SU1279531A3 - Method of producing derivatives of thiazolinotriazine - Google Patents

Abstract

The invention relates to a thiazolinotriazine derivative (I) of the general formula O Hc C - L - -, (R i) where R, - I, halo, methyl; I-cyclohexyl, phenyl, unsubstituted or substituted by a methyl group or a nitro group, X is O, or R, is H, Hj is cyclohexyl, X is S, which have fungicidal activity. To reveal the biological activity of the synthesized compounds I based on the reaction of the compound Ti f (BjPh iS greR, with phosphogen or trichloromethyl chloroformate in the presence of a base, such as Y, K-dimesh1anilin, in a medium-inert organic solvent such as ethyl acetate or chloroform, at a temperature of 5 s followed by aging. mixtures at room temperature or at the boiling point of the solvent used. Crystalline substances; on table 3. about 01 co

Description

eleven

The invention relates to a process for the preparation of new thiazolinotriazine derivatives of the general formula

fl)

where R. is hydrogen, halo, or methyl radical;

R is cyclohexyl, phenyl, unsubstituted or substituted by a methyl group or a nitro group;

X is an oxygen atom;

or R,

hydrogen;

R is cyclohexyl; X is a sulfur atom, possessing fungicidal activity.

The purpose of the invention is to obtain new thiazolinotriazine derivatives having fungicidal activity.

Example 1. Preparation of 3-cyclohexyl-6-methyl-7-phenyl-3,4-dihydro-2-H-thiazolino (3,2-a) -1,3,5-triazin-2,4- dione.

3.4 g of 1- (5-phenyl-4-methyl-D-thiazo-Lin-2-yl) -3-cyclohexyl urea and 2.6 g of N ' K-dimethylaniline are dissolved in 70 ml of ethyl acetate and at 5 ° C at while stirring, 10 ml of ethyl acetate is added dropwise, in which 1.3 g of trichloromethyl chloroformate is dissolved.

After stirring for 1 hour at 5 ° C, the resulting reaction mixture is washed with water, dried over anhydrous magnesium sulphate and the solvent is distilled off. The resulting residue is recrystallized from ethanol, yielding 2.8 g of the desired product with mp, 168-169 ° s

Example 2. Preparation of 3-cyclohexyl-6-methyl-7- (4-methylphenyl) -3,4-dihydro-2H-thiazolino (3,2-a) -1,3,5-triazin-2.4 -dione.

0.9 g of 1- (4-methyl-5-) 4-methylphenyl- (-thiase olino-2-yl) -3-cyclohex of chenylamine and 0.6 g of N, N-dimethylaniline are dissolved in 30 ml of ethyl acetate and with stirring, 10 ml of ethyl acetate is added dropwise, in which 0.4 g of trichloromethyl chloroformate is dissolved.

20

25

2795312

After stirring for 1 h at 5 s, the resulting reaction mixture was washed with water, dried over anhydrous magnesium sulphate and the solvent was distilled off.

5 Then, the obtained crystals are washed with ligroin and as a result, 0.45 g of the desired product is obtained with mp 162-165 ° C.

EXAMPLE 3. Preparation of 3-cyclohexyl-6-methyl-7-phenyl-3,4-dihydro-2H-thiazolino (3 5 2-a) -J, 3,5-triazin-2-thioxo -4-she

2.0 g of 1- (5-phenyl-4-methyl-L-thiazolin-2-yl) -3-cyclohexylthiourea

 and 1.45 g of S, K-diametylaniline is dissolved in 80 ml of ethyl acetate and at 5 ° C with stirring 10 ml of ethyl acetate is added dropwise in which 1.2 g of trichloromethyl chloroformate is dissolved.

After 30 min stirring at the indicated temperature; the reaction mixture is heated under reflux for 3 hours and then cooled to room temperature. The reaction mixture is then washed with water and dried over anhydrous magnesium sulphate, and the solvent is distilled off. The resulting residue is recrystallized from methanol, and 1.0 g of the desired product is obtained with mp 192193 ° C.

;

PR I MER 4. Obtaining trans-7j (p-chlorophenyl) -6-methi-3-cyclohexyl-3,4-dihydro-2H-thiazolino (3,2-a) -1,3, 5-triazine -2,4-dione.

4 g of 1- (trans-5) -p-chlorophenyl- (4-methyl U-thiazolin-2-yl) -3-cyclohexyl 40 urea and 3.3 g of N, N-dimethylaniline are dissolved in 50 ml of ethyl acetate and then 1.25 g of trichloromethyl chloroformate is added dropwise. The mixture is kept for 30 minutes while stirring

45 at and another 30 min at room temperature. Water is then added to the oil layer. The oil layer is separated, washed with water and dried over anhydrous magnesium sulphate, and the solvent is removed by distillation. The resulting crystals are washed with ligroin and 3.5 g of the expected product are obtained with a mp. 132-134 ° C.

