CS212697B1 - Method for Refining Ethyl Ethyl Acetyl Acetate - Google Patents

Abstract

A method for refining ethyl isopropylacetoacetate, prepared by isopropylation of ethyl acetoacetate salt, comprising treating the reaction mixture, after separation of inorganic products by extraction with water, with phenylhydrazine at a temperature of 20 to 80 °C. The unwanted ethyl acetoacetate preferentially reacts to give products from which ethyl isopropylacetoacetate is easily separated by distillation. Ethyl isopropylacetoacetate is an important intermediate for the pharmaceutical and chemical industries.

Description

The present invention relates to a process for refining ethyl isopropyl acetate, prepared by isopropylation of an alkali metal salt of ethyl acetate.

Ethyl isopropyl acetoacetate is prepared by treating isopropyl acetate sodium salt in an anhydrous medium by treating isopropyl iodides, which may be diisopropyl sulfate, isopropyl iodide or isopropyl bromide. The reaction proceeds according to the scheme:

X-CH + CH ₃ COCH (Na) COOC ₂ H ₅ - → CH 2 OCHCO ₃ COOC ₂ H ₅ + NaX ₃ where X is an iodide, bromide or sulfate moiety. The reaction rate constant is rather small, so that the reaction cannot be completely converted in real time and a certain amount of ethyl acetate is always present in the reaction mixture after extraction of the inorganic reaction products with water.

Due to the further synthetic use of ethyl isopropylacetate, which may be, for example, reaction with phenylhydrazine to form 1-phenyl-3-methyl-4-isopropylpyrazolone to give methyl isopropylantipyrine, an important antipyretic, the presence of ethyl acetate is undesirable an antipyrine was formed which would have to be separated from the final pharmaceutical product by intensive crystallization. The only effective procedure, based on current knowledge, was the rectification separation of ethyl acetate.

Although the boiling points of the two components are relatively far apart, 180, respectively.

201 ° C at atmospheric pressure, there are enormous demands on rectification equipment, especially because, due to the instability of distilled substances, the rectification equipment must operate at a pressure of at most 133 Pa. The process for refining ethyl isopropylacetate according to the present invention is based on the finding that ethyl acetate is much easier to react with phenylhydrazine than ethyl isopropyl acetate.

SUMMARY OF THE INVENTION The reaction mixture obtained by isopropyl acetate of ethyl acetate is treated with phenylhydrazine, after the separation of the inorganic products by extraction with water, which is added in an amount of 1 to 3 moles per 1 mol of unreacted ethyl acetate, present at 20 to 80. Deň: 32 ° C. Under these conditions, ethyl acetate is preferably reacted to the fumes from which ethyl isopropyl acetate is readily separated by simple distillation. The reaction products are 1-phenyl-3-methylpyrazolone, respectively. 1-phenyl-3-methyl-4-isopropylpyrazolone.

The method according to the invention is further illustrated by the following examples:

Example 1

To 1,210 g of a solution containing 0.8% ethyl acetate and 18.2% ethyl isopropyl ethyl acetate prepared by alkylation of sodium ethyl acetate with dilsopropylsulfate in chlorobenzene was added 11.3 g of phenylhydrazine while stirring and maintaining the temperature at 50 ° C. After one hour, the reaction mixture was subjected to simple vacuum distillation. Fractions were obtained:

1. Chlorobenzene 943 g, boiling in the range of 29 to 32 ° C at 3.3 kPa

2. an intermediate fraction of 25 g, boiling in the range of 32 to 80 ° C at 3.3 kPa

3. Ethyl isopropylacetate 205 g, boiling in the range 55 to 58 ° C at 115 Pa.

The third fraction contained 0.4% ethyl acetate as analyzed. The yield was 93% of product, based on the amount of ethyl isopropylacetate taken for refining.

2,2697

Example 2

500 g of the reaction mixture obtained in the same manner as in Example 1 and containing 3.8% ethyl acetate, 17.6% ethyl isopropylacetate in chlorobenzene was freed from chlorobenzene by simple vacuum distillation to obtain:

090 g of chlorobenzene and 400 g of a mixture of 19% chlorobenzene, 4% ethyl acetate and 67% ethyl isopropyl acetate. 71 g of phenylhydrazine was added to the mixture at 40 ° C with stirring, and after one hour of standing, the reaction mixture was distilled by simple distillation. Two fractions were obtained:

1. an intermediate fraction of 85 g, boiling in the range of 25 to 80 ° C at 3.2 kPa

2. Ethyl ethyl isopropyl acetate acetate 240 g, boiling in the range 56 to 59 ° C at 120 Pa.

According to gas chromatography analysis, ethyl isopropylacetate contained 0.3% ethyl acetate. The refining yield was 91%.

Example 3

890 g of the reaction mixture obtained in the same manner as in Example 1 and containing 2.4% ethyl acetate and 18% ethyl isopropylacetate in chlorobenzene were freed from chlorobenzene by simple vacuum distillation to obtain:

650 g of chlorobenzene and 240 g of a mixture containing 23% chlorobenzene, 9% ethyl acetate and 68% ethyl isopropyl acetate. To this mixture was added at 20-25 ° C

21.3 g of phenylhydrazine and the reaction mixture after homogenization was allowed to stand for 24 hours. It was then separated by simple vacuum distillation into two fractions:

1. an intermediate fraction of 65 g, boiling in the range of 25 to 80 ° C at 3.2 kPa

2. Ethyl isopropylacetate 150 g, boiling in the range of 56 to 59 ° C at 20 Pa.

Analysis by gas chromatography showed that ethyl isopropylacetate, second fraction, contained 0.1% ethyl acetate. The yield was 92%.

Claims (1)

SUBJECT OF THE INVENTION Process for refining ethyl isopropyl acetate, prepared by isopropylation of an alkali metal salt of ethyl acetate, characterized in that the reaction mixture from isopropylation, free of inorganic products by reaction with water extraction, is treated with phenylhydrazine added in an amount of 1 to 3 moles per 1 mol of unreacted ethyl acetate. at 20-80 ° C, then ethyl isopropyl acetate is separated by distillation.