KR900007546B1 - 5h-1,3,4-thiadiazolo(3,2-a)pyrimidine-5-ones and its agricultural and horticultural composition - Google Patents

Abstract

5H-1,3,4-Thiadiazolo(3,2-a)pyrimidine-5-one derivatives of formula (I) are prepd. In the formula, X is hydrogen, halogen, methyl, ethyl, methoxy, ethoxy, phenyl, phenoxy, cyano or nitro; Y is hydrogen, halogen, haloalky, chloroalkyl, alkoxy, alkynyl or cyano opt. substd. by phenyl, or C2-3 alkynyl opt. substd. by phenyl or chloroalky. Cpds. are useful as agricultural and horticultural herbicides.

Description

5H-1, 3, 4-thiadiazolo [3,2-a] pyrimidin-5-one derivatives and agricultural and horticultural fungicide compositions containing the same

The present invention relates to a novel class of 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one derivatives and novel agrohorticultural germicidal compositions containing the derivatives.

Until now, it is known that 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one derivatives have physiological activity, and their applications have been studied as various medicines.

For example, the 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one derivative represented by the following general formula

Wherein R ₁ represents an alkyl group or an aryl group, R ₂ represents an on-hydrogen atom, a halogen atom, a nitro group, a carboalkoxy group or an alkyl group, R ₃ represents an alkyl group or an aralkyl group, and Y ₁ represents -SO- or -SO _2- .) It is known to be effective in suppressing the reproduction of cancer cells (Japanese Patent Laid-Open No. 52-118494 (1977)).

5H-1, 3, 4-thiadiazolo [3,2-a] pyrimidin-5-one derivative represented by the following general formula and

Wherein R ₄ represents a 1H-tetrazol-5-yl group, a 2H-tetrazol-5-yl group, a carboxyl group or an alkoxycarbonyl group, and R ₅ is aryl unsubstituted or substituted with an alkyl, alkoxy group, hydroxy group or halogen Heteroaryl group, X ₁ is an alkylene group, alkenylene group or alkyne which may have an oxygen atom, a sulfur atom or -SO ₂ -at its terminal and may be substituted with one or more straight chain alkyl groups, cyclic alkyl groups or R ₅ And their physiologically acceptable salts are known to have excellent antiallergic activity (Japanese Patent Laid-Open No. 58-177997 ('83)).

As mentioned above, to date, several kinds of 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one derivatives are known. However, their biological activity relates to medicine and is not known about its biological activity as pesticides.

It is an object of the present invention to prepare novel 5H-1, 3, 4-thiadiazolo [3,2-a] pyrimidin-5-one derivatives having excellent biological activity as pesticides and useful agricultural and horticultural fungicides containing the derivatives. To provide.

The present inventors have concentrated on the thiadiazolopyrimidin-5-one framework known to be useful as a medicament to synthesize many novel derivatives thereof. As a result, the inventors have found that certain types of 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one derivatives exhibit very good biological activity as agricultural fungicides. On the basis of this, the inventors have completed the present invention.

That is, the present invention provides a 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one derivative represented by the following general formula (I) and an agricultural / horticultural germicidal composition containing the derivative do.

X is a hydrogen atom, a halogen atom, an alkyl group. An alkoxy group, a phenyl group, a phenoxy group, a cyano group or a nitro group, and Y is an alkynyl group which may be substituted with a hydrogen atom, a halogen atom, a haloalkyl group, an alkoxy group, or a phenyl group, or a cyano group.

Preferred compounds are those in which general formula (I) is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group or a phenyl group, Y is a hydrogen atom, a halogen group, a chloroalkyl group or a phenyl group or a C ₂ -C ₃ alkyne which may be substituted It is a compound which is a diary and a cyano group.

A more preferable compound is a compound in which X is a hydrogen atom, a halogen atom, a methyl group, an ethyl group, a methoxy group, an ethoxy group or a phenyl group in general formula (I), and Y is a hydrogen atom, a halogen atom or a cyano group.

Further preferred compounds are those in which X is a hydrogen atom in formula (I) and Y is a halogen atom, a hydrogen atom or a cyano group, and in general formula (I), X is a halogen atom, a methyl group, an ethyl group, a methoxy group, an ethoxy group or It is also preferable that it is a phenyl group and Y is a hydrogen atom.

Most preferred compounds include 2-benzylsulfonyl-7-fluoro-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one, 2-benzylsulfonyl-6-methyl- 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one, 2-benzylsulfonyl-6-methoxy-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one, 2-benzylsulfonyl-6-fluoro-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one, 2-benzyl Sulfonyl-6-chloro-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one, 2-benzylsulfonyl-5H-1, 3, 4-thiadiazolo [ 3, 2-a] pyrimidin-5-one and 2-benzylsulfonyl-7-cyano-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one .

The 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one derivatives of the present invention are novel compounds and specific examples thereof are shown in Table 1. Compound numbers indicated therein are referred to hereinafter to denote compounds.

TABLE 1

* Disassembled

Compounds of the present invention can be prepared by oxidizing the compound represented by the following general formula (II),

X and Y in the formula are the same as in the general formula (I).

Oxidation of the compound of formula II can be prepared by any method used for the oxidation of organosulfurized compounds.

Examples of applicable oxidizing agents include hydrogen peroxide, organic peracids such as m-chloroperbenzoic acid, oxone (trade name, reagents containing potassium peroxosulphate marketed by DuPont).

