JPH0526787B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing 5-mercapto-1,2,3-thiadiazole salt. 5
-Mercapto-1,2,3-thiadiazole salt has various uses as an intermediate for pharmaceuticals, agricultural chemicals, and the like.

A conventional method for producing it is, for example, a method in which chloroacetaldehyde ethoxycarbonyl hydrazone and thionyl chloride are allowed to react, and then mercapto is formed [JP-A-53-23974]. A method using a diazo compound [Tetrahedron
Letters, 26 2389 (1973)] etc. are known.

However, these known methods cannot be said to be advantageous production methods from an industrial perspective because the raw materials are unstable or difficult to handle.

Therefore, the present inventors have conducted extensive research with the aim of establishing a method that can industrially advantageously produce 5-mercapto-1,2,3-thiadiazole salt in good yield. I came up with an invention.

The present invention involves carrying out a condensation reaction between trihaloacetaldehydes and hydrazines in a solvent, reacting the reaction product with a sulfide salt and/or a hydrogen sulfide salt,
The present invention relates to a method for producing 5-mercapto-1,2,3-thiadiazole salt, which is characterized in that a halogen is then added to the reaction solution.

According to the present invention, the raw materials used are stable and relatively easy to handle, the reaction is simple, and the yield of 5-mercapto-1,2,3-thiadiazole salt is high, so it is extremely advantageous industrially. 5-
An advantage is that mercapto-1,2,3-thiadiazole can be produced.

In the present invention, as trihaloacetaldehydes, chloral, chloral hydrate, tribromoacetaldehyde, triiodoacetaldehyde, etc. are preferably used.

Further, as hydrazines, formulas having an arylsulfonyl group or an alkylsulfonyl group such as p-toluenesulfonylhydrazide, benzesulfonylhydrazide, p-xylenesulfonylhydrazide, methanesulfonylhydrazide, ethanesulfonylhydrazide, etc. A hydrazine compound represented by the formula (wherein R represents an alkyl group or an aryl group) is preferably used.

The condensation reaction between trihaloacetaldehydes and hydrazines proceeds almost quantitatively, and the formula (In the formula, X represents a halogen atom of the trihaloacetaldehyde used, and R represents an alkyl group or an aryl group of the hydrazine used.) A trihaloacetaldehyde hydrazone compound represented by the following formula is produced.

The amount of hydrazine to be used relative to trihaloacetaldehyde may be equimolar, but in order to complete the reaction, it is preferable to use hydrazine in somewhat excess, generally about 1.1 times the mole. The appropriate reaction temperature is -20 to 50°C, preferably 0 to 10°C, and the reaction time is not particularly limited, but generally
It is 0.5 to 3 hours. Examples of solvents include water, lower alcohols such as methyl alcohol, ethyl alcohol, isopropyl alcohol, and t-butyl alcohol, aromatic hydrocarbons such as benzene, xylene, and toluene, and carbon halides such as methylene chloride, carbon tetrachloride, and chloroform. Examples include hydrogen, and among these, water, lower alcohols, and the like are preferred.

The reaction product obtained by the condensation reaction of trihaloacetaldehydes and hydrazines in a solvent is obtained by isolating the reaction product from the reaction solution by a method known per se such as concentration and recrystallization, and then preparing the next sulfide salt and/or hydrogen sulfide. Although it may be used in the reaction with a salt, it is easier to perform the reaction by adding the sulfide salt and/or hydrogen sulfide salt to the reaction solution containing the reaction product without isolating the reaction product from the reaction solution. This method is suitable because it can be simplified, there is no loss of reaction products due to isolation operations, and the solvent used in the condensation reaction can be used as is.
In addition, when the reaction product is isolated and reacted with sulfide salt and/or hydrogen sulfide salt, it is necessary to use a new solvent.
The same as in the case of the condensation reaction described above is suitable.

The reaction temperature when reacting the reaction product with the sulfide salt and/or hydrogen sulfide salt is suitably 40°C or lower, preferably -10 to 40°C, and the reaction time is generally about 0.5 to 1.5 hours. . By reacting the reaction product with a sulfide salt and/or a hydrogen sulfide salt,
A 5-mercapto-1,2,3-thiadiazole salt and some precursors are formed.

Examples of the sulfide salts include sulfide salts of alkali metals and alkaline earth metals such as sodium sulfide, potassium sulfide, rubidium sulfide, lithium sulfide, calcium sulfide, barium sulfide, throtontium sulfide, magnesium sulfide, and ammonium sulfide. However, among these, alkali metal sulfide salts are preferably used. Hydrogen sulfides include alkali metal and alkaline earth metal hydrogen sulfides such as sodium hydrogen sulfide, potassium hydrogen sulfide, calcium hydrogen sulfide, etc. Among these, alkali metal hydrogen sulfides are preferred. used. A plurality of types of these sulfide salts and hydrogen sulfide salts may be used.

The amount of sulfide salt and hydrogen sulfide salt used depends on the reaction product (trihaloacetaldehyde hydrazone compound).
It is generally preferably 1 to 5 times, particularly 2 to 3.5 times by mole, per 1 mole.

