JP2717995B2 - Production method of 1,2,3-triazole - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel process for producing 1,2,3-triazole. 1,2,3-Triazole is useful, for example, as a raw material for producing a pharmaceutically useful antibiotic.

[0002]

2. Description of the Related Art A conventional method for synthesizing 1,2,3-triazole is that azide derivative is reacted with acetylene to synthesize 1-substituted-1,2,3-triazole and then reduced. A method for removing a substituent (Japanese Patent Application Laid-Open No. 1-143861) is known.

In this method, the stability (explosiveness) of the azide derivative becomes a problem, and the presence of the azide derivative in the reaction system complicates the heat management for explosion prevention in the synthesis, isolation and purification steps, and controls the reaction. Is not easy. Moreover,
Depending on the type of substituent of the azide derivative, it is necessary to synthesize a low molecular weight product from a high molecular weight raw material,
There were problems such as a very poor reaction efficiency.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to provide an industrial method for producing 1,2,3-triazole which can solve the problems of the conventionally known production methods.

[0005]

According to the present invention, there is provided a compound represented by the general formula [I]:

Wherein X represents a halogen atom and R represents a hydrocarbon group, and a hydrazone derivative represented by the general formula [II]:

The present invention relates to a method for producing 1,2,3-triazole represented by the following formula:

The hydrazone derivative used in the present invention is
It is a compound represented by the general formula [I]. In the above formula, X represents a halogen atom such as a chlorine atom, a bromine atom and an iodine atom, and R represents a hydrocarbon group, for example, a methyl group, an ethyl group,
A lower alkyl group having 1 to 5 carbon atoms such as a propyl group and a butyl group; a phenyl group which may be substituted with a methyl group, a nitro group or a halogen atom.

The hydrazone derivative used in the present invention is
It is produced from a dihalogen-substituted acetaldehyde and a substituted hydrocarbon sulfonylhydrazine (eg, lower alkylsulfonylhydrazine, optionally substituted benzenesulfonylhydrazine, etc.) [Chem
Ber, 108 402 (1975)].

The hydrazone derivatives used in the present invention include 2,2-dichloroacetaldehyde-p-toluenesulfonylhydrazone, 2,2-dichloroacetaldehyde-benzenesulfonylhydrazone, and 2,2-dichloroacetaldehyde-methanesulfonyl. Hydrazone,
2,2-dichloroacetaldehyde-ethanesulfonylhydrazone, 2,2-dibromoacetaldehyde-p-
Toluenesulfonylhydrazone, 2,2-dibromoacetaldehyde-benzenesulfonylhydrazone, 2,2
-Dibromoacetaldehyde-methanesulfonylhydrazone, 2,2-dibromoacetaldehyde-ethanesulfonylhydrazone and the like.

The amount of ammonia used in the present invention is usually 2 to 100 mol, preferably 2 to 50 mol, per 1 mol of the hydrazone derivative. As the ammonia, liquid ammonia, an aqueous ammonia solution and an ammonia solution dissolved in an organic solvent can be effectively used in the reaction of the present invention.

[0010] In the production method of the present invention, when liquid ammonia is used, a reaction solvent is not particularly required since the reaction proceeds without solvent.

In the production method of the present invention, when an aqueous ammonia solution or an ammonia solution dissolved in an organic solvent is used, the solvent is water or any solvent that sufficiently dissolves the hydrazone derivative and ammonia and does not interfere with the reaction. Solvents can be used alone or as a mixture. For example, methanol, ethanol, propanol, isopropanol, aliphatic alcohol solvents such as butanol, methyl ether, ethyl ether, propyl ether, ether solvents such as methyl propyl ether, chloroform, halogenated hydrocarbon solvents such as methylene chloride, Organic solvents such as dimethylsulfoxide, dimethylformamide and acetonitrile can be mentioned. Particularly, lower alcohols such as methanol and ethanol are preferable.

In the reaction of the present invention, the reaction temperature is-
The temperature is preferably from 30 to 100C, particularly preferably from about -10 to 80C. The reaction pressure is sufficient at normal pressure, but may be increased if necessary.

In the reaction of the present invention, the reaction time depends on the reaction temperature, the raw materials and the like, but is usually 1 to 24 hours, particularly preferably 1 to 12 hours.