In addition to the oxidizing agent, an acid catalyst such as acetic acid and a metal catalyst such as sodium tungstate can be used to promote the oxidation reaction.

Examples of the solvent used in the oxidation reaction include water; Halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, chlorobenzene and the like; Fatty acids such as acetic acid and propionic acid, ketones such as acetone and methyl ethyl ketone; Amides such as dimethylformamide and dimethylacetamide; Alcohols such as methyl alcohol and ethyl alcohol; Hydrocarbons such as hexane, petroleum ether and benzene.

Oxidation can be carried out in the temperature range from -20 ° C to the boiling point of the solvent used.

The amount of oxidant used is usually twice or more than the same amount of the compound used of the general formula (II), and there is no specific limitation thereto.

The general formula (II) compound is a novel substance, and 2-amino-5-benzylthio-1, 3, 4-thiadiazole (III) is β-ketoester derivative (IV), β-formyl ester or 2 2-amino-5-benzylthio-1, 3, 4-thiadia by the following three methods (A, B or C), which are reacted with a propeneate derivative (VI) or a malonate derivative (X). It can be prepared from sol (III).

2-amino-5-benzylthio-1, 3, 4-thiadiazole (III) can be prepared by a generally applied method for preparing known 1, 3, 4-thiadiazole according to the following reaction overview. have.

U ¹ and U ² here represent a halogen atom.

Manufacturing process A: The method using (beta) -ketoester derivative (IV).

Wherein X ¹ is a hydrogen atom or a halogen atom, Y ¹ is a haloalkyl group and R ¹ is an alkyl group.

Compounds of formula (V) are formulated in formula (IV) in the presence of liquefied reagents such as polyphosphoric acid, boron trifluoride ether acid, sulfuric acid, etc. in high boiling point solvents or in the presence or absence of relatively high It can be prepared by reacting the compound with 2-amino-5-benzylthio-1, 3, 4-thiadiazole (III).

Compounds of formula (IV) are known and can be prepared by conventional processes. Some of them are usually applicable.

Compounds of formula (V) wherein X ¹ is a halogen atom can be prepared by halogenating the corresponding compound wherein X ¹ is a hydrogen atom. As the halogenating agent, for example, chlorine, sulfuryl chloride, bromine, iodine monochloride and the like can be used. If desired, metal halides such as zinc chloride, iron (III) halide and the like can be used as catalyst. Zinc chloride and the like can also be used as the hydrogen halide acceptor.

Manufacturing process B: The method using (beta) -formyl ester or 2-propennoate.

Wherein X ² is a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, a phenyl group or a phenoxy group, R ² is an alkyl group and R ³ is a hydroxy group or an alkoxy group.

The compound of formula (VII) is prepared by reacting the compound of formula (VI) with 2-amino-5-benzylthio-1, 3, 4-thiadiazole (III) in the same manner as in Production Step A. Can be.

A compound of formula (X) wherein X ² is a halogen atom can be prepared by halogenating a compound in which X ² is a hydrogen atom. In addition, as the X ² substituent, a halogen atom, preferably an iodine atom, may be converted to a cyano group.

Wherein X ^2b is a halogen atom and X ³ is a cyano group. Halogenation can be carried out in the same manner as in the production process A described above.

As the X ^2b substituent, a halogen atom, preferably an iodine atom, can be converted to a cyano group. As preferred cyanating agents, sodium cyanide and copper cyanide are used simultaneously in the presence of a dimethylformamide solvent.

Compounds of formula (VI) are known or otherwise can be prepared by conventional methods. Some of them are usually applicable.

Manufacturing process C: The method using a malonate derivative.

The compound of the general formula (II) wherein Y is a halogen atom, an alkynyl group or a cyano group can be prepared by the following production process.

Wherein X ⁴ is a hydrogen atom or an alkyl group, Y ² is a halogen atom, Y ³ is an alkynyl group or cyano group and R ⁴ is a phenyl group or a substituted phenyl group.

The reaction of the compound of formula (VII) with 2-amino-5-benzylthio-1, 3, 4-thiadiazole (III) was carried out using chloro according to the procedure described in Formagic 33, H 11-13 (1978). It is carried out in relatively high boiling solvents such as benzene. The hydroxyl group of the compound of formula (VII) can be converted to a halogen atom by conventional methods. If desired, the compound of formula IV is halogen replaced. Halogen atoms, preferably iodine atoms, can be converted to alkynyl or cyano groups.

Examples of halogenating agents that can be used include phosphorus oxychloride, phosphorus pentachloride and the like. If desired, solvents such as toluene, hydrogen halide acceptors such as N, N-dimethylaniline, etc. may be used. Halogen replacement can be carried out using hydroiodic acid, potassium fluoride and the like.

In the general formula (XI), the compound wherein Y ³ is a cyano group or an alkynyl group is selected from the group consisting of a cyano group according to the cyanation reaction procedure described in the preparation process B or a halogen atom Y ² , It can be prepared by converting to an alkynyl group by the method described below.

Compounds in which Y ³ is an alkynyl group in formula (XI) are alkylacetylene, ethynyltrimethyl in the presence of bis (triphenylphosphine) palladium (II) chloride, a catalyst such as iodide and a hydrogen halide acceptor such as triethylamine. It can be prepared by reacting an alkyne compound such as silane or the like with a compound in which Y ² is a halogen atom, preferably an iodine atom, in the general formula. If necessary, a protecting group such as trimethylsilyl bonded to an alkynyl group is removed with a base such as potassium carbonate, tetraalkyl ammonium fluoride and the like.

