GB840358A - Improvements in or relating to the manufacture of n-mono-substituted piperazines - Google Patents

Abstract

N-mono-substituted piperazines are prepared by reacting, in the presence of an organic or aqueous organic solvent, an alkylating agent containing up to 6 carbon atoms or an aralkylating agent with a monopiperazinium salt derived from an acid with dissociation constant lying below the second acid dissociation constant of the piperazine in the solvent system used for the condensation. Suitable monopiperazinium salts are, for example, those derived from acetic, succinic, citric, benzoic, toluene-p-sulphonic, hydrochloric, hydrobromic and sulphuric acids. Suitable alkylating agents are, for example, methyl and ethyl sulphates and alkyl halides. Suitable aralkylating agents are halides of formula Hal.(CH2)nAr in which n is not greater than 6 and Ar is an aromatic nucleus, particularly a phenyl, naphthyl or diphenyl nucleus, which may be additionally substituted by alkyl, alkoxy, halogen or nitro groups. The alkylating or aralkylating agent may have two reactive centres, e.g. it may be an aliphatic or araliphatic a .o -dichloride dibromide or diiodide. Suitable solvents are alkanols containing up to 5 carbon atoms, dioxan, and ethoxyethanol with or without the addition of water. The monopiperazinium salts used as starting materials may be prepared by reacting the corresponding acid with piperazine hexahydrate and may be formed in situ. Examples are given of the preparation of (a) N-substituted piperazines in which the N-substituent is m-methylbenzyl, methyl, n-amyl, o-methylbenzyl, p-methoxy benzyl, p - chlorobenzyl, a - naphthylmethyl, 6 - (1.2.3.4 - tetrahydronaphthyl) - methyl, b - phenethyl, g - phenylpropyl, 6 - phenylhexyl, g - o - toloxypropyl, g - 2.6 - xyloxypropyl and ethyl; and (b) 1.3 - bis - Npiperazino propane and 1.2-bis-N-piperazinoethane.