on the first leaf was investigated, and an index of
control was determined by the standards for evaluation
described above. They results shown in Table 6 were
obtained.
Table 6
Index: of Control Index of Control
Compound No . 1-2 5 tam 3:L ppm Compound No . 12 5 ppm 3_ 1 ppm
3-b 5 - 8 5
- 99 -
13409 49
Table 6(cont'd
Index of Control Index of Control
Compound No. 125 ppm ~l ppm Compound No. 125 ppm 31 ppm
9-b 5 - 32-b 5 -
10-b 5 - 33 5 -
12 5 - 33-b 5 -
14-b 5 - 36 5 -
15-b 5 - 37 5 -
16-b 5 - 39-b - 5
17 5 - 40-b - 5
17-b 5 - 41 - 5
18 - 5 46-a 5 -
18-b 5 - 48 4 -
19 5 - 51 5 -
20-b 5 - 51-b 5 -
22 5 - 52 5 -
23 5 - 53-b 5 -
23-a 5 - 56-b 5 -
23-b 5 - 57-b - 5
24-b - 5 58-b - 5
25 - 4 59-b - 5
26 - 5 60-b - 5
26-b 5 - 61-b - 5
27-b 5 - 65-b 5 -
28-b 5 - 67-b 5 -
29-b 5 - 68-b - 4
30-b 5 - 69-b 4 -
- 100 -
X13409 49
Table 6 l cont' d
Inde:c of Control Index of Control
Compound No. 125 ppm 31 ppm Compound No. 125 ppm 31 ppm
70-b 5 - 138-b - 5
72 ~- 5 141 4 -
74 ~- 4 142-a 5 5
76-b '~ - 145-b - 5
88 ~- 5 146-b - 5
101 4 - 147-b 5 5
103-b 5 - 148-b 5 5
106-b !i - 149-b - 5
111-b -- 5 150-b 5 -
112-b !i 5 151 - 5
113-b !i 5 151-b 5 5
119-b 5 5 152-b - 3
120-b 5 5 153-b - 5
121-b .'i 5 154-b - 5
125-b -- 5 155-b - 5
126-b -- 5 156-b - 5
128-b -- 5 157-b - 5
129-b -- 5 160-b 5 5
130-b 5 5 166 5 3
132-b -- 5 167-b 5 5
133-b 5 4 169-b 5 5
134 5 5 170-b 5 5
135-b 4 - 171-b 5 5
136-b -- 3 173-b 4 -
- 101 -
1~~09 49
Table 6 (cont'd
Inde:~c of Control Index of Control
Compound No. 125 perm31 ppm Compound No. 125 ppm 31 ppm
180 5 - 201-b 4 -
181-a - 5 203-b 3 -
181-b - 5 208-b 4 3
185-b - 5 209-b 5 -
186-b - 5 210-b 4 -
187-b - 5 212-b 5 5
189-b 5 5 213-b - 5
190 5 4 214-b - 5
1 Test Example 5
Test on :~_ystem:ic effect against cucumber
downy mildew
Cucumber (cultivars: Suyo) was cultivated in a
polyethylene pot having a diameter of 7.5 cm. When
cucumber reached the two-leaf stage, 15 ml of a solution
obtained from each of test compounds adjusted to a
predetermined concentration was drenched on the surface of
soil using a pipette" After keeping the pots in a
constant temperature chamber of 22 to 24°C for 2 days, a
spore suspension of fungi of downy mildew
(Pseudoperonospor,a cubensis) was inoculated. Six days
after the inoculation, an area of lesion on the first leaf
was investigated, and .an index of control was determined
- 102 -
~~~os ~~
1 by the standard~~ for evaluation described above. The
results shown in Table 7 were obtained.
Table 7
Index of Control
(:o-mpound No. 500 ppm 125 ppm
1 5 3
14-b 5 5
15-b - 5
17 5 4
29-b 5 5
30-b 5 5
37 5 5
52 5 5
53-b 5 5
-Test Example 6
Test on preventive effect against tomato late blight
Tomato (c:ultivars: Ponderosa) was cultivated in a
polyethylene pot having, a diameter of 7.5 cm. When tomato
reached the four-leaf :stage, 10 ml of a solution obtained
from each of test compounds adjusted to a predetermined
concentration way, spra:yed over tomato using a spray gun.