The compound of formula (X) wherein X ⁴ is a hydrogen atom can be nitrided and then the hydroxyl group at the 7-position can be converted to a halogen atom and the halogen atom can be converted to an alkoxy group.

Wherein Y ^2b is a halogen atom and Y ⁵ is an alkoxy group.

Compounds of formula (XIV) may be prepared by treating compounds of formula (IXb) with fuming nitric acid, if desired, in the presence or absence of a solvent such as acetic acid.

The general formula (XV) compound can be prepared in the same manner as in the preparation of the general formula (VII) compound. Compounds of formula (XVI) can be prepared by reacting a compound of formula (XV) with an alcohol in the presence of a solvent with a hydrogen halide acceptor such as pyridine.

Compounds of formula (XIII) are known and can be prepared by conventional methods.

The compound of the present invention is that the 5H-1, 3, 4-thiadiazolo [3,2-a] pyrimidin-5-one derivative of the general formula (I), wherein the substituent is as described above, is an excellent biological agent useful as agrohorticultural fungicide. Have activity.

The compounds of the present invention can be used alone or as agrohorticultural fungicides or they are usually mixed with carriers, surfactants, dispersants or auxiliaries in a conventional manner and used as dusting agents, wettable powdering agents, emulsifying concentrates, granules or pellets. Are manufactured. Suitable carriers are solid carriers such as talc, bentonite, clay, kaolin, diatomaceous earth, white carbon, vermiculite, slaked lime, siliceous sand, ammonium sulfate, urea, and liquid carriers such as isopropyl alcohol, xylene, cyclohexanone . Examples of surfactants and dispersants include sulfate alcohol ester salts, alkylarylsulfonates, lignosulfonates, diarylmethane polysulfonates, polyoxyethylenealkylarylethers, polyoxyethylene sorbitan monoalkylates, and the like. Examples of adjuvants include carboxymethyl cellulose, polyethylene glycol, gum arabic and the like. These agents are applied on their own or diluted to a suitable concentration according to the application.

In the formulation, the concentration of the active ingredient is selected to the extent necessary. However, it is generally 0.5-20% by weight for dust or granules and 5-80% by weight for emulsions and water dispersions.

The amount of the agricultural or horticultural fungicide of the present invention varies depending on the type of compound used, the type of disease, the disease tendency, the degree of damage, environmental conditions, the type of the preparation, and the like. In the case of dusts or granules, when the formulation is applied on its own, the concentration of the active ingredient is chosen so that 10 to 500 g per 10 ares are applied. In the case of emulsions or water dispersions the concentration of the active ingredient is 10-2000 ppm.

The 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one derivative of the present invention is a novel compound and belongs to the genus Alternaria. pervidis), apple spot pattern disease, pear black spot pattern disease, etc. It shows excellent control effect, and can control cucumber gray mold disease, cucumber pressing disease and rice fever. This activity shows the effects of both prophylaxis and treatment and is long lasting. The compounds are also very nontoxic to the crops themselves and to thermo and aquatic animals.

The present invention will now be described in detail with reference to examples, in which the percentages are by weight.

Preparation Example 1

Synthesis of 2-benzylthio-6-methyl-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one

21.1 g of 2-amino-5-mercapto-1, 3, 4-thiadiazole and 6.9 g of sodium hydroxide were dissolved in a mixture of 40 ml of water and 45 ml of ethanol. 19.6 g of benzyl chloride was added to the solution, and the mixture was stirred at 50 ° C for 1 hour. After cooling, water was added to the reaction mixture, and the formed precipitate was separated by filtration and washed with water and ethanol / n-hexane (1: 1) mixture, respectively. The treated precipitate was then dried under reduced pressure to give 32.5 g of 2-ino-5-benzylthio-1, 3, 4-thiadiazole. m.p. 159-161 ° C., yield 94%.

Thus 5.6 g of 2-amino-5-benzylthio-1, 3, 4-thiadiazole and 3.6 g of 3-hydroxy-2-methyl-2-propionate were mixed together with 7.5 g of polyphosphoric acid and the mixture was 45 Stir to 130-150 ° C. for minutes. After cooling, water was added to the reaction mixture and the mixture was extracted with chloroform. The organic layer was washed with aqueous sodium hydrogen carbonate solution and water, respectively, and dried over anhydrous sodium sulfate. The solvent was distilled off and the residue was recrystallized from ethanol. This gave 4.4 g of 2-benzylthio-6-methyl-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one. m.p. 130-132 ° C., yield 61%.

Preparation Example 2

Synthesis of 2-benzylthio-7-chloro-6-methyl-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one

A mixture of 19.3 g of 2-amino-5-benzylthio-1, 3, 4-thiadiazole, 41.3 g of bis (2, 4, 6-trichlorophenyl) -2-methylmalonate and 60 ml of chlorobenzene was mixed for 1 hour. Stir at 135-140 ° C. After cooling n-hexane was added to the reaction mixture and the precipitate formed was separated by filtration. 23.9 g of 2-benzylthio-7-hydroxy-6-methyl-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidine-5-borne by washing the separated precipitate with n-hexane Got. m.p. 247-250 ° C., yield 91%.

