KR840000929B1 - Process for preparing 5-amino-1,2,3-thiadiazoles - Google Patents

Abstract

Title compds.(I; R = H, lower alkyl or lower aryl) were prepd. by the reaction of diazoacetonitrile(II) and hydrogen sulfide or its salts in the presence of base. Thus, treating 0.07 mol diazoacetonitrile with hydrogen sulfide in methylene chloride contg. 15 g triethylamine to give 1.4g 5-amino-1, 2, 3-thiadiazole.

Description

Method for preparing 5-amino-1,2,3-thiadiazole

The present invention relates to a process for preparing 5-amino-1,2,3-thiadiazole of the following structural formula (I), which is useful as a raw material in the pharmaceutical and agrochemical fields.

In the above structural formula,

R is hydrogen, lower alkyl or aryl group.

Typically, 5-amino-1,2,3-thiadiazole is prepared by reacting chloroaldehyde ethoxycarbonylhydrazine with thionyl chloride followed by amination of the product (German Publication No. P26 39 994). ) And; A method of reacting acetylisothiocyanate with diazomethane (Chem. Ber. 99,1618-31 (1966)) and the like are shown.

However, such a conventional method is expensive in terms of starting materials and has a problem in that it requires a lengthy process in the preparation of starting materials.

The present inventors studied a method for industrially preparing 5-amino-1,2,3-thiadiazole, and as a result, the diazoacetonitrile was reacted with hydrogen sulfide or a salt of hydrogen sulfide in a solvent and in the presence of a base. The object was achieved by inventing a method for producing.

The process of the present invention can be represented by the following scheme.

Where R is as above.

Lower alkyl groups in R include alkyl groups having 1 to 6 carbon atoms such as methyl, ethyl, propyl, butyl, petyl and hexyl.

Aryl groups represented by R also include phenyl, P-tolyl, P-ethylphenyl and naphthyl.

This reaction can be carried out in a simple process, for example, by dissolving diazoacetonitrile in a solvent and passing hydrogen sulfide in the presence of a base in this solution or injecting a salt of hydrogen sulfide into the solution.

Diazoacetonitrile used as starting material in this process is a material that is difficult to handle because of explosiveness or instability. However, this material is completely safe in solvents such as ether or methylene chloride.

Diazoacetonitrile can be readily prepared and obtained by reacting aminoacetonitrile with sodium nitrite followed by extraction with ether, methylene chloride and the like. The solvent used here is also suitable as a solvent in the reaction of the present invention. Therefore, in the present invention, the diazoacetonitrile obtained as described above is used in situ, without liberation, and thus there is no disadvantage such as being dangerous or difficult to handle.

This amino acetonitrile is a precursor of glycine, which is available in large quantities on the market, is inexpensive and readily available. Therefore, the process of the present invention has the advantage that the cost of the starting material is cheaper than the conventional process and the preparation of the starting material is much simpler.

As the solvent used in the present invention, any solvent which is inert to the reaction and capable of dissolving diazoacetonitrile can be used, for example, aliphatic hydrocarbons such as n-hexane and n-heptane; Alicyclic hydrocarbons such as cyclohexane; Halogenated hydrocarbons such as chloroform, methylene chloride, carbon tetrachloride, trichloroethylene, 1,2-dichloroethylene, 1,2-dichloroethane and the like; Ethers such as diethyl ether, dioxane, methyl cellosolve, ethyl cellosolve and the like; Alcohols such as methanol, ethanol and water. However, industrially, it is advantageous to use a solvent such as methylene chloride, ether, chloroform or n-hexane used as the extract when synthesizing diazoacetonitrile.

When using hydrogen sulfide, the base must be used together. At this time, both organic or inorganic bases can be used.

Organic bases include methylamine, ethylamine, n-propylamine, isopropylamine, n-butylamine, dimethylamine, diethylamine, trimethylamine, triethylamine, tributylamine, allylamine, α-ethoxyethyl It is effective to use amine-based compounds such as amines, pyridine, ethylenediamine, hexamethylenediamine, hexamethyleneimine, hexamethylenetetraamine, hydroxylamine and the like.

The organic base is used in an amount of 0.1 moles or more, preferably 0.5 to 5 moles, per mole of diazoacetonitrile as a starting material.

As an inorganic base, Alkali metal hydroxides, such as sodium hydroxide and potassium hydroxide; Alkalimine metal hydroxides such as calcium hydroxide and arsenic hydroxide; Alkoxides such as sodium methoxide and sodium ethoxide; Metal amides such as sodium amide, potassium amide and the like; Ammonia; It is effective to use hydrazine or the like. It is preferable to dissolve this inorganic base in the solvent mentioned above before use. In terms of yield or economical efficiency of the desired product, the inorganic base is preferably used in an amount of 0.05 g equivalent or more, preferably 0.1 to 0.5 g equivalent, per mole of diazoacetonitrile as a starting material.

When using hydrogen sulfide, hydrogen sulfide is injected into the process equipment for 0.1 to 2 hours so that the amount is equal to diazoacetonitrile and the actual amount of animal.

