Patent GB-807835-A (GB)
Title: New tertiary amines and their salts and process for their preparation
IPC: C07D295/03
Filed: 1955-09-23
Abstract: The invention comprises amines of the general formula <FORM:0807835/IV (b)/1> and acid addition and quaternary salts thereof, wherein R is a hydrogen atom or an alkyl or alkoxy group of 1-6 carbon atoms, R1 and R2 are each an alkyl or hydroxyalkyl group of 1-6 carbon atoms or a cycloalkyl or monocyclic aryl group or an alkyl group of 1-6 carbon atoms bearing a monocyclic aryl substituent or NR1R2 together for a heterocyclic ring which may optionally contain a further hetero-atom and Y is a substituted or unsubstituted aralkyl group or an alkyl group of 3-12 carbon atoms.  The amines are prepared by treating an aminopropionitrile of the formula <FORM:0807835/IV (b)/2> with an organomagnesium halide of the formula Hal-Mg-Y, in an inert solvent such as ether, dibutyl ether, dioxan, benzene or benzene/tetrahydrofuran, preferably at the boiling-point of the solvent, and hydrolysing the resulting condensation product to give the amine.  The products may be converted into their acid addition salts such as the hydrochloride, hydrobromide, sulphate, phosphate, nitrate, acetate, propionate, butyrate, valerate, oxalate, malonate, succinate, maleate, fumarate, lactate, tartrate, citrate, malate, benzoate, phthalate, cinnamate, salicylate, nicotinate or furan-2-carboxylate or into their quaternary salts with alkyl halides, dimethyl sulphate, diethyl sulphate, alkyl p-toluenesulphonates, cyclohexyl halides or cyclopentyl halides. Preferred products include the o -phenyl derivatives of 4-pyrrolidino-pentane, 4-piperidino-pentane, 5-pyrrolidino-hexane, 3-pyrrolidino-2-methylbutane and 1 - phenyl - 3 - dimethylaminobutane.  Specified products prepared in the examples include (a) phenethylamines; a -nonyl - N:N - diethyl -, a  - benzyl - N:N - di - n - butyl -, a  - phenethyl - N:N - dimethyl -, a  - (a - phenylethyl) - N:N - diethyl -, a  - phenethyl - N:N - diethyl -, a - phenethyl - N:N - di-n-butyl- and a -p-isopropyl-phenethyl-N:N-diethyl-; (b) morpholines; N-[a -(g -phenylpropyl) - p - methylphenethyl] -, N - [a  - (b  - p - isopropylphenyl - isopropyl) - phenethyl] - an N - a  - isopropyl - phenethyl -; (c) piperidines; N - a  - (g  - phenylpropyl) - phenethyl - and N - a -propyl-phenethyl-, and (d) pyrrolidines; N-[a - (b  - p - isopropylphenyl - isopropyl) - phenethyl] -, N - a  - propyl - phenethyl -, N - a  - butyl - phenethyl -, N - a  - isopropyl - phenethyl -, N - a  - (a  - phenylethyl) - phenethyl -, N - a  - phenethyl - phenethyl -, and N - a  - benzyl - phenethyl.  a - Tertiary - aminopropionitriles of the formula II used as starting materials, such as 2 - phenyl - 1 - piperidino - propionitrile, 2 - phenyl - 1 - diethylamino - propionitrile and 2 - p - methylphenyl - 1 - morpholino - propionitrile are made by known methods, for example by the reaction of an aldehyde such as a phenyl acetaldehyde with potassium cyanide and an amine of the formula NHR1R2.  3 - (4 - Isopropylphenyl) - 2 - methyl - 1 - pyrrolidino - butyronitrile is made by the action of sodium bisulphite, pyrrolidine and potassium cyanide on cyclamen aldehyde.