GB640168A - Improvements in or relating to the preparation of 4-aryl-4-aminomethyl-piperidine derivatives - Google Patents

Abstract

4-Aryl-4-aminomethylpiperidine derivatives of the general formula <FORM:0640168/IV (b)/1> wherein Ar represents an aromatic radical (carbocyclic or heterocyclic, preferably monocarboxylic, such as phenyl, naphthyl, thienyl, pyridyl or quinolyl, optionally carrying substituents, e.g. alkyl, aralkyl or aryl groups, halogen atoms such as chlorine, bromine or iodine, tertiary amino groups such as dimethylamino, piperidino or morpholino, or alkoxy or aryloxy groups), X represents one of the following carboxylic acyl radicals: carbamyl (-CONH2), N-substituted carbamyl (e.g. N-ethyl- or N : N-dimethyl-carbamyl), carbalkoxy (e.g. carbomethoxy, carbethoxy, carboisobutoxy or carbo-n-hexoxy), alkanoyl (e.g. acetyl, isobutyryl, valeryl or cyclopentanecarboyl) or aroyl (e.g. benzoyl, p-toluyl, a -naphthoyl or 2-thenoyl), and Y represents hydrogen, or X as defined above, or a monovalent hydrocarbon radical (e.g. methyl, ethyl, n-butyl, n-hexyl, cyclohexyl, benzyl, phenethyl, phenyl or naphthyl), are manufactured by treating the corresponding free amino compounds (X=H) with a carboxylic acylating agent on nitrourea. Suitable acylating agents are acid chlorides (carbamyl and N - substituted carbamyl chlorides, alkyl chlorocarbonates, and alkanoyl and aroyl chlorides) or acid anhydrides. When the 1-position in the starting materials is unsubstituted (i.e. Y=H), acylation will occur at this position as well as in the aminomethyl group, but products in which Y represents hydrogen are obtainable if the 1-position is originally occupied by a benzyl group which is removed, after the acylation, by hydrogenation in the presence of a palladium catalyst. Examples describe the preparation of compounds containing certain of the groups specified for X and Y above. The products, in the form of free bases or salts (e.g. with sulphuric, hydrochloric, hydrobromic, phosphoric, sulphamic, acetic, citric, benzoic or cinnamic acid) are useful as analgesic, antispasmodic or sedative agents. 4 - Aryl - 4 - aminomethylpiperidines, of the general formula above in which X represents hydrogen, are obtainable by catalytic hydrogenation of the corresponding 4-cyanopiperidines using Raney nickel in the presence of excess of ammonia. The Specification as open to inspection under Sect. 91 comprises also the manufacture of compounds of the general formula above in which X or Y or both may represent a guanyl radical or a hydrocarbon-substituted guanyl radical (e.g. N-methylguanyl, N : N-diethylguanyl or N : N1-dimethylguanyl, also aralkyl-or cycloalkyl-substituted guanyl radicals), these groups being introduced by the action of guanylating agents such as cyanamide or an S-methylthiouronium salt, including N-mono-, -di- or -tri-hydrocarbon-substituted-S-methyl-thiouronium salts. Examples of this process are included. This subject-matter does not appear in the Specification as accepted.