Benzothiazole derivatives and methods of use

The present invention relates to a novel benzothiazole derivative of the following general formula (I) or its (E) , (Z)isomer, and processes for preparation thereof, ##STR1## in which R.sup.1, R.sup.2 and R.sup.3 independently of one another represent hydrogen, halogen, straight and branched (C.sub.1 -C.sub.8)alkyl, (C.sub.1 -C.sub.8)halogenoalkyl or (C.sub.1 -C.sub.8)alkoxy, PA1 X represents N or CH, PA1 Y represents a group -OR.sup.4, SR.sup.5 or ##STR2## R.sup.4, R.sup.5, R.sup.6 and R.sup.7 independently of one another represent hydrogen, straight and branched (C.sub.1 -C.sub.16)alkyl, (C.sub.3 -C.sub.8)alkenyl, (C.sub.3 -C.sub.8)alkynyl, (C.sub.3 -C.sub.8)cycloalkyl, alkyl substituted with (C.sub.1 -C.sub.6)alkoxy or (C.sub.1 -C.sub.6)halogenoalkyl, or represent a substituted phenyl, phenylacyl or benzyl group wherein the possible substituent on the phenyl, phenylacyl or benzyl group includes halogen, straight and branched (C.sub.1 -C.sub.8)alkyl, (C.sub.1 -C.sub.8)alkoxy, (C.sub.3 -C.sub.8)alkenyl, (C.sub.3 -C.sub.8)alkynyl, phenoxy, nitro, cyano and a five- or six-membered heterocyclic group containing one to four nitrogen atoms. The compound of formula (I) is useful for combating phythopathogenic organisms and fungi present on animal.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention relates to a novel benzothiazole derivative having 
the following general formula (I), 
##STR3## 
in which R.sup.1, R.sup.2 and R.sup.3 independently of one another 
represent hydrogen, halogen, straight and branched (C.sub.1 
-C.sub.8)alkyl, (C.sub.1 -C.sub.8) halogenoalkyl or (C.sub.1 
-C.sub.8)alkoxy, 
X represents N or CH, 
Y represents a group -OR.sup.4, -SR.sup.5 or 
##STR4## 
and R.sup.4, R.sup.5, R.sup.6 and R.sup.7 independently of one another 
represent hydrogen, straight and branched (C.sub.1 -C.sub.16)alkyl, 
(C.sub.3 -C.sub.8) alkenyl, (C.sub.3 -C.sub.8)alkynyl, (C.sub.3 
-C.sub.8)cycloalkyl, alkyl substituted with C.sub.1 -C.sub.6)alkoxy or 
(C.sub.1 -C.sub.6)halogenoalkyl, or represent a substituted phenyl, 
phenylacyl or benzyl group wherein the possible substituent on the phenyl, 
phenylacyl or benzyl group includes halogen, straight and branched 
(C.sub.1 -C.sub.8)alkyl, (C.sub.1 -C.sub.8)alkoxy, (C.sub.3 
-C.sub.8)alkenyl, (C.sub.3 -C.sub.8)alkynyl, phenoxy, nitro, cyano and a 
five- or six-membered heterocyclic group containing one to four nitrogen 
atoms. 
The present invention also relates to a process for preparation of the 
benzothiazole derivative of formula(I), as defined above, and the use of 
the benzothiazole derivative(I) for combating phythopathogenic organisms 
and fungi present on animal. 
2. Background Art 
In 1977, Anke et. al. (J. of Antibiotics 30, 806 (1977)) have reported 
strobillurin A having a potent and broad-spectrum microbicidal activity: 
##STR5## 
Thereafter, many studies for providing numerous compounds analogous to 
strobillurin A have been made. 
In 1987, European Laid-open Patent Publication No. 299694 (Cliff, et. al.) 
has disclosed the compound of formula (III) having a potent microbicidal 
activity against various fungi, particularly against apple scab causative 
organism (Venturia inaequalis), grape downy mildew causative organism 
(Plasmopara viticola) etc. 
##STR6## 
In addition, numerous analogous compounds including the compound of formula 
(IV) disclosed in German Laid-open Patent Publication No. 3,939,258 
(Klausener, 1989) and the compound of formula (V) disclosed in European 
Laid-open Patent Publication No. 480,798 (Benoit), both of which are 
bicyclic compounds similar to the compound (I) according to the present 
invention and have been reported as having a potent microbicidal activity, 
have been developed. 
##STR7## 
On the basis of the above mentioned prior art, the present inventors have 
prepared numerous strobillurin A analogous compounds and studied their 
microbicidal activities. As a result, we have found that a certain 
compound having a benzothiazole derivative as the lipophilic group 
exhibits potent broad-spectrum microbicidal activity against 
phythopathogenic organisms and fungi present on animal. 
Therefore, it is an object of the present invention to provide a novel 
benzothiazole derivative of formula(I), as defined above, which has a 
potent broad-spectrum microbicidal activity. 
It is a further object of this invention to provide a process for preparing 
the novel benzothiazole derivative of formula(I). 
It is a further object of this invention to provide a use of the novel 
benzothiazole derivative of formula(I) for combating phythopathogenic 
organisms and fungi present on animal. 
The foregoing has outlined some of the more pertinent objects of the 
present invention. These objects should be construed to be merely 
illustrative of some of the more pertinent features and applications of 
the invention. Many other beneficial results can be obtained by applying 
the disclosed invention in a different manner or modifying the invention 
within the scope of the disclosure. Accordingly, other objects and a more 
thorough understanding of the invention may be had by referring to the 
disclosure of invention, in addition to the scope of the invention defined 
by the claims. 
DISCLOSURE OF INVENTION 
In one aspect, the present invention relates to a novel benzothiazole 
derivative having the following general formula (I), 
##STR8## 
in which R.sup.1, R.sup.2 and R.sup.3 independently of one another 
represent hydrogen, halogen, straight and branched (C.sub.1 
-C.sub.8)alkyl, (C.sub.1 -C.sub.8) halogenoalkyl or (C.sub.1 
-C.sub.8)alkoxy, 
X represents N or CH, 
Y represents a group -OR.sup.4, -SR.sup.5 or 
##STR9## 
and R.sup.4, R.sup.5, R.sup.6 and R.sup.7 independently of one another 
represent hydrogen, straight and branched (C.sub.1 -C.sub.16)alkyl, 
(C.sub.3 -C.sub.8) alkenyl, (C.sub.3 -C.sub.8)alkynyl, (C.sub.3 
-C.sub.8)cycloalkyl, alkyl substituted with (C.sub.1 -C.sub.6)alkoxy or 
(C.sub.1 -C.sub.6)halogenoalkyl, or represent a substituted phenyl, 
phenylacyl or benzyl group wherein the possible substituent on the phenyl, 
phenylacyl or benzyl group includes halogen, straight and branched 
(C.sub.1 -C.sub.8)alkyl, (C.sub.1 -C.sub.8)alkoxy, (C.sub.3 
-C.sub.8)alkenyl, (C.sub.3 -C.sub.8)alkynyl, phenoxy, nitro, cyano and a 
five- or six-membered heterocyclic group containing one to four nitrogen 
atoms. 
Since the compound of formula (I) contains one carbon-carbon or 
carbon-nitrogen double bond in its structure, the compound of formula (I) 
can exist in the form of two separable geometric isomers, i.e. (E)-isomer 
and (Z)-isomer. The present invention also includes (E)-isomer and 
(Z)-isomer of the compound of formula (I). 
The compound of formula (I) according to the present invention is active 
against various pathogenic organisms, particularly against 
phythopathogenic organism and fungi present on animal. Such pathogenic 
organisms include Erysiphe graminis causative of powdery mildew, 
Plasmopara viticola causative of grape downy mildew, Pyricularia oryzae 
causative of rice blst, Rhizoctonia solani causative of rice sheath 
blight, Botrytis cinerea causative of gray mold, Puccinia recondita 
causative of wheat rust, Venturia inaequalis causative of apple scab, 
etc., and further pathogenic organisms causative of other powdery mildew 
and rust, and also other pathogens such as Deuteromycetes, Ascomycetes, 
Phycomycetes and Basidiomycetes. 
