SU403164A1 - - Google Patents

Description

METHOD FOR PRODUCING CHLORACYLANE DERIVATIVES

one

The invention relates to an improvement in the process for the preparation of chloroacylanilide derivatives, which can be used as biologically active compounds.

A known method for producing derivatives of chloroacyl anilides of general formula I

B1.,

one

. % .4 CO-C-C1 h. I

All

RI

where RI is a phenyl or alkyl group; R2 is hydrogen or halogen; Rs is hydrogen or alkyl with one to four C atoms; Xi is hydrogen, halogen or methyl

Group; X2 is hydrogen, halogen or methyl

Group.

The method is that aniline derivative of general formula II

NH-RI

where Xl Ho, RI have the indicated meanings, are reacted with an acylating agent, chlorocarboxylic acid chloride, in the medium of an organic solvent in the presence of an aqueous alkali solution while cooling to a temperature not higher than 0 ° C, followed by isolation of the target product by a known technique.

The disadvantage of this method is

the complexity of the process and the low yield of the target product, associated with the direct production of the raw material, chlorocarboxylic acid chloride, before the acylirovanium process (the latter is variegated

products and easily hydrolyzed). In order to eliminate the above mentioned disadvantages, it is proposed to use chlorocarboxylic acid of general formula as an acylating agent.

C1-o-g, 6oi

.

where Ro, RS have the indicated meanings, and conduct the process in an anhydrous medium

in the presence of phosphorus trichloride.

The process is conducted at a temperature of from 80 ° C, preferably from 100 ° C, to the boiling point of the reaction mixture.

The proposed method allows to obtain the desired product with a yield of approximately 62-79%.

Example 1. Preparation of N-isopronyl chloroacetanilide.

To 20 g (0.21 mol) of monochloracetic acid is added dropwise with stirring at 65 ° C 13.7 g (0.1 mol) of phosphorus trichloride. 27 g (0.2 mol) of N-isopropyl-propylin are added simultaneously. The reaction mixture was changed at 100– for 3 hours, the excess phosphorus trichloride was distilled off with a vacuum pump, the residue was cooled to 80 and poured, with vigorous unmixing, into water, continuing stirring until precipitation occurred. The material is filtered off, washed with water and dried. Obtain 35.5 g of crystalline raw product straw color with t. Nl. . After recrystallization from hexanol, 34 g of pure product with m.p. , yield 77% of theory.

Calculated,%: C1 16,74.

Found%: C1 16.7.

Example 2. Obtaining N-methylchloroacetanilide.

To 5 g (0.047 mol) of methylaniline, 2.1 ml (0.0235 mol) of phosphorus trichloride was added over the canals to stirring and cooling. 4.4 g (0.047 mol) of monochloroacetic acid are added to the white precipitate, the reaction mixture is kept for 1.5 hours at 100 ° C, 20 ml of water is added, the mixture is heated to 80 ° C and stirred until a precipitate forms while cooling. The precipitate is filtered off, washed with water, heated to 80 ° C and dried with air. 6.4 g of crude product are obtained with an mp. 66 ° C. After non-recrystallization from isopronanol, 6 g of pure product are obtained with a mp. 70 ° C, yield 70% of theory.

Calculated,%: C1 19.40.

Paydeno,%; C1 19.4.

Example 3. Obtaining N-methyldichloroacetanilide.

2.1 ml (0.02535 mol) of phosphorus trichloride were added dropwise to 5 g (0.047 mol) of methylaniline, then 6 g of trichloroacetic acid, and the reaction mixture was kept at 100 ° C for 75 minutes. 20 ml of water are added and the mixture is heated to 80 ° C and cooled while stirring.

The precipitate is filtered off, washed with water and dried. Obtain 8.7 g of white crystalline raw No product with so nl. 60 ° C. After recrystallization from isopropanol, a pure product is obtained with a m.p. 69 ° C, yield 79% oi theory.

Calculated,%: C1 32,59.