In the present invention, diazoacetonitrile may be reacted with a salt of hydrogen sulfide to obtain 5-amino-1,2,3-thiadiazole. Hydrogen sulfide salts that can be used include organic and inorganic salts.

The organic salts of hydrogen sulfide include hydrogen sulfide and methylamine, ethylamine, n-propylamine, isopropylamine, n-butylamine, dimethylamine, trimethylamine, triethylamine, tributylamine, allylamine, 2-ethoxy ethyl Salts with amine type organic bases such as amines, pyridine, ethylenediamine, hexamethylenediamine, hexamethyleneimine, hexamethylene tetraamine, hydroxylamine and the like are effectively used. Such salts can be readily prepared by passing hydrogen sulfide gas through a solution of these organic bases dissolved in an equimolar amount of the above-mentioned solvent. In general, it is preferable to supply the solution prepared as described above to the reaction.

As inorganic salts of hydrogen sulfide, it is effective to use alkali metal salts, alkaline earth metal salts and ammonium salts of hydrogen sulfide. Typical examples 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. Such hydrogen sulfide inorganic salts are preferably dissolved in a small amount of water or alcohol before use and supplied to the reaction.

The hydrogen sulfide salt is preferably used in an amount of 1 mole or more, preferably 1.1 to 1.5 moles, per mole of diazoacetonitrile as a starting material.

The contact reaction is carried out at normal pressure and relatively low temperature, i.e., below 20 ° C, preferably at -5 ° C to 15 ° C, since the starting material diazoacetonitrile is at risk of decomposition at high temperatures.

Upon completion of the contact reaction, the desired 5-amino-1,2,3-thiadiazole is partially precipitated, which is collected by filtration. The resulting filtrate is concentrated to precipitate the desired product remaining in the mother liquor.

The invention is illustrated by the following examples.

Example 1

300 g of a solution of 0.07 mol of diazoacetonitrile in methylene chloride is placed in a reactor and stirred while maintaining the temperature of the mixture at 3 ° C. 15 g of triethylamine is added dropwise to the mixture over 5 minutes, and hydrogen sulfide gas is injected for 30 minutes at a rate of 52 ml / min. Seven minutes after the start of hydrogen sulfide gas injection, crystals of the desired product begin to precipitate. After hydrogen sulfide gas was injected, the mixture was stirred for 15 minutes and filtered to obtain 3.2 g of precipitated product. The filtrate is then concentrated under reduced pressure at a temperature of 10 ° C. or lower to give 1.4 g of the desired product crystals.

Example 2-10

Only the starting materials, the solvent, the base and the amount of use thereof were changed as shown in Table 1, and the experiment was carried out by the method of Example 1. The results are shown in Table 1.

TABLE 1

Example 11

200 g of a solution of 0.07 moles of diazoacetonitrile dissolved in methylene chloride and 80 ml of n-hexane are placed in a reactor, and the mixture is kept at about 0 ° C. and stirred. 15 g of triethylamine was added dropwise over 15 minutes, and hydrogen sulfide gas was passed for 30 minutes at a rate of 52 ml / min, followed by filtration and concentration to 5.3 g of 5-amino-1,2,3-thiadiazole. To obtain.

Example 12

200 g of a solution of 0.083 moles of diazoacetonitrile dissolved in methylene chloride and 80 ml of n-hexane are placed in a reactor, and the mixture is kept at about 5 ° C. and stirred. To this was added 7 g of triethylamine dropwise over 5 minutes, hydrogen sulfide gas was passed through at a rate of 28 ml / min for about 30 minutes, then filtered and concentrated to 6.2 g of 5-amino-1,2,3-thiadiazole. To obtain.

Example 13

300 g of a solution of 0.08 moles of diazoacetonitrile dissolved in methylene chloride and 9 g of diethylamine were added to a reactor, and the mixture was kept at about 30 ° C. and stirred. Hydrogen sulfide gas is passed at a rate of 52 ml / min for about 45 minutes, then filtered and concentrated to yield 4.5 g of 5-amino-1,2,3-thiadiazole.

Example 14

200 ml of a solution of 0.07 moles of diazoacetonitrile dissolved in ethanol is placed in a reactor and stirred at -3 ° C. To this stirred solution, 100 ml of a solution of 0.07 mol of anhydrous sodium hydrogen sulfide dissolved in ethanol was added over 30 minutes, followed by stirring at the same temperature for 15 minutes to give 3.9 g of 5-amino-1,2,3-thiadiazole. Obtained.

Example 15

250 ml of a solution of 0.07 moles of diazoacetonitrile dissolved in methyl alcohol is placed in a reactor and stirred while maintaining the temperature of the solution at -3 ° C. To this stirred solution, 20 ml of a solution of 0.015 mol of sodium methoxide dissolved in methyl alcohol is added over 5 minutes. Hydrogen sulfide gas was injected therein at a rate of 50 ml / min for 30 minutes, and then the reaction mixture was further stirred at the same temperature for 15 minutes to obtain 2.9 g of 5-amino-1,2,3-thiadiazole.