When adding a halogen to a reaction solution obtained by reacting a reaction product with a sulfide salt and/or a hydrogen sulfide salt, the temperature of the reaction solution is maintained at about -10 to 10°C, and after adding the halogen, It is suitable to stir at a temperature of 10 to 50°C, preferably 20 to 30°C, generally for about 20 to 90 minutes, preferably about 30 to 60 minutes. Examples of the halogen to be added include chlorine, bromine, and iodine, and among these, bromine, chlorine, and the like are preferably used.

It is desirable to add halogen to an extent that does not make the reaction solution acidic.The amount of halogen added varies depending on the amount of sulfide salt, hydrogen sulfide salt, etc. used, the amount of precursor produced, etc., but in general, trihaloacetaldehyde is added. 0.1 to 0.5 per mole of hydrazone compound
Appropriate mole times, preferably about 0.2 to 0.3 times the mole amount.

By adding a halogen to the reaction solution of sulfide salt and/or hydrogen sulfide salt, 5-mercapto- corresponding to sulfide salt, hydrogen sulfide salt, etc.
The 1,2,3-thiadiazole salt is obtained in a higher yield than without addition of halogen.

Isolation of 5-mercapto-1,2,3-thiadiazole salt from the reaction solution after addition of a halogen can be accomplished, for example, by separating the inorganic salt produced by the reaction and then concentrating the reaction solution to remove the solvent. This can be easily carried out by distilling off and separating the crystals from the concentrated solution, and if necessary, by recrystallizing the obtained crystals according to a conventional method, highly pure 5-mercapto-1 can be obtained. , 2,3-thiadiazole salts.

Example 1 After dissolving 16.5 g of chloral hydrate in 200 ml of methanol, 18.6 g of para-toluenesulfonyl hydrazide was added as a powder at about 25°C while stirring.
Thereafter, stirring was continued at about 25° C. for 1 hour to cause chloral hydrate to react with para-toluenesulfonyl hydrazide.

After the reaction, 72.0 g of sodium sulfide nonahydrate was added while stirring the reaction solution vigorously without isolating the reaction product.
was added over about 15 minutes, and stirring was continued for 1 hour at about 25°C to carry out the reaction.

Next, the reaction solution was cooled to approximately -5°C, 4.8g of bromine was added, and the temperature was gradually raised to 20°C.
Stir for 40 minutes. The reaction solution after stirring had a reddish-brown color, and inorganic salts such as sodium chloride and sodium bromide were precipitated.

After removing the precipitated inorganic salt, the solvent was distilled off from the reaction solution under reduced pressure, and the resulting crude product was recrystallized using a water-methanol-methylene chloride mixed solvent to give 5-mercapto-1,2 , 11.4 g of sodium salt dihydrate of 3-thiadiazole was obtained. The yield based on chloral hydrate was 64.7%.

Example 2 The reaction was carried out in the same manner as in Example 1, except that 2.2 g of chlorine was used instead of bromine in Example 1, and sodium salt dihydrate of 5-mercapto-1,2,3-thiadiazole was prepared. 11.3g was obtained. The yield based on chloral hydrate was 64.2%.

Example 3 The reaction was carried out in the same manner as in Example 1, except that 7.6 g of iodine was used instead of bromine in Example 1, and sodium salt dihydrate of 5-mercapto-1,2,3-thiadiazole was prepared. 11.0g was obtained. The yield based on chloral hydrate was 62.4%.

Example 4 Except for using 28.1 g of tribromoacetaldehyde instead of chloral hydrate in Example 1,
The reaction was carried out in the same manner as in Example 1 to obtain 10.7 g of sodium salt dihydrate of 5-mercapto-1,2,3-thiadiazole. The yield based on tribromoacetaldehyde was 60.8%.

Example 5 Instead of sodium sulfide nonahydrate in Example 1,
Example 1 except that 33.1 g of potassium sulfide was used.
The reaction was carried out in the same manner as 5-mercapto-
12.2 g of potassium salt dihydrate of 1,2,3-thiadiazole was obtained. The yield based on chloral hydrate is
It was 63.4%.

Example 6 Instead of sodium sulfide nonahydrate in Example 1,
The reaction was carried out in the same manner as in Example 1, except that 16.8 g of sodium hydrogen sulfide was used, and 10.9 g of sodium salt dihydrate of 5-mercapto-1,2,3-thiadiazole was obtained. The yield based on chloral hydrate was 61.9%.

Example 7 Instead of para-toluenesulfonyl hydrazide in Example 1, 10.9 g of methanesulfonyl hydrazide
The reaction was carried out in the same manner as in Example 1, except that 10.2 g of sodium salt dihydrate of 5-mercapto-1,2,3-thiadiazole was obtained. The yield based on chloral hydrate was 57.9%.

Example 8 Instead of para-toluenesulfonyl hydrazide in Example 1, benzelsulfonyl hydrazide 17.2
The reaction was carried out in the same manner as in Example 1, except that g was used, and 11.1 g of sodium salt dihydrate of 5-mercapto-1,2,3-thiadiazole was obtained.

The yield based on chloral hydrate was 63.1%.

Claims (1)

[Claims] 1. 5- characterized in that trihaloacetaldehydes and hydrazines are subjected to a condensation reaction in a solvent, the reaction product is reacted with a sulfide salt and/or a hydrogen sulfide salt, and then a halogen is added to the reaction solution.
Method for producing mercapto-1,2,3-thiadiazole salt.