JPS6041068B2 - Method for producing 5-amino-1,2,3-thiadiazoles - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing 5-amino-1,2,3-thiadiazoles.

5-Amino-1,2,3-thiadiazoles are used as pharmaceuticals,
It has various uses as a raw material for agricultural chemicals, etc.

Conventionally, its production method involves, for example, reacting chloraldehyde ethoxycarbonylhydrazine with thionyl chloride,
Next, the amination method (West German Patent Publication No. 2,636)
, No. 994), a method for reacting acetylysothiocyanate and diazomethane (Chem. Techniques r.99 1),
618-31 (1966)), etc. are known.

However, these known methods have problems such as the raw materials are expensive and require long and complicated steps for preparing the raw materials, and cannot necessarily be said to be economically advantageous methods.

The present inventors aimed to establish an industrially advantageous manufacturing method for 5-amino-1,2,3-thiadiazoles,
I conducted extensive research.

As a result, if diazoacetonitriles are reacted with hydrogen sulfide in a solvent, it is possible to produce 5-amino-1,2-
, 3-thiadiazoles can be produced, and the present invention was achieved. Diazoacetonitrile, which is a raw material for the present invention, is explosive and unstable to handle.
substance, but there is no such danger in solvents such as ether and methylene chloride.

This diazoacetonitrile is easily synthesized and obtained by reacting aminoacetonitrile with sodium nitrite in an acidic aqueous solution and extracting with a solvent such as ether or methylene chloride.

The solvent used here is also suitable as a solvent in the reaction of the present invention, as described below. Therefore, in the present invention, the diazoacetonitrile solution prepared in this manner is used as it is without isolating the diazoacetonitrile. All risks or handling necessities are avoided. Furthermore, the aminoacetonitrile used in the preparation of the raw material of the present invention is a precursor of glycine, which is a type of amino acid that is commercially available in large quantities, and is inexpensive and easily available.

Therefore, the present invention has the advantage that the raw materials are cheaper and preparation of the raw materials is simpler than the known methods. Any solvent that can be used in the present invention is useful as long as it is inert to the reaction and dissolves the diazoacetonitrile.

Examples include linear saturated hydrocarbons such as n-hexane and n-hebutane, cyclic saturated hydrocarbons such as cyclohexane, chloroform, methylene chloride, carbon tetrachloride, trichloroethylene, and 1,2-dichloroethylene. , halogenated hydrocarbons such as 1,2-dichloroethane, ethers such as diethyl ether, dioxane, methyl cellosolve, and ethyl cellosolve, alcohols such as methyl alcohol and ethyl alcohol, aromatic compounds such as chlorobenzene, dichlorobenzene, and nitrobenzene, and water. These are usually used alone, but they may be used in combination. The hydrogen sulfide salt used may be either an organic salt or an inorganic salt.

Examples of organic salts of hydrogen sulfide include methylamine, ethylamine, and n-ph.

Lopylamine, isopropylamine, n-butylamine, dimethylamine, diethylamine, trimethylamine, triethylamine, tributylamine, furylamine, 2-ethoxyethylamine, pyridine, ethylenediamine, hexamethylenediamine, hexamethyleneimine, hexamethylenetetramine, hydroxylamine, etc. Salts of amine organic bases and hydrogen sulfide are effective. These organic bases of hydrogen sulfide are easily prepared by blowing approximately equimolar hydrogen sulfide gas to the organic base into a solution of the organic base in the above-mentioned solvent, and it is usually preferable to subject the prepared solution to the reaction. Also, effective inorganic salts of hydrogen sulfide include alkali metal salts, alkali metal salts, and ammonium salts of hydrogen sulfide.

Specific examples thereof include sodium sulfide, sodium hydrogen sulfide, potassium sulfide, potassium hydrogen sulfide, calcium sulfide, calcium hydrogen sulfide, magnesium sulfide, magnesium hydrogen sulfide, ammonium sulfide, and ammonium hydrogen sulfide. These inorganic salts of hydrogen sulfide are
It is usually best to dissolve it in a small amount of water or alcohol and use it for the reaction. The hydrogen sulfide salt is preferably used in an amount of 1 mol or more, preferably in the range of 1.1 to 1.5 mol, per 1 mol of the raw material diazoacetonitrile, in view of the yield of the target product or economic efficiency.

If the reaction temperature is too high, the raw material diazoacetonitrile may decompose, so the reaction temperature is preferably 20 oo or less.
The process is carried out at a temperature of 5-lyo and under normal pressure for 0.1-1 hour.