Preferably, in the compound of formula(I) R.sup.1, R.sup.2 and R.sup.3 
independently of one another represent hydrogen, fluoro, chloro, methyl or 
ethyl and R.sup.4, R.sup.5, R.sup.6 and R.sup.7 independently of one 
another represent hydrogen, straight and branched(C.sub.1 -C.sub.6)alkyl, 
(C.sub.3 -C.sub.6)alkenyl or (C.sub.3 -C.sub.6)alkynyl. More preferably, 
in the compound of formula(I) R.sup.4, R.sup.5, R.sup.6 and R.sup.7 
independently of one another represent a phenyl group substituted with 
straight and branched (C.sub.1 -C.sub.6)alkyl, (C.sub.3 -C.sub.6)alkenyl, 
(C.sub.1 -C.sub.6)alkoxy, (C.sub.3 -C.sub.6)alkynyl, phenoxy, halogen, 
pyridinyl, pyrimidinyl, thiazolyl or imidazolyl on 2-, 3- or 4-position. 
In another aspect of the present invention, it has been also found that the 
compound of formula (I) wherein Y is 
##STR10## 
said compound being represented by formula (I'), can be prepared by the 
process characterized in that: 
(a) a compound of formula (VI) is substituted with a halogen and then 
reacted with an alkyl or acyl halide under basic condition to obtain a 
compound of formula (VII), 
(b) the compound of formula (VII) is subjected to a halogen-lithium 
substitution reaction and then reacted with dimethyloxalate to obtain a 
compound of formula (VIII), and 
(c) the compound of formula (VIII) thus obtained is reacted with 
methoxylamine under basic condition or subjected to a Wittig reaction with 
a phosphorus ylide, 
##STR11## 
in which R.sup.1, R.sup.2 and R.sup.3 independently of one another 
represent hydrogen, halogen, straight and branched (C.sub.1 
-C.sub.8)alkyl, (C.sub.1 -C.sub.8)halogenoalkyl or (C.sub.1 
-C.sub.8)alkoxy, 
X represents N or CH, 
R.sup.6 and R.sup.7 independently of one another represent hydrogen, 
straight and branched (C.sub.1 -C.sub.16)alkyl, (C.sub.3 -C.sub.8)alkenyl, 
(C.sub.3 -C.sub.8)alkylnyl, (C.sub.3 -C.sub.8)cycloalkyl, alkyl 
substituted with (C.sub.1 -C.sub.6)alkoxy or (C.sub.1 
-C.sub.6)halogenoalkyl, or represent a substituted phenyl, phenylacyl or 
benzyl group wherein the possible substituent on the phenyl, phenylacyl 
and benzyl group includes halogen, straight and branched (C.sub.1 
-C.sub.8)alkyl, (C.sub.1 -C.sub.8)alkoxy, (C.sub.3 -C.sub.8)alkenyl, 
(C.sub.3 -C.sub.8)alkynyl, phenoxy, nitro, cyano and a five- or 
six-membered heterocyclic group containing one to four nitrogen atoms, and 
Hal represents a halogen atom. 
The compound of formula (VI) which is required as a starting material in 
the above process can be synthesized according to the following two 
different methods which have been described in literature, Organic 
Synthesis, Coll. Vol. 3, 76(1955) and Organic Synthesis, Coll. Vol. 3, 734 
(1955). Specifically, the benzothiazole derivative of formula(VI) can be 
prepared by reacting a substituted aniline with ammonium thiocyanate to 
prepare a thiourea which is then cyclized. Alternatively, the compound of 
formula (VI) can also be prepared by reacting aniline with benzoyl 
thiocyanate to obtain benzoyl thiourea, and then removing a benzoyl group 
with a base (see Organic Synthesis, Coll. Vol. 3, 734(1955)). 
The compound of formula (VII) can be prepared starting from the compound of 
formula (VI), for example, by introducing a bromo substituent into 
4-position of benzothiazole group and then reacting an amino group present 
in 2-position with an alkyl halide or an acyl halide under basic 
condition. This reaction is based on a specific substitution property of 
the compound of formula(VI), that is, when R.sup.2 in the compound of 
formula (VI) is not hydrogen but alkyl (e.g. methyl, ethyl, etc.) or 
halogen (e.g. fluoro, chloro, etc.), then only the 4-position of 
benzothiazole nucleus can be halogenated. 
The compound of formula (VIII) can be synthesized from the compound of 
formula (VII) by replacing halogen with lithium according to a 
halogen-lithium substitution reaction and subsequently reacting with 
dimethyloxalate. Suitable lithium compound which can be used in this 
reaction is n-butyl lithium, sec-butyl lithium, tert-butyl lithium, etc; 
and a suitable solvent which can be used is an ether such as 
tetrahydrofuran, diethylether, dimethoxyethane and the like. 
The desired compound of formula (I') wherein X is N can be synthesized by 
reacting the compound of formula (VIII) with methoxylamine under basic 
condition and, alternatively, the compound of formula (I') wherein X is CH 
is prepared by means of a Wittig reaction with phosphours ylide. 
In this reaction, a suitable base is an organic base such as triethylamine, 
pyridine and the like, and an inorganic base such as sodium hydrogen 
carbonate, sodium carbonate, potassium carbonate and the like; and a 
suitable solvent is a ketone such as acetone, methylethylketone and the 
like, an ether such as tetrahydrofuran, diethylether and the like, a 
halogenated hydrocarbon such as dichloromethane, dichloroethane, 
chloroform and the like, and alcohol such as methanol, ethanol and the 
like etc., with an alcohol being most preferably used. The reaction 
temperature is 0.degree. C. to 120.degree. C. and most preferably 
20.degree. C. to 80.degree. C. 
In the Wittig reaction with phosphonium salt, for example, 
methoxymethyltriphenyl phosphonium chloride can be used as the phosphonium 
salt; a base which can be used is butyl lithium, potassium t-butoxide, 
sodium ethoxide, sodium methoxide, dimsyl (dimethylsulfoxide) anion and 
the like; and a suitable solvent which can be used is an ether such as 
tetrahydrofuran, diethyl ether and the like. 
Further, according to the present invention the compound of formula (I) 
wherein Y is -OR.sup.4, said compound being represented by formula (I"), 
can be prepared by the process characterized in that: 
(a) a compound of formula (VI') is diazotized with sodium nitrite and then 
substituted with a halogen to obtain a compound of formula (IX), 
(b) the compound of formula (IX) is reacted with an alcohol under basic 
condition to obtain a compound of formula (X), and 
(c) the compound of formula (X) is subjected to a halogen-lithuim 
substitution reaction and then reacted with dimethyloxalate to obtain a 
keto ester which is then reacted with methoxylamine under basic condition 
or subjected to a Wittig reaction with phosphorus ylide, 
##STR12## 
in which R.sup.1, R.sup.2 and R.sup.3 independently of one another 
represent hydrogen, halogen, straight or branched (C.sub.1 -C.sub.8)alkyl, 
(C.sub.1 -C.sub.8)halogenoalkyl or (C.sub.1 -C.sub.8)alkoxy, 
X represents N or CH, 
R.sup.4 represents hydrogen, straight and branched (C.sub.1 
-C.sub.16)alkyl, (C.sub.3 -C.sub.8)alkenyl, (C.sub.3 -C.sub.8)alkynyl, 
(C.sub.3 -C.sub.8)cycloalkyl, alkyl substituted with (C.sub.1 
-C.sub.6)alkoxy or (C.sub.1 -C.sub.6)halogenoalkyl, or represents a 
substituted phenyl, phenylacyl or benzyl group wherein the possible 
substituent on the phenyl, phenylacyl and benzyl group includes halogen, 
straight and branched (C.sub.1 -C.sub.8)alkyl, (C.sub.1 -C.sub.8)alkoxy, 
(C.sub.3 -C.sub.8)alkenyl, (C.sub.3 -C.sub.8)alkynyl. phenoxy, nitro, 
cyano and a five- or six-membered heterocyclic group containing one to 
four nitrogen atoms, and 
Hal is a halogen atom. 
