Patent GB-723940-A (GB)
Title: N-aralkyl-1-(p-hydroxyphenyl)-2-amino-butanols-(1)
Filed: 1952-07-15
Abstract: The invention comprises N-aralkyl-1-(parahydroxyphenyl) - 2 - amino - butanols - (1) of the general formula <FORM:0723940/IV (b)/1> wherein X is a phenyl group and R is a bivalent alkyl residue having 1 to 5 carbon atoms and may be of the form -(CH2)n-, where n is 1 to 5, or <FORM:0723940/IV (b)/2> , where y is 0 to 3.  The compounds are prepared (1) by conversion of the corresponding ether or ester of the formula <FORM:0723940/IV (b)/3> in which R1 is a benzyl or sulphonic acid residue, e.g. a toluene-sulphonyl residue, using known methods such as catalytic hydrogenation in the presence of a palladium or nickel catalyst to remove the benzyl group or treatment with acid or alkali to remove the sulphonic group (2) by condensing a diketone of the formula (p) HO-C6H4-CO-CO-CH2-CH3 with an amine of formula XR-NH2 to form a Schiff's base which is simultaneously or subsequently reduced, the subsequent reduction, for example, being carried out in an organic solvent with a metal such as aluminium or magnesium or a metal alloy such as aluminium amalgam, while the simultaneous reduction, for example, may be effected by hydrogenation in the presence of a precious metal catalyst (3) by condensing 1 - (para - hydroxyphenyl) - 2 - amino - 1 - butanol or 1 - (para - hydroxy - phenyl) - 2 - amino - 1 - butanone with an aldehyde of general formula X-CHO or preferably XR2-CHO, wherein R2 is a hydrocarbon residue having 1 to 4 carbon atoms (e.g. cinnamic and hydrocinnamic aldehydes), or with a ketone of general formula R3-CO-R4X, wherein R3 is methyl and R4 is a hydrocarbon residue in which the sum of the carbon atoms contained in R3 and R4 is 2 to 4 (e.g. phenyl, benzyl and benzal acetone), and simultaneously or subsequently effecting catalytic hydrogenation in the presence of a precious metal catalyst, preferably palladium oxide-barium sulphate or platinum oxide (4) by catalytic reduction of 1-(parahydroxyphenyl) - 2 - nitro - 1 - butanol dissolved in an organic solvent and in the presence of aldehydes X-CHO or XR2-CHO, or ketones R3-CO-R4X, using Raney nickel or a precious metal catalyst (5) by the reduction of a compound of the general formula <FORM:0723940/IV (b)/4> with hydrogen in the presence of a precious metal catalyst.  The final products in each case are obtained as mixtures of stereoisomeric racemates which may be separated by crystallization of their salts or of the free bases. The examples describe the preparation of 1-(parahydroxyphenyl) - 2 - (a  - methyl - g  - phenyl - propylamino) - butanol - (1), 1 - (para - hydroxyphenyl) - 2 - (a  - methyl - b  - phenyl - ethyl - amino) - butanol - (1), 1 - (para - hydroxy - phenyl) - 2 - (g  - phenyl - propylamino) - butanol-(1), 1 - (para - hydroxyphenyl) - 2 - (d  - phenyl - butylamino) - butanol - (1), 1 - (para - hydroxy - phenyl) - 2 - (a  - phenyl - ethylamino) - butanol - (1) and salts thereof.  1 - (Para - benzylhydroxyphenyl) - 2 - (a  - methyl - g  - phenyl - propylamino) - butanone, 1 - (para - benzylhydroxyphenyl) - 2 - (d  - phenyl - butylamino) - butanone and 1 - (para - benzyl - hydroxyphenyl) - 2 - (a  - phenyl - ethylamino) - butanone are prepared by brominating 1-parabenzylhydroxy-butyrophenone and reacting the product with 1-phenyl-3-aminobutane, 1-phenyl - 4 - aminobutane and a  - phenyl - ethylamine respectively.  1 - (para - benzylhydroxyphenyl) - 2 - (a  - methyl - g  - phenyl - propylamino) - butanol -(1) is prepared by hydrogenating 1-(para-benzylhydroxyphenyl) - 2 - (a  - methyl - g  - phenyl - propylamino) - butanone with platinum oxide in methanol.  1 - (para - hydroxyphenyl) - 2 - (d  - phenyl - butylamino) - butanone and 1 - (para - hydroxy - phenyl) - 2 - (a  - phenyl - ethylamino) - butanone are prepared by hydrogenolytic debenzylation of the corresponding para-benzylhydroxyphenyl p  compounds using a palladium-barium sulphate catalyst. Specification 368,613 is referred to.