Patent GB-881639-A (GB)
Title: New hydrazinium compounds, their production and pharmaceutical compositions containing them
IPC: C07D211/98
Filed: 1960-02-12
Abstract: The invention comprises compounds of the formula <FORM:0881639/IV (b)/1> wherein R is a lower alkyl radical and X is an anion bearing the charge n, the piperidine nucleus being substituted by a radical R1 and optionally also by a radical R11, R1 being a hydroxy lower alkyl, alkoxycarbonyl, acyloxy or acyloxy lower alkyl radical, "acyloxy" being defined as phenylcarbamoyloxy, benzoyloxy, mandeloyloxy, diphenylacetoxy, benzilyloxy or fluorene-9-carbonyloxy, and "lower alkyl" referring to alkyl radicals of at most 7 carbon atoms, and R11 being a phenyl radical.  They may be prepared by reacting chloramine or hydroxylamine-O-sulphonic acid with the appropriate N-alkyl-piperidine.  Anions may be exchanged by metathesis.  In Examples (1) 1-methyl-3-hydroxymethyl piperdine and chloramine give 1-amino-1-methyl-3-hydroxymethylpiperidinium chloride (picrate and hexafluorophosphate also prepared); (2) the product of (1) and phenyl isocyanate give 1-methyl-1-amino-3-(N-phenylcarbamoyloxy)-methylpiperidinium chloride (picrate also prepared); (3) the product of (1) and diphenylacetyl chloride give 1-amino-1-methyl - 3 - diphenylacetoxymethylpiperidinium-chloride; (4) 1-ethyl-3-diphenyl-acetoxy piperidine and chloramine give 1-amino-1-ethyl-3-diphenyl-acetoxypiperidinium chloride; (5) and (6) the product of (4) is converted into the corresponding diethylbarbiturate, benzoate and tartrate; (7) fluorene-9-carboxylic acid and thionyl chloride give fluorene-9-carboxylic acid chloride, this with 1-methyl-4-hydroxypiperidine gives 4-(fluorene-9-carbonyloxy)-1-methylpiperidine hydrochloride and this (as the free base) with chloramine gives 1-amino-1-methyl-4-(fluorene-9-carbonyloxy)-piperidinium chloride (picrate and hexafluorophosphate also prepared); (8) 4-carboethoxy-4-phenyl-1-methyl-piperidine and chloramine give 1 - amino - 1 - methyl - 4 - phenyl - 4 - carboethoxy-piperidinium chloride (picrate and hexafluorophosphate also prepared); and (9) and (10) the product of (8) is converted into the corresponding iodide, nitrate, ferrocyanide and ferricyanide and the salts with amphomycin, penicillin and o-acetoxy-benzoic acid.  An extensive list of further suitable anions X is also provided. Specifications 858,488, and U.S.A.  Specifications 2,678,258 and 2,710,248 are referred to.ALSO:Pharmaceutical compositions comprise a compound of the formula <FORM:0881639/VI/1> (wherein R is a lower alkyl radical and X is an anion bearing the charge n, the piperidine nucleus being substituted by a radical R1 and optionally also by a radical R11, R1 being an hydroxy lower alkyl, alkoxycarbonyl, acyloxy or acyloxy lower alkyl radical, "acyloxy" being defined as phenylcarbamoyloxy, benzoyloxy, mandeloyloxy, diphenylacetoxy, benzilyloxy or fluorene-9-carbonyloxy, and "lower alkyl" referring to alkyl radicals of at most 7 carbon atoms and R11 being a phenyl radical) in admixture with a solid or liquid pharmaceutical carrier.  Specific examples of X are those listed in Specification 880,974, and ferrocyanide, ferricyanide and amphomycinate.  Specification 858,488 and U.S.A. Specifications 2,678,258 and 2,710,248 also are referred to.