The compound of formula (IX) can be prepared from the compound of formula 
(VI') by means of a Sandmeyer reaction (cf. J. Chem. Soc. 87, 1946), in 
which the amine is diazotized with sodium nitrite and then reacted with a 
halogen compound such as bromine. 
The compound of formula (IX) is then reacted with alcohol under basic 
condition to prepare the compound of formula(X). 
In this reaction, a hydride such as potassium hydride, sodium hydride and 
the like, an alkoxide such as sodium methoxide, sodium ethoxide, potassium 
t-butoxide and the like, and inorganic base such as sodium bicarbonate, 
sodium carbonate, potassium carbonate and the like, etc., can be used as a 
base; an ether such as tetrahydrofuran, diethylether, etc., a halogenated 
hydrocarbon such as dichloromethane, dichloroethane, etc., a nitrile such 
as acetonitrile, etc., a polar solvent such as dimethylformamide, 
dimethylsulfoxide, dimethylacetamide, etc., and the like solvents can be 
used as a suitable solvent. The reaction can be carried out at the 
temperature between 0.degree. C. and 120.degree. C. and most preferably 
between 20.degree. C. and 80.degree. C. 
The preparation of the compound of formula (I") from the compound of 
formula (X) can be practiced in the same manner as outlined in the steps 
(b) and (c) for preparation of the compound of formula (I'). 
The compound of formula (I) wherein Y represents -SR.sup.5, said compound 
being represented by formula (I'"), can be prepared from a compound of 
formula (XII) following the same synthetic method as outlined in the steps 
(b) and (c) for preparation of the compound of formula (I'), 
##STR13## 
in which R.sup.1, R.sup.2 and R.sup.3 independently of one another 
represent hydrogen, halogen, straight or branched (C.sub.1 -C.sub.8)alkyl, 
(C.sub.1 -C.sub.8)halogenoalkyl or (C.sub.1 -C.sub.8)alkoxy, 
X represents N or CH, 
R.sup.5 represents hydrogen, straight and branched (C.sub.1 
-C.sub.16)alkyl, (C.sub.3 -C.sub.8)alkenyl, (C.sub.3 -C.sub.8)alkynyl, 
(C.sub.3 -C.sub.8)cycloalkyl, alkyl substituted with (C.sub.1 
-C.sub.6)alkoxy, or (C.sub.1 -C.sub.6)halogenoalkyl, or represents a 
substituted phenyl, phenylacyl or benzyl group wherein the possible 
substituent on the phenyl, phenylacyl or benzyl group includes halogen, 
straight and branched (C.sub.1 -C.sub.8)alkyl, (C.sub.1 -C.sub.8)alkoxy, 
(C.sub.3 -C.sub.8)alkenyl, (C.sub.3 -C.sub.8)alkynyl, phenoxy, nitro, 
cyano and a five- or six-membered heterocyclic group containing one to 
four nitrogen atoms, and 
Hal is a halogen atom. 
The compound of formula (XII) which is required as starting compound for 
preparation of the compound of formula (I'") can be obtained following 
different two methods. In the first variant, the compound of formula (IX) 
as defined above is reacted with sodium hydrogensulfide to obtain a 
compound of formula (XI) which is then reacted with a halogenide compound 
under basic condition to obtain the compound of formula (XII). 
Alternatively, according to the second variant the compound of formula 
(XII) can be prepared by reacting a halogenide compound with sodium 
hydrogen-sulfide to obtain a thiol which is then reacted with the compound 
of formula (IX) as defined above under basic condition. 
##STR14## 
In the above formula (XI), R.sup.1, R.sup.2, R.sup.3 and Hal are defined as 
previously described. In said two variants for preparing the compound of 
formula (XII), the reaction conditions are substantially identical to 
those previously described in the procedure for preparation of the 
compound of formula(X). 
In preparing the compound of formula (XI), a suitable solvent which can be 
used is an ether such as tetrahydrofuran or diethyl ether, a halogenated 
hydrocarbon such as dichloromethane or dichloroethane, a nitrile such as 
acetonitrile, an alcohol such as methanol, ethanol; propanol, etc., a 
polar solvent such as dimethylformamide, dimethylsulfoxide, 
dimethylacetamide, etc., and the like solvents. The reaction can be 
practiced at the temperature between 0.degree. C. and 120.degree. C. and 
most preferably between 20.degree. C. and 80.degree. C. 
In the first variant, the compound of formula (XII) can be obtained by 
reacting the compound of formula (XI) with a halogenide compound under 
basic condition. For this purpose, a suitable base which can be used is a 
hydride such as potassium hydride, sodium hydride, etc., an alkoxide such 
as sodium methoxide, sodium ethoxide, potassium dibutoxide, etc., an 
inorganic base such as sodium bicarbonate, sodium carbonate, potassium 
carbonate, etc., and the like bases ; and a suitable solvent which can be 
used is an ether such as tetrahydrofuran, diethylether, etc., a 
halogenated hydrocarbon such as dichloromethane, dichloroethane, etc., a 
nitrile such as acetonitrile, etc., a polar solvent such as 
dimethylformamide, dimethylsulfoxide, dimethylacetamide, etc., and the 
like solvents. The reaction can be carried out at the temperature between 
0.degree. C. and 150.degree. C. and most preferably between 20.degree. C. 
and 80.degree. C.

The present invention will be more specifically illustrated by the 
following examples but it should be understood that the present invention 
is not limited to these examples in any manner. 
Preparation 1 
Synthesis of 4-methylphenylthiourea 
10.7 g of 4-toluidine was added dropwise to 27% aqueous sulfuric acid 
solution which contains 5.4 g of sulfuric acid. After the reaction mixture 
was heated to 75.degree. C., 8.4 g of ammonium thiocyanate in a solid 
state was slowly added thereto. Upon complete addition, the reaction 
mixture was stirred for 20 hours at 80.degree. C. to 90.degree. C. After 
adding toluene, the whole mixture was refluxed for one hour, cooled to 
room temperature and then adjusted to pH 7.5 to 8 by slowly adding ammonia 
water. The resulting white solid was filtered, washed once with each of 
water and toluene and then dried under reduced pressure to obtain the 
title compound as a white solid (Yield: 78.5%). 
.sup.1 H NMR(CDCl.sub.3): 2.34(3H, s), 6.2(2H, br s, --NH.sub.2), 7.15(4H, 
q), 7.98(1H, br s, --NH--) 
Preparation 2 
Synthesis of 2-amino-6-methylbenzothiazole 
15 ml of concentrated sulfuric acid was added to 8.3 g of the compound 
prepared in Preparation 1 and the temperature of the mixture was raised to 
80.degree. C. After 0.5 g of 48% hydrobromic acid was slowly added, the 
reaction mixture was stirred for 2 hours at 80.degree. C. and then cooled 
to room temperature. The reaction solution was slowly introduced into cold 
water and then adjusted to pH9 to 10 by adding ammonia water. The whole 
mixture was stirred for one hour while heating at 70.degree. C., and then 
cooled to room temperature. The mixture was extracted two times with 
dichloroethane and the combined extract was dried with anhydrous sodium 
sulfate and evaporated to obtain the title compound as a yellow solid 
(Yield: 84% ). 
