クロルアンフェニコール合成研究 (第8報)

有機酸による1-p-Nitrophenyl-2-amino-1, 3-propanediolのアシル化

抄録

By heating 1-p-nitrophenyl-2-amino-1, 3-propanediol (aminodiol) (I) with an excess of dichloroacetic acid by themselves at 130-140° or in toluene, N, O, O-tri(dichloroacetyl)-aminodiol, m.p. 142-143°, is obtained. In the case of heating in butanol, N-dichloroacetylaminodiol (chloramphenicol), m.p. 150-151°, is obtained