After keeping thE~ pots in a constant temperature chamber
of 22 to 24°C over one day and one night, a zoosporangium
suspension of fungi of late blight (Phytophthora
infestans) was inoculated. Five days after the
inoculation, an area of lesion on the leaves was
investigated, and an index of control was determined by
- 103 -
X3409 49
the standards for' evaluation described above. The results
shown in Table 8 were obtained.
Table 8
Index of Control
Compound No. 125 ppm 31 ppm 8 ppm
3 ~-b - 5 -
4 5 4 -
5 5 -
6 5 4 -
7 5 5 -
8 5 5 -
9--b - 5 -
--b - - 5
12 - 5 3
14--b - 5 -
--b - 4 -
16--b - 5 4
17 5 5 -
17 --b 5 5 -
18 - 5 -
18--b - 5 -
19 - 5 -
2 0 --b - 5 -
21 - 5 -
- 104 -
13409 4g
Table 8 ( cont'
d )
Index of Control
Compound No. 125 ppm 31 ppm 8 ppm
22 - 5 -
23 5 5 -
2 3 --a - 5 -
23--b - 5 -
2 4 --b - 5 5
25 - 5 5
26 - 5 -
26--b - 5 -
27--b - 5 -
28--b - 5 -
29--b 5 5 -
30--b - 5 -
32-~b 5 5 -
33 5 5 -
33-~b - 5 -
34 4 4 -
36 5 5 -
37 - 5 -
39-b - - 5
40-b - 5 5
41 - 5 5
42-a - 5 -
42-b - 5 -
43 - - 5
- 105 -
X3409 49
Table 8 (cont'd)
Index of Control
C- ompound N~o. 125 ppm 31 ppm 8 ppm
45 5 5 -
46-a 5 5 -
48 5 5 -
49 5 3 -
50 4 - -
51 5 5 -
51--b 5 5 -
52 5 4 -
53--b 5 5 -
5 5--b - 4 5
56--b - 5 -
57--b - - 5
58--b - 5 5
59--b - - 5
60--b - 5 -
61--b - 5 5
6 5--b - 5 -
66 5 5 -
6 7--b - - 5
6 8--b - - 5
7 0 --b - - 5
72 - - 5
7 3--b - 4 -
74 - - 5
- 106 -
13409 49
Table 8 (cont'd)
Index of Control
Compound No. 125 ppm 31 ppm 8 ppm
75-~b - 5 -
76-b - 5 -
84 - - 5
88 - - 5
101 5 5 -
103 5 - -
104 5 4 -
105 5 4 -
106-b 5 4 -
111-b - - 4
112-b - 5 5
113-b - - 5
114 - 5 5
119-b - 5 5
120-b - 5 5
121-b - 5 5
122-b - 5 5
123-b - 5 5
124-b - 5 5
125-b - - 5
126-b - - 5
128-b - 5 4
129-b - 5 5
130-b - 5 5
- 107 -
~3~09 49
Table 8 (cont'd)
Index of Control
C- ompound No 12 5 ppm 31 ppm 8 ppm
.
132--b - 5 5
133--b - - 5
134 - 5 5
135--b - 5 5
136--b - - 5
137--b - - 5
138--b - _ 4
141 - 5 5
142--a - 5 5
14 5--b - - 4
146--b - 5 5
147--b - 4 3
148--b - 4 -
149--b - - 5
151 - - 5
151--b - 5 5
152--b - - 5
153--b - - 5
154--b - - 5
15 5--b - - 5
156--b _ _ 5
157--b - - 5
- 108 -
~3~Og 49
Table 8 (cont'd)
Index of Control
Compound No. 125 ppm 31 ppm 8 ppm
160-~b - 5 5
166 - 5 3
167-b - 5 5
169-b - 5 5
170-b - 5 3
171-b - 5 -
173-b - 4 3
174-b - 4 -
180 - - 5
181-b - 5 5
182-b - 5 5
185-b - - 5
186-b - - 5
187-b - - 5
189-b - 5 4
190 - 4 -
201-b - 5 5
202-b - 5 5
203-b - 4 5
2 0 5-.b - - 5
206-b - 5 5
207-b - 5 -
208-b - 5 5
- 109 -
~~~o~ ~s
Table 8 (cont'd
Index of Control
Compcmnd No. 125 ppm 31 ppm 8 ppm
209--b - 4 -
210-~b - 4 3
211-~b - 4 -
212-~b - 5 3
213-~b - 5 5
214-~b - 5 5
1 Test Example 7
Test on systemic effect against
tomato late blight
Tomato (cultivars: Ponderosa) was cultivated in a
polyethylene pot laaving a diameter of 7.5 cm. When tomato
reached the four-leaf ~~tage, 15 ml of a solution obtained
from each of test compounds adjusted to a predetermined
concentration was drenched on the surface of soil using a
pipette. After keeping the pots in a constant temperature
chamber of 22 i:o 24°C for 2 days, a zoosporangium
suspension of :Fungi of late blight (Phytophthora
infestans) was inoculated. Five days after the
inoculation, an area of lesion on the leaves was
investigated, and an index of control was determined by
the standards for evaluation described above. The results
shown in Table 9 cvere olbtained.