.sup.1 H NMR(CDCl.sub.3): 2.40(3H, s), 5.5(2H, br s, --NH.sub.2), 7.12(1H, 
d), 7.41(2H, t) 
EXAMPLE 1 
Synthesis of 2-amino-4-bromo-6-methylbenzothiazole 
16.4 g of 2-amino-6-methylbenzothiazole was dissolved in 500 ml of 
chloroform. To this solution was added dropwise 16.0 g of bromine 
dissolved in 10 ml of chloroform at room temperature. The reaction mixture 
was stirred for 2 hours and then washed once with 10% aqueous sodium 
hydroxide solution and water, respectively. The organic layer was 
separated, dried with anhydrous sodium sulfate and then evaporated to 
obtain the title compound in the yield of 92%. 
.sup.1 H NMR(CDCl.sub.3): 2.41(3H, s), 5.94(2H, br s, --NH2), 7.32(2H, s) 
EXAMPLE 2 
Synthesis of 2-(N,N'-dimethyl)amino-4-bromo-6-methylbenzothiazole 
2.43 g of the compound obtained in Example 1, 0.82 g of sodium hydroxide, 
2.88 g of methyl iodide and 30 ml of acetonitrile were introduced into a 
reaction vessel and the reaction mixture was refluxed for one hour. 
Acetonitrile was then evaporated under reduced pressure and the residue 
was extracted with diethylether and water. The organic layer was 
separated, dried with anhydrous sodium sulfate, evaporated and then 
subjected to column chromatography to separate the desired product as a 
yellow solid in the yield of 66%. 
.sup.1 H NMR(CDCl.sub.3):2.35(3H, s), 3.21(6H, s), 7.30(2H, s) 
EXAMPLE 3 
Synthesis of methyl[2-(N,N'-dimethyl)amino-6-methylbenzothiazol-4-yl]keto 
acetate 
A solution of 0.55 g of 2-(N,N'-dimethyl)amino-6-methylbenzothiazole in 5 
ml of diethylether was slowly added dropwise to 10 ml of diethylether 
solution of n-butyl lithium (1.26 ml as 2.5M hexane solution) at 
-78.degree. C. and the mixture was stirred for 30 minutes. 5 ml of 
diethylether solution containing 0.22 g of dimethyloxalate was slowly 
added dropwise thereto and the temperature was raised gradually to room 
temperature. The whole mixture was washed with ammonium chloride solution 
and the separated organic layer was dried with anhydrous sodium sulfate 
and then evaporated to obtain the title compound as a yellow liquid in the 
yield of 77%. 
.sup.1 H NMR(CDCl.sub.3):2.41(3H, s), 3.20(6H, s), 3.96(3H, s), 7.63(1H, 
s), 7.74(1H, s) 
EXAMPLE 4 
Synthesis of (E,Z)-methyl 
2-[2-(N,N'-dimethyl)amino-6-methylbenzothiazol-4-yl]-2-methoxyiminoacetate 
##STR15## 
0.28 g of the compound prepared in Example 3, 0.09 g of methoxylamine 
hydrochloride, 0.08 g of potassium carbonate and 1 ml of ethanol were 
introduced into a reaction vessel and the mixture was refluxed for one 
hour. After cooling, ethanol was evaporated under reduced pressure and the 
residue was extracted with ethyl acetate and water. The ethyl acetate 
layer was separated, dried with anhydrous sodium sulfate, evaporated and 
then subjected to column chromatography to obtain E-isomer and Z-isomer of 
the title compound in the yield of 15% and 68%, respectively. 
E-isomer 
.sup.1 H NMR (CDCl.sub.3):2.39(3H, s), 3.15(6H, s), 3.92(3H, s), 4.05(3H, 
s), 7.43(1H, s), 7.57(1H, s) 
Z-isomer 
.sup.1 H NMR(CDCl.sub.3): 2.40(3H, s), 3.19(6H, s), 3.88(3H, s), 4.10(3H, 
s), 7.42(1H, s), 7.61(1H, s) 
EXAMPLE 5 
Synthesis of (E,Z)-methyl 
2-[2-(N,N'-dimethyl)amino-6-methylbenzothiazol-4-yl]-3-methoxypropenoate 
##STR16## 
To 30 ml of tetrahydrofuran solution containing 3.4 g of 
methoxymethyltriphenylphosphonium chloride was added 0.9 g of potassium 
t-butoxide at room temperature and the mixture was stirred for 30 minutes. 
10 ml of tetrahydrofuran solution containing 1.4 g of methyl 
[2-(N,N'-dimethyl)amino-6-methylbenzothiazol-4-yl]keto acetate was added 
dropwise thereto and then the mixture was refluxed for 2 hours. After 
cooling, tetrahydrofuran was evaporated under reduced pressure and the 
residue was extracted with ethyl acetate and water. The ethyl acetate 
layer was separated, dried with anhydrous sodium sulfate, evaporated and 
then subjected to column chromatography to obtain E-isomer and Z-isomer of 
the title compound in the yield of 12% and 58%, respectively. 
E-isomer 
.sup.1 H NMR(CDCl.sub.3): 2.38(3H, s), 3.17(6H, s), 3.71(3H, s), 3.89(3H, 
s), 6.88(1H, s), 6.94(1H, s), 7.30(1H, s) 
Z-isomer 
.sup.1 H NMR(CDCl.sub.3): 2.37(3H, s), 3.15(6H, s), 3.68(3H, s), 3.82(3H, 
s), 7.05(1H, s), 7.29(1H, s), 7.52(1H, s) 
EXAMPLE 6 
Synthesis of 2,4-dibromo-6-methylbenzothiazole 
4.7 g of 2-amino-4-bromo-6-methylbenzothiazole, 14 ml of 48% bromic acid 
solution and 10 g of bromine were introduced into a reaction vessel while 
keeping the temperature at 10.degree. C. To this mixture was slowly added 
dropwise 10 ml of aqueous solution containing 3.5 g of sodium nitrite at 
0.degree. C. and the whole mixture was stirred for 2 hours. Then, 15 ml of 
40% sodium hydroxide solution was slowly added dropwise while keeping the 
temperature below 20.degree. C. and the reaction mixture was stirred for 
one hour and extracted with diethyl ether. The extract was dried with 
anhydrous sodium sulfate and evaporated to obtain the title compound in 
the form of transparent liquid (Yield: 91%). 
.sup.1 H NMR(CDCl.sub.3): 7.29(2H, s), 2.44(3H, s) 
EXAMPLE 7 
Synthesis of 4-bromo-2-allylmercapto-6-methylbenzothiazole 
1.20 g of allyl bromide, 0.7 g of sodium hydrogensulfide and 10 ml of 
dichloromethane were introduced into a reaction vessel and then the 
mixture was refluxed for one hour and washed with water under cooling. The 
dichloromethane layer was separated, dried with anhydrous sodium sulfate 
and distilled under reduced pressure to remove dichloromethane to obtain 
1.0 g of allyl mercaptan. 
1.0 g of allyl mercaptan prepared above, 3.1 g of 
2,4-dibromo-6-methyl-benzothiazole, 0.4 g of sodium hydroxide, 10 ml of 
tetrahydrofuran and 10 ml of water were mixed together and the obtained 
mixture was stirred for 3 hours at room temperature and then extracted 
with ethyl acetate. The extract was dried with anhydrous sodium sulfate 
and evaporated to obtain the title compound in a liquid state (Yield: 
92.5%). 
.sup.1 H NMR(CDCl.sub.3): 2.41(3H, s), 4.00(2H, d), 5.20(1H, d), 5.42(1H, 
d), 6.01(1H, m), 7.44(2H, d) 
EXAMPLE 8 
Synthesis of 4-bromo-2-mercapto-6-methylbenzothiazole 
3.1 g of 2,4-dibromo-6-methylbenzothiazole, 1.0 g of sodium hydrogensulfide 
and 30 ml of methanol were mixed and the obtained mixture was refluxed for 
one hour, cooled to room temperature and then distilled under reduced 
pressure to remove methanol. The residue was extracted with 
dichloromethane by adding water and dichloromethane. The dichloromethane 
layer was dried with anhydrous sodium sulfate and evaporated to obtain the 
title compound in a solid state (Yield: 84%). 
