RU1768598C - Method of 2-methyl-4(5)-nitroimidazole synthesis - Google Patents

Abstract

Usage: as an intermediate in the synthesis of biologically active substances. SUMMARY OF THE INVENTION: Product: 2-methyl-4 (5) -nitroimidazole, BP CzNdMz02, mp 252-4 ° C, 90% yield. Reagent 1: 2-mstilimidazole. Reagent 2 CH3CO-OH Reagent 3: HaS04. Reagent 4: (CH3CO) aO. Reagent 5 HMO3 Reaction conditions: molar ratio of reagents 1.2.3: 4: 5 1: 3- З. ГГ-1,5 3-3,1.2-2,5 at 18-20 ° С, 4tab.

Description

The invention relates to imidazole nitro derivatives, and more particularly, to an improved method for the preparation of 2-methyl-4 (5} -nitroimidazole, which is an intermediate in the synthesis of 1- (ft-oxystyl) -2-methyl-5-nitroimidazole (metron idaol) -p To the genus KTA, in particular of practical interest as an anti-trichomonas agent.

A known method for producing 2-methyl-4 (5) -nitroimidazole by nitration of 2-methylimidazole with a mixture of nitric and sulfuric acids at an elevated temperature, pouring the reaction mixture onto ice and neutralizing with ammonia.

The closest in technical essence and the achieved result is a method for producing 2-methyl-4 (5) -itroimidazole by nitration of 2-methylimidazole with a mixture of concentrated sulfuric and nitric acids and neutralizing the reaction mixture with ammonia.

The disadvantages of the known methods are the low yield of 2-methyl-4 (5) -nitroimidazole, the low technological quality of the process due to the difficulty of controlling the temperature regime by alternating dosing of acids, the high reaction temperature, and the formation of a large amount of the mother liquor of inorganic salts after neutralization.

The aim of the invention is to increase the yield and simplify the process.

This goal is achieved by treating 2-methylimidazole in acetic acid with sulfuric acid in the presence of acetic anhydride, followed by nitration with nitric acid at a temperature of 18-20 ° C at a ratio of 2-methylimidazole: acetic acid: sulfuric acid: acetic anhydride: nitric acid, equal to 1: 3-3.1: 1-1.5: 3-3.1: 2-2.5.

Example, A suspension of 0.82 g (0.01 m) of 2-methylimidazole in 1.71 ml (0.03 m) of acetic acid is cooled to 10 ° C, 1.08 ml (0.01 m) of sulfuric acid (, 84) and 2.83 ml (0.03 m) of acetic anhydride are added. The reaction mixture is maintained.

cl

with

Xi

30 min at 60-65 ° С, 0.84 ml (0.02 m) of nitric acid are cooled and added dropwise (, 5). It is kept for 3-3.5 hours at 18-20 ° C, cooled, neutralized with a 25% aqueous ammonia solution to a pH of 6.5-7, filtered off, washed with water, and dried. 1.13 g (90%) of 2-methide-4- (5) - nitroimidazole are obtained with a melting point of 252 ° C.

Identification of the product of a complete breakdown of the mixture of Tz AvedoMo known by the sample and comparing them 1 / 1KGSP with CT

The data from the steel trials of tuffedoma, Table 1-4. , - The ratio of the components 2-mstipi midazole: sulfuric acid: nitric acid 1: 1-1.5: 2-2.5, temperature 10-2 0 ° С.

The ratio of the components 2-methylimidzozole: acetic acid: acetic anhydride; nitric acid 1: 3-3.1: 3-3.1: 2-2.5, reaction temperature 18-20 ° С.

The ratio of components 2 is methylimidazole: acetic acid: sulfuric acid: acetic anhydride 1: 3-3.1: 1-1.5.3-3.1, the reaction temperature is 18-20 ° C.

The ratio of the components 2-methylimidazole: acetic acid: sulfuric acid: nitric acid 1: 3-3.1: 1-1.5: 3-3.1: 2-2.5,

From the data table. 1-4 it is seen that when the molar ratio of the components of 2-methylimidazole: acetic acid: sulfuric acid: nitric acid decreases, the yield of 2-methyl-4 (5) -nitro01 / midezole decreases. An increase in the molar ratios of the components has practically no effect on the yield. Both a decrease and an increase in the reaction temperature lead to a significant decrease in the yield of 2-methyl-4 (5) -nitroimidazole,

Optimum conditions for the preparation of 2-methyl-4 (5) -nitroimidazole are the molar ratio of the components 2-methylimidazole: acetic acid: sulfuric acid: acetic anhydride; nitric acid 1.3-3.1: 1-1.5: 3-3.1.2-2.5, reaction temperature 18-20 ° C.

The advantages of this method, in comparison with the prototype, are:

- an increase in the yield of 2-methyl-4 (5) -nit; roimidazole from 54 to 90%;

- simplification of the technological process: lowering the reaction temperature from 130-150 ° C to 18-20 ° C, no need

adjusting the reaction rate by alternating dosing of acids, reducing the consumption of mineral acids per mole of 2-methylimidazole;

- neutralization of inorganic acids in a dilute acetic acid solution

Claims (1)

The claims A method for producing 2-methyl-4 (5) -nitro-imidazole by treating the starting 2-methylimidazole with sulfuric acid and further nitration with nitric acid, characterized in that, in order to increase the yield and simplify the process, sulfuric acid is treated acetic acid medium with the addition of acetic acid anhydride, nitration is carried out at 18-20 ° C and the molar ratio of 2-methylimidazole: acetic acid: sulfuric acid: acetic anhydride: nitric acid is 1: 3-3, 1: 1-1.5: 3-3.1: 2-2.5. Table 1 Effect of the molar ratio of acetic anhydride vi acetic acid on the yield of 2-methyl4 (5) - nitroimidazole. Table 2: Effect of the molar ratio of sulfuric acid on the yield of 2-methyl-4 (5) - nitroimidazole TABLE 3 Effect of the molar ratio of nitric acid on the yield of 2-methyl-4 (5) - nitroimidazole Table 4 Effect of reaction temperature on the yield of 2-methyl-4 (5) - nitroimidazole.