- 110 -
13~~9 4~
Table 9
Index of Control
Compound No. 500 ppm 125 ppm
3-b - 4
10-b 5 5
16-b - 4
17-b 5 4
19 4 4
20-b 5 4
22 5 4
27-b 5 5
:28-b 5 -
~4 0 -b 5 5
!i l 5 5
!51-b 5 5
!i 7 -b - 4
!i 8-b 5 3
!i9-b - 4
',7 6 -b - 5
Test Example 8
Test on prcsventive effect against rice blast
Rice plant (cultivars: Chukyo Asahi) was
cultivated in a polyethylene pot having a diameter of 7.5
cm. When rice plant reached the four-leaf stage, 20 ml of
a solution obtained from each of test compounds adjusted
to a predeterminE~d concentration was sprayed over rice
plant using a spray gun. After keeping the pots in a
- 111 -
13 ~ ~~ ~9
1 constant temperai:ure chamber of 22 to 24°C over one day
and one night, a spore suspension of fungi of blast
(Pyricularia ory~;ae) was inoculated. Five days after the
inoculation, a number of lesion was investigated, and an
index of control was determined by the standards for
evaluation described above. The results shown in Table 10
were obtained.
Table 10
Index of Control
(:ompound No. 500 ppm
27-b 4
48 3
53-b 3
55-b 4
134 3
167-b 3
2'01-b 4
2 ~0 2-b 4
Test Example 9
Test on preventive effect against rice sheath blight
Rice plant (cultivars: Chukyo Asahi) was
cultivated in a polyethylene pot having a diameter of 7.5
cm. When rice plant reached the five-leaf stage, 20 ml of
a solution obtair.~ed from each of test compounds adjusted
to a predetermined concentration was sprayed over rice
plant using a spray gun. After keeping the pots in a
constant temperature chamber of 22 to 24°C over one day
- 112 -
~! 3 4 09 49
1 and one night, rice straw in which fungi of sheath blight
(Rhizoctonia solani) had been previously incubated was set
between leaf sheath portions to inoculate. After keeping
the pots in an inoculation room having a temperature of
28°C and a humidity of 100 for 5 days, a length of lesion
was investigated, and an index of control was determined
by the standards for evaluation described above. The
results shown in Table 11 were obtained.
Tahla 11
Index of Control
C'.ompound No. 500 ppm
6 3
:21 3
27-b 3
:34 3
!51-b 3
!i 3 -b 3
104 3
Test Example 10
Test on preventive effect against oat crown rust
Oats (cultivars: Zenshin) were cultivated in a
polyethylene pot having a diameter of 7.5 cm. When oats
reached the two-leaf stage, 10 ml of a solution obtained
from each of test comb>ounds adjusted to a predetermined
concentration was sprayed over oats using a spray gun.
After keeping the pots in a constant temperature chamber
of 22 to 24°C over' one day and one night, conidia of fungi
- 113 -
X3409 49
1 of crown rust (I?uccinia coronata) were inoculated. Ten
days after the inocu:Lation, an area of lesion on the
second leaf was investigated, and an index of control was
determined by the standards for evaluation described
above. The results shown in Table 12 were obtained.