.sup.1 H NMR(CDCl.sub.3): 2.41(3H, s), 7.18(1H, s), 7.27(1H, s) 
EXAMPLE 9 
Synthesis of 4-bromo-2-n-butylmercapto-6-methylbenzothiazole 
To 10 ml of tetrahydrofuran solution containing 0.52 g of 
4-bromo-2-mercapto-6-methylbenzothiazole was added 50 mg of sodium hydride 
at 0.degree. C. After adding 0.28 g of n-bromobutane, the whole mixture 
was refluxed for 2 hours, distilled under reduced pressure to remove 
tetrahydrofuran and then extracted with ethyl acetate by adding water and 
ethyl acetate. The ethyl acetate layer was dried with anhydrous sodium 
sulfate and evaporated under reduced pressure to obtain the title compound 
in a yellow liquid state (Yield: 66%). 
.sup.1 H NMR(CDCl.sub.3): 0.95(3H, t), 1.51(2H, m), 1.82(2H, m), 2.41(3H, 
s), 3.33(2H, t), 7.44(2H, d) 
EXAMPLE 10 
Synthesis of methyl (2-n-butylmercapto-6-methylbenzothiazol-4-yl)keto 
acetate 
0.8 ml of t-butyl lithium solution was slowly added dropwise at -78.degree. 
C. to 10 ml of diethyl ether solution containing 0.40 g of 
4-bromo-2-n-butyl-mercapto-6-methylbenzothiazole, and the mixture was 
stirred for 30 minutes. To this mixture was added dropwise 10 ml of 
diethyl ether solution of dimethyloxalate (0.15 g) at -78.degree. C. Then, 
the reaction mixture was stirred for one hour and the temperature was 
raised to room temperature. The reaction solution was washed with ammonium 
chloride solution and the organic layer was separated, dried with 
anhydrous sodium sulfate, evaporated and then subjected to column 
chromatography to obtain the title compound in the yield of 46%. 
.sup.1 H NMR(CDCl.sub.3): 0.97(3H, t), 1.50(2H, m), 1.79(2H, m), 2.50(3H, 
s), 3.33(2H, t), 3.98(3H, s), 7.81(2H, d) 
EXAMPLE 11 
Synthesis of 
(E,Z)-methyl-2-(2-n-butylmercapto-6-methylbenzothiazol-4-yl)-2-methoxyimin 
o acetate 
##STR17## 
0.5 g of methyl (2-n-butylmercapto-6-methylbenzothiazol-4-yl) keto acetate 
was mixed with 0.13 g of methoxylamine hydrochloride, 0.2 g of potassium 
carbonate and 10 ml of ethanol, and then the mixture was refluxed for one 
hour and distilled under reduced pressure to remove ethanol. The residue 
was extracted with ethyl acetate by adding water and ethyl acetate. The 
ethyl acetate layer was dried with anhydrous sodium sulfate, evaporated 
and then subjected to column chromatography to obtain E-isomer and 
Z-isomer of the title compound in the yield of 28% and 63%, respectively. 
E-isomer 
.sup.1 H NMR(CDCl.sub.3): 0.95(3H, t), 1.48(2H, m), 1.78(2H, m), 2.47(3H, 
s), 3.29(2H, t), 3.80(3H, s), 4.09(3H, s), 7.24(1H, s), 7.59(1H, s) 
Z-isomer 
.sup.1 H NMR(CDCl.sub.3): 0.96(3H, t), 1.49(2H, m), 1.76(2H, m), 2.45(3H, 
s), 3.31(2H, t), 3.90(3H, s), 4.09(3H, s), 7.58(1H, s), 7.68(1H, s) 
Typical compounds of formula (I) according to the present invention are 
listed in the following Table 1 and Table 2. 
TABLE 1 
__________________________________________________________________________ 
##STR18## 
Compound 
No. R.sup.1 
R.sup.2 
R.sup.3 
X R.sup.6 R.sup.7 .sup.1 H NMR(CDCl.sub.3) 
Isomer. 
__________________________________________________________________________ 
1 H CH.sub.3 
H N CH.sub.3 CH.sub.3 see Example 4 E 
2 H CH.sub.3 
H N CH.sub.3 CH.sub.3 see Example 4 Z 
3 H CH.sub.3 
H C CH.sub.3 CH.sub.3 see Example 5 E 
4 H CH.sub.3 
H C CH.sub.3 CH.sub.3 see Example 5 Z 
5 H CH.sub.3 
H C 
##STR19## 
##STR20## 
2.37(3H, s), 3.71(3H, s), 3.90 (3H, 
s), 4.10(4H, d), 5.22(4H, 2d), 
5.82(2H, m), 6.88(1H, s), 6.94(1H, s), 
7.30(1H, s) E 
6 H CH.sub.3 
H C 
##STR21## 
##STR22## 
2.36 (3H, s), 3.66 (3H, s), 3.84 (3H, 
s), 4.08(4H, d), 5.22(4H, 2d), 
5.82(2H, m), 7.01(1H, s), 7.30 (1H, 
s), 7.52(1H, s) Z 
7 H CH.sub.3 
H N 
##STR23## 
##STR24## 
0.96(6H, m), 1.50(4H, m), 1.71 (4H, 
d), 2.35(3H, s), 2.93(2H, t), 3.30(2H, 
m), 3.69(3H, s), 3.84 (3H, s), 
6.82(1H, s), 6.95(1H, s), 7.29(1H, 
E) 
8 H CH.sub.3 
H N 
##STR25## 
##STR26## Z 
9 H CH.sub.3 
H N 
##STR27## 
H 2.34(3H, s), 3.89(3H, s), 4.06 (3H, 
s), 4.81(2H, s), 5.50(1H, brs), 
7.30(6H, m), 7.40(1H, 
E) 
10 H CH.sub.3 
H N 
##STR28## 
H Z 
11 H F H N 
##STR29## 
##STR30## 
3.84(3H, s), 4.04(3H, s), 4.08 (4H, 
d), 5.25(4H, 2d), 5.80(2H, m) 7.20(1H, 
2d), 7.32(1H, 2d) 
E 
12 H F H N 
##STR31## 
##STR32## 
3.89(3H, s), 4.04(3H, s), 4.08 (4H, 
2d), 5.25(4H, 2d), 5.82(2H, m), 
7.33(1H, 2d), 7.50(1H, 
Zd) 
13 F F F N CH.sub.3 CH.sub.3 3.18(6H, s), 3.95(3H, s), 
E.09 
(3H, s) 
14 F F F N CH.sub.3 CH.sub.3 3.19(6H, s), 3.97(3H, s), 
Z.09 
(3H, s) 
15 H Cl H C CH.sub.3 CH.sub.3 3.19(6H, s), 3.72(3H, s), 
E.92 
(3H, s), 6.86(1H, s), 6.97(1H, s), 
7.35(1H, s) 
16 H Cl H C CH.sub.3 CH.sub.3 3.19(6H, s), 3.70(3H, s), 
Z.89 
(3H, s), 7.01(1H, s), 7.30(1H, s), 
7.50(1H, s) 
17 H CH.sub.3 
H N 
##STR33## 
H E 
18 H CH.sub.3 
H N 
##STR34## 
H Z 
19 H CH.sub.3 
H N 
##STR35## 2.41(3H, s), 3.65(4H, t), 3.80 (4H, 
t), 3.89(3H, s), 4.07(3H, s), 7.46(1H, 
s), 7.58(1H, s) Z 
__________________________________________________________________________ 
TABLE 2 
__________________________________________________________________________ 
##STR36## 
Compound 
No. R.sub.1 
R.sub.2 
R.sub.3 
X Y .sup.1 H NMR(CDCl.sub.3) 
Isomer. 
