GB631685A - Improvements in or relating to the preparation of piperazine mono carboxamides - Google Patents

Abstract

Piperazine mono carboxamides of the general formula <FORM:0631685/IV (b)/1> where R is hydrogen or an alkyl radical and R1 and R11 are hydrogen or alkyl radicals or may with the nitrogen atom form a heterocyclic ring, are prepared by mixing piperazine or an N-alkyl piperazine with a carbamyl chloride preferably at 0 DEG -40 DEG C. in a solvent such as chloroform, carbon tetrachloride, ethyl acetate or water. When an organic solvent is used the product may be recovered by saturating the reaction mixture with hydrogen chloride to precipitate any unreacted piperazine as the hydrochloride and concentrating the reaction mixture to recover the product. When the reaction is carried out in water, in the presence of alkali, the reaction mixture may be saturated with potassium carbonate or ammonium sulphate, extracted with ether or chloroform, dried and distilled to give the product. Compounds obtained according to the invention include those in which R is hydrogen, methyl, ethyl or isopropyl and R1 and R11 are hydrogen, methyl, ethyl, propyl, isopropyl, butyl, t.-butyl, amyl, hexyl, or NR1R11 is a morpholine, piperazine or piperidine ring. The products are used in the treatment of filiarisis or the treatment of ascrids in dogs. In examples, the preparation according to the invention is described of: (1), (2) and (5), 1-methyl-4-piperazine-N : N-diethyl carboxamide hydrochloride; (3) 1-methyl-4-piperazine-N : N-dimethyl carboxamide hydrochloride; (4) 1-methyl-4-piperazine-N : N-diisopropyl carboxamide hydrochloride; (6) 1-methyl-4-piperazine-N-ethyl carboxamide hydrochloride; (7) 1-isopropyl-4-piperazine-N : N-diethyl carboxamide hydrochloride; (8) 4-(1-methyl-4-piperazyl carbox) - 1 - methylpiperazide; (9) 1 - piperazine - N : N-diethyl carboxamide; and (10) 1-piperazine-N : N-dimethyl carboxamide. Where the examples result in the formation of hydrochloride salts the free base may be formed by treatment with mild alkali. Diisopropyl carbamyl chloride is prepared by the reaction of phosgene with diisopropyl amine. 1-Isopropyl piperazine is prepared by reacting 1-carbethoxy piperazine with isopropanol, heating with concentrated hydrochloric acid to give 1-isopropyl piperazine and reacting with alkali to form the free base. The Specification as open to inspection under Sect. 91 comprises also the preparation of piperazine monocarboxamides in which the groups R1 and R11 may be aromatic radicals. This subject-matter does not appear in the Specification as accepted.