Thus obtained 2-benzylthio-7-hydroxy-6-methyl-5H-1, 3,4-thiadiazolo [3,2-a] pyrimidin-5-one 18.3 g, 13.1 g phosphorus pentachloride and oxychloride 36.8 g of phosphorus was stirred at 85-95 ° C. for 1.5 h. The reaction mixture was then concentrated under reduced pressure and the residue was dissolved in toluene. The organic layer was washed with aqueous potassium carbonate solution and water, respectively, and dried over anhydrous sodium sulfate. The solvent was distilled off and the residue was purified by silica gel column chromatography using ethyl acetate / toluene (3: 7) mixture as eluent.

The solvent was then distilled to give 14.0 g of 2-benzylthio-7-chloro-6-methyl-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one. m.p. 102-104 ° C., yield 72%.

Preparation Example 3

Synthesis of Compound 2

2.8 g of 2-benzylthio-6-methyl-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one prepared in Preparation Example 1 was added to 75 ml of ethanol at 60 ° C. The mixture was warmed up and dissolved. To this solution was added 35.7 g aqueous suspension of oxone in 150 ml of water and the mixture was stirred at 60 ° C. for 2 hours. After cooling, water was added to dissolve the inorganic material, and the precipitated crystals were collected by filtration. The crystals were recrystallized from ethanol to obtain 1.6 g of 2-benzylsulfonyl-6-methyl-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one. m.p. 171-173 ° C., yield 52%.

Preparation Example 4

Synthesis of Compound 9

4.9 g of 2-benzylthio-7-chloro-6-methyl-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one were dissolved in methanol. To the solution was added 69.2 g of oxone aqueous suspension in 240 ml of water and the mixture was stirred at 60 ° C. for 1 h 45 min. After cooling, the reaction mixture was extracted with chloroform, and the organic layer was washed with an aqueous sodium thiosulfate solution and water, and dried over anhydrous sodium sulfate. The solvent was distilled off and the residue was recrystallized from a toluene / ethanol (1: 1) mixture. This gave 3.3 g of 2-benzylsulfonyl-7-chloro-6-methyl-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one. m.p. 211-213 ° C., yield 62%.

Preparation Example 5

Synthesis of 2-benzylsulfonyl-6-methoxy-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one (Compound 12)

5.1 g of 2-benzylthio-6-methoxy-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one was dissolved in 155 ml of methanol. A suspension of 46.2 g of oxone in 160 ml of water was added to the methanol solution and the mixture was stirred at 60-65 ° C. for 50 minutes. After cooling, the mixture was extracted with chloroform and the organic layer was washed with aqueous sodium thiosulfate solution, aqueous sodium hydrogen carbonate solution and water. The organic phase was dried over anhydrous sodium sulfate, the solvent was distilled off and the residue was recrystallized from a toluene / ethanol mixture to give 2-benzylsulfonyl-6-methoxy-5H-1, 3, 4-thiadiazolo [3, 2-a] 2.8 g of pyrimidin-5-one were obtained. m.p. 204-206 ° C., yield 50%.

Preparation Example 6

Synthesis of 2-benzylsulfonyl-7-ethynyl-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one (Compound 15).

2.3 g of 2-benzylthio-7-ethynyl-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one was dissolved in 100 ml of acetic acid. To this solution was added 0.12 g of sodium tungstate dihydrate and the solution was warmed to 50 ° C. 12.0 g of 30% hydrogen peroxide was dissolved in 50 ml of acetic acid and the solution was added dropwise to the acetic acid solution, and the resulting solution was warmed to 50-60 ° C. and stirred at that temperature for an hour and a half. After cooling the solution was diluted with water and extracted with chloroform. The organic layer was washed with aqueous sodium thiosulfate solution and water and then dried over anhydrous sodium sulfate. The solvent was distilled off and the residue was washed with ethanol to obtain 1.1 g of 2-benzylsulfonyl-7-ethynyl-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one. . m.p. 101-106 ° C., yield 43%.

Preparation Example 7

Synthesis of 2-benzylthio-6-methoxy-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one (intermediate)

70.3 g of 2-amino-5-mercapto-1, 3, 4-thiadiazole and 23.0 g of sodium hydroxide were dissolved in a mixture of 190 ml of water and 150 ml of ethanol. 65.2 g of benzyl chloride was added to the solution, and the resultant solution was warmed to 50 ° C and stirred for 1 hour at ionicity. After cooling water was added to the solution and the precipitate formed was separated by filtration. The residue was washed with water and ethanol / hexane mixtures and dried under reduced pressure. Thus, 108.1 g of 2-amino-5-benzylthio-1,3,4-thiadiazole was obtained. m.p. 159-161 ° C., yield 94%.

Thus obtained 4-amino 2-amino-5-benzylthio-1, 3, 4-thiadiazole, 3.2 g of 3-hydroxy-2-methoxy-propenoic acid propyl and 1 lg of polyphosphoric acid were heated to 135 ° C. for 20 minutes. Was stirred. After cooling chloroform and water were added thereto and extracted. The organic layer was washed with aqueous sodium hydrogen carbonate solution and water and dried over anhydrous sodium sulfate. 5.1 g of 2-benzylthio-6-methoxy-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one by distilling off the solvent and washing the residue with an ethanol / hexane mixture Got. Yield 93%. The compound was recrystallized from ethanol.