__________________________________________________________________________ 
20 H CH.sub.3 
H N OCH.sub.3 2.48(3H, s), 3.86(3H, s), 4.08(3H, 
E), 
4.11(3H, s), 7.24(1H, s), 7.48(3H, s) 
21 H CH.sub.3 
H N OCH.sub.3 2.43(3H, s), 3.93(3H, s), 4.05(3H, 
Z), 
4.12(3H, s), 7.50(1H, s), 7.66(1H, s) 
22 H CH.sub.3 
H N OCH.sub.2 CH.sub.3 
1.19(3H, t), 2.44(3H, s), 3.87(3H, 
E), 
4.08(3H, s), 4.40(2H, q), 7.25(1H, s), 
7.49(1H, s) 
23 H CH.sub. 3 
H N OCH.sub.2 CH.sub.3 
1.20(3H, t), 2.44(3H, s), 3.90(3H, 
Z), 
4.08(3H, s), 4.41(2H, q), 7.49(1H, s), 
7.66(1H, s) 
24 H CH.sub.3 
H N 
##STR37## 1.02(3H, t), 1.82(2H, m), 2.43(3H, s), 
3.85(3H, s), 4.08(3H, s), 4.43(2H, t), 
7.28(1H, s), 7.48(1H, s) 
E 
25 H CH.sub.3 
H N 
##STR38## 1.03(3H, t), 1.83(2H, m), 2.41(3H, s), 
3.91(3H, s), 4.06(3H, s), 4.43(2H, t), 
7.48(1H, s), 7.64(1H, s) 
Z 
26 H CH.sub.3 
H N 
##STR39## 2.43(3H, s), 3.83(3H, s), 4.08(3H, s), 
4.95(2H, d), 5.25-5.48(2H, q), 6.04 (1H, 
m), 7.23(1H, s), 7.47(1H, 
E) 
27 H CH.sub.3 
H N 
##STR40## 2.43(3H, s), 3.90(3H, s), 4.09(3H, s), 
4.98(2H, d), 5.31-5.50(2H, q), 6.10 (1H, 
m), 7.49(1H, s), 7.64(1H, 
Z) 
28 H CH.sub.3 
H N 
##STR41## 1.89(3H, s), 2.43(3H, s), 3.8H(3H, s), 
4.08(3H, s), 5.04(2H, q), 7.24(1H, s), 
7.48(1H, s) E 
29 H CH.sub.3 
H N 
##STR42## 1.88(3H, s), 2.43(3H, s), 3.92(3H, s), 
4.08(3H, s), 5.05(2H, q), 7.48(1H, s), 
7.65(1H, s) Z 
30 H CH.sub.3 
H N O(CH.sub.2).sub.11 CH.sub.3 
0.89(3H, t), 1.20-1.50(18H, m), 
E.81 
(2H, m), 2.42(3H, s), 3.85(3H, s), 
4.08(3H, s), 4.46(2H, t), 7.22(1H, s), 
7.48(1H, s) 
31 H CH.sub.3 
H N O(CH.sub.2).sub.11 CH.sub.3 
0.89(3H, t), 1.20-1.50(18H, m), 
Z.81 
(2H, m), 2.42(3H, s), 3.91(3H, s), 
4.08(3H, s), 4.48(2H, t), 7.48(1H, s), 
7.64(1H, s) 
32 H CH.sub.3 
H N 
##STR43## 2.46(3H, s), 3.78(3H, s), 4.07(3H, s), 
7.25-7.53(7H, m) E 
33 H CH.sub.3 
H N 
##STR44## 2.47(3H, s), 3.40(3H, s), 4.06(3H, s), 
7.25-7.73(7H, m) Z 
34 H CH.sub.3 
H N 
##STR45## 2.46(3H, s), 3.87(3H, s), 4.04(3H, s), 
7.28(1H, s), 7.29-7.41(4H, q), 7.52 (1H, 
s) E 
35 H CH.sub.3 
H N 
##STR46## 2.47(3H, s), 3.42(3H, s), 4.03(3H, s), 
7.38(4H, q), 7.52(1H, s)7.71(1H, 
Z) 
36 H CH.sub.3 
H N 
##STR47## 2.24(3H, s), 2.45(3H, s), 3.74(3H, s), 
4.04(3H, s), 7.25(6H, m), 7.50(1H, 
E) 
37 H CH.sub.3 
H N 
##STR48## 2.25(3H, s), 2.42(3H, s), 3.30(3H, s), 
4.02(3H, s), 7.25(5H, m), 7.51(1H, s), 
7.70(1H, s) Z 
38 H CH.sub.3 
H N 
##STR49## 2.24(6H, s), 2.46(3H, s), 3.72(3H, s), 
4.05(3H, s), 7.10(3H, m), 7.25(1H, s), 
7.49(1H, s) E 
39 H CH.sub.3 
H N 
##STR50## 2.24(6H, s), 2.43(3H, s), 3.22(3H, s), 
4.01(3H, s), 7.06(3H, m), 7.50(1H, s), 
7.68(1H, s) Z 
40 H CH.sub.3 
H N 
##STR51## 1.36(6H, d), 2.43(3H, s), 2.92(1H, m), 
3.79(3H, s), 4.06(3H, s), 7.10-7.38 (5H, 
m), 7.50(1H, s) E 
41 H CH.sub.3 
H N 
##STR52## 1.29(6H, d), 2.43(3H, s), 3.95(1H, m), 
3.35(3H, s), 4.04(3H, s), 7.13(3H, m), 
7.32(1H, m), 7.51(1H, s), 7.72(1H, 
Z) 
42 H CH.sub.3 
H N 
##STR53## 2.46(3H, s), 3.75(3H, s), 3.80(3H, s), 
4.06(3H, s), 6.78-6.97(3H, m), 7.27 (2H, 
m), 7.52(1H, s) E 
43 H CH.sub.3 
H N 
##STR54## 2.44(3H, s), 3.42(3H, s), 3.83(3H, s), 
4.04(3H, s), 6.78-6.96(3H, m), 7.31 (1H, 
t), 7.51(1H, s), 7.73(1H, 
Z) 
44 H CH.sub.3 
H N 
##STR55## 2.45(3H, s), 3.79(3H, s), 4.08(3H, s), 
4.53(2H, d), 5.25-5.45(2H, q), 6.02 (1H, 
m), 6.78-6.96(3H, m), 7.26(2H, m), 
7.51(1H, s) E 
45 H CH.sub.3 
H N 
##STR56## 2.42(3H, s), 3.45(3H, s), 4.06(3H, s), 
4.53(2H, d), 5.20-5.44(2H, q), 6.02 (1H, 
m), 6.77-6.97(3H, m), 7.30(1H, t), 
7.52(1H, s), 7.72(1H, s) 
Z 
46 H CH.sub.3 
H N 
##STR57## 1.32(6H, d), 2.45(3H, s), 3.80(3H, s), 
4.07(3H, s), 4.51(1H, m), 6.76-6.96 (3H, 
m), 7.27(2H, m), 7.51(1H, 
E) 
47 H CH.sub.3 
H N 
##STR58## 1.32(6H, d), 2.45(3H, s), 3.49(3H, s), 
4.06(3H, s), 4.54(1H, m), 6.76-6.96 (3H, 
m), 7.30(1H, t), 7.52(1H, s), 7.72 (1H, 
s) Z 
48 H CH.sub.3 
H N 
##STR59## 2.43(3H, s), 3.79(3H, s), 4.08(3H, s) 
6.85-7.19(6H, m), 7.26-7.45 (4H, m), 
7.50(1H, s) E 
49 H CH.sub.3 
H N 
##STR60## 2.44(3H, s), 3.47(3H, s) 4.06(3H, s), 
6.84-7.20(6H, m) 7.25-7.45(3H, m), 
7.51(1H, s), 7.71(1H, s) 
Z 
50 H CH.sub.3 
H N 
##STR61## 2.45(3H, s), 3.80(3H, s), 4.07(3H, s), 
6.88(4H, s), 7.28(2H, m), 7.81(1H, s), 
8.65(2H, d) E 
51 H CH.sub.3 
H N 
##STR62## 2.45(3H, s), 3.45(3H, s), 4.06(3H, s), 
6.84(4H, m), 7.30(1H, t), 7.51(1H, s), 
7.70(1H, s), 8.66(2H, d) 
Z 
