KR910009415B1 - Process for the preparation of bis-(phemoxy) acethyl-dimethyl amide - Google Patents

Abstract

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Description

Method for preparing bis (phenoxy) acetyl NN-dimethyl amide

The present invention relates to a process for the preparation of bis (phenoxy) acetyl NN-dimethyl amide.

Bis (phenoxy) acetyl NN-dimethyl amide is useful as an intermediate compound for preparing compounds having antidepressant properties, ie NN-dimethyl di-phenoxy-ethylamine, useful for treating humans. Bis (phenoxy) acetyl NN-dimethyl-amide has already been prepared by reacting bis (phenoxy) acetyl chloride or ethyl bis (phenoxy) acetate with dimethylamine in a benzene medium. Unfortunately, benzene is a toxic solvent and could not be used stably on a large scale. It is a bit toxic. Moreover, bis (phenoxy) acetyl chloride is difficult to prepare and slightly unstable. Moreover, such condensation delays product yield and yields compounds that are difficult to purify.

It is therefore an object of the present invention to provide a method for producing simpler, more effective and less harmful bis (phenoxy) acetyl NN-dimethylamide. It is characterized by reacting a compound selected from the group consisting of dichloro-acetyl NN-dimethyl-amide and dibromo-acetyl NN-dimethyl-amide with phenols.

Phenol is also better used in the form of their metal salts, for example sodium or potassium salts. It is also preferred that the reaction is carried out in the presence of an agent which binds an acid, for example sodium alcohol acid. The reaction is also better to use excess phenol. The condensation reaction is preferably reacted at a high temperature at a temperature of 80-110 ° C., preferably at a temperature of 100 to 110 ° C. The reaction can also be carried out under atmospheric pressure but preferably under a pressure of 2 to 6 bars. If desired condensation can be carried out in an inert solvent such as, for example, alkanols, more particularly lower alkanols such as ethanol.

Dichloro- or dibromo-acetyl NN dimethyl-amide can be prepared, for example, by reacting an ester such as methyl ester of dichloro- or dibromoacetic acid with dimethylamine under pressure. It is also convenient to use excess dimethyl-amine. More specifically, it is preferable to prepare the starting material and to condense the starting material with phenol in the same operation procedure.

According to the invention, the present inventors have dimethyl acetic acid and dibromo acetic acid dimethyl as a derivative of the carboxyl functional group of an acid selected from the group comprising, for example, an alkyl ester having 1 to 6 carbon atoms in the alkyl chain of the above-mentioned acid. An improved method of producing bis (phenoxy) acetyl NN-dimethyl amide by reacting with amines and phenols has been found.

As a solvent for this reaction, an excess of inert solvent or dimethyl-amine which does not react under the experimental conditions of this reaction, such as ethanol, may be used. Condensation in the same vessel is preferably carried out in a temperature range of 80 to 110 ° C. under a pressure of 2 to 6 bar. In the reaction in one vessel, it is preferred to use excess dimethylamine and excess phenol. Phenol can be used in condensation in one container on its own or in the form of metal salts such as sodium or potassium salts.

The following examples are given to illustrate the invention and do not limit it in any way.

EXAMPLE

4.7 g of sodium is added in portions to 100 ml ethanol in a drying flask. To this solution is carefully added 19.27 g (0.205 mole) of phenol previously dissolved in 25 ml ethanol to obtain a solution of sodium phenoxide.

The solution of sodium phenoxide is introduced into a pressurized flask, which has been previously cooled in a bath of dry carbon dioxide and acetone. To this is added 12 ml of dimethyl-amine (0.2 moles) and 14.3 g (0.1 moles) of methyl dichloro acetate. The pressurized flask is sealed and heated to 110 ° C. with shaking for 16 hours.

The sodium chloride formed is then removed by chilling the pressure flask and filtering the contents. Distillation of the orange ethanol filtrate gives a dark orange viscous residue. Then take 20 ml 5% sodium hydroxide. The whole mixture is extracted six times with ether (twice with 70 ml, once with 50 ml and three times with 40 ml). Combine the ethereal extracts and wash with water until the wash is neutral. The organic phase is then dried over sodium sulphate and the excess is removed by filtration and the solvent is distilled off. 19.5 g of an orange residue are collected and then distilled under reduced pressure to give two fractions. Fractions boiling at high temperature boil at 175-176 ° C. under a pressure of about 0.2 mm Hg and are recovered as yellow crystalline residue, with a melting point of about 80 ° C. After recrystallization from a mixture of 500 ml petroleum ether and 50 ml ethyl ether, the yellow residue is converted into a pure compound in the form of pale yellow crystals with a melting point of 84 ° C. The infrared spectrum of this compound is identical to that of a reliable sample. Obviously, various modifications of the above described methods can be carried out without departing from the spirit of the invention.

Claims (8)

The functional derivatives of the carboxyl functional groups of compounds selected from the group consisting of dichloro-acetic acid and dibromo acetic acid are reacted in themselves with dimethylamide to dichloro-acetyl NN-di-methyl-amide or dibromo-acetyl NN-di-methyl A process for producing bis (phenoxy) acetyl NN-dimethyl amide, characterized by obtaining an amide and reacting the obtained compound with phenol, respectively. The process according to claim 1, wherein the phenol is used in the form of a metal salt or the reaction is carried out in the presence of an agent which binds an acid. The method of claim 1 or 2, wherein the phenol is used in excess. The method of claim 1 wherein the functional derivative of the carboxyl functional group is an alkyl ester. The process according to claim 1, wherein the reaction is carried out in an excess of dimethyl-amine as solvent or in an inert solvent which does not react under the experimental conditions used. The method of claim 1, wherein the reaction is performed within a temperature range of about 80 ° C. to about 100 ° C. 7. The method of claim 1 wherein the reaction is carried out under a pressure of 2 to 6 bar s. The process according to claim 1, wherein excess dimethyl-amine and excess phenol are used to carry out the reaction.