CS196755B1 - Method of preparing 1-/2,3,5-trimethyl-4-acetoxyphenoxy/-2,3-epoxy propane - Google Patents

Description

2,3,5-trimethyl-4-acetoxyphenoxy) -2,

The present invention provides a process for preparing l- (2, 3, 5-trimethyl-4-acetoxyphenoxy) -2, 3 ^J epoxypropane of formula I.

Q-GH.-GH-CH11- (2,3,5-trimethyl-4-acetoxyphenoxy) -2,3-epoxypropane is a raw material for the preparation of the Czechoslovak β-adrenolytic 1- (2,3,5-trimethyl-4- acetoxyphenoxy) -3-isopropylamino-2-propanol (Trimepranol).

To date, 1- (2,3,5-trimethyl-4-acetoxyphenoxy) -2,3-epoxypropane is prepared by condensing 2,3,5-trimethyl-4-acetophenol with a 5 molar excess of epichlorohydrin in acetone as an inert solvent (L. Bláha, J. Weichet, J. Hodrová, V. Trčka (CS-patent 143 069). A 1.5 molar excess of anhydrous potassium carbonate is used as the base. According to the patent, the reaction mixture is refluxed for 8 hours. Then acetone and excess epichlorohydrin are distilled off in vacuo and the product is obtained by extraction into benzene followed by crystallization from ethanol.

This preparation process is time-consuming, requiring separation of the acetone-epichlorohydrin mixture and regeneration of acetone, epichlorohydrin and benzene or toluene.

These drawbacks are substantially eliminated by the novel process for the preparation of 1- (2,3,5-trimethyl-4-acetoxyphenoxy) -2,3-epoxypropane according to the invention, which consists in the condensation of 2,3,5-trimethyl- 4-acetoxyphenol with a 3-5 molar excess of epichlorohydrin in the presence of 0.5-2 moles of anhydrous potassium carbonate is catalyzed either by the addition of a quaternary ammonium base of the type R1, R2, R3, R4, N + X-, where R1 and R2 are methyl, R 1 and R 4 are alkyl of 1 to 16 carbon atoms or benzyl, optionally phenyl and X is OH, Br -, Cl +, in an amount of 0.5-15% by weight based on the phenol used or by addition of a strong basic anion exchange with quaternary ammonium functional groups in an amount of 2 to 10% by weight based on the phenol used.

The addition of a catalytic amount of these compounds increases the reaction rate of the formation of the intermediate 1- (2,3,5-trimethyl-4-aceto196755 xyphenoxy) -3-chloro-2-propanol by transfer

OH ^- anions.

The advantages of the novel process according to the invention are that the yields of 1- (2,3,5-trimethyl-4-acetoxyphenoxy) -2,3-epoxypropane are 10-15% higher than the flood process, no separation of the acetone-epichlorohydrin mixture , regenerating acetone and using benzene or toluene. By reducing the molar ratio of potassium carbonate and omitting acetone, the capacity of the production plant is doubled, which is associated with saving energy, water and time, etc., without any treatment. The condensation time alone using the novel process of the invention is reduced from 8 to 5 hours.

In the following the subject matter of the invention is illustrated by way of example, without being limited to:

Example 1

19.4 g (0.1 mol) of 2,3,5-trimethyl-4-acetoxyphenol, 46.2 g (0.5 mol) of epichlorohydrin, 14 g (0.1 mol) of anhydrous potassium carbonate, 0.5 g (2.5 wt% on phenol used) dimethylbenzyl laurylammonium bromide was refluxed at 112-115 ° C for five hours. The solid is filtered from the reaction mixture and the epichlorohydrin is distilled off in vacuo. The condensation yield is 86% 1- (2,2,5-trimethyl-4-acetoxyphenoxy) -2,3-epoxypropane.

Example 1 a d 2

19.4 g (0.1 mol) of 2,3,5-trimethyl-4-acetoxyphenol, 46.2 g (0.5 mol) of epichlorohydrin, 14 g (0.1 mol) of potassium carbonate, 1g (5% by weight) to the phenol used) of a strong basic anion exchange resin (DOWEX, type 1) is refluxed at

112-116 ° C for 5 hours. The solid is filtered off from the reaction mixture and excess epichlorohydrin is distilled off in vacuo. The yield of 1- (2,3,5-trimethyl-4-acetoxyphenoxy) -2,3,5-epoxypropane is 91%.

Example 3

19.4 g (0.1 mol) of 2,3,5-trimethyl-4-acetoxyphenol, 46.2 g (0.5 mol) of epichlorohydrin, 14 g (0.1 mol) of potassium carbonate, 0.5 wt% . (per phenol used) trimethyl benzylammonium hydroxide was refluxed at 114-116 ° C for five hours. The solid is filtered off from the reaction mixture and excess epichlorohydrin is distilled off in vacuo. The condensation yield of 1- (2,3,5-trimethyl-4-acetoxyphenoxy) -2,3-epoxypropane is 82%.

Example 4

A mixture of 582 g of 2,3,5-trimethyl-4-acetoxyphenol, 1386 g of epichlorohydrin, 420 g of anhydrous potassium carbonate and 30 g of a strong basic anion exchange resin (e.g. Wofatit SBW) is refluxed at 110-115 ° C for five hours. The reaction mixture is then cooled to 60-70 ° C, 980 g of water are added and stirred for 15 minutes. After separation, excess epichlorohydrin is distilled off from the organic layer at a vacuum of 13 to 10 torr and a bath temperature of 90-100 ° C. The aqueous anion exchange layer was shaken twice with 250 ml of benzene. The combined benzene fractions were added to the bulk after the benzene was distilled off in vacuo. The mixture thus obtained was dissolved in 1100 ml of ethanol and allowed to crystallize at 0 ° C. Yield 660 g, which is 88% of the theory of 1- (2,3,5-trimethyl-4 acetoxyphonoxy) -2,3-epoxypropane, m.p. 71-73 ° C.

Claims (1)

SUBJECT Process for preparing 1- (2,3,5-trimethyl-4-acetoxyphenoxy) -2,3-epoxypropane by condensation of 2,3,5-trimethyl-4-acetoxyphenol with epichlorohydrin in the presence of anhydrous potassium carbonate, characterized in that the condensation is catalyzed by the addition a quaternary ammonium base of the type R 1 R 2 R 3 R 4 N + X -, wherein R 1 and R 2 is methyl and R 3 R 4 are alkyl having 1 to 16 carbon atoms or henzyl, optionally phenyl, and X - is OH - Br ^- , Cl. ^- in an amount of 0.5-15% by weight. % based on the phenol used, or by the addition of a strongly basic anion exchanger having quaternary ammonium functional groups in an amount of 2-10% by weight; based on the phenol used.