Patent GB-711905-A (GB)
Title: 1-(úÝ-hydroxyphenyl)-1-hydroxy-2-aralkylaminopropanes
Filed: 1951-05-15
Abstract: The invention comprises compounds of the formula (m)HO - C6H4 - CHOH - CH(CH3) NH-R-C6H5, in which the C6H5 group may be substituted, e.g. by alkyl groups; R is a straight or branched alkylene chain of 2-5 carbon atoms with at least two between the -NH- and the -C6H5 residues.  The compounds are made as follows: (1) reduction of the corresponding ketones with aluminium amalgam or catalytic hydrogenation; (2) from the m-benzyloxy compounds by catalytic hydrogenation; (3) from their derivatives esterified at the phenolic hydroxy group with carboxylic or sulphonic acids, by acid or alkaline hydrolysis; (4) from the benzyl ethers of the corresponding ketones by catalytic hydrogenation; (5) by catalytic hydrogenation of a mixture of (m)HO-C6H4 CHOH-CH(CH3)-NH2 or the m-benzyloxy compound and the appropriate aralkyl or aralkenyl aldehyde or ketone; (6) by catalytic hydrogenation of a mixture of (m)HO-C6H4-CO-CH(CH3)-NH2 or its benzyl ether and the appropriate aralkyl or aralkenyl aldehyde or ketone; (7) by catalytic hydrogenation of a mixture of (m) HO-C6H4-CHOH-CO-CH3 or the m-benzyloxy compound and the appropriate aralkylamine; (8) by catalytic hydrogenation of a mixture of (m) HO-C6H4-CO-CO-CH3 or its benzyl ether and the appropriate aralkylamine.  Method (5)-(8) proceed via aldehyde-ammonias and Schiff's bases.  Salts such as hydrohalides may be obtained by using corresponding salts of the starting materials, from which the free bases may be prepared.  Examples are given of the production of 1 - (m - hydroxyphenyl) - 2 - (b  - phenylethylamino) - propanol by methods (1), (7) and (8), 1-(m-hydroxyphenyl)-2-(a -methyl - b  - phenylethylamino) - propanol by methods (4) and (5), 1-(m-hydroxyphenyl)-2-(g -phenylpropylamino)-propanol by methods (2), (3), (4) and (5), 1-(m-hydroxyphenyl)-2-(a -methyl - g  - phenylpropylamino) - propanol by methods (1), (4) and (7) and 1-(m-hydroxyphenyl) - 2 - (a  - methyl - g  - phenylbutylamino)-propanol by methods (4) and (5).  In method (7) an optically active product is obtained by using an active m-hydroxyphenylacetyl-carbinol as starting material.  Different geometrical isomers may be obtained by the different methods. Compounds of the formula (m)ZO-C6H4-CHOH-CH(CH3) -NH-R-C6H5, where Z is benzyl or a carboxylic or sulphonic ester group are made by methods analogous to (1), (5), (6), (7) and (8) above.  The preparation of 1 - (m - benzyloxyphenyl) - 2 - (g  - phenylpropylamino)-propanol hydrobromide and the corresponding p - toluenesulphonyloxy compound (hydrochloride) by method (1) is described.  Compounds of the formula (m) XO-C6H4-CO-CH(CH3)-NH-R-C6H5, where X is hydrogen, benzyl, or a carboxylic or sulphonic ester group are made by treating (m)XO-C6H4-CO-CH(CH3)-Hal with the appropriate aralkylamine. Examples describe the preparation of such compounds where X is benzyl and R is -CH2-CH2-, -CH2-CH2-CH2-, -CH(CH3)-CH2-CH2- and -CH(CH3)-CH2-CH(CH3)-, and also where X is a p-toluenesulphonic ester group and R is -CH2-CH2-CH2-.  Those where X is H may also be prepared by catalytic hydrogenation of the benzyl ethers. Such preparation is described where R is -CH2-CH2-and -CH2-CH2-CH2-.  m - Benzyloxy - a  - bromo - propiophenone is made from m-benzyloxybenzaldehyde by conversion into the oxime, dehydration to m-benzyloxybenzonitrile, reaction with ethyl magnesium bromide to give m-benzyloxy-propiophenone and final bromination.  m - (p - Toluenesulphonyloxy) - a  - bromo - propiophenone is made by esterifying m-hydroxypropiophenone with p-toluenesulphonyl chloride and brominating the product.  1 - (m - Hydroxyphenyl) - 2 - aminopropanol is prepared (as hydrochloride) by catalytic hydrogenation of m-benzyloxy-isonitroso-propiophenone.  Specification 368,613 is referred to.