Patent GB-795131-A (GB)
Title: Improvements in or relating to the preparation of primary alcohols
Filed: 1955-02-23
Abstract: Primary alcohols are prepared by the reduction of carboxylic acids or their functional derivatives, for example esters, halides and anhydrides, with an alkaline earth metal borohydride.  The reduction is preferably carried out in an hydroxy-free medium, e.g. ether or tetrahydrofuran, at temperatures in the range - 10 DEG  to + 80 DEG C., but hydroxylic solvents such as ethanol may be used at - 10 DEG to - 50 DEG  C.  Instead of using alkaline earth metal borohydrides, the reduction may be effected with a mixture of an alkaline earth metal salt and a complex metal borohydride, the metal component of which is not an alkaline earth metal, e.g. an alkaline earth iodide or bromide with sodium or potassium borohydride.  The reduction is highly selective leaving nitro groups and double bonds unaffected. This method of reduction may be applied to all types of carboxylic acid esters, e.g. aliphatic, aromatic and aryl aliphatic esters and particularly for alpha-aminoacids and their functional derivatives. Thus, both the threo and erithro-modifications of p-nitrophenyl serine esters, or N-acyl derivatives thereof are reduced to 1-(p-nitrophenyl)-2 - amino - 1 : 3 dihydroxypropane and its N-acyl derivatives, respectively.  In examples: (1) and (2) p-nitrobenzoic acid ethyl ester is reduced to p-nitrobenzylalcohol with calcium iodide and sodium borohydride in tetrahydrofuran or ether; (3) threo-p-nitrophenyl serine ethyl ester N-acetate is reduced to threo-1-(p-nitrophenyl) - 2 - acetamido - 1 : 3 - dihydroxypropane as in (1); (4) 2-(p-nitrophenyl)-serine ethyl ester is reduced with calcium chloride and sodium borohydride in ethanol, the product is converted to the benzal and the latter to threo-1 - (p - nitrophenyl) - 2 - amino - 1 : 3 - dihydroxypropan hydrochloride from which the free base is liberated; (5) D(-)-threo-2-(p-nitrophenyl)-serine is esterified with ethanol and reduced as in (4) to the D(-)-threo-aminodiol; (6) threo-p-nitrophenyl serine methyl ether ethyl ester is reduced as in (1) to threo-1-(p-nitrophenyl)-1-methoxy - 2 - amino - 3 - hydroxypropane; (7) p-nitrobenzoic acid ethyl ester is reduced with calcium borohydride to p-nitrobenzyl alcohol; (8) p-nitrobenzoic acid ethyl ester is reduced as in (4); (9) threo-beta-phenylserine ethyl ester is reduced as in (4) to threo-1-phenyl-2-amino - 1 : 3 - dihydroxypropane, the product is converted to the p-nitrobenzoylamino compound or benzalamino compound and thence to the free base; (10) ethyl benzoate is reduced to benzyl alcohol with calcium borohydride; (11) phenyl acetic acid ethyl ester is reduced as in (10) to beta-phenyl ethanol; (12) threo-beta-phenylserine ethyl ester is reduced with strontium iodide and sodium borohydride, the product is converted to the benzal compound of threo - 1 - phenyl - 2 - amino - 1 : 3 dihydroxypropane or separated by extraction; (13) Example (12) is repeated using barium iodide; (14) threo-p-nitro-beta-phenylserine ethyl ester reduced as in (12) to threo-p-nitrophenylserinol; (15) p-nitrobenzoyl chloride is reduced to p-nitrobenzoyl alcohol with calcium borohydride. Specifications 699,821 and 795,130 are referred to.ALSO:In the reduction of carboxylic acids to primary alcohols, calcium, strontium, or barium borohydrides are used, which may be in a hydroxyl-free medium, e.g. ether or tetrahydrofuran, or a hydroxylic solvent, e.g. ethanol.  In Examples 4, 8, 9, calcium chloride dissolved in absolute ethanol is reacted with sodium borohydride which may also be dissolved in absolute ethanol.  In Examples 12, 13, strontium or barium iodide dissolved in tetrahydrofuran is reacted with powdered sodium borohydride. Specifications 699,821, [Group IV (b)], and 795,130 are referred to.