Patent GB-454042-A (GB)
Title: Manufacture of hydroaromatic amino-alcohols and derivatives thereof
Filed: 1935-05-30
Abstract: Hydroaromatic aminoalcohols and derivatives thereof are obtained by hydrogenating acylaminophenols or their derivatives in the presence of a base metal and an organic solvent, and saponifying the products if desired.  When both stereoisomeric forms of a hydroaromatic acylaminoalcohol or derivative are produced during the hydrogenation, these may be separated by fractional crystallization.  As starting materials there may be used simple acylaminophenols, e.g. acetyl-, propionyl- or benzoyl - aminophenols, or their O - acyl derivatives, or derivatives having substituents, e.g. alkyl, aryl or arlkyl groups, in the nucleus or at the oxygen or the nitrogen atom, or the polynuclear analogues of the acylaminophenols.  In the examples: (1) p-acetaminophenol is hydrogenated at 180 DEG  C. in alcoholic solution in the presence of a nickel catalyst; a mixture of cis- and trans-p-acetaminocyclohexanol is obtained, and is separated by fractional crystallization from acetone; the products are then saponified with hydrochloric acid to yield cis- and trans-p-aminocyclohexanol; p-stearylaminophenol similarly yields stereoisomeric p - stearylaminocyclohexanols, from which the stereoisomeric p-aminocyclohexanols are obtainable by saponification; (2) o-acetaminophenol is hydrogenated at 180 DEG  C. in decahydronaphthalene solution in the presence of nickel; a mixture of cis- and trans-o-acetaminocyclohexanol is obtained, and is separated by fractional crystallization from acetone or ethyl acetate; the products are then saponified with hydrochloric acid to yield cis- and trans-o-aminocyclohexanol; (3) m-acetaminophenol is hydrogenated at 160 DEG  C. in alcoholic solution in the presence of a nickel-cobalt catalyst; a single m-acetaminocyclohexanol is obtained, and yields a m - aminocyclohexanol when saponified with sulphuric acid; (4) p-benzaminophenol is hydrogenated in alcoholic solution at 150--170 DEG  C. in the presence of nickel; trans - p - hexahydrobenzaminocyclohexanol is obtained, and yields trans-p-aminocyclohexanol on saponification; o-hexahydrobenzaminocyclohexanol is similarly obtainable from o-benzaminophenol in decahydronaphthalene solution; (5) acetyl-p-phenetidine is hydrogenated at 170--180 DEG  C. in alcoholic solution in the presence of nickel; a mixture of the cis- and trans-forms of p-acetaminocyclohexanol ethyl ether is obtained and is separated by means of ether; the acetyl groups may then be removed by saponification; o- and m-acetaminocyclohexanol ethyl ethers and the corresponding free amino compounds are similarly obtainable; (6) acetyl-p-anisidine, treated as in example 5, yields p-acetaminocyclohexanol methyl ether and the corresponding free amino compound; o-acetaminocyclohexanol methyl ether and the corresponding free amino compound are similarly obtainable; (7) p-acetaminophenol allyl ether is hydrogenated in alcoholic solution, first in the cold and then at 180 DEG  C., in the presence of nickel; a mixture of the cis- and trans-forms of p-acetaminocyclohexanol propyl ether is obtained and is separated by means of water; the corresponding free amino compounds are obtained by saponification; (8) N-methyl-p-acetaminophenol (prepared by acetylating N-methyl-p-aminophenol) is hydrogenated at 170--180 DEG  C. in alcoholic solution in the presence of nickel; the cis- and trans-N-methyl-p-acetaminocyclohexanols so obtained are separated by means of ethyl acetate, and are saponified to the corresponding N-methyl-p-aminocyclohexanols.