EXAMPLE 5 Preparation of trans-755 (p-chlorophenyl) -6-methyl-3-cyclohexyl-3,4-dihydro-2H-thiazolino (3,2-a) -1, 3,5-triazine -2,4-dione.

4 g of 1-trans 5- (p-chlorophenyl) -4-methyl- & -thiazolin-2-yl-3-3-cyclohexyl urea and 3.3 g of S, S-dimethyl anilyl are not dissolved in 50 ml of chloroform and 1.25 g of phosgene are introduced into the mixture with stirring. The resulting mixture was stirred for 30 minutes at 5 ° C and then for another 30 minutes at room temperature. The resulting mixture is treated according to the method described in example 4, and the result is 3.8 g of the target product with t, pieces 132-.

In tab. listed typical compounds obtained according to the proposed method.

Preparation of the starting compound: trans-6-trans-2-amino-5- (para-chlorophenyl) -4-methyl---thiazoline.

2.65 g of sodium metal are dissolved in 180 ml of ethanol and 27.4 g of threo-1-chloro-1- (p-chlorophenyl) -2-propylamine hydrochloride and 8.7 g of thiourea are added to the stirred solution. After refluxing the mixture for 3 hours, the reaction mixture is cooled and drunk into water. It is alkalinized with 10% sodium hydroxide solution and extracted with chloroform. The solvent is removed and a mixed solution is added to the residue.

benzene-hexane and 16.7 g of crude crystals are obtained. They are purified on chlorine-chromatographic. column and the result is 7.1 g of the target product with so pl. 122-123 C. Example 7: Preparation of cis-2-amino-5- (para-chlorophenyl) -4-methyl-L-thiazoline.

10.5 g of threo-1-chloro-1- (p-chlorophenyl) -2-propylaminohydrochloride and 10.5 g of potassium thiocyanate are added to 60 ml of methylcellosolve and 10.5 g of potassium thiocyanate and the mixed solution is maintained at 5 hours with stirring. The mixed solution was poured into ice water and extracted with ethyl acetate. The solvent is distilled off and the residue is washed with ligroin, whereby 4.7 g of the expected product are obtained with mp 1.143-145 C.

EXAMPLE 8 Preparation of 1-trans 5- (para-chlorophenyl) -4-methyl-L-triazo-lin-2-yl 2 -3-cyclohexyl urea.

In 50 ml of THF, 5 g of trans-2-ami o-5- (para-hporpenyl) -4-methyl-D-thiazoline is dissolved and added with stirring to a solution of 2.8 g of qi

„., H. / Average D. 1 in treated vines, „

% effective protection - (---- S-,) x 100.

Average D.1 for untreated vines

fO

f5

20

25

five

0

thirty

five

five

clohexyl isocyanate. After the reaction mixture is kept at room temperature for 30 minutes, it is poured into water and the crystals are filtered and dried; . The result is 7.2 g of the desired product with T. PL.112-1IB C.

The fungicidal action of the proposed compounds is illustrated by the following tests.

The test for controlling the proper powdery mildew of cucumbers. 5 ml of an aqueous suspension containing the desired amount of each compound were sprayed onto cucumber seedlings planted in the most often (variety Sat-sukimi dori), which are in the 1.5-leaf stage, and each treated plant was sucked in air. Then, the powdery mildew pathogen was inoculated with Pseudoperonospora cubesis and the test plants were kept in a greenhouse in order to cause disease.

The appearance of cucumber plants infected with moss dew was investigated, and the phytotoxic effect and disease control effect was evaluated in comparison with the disease state of foliage of untreated cucumber plants.

The results are in the table.2.

Test to combat the powdery mildew of grapes. Biennial grape vines (view Delaware) were sprayed with an aqueous solution of each of the compounds 3.11 and 18 September. After spraying, these vines were naturally infected in the field. The development of the disease of downy mealy growth on each of the vines was assessed on September 18 and 28.

The protective effect of each of the compounds was evaluated as follows. The rate of disease -% affected leaves vania

0O (healthy)

211-25

326-50

The degree of disease (A.1) - (Each disease indicator x Number of observed leaves) 4 x Number of observed leaves.

The results are shown in table 3.