Paydepo,%: C1 32,7.

Example 4. Preparation of N-isopropyl-2-chlorobutyrylaiylin.

1.08 ml (0.0122 mol) of phosphorus trichloride, then 2.66 g (0.0185 mol) of N-chloroacid acid were added to 2.5 g (0.0185 mol) of isopropyl-propylin in 10 ml of anhydrous benzene. The reaction mixture is heated on an oil bath with reverse non-distillation for 3 hours, then the solvent is distilled off in vacuo, the residue is poured into water. The mixture is alternated until oily product is precipitated. The product is filtered, nromivat water n Sunsht. 3.2 g of crude product are obtained. After non-recrystallization from a mixture of water and methanol, 2.88 g of pure product with m.p. 53 ° C, yield 65% of theory.

Calculated,%: C1 14.96. Paydeno,%: C1 15.0.

Example 5. Poluchenpe N-fayyldichloroacetanilide.

To a solution of 6 g (0.0355 mol) of diphenylamine

4.7 g (0.0355 mol) of dichloroacetic acid and 2.2 ml of phosphorus trichloride are added to 15 ml of anhydrous benzene. The reaction mixture is heated under reflux for 4.5 hours, the benzene is distilled off in vacuo, the residue is suspended in water, filtered, washed with water and dried. 6.5 g of a light yellow crude product are obtained. After non-recrystallization from ethanol, 6.15 g of pure product are obtained with a mp. 78-79 ° C. Output 62% of theory.

Calculated,%: C1 25.90. Paydeno,%: C1 26.0.

Example 6 Preparation of N-methyl-n-chlorfeiyl chloroacetamide

To 5.6 g (0.0396 mol) of a solution of N-methyl-dchloroaniline in 20 ml of anhydrous benzene, 2.7 g (0.0198 mol) of phosphorus trichloride and 3.8 g (0.04 mol) of chloroacetic acid are added. The reaction mixture was allowed to reflux for 4 hours, then

the solvent is distilled off in vacuo, the residue is taken up in 25 ml of water at 80 ° C, then cooled with vigorous stirring. The product is filtered, washed with water and dried. 6.6 g of crude product are obtained. After recrystallization from ethanol, 6.35 g of pure product with m.p. 168 ° C, yield 74% of theory.

Calculated,%: C1 32,75. Paydeno,%: C1 32.70.

Example 7. Preparation of N-3-dimethylchloroacetanilide.

4.2 g (0.0346 mol) of N-methyl-l (-toluidine is dissolved in 15 ml of anhydrous benzene. 2.37 g (0.0173 mol) of phosphorus trichloride and 3.32 g (0.0346 mol) are added. a) Chloroacetic acid. The reaction mixture is boiled under reflux for 2 hours, then poured into 20 ml of water at 80 ° C and cooled while stirring. 5.05 g of crude product is obtained; after recrystallization from alcohol, 4.76 g of pure product are obtained mp 71 ° C, yield 70% of theory. Calculated,%: CI 18.02.

Paydeno,%: C1 18.1.

Subject invention

The method of obtaining derivatives of chloroacyl and the general formula

R.

T -CO-C-C1

R,

RI

where RI is phenyl or alkyl group with

one to four C atoms; R2 is hydrogen or halogen; Ks is hydrogen or alkyl with one to four C atoms; Xi is hydrogen, halogen or methyl

Group; X2 is hydrogen, halogen or methyl

Group;

by reacting an aniline derivative of the general formula

Xi

NH-Ri

Ho

where X |, X0, RI have the indicated values, with an acylated agent, followed by separation of the non-product by a known technique, with the fact that, with a technological process and increase in the yield of the target product, as chlorinated carboxylic acid of general formula

Ro

C1 C-SOOI

RS

where RQ and Ra have ukazapnye values, and

the process is conducted in a waterless environment in the presence

phosphorus trichloride irp temperature from

80 ° C to the boiling point of the reaction

mixes.