Preparation Example 8

Synthesis of 2-benzylthio-7-ethynyl-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one (intermediate)

A mixture of 44.7 g of 2-amino-5-benzylthio-1, 3, 4-thiadiazole, 98.1 g of bis (2, 4, 6-trichlorophenyl) malonate and 140 ml of chlorobenzene was heated to 130-140 ° C. And stirred for 20 minutes. After cooling hexane was added to the mixture and the precipitate formed was separated by filtration. The solid was washed with hexane to give 57.1 g of 2-benzylthio-7-hydroxy-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one. Yield 98%.

A mixture of 31.7 g of 2-benzylthio-7-hydroxy-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one, 24.0 g of phosphorus pentachloride and 117 g of phosphorus oxychloride thus obtained Was heated to 70-80 ° C. and stirred for 25 minutes.

After cooling the reaction mixture was concentrated under reduced pressure and chloroform and water were added to the residue. The organic layer was washed with aqueous sodium hydrogen carbonate solution and water and dried over anhydrous sodium sulfate. The solvent was distilled off and the residue was separated by silica gel column chromatography using ethyl acetate / hexane mixture as eluent to separate 2-benzylthio-7-chloro-5H-1, 3, 4-5H-1, 3, 4- 8.5 g of thiadiazolo [3,2-a] pyrimidin-5-one were obtained. m.p. 138-140 ° C., yield 25%.

A mixture of 12.2 g of 2-benzylthio-7-chloro-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one and 124 g of 57% hydrogen iodide was thus obtained 100-105. Heated to C and stirred for 4 h. After cooling the mixture was filtered and the solid was washed with water and dissolved in chloroform. The organic layer was washed with aqueous sodium hydrogen carbonate solution, aqueous sodium thiosulfate solution and water and dried over anhydrous sodium sulfate. The solvent was distilled off to obtain 13.9 g of 55% pure 2-benzylthio-7-iodo-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one. Yield 48%.

55% pure 2-benzylthio-7-iodo-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one obtained in a mixture of 30 ml of triethylamine and 60 ml of tetrahydrofuran 7.0 g were dissolved and 0.68 g of bis (triphenylphosphine) palladium (II) chloride and 0.18 g of copper iodide were added to the solution. To 20 ml of triethylamine, 3.8 g of ethynyl-trimethylsilane was added dropwise to the solution. The resulting solution was heated to 68-70 ° C. and stirred for 4 hours. After cooling, the reaction mixture was filtered and the filtrate was concentrated under reduced pressure.

The residue was separated by silica gel column chromatography using an ethyl acetate / hexane mixture as eluent to separate 2-benzylthio-7-trimethylsilylethynyl-5H-1, 3, 4-thiadiazolo [3, 2-a]. 4.2 g of pyrimidin-5-one were obtained.

In 50 ml of tetrahydrofuran, 4.1 g of 2-benzylthio-7-trimethylsilylethynyl-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one were dissolved and the solution was acetone. Cooled to -65 ° C in a dry ice bath. A solution of 0.16 g of tetrabutylammonium fluoride in 50 ml of tetrahydrofuran was added dropwise to the cooled solution, and the resulting solution was stirred for 10 minutes at -60 to -65 deg. After returning to room temperature, the reaction mixture was filtered, and ether and water were added to the filtrate and extracted.

The organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off and the residue was separated by silica gel column chromatography using an ethyl acetate / hexane mixture as eluent to separate 2-benzylthio-7-ethynyl-5H-1, 3, 2.3 g of 4-thiadiazolo- [3, 2-a] pyrimidin-5-one were obtained. m.p. 112-120 ° C., yield 65%.

Preparation Example 9

Synthesis of 2-benzylsulfonyl-7-cyano-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one

3 g of 2-benzylthio-7-cyano-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one were dissolved in 60 ml of acetic acid. To this solution was added 0.12 g of sodium tungstate dihydrate and the solution was warmed to 45 ° C. To this acetic acid solution was added dropwise a 5.6 g solution of 30% hydrogen peroxide solution in 30 ml of acetic acid. The solution was then stirred at 45-50 ° C. for 3 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, diluted with water and extracted with chloroform. The organic layer was washed with sodium thiosulfate solution and water, respectively, and dried over anhydrous sodium sulfate. The solvent was distilled off and the residue was recrystallized from ethanol to obtain 1.1 g of 2-benzylsulfonyl-7-cyano-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one. . m.p. 214-217 ° C., yield 33%.

Preparation Example 10

Synthesis of 2-benzylsulfonyl-6-cyano-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one

0.3 g of 2-benzylthio-6-cyano-5H-1, 3,4-thiadiazolo [3,2-a] pyrimidin-5-one in 10 ml of acetic acid was dissolved therein and 17 mg of sodium tungstate dihydrate Was added. 2.3 g of 30% hydrogen peroxide was slowly added dropwise to the solution so that the temperature of the reaction mixture did not exceed 50 占 폚. After the addition of hydrogen peroxide was completed, the reaction mixture was stirred at 50 ° C for 3 hours. After the reaction, the reaction mixture was cooled and diluted with water. The precipitated crystals were collected by filtration and washed with water. The crude crystals were recrystallized from ethanol to give 0.17 g of 2-benzyl-sulfonyl-6-cyano-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one. m.p. 219-221 ° C., yield 51%.

