Patent GB-834290-A (GB)
Title: Substituted piperidines
Inventor: YOUNG EDWIN HARRY PATERSON
IPC: C07D295/088
Filed: 1957-02-13
Abstract: The invention comprises compounds of the general formula <FORM:0834290/IV (b)/1> wherein R stands for hydrogen or for an alkyl radical or for an alkenyl radical of not more than 6 carbon atoms, the alkyl radical being optionally substituted by halogen atoms, free hydroxy etherified or esterified hydroxy groups, R1, R2, R3 and R4, which may be the same o different, stand for methyl or ethyl radicals, and the piperidine ring (A) may optionally be further substituted by a lower alkyl radical (C1-6), a phenyl radical, or a dialkylaminoalkylamino radical, provided that when the ring A contains no further substituents in positions 3, 4 or 5, then R, R1, R2, R3, R4 together contain more than 4 carbon atoms; non-toxic pharmaceutically-acceptable acid addition salts and quaternary salts wherein the ring nitrogen atom is linked to two methyl radicals, i.e. where R stands for methyl and the nitrogen atom is further methylated; and the preparation thereof: (1) by reducing compounds of the general formula <FORM:0834290/IV (b)/2> preferably by the Clemmensen or Wolf-Kishner methods; (2) by reducing the corresponding tetrahydropyridine compounds of the formula <FORM:0834290/IV (b)/3> where the ring (B) may optionally be further substituted by a lower alkyl or a phenyl radical, the reduction being carried out preferably by using hydrogen and a hydrogenation catalyst or by using sodium ethanol; (3) by alkylation of a compound of the formula <FORM:0834290/IV (b)/4> preferably by the use of an alkyl or alkenyl halide or sulphate or an alkyl sulphonate and in the presence of an acid-binding agent, or when R is a methyl or b -hydroxethyl radical by a formaldehyde/formic acid mixture or ethylene chlorohydrin respectively; (4) (wherein R stands for an alkyl radical containing a terminal acyloxy radical) by acylating the corresponding compounds wherein R stands for an alkyl radical containing a terminal hydroxy group, preferably by use of an acid anhydride or acid chloride in the presence of an inert solvent; (5) (wherein R stands for an alkyl radical containing a terminal alkoxy group), by reacting the corresponding compound wherein R is an alkyl radical containing a terminal halogen atom and an alkali metal alkoxide, preferably in the presence of the alcohol from which the alkoxide is derived; (6) (for the quaternary ammonium compounds) by methylating the corresponding tertiary bases wherein R stands for a methyl radical, preferably by an alkyl halide in the presence of an inert solvent; and (7) (wherein the piperidine ring (A) is substituted in the 4-position by a dialkylaminoalkylamino radical) by reductive alkylation of the corresponding 4-piperidone with a dialkylaminoalkylamine in the presence of hydrogen, and a platinum hydrogenation catalyst. The invention also comprises the preparation of 1 - b  - chloroethyl - 2:2:6:6 - tetramethylpiperidine by reacting the corresponding hydroxy ethyl compound with thionyl chloride.  The Provisional Specification further discloses that R1, R2, R3 and R4 may be hydro carbon radicals which may be substituted, for example, by a hydroxy group, the ring (A) may be further substituted by a halogen atom, amino, acylamino, alkoxy or hydrocarbon radicals, the last named of which may be optionally substituted by hydroxy or alkoxy radicals or halogen atoms.  1:2:2:6:6 - Pentamethyl - D 3,4 - tetrahydropyridine hydrochloride is prepared from thionyl chloride and 4 - hydroxy - 1:2:2:6:6 - pentamethylpiperidine; and 4-ethyl-4-hydroxy-2:2:6:6-tetramethylpiperidine and its hydriodide are prepared by reducing 4-ethynyl-4-hydroxy2:2:6:6-tetramethylpiperidine.