Index of Control
Compound No. 500 ppm
4 3
14-b 3
44 4
52 4
59-b 3
104 4
172-b 4
180 5
1 !~ 0 3
Test Example 11
Test on preventive effect against turnip clubroot
Soil contaminated with fungi of clubroot
(Plasmodiophora brassicae) was filled in a 1/14,000 a
(1/140 m2) pot, and 20 ml of a solution obtained from each
of test compounds adjusted to 4 kg/10 a and 1 kg/10 a
calculated as the active ingredient was drenched on the
surface of the soil using a pipette. One day after
treatment, the soil was mixed over the whole layers, and
turnip (cultivars: Kanamachi Kokabu) was seeded. The
- 114 - '
1409 49
turnip was grown in a greenhouse. Thirty days after the
seeding, a degree of clubroot formation was investigated,
and an index of control was determined by the standards
for evaluation described below. The results shown in
Table 13 were obtained.
Standards for evaluation
[Index of Control] [Degree of Occurrence of Clubroot]
5: formation of clubroot . none
4: " . slight
3; " . medium
2: " . many
1: " . abundant
Index of Control
Compound No. 4 kq/10 a 1 kg/10
a
1 5 -
4 4 -
5 5 5
6 5 5
7 5 5
8 5 5
9-b 5 4
10-b - 5
12 - 5
14-b 5 5
15-b - 5
16-b 5 5
- 115 -
X3409 49
Table 13 ( cont' d)
Index of Control
C'om ound 4 kq/10 a 1 kg/10
No. a
17 - 5
17-b - 5
18 5 5
18-b - 5
19 5 5
20-b 5 4
21 5 5
22 5 5
23 5 ~ 5
23-a - 4
23-b - 4
24-b - 5
26 5 4
26-lb - 5
27-lb 5 5
29-b - 5
3 0-b - 5
32-b - 5
33 5 5
33-b - 5
34 5 5
36 5 5
37 5 5
39-t> - 5
- 116 -
' 3 4~ 0 9 4 9,
Table 13 (cont'd
Index of Control
!~ompound No. 4 kq/10 a 1 kq/10
a
40-b - 5
42-a - 5
42-b - 5
46-a 5 -
49 - 4
50 5 5
51 5 5
51--b 5 5
52 - 5
53--b 5 4
55--b - 5
56--b - 5
58--b - 5
59--b 5 5
65--b - 5
67--b - 5
6 8--b - 5
7 3--b 4 -
88 - 4
105 4 -
106 5 -
180 5 5
201--b - 5
202--b - 5
- 117 -
°
3409 49
Table 13 ( cont' d )
Index of Control
Compound No. 4 kq~l0 a 1 kg/10 a
206-b - 5
207-b - 5
1 Vest Example 12
Antimicrobial test (phytopathoqenic fungi)
Mycelial disc (agar punching) of preincubated
Pythium aphanidermatum was transplanted on potato-dextrose
agar medium (PDA medium) containing 100 ppm of
streptomycin and 100 ppm of each of test compounds. After
incubation at 22°C for 48 hours, a diameter of mycelium
was measured. Inhibition of hyphal growth (~) was
determined by the following equation. The results shown
in Table 14 were obtained.
Diameter of mycelium in treated plot
inhibition of hyphal growth (%) _=100 - X 100
Diameterofmycelium in non-treated plot
Inhibition of
Compound No. Hyphal Growth
3--b 10 0
5 95
7 100
9 --b 10 0
10--b 100
14-~b 100
15-~b 100
- 118 -
~~409 ~9
Table 14 (cont'd)
Inhibition of
Compour.~d No. Hyphal Growth
16-b 100
17 100
17-b 100
23 100
27-b 100
28-b 100
29-:b 100
30-ib 100
31 100
33 100 ($)
34 100
36 100
37 100
45 100
49 100
53-ti 100
101 100
103 100
104 100
105 100
- 119 -
~3~09 ~9
Table 14 (cont'd)
Inhibition of
Compound No. Hyphal Growth
106 100
180 100
1
TEest Example 13
Miticidal test on adults of two-spotted spider mites
Kidney bean (cultivars: Edogawa Saito) was
cultivated in a polyethylene pot having a diameter of 7.5
cm. When kidney bean reached the primary leaf stage, one
primary leaf was left" and other leaves were cut out.
After infesting about 30 adults of two-spotted spider mite
(Tetranychus urti.cae: resistant to Dicofol and organic
phosphorus insecticides), the seedlings were immersed in
20 ml of a solut_~on obtained from each of test compounds
adjusted to a pi:edetermined concentration for about 10
seconds. After drying, the seedlings were allowed to
stand in a constant temperature chamber of 26°C with
lighting. Two days after releasing the mites, numbers of
dead mites were investigated, and a mortality (%) was
determined by the following equation. The results shown
in Table 15 were obtained.
