GB1157637A - Process for the Production of Tertiary-Amino Alkylated Primary Amines - Google Patents

Abstract

1,157,637. Tertiary-amino-alkylated primary amines. STERLING DRUG Inc. 1 July, 1966 [1 July, 1965], No. 29636/66. Heading C2C. Tertiary-amino-alkylated primary amines are obtained by a process which comprises (a) catalytically hydrogenating 2-methylene-glutaronitrile to produce 2-methylglutaronitrile, (b) reductively alkylating 2-methyl-glutaronitrile in the presence of an amine, HNR 1 R 2 , to produce 2-methyl-5-NR 1 R 2 -valeronitrile, (c) hydrolysing 2 - methyl - 5 - NR 1 R 2 - valeronitrile, preferably in an aqueous mineral acid, to produce 2-methyl-5-NR 1 R 2 -valeramide and treating the latter with an aqueous alkaline solution of an alkali metal hypohalite to produce 2-amino-5-NR 1 R 2 -pentane, where NR 1 R 2 is a tertiary amino group and R 1 and R 2 are the same or different and represent lower or higher alkyl, hydroxy lower or higher alkyl, lower alkoxy higher or lower alkyl, di-lower alkylamino lower or higher alkyl, C 3-7 cycloalkyl, phenyl or substituted phenyl, said substituents being hydroxy, lower alkoxy, dilower alkylamino, trifluoromethyl, lower alkylmercapto or halo, or R 1 and R 2 taken together form a heterocyclic ring containing at least one heteroatom, the terms " lower " and " higher " denoting C 1-8 and C 8-18 respectively. The first step of the process to produce 2-methyl glutaronitrile is suitably effected at 60-80‹ C. under a pressure of 100-200 p.s.i. hydrogen in the presence of a catalyst such as palladium, platinum, Raney cobalt or Raney nickel which may be supported on a carrier such as carbon, barium sulphate, strontium carbonate, calcium carbonate or alumina. The reductive alkylation in the second stage is preferably effected at 90-110‹ C. under a hydrogen pressure of 100- 500 p.s.i. employing the same catalyst as in the first stage. The hydrolysis in the third of the process is preferably conducted at 60-65‹ C. in 85-95% sulphuric or phosphoric acid. The Hofmann type reaction in the final step of the process is conducted in a conventional way suitably starting the reaction at about 0‹ C. and completing the reaction by heating to about 75-100‹ C. The intermediates formed in the above steps may be isolated together with smaller amounts of the corresponding 4-methyl- 5-t-amino substituted isomers which are also formed.