12795316

X is an oxygen atom;

or R, is hydrogen;

 cyclohexyl;

SNS-g-1 X A II S t ntaiKg

Claims (3)

 cm 1 The invention relates to a process for the preparation of new thiazolinotriazine derivatives of the general formula where R. is hydrogen, halo or methyl radical; R is cyclohexyl, phenyl, unsubstituted or substituted by a methyl group or a nitro group; X is an oxygen atom; or R, hydrogen; R is cyclohexyl; X is a sulfur atom, possessing fungicidal activity. The purpose of the invention is to obtain new thiazolinotriazine derivatives having fungicidal activity. Example 1. Preparation of 3-cyclohexyl-6-methyl-7-phenyl-3,4-dihydro2-H-thiazolino (3,2-a) -1,3,5-triazine 2,4-dione. 3.4 g of 1- (5-phenyl-4-methyl-D-thyaz Lean-2-yl) -3-cyclohexyl urea and 2.6 g of N ' K-dimethylaniline are dissolved in 70 ml of ethyl acetate and at 5 ° C with stirring 10 ml of ethyl acetate is added dropwise in which 1.3 g of trichloromethyl chloroformate is dissolved. After stirring for 1 hour at 5 ° C, the resulting reaction mixture is washed with water, dried over anhydrous magnesium sulphate and the solvent is distilled off. The resulting residue is recrystallized from ethanol, resulting in A gain of 2.8 g of the desired product is obtained with a melting point of 168-169 ° C. Example 2. Preparation of 3-cyclohexyl-6-methyl-7- (4-methylphenyl) -3,4 dihydro-2H-thiazolino (3,2-a) -1,3,5triazin-2, 4-dione. 0.9 g of 1- (4-methyl-5-) 4-methylphenyl (& thiaz olino-2-yl) -3-cyclo g ek silmovein and 0.6 g H, N-dimethylaniline are dissolved in 30 ml of ethyl acetate; and 10 ml of ethyl acetate, in which 0.4 g of trichloromethyl chlorophosphate is dissolved, are added dropwise with stirring. 312 After stirring for 1 hour at 5 ° C, the resulting reaction mixture was washed with water, dried over anhydrous magnesium sulphate and the solvent was distilled off. Then, the obtained crystals are washed with ligroin and as a result 0.45 g of the expected product is obtained with mp 1662165 ° C. EXAMPLE 3. Preparation of 3-cyclohexyl-6-methyl-7-phenyl-3, 4-dihydro2H-thiazolino (3 5 2-a) -J, 3,5-triazin2-thioxo-4-one. 2.0 g of 1- (5-phenyl-4-methyl-L-thiazolin-2-yl) -3-cyclohexylthiourea and 1.45 g N, C-diametylaniline are dissolved in 80 ml of ethyl acetate and at 5 ° C with stirring 10 ml of ethyl acetate in which 1.2 g of trichloromethyl chloroformate is dissolved are added dropwise. After 30 min stirring at the indicated temperature; the reaction mixture is heated under reflux for 3 hours and then cooled to room temperature. The reaction mixture is then washed with water and dried over anhydrous magnesium sulphate, and the solvent is distilled off. The resulting residue is recrystallized from methanol and as a result 1.0 g of the expected product is obtained with mp 192Pr and M4. Preparation of trans-7 (p-chlorophenyl) -6-methi-3-cyclohexyl 3, 4-dihydro- 2H-thiazolino (3,2-a) -1,3, 5-triazin-2,4-dione. 4 g of 1- (trans-5) -p-chlorophenyl- (4-methyl U-thiazolin-2-yl) -3-cyclohexyl urea and 3.3 g of N, N-dimethylaniline are dissolved in 50 ml of ethyl acetate and then dropwise 1.25 g of trichloromethyl chloroformate is added to the mixture. The resulting mixture is kept for 30 minutes with stirring, and for a further 30 minutes at room temperature. Water is then added to the oil layer. The oily layer was separated, washed with water and dried over anhydrous magnesium sulphate, and the solvent was removed by distillation. The resulting crystals are washed with ligroin and 3.5 g of the expected product are obtained with a mp. 132-134 ° C. EXAMPLE 5: Preparation of trans-7 (p-chlorophenyl) -6-methyl-3-cyclohexyl 3, 4-dihydro-2H-thiazolino (3,2-a) -1, 3,5-triazin-2 , 4-dione. 4 g of 1-trans 5- (p-chlorophenyl) -4 methyl- & -thiazolin-2-yl1-3-cyclohexylurea and 3.3 g of S, S-dimethylanil are not dissolved in 50 ml of chloroform and 1.25 g of phosgene are introduced into the mixture with stirring. The resulting mixture was stirred for 30 minutes at 5 ° C and then for another 30 minutes at room temperature. The resulting mixture is treated according to the procedure described in Example 4, and as a result, 3.8 g of the desired product is obtained with t, pieces 133134 0. In tab. Lists typical connections obtained according to the proposed method. Preparation of the starting compound: trans 6-trans-2-amino-5- (para-chlorophenyl) 4-methyl-y-thiazoline. 