Numberofdead mites
Mortality (%)= X 100
Number of released mites
- 120 -
x'3409 49
Table 15
Mortalit y ($)
!~ompound No. 800 ppm 200
ppm
9-b 100 100
10-b 100 100
14-b 100 100
15~-b 100 100
23 100 100
23-a 100 -
23-b 91 -
26-b 100 -
29--b 100 100
36 100 100
40--b 100 100
41 100 -
52 100 100
57--b 100 -
58--b 100 -
72 100 -
88 100 -
101 100 100
112--b 100 -
113--b 100 100
119--b 100 100
- 121 -
Table 15 (cont'd)
Mortality (~)
!~ompound No. 800 ppm 200 ppm
133-b 100 90
151-b 100 -
167-b 100 87
169-b 100 100
172-b 100 -
205-b 100 -
1 Test Example 14
Ovicidal test on two-spotted spider mites
Kidney bean with only one primary leaf was
transplanted on a polyethylene pot. After infesting
adults of two-spotted spider mite (Tetranychus urticae)
and ovipositing for 24 hours, the adults were removed.
Then, the kidney bean described above was immersed in 20
ml of a solution obtained from each of test compounds
adjusted to a predetermined concentration for about 10
seconds. After drying, the kidney bean was kept in a
constant temperature chamber of 26°C with lighting. Five
to seven days after thEa treatment, a state of hatching was
investigated, and an c'vicidal rate ($) was determined by
the following equation. The results shown in Table 16
were obtained. Death immediately after hatching was
regarded to be ovicidal..
- 122 -
~1~~~9 h9
Number of killed eggs
Ovicidal Rate I;%)= X 100
Numberofoviposited eggs
Table 16
Ovicidal Rate
C:o- mpound 800 ppm
No.
10-b 100
15-b 100
26-b 100
29-b 100
30-b 70
40-b 100
52 98
57-b 90
gg 100
101 100
113-b 100
119-b 100
133-b 100
167-b 100
169-b 100
1 Test Example 15
Insecticidal test on small brown planthoppers
Young seE~dlings of rice plant were immersed in 20
ml of a solution obtained from each of test compounds
adjusted to a predetermined concentration for about 10
seconds. After drying, the root was wrapped with wet
- 123 -
1309 ~9
1 absorbent cotton and put in a test tube. Then, 10 larvae
of second to third instar of small brown planthoppers
(Laodelphax striatellu:>) were released in the test tube,
and the opening of the test tube was covered with gauze.
The test tube was kept in a constant temperature chamber
of 26°C with lighting. Five days after the release of the
larvae, numbers of dead insects were investigated, and a
mortality rate (~) was determined by the following
equation. The results shown in Table 17 were obtained.
Numberofdead insects
Mortality (%)= X 100
Numberofreleased insects
Table 17
Mortality
C'.o_ mpound 800 ppm 200 ppm
No.
14-~b 100 100
15-~b 100 80
40-~b 100 -
113-~b 100 -
119-~b 100 -
133-~b 100 -
151-~b 100 -
- 124 -
1309 ~g
1 Test Example 16
Insecticidal test on green peach aphids
A piece of cabbage leaf was immersed in 20 ml of a
solution obtained. from each of test compounds adjusted to
a predetermined concentration for about 10 seconds,
followed by drying. wet filter paper was put on a petri
dish having a diameter of 9 cm, and the air-dried leaf
piece was put thereon. Apterous viviparous females of
green peach aphids (Myzus persicae) were released on the
leaf. The petri dish was covered and kept in a constant
temperature chamber of 26°C with lighting. Two days after
release of the insects, numbers of dead insects were
investigated, an~i a mortality ($) was determined in the
same manner as Test Example 15 described above. The
results shown in Table 18 were obtained.
Table 18
Mortality (~)
(.o_ mpou:nd No. 800 ppm
7. 7 0
32-b 70
52 90
Test Example 17
Insecticidal_ test on common cutworms
A piece of cabbage leaf was immersed in 20 ml of a
solution obtained from each of test compounds adjusted to
a predetermined concentration for about 10 seconds
followed by drying. Wet filter paper was put on a petri
- 125 -
X3409 49
1 dish having a diameter of 9 cm, and the air-dried leaf
piece was put thereon. Second to third instar larvae of
common cutworms (SpodC>ptera litura) were released on the
leaf. The petri dish was covered and kept in a constant
temperature chamber of 26°C with lighting. Five days
after release of the larvae, numbers of dead insects were
investigated, and a mortality ($) was determined in the
same manner as Test Example 15 described above. The
results shown in Table 19 were obtained.
