Patent GB-673864-A (GB)
Title: Process for obtaining organic amino diols
Filed: 1949-08-22
Abstract: Acid addition salts of (dl)-q -amino diols of the formula <FORM:0673864/IV (b)/1> where Y is hydrogen or an -NO2 group, R1 and R2 are the same or different and represent hydrogen, halogen, alkyl or alkoxy radicals, R3 is hydrogen or an alkyl radical, and X is halogen, or the bases corresponding to such salts, are obtained by treatment with thionyl chloride of (dl)-reg. amino diol derivatives of the formula <FORM:0673864/IV (b)/2> where R4 represents hydrogen or an acyl, e.g. aliphatic acyl, halogen substituted aliphatic acyl, benzoyl, substituted benzoyl or araliphatic radical, followed by hydrolysis of the intermediate compound so formed, and when the free base is desired, by neutralization of the salt.  It is postulated that the intermediate compound has the formula <FORM:0673864/IV (b)/3> where R may be alkyl, halogen-substituted alkyl, phenyl, substituted phenyl or aralkyl.  The alkyl, alkoxy, or aliphatic radicals contain not more than 4 carbon atoms.  The reaction with thionyl chloride is carried out below 50 DEG  C., preferably at 20 DEG  to 35 DEG  C., either in a solvent, e.g. benzene, toluene, xylene, chloroform or carbon tetrachloride, or preferably in presence of excess thionyl chloride.  The hydrolysis is carried out by heating the reaction mixture at 60 DEG  to 110 DEG  C. with at least sufficient water to hydrolyse the intermediate product and excess thionyl halide.  The products are recovered by evaporation to dryness, extraction or (free bases) by filtration.  The process may be applied to a mixture of (dl)- reg. and (dl)-q  forms of an amino diol derivative.  It is postulated that the (dl)-q -diastereoisomer yields an intermediate of the formula <FORM:0673864/IV (b)/4> and is not changed in structural configuration during the process, although the acyl group or groups are removed, and the product is solely a (dl)-q  amino diol acid addition salt.  Examples describe the preparation of (1a), (dl)-q 1-p-nitrophenyl - 2 - aminopropane - 1,3 - diol and (1b) the corresponding hydrochloride, from (dl) - reg. - 1 - p - nitrophenyl - 2 - acetamido - propane-1,3-diol; (1c) and (1d), (dl)-q -1-p-nitrophenyl 2-aminopropane-1,3-diol and its hydrochloride from (c) (dl)-reg.-1-p-nitrophenyl-2-acetamido - 3 - acetoxypropane - 1 - ol, and (d) a mixture of (dl)-reg.- and (dl)-q -1-p-nitrophenyl - 2 - acetamidopropane - 1,3 - diol; (2) (dl) - q  - 1 - phenyl - 2 - aminopropane - 1,3 - diol and its hydrochloride or hydrobromide are prepared from (a), (dl)-reg.-1-phenyl-2 acetamidopropane-1,3 diol, (b), (dl)-reg.-1-phenyl-2-acetamido - 3 - acetoxypropane - 1 - ol and thionyl bromide, (c), (dl)-reg.-1-phenyl-2-benzamidopropane-1,3-diol or (dl)-reg.-1-phenyl-2-chloracetimidopropane-1,3-diol, (d), a mixture of (dl)-reg.- and (dl)-q -1-phenyl-2-acetamidopropane-1,3-diol; (3) (dl)-q -1-o-methyl-p-nitrophenyl - 2 - aminopropane - 1,3 - diol and (dl)-q - 1 - o - methylphenyl - 2 - aminopropane - 1,3 - diol from (dl)-reg.-1-o-methyl-p-nitrophenyl-2-propionamidopropane-1,3-diol and (dl)-reg.-1-o - methylphenyl - 2 - propionamidopropane - 1,3-diol respectively; (4) (dl)-q -1-m-methoxyphenyl-2-aminopropane-1,3-diol and (dl)-q -1-p-nitro-m-methoxyphenyl - 2 - aminopropane - 1,3 - diol from (dl) - reg. - 1 - m - methoxyphenyl - 2 - phenylacetamidopropane - 1,3 - diol, and (dl) - reg. - 1 - p - nitro - m - methoxyphenyl - 2 - phenylacetamidopropane-1,3-diol respectively; (5) (dl) - q  - 1 - (31,41 - dimethylphenyl) - 2 - aminopropane-1,3-diol, and (dl)-q -1-(21-nitro-41,51 - dimethylphenyl) - 2 - aminopropane - 1,3 - diol from (dl)-reg.-1-(31,41-dimethylphenyl)-2-acetamido - 3 - benzoxypropane - 1 - ol and (dl) - reg. - 1 - (21 - nitro - 41,51 - dimethylphenyl)-2 - acetamido - 3 - benzoxypropane - 1 - ol; (6) (dl) - q  - 3 - (31 - chloro - 51 - nitrophenyl) - 2 - aminobutane-1,3-diol from (dl)-reg.-3-(31-chloro-51 - nitrophenyl) - 2 - acetamido - 1 - acetoxybutane - 3 - ol and (dl) - q  - 3 - (31,51 - dichlorophenyl)-2-aminobutane-1,3-diol from (dl)-reg.-3 - (31,51 - dichlorophenyl) - 2 - acetamido - 1 - acetoxybutane - 3 - ol.  Except where stated thionyl chloride is employed.  The free base is liberated by making the reaction mixture alkaline with ammonia or sodium hydroxide.  The products are suitable as intermediates of antibiotics; those of (1) and (2) may be used in preparing (l) - q  - 1 - p - nitrophenyl - 2 - dichloracetamido-propane-1,3-diol.  To prepare the starting materials, e.g. (dl)-reg.-acylamido acyloxy alcohol, the corresponding (dl)-reg. amino diol is acylated with an acyl anhydride at about 70 DEG  C., or with an acyl halide, anhydride or ester in aqueous medium in the presence of basic substance.  The alcohol compound so obtained gives the corresponding (dl)-reg. acylamido diol by hydrolysis with one equivalent of alkali in cold aqueous acetone.  The (dl)-reg.-acylamido diol compound may be acylated at about 70 DEG  C. with another acyl anhydride.  Reference is made to Specifications 652,273 and 652,274.  The Specification as open to inspection under Sect. 91 includes the conversion of the products of examples 2(a) and 2(d) to (dl)-q -1-phenyl-2-acetamido-1,3-diacetoxypropane by treatment with acetic anhydride and pyridine.  The product of example 3(b) is converted to the sulphate.  The free base obtained in example (4) is converted to salts such as the tartrate, camphor sulphonate or benzoate by reaction with an alcoholic solution of the corresponding acid.  This subject-matter does not appear in the Specification as accepted.