CS218508B1 - Process for preparing D, L-threo-2-acetamido-1- (4-nitrophenyl) -1,3-propanediol - Google Patents

Abstract

Method for the production of D,L-threo-2-acetamido-O-1-(4-nitrophenyl)-1,3-propanediol II by reduction of 2-acetamido-3-hydroxy-1-(4-nitrophenyl)-1-propanone I by the action of 2-propanolate or a mixture of 2-propanolate and chloro-bis-2-aluminum propanate. The method according to the invention consists in that the reduction is carried out with a mixture of 2-propanol and aluminum chloroO-bis-2-propanol enriched with zinc or iron, or their salts with inorganic or organic acids in an amount of 1.2.10-4 to 0.5 mol. % based on 1 mol of aluminum used, at a temperature of 30 to 85 CC, with the starting ketone I being added to the reducing agent in portions over a period of 0.1 to 5 hours and the resulting acetone being preferably distilled off from the reaction mixture in the range of 20 to 80%.

Description

The invention relates to a process for the preparation of D, L-threo-2-acetamido-1- (4-nitrophenyl) -1,3-propanediol (II) by reducing 2-acetamido-3-hydroxy-1- (4-nitrophenyl) -l-propanone (I) by the action of 2-propanolate or a mixture of 2-propanolate and aluminum chloiro-bi-2-propanolate by the so-called Meerwein, Ponndorf and Verley reduction.

The reduction of 2-acetamido-3-hydroxy-1- (4-nitrophenyl) -1-propanone (I) to diol II is one of the steps in the production of the antibiotic chloramphenicol. A mixture of aluminum 2-propanolate and aluminum chloro-bls-2-propanolate is prepared according to the known process, which results in a conversion of ketone I to diol II of 75-83%.

A disadvantage of this process is the conversion of unreacted or ketone I into substances that contaminate and significantly reduce the yield of the reduction product.

These disadvantages are overcome by the process of the present invention, which consists in reducing the ketone of 2-aceitamido-3-hydroxy-1- (4-nitrophenyl) -1-propanone to D, L-threo-2-acetamido-1- The (4-nitrophenyl) -1,3-propanediol is carried out with a mixture of 2-propanolate and aluminum chloiro-bis-2-propanolate enriched with zinc or iron, respectively. their salts with inorganic or organic acids in an amount of 1.2.10 ^-4 to 0.5 mol. Based on 1 mol of aluminum used, at a temperature of 30 to 85 ° C, the starting ketone is added to the reducing agent in portions over a period of 0.1 to 5 hours, and the acetone formed from the reaction mixture is preferably from 20 to 80 ° / os distills off.

The effect of zinc and iron and their salts results in a faster, less disturbed reduction of the ketone I with 92-98% diol II conversion by side reactions.

O-CH 2 -CO-CH-CH 2 OH ₃

Substance I

Examples

Example 1

To 4.0 g of aluminum shavings and 0.4 g of zinc powder was added 50 ml of 2-propanol and 2.5 ml of carbon tetrachloride. After the addition of 0.01 g of sublimate, the reaction mixture was heated to 75 ° C. After dissolution of aluminum, a suspension of 20.0 g of ketone I in 30 ml of 2-propanol was added to the resulting mixture. After distilling off about half of the acetone formed, the reaction mixture was quenched with 54 mL of a 5% aqueous 2-propanol solution. The resulting precipitate of aluminum complex and diol II was filtered off and the separated complex was dissolved in 200 ml of 10% aqueous ethanol solution. After alkalization to pH 7.5, the precipitated hydroxide was filtered off. Evaporation of the filtrate afforded 19.6 g (98%) of diol II.

at

Fabric II

Example 1 a d 2

50 ml of 2-propanol and 2.5 ml of carbon tetrachloride were added to a mixture of 0.2 g of iron powder and 4.0 g of aluminum shavings. After the addition of 0.01 g of sublimate, the reaction mixture was heated to 75 ° C. After all the aluminum had dissolved, the ketone I was reduced and the diol II was isolated as described in Example 1. 18.5 g (93%) of the diol II were obtained. Example 1 a d 3

To a mixture of 4.0 g of aluminum shavings and 0.1 g of zinc chloride was added 50 ml of 2-propanol and 2.5 ml of carbon tetrachloride. After the addition of 0.01 g of sublimate, the reaction mixture was heated to 75 ° C. After all the aluminum had dissolved, a suspension of 20.0 g of ketone I in 30 ml of 2-propanol was added to the resulting mixture. The procedure was as described in Example 1. The yield was 94% of diol II.

Claims (1)

Process for the preparation of D, L-threo-2-acetamide ^and ol- (4-nitrophenyl) -1,3-propanediol by reduction of 2-acetamido-3-hydroxy-1- (4-nitrophenyl) -1-propanone by 2-propanoate or a mixture of aluminum 2-propanolate and aluminum chloro-bis-2-propanolate characterized in that the reduction is carried out with a mixture of aluminum 2-propanolate and aluminum chloro-bis-2-propanolanite enriched with zinc or iron, or their inventive salts with inorganic or organic with acids in an amount of 1.2.10 ^-4 to 0.5 mol%, based on 1 mol of ¹ aluminum used, at a temperature of 30 to 85 ° C, the starting ketone being added to the reducing agent in portions over a period of 0.1 to 5 hours; and The resulting acetone is preferably distilled off from the reaction mixture by 20 to 80%.