Patent GB-620690-A (GB)
Title: Manufacture of araliphatic amines
Filed: 1946-05-27
Abstract: Araliphatic amines of the general formula <FORM:0620690/IV (b)/1> where R1 is a substituted or unsubstituted diphenyl ether radicle, R2 is hydrogen or alkyl, and R3 and R4 are methyl or ethyl groups, are prepared by converting, by known methods, a ketone <FORM:0620690/IV (b)/2> into the corresponding amine which, if primary, is then further substituted by R4 to form the required secondary amine; substituents in R1 may also be changed in the process of the invention.  Specified known methods are: reduction of the ketone, in the presence of an amine or ammonia, with aluminium amalgam or catalytically activated hydrogen; condensation of the ketone with formamide, or the primary amines corresponding to the formyl compounds, and followed by hydrolysis; reduction of the ketone to the secondary alcohol and reaction of the halide of the latter with ammonia or a primary amine; and finally reduction of oximes or hydrazones of the ketone.  Ketones of the general formula may be prepared by aralkylating ketones which contain replaceable hydrogen at an a -carbon atom.  Substituent groups in the diphenyl ether radical may be reacted further, e.g. nitro group into hydroxyl group via the amino group, or alkoxy and acyloxy groups may be hydrolysed. In example (1), 1-[411-methoxyphenoxy)-phenyl]-pentanone-3 (prepared by reaction of 4 - (41 - methoxyphenoxy) - benzaldehyde and methylethylketone, followed by hydrogenation) is reduced with aluminium amalgam in the presence of aqueous methylamine to give 1 - [41 - (411 - methoxyphenoxy) - phenyl] - 3 - N - methylaminopentane. In example (2), 1-[41-(411 - methoxyphenoxy) - phenyl] - 2 - methylpentanone-3 (prepared from 4-(41-methoxyphenoxy)-benzyl chloride, diethylketone and sodamide) is treated in the same way with ethylamine to give 1-[41-(411-methoxyphenoxy) -phenyl]-2-methyl-3-N-ethylaminopentane.  This same amine can be prepared from ethylamine and 1 - [41 - (411 - methoxyphenoxy) - phenyl] - 2 - methyl-3-bromopentane (prepared by action of phosphorus tribromide on 1-[41-(411-methoxyphenoxy)-phenyl] - 2 - methylpentanol - 3, which is produced by hydrogenation of the corresponding ketone. In example (3), 1-[41-(411-methoxyphenoxy) - phenyl] - 2 - methylpentanone - 3 is heated with formamide and then acid hydrolysed to give 1 - [41 - (411 - methoxyphenoxy) - phenyl]-2-methyl-3-aminopentane.  The latter may also be prepared by reduction of the oxime of 1-[41-(411-methoxyphenoxy)-phenyl]-2-methylpentanone-3 using sodium amalgam.  The product is then alkylated with formamide and aluminium amalgam.  In example (4), 1-[41-(411-aminophenoxy) -phenyl]-2-methyl-3-N-ethylaminopentane is diazotized and then hydrolysed to give 1-[41-(411-hydroxyphenoxy)-phenyl] - 2 - methyl - 3 - N - ethylaminopentane.  Other products of a similar type are specified.  The Specification as open to inspection under Sect. 91 refers also to the preparation of compounds of the general formula above in which R3 is alkyl or cycloalkyl, and R4 is hydrogen, a saturated or unsaturated alkyl or cycloalkyl radical or an aralkyl radical.  This subject-matter does not appear in the Specification as accepted.