Example 16

100 ml of a solution of 0.05 moles of diazoacetonitrile dissolved in methylene chloride was placed in a reactor and stirred at -7 ° C. To this stirred solution, 100 ml of a 50% solution of 3.90 g (0.05 mol) of anhydrous sodium sulfide (Na ₂ S) dissolved in ethanol was added over 30 minutes, followed by stirring at the same temperature for 15 minutes, to 2.4 g of 5-amino. -1,2,3-thiadiazole is obtained.

Example 17

A solution of 4.7 g (0.07 mol) of diazoacetonitrile in 250 ml of methyl alcohol is placed in a reactor and stirred while maintaining the temperature of the solution at -3 ° C. To this stirred solution, 20 ml of a solution of 0.8 g (0.015 molar equivalents) of sodium methoxide in methyl alcohol is added over 5 minutes. Hydrogen sulfide gas was infused at a rate of 50 ml / min for 20 minutes, and the reaction mixture was further stirred at the same temperature for 15 minutes, and then filtered, concentrated and extracted. 4.3 g of 5-amino-1,2,3-thiadiazole Is obtained.

Example 18-24

Only the starting materials, the solvent, the inorganic base and the amount used thereof are changed as shown in Table 2, and the experiment is carried out by the method of Example 17. The results are shown in Table 2.

TABLE 2

Example 25

A solution of 4.7 g (0.07 mol) of diazoacetonitrile in 250 ml of dioxane is placed in a reactor and stirred while maintaining the temperature of the solution at 0 ° C. To this stirred solution is added a solution of 0.84 g (0.02 mol) of sodium hydroxide in 5 ml of water. Hydrogen sulfide gas was added thereto at a rate of 50 ml / min for 20 minutes, and then the reaction mixture was further stirred for 15 minutes, filtered, concentrated and extracted to obtain 3.7 g of 5-amino-1,2,3-thiadiazole.

[Example 26-33]

Various hydrogen sulfide salts are prepared by passing hydrogen sulfide, which is an equimolar amount of organic base, through a solution dissolved in various solvents previously measured in 50 ml portions of various organic bases.

A solution of 4.7 g (0.07 mol) of diazoacetonitrile in 200 ml of methylene chloride is placed in a reactor. While maintaining the solution at about −3 ° C., each hydrogen sulfide solution prepared above was added dropwise over 30 minutes. The reaction mixture is further stirred for 10 minutes.

The reaction product is filtered, concentrated and extracted to give 5-amino-1,2,3-thiadiazole.

The solvents, bases and amounts thereof used in the hydrogen sulfide solution are shown in Table 3. The yield of 5-amino-1,2,3-thiadiazole is also shown in Table 3.

TABLE 3

Example 34

The experiment was carried out in the same manner as in Example 26 except for using 6.6 g (0.07 mol) of ethyl diazoacetonitrile instead of diazoacetonitrile.

As a result, 6.3 g of 4-ethyl-5-amino-1,2,3-thiadiazole was obtained.

Example 35

A solution of 4.7 g (0.07 mole) of diazoacetonitrile dissolved in 300 ml of carbon tetrachloride was placed in a reactor and maintained at about 5 ° C. Add dropwise for 45 minutes. After stirring the reaction mixture for 10 minutes, the reaction product is filtered and concentrated to give 5-amino-1,2,3-thiadiazole.

Example 37-41

Except for using an aqueous solution of various inorganic salts of hydrogen sulfide instead of a solution of anhydrous sodium sulfide in ethyl alcohol, the experiment was carried out in the same manner as in Example 36. The amount of water used to dissolve the inorganic salt is 5 ml in Examples 37 and 38, 10 ml in Examples 39 and 40, and 15 ml in Example 41. Hydrogen sulfide inorganic salts used, their amount and the yield of 5-amino-1,2,3-thiadiazole are shown in Table 4 below.

TABLE 4

Example 42

A solution of 4.7 g (0.07 mol) of diazoacetonitrile in 200 ml of methylene chloride is placed in a reactor. The temperature of the solution is maintained at about 3 ° C., and 10 ml of a solution of 4.1 g (0.07 mol) of anhydrous sodium hydrogen sulfide in 10 ml of water is added dropwise over 30 minutes, and the reaction mixture is further stirred for 10 minutes. Filtration, concentration and extraction of the reaction product yielded 4.1 g of 5-amino-1,2,3-thiadiazole.

Example 43

The same procedure as in Example 42 was carried out using 6.6 g (0.07 mol) of ethyl diazoacetonitrile instead of diazoacetonitrile.

As a result, 6.0 g of 4-ethyl-5-amino-1,2,3-thiadiazole are obtained.

Example 44

Using the same procedure as in Example 42 using 10.0 g (0.07 mole) of phenyl-diazoacetonitrile instead of diazoacetonitrile, 8.1 g of 4-phenyl-5-amino-1,2,3-thiadia A sol is obtained.

Claims (1)

Preparation of 5-amino-1,2,3-thiadiazole of the following structure (I) by contacting diazoacetonitrile of the following formula (II) with hydrogen sulfide in a solvent, in the presence of a base, or with a hydrogen sulfide salt Way.

R in the above formula represents a hydrogen atom, a lower alkyl group or an aryl group.