KR800001147B1 - Process for 1-alkyl-2-(phenoxyl methyl)-s-nitro-imidazole - Google Patents

Abstract

Title imidazoles (I, R1 = methyl, R2 = methylsulfonyl, ethylsulfonyl, R3 = H, methyl, halogen) are prepd. by oxidation of 1-methyl-2-(penoxymethyl)-5-nitroimidazoles (II, A = sulfur atom, sulfoxide group(-s) at 40o-60oC in solvent. Thus, 27.9g l-methyl-2-(4-methylthio-phenoxy-methyl)-5-nitroimidazole) was dissolved in 250ml acetic anhydride and heated with 30% hydroperoxide 24.3g at 60oC for 1hr. to give 29g 1-methyl-2-(4-methylsulfonyl-phenoxymethyl)-5-nitroimidazole.

Description

Method for preparing 1-alkyl-2- (phenoxymethyl) -5-nitro-imidazole

The present invention relates to a process for preparing 1-alkyl-2- (phenoxymethyl) -5-nitro-imidazole, the following structural formula (I) useful as a drug.

In the above structural formula

R1 represents methyl.

R2 represents methylsulfonyl or ethylsulfonyl.

R 3 represents halogen, such as hydrogen, methyl or fluorine, chlorine, cancelled or iodine.

1-alkyl-2- (phenoxymethyl) -5-nitro-imidazoles of the following structural formulas, methods for preparing these compounds, pharmaceuticals and uses containing them are known from German Publication No. 2,459,395.

In the above structural formula

R ¹ represents methyl or ethyl.

R ² represents trifluoromethyl, trichloromethyl, nitro, cyano, methylsulfonyl or ethylsulfonyl.

R ³ represents hydrogen, fluorine, chlorine cancellation, iodine, trifluoromethyl, trichloromethyl, nitro or cyano.

The serial application numbers submitted here are 1-methyl-2- (phenoxymethyl) -5-nitro-imidazoles of the following structural formulas, methods for preparing these compounds, drugs containing them, and uses thereof.

In the above structural formula

R ₂ represents nitro, cyano, methylsulfonyl or ethylsulfonyl.

R ¹ represents methyl or halogen.

Further development of the No. 2,459,395 in the German publication name, the oxidation of 1-methyl-2- (phenoxymethyl) -5-nitro-imidazole of the following structural formula II

(Wherein A is a sulfur atom or a sulfoxide group (-SO-),

R is methyl or ethyl, R 1 is methyl,

R3 is hydrogen, methyl or halogen such as fluorine, chlorine, clear, iodine)

A process for preparing 1-alkyl-2- (phenoxymethyl) -5-nitro-imidazole of formula (I) was found.

(In the structure, R ¹ is metal, R ² is methylsulfonyl or ethyl selfonyl, and R ³ is hydrogen, methyl or fluorine, chlorine, cancellation, halogen such as iodine.)

The 1-methyl-2- (phenoxymethyl) -5-nitro-imidazoles of formula II used as starting material are disclosed in German Publication No. 2,531,303. These compounds can be obtained from 1-methyl-2-chloromethyl-5-nitro-imidazole (obtainable in accordance with German Publications 1,595,929 and 1,470,102) and optionally dimethylformamide and calcium carbonate Is substituted with alkylmercaptophenol or alkylsulfinylphenol (which can be obtained by optionally continuing oxidation of the corresponding mercaptophenol and dialkylsulfate onto the pibenzoin phase).

Suitable starting compounds of formula II are for example

For oxidation, it is advantageous to use one mole or two moles of oxidant. In many cases it is advantageous to use excess oxidant. At least 2 molar equivalents of oxidant are required when the corresponding sulfide (A = -S-, structural acid II) is used as starting material.

One molar equivalent of oxidant should be used when the corresponding sulfoxide (A = -S-, structural acid II) is used as starting material.

Suitable oxidizing agents are for example hydrogen peroxide or ferrasides, for example peracechin, phyrifluoroacetinic acid, chloroperbenzoic acid, in particular 3-chloroperbenzophosphoric acid, nitric acid, chromic acid and salts thereof, chromic acid anhydride, per Manganate, hypochlorous acid, chlorate, perchlorate and iodide or nitric oxide, in particular dinitrogenteroxide.

The oxidation reaction is preferably carried out in a solvent or a dispersant. Conversely, solvents which are not affected by oxidizing agents such as acetin or trifluoroacetinic acid are particularly suitable. When using perbenzoic acid, alternatively methylene chloride or chloroform is a suitable solvent. The oxidation reaction is generally carried out at a temperature of 0-100 ° C., in particular 40-60 ° C. The reaction time varies from several minutes to several hours depending on the reaction conditions.

The product of the process according to the invention can be separated from the precipitate by diluting the reaction solution in water or by evaporating the organic solvent under reduced pressure. Optional purification can be done by recrystallization from a suitable solvent or solvent mixture. The following examples illustrate the invention.

Example 1

1-Methyl-2- (4-methylsulfonyl-phenoxymethyl) -5-nitro-imidazole

27.9 g of 1-methyl-2- (4-methylsulfonyl-phenoxymethyl) -5-nitro-imidazole) melting point 116 ° C.) are dissolved in 250 ml of glacial acetic acid, and 24.3 g (0.25 mol) of 30% hydrogen peroxide at room temperature. Add dropwise with stirring. The exothermic reaction raises the temperature to about 45 ° C. The batch is then heated at 60 ° C. for 1 hour with stirring. After cooling to room temperature the batch is placed in 800 ml of ice water mixture and the precipitate is suction filtered. Wash with water and recrystallize from isopropanol by adding activated carbon.

29 g of 1-methyl-2- (4-methylsulfonyl-phenoxymethyl) -5-nitro-imidazole (= 93% of theory) are obtained in the form of a yellow crystalline having a melting point of 157 ° C.

Instead of the starting material 1-methyl-2- (4-methylsulfonyl-phenoxymethyl) -5-nitro-imidazole, the corresponding sulfoxides, ie 1-methyl-2- (4-methylsulcinyl-phenoxy Dimethyl) -5-nitro-imidazole (melting point 130 ° C.) may be used. In this case, half the amount of hydrogen peroxide may be used. In the same manner, the following compounds can be prepared.

Claims (1)

Characterized by oxidizing 1-methyl-2- (phenoxymethyl) -5-nitro-imidazole of formula

(Wherein A is a polysulfur atom or sulfoxide group (-SO-), R is methyl or ethyl, R ¹ is methyl and R ³ is hydrogen, methyl or halogen.) 1-alkyl- of formula (I) Method for preparing 2- (phenoxymethyl) -5-nitro-imidazole.

(Wherein R ¹ is methyl, R ² is methylsulfonyl or ethylsulfonyl and R ³ is hydrogen, methyl or halogen).