Table 19
Mortality (~)
Co. mpou.nd No. 800 ppm
2~6-b 100
40-b 100
6'7-b 10 0
6.B-b 100
72 100
74 100
Formula tion examples of the present invention are
described below, but t:he compounds, dose in formulations,
type of formulations, etc. in the present invention are
not deemed to be limited to those described below.
Formulation Example 1 ~Wettable powder)
(a) Compound No. 5 50 parts by weight
(b) Kaolin 40 "
(c) Sodium lignin sulfonate 7 "
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?3~~949
1 (d) Dialkylsulfosuccinate 3 "
The above components are uniformly
mixed.
Formulation owder)
Example
2 (Wettable
p
(a) Compound No. 17-b 20 parts by weight
(b) Kaolin 72
(c) Sodium lignin sulfonate 4 "
(d) Polyoxyethylene alkylaryl 4 "
ether
The above components are uniformly
mixed.
Formulation owder)
Example
3 (Wettable
p
(a) Compound No. 18-b 6 parts by weight
(b) Diatomaceous earth 88 "
(c) Dialkylsulfosuccinate 2 "
(d) Polyoxyethylene alkylaryl 4 "
sulfate
The above components are uniformly
mixed.
Formulation owder)
Examp:l_e
4 (Wettable
p
(a) Kaolin 78 parts by weight
(b) Sodium S-naphthalene- 2 "
sulfonate-formaldehyde
condensate
(c) Polyoxyethylene alkylaryl 5 "
sulfate
(d) Fine silica 15 "
A mixture of the above components Compound
and No.
22 are mixed in a weight ratio 4:1.
of
Formulation owder)
Example
5 Wettable
p
(a) Compound No. 16-b 10 parts by weight
(b) Diatomaceous earth 69 "
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~3~~9 49
1 (c) Calcium carbonate powder 15 "
(d) Dialkylsulfosuccinate 1 "
(e) Polyoxyethylene~ alkylaryl3 "
sulfate
(f) Sodium S-naphthalene- 2 "
sulfonate-formaldehyde
condensate
The above compc>nents are uniformly
mixed.
Formulation
Example
6 (Wettable
powder)
(a) Compound No. 1T-b 20 parts by weight
(b) Kaolin 62.4 "
(c) Fine silica 12.8 "
(d) Alkylaryl sulfonate 1.6 "
(e) Polyoxyethylene alkylaryl 2.4 "
sulfate
(f) Polyoxyethylene alkylaryl 0.8 "
ether
The above components are uniformly
mixed.
Formulation
Example
7 Dust
(a) Compound No. 2:3 5 parts by weight
(b) Talc 94.5 "
( c ) Lower alcohol phosphate 0 . 5 "
The above components are uniformly
mixed.
Formulation
Example
8 (Dust
(a) Compound No. lEi-b 0.2 parts by weight
(b) Calcium c:arbon<~te powder98.8 "
(c) Lower alc;ohol phosphate 1.0 "
The above components are uniformly mixed.
Formulation Example 9 i;Emulsifiable concentrate)
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1 (a) Compound No. 2Ei 20 parts by weight
(b) Xylene 60 "
(c) Polyoxyet:hylenE~ alkylaryl 20 "
ether
The abovE~ components are mixed and dissolved.
Formulation Exam~~le 10 ('Suspension concentrate)
(a) Compound No. 151 10 parts by weight
(b) Corn oil
(c) Polyoxyet:hylene caster oil 12 "
(d) Bentonite-alkylamine 1 "
complex
The above components are uniformly mixed and
pulverized.
Formulation Example 11 (Granule)
(a) Compound No. 33-b 1 parts by weight
(b) Bentonite 61 "
(c) Kaolin 33 "
(d) Sodium lignin ;sulfonate 5 "
A suitable amount of water required is added to
the above componE~nts, followed by mixing and granulating.
While the invention has been described in detail
and with reference to specific embodiments thereof, it
will be apparent to one skilled in the art that various
changes and modifications can be made therein without
departing from the spirit and scope thereof.
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