DE2853732A1 - Prepn. of di:propyl-acetic acid - by reacting di;ethyl malonate with propyl bromide and heating the resulting di:propyl-malonic acid - Google Patents

Abstract

Dipropylacetic acid (I) is made by first reacting diethylmalonate (II) with n-propylbromide (III) in the presence of NaOMe. The resulting dipropylmalonic ester (IV) is saponified with an alkali to give dipropylmalonic acid (V). The (V) is recovered and heated to give (I) with splitting off of CO2. The process gives high yields of (I). The prod. is completely free from by-prods. and thus has a high degree of purity. The crystalline (V) is heated to >160 degrees C until evolution of CO2 has ceased, then the residue is distilled to give high purity (I).

Description

Process for the preparation of di-n-propyl acetic acid

The invention relates to a new method for producing the for Di-n-propyl acetic acid for pharmaceutical purposes. It is characterized by that diethyl malonate in the presence of sodium ethylate with n-propyl bromide converts, the resulting dipropylmalonic ester saponified by means of alkali, the resulting dipropylmalonic acid is separated off and this is split off by heating converted from carbon dioxide into di-n-propyl acetic acid.

For the steps of the process outlined, one can, for example use the route described below.

Malonic acid diethyl ester and n-propyl bromide are required Molar ratio with the essentially equivalent amount of sodium ethylate in ethanol implemented at elevated temperature.

When the reaction has ended, the excess alcohol is distilled off and treating the residue with aqueous alkali at an elevated temperature. After removal the remaining amount of solvent is acidified with mineral acid and the reaction product brought to crystallization by cooling.

The crystalline dipropylmalonic acid is separated off and stirring is carried out gradually heated to temperatures above 160 C. The process continues until until the splitting off of carbon dioxide has ended. The remaining residue will distilled, very pure dipropylacetic acid being obtained in high yield.

The product obtained is completely free of by-products like them can result from monosubstitution of the malonic ester.

Example: 0 For a mixture of 4.81 parts by weight heated to 60 - 62 ° C Diethyl malonate and 7.38 parts by weight of n-propyl bromide are allowed to form a solution of 3.24 parts by weight of sodium methylate (100%) in 30 parts by volume of ethanol within flow from 4 - 5 hours. Then as long as reflux, at about 740 C, heated until the pH of the reaction mixture is about 9. After this Distilling off 27 parts by volume of alcohol becomes 11.5 parts by weight of a concentrated (44.3% own), aqueous potassium hydroxide solution added.

The mixture is kept at reflux temperature for 4 hours, then cooled and, after adding 13 parts by volume of water, heated to 1000 c for as long as up to 15-16 parts by volume of distillate are obtained.

9.93 parts by weight are added to the residue, which has been cooled to about 800 ° C. concentrated hydrochloric acid (37.5%) was added. The pH must be in strongly acidic range (around 1). Under gradually increasing cooling will cooled down to + io0 c.

The reaction product then crystallizes.

After prolonged stirring at loOC, it is centrifuged and with cold Washed with water. After drying, 2.56 parts by weight of pure di-n-propylmalonic acid are obtained. It is almost pure white, coarsely crystalline, has a melting point of 154 - 1560 C and a content (titrated) of 99.5%.

The content of monopropylmalonic acid (determined by gas chromatography) is below 0.2%.

The dry product is now with stirring and a gradual increase in temperature heated to 160 - 165 C. If the development of carbon dioxide starts with foaming, then the reaction temperature is kept as constant as possible by careful supply of heat held at 165-170 ° C. until the evolution of gas has ceased. The obtained, liquid Immediately thereafter, the reaction product is distilled off under reduced pressure. The main fraction passing between 117 - 1240 C (at 12 - 15 Torr) consists of Over 99% colorless, water-clear di-propyl-acetic acid.

1.86 parts by weight are obtained, corresponding to a yield of 95 %, based on dipropylmalonic acid, or 42.9% based on diethyl malonate used.

Claims (1)

Claim: Process for the production of dipropylacetic acid, characterized in that diethyl malonate in the presence of sodium ethylate reacts with n-propyl bromide, the resulting dipropylmalonic ester by means of alkali saponified, the resulting dipropylmalonic acid is separated off and heated under Splitting off of carbon dioxide converted into di-n-propyl acetic acid.