PL158225B1 - Method for manufacturing 2-chlormethylthiopen - Google Patents

Abstract

A method of producing 2-chloromethylthiophene, characterized in that 2-thienylmethanol is treated with hydrochloric acid in organic solvent environment, where the organic solvent does not mix with water, and in the presence of quaternary ammonium salt or aliphatic tertiary amine, which act as the phase transfer catalyst.

Description

REPUBLIC

POLAND

@ PATENT DESCRIPTION ® PL® 158225 © Bl

Application number: 279868 / CTs

IntCP:

C07D 333/12

Patent Office of the Republic of Poland

Date of notification: 09/06/19 ⁸⁹

Method for the production of 2-chloromethylthiophene

Application announced:

10/12/1990 BUP 25/90

The grant of the patent was announced on: August 31, 1992, WUP 08/92

The holder of the patent:

Warsaw Pharmaceutical Works Polfa ”, Warsaw, PL

Warsaw University of Technology, Warsaw, PL

Inventors:

Andrzej Jończyk, Warsaw, PL Michał Fedoryński, Warsaw, PL Irena Kmiotek-Skarżyńska, Warsaw, PL Wiesława Kiełbasinska, Milanówek, PL Zbigniew Wróbel, Warsaw, PL Marek Gnyś, Warsaw, PL Andrzej Tyrał, Warsaw, PL

A method for the preparation of 2-chloromethylthiophene, characterized in that 2-thienylmethanol is treated with hydrochloric acid in a water-immiscible organic solvent and in the presence of a quaternary ammonium salt or an aliphatic tertiary amine acting as an interphase transfer catalyst.

PL 158 225 Bl

METHOD OF MANUFACTURING 2-CHLOROMETHYLTHIOPHENE

Claims (2)

1. The method of preparation of 2-chloromethylthiophene, characterized by the fact that 2-thienythomethanthyl is treated with hydrochloric acid in an organic solvent, immiscible with water and in the presence of a quaternary ammonium salt or an aliphatic tertiary amine, acting as a transfer catalyst interphase. 2. The method according to p. The process of claim 1, wherein the organic solvent is methylene chloride. *** The object of the invention is a process for the production of 2-chloromeeytothiophene, an important compound in organic synthesis. This compound is used for the preparation of thienytacetic acid and nitrile, intermediates for the synthesis of ceialosporin antibiotics or thiethophosphotic acid esters, intermediates for the synthesis of the anti-migraine drug Pizethene and an anti-asthmatic drug called Ketiotifen. 2-Chlortmethytothiophene is obtained by chloromethylation of thioene as described in the above-described chemical methods (K.B. Wiberg, H.F.Mc Shane, Org. Synth., Coli. vol. III, ed, E.C. Horning, John Wiley, London 1955, p.197). The process is dangerous, difficult to control on a larger scale, and the resulting product is very contaminated and requires purification by vacuum rectification. There are known cases of rapid decomposition of the reaction mixture both during the chloromethylation of thioene and during distillation. The yield of the so-called 2-chlortromethylthiotene is 40%. Another method of obtaining the title compound is the replacement of the hydroxyl group in 2-ttenithomethanol with a chlorine atom using strong chlorinating reagents such as thionyl chloride (Organic Preparation, Collective Tuman, edited by B. Bochwica, PWN, Warsaw 1975, p. 216). 2-Chltromethylthiophene obtained by this method is also contaminated and requires cleaning. In addition, this process produces a large amount of troublesome, difficult to neturalize liquid and gaseous wastes. The object of the invention is to eliminate the above-indicated disadvantages and to develop a process that can be safely operated on an industrial scale. In the process according to the invention, 2-thienylmethinol is treated with hydrochloric acid in a water-immiscible organic solvent, preferably methylene chloride, and in the presence of a quaternary ammonium salt or an alpha-lily amine acting as a misdriphase transfer catalyst. The 2-chloromethylthiophene obtained in this way, with an content of more than 90%, is sufficiently pure and can be used directly for chemical syntheses. EXAMPLE 1 500 g of 2-thienythomethinol, 1.5 L of methylene chloride, 1.5 L of hydrochloric acid and 4 g of aliquate 336 were placed in a flask. Stirring and heating were turned on. After reacting for 5 hours, the layers were separated, and the aqueous layer was extracted with methylene chloride. The organic vegetable, after washing with water, was made alkaline with sodium carbonate and then dried with a drying agent. 800 ml of triethylphosphite were added to the solution obtained in this way. Methylene chloride was distilled off and heated for 2 hours. The obtained thienythiphosphonic acid ester was purified by distillation to give 831 g of the ester, i.e. 81% yield based on 2-ttenithomttanol. 158 225 Example II. 30 g of 2-thienylmethanol, 90 ml of methylene chloride, 90 ml of hydrochloric acid and 0.3 g of aliquat 336 were placed in the flask. The stirring and heating were started. After reacting for 5 hours, the layers were separated, and the aqueous layer was extracted with methylene chloride. The organic layer, after washing with water, was made alkaline with sodium carbonate and then dried with a drying agent. The methylene chloride was distilled off in a vacuum evaporator. The resulting 2-sosób chloromeiiotiofen added dropwise at a temperature of 80 ° C to a solution of 25 g of potassium cyanide in 40 ml of water and 0.4 g aliąuatu 336. The reaction was carried out for 3 hours, the mixture was cooled and the layers separated · ^To the ^organic layer water was added a new portion of the catalyst, and then added dropwise 2-chloroIneiyyotiofen yield after the reaction minimum ioośó cyanide in the aqueous layer by distilling otrymanego product says for ^an 27.2 g of the nitrile tienyZoocZowego, which is wćlajności 84% based on 2-tieπyZomitanzl.