After the reaction, a part of the target 5-amino-1,2,3-thiadiazole is precipitated, so the remaining target product can be obtained by collecting it in a furnace and further concentrating and extracting the furnace liquid.

Next, examples of the present invention will be given.

Examples 1 to 8 Various hydrogen sulfide salt solutions were prepared by dissolving predetermined amounts of various organic bases in various solvents 50', and then blowing in hydrogen sulfide gas in an approximately equimolar amount to the organic base.

A solution of 4.7 moles (0.07 mol) of diazoacetonitrile dissolved in 200 moles of methylene chloride was placed in the reaction vessel, and the contents were maintained at about -3°C. Next, while stirring the contents, the hydrogen sulfide salt solution prepared above was added over a period of 3 minutes, and then the solution was stirred for another 1 minute. From the reactant, 5-amino-1 is obtained by filtration, concentration and extraction operations.
, 2,3-thiadiazole was obtained.

Table 1 shows the type of solvent used to prepare the hydrogen sulfide salt solution, the type and amount of organic base used, and the 5-amino-
The yield of 1,2,3-thiadiazole is shown.

Table 1 Example 9 An experiment was carried out in the same manner as in Example 1, except that 6.6 moles (0.07 mol) of ethyldiazoacetonitrile was used in place of diazoacetonitrile.

As a result, 6.3 ml of 4-ethyl-5-amino-1,2,3-thiadiazole was obtained. Example 10 An experiment was conducted in the same manner as in Example 1, except that 10.0 mol (0.07 mol) of phenyldiazoacetonitrile was used in place of diazoacetonitrile.

As a result, 8.6 ml of 4-phenyl-5-amino-1,2,3-thiadiazole was obtained. Example 11 A solution of 4.7 mm (0.07 mol) of diazoacetonitrile dissolved in 300 mm of carbon tetrachloride was placed in a reaction vessel, and the contents were maintained at about 5°C.

Then, while burning the contents, add anhydrous sodium sulfide5.
A solution prepared by dissolving 5 mol (0.07 mol) in 5 t% ethanol aqueous solution was added over a period of 45 minutes, and then an additional 10 mol was added.
I performed rope worship for a minute. 5-amino-1,2,3-thiadiazole was obtained from the reaction product by filtration, concentration, and extraction.

Examples 12 to 16 Instead of a solution of anhydrous sodium sulfide dissolved in an aqueous ethanol solution, a predetermined amount of various hydrogen sulfide inorganic salts was used in Example 12.
The experiment was carried out in the same manner as in Example 11, except that in Examples 14 and 15, 10 parts of water were used, and in Example 16, 15 parts of water were used. Ta.

Table 2 shows the types and amounts of hydrogen sulfide inorganic salts used in Examples 11 to 16, and the amount of 5-amino-1,2,3-thiadiazole produced.

Table 2 Example 17 A solution of 4.7 moles (0.07 mol) of diazoacetonitrile dissolved in 200 moles of methylene chloride was placed in a reaction tank.
The contents were maintained at approximately 3°C.

Next, while the contents were being transferred to the ocean, a solution of 4.1 moles of anhydrous sodium hydrogen sulfide (0.07 mol) dissolved in 10 moles of water was added over a period of 30 minutes, and the mixture was stirred for another 10 minutes. . From the reaction product, 4.1 hours of 5-amino-1,2-3-thiadiazole was obtained by heating, concentrating and extracting. Example 18 An experiment was conducted in the same manner as in Example 17, except that 6.69 (0.07 mol) of ethyldiazoacetonitrile was used in place of diazoacetonitrile.

As a result, 6.0 g of 4-ethyl-5-amino/-1,2'3-thiadiazole was obtained. Example 19 Except that 10.0 mol (0.007 mol) of phenyldiazoacetonitrile was used instead of diazoacetonitrile,
An experiment was conducted in the same manner as in Example 17.

Claims (1)

[Claims] 1 Diazoacetonitrile represented by the formula ▲ Numerical formula, chemical formula, table, etc. ▼ (wherein R represents a hydrogen atom, a lower alkyl group, or an aryl group) is sulfurized in a solvent. 5-Amino-1,2,3- represented by the formula ▲Mathematical formula, chemical formula, table, etc.▼ (wherein R has the same meaning as above), which is characterized by reaction with a hydrogen salt. Production method of thiadiazoles.