2.65 metallic sodium is dissolved in 180 ml of ethanol and 27.4 g of threo-1-chloro-1- (para-chlorophenyl) -2-propylamine hydrochloride and 8.7 g of thiourea are added to the stirred solution. After the mixture was boiled under reflux for 3 hours, the reaction mixture was cooled and drunk into water. It is alkalinized with 10% sodium hydroxide solution and extracted with chloroform. The solvent is removed and a mixed solvent of benzene-hexane is added to the residue and 16.7 g of crude crystals are obtained. They are purified on chlorine-chromatographic. column and the result is 7.1 g of the target product with so pl. 122-123C. PRI me R 7. Getting CIS-2-amino-5- (para-chlorophenyl) -4-methyl-L thiazoline. 10.5 g of threo-1-chloro-1- (para-chlorophenyl) -2-propylaminohydrochloride and 10.5 g of potassium thiocyanate are added to 60 ml of methylcellosolve and 10.5 g of potassium thiocyanate and the mixed solution is maintained at 5 hours with stirring. The mixed solution was poured into ice water and extracted with ethyl acetate. The solvent is distilled off and the residue is washed with ligroin, whereby 4.7 g of the expected product are obtained with mp 1.143145C. EXAMPLE 8 Preparation of 1-trans 5- (para-chlorophenyl) -4-methyl-L-triazo-lin-2-yl 2 -3-cyclohexyl urea. In 50 ml of THF, 5 g of trans-ami o-5- (para-hporpenyl) -4-methyld-thiazoline is dissolved and added with stirring to a solution of 2.8 g qi. / Average% effective protection - (--- Average clohexyl isocyanate. After the reaction mixture is kept at room temperature for 30 minutes, it is poured into water and then the crystals are filtered and dried; the result is 7.2 g of the desired product with T. PL.112-1IB C. The fungicidal action of the proposed compounds is illustrated by the following tests: A test for controlling the proper powdery mildew of cucumbers. 5 ml of an aqueous suspension containing the desired amount of each compound was sprayed onto the cucumber seedlings (p Satsukusimidori species), which is in the 1,5-leafing stage, and each treated plant was dried in air, then the powdery powdery mildew pathogen Pseudoperonospora cubensis was inoculated and the test plants were kept in the greenhouse in order to cause the disease. Investigated the appearance of cucumber plants infected downy mildew, and the phytotoxic effect and disease control effect were evaluated in comparison with the disease state of foliage of unprocessed cucumber plants. The results are in the table.2. Test to combat the powdery mildew of grapes. Biennial grape vines (view Delaware) were sprayed with an aqueous solution of each of the compounds 3.11 and 18 September. After spraying, these vines were naturally infected in the field. The development of a downy powdery growth on each of the vines was assessed on September 18 and 28. The protective effect of each of the compounds was evaluated as follows. The number of diseased and affected leaves 0O (Healthy) 211-25 326-50 disease heat (D.1) - (Each disease provider Number of observed leaves) 4 x Number of leaves observed. D. 1 in treated vines, „S-,) x 100. D. 1 in untreated vines 12795 The results are shown in Table. 3. The claims of the method of producing thiazolintriazine derivatives of the general formula O T4 I 1 S -Nf X 15 R. - hydrogen, halogen or methyl radical; cyclohexyl, phenyl, noname. whelping or substituted methyl group or nitro group; solvent, such as ethyl acetate or chloroform, at 5 ° C, followed, if necessary, by keeping the reaction mixture at room temperature or at the boiling point of the solvent used. Table I 16 X is an oxygen atom; or R, is hydrogen; cyclohexyl; X is a sulfur atom, characterized in that the compound of the general formula CH3-g-1 X A II S t ntaiKg where R, R, and X have the indicated values ™ are "reacted with phosgene or trichloromethyl chloroformate in the presence of a base such as N, N-dimethylaniline inert environment CH, CH, Trance p 1.5928 Cis 162-165 About Trans. 136-138 Cis 183-184 Sho H eight 1279531 Continuation of table 1 180-182 GL table 2 1279531О Continuation of table.2 „ II Comparative compound BUT Comparative compound Tetrachlorophthalonitrile 12795312  Continuation of table 2 eleven Also ABOUT r-N -% - 5) -CH3 4Vo Table3