DE3147150A1 - Novel process for the preparation of epoxypropane derivatives - Google Patents

Abstract

The invention relates to a process for the preparation of epoxypropane derivatives by reaction of phenoxides with epichlorohydrin in a solvent mixture of water and dimethyl sulphoxide of the composition 1:0.05 to 1:2.

Description

New process for the production of epoxypropane

derivatives The present invention relates to a novel advantageous one Process for the production of epoxypropane derivatives.

Such epoxypropane derivatives are valuable starting products numerous chemical reactions. In particular, they are as immediate preliminary stages for compounds with B-receptor blocking effects that are valuable drugs represent, of importance.

It is already known to use epoxy propane compounds from various organic solvents in the presence of alkali ions To produce phenolates and epichlorohydrin (cf.

DOS 1 815 808). In the technical implementation of these procedures was previously preferably in an anhydrous medium in the presence of alkali alcoholate worked (see. The embodiments in DE-OS 1 815 808).

It has surprisingly been found that epoxypropane derivatives of the general formula (I) in which R1 stands for a straight-chain or branched alkanoylamino radical with up to 10 carbon atoms and R2 stands for an alkyl radical with up to 6 carbon atoms, obtained when phenolates of the general formula (II) in which R1 and R2 have the meaning given above and M is an alkali or alkaline earth metal, with epichlorohydrin of the formula (III) in a solvent mixture of water and dimethyl sulfoxide of the composition 1: 0.05 to 1: 2, preferably 1: 0.2 to 1: 1.2 at temperatures between 10 and 50 "C, preferably at 15 to 30" C. , in the presence of alkali hydroxide.

Water / dimethyl sulfoxide ratios are very particularly preferred from 1: 0.4 to 1: 0.9.

With knowledge of the state of the art, it could not be expected that consisting of the use of the specific solvent according to the invention from dimethyl sulfoxide and water in the specified proportions, the epoxypropane compounds can be obtained in such high yields and in such purity. The inventive Process has the following advantages over the previously known processes: a) The epoxypropane derivatives are obtained in higher yield; b) the reaction product contains the epoxypropane derivatives in higher purity, so that expensive cleaning steps not applicable for further implementation; c) the reaction takes place practically at room temperature, so that there are no major energy costs; d) through the use of cheap alkali the use of alcoholates can be avoided.

The following table shows that when using (les according to the invention Solvent mixture DMSO / water gives better yields and higher purities than using mixtures of alcohol, dimethylformamide (D! F) and acetone with water.

Table conversion of phenolates of the formula (II) with epichlorohydrin. Organic solvent: water in a ratio of 0.6: 1 each.

Yield *) in content of yield. in% impurity in relation to% pure substance Methanol / water 82.4 31.1 56.8 ethanol / water 81.8 28.4 58.6 isopropanol / water 81.8 30.4 56.9 acetone / water 77.8 28.3 55.8 DMF / water 69.0 30.4 48.0 DMF / NaOEt 92.0 40.4 54.8 water 91.0 38.0 56.4 DMSO / water 91.5 16.8 76.1 The yield data refer in all cases listed to directly incurred, no further purified product.

The further implementation of the epoxypropane derivatives into valuable active pharmaceutical ingredients takes place e.g. by reaction with alkylamines in inert organic solvents by customary methods (cf. DT-OS 1 815 808).

The production of epoxy propane derivatives is of particular interest of the general formula (1), in which R1 represents an alkanoylamino radical with up to 6 carbon atoms and R2 is an alkyl radical with up to 4, in particular with up to 2, carbon atoms.

Particularly suitable alkali hydroxides are sodium and potassium hydroxide, especially sodium hydroxide.

Examples Example 1 360 parts by weight of 5% strength sodium hydroxide solution, 100 parts by weight of 2-acetyl-4-n-butyramido-phenol, 83.3 parts by weight of epichlorohydrin and 200 parts by volume of DMSO are combined and stirred for 24 hours at room temperature . The precipitate is filtered off with suction, washed with water and dried. Yield: 114 parts by weight (91.5%) from melting point.

130-1320C and a content of 83.2%.

Comparative experiments 1 to 6 in the table were carried out analogously to the example 1 carried out. Instead of DMSO, the specified organic solvent was used in each case used.

Examples 2-5 Examples 2-5 are carried out as in Example 1; however, instead of 200 parts by volume of DMSO, the amounts given below are used used.

DMSO training in content of yield. in% vol.% based on union to parts in% to pure substance Example 2 100 90.0 24.1 68.3 Example 3 300 86r2 22.5 66.8 Example 4 400 81.8 20.7 64.9 Example 5 500 61.7 18.2 50.5 Example 6 Procedure as in Example 1, but instead of 5% sodium hydroxide solution, 5% strength Potash used.

Yield: 90.5% with a content of 82.5%.

Claims (4)

Claims 1) Process for the preparation of epoxypropane derivatives of the general formula (I) in which R1 stands for a straight-chain or branched alkanoylamino radical with up to 10 carbon atoms and R2 stands for an alkyl radical with up to 6 carbon atoms, characterized in that phenates of the general formula (II) in which R1 and R2 have the meaning given above and M is an alkali or alkaline earth metal, with epichlorohydrin of the formula (IIT) in a solvent mixture of water and dimethylsulfoxide of the composition 1: 0.05 to 1: 2 at temperatures between 10 and 50 "C in the presence of alkali metal hydroxide. 2) Process according to claim 1, characterized in that in a solvent mixture of water and dimethyl sulfoxide of the composition 1: 0.2 works up to 1: 1.2. 3) Method according to claims 1 and 2, characterized in that that the reaction is carried out at temperatures between 15 and 30 "C. 4) Process according to claim 1 to 3 for the preparation of compounds of the general formula (I), in which R1 represents a straight-chain or branched one Alkanoylamino radical with up to 6 carbon atoms and R2 stands for an alkyl radical up to. 4 carbon atoms.