Preparation Example 11

Synthesis of 2-benzylsulfonyl-7-methoxy-6-nitro-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one

2.1 g of 2-benzylthio-7-methoxy-6-nitro- [3,2-a] pyrimidin-5-one was dissolved in 20 ml of acetic acid and 0.1 g of sodium tungstate dihydrate was added thereto. 2 g of 30% hydrogen peroxide solution was slowly added dropwise to the solution so that the temperature of the reaction mixture did not exceed 50 占 폚. After the addition of hydrogen peroxide, the reaction mixture was stirred at 50 ° C. for 1 hour. After the reaction was completed, the reaction mixture was cooled and diluted with water. The precipitated crystals were collected by filtration and washed with water. Crude crystals were recrystallized from ethanol to give 1.8 g of 2-benzyl-sulfonyl-7-methoxy-6-nitro-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one Got. m.p. 216-2l 8 ° C., yield 80%.

Preparation Example 12

Synthesis of 2-benzylthio-7-cyano-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one

In 120 ml of dimethylformamide, 9 g of 90% pure 2-benzylthio-7-iodo-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one was dissolved and 3.05 g of copper cyanide. And 1.57 g of sodium cyanide were added thereto.

)을 건조된 유기층에 첨가하여서 유기층을 잘 혼들었다. 플로리실을 분리한후 용제를 증류하여서 2-벤질티오-7-시아노-5H-1, 3, 4-티아디아졸로[3, 2-a]피리미딘-5-온 3.0g을 얻었다. 수율 50%.The reaction mixture was heated to 100 ° C. and stirred at that temperature for 1 hour. After the reaction, the reaction mixture was cooled, diluted with water, and extracted with chloroform. The organic layer was washed with water and chloroform was distilled off. Water was added to the residue and the mixture was extracted with toluene. The organic layer was washed with water and dried over anhydrous sodium sulfate. Florisil

) Was added to the dried organic layer to mix well. After the florisil was separated, the solvent was distilled off to obtain 3.0 g of 2-benzylthio-7-cyano-5H-1, 3,4-thiadiazolo [3,2-a] pyrimidin-5-one. Yield 50%.

[Florisyl® is a highly selective magnesium silicate sorbent.]

Preparation Example 13

Synthesis of 2-benzylthio-6-cyano-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one

15.5 g of 2-amino-5-benzylthio-l, 3, 4-thiadiazole, 10 g of ethyl 3-ethoxy-propenoate, 15 g of polyphosphoric acid, and 150 ml of xylene were mixed and stirred vigorously for 30 minutes. After the reaction was completed, the reaction mixture was cooled. Water was added to the reaction mixture and the mixture was extracted with toluene. The organic layer was washed with aqueous sodium bicarbonate solution and water, respectively, and dried over anhydrous sodium sulfate. The solvent was distilled off and the residue was recrystallized from an ethanol / hexane mixture to give 10.3 g of 2-benzylthio-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one. Yield 54%.

Thus, 5 g of 2-benzylthio-5H-1, 3, 4-thiadiazolo [3,2-a] pyrimidin-5-one and 5 g of zinc chloride were added to 500 ml of acetic acid. 6 g of iodine monochloride was added to the mixture and the mixture was stirred at 70-80 ° C. for 1 hour. After the reaction, the reaction mixture was cooled and sodium chloride solution was added. The precipitated crystals were collected by filtration and washed with water and isopropyl ether to give 2-benzylthio-6-iodo-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one 1.3 g was obtained. Yield 18%.

1.3 g of 2-benzylthio-6-iodine-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one thus obtained were dissolved in 15 ml of dimethylformamide. 0.6 g of copper cyanide and 0.3 g of sodium cyanide were added to the solution, and the mixture was stirred at 130 ° C. for 3 hours. After the reaction was completed, the reaction mixture was cooled and water and toluene were added to the mixture to stir the mixture well. The mixture was filtered to remove insolubles. The organic layer of the filtrate was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure.

The obtained crude crystals were recrystallized from ethanol to obtain 0.3 g of 2-benzylthio-6-cyano-5H-1, 3,4-thiadiazolo [3,2-a] pyrimidin-5-one. Yield 31%.

Preparation Example 14

Synthesis of 2-benzylthio-7-methoxy-6-nitro-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one

24 g of 2-benzylthio-7-hydroxy-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one were suspended in 250 ml of acetic acid and warmed to 40 ° C. 7.9 g of fuming nitric acid was added dropwise to this suspension. After completion of nitric acid the reaction mixture was stirred at 40 ° C. for 5 hours. After the reaction was completed, the reaction mixture was cooled and water was added thereto.

The precipitated crystals were collected by filtration, washed with water and dried under reduced pressure. This gave 24 g of 2-benzylthio-7-hydroxy-6-nitro-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one. Yield 87%.

Thus obtained 2-benzylthio-7-hydroxy-6-nitro- [3,2-a] pyrimidin-5-one 24g, phosphorus oxychloride 40ml, N, N-dimethylaniline 8.6g were mixed and the mixture was mixed with 30 Stirred to reflux for minutes.

After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in toluene. The toluene solution was carefully washed twice with water and then with sodium hydroxide solution. The solution was also washed with water until the wash liquid was neutralized. The toluene solution was then dried over anhydrous magnesium sulfate and treated with florisil. The solvent was distilled off under reduced pressure and the residue was washed with isopropyl ether to give 2-benzylthio-7-chloro-6-nitro-5H-l, 3, 4-thiadiazolo [3, 2-a] pyrimidine-5 19.5 g of -on was obtained. Yield 77%.