52 H CH.sub.3 
H N SCH.sub.3 2.46(3H, s), 2.72(3H, s), 3.84(3H, 
E), 
4.09(3H, s), 7.26(1H, s), 7.59(1H, s), 
53 H CH.sub.3 
H N SCH.sub.3 2.46(3H, s), 2.75(3H, s), 3.92(3H, 
Z), 
4.10(3H, s), 7.24(1H, s), 7.60(1H, s) 
54 H CH.sub.3 
H N 
##STR63## 2.47(3H, s), 3.84(3H, s), 3.92(2H, d), 
4.08(3H, s), 5.15(1H, d), 5.32(1H, d), 
6.00(1H, m), 7.24(1H, s), 7.60(1H, 
E) 
55 H CH.sub.3 
H N 
##STR64## 2.47(3H, s), 3.91(3H, s), 3.93(2H, d), 
4.09(3H, s), 5.17(1H, d), 5.37(1H, d) 
6.00(1H, m), 7.60(1H, s), 7.70(1H, 
Z) 
56 H CH.sub.3 
H N 
##STR65## 1.3(3H, t), 2.45(3H, s), 3.27(2H, q), 
3.85(3H, s), 4.09(3H, s), 7.24(1H, s), 
7.58(1H, s) E 
57 H CH.sub.3 
H N 
##STR66## 1.3(3H, t), 2.45(3H, s), 3.27(2H, q), 
3.88(3H, s), 4.09(3H, s), 7.58(1H, s), 
7.68(1H, s) Z 
58 H CH.sub.3 
H N 
##STR67## see Example 11 E 
59 H CH.sub.3 
H N 
##STR68## see Example 11 Z 
60 H CH.sub.3 
H N 
##STR69## 0.90(3H, t), 1.22-1.50(6H, m), 1.78 (2H, 
m), 2.46(3H, s), 3.28(2H, t), 3.85 (3H, 
s), 4.08(3H, s), 7.24(1H, s), 7.58 (1H, 
s) E 
61 H CH.sub.3 
H N 
##STR70## 0.89(3H, t), 1.23-1.52(6H, m), 1.77 (2H, 
m), 2.46(3H, s), 3.30(2H, t), 3.91(3H, 
s), 4.08(3H, s), 7.59(1H, s), 7.69(1H, 
Z) 
62 H CH.sub.3 
H N 
##STR71## 1.45(6H, d), 2.46(3H, s), 3.84(3H, s), 
4.07(3H, s), 4.08(1H, m), 7.24(1H, s), 
7.59(1H, s) E 
63 H CH.sub.3 
H N 
##STR72## 1.49(6H, d), 2.44(3H, s), 3.89(3H, s), 
4.07(1H, m), 4.09(3H, s), 7.60(1H, s), 
7.68(1H, s) Z 
64 H CH.sub.3 
H N 
##STR73## 1.10(6H, d), 2.11(1H, m), 2.42(3H, s), 
3.21(2H, d), 3.87(3H, s), 4.08(3H, s), 
7.25(1H, s), 7.59(1H, s) 
E 
65 H CH.sub.3 
H N 
##STR74## 1.70(3H, d), 2.46(3H, s), 3.87(3H, s), 
4.00(2H, d), 4.10(3H, s), 5.55-5.90 (2H, 
m), 7.25(1H, s), 2.60(1H, 
E) 
66 H CH.sub.3 
H N 
##STR75## 1.72(3H, d), 2.46(3H, s), 3.89(3H, s), 
3.90(2H, d), 4.10(3H, s), 5.55-5.90 (2H, 
m), 7.60(1H, s), 7.70(1H, 
Z) 
67 H CH.sub.3 
H N 
##STR76## 1.25-1.65(6H, m), 1.79(2H, m), 2.13 (2H, 
m), 2.45(3H, s), 3.82(3H, s), 3.85 (1H, 
m), 4.08(3H, s), 7.24(1H, s), 7.57 (1H, 
s) E 
68 H CH.sub.3 
H N 
##STR77## 1.20-1.65(6H, m), 1.80(2H, m), 2.15 (2H, 
m), 2.44(3H, s), 3.89(8H, s), 3.90 (1H, 
m), 4.08(3H, s), 7.59(1H, s), 7.66 (1H, 
s) Z 
69 H CH.sub.3 
H N 
##STR78## 2.46(3H, s), 3.84(3H, s), 4.07(3H, s) 
4.53(2H, s), 7.28(5H, m), 7.26(1H, s), 
7.59(1H, s) E 
70 H CH.sub.3 
H N 
##STR79## 2.50(3H, s), 3.85(3H, s), 4.10(3H, s) 
4.59(2H, s), 7.35(5H, m), 7.60(1H, s), 
7.71(1H, s) Z 
71 H F H N 
##STR80## 3.86(3H, s), 4.10(3H, s), 4.55(2H, s), 
7.19(1H, d), 7.30(5H, m), 7.36(1H, 
E) 
72 H F H N 
##STR81## 3.88(3H, s), 4.06(3H, s), 4.59(2H, s), 
7.39(6H, m), 7.50(1H, d) 
Z 
73 F F F N 
##STR82## 3.88(3H, s), 4.11(3H, s), 7.33(5H, 
E) 
74 H CH.sub.3 
H N 
##STR83## 2.44(3H, s), 3.86(3H, s), 4.08(3H, s), 
7.22(1H, s), 7.47(1H, s), 7.46-7.71 (5H, 
m) E 
75 H CH.sub.3 
H N 
##STR84## 2.44(3H, s), 3.85(3H, s), 4.09(3H, s), 
7.45-7.72(7H, m) Z 
__________________________________________________________________________ 
Biological examples 
The microbicidal effect of the active compound according to the present 
invention was examined using the following phythopathogenic organisms. 
Pyricularia oryzae (PO): rice blast (RCB) 
Rhizoctonia solani (RS): rice sheath blight (RSB) 
Botrytis cinerea (BC): cucumber gray mold (CGM) 
Phytophthora infestans (PI): tomato late blight (TLB) 
Puccinia recondita (PR): wheat leaf rust (WLR) 
Erysiphe graminis (EG): barley powdery mildew (BPM) 
To determine the preventive effect of the compound according to the present 
invention against phythopathogenic organisms, the active compound was 
dissolved in 10% acetone solution and then Tween-20 was added in the 
concentration of 250 ppm to prepare a suitable test preparation of active 
compound. Host plants in a certain size were sprayed with the test 
preparation in an amount of 50 ml per each plant on their leaves. The 
plants were remained for 24 hours at room temperature to volatilize the 
solvent and water and then were inoculated with phythopathogenic organisms 
as prepared below. All tests were repeated two times. 
Test 1 
Fungicidal effect on rice blast causative organism 
Rice blast causative organism(Pyricularia oryzae) was inoculated on rice 
bran-agar medium (Rice Ploish 20 g, Dextrose 10 g, Agar 15 g, D.W. 1 L) 
and incubated in an incubator at 26.degree..+-.2.degree. C. for 2 Weeks. 
