Patent GB-766682-A (GB)
Title: Process for converting optically active aminodiols into racemic aminodiols
Filed: 1954-05-28
Abstract: The DL-threo form of 1-phenyl- or 1-p-nitrophenyl - 2 - amino - 1 : 3 - propanediol is prepared from the D-erythro or L-threo form thereof by a process which comprises removing the asymmetry of carbon atom 1 by oxidizing, after previous N-acylation or N,O3-diacylation of the starting material, the secondary carbinol group to a keto group, treating the resulting substituted propiophenone with a basic substance, and reforming the original aminodiol chain on the resulting optically inactive substance.  The oxidation step is advantageously effected by means of halogens or compounds liberating them (e.g. bromine or sodium bromate) in aqueous solution at 0-50 DEG C., preferably in the presence of actinic light and, when using sodium bromate, in the presence of hydrobromic acid.  When the starting material is acylated on the amino group only, the treatment with a basic substance, which may be inorganic (e.g. sodium or potassium hydroxide or sodium bicarbonate) or organic (e.g. a primary, secondary or tertiary aliphatic, carbocyclic or heterocyclic amine, especially anhydrous pyridine, piperidine or N-ethylpiperidine, an alkali metal alcoholate or enolate, an alkali metal salt of an organic acid or an organometallic derivative of an alkali metal), is preferably effected at 0-60 DEG  C., and brings about direct racemization, after which reformation of the aminodiol chain can be effected by reduction and hydrolysis.  When the starting material is N,O3-diacylated, the treatment with a basic substance, which is preferably effected at room temperature, causes the splitting off of the elements of the acylating acid to produce a racemic a -acylaminoacrylophenone (p-nitro substituted or not), from which DL-threo- and DL-erythro-1-phenyl- or -1-p-nitrophenyl - 2 - acylamino - 1 : 3 - propanediols are obtained by an addition reaction with a hydrohalic acid (preferably dissolved in an ether, the halogen entering the b -position) followed by reduction of the keto group (e.g. with metal hydrides such as sodium, potassium or lithium borohydride or lithium aluminium hydride, or an aluminium alcoholate such as aluminium isopropylate in the presence of excess of the alcohol), replacement of the halogen by an hydroxy group by the action of alcoholic alkali metal hydroxide (e.g. in the cold for 10-15 hours or in the warm for 5-30 minutes), and hydrolysis of the acylamino group.  The DL-threo and DL-erythro compounds may be separated by fractional crystallization immediately before or immediately after the replacement of the halogen, and the DL-erythro-acylaminodiol (alone or mixed with the DL-threo compound) may be epimerized (e.g. by formation and splitting of the corresponding cyclic sulphite) to give a further yield of the DL-threo-aminodiol. Examples illustrate the various alternative processes, the acyl groups introduced being dichloroacetyl, acetyl, propionyl, chloroacetyl and benzoyl.  Specification 715,128 is referred to.  Reference has been directed by the Comptroller to Specifications 652,273, 652,279, 673,864, 689,559 and 711,018.