STUDIES RELATED TO THE SYNTHESIS OF CHLORAMPHENICOL.Ⅳ ON THE REDUCTION WITH ALUMINIUM CHLORO-ALCOHOLATES

Aluminium chloro-isopropylate was prepared from aluminium chloride and a solution of aluminium isopropylate. A study on the rate of reduction of DL-α-acetamino-β-hydroxy-p-nitropropiophenone showed that, a mixture of aluminium isopropylate and the chloro-isopropylate containing approximately 39% molar ratio of the latter was optimal for the reduction. In addition to this improvement, we have devised a new way in working up the reaction product. The principle was that, when an excess of hydrochloric acid (20%) was added to the concentrated mass of the reaction, aluminium was converted to the highly soluble aluminium chloride, whilst DL-threo-1-p-nitrophenyl-2-acetamino-1, 3-diol formed in reduction was hydrolysed in situ to the hydrochloride of DL-threo-1-p-nitro-phenyl-2-amino-1, 3-diol which was relatively insoluble in the cold. Upon cooling, the hydrochloride of the amino-diol crystallized out was collected by filtration, and got rid of the majority of aluminium chloride by repeated washing with cold hydrochloric acid (20%), from which the free base could be obtained in overall yields of over 70% of theory against the initial DL-α-acetamino-β-hydroxy-p-nitro-propiophenone. Reduction with aluminium chloro-ethylate was attempted, but the yield was less satisfactory. However, it was discovered that the solubility of aluminium ethylate was much improved in the presence of the chloro-ethylate.