Patent GB-980008-A (GB)
Title: New primary amines and process for their production
IPC: A61K31/135
Filed: 1963-05-30
Abstract: The invention comprises compounds of the general formula <FORM:0980008/C2/1> and their acid addition salts, wherein R denotes a hydrogen atom, a methyl or ethyl group, n denotes 0 to 3 whereby the group (CH2)n-CHR-possesse at most 4 carbon atoms, R1 denotes a tertiary alkyl group of 4 to 6 carbon atoms and wherein the phenyl nucleus is addition substituted by a hydroxyl group and/or a tertiary alkyl group with 4 to 6 carbon atoms and/or by one or two alkyl groups of 1 to 4 carbon atoms and the preparation thereof by treating (a) a compound of the formula <FORM:0980008/C2/2> wherein X denotes either a radical convertible by reduction into a CHR-NH2 group or a CHR-NH2 group if there are present in the starting material of formula II instead of hydrogen atoms, hydrogenolytically removable radicals or one or more carbonyl groups or one or more non-aromatic double bonds, with a reducing agent, or (b) a compound of formula I which, instead of the amino group, contains a radical capable of being replaced by an amino group, with ammonia or an ammonia-yielding agent, or (c) a compound with the basic structure of formula I which contains an etherified or esterified hydroxy group in the phenyl nucleus, and/or whose amino group contains a substituent which can be replaced by H, to set free the hydroxy and/or amino group or (d) a primary amine of formula I with a physiologically compatible acid, to convert the base into an acid addition salt or (e) an acid addition salt of formula I with a strong base to liberate the base of formula I.  Starting materials suitable for use in process (a) are azides, hydrazides, hydrazones, nitriles, imines, oximes, esterified oximes or nitro compounds.  Hydrogenolytically removable residues include halogen atoms, benzyl or substituted benzyl groups, aryl sulphonyl groups (present at an amino group), hydroxy groups optionally etherified or esterified and amino or alkylated amino groups in the a -position to the phenyl radical. Groups or atoms replaceable by an amino group in process (b) include halogen atoms, hydroxy, acyloxy, secondary and tertiary amino groups, and amino groups in process (c) containing a substituent which can be replaced by H include acylamino and isocyanate groups.  4 - Tert. - butyl - 3 - hydroxy - 2,6 - dimethylphenylacetone and a mixture of the syn- and anti-forms of its oxime are prepared from the corresponding benzyl cyanide and methyl magnesium iodide and reaction of the ketone with hydroxylamine.  4 - (41 - Tert. - butyl - 31 - hydroxy - 21, 61 - dimethyl - phenyl) - butane - 2 - one is prepared from the benzyl chloride by the acetoacetic acid synthesis. 4 - 41 - Tert. - butyl - 21,61 - dimethylphenyl) - butane-2-one oxime is prepared from the ketone and hydroxylamine.  4 - Tert.- amyl - 3 - hydroxy - 2,6 - dimethyl - benzyl cyanide is prepared by chloromethylation of the phenol and reaction with sodium cyanide. Similarly are prepared 3-hydroxy-2,6-dimethyl-4 (31 - methylpentyl - 31) - benzyl cyanide and 2,4 - di - tert. - butyl - 6 - methyl benzyl cyanide.  N,N,O - Triacetyl - 4 - tert. - butyl - 3 - hydroxy - 2,6 - dimethylphenethylamine is prepared from the free hydroxy-substituted amine by reaction with acetic anhydride and partial saponification of the triacetyl compound yields N-acetyl-4-tert. - butyl - 3 - hydroxy - 2,6 - dimethylphenethylamine.  Pharmaceutical compositions comprise compounds of the Formula I in admixture with a carrier, and may be in the form of tablets, dragees, solutions, suspensions, emulsions, ointments and creams. The compounds show tuberculostatic and tuberculocidal activity.  Specification 967,594 is referred to.