Patent GB-866681-A (GB)
Title: N-substituted piperidines
Inventor: BRETHERICK LESLIE
IPC: C07D211/98
Filed: 1958-05-22
Abstract: The invention comprises compounds of the general formula: <FORM:0866681/IV (b)/1> and their acid addition salts wherein R1 represents a hydrogen atom or a methyl or ethyl group, and R11 represents a hydrogen atom or R1 and R11 together represent a methylene, ethylidene or allylidene group, R2 represents a hydrogen atom or a methyl group, R41 represents a hydrogen atom or a C1-3 alkyl group and R3 and R4 each represent a hydrogen atom or together represent a single bond and the preparation thereof, wherein R1 and R11 represent hydrogen atoms, by reducing a compound of the general formula:  <FORM:0866681/IV (b)/2> or by reacting a compound of the general formula: <FORM:0866681/IV (b)/3> with hydroxylamine-O-sulphonic acid; wherein R1 and R1 together represent a methylene, ethylidene or allylidene group, by reacting a compound of (I) wherein R1 and R11 both represent hydrogen atoms with an aldehyde R5CHO wherein R5 represents a hydrogen atom or a methyl or a vinyl group, or a derivative thereof such as an acetal, thioacetal, diacyl derivative or a bisulphite addition compound; and wherein R1 represents a methyl or ethyl group and R11 represents a hydrogen atom, by alkylating a compound (I) where in R1 and R11 are hydrogen atoms or by reducing a compound of the general formula: <FORM:0866681/IV (b)/4> The first Provisional Specification relates to compounds (I) wherein R1 and R11 additionally both represent lower alkyl groups and to quaternary ammonium salts of the bases in general.  1-Nitroso-2,2,6,6- tetramethyl-1,2,5,6- tetrahydropyridine is prepared from sodium nitrite and 2,2,6,6-tetramethyl-1,2,5,6-tetrahydropyridine.  Similarly are prepared 1-nitroso-2,2,6-trimethylpiperidine and 1-nitroso-2,2,4,6,6-pentamethyl-1,2,5,6-tetrahydropyridine. 2,2,4,5,6- Pentamethyl-1,2,5,6- tetrahydropyridine hydriodide is prepared by reacting methyl magnesium iodide with 2,2,6,6-tetramethylpiperid-4-one and heating the hydriodide of the 2,2,4,6,6-pentamethylpiperidin-4-ol so formed. 1-Formylamino-2,2,6,6- tetramethylpiperidine is prepared from formic acid and 1-amino-2,2, 6,6-tetramethylpiperidine.ALSO:Pharmaceutical compositions comprise a pharmaceutical carrier together with compounds of the general formula <FORM:0866681/VI/1> or their acid addition salts wherein R1 represents a hydrogen atom, a methyl or an ethyl group and R11 represents a hydrogen atom or R1 and R11 together represent a methylene, ethylidene or allylidene group, R2 represents a hydrogen atom or a methyl group, R14 represents a hydrogen atom or a C1-3 alkyl group and R3 and R4 represent a hydrogen atom or together represent a single bond.  Acid addition salts include hydrohalides, phosphates, nitrates, sulphates, maleates, fumarates, citrates, tartrates, methanesulphonates and ethane disulphonates. Compositions are suitable for oral or parenteral administration and are in the form of tablets, pills, dispersable powders, granules, emulsions, suspensions, syrups and elixirs. Examples are given of tablets containing 1 - amino - 2,2,6,6 - tetramethylpiperidine hydrogen tartrate and 1-methyleneamino-2,2,6,6 - tetramethylpiperidine hydrogen tartrate and injectable aqueous solutions containing 1 - amino - 2,2,6,6 - tetramethylpiperidine and 1 - methylamino - 2,2,6,6 - tetramethylpiperidine hydrochlorides.