SU222399A1 - METHOD OF OBTAINING O-CAR BAM DERIVATIVES AND DET-METIL-N-KAPBOALKOKSIHYDOPOXICILAMIHA - Google Patents

Description

This invention relates to a process for the preparation of O-carbamidomethyl-M-carboalkoxyhydroxylamine derivatives of the general formula

R N - COOZ I O - CH - CONHX,

where r

alkyl or aryl containing chlorine or methyl as a substituent;

X - H, alkyl, aryl; Y is H, alkyl, aryl, CHoCl; Z is alkyl.

The compounds have physiologically active properties and can be obtained by reacting M-alkyl- (L-aryl) -M-carboalkoxyhydroxylamine with unsubstituted or substituted amides of a-chloroalkylcarboxylic acids with nitrogen and in the a-position in the presence of caustic alkalis and in an environment of a homogeneous hydroorganic solvent at a temperature not exceeding 25 ° C.

Example 1. O-Carbamidomethyl-M-Carboisopropoxy-M-tolylhydroxylamine.

-tolylhydroxylamine in 6 ml of dioxane and 2.8 g (0.03 mol) of a-chloroacetampe in 40 ml of water-dioxane solution (water to dioxai 1: 2). With good stirring and a temperature of about 20 ° C, 30 needles 1 and 1 are gradually added dropwise to the mixture. an aqueous solution of sodium hydroxide, after which the reaction mixture is stirred at room temperature for 9 hours. At the end of the reaction, the mixture is extracted with benzene (3 times 50 ml each). To remove unreacted X-Carboisopropoxy-M-; g - tolylhydroxylame Ea, the combined benzene extracts are washed with 1% sodium hydroxide solution, then with water until neutral of the wash water and dried over anhydrous magnesium sulphate. The solvent is distilled off from the dried benzene solution to obtain an oily substance, which crystallizes by adding a small amount of hexane and rubbing the mixture with a glass rod. Yield 7 g (87.5% of theoretical); m.p. (from hexane).

Chromatography in a thin layer appears as an intensely colored spot (solvent system hexane-acetone 3: 2, developer universal).

Calculated,%: C 58.63; H 6.81; N 10.52.

Similarly, but using acetone as an organic solvent instead of dioxane, the following is obtained:

O-carbamidomethyl-Y-carboisopropoxy - N methyl hydroxylamine, O-carbamidomethyl - N carboxy propoxy-M-phenyl hydroxylamine. Yield 74.9% of theoretical; m.p. 82-83 ° C (pz mixtures of methyl alcohol - water).

Found,%: N 10.85; 11.11.

CioHiaNsOi.

Calculated,%: N 11.10.

O- (Sat-Chloromethyl-urea); 0- (a-phenylcarbamidomethyl) -H-carboisopropoxy-H-phenylhydroxylamine;

O-carbamidomethyl-N-carbethoxy-M - phenylhydroxylamine; yield 60%; m.p. 92-93 ° C (from hexane).

Found,%: N 12.28; 12.32.

CilHl4N2O4.

Calculated,%: N 12.38.

O- (K-Phenylcarbamidomethyl) -M - carboisopropoxy-M-phenylhydroxylamine.

Example 2. O- (N-Methylcarbamidomethyl) H-carboisopropoxy-M-phenylhydroxylamine.

Analogously to example 1 of 9.75 g (0.05 mol) N-carboisopropoxy-M-phenylhydroxylamine, 5.37 g (0.05 mol) of N-methylchloroacetamide, 50 ml of 1N. NaOH with stirring in aqueous dimethylformamide at 20-25 ° C for 6.5-7 hours to get 7.5 g of substance with so pl. 40-41 ° C (from hexane).

Found,%: N 10.58; 10.51.

CisHigNaOi.

Calculated,%: N 10,52.

Example 3. O-Carbamidomethyl-H-carboisopropoxy-N-3-chlorophenylhydroxylamine.

Analogously to example 1 of 6.88 g (0.03 mol) of K-carbo-isopropoxy-M-3 - chlorophenylhydroxylamine, 2.82 g (0.03 mol) of chloroacetamide and 30 ml of 1N. NaOH with stirring for 7 hours at 22–24 ° C gives 5.2 g of weighed oil, m.p. 68-70 ° C (from hexane).

Found,%: N, 9.68 and 9.78, CiaHisNaOiCI.

Calculated,%: N 9.76.

Example 4. O-Carbamidomethyl-N-carbopropoxy-N-phenylhydroxylamine.

Similarly, from 6.85 g (0.039 mol) of N-carbopropoxy-N-phenylhydroxylamine, 3.65. E (0.039 lyul) chloroacetamide and 39% ln. NaOH get 5 g of substance with so pl. 62.5-63 ° C.

Found,%: N 11,32; 11.09; C, 57.27; 57.09; H 6.40; 6.69.

CisHieNaOi.

Calculated,%: N 11,10; C 57.13; H 6.38.

Example 5. 0-Carbamidomethyl-N-carbo-iso propoxy-N-W-tolylhydroxylamine. Similarly, from 2.3 g (0.0158 mol) of N-Carboisopropoxy-H-W-tolylhydroxylamine, 1.48 g (0.0158 mol) of chloroacetamide and 16 ml of 1N. NaOH with stirring for 6 hours at 20-25 ° C gives 2.46 g of substance with mp. 68 ° C.

Found,%: N 10.50; 10.55; C 58.63; 58.45; H 6.68; 6.52.

CisHigNaOi.

Calculated,%: N 10,52; C 58.63; H 6.81. Subject invention

The method of obtaining the derivatives of O-carbamidomethyl-N-carboalkoxyhydroxylamine General formula

R - N - COOZ

O - CH - CONHX, 1 U

where R is alkyl or aryl containing chlorine or methyl in the nucleus as a substituent;

X - H, alkyl, aryl;

Y is H, alkyl, aryl, CH2Cl;

Z is alkyl,

characterized in that N-alkyl- (N-apyl) -N-carboalkoxyhydroxylamine is reacted with unsubstituted or substituted under nitrogen and in the a-position with amide of a-chloroalkylcarboxylic acid in the presence of caustic alkali in an environment of a homogeneous aqueous organic solvent at a temperature not exceeding 25 ° WITH.