In the reaction of the present invention, the method of contacting the hydrazone derivative with ammonia is not particularly limited. For example, when liquid ammonia is used, a method of mixing and stirring the hydrazone derivative with liquid ammonia can be used.At this time, the hydrazone derivative is dissolved in a small amount of an organic solvent, and the solution is dropped into liquid ammonia. The reaction may be carried out in a homogeneous state with stirring and dissolution. In addition, a method of mixing and stirring an aqueous ammonia solution or an ammonia solution dissolved in an organic solvent and a hydrazone derivative can also be mentioned. At this time, the hydrazone derivative is dissolved in a small amount of an organic solvent and dropped into the ammonia solution. The reaction may be carried out while stirring and dispersing.

In the reaction of the present invention, when liquid ammonia is used, after completion of the reaction carried out in a closed vessel, unreacted ammonia is distilled off, and the residue is dissolved in methylene chloride or chloroform. 1,2,3-Triazole can be obtained in a high yield by filtering off salts free from acetic acid and concentrating and separating by distillation or column chromatography.

In the reaction of the present invention, when an aqueous ammonia solution or ammonia dissolved in an organic solvent is used, water or the organic solvent is distilled off after completion of the reaction performed in a closed or non-closed vessel. Is dissolved in methylene chloride or chloroform, insoluble salts are separated by filtration, concentrated, and then separated by distillation or column chromatography to obtain 1,2,3-triazole in high yield.

[0017]

EXAMPLES Next, the present invention will be described in more detail with reference to examples and reference examples, but the present invention is not limited to the following examples unless it exceeds the gist of the present invention.

Reference Example 1 2,2-Dichloroacetaldehyde-p-toluenesul
In a 500 ml three-necked round bottom flask equipped with a honylhydrazone thermometer and a stirrer, p-toluenesulfonylhydrazine 41.5 was added.
g and 280 ml of propionic acid were charged, stirred under suspension, and cooled with ice. When the temperature was cooled to 15 ° C., 25 g of dichloroacetaldehyde was added as a solid and added for about 1 hour.
The stirring was continued while maintaining the temperature at 15 ° C.
The mixture was cooled on ice until the temperature reached 0 ° C., allowed to stand for 3 hours or more while maintaining the temperature at 0 ° C., and the precipitated crystals were filtered and dried to obtain 37.2 g of 2,2-dichloroacetaldehyde-p-toluenesulfonylhydrazone. . 122.5-123 ° C
(Literature value 123 ° C)

Example 1 200 m with a 1,2,3-triazole stirrer, a gas blowing tube and a dropping funnel
40 ml of methanol saturated with ammonia was charged into a 1-neck three-necked round bottom flask, and the 2,2-dichloroacetaldehyde-p-toluenesulfonylhydrazone obtained in Reference Example 1 obtained in Reference Example 1 was dissolved in 60 ml of methanol from a dropping funnel. Add methanol solution and stir for 22 ±
The reaction was performed for 2 hours in a temperature range of 5 ° C. After the completion of the reaction, by-product inorganic salts were removed with a glass filter, and the reaction solution was concentrated with an evaporator. When the reaction concentrate was quantified by gas chromatography absolute calibration curve method, 0.95 g of 1,2,3-triazole was produced (reaction yield to 2,2-dichloroacetaldehyde-p-toluenesulfonylhydrazone; 50.5%). did. The reaction concentrate was subjected to silica gel column chromatography using ethyl acetate: hexane = 1: 1 as a developing solvent to obtain 1,2,3-triazole (0.9 g). As a result of structural analysis of the product by NMR and MS spectra, it was confirmed that the product agreed with the standard product.

Example 2 The procedure of Example 1 was repeated except that the reaction temperature was 0 ° C., and 1,2,3-triazole (1.23 g) was obtained.

Example 3 The reaction and post-reaction operations were carried out in the same manner as in Example 1 except that the reaction temperature was changed to 9 hours to obtain 1,2,3-triazole (1.50 g).

According to the present invention, 1,2,3-triazole can be produced in a safe manner and with good reaction efficiency.

Claims (1)

(57) [Claims] 1. A hydrazone derivative represented by the general formula [I] (wherein, X represents a halogen atom and R represents a hydrocarbon group), and reacted with ammonia. And a method for producing a 1,2,3-triazole represented by the general formula [II].