CS242133B1 - Process for the preparation of bis- (4-acetamidophenoxy) ethyl ether - Google Patents

Abstract

Method for producing bis-//? -(4-acetamidophenoxy)ethyl/ether by reaction of 2,2-dichlorodiethyl ether with 4-acetamidophenol. The essence of the method is to carry out the reaction in an environment of n-butyl alcohol or isobutyl alcohol in the presence of butyl alcoholate or sodium or potassium isobutyl alcoholate. The substance is used as an anthelmintic, especially in sheep breeding.

Description

The present invention relates to a process for the preparation of bis - N - (acetamidophenoxy) ethyl ether by reacting 2,2 ^% dichlorodiethyl ether with 4-acetamidophenol in n-butyl or isobutyl alcohol and a base in the optional presence of iodide ions and adding an aprotic solvent. The substance has significant biological effects and is therefore used as an anthelmintic especially in sheep breeding.

The general preparation of these compounds is described by reacting 4-acetamidophenol with an ether of formula

X. .CEL · · 0¾. 0. CBL. OBJECTIVE. X, wherein X is chlorine, bromine, iodine, optionally arylsulfonyloxy, in an organic solvent environment, e.g. Alcohol, a polar aprotic solvent under the catalytic action of an iodide ion, using sodium hydride, sodium or potassium hydroxide, sodium or potassium methoxide or potassium carbonate as the base, but in the presence of an aliphatic ketone, e.g. acetone.

Said processes according to the individual variants have a number of disadvantages, such as difficult regeneration of individual solvents from their mixture, low degree of regeneration of dimethylsulfoxide due to its low thermal stability, demanding disposal of distillation residues with respect to ecological requirements etc. · The common feature of all variants is relatively low yield on key raw materials not exceeding 60% of theory and product quality, which must be ensured by multiple crystallizations from solvent ·

The above-mentioned disadvantages are overcome by the method of preparation of the bis-? - (4-acetamidophenoxy) ethyl ether by reaction of 2,2'-dichlorodithiol with 4-acetamidophenol in n-butyl or isobutyl alcohol and a base in the presence of iodide ions

242,133 and a polar solvent of the invention. The principle is that the reaction is carried out in the presence of sodium or potassium butyl or isobutyl alcohol. The process according to the invention yields a product of very good quality and high yield.

A small amount of sodium or potassium iodide and dimethyl sulfoxide may be added as a catalyst. The necessary butyl alcoholates can be prepared, for example, by reacting the alcohol with sodium or potassium hydroxide by means of azeotropic drainage using a sufficiently efficient rectification column, or by using directly the hydroxyl which forms the butyl alcohol in equilibrium with butyl alcohol. The reaction with 4-acetamidophenol is then carried out with the 2,2-diohlorodiethyl ether for several hours, preferably under a protective atmosphere, to prevent oxidation of the product. After completion of the reaction, the inorganic fractions are removed either by hot filtration of the reaction mixture or by extraction with water at elevated temperature, whereupon the filtrate is preferably azeotropiated, thereby reducing the solubility of the product.

After clering and subsequent filtration, the product is isolated which is chromatographically pure. If desired, the product can be recrystallized from n-butyl or isobutyl alcohol containing 0 to 25% water or from 50 to 80% ethanol. to obtain a pharmaceutical grade product. The mother liquors after recrystallization by foxes and subsequent azeotropic dewatering can be used as a batch for further operation in the self-reaction phase. A yield of about 70% of theory is obtained. The 4-aoetoamidophenol used may not be pure, an industrial product containing, for example, 4-chloroacetanilide may be used.

In order that the invention may be more fully understood, the following examples are provided.

Example 1

800 ml of isobutyl alcohol and 88 g of sodium hydroxide were introduced into the flask. Azeotropic dewatering of the resulting sodium isobutyrate solution was carried out with 119.0 g of 2,2 ' -dichlorodiethyl ether and 284 g of 4-acetamidophenol containing 15,4-4-chloroacetanilide and 10 ml of dimethylsulfoxide.

After refluxing for 3 h, they were filtered while hot

242 133 inorganic salts, the filtrate was gradually cooled to 0 ° C. After drying at 80 ° C, 220 g of the product were obtained, mp, 162.5-163 ° C, which is 73% of the theoretical yield.

The same result was obtained using potassium isobutyl alcoholate.

Example 2

250 ml of methanol were added to the flask in which 24.6 g of sodium metal was dissolved. Then 700 ml of n-butyl alcohol was added and the methanol present was distilled off by means of a column. To the resulting sodium butanolate solution was added 158.7 g of 4-acetamidophenol and 71.5 g of 2,2'-dichlorodiethyl ether and 1.0 g of potassium iodide. After refluxing for 5 h, 150 ml dest. water and at 80 ° C the aqueous phase containing the reaction sodium chloride was separated. The organic phase was about

azeotropically dewatered, sclerated filtrate gradually cooled to 5 ° C. The product was isolated and washed with 300 ml of n-butanol. After drying at 80 ° C, 122 g of product are obtained, m.p. 158-158.5 ° C, 65.5% of theory.

Claims (1)

SUBJECT OF THE INVENTION 242 133 A process for the bisTβ - (4-acetamidophenoxy) ethyl ether reaction of 4-acetamido-phenol and 2,2'-dichlorodiethyl ether in n-butyl or isobutyl alcohol and a base in the presence of iodide ions and a polar aprotic solvent, optionally characterized in that the reaction is carried out in the presence of sodium or potassium butyl or isobutyl alcohol in an amount of 1.8 to 4 moles per 1 mol of 2,2'-dichlorodiethyl ether;