The surface of medium on which organisms were grown was scraped with a 
rubber sweeper to remove aerial mycelium. The medium was then placed on a 
shelf (25.degree. C. to 28.degree. C.) lighted by fluorescent lamp for 48 
hours to develop spores. The developed conidiospore was added to 
sterilized distilled water to prepare a conidia suspension (10.sup.6 
spores/ml) and 3-4 leaves stage rice plants (variants: Nak Dong) sensitive 
to rice blast was sprayed with the conidia suspension prepared above until 
dripping wet. 
The inoculated rice plants were placed in a humidity chamber under dark for 
24 hours and then in a humidistat at temperature of 
26.degree..+-.2.degree. C. and a relative humidity of 90% and over for 5 
days. Thereafter, the infected area on rice plants was measured on a fully 
developed leaf just below the top leaf of 3-4 leaves stage rice plant. The 
fungicidal effect of the active compound was determined from the measured 
infected area by comparing with the standard infected area. 
Test 2 
Fungicidal effect on rice sheath blight causative organism 
An appropriate amount of wheat bran was introduced into a 1 L incubation 
bottle, sterilized and then incubated with a fragment of potato-agar 
medium on which rice sheath blight causative organism (Rhizoctonia solani 
AG-1) was grown for 3 days. The incubated mycelium mass was ground in a 
suitable size. A pot (5 cm) in which 2-3 leaves stage rice plants 
(variants: Nak Dong) were grown was inoculated uniformly with the mycelium 
and incubated in a humidity chamber (28.degree..+-.1.degree. C.) and then 
placed in a humidistat at relative humidity of 80% and over for 5 days. 
Thereafter, the occurrence of plant disease was determined by measuring 
the infected area on the sheath of 2-3 leaves stage rice seedling which is 
then compared with a comparative table for the ratio between the total 
sheath area and the infected area. 
Test 3 
Fungicidal effect on cucumber gray mold causative organism 
Gray mold causative organism (Botrytis cinerea KCI) isolated from cucumber 
was inoculated on potato-agar medium (PDA). This plate was incubated in an 
incubator at 25.degree. C. under dark for 15 days to develop spores. The 
spores developed on the medium were collected and filtered with a gauze to 
harvest the spore which was then suspended in a sterilized water in the 
concentration of 10.sup.6 spores/ml. 
One leaf stage cucumber was sprayed with the spore suspension prepared 
above and then placed in a humidity chamber at 20.degree. C. for 3 days. 
Thereafter, the infected area on one leaf of cucumber was measured. 
Test 4 
Fungicidal effect on tomato late blight causative organism 
A V-8 juice agar medium (V-8 juice 200 ml, CaCO.sub.3 4.5 g, agar 15 g, 
distilled water 800 ml) was inoculated with tomato late blight causative 
organism (Phytophthora infestans) and placed at 20.degree. C. under light 
for 16 hours and then under dark for 8 hours, and incubated for 14 days to 
develop spores. A sterilized distilled water was added to the medium and 
shaked to remove zoosporangium from the lawn. The zoosporangium was 
filtered through 4-fold scrap of cloth and then adjusted in the 
concentration of 1.times.10.sup.5 zoospore/ml to prepare an inoculum. 
Tomato seedlings were sprayed with the inoculum and then placed in a 
humidity chamber at 20.degree. C. for one week and subsequently in a 
humidistat at 20.degree. C. and 80% and over relative humidity for 4 days. 
Thereafter, the infected area on the first and second leaves of tomato was 
measured. 
Test 5 
Fungicidal effect on wheat leaf rust causative organism 
Wheat leaf rust causative organism (Puccinia recondita) was subcultured 
directly on plants in a laboratory and used as a test organism. To 
subculture the organism and determine the fungicidal effect of active 
compound, 15 grains of wheat seed (variants: Eunpa) were sowed in a 
disposable pot (diameter: 6.5 cm) and then cultivated in a greenhouse to 
one-leaf stage, which was then placed in a humidity chamber at 20.degree. 
C. for one day and transferred to a humidistat at 20.degree. C. and 70% 
relative humidity. The organism was inoculated on wheat plants to induce 
infection. Evaluation was carried out 10 days after the inoculation by 
measuring the infected area. 
Test 6 
Fungicidal effect on barley powdery mildew causative organism 
Barley powdery mildew causative organism (Erysiphe graminis f.sp. hordei) 
was subcultured in a laboratory and used as a test organism. To subculture 
the organism and determine the fungicidal effect of active compound, 15 
grains of barley seed (variants: Dongbori No. 1) were sowed in a pot 
(diameter: 6.5 cm) and then cultivated in a greenhouse to one-leaf stage, 
on which the spore of powdery mildew causative organism was inoculated to 
induce infection. The inoculated bareley plants were transferred to a 
humidistat at 22.degree. to 24.degree. C. and 50% relative humidity and 
placed therein for 7 days. Thereafter, the infected area was measured. 
The fungicidal effect of each tested active compound at the concentration 
of 250 ppm was graded on the basis of the following criteria. The result 
is listed in the following Table 3. 
TABLE 3 
______________________________________ 
Fungicidal effect of the compound of formula (I) 
______________________________________ 
Inhibition 
rate Grade 
.gtoreq.90% 
A 
60-89% B 
.ltoreq.59% 
C 
______________________________________ 
Compound No. 
RCB RSB CGM TLB WLR BPM 
______________________________________ 
1 B C C C B B 
2 B C C C A B 
3 B C C C A A 
4 C C C C A B 
5 B C C C A B 
6 C C C C A B 
7 B C C C C B 
8 C C C C C B 
9 -- -- -- -- -- -- 
10 -- -- -- -- -- -- 
11 C C B C B A 
12 C C B C B A 
13 B C C C B A 
14 B C C C B A 
15 -- -- -- -- -- -- 
16 -- -- -- -- -- -- 
17 -- -- -- -- -- -- 
18 -- -- -- -- -- -- 
19 C C B C A C 
20 C C C B A C 
21 C C C B B C 
22 C C B C A B 
23 C C B C A C 
24 C C C C A A 
25 C C C B A A 
26 B B C B A A 
27 B B C C A A 
28 C C C C A A 
29 C B C C A A 
30 C C C C C A 
31 C C C C C A 
32 -- -- -- -- -- -- 
33 -- -- -- -- -- -- 
34 -- -- -- -- B A 
35 -- -- -- -- B A 
36 A B C C A A 
37 A C C C A A 
38 -- -- C C B A 
39 C C C C C A 
40 -- -- -- -- -- -- 
41 -- -- -- -- -- -- 
42 A A C B A A 
43 C C C C A A 
52 A B C B A A 
53 A B C C A A 
54 C C B C A A 
55 C C C C A A 
44 A B C B A A 
45 B C C C A A 
46 A A C B A A 
47 C C C C A A 
48 -- -- -- -- -- -- 
49 -- -- -- -- -- -- 
50 B B C B A A 
51 B C B C A A 
56 -- -- -- -- -- -- 
57 -- -- -- -- -- -- 
58 C C C C A A 
59 C C C C A A 
60 A C B B A A 
61 C C C C A A 
62 C C C C A A 
63 C C A C A A 
64 -- -- -- -- -- -- 
65 -- -- -- -- -- -- 
66 -- -- -- -- -- -- 
67 C C C B B A 
68 C C C A C B 
69 -- -- -- -- -- -- 
70 -- -- -- -- B A 
71 -- -- -- -- B A 
72 -- -- -- -- B A 
73 C C A C C C 
74 C C A B C C 
75 C C A B C C 
______________________________________ 
The more pertinent important features of the present invention have been 
outlined above in order that the detailed description of the invention 
which follows will be better understood and that the present contribution 
to the art can be fully appreciated. Those skilled in the art can 
appreciate that the conception and the specific embodiment disclosed 
herein may be readily utilized as a basis for modifying or designing other 
structures for carrying out the same purposes of the present invention. 
Further, those skilled in the art can realize that such equivalent 
constructions do not depart from the spirit and scope of the invention as 
set forth in the claims.