Thus, 3 g of 2-benzylthio-7-chloro-6-nitro-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one were dissolved in 50 ml of ethanol and 0.8 g of pyridine Added. The solution was stirred at reflux for 30 minutes. After the reaction, the reaction mixture was cooled and poured into water. The resulting mixture was extracted with toluene.

The organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was washed with isopropyl ether. This gave 2.1 g of 2-benzylthio-7-methoxy-6-nitro-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one. Yield 70%.

Sanction Example 1

Dust sanction

2% of compound (1), 5% of diatomaceous earth, and 93% of clay were mixed and ground to prepare dust.

Sanction Example 2

Wettable powder

50% of Compound (2), 45% of diatomaceous earth, 2% of sodium dinaphthylmethanesulfonate, and 3% of sodium lignosulfonate were mixed and ground to prepare a wettable powder.

Sanction Example 3

Emulsifiable concentrate

30% compound (3), 20% cyclohexanone, 11% polyoxyethylene alkylaryl ether, 4% alkylbenzenesulfonate calcium and 35% methylnaphthalene were uniformly mixed to prepare an emulsifiable concentrate.

Sanction Example 4

Granule

5% of compound (4), 2% of sodium salt of lauryl alcohol sulfate ester, 5% of lignosulfonate, 2% of carboxymethylcellulose, and 86% of clay were ground by mixing uniformly. 20% water was added to the mixture and kneaded to prepare 14-32 mesh granules using an extruder granulator. The granules were dried.

Exam 1

Preventive Effect on Black Spotted Black Spots (Brassica rapa var.pervidis)

Chinese seeds were sprinkled with 12 seeds in each plastic pot of 9 cm x 9 cm, and grown in the greenhouse for 7 days in the cotyledon stage. The water-dispersible preparation prepared according to Preparation Example 2, diluted to 50 ppm with water, was sprayed at a rate of 10 ml per pot. After the sprayed material was air dried, the pathogenic bacteria of the black pattern bottle were sprayed into the plants with a spore suspension, and the pot was kept in a moisture chamber at 30 ° C. After 3 days, the number of injury was calculated and the average number per leaf was recorded. Control values were calculated according to the following definition.

The results are shown in Table 2.

TABLE 2-1

Table 2-2

Exam 2

Restraint of apple branch pattern disease

Young twigs with 6-7 leaves isolated from apple trees (kind: India) were placed in glass cylinders. The water-jetty preparation prepared according to Preparation Example 2 was diluted to 1500 ppm with water and sprayed there. After air drying, the plants were sprayed with a spore suspension of pathogenic bacteria (Alternaria mali) of black spots, and the bacteria were added and maintained in a moisture chamber at 28 ° C. After 4 days, the injury index was calculated according to the following standard and the control value was calculated.

N = total number of test leaves

N ₀ = Unspoiled leaves

n ₁ = Number of injured leaves with 5% or less injury

n ₂ = Number of injured leaves with 5-10% injury

n ₃ = Number of injured leaves with damage of 11-25% or less

n ₄ = Number of injured leaves whose injury is less than 26-50%

n ₅ = Number of injured leaves with 51% or less injury

The results are shown in Table 3.

TABLE 3

Test 3

Prevention of cucumber gray mold disease

Cucumber (type: Sagami-hanjiro) seeds were grown in a greenhouse for 7 days with 12 seeds per pot in a 9 cm x 9 cm square plastic pot. The young seedlings grown in the cotyledon stage were diluted with water to 500 ppm of active ingredient concentration prepared according to Preparation Example 2 and sprayed at a rate of 10 ml per pot. After the sprayed preparation was air dried, the plants were sprayed with a uniform mycelium suspension of a liquid culture medium of Botrytis cinearea, and the pot was kept in a humid chamber at 20-23 ° C. Four days later, the infection was examined for all ports.

Infection Index

0: not infected

1: Infected area is less than 25%

2: Infected area is less than 26-50%

3: Infected area is less than 51-75%

4: Infected area is more than 75%

The results are shown in Table 4.

TABLE 4

Test 4

(Test on the effect of preventing Pseudoperonospora cubensis)

Cucumber (cv. Sagamihanjiro) was sprinkled with 12 seeds each in a 9 cm x 9 cm plastic pot. Seeds were grown in a greenhouse for 7 days.

The wettable powder prepared according to Preparation Example 2 containing the body compound was diluted with water at a concentration of 500 ppm of the active ingredient, and the obtained aqueous formulation was added to the cucumber seedlings in the cotyledon stage at a rate of 10 ml per pot. After air drying, the seedlings were inoculated with a cucumber suspension and a suspension of Pseudoperonospora cubensis, and then placed in a 20-22 ℃ moisture chamber. Injected disease injury was tested after 7 days. Disease index and control value (%) were calculated according to the following definition.

Disease grade

n ₀ : number of healthy leaves

n ₁ : Number of leaves infected less than 1/3

n ₂ : 1/3 to 2/3 number of infected leaves

n ₃ : Number of leaves infected more than 2/3

Where N represents the total number of leaves tested.

The results are shown in Table 5.

Claims (17)

5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one derivative represented by the following general formula (I).

Wherein X is a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, a phenyl group, a phenoxy group, a cyano group or a nitro group, and Y is an alkynyl group which may be substituted with a hydrogen atom, a halogen atom, a haloalkyl group, an alkoxy group, or a phenyl group It is a cyano group. The compound of claim 1, wherein in formula (I), X is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group or a phenyl group, and Y is a C _2- which may be substituted with a hydrogen atom, a halogen group, a chloroalkyl group or a phenyl group. 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one derivative, characterized in that it is a ₃ alkynyl group and a cyano group. The compound of claim 2, wherein in the general formula (I), X is a hydrogen atom, a halogen atom, a methyl group, an ethyl group, a methoxy group, an ethoxy group or a phenyl group, and Y is a hydrogen atom, a halogen atom or a cyano group. l, 3,4-thiadiazolo [3,2-a] pyrimidin-5-one derivative. 4. 5H-1, 3, 4-thiadiazolo [3, 2-a] according to claim 3, wherein in formula (I), X is a hydrogen atom and Y is a hydrogen atom, a halogen atom or a cyano group. Pyrimidin-5-one derivatives. 4. The 5H-1, 3, 4-thiadiazole according to claim 3, wherein in the general formula (I), X is a halogen atom, a methyl group, an ethyl group, a methoxy group, an ethoxy group or a phenyl group, and Y is a hydrogen atom. [3, 2-a] pyrimidin-5-one derivatives. The method of claim 1, wherein the derivative is 2-benzylsulfonyl-7-fluoro-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one, 2-benzylsulfonyl -6-methyl-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one, 2-benzylsulfonyl-6-methoxy-5H-1, 3, 4-thia Diazolo [3, 2-a] pyrimidin-5-one, 2-benzylsulfonyl-6-fluoro-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidine-5- On, 2-benzylsulfonyl-6-chloro-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one, 2-benzylsulfonyl-5H-1, 3, 4 -Thiadiazolo [3, 2-a] pyrimidin-5-one or 2-benzylsulfonyl-7-cyano-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidine- 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one derivative, characterized in that it is 5-one. And 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one derivatives represented by the following general formula (I)

Wherein X is a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, a phenyl group, a phenoxy group, a cyano group or a nitro group, and Y is an alkynyl group which may be substituted with a hydrogen atom, a halogen atom, a haloalkyl group, an alkoxy group, or a phenyl group It is a cyano group) Agricultural horticultural sterilization composition comprising a carrier that can be accommodated for agricultural horticulture. The 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one represented by the general formula (I) is a hydrogen atom, a halogen atom , A lower alkyl group, a lower alkoxy group or a phenyl group, and Y is a C _2-3 alkynyl group, a cyano group which may be substituted with a hydrogen atom, a halogen group, a chloroalkyl group, or a phenyl group. The 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one represented by the general formula (I) is a hydrogen atom, a halogen atom, a methyl group, an ethyl group, A horticultural germicidal composition, wherein the compound is a methoxy group, an ethoxy group or a phenyl group and Y is a hydrogen atom, a halogen atom or a cyano group. The 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one represented by formula (I) is X is a hydrogen atom, Y is a hydrogen atom, a halogen atom Or a horticultural sterilization composition, characterized in that the compound is a cyano group. The 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one represented by the general formula (I) is a halogen atom, a methyl group, an ethyl group, a methoxy group, A horticultural germicidal composition comprising an ethoxy group or a phenyl group and Y is a hydrogen atom. 10. The compound of claim 8, wherein 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one represented by formula (I) is 2-benzylsulfonyl-7-fluoro-5H. -1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one, 2-benzylsulfonyl-6-methyl-5H-1, 3, 4-thiadiazolo [3, 2- a] pyrimidin-5-one, 2-benzylsulfonyl-6-methoxy-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one, 2-benzylsulfonyl -6-fluoro-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one, 2-benzylsulfonyl-6-chloro-5H-1, 3, 4-thia Diazolo [3, 2-a] pyrimidin-5-one, 2-benzylsulfonyl-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one or 2-benzyl A horticultural germicidal composition characterized in that the sulfonyl-7-cyano-5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one. 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one derivative represented by formula (II).

Wherein X is a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, a phenyl group, a phenoxy group, a cyano group, or a nitro group, and Y is an alkynyl group which may be substituted with a hydrogen atom, a halogen atom, a haloalkyl group, an alkoxy group, or a phenyl group Or cyano group. The compound of claim 13, wherein X in formula (II) is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group or a phenyl group, and Y is a C ₂ which may be substituted with a hydrogen atom, a halogen group, a chloroalkyl group or a phenyl group. 5H-1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one derivative, characterized in that the group is _-3 alkynyl or cyano group. 15. The 5H according to claim 14, wherein X in formula (II) is a hydrogen atom, a halogen atom, a methyl group, an ethyl group, a methoxy group, an ethoxy group or a phenyl group, and Y is a hydrogen atom, a halogen atom or a cyano group. -1, 3, 4-thiadiazolo [3, 2-a] pyrimidin-5-one derivatives. 15. The 5H-1, 3, 4-thiadiazolo [3, 2-, wherein X in formula (II) is a hydrogen atom, and Y is a hydrogen atom, a halogen atom or a cyino group. a] -pyrimidin-5-one derivative. 15. The 5H-1, 3, 4-thiadiazole according to claim 14, wherein X in General Formula (II) is a halogen atom, a methyl group, an ethyl group, a methoxy group, an ethoxy group or a phenyl group and Y is a hydrogen atom. [3, 2-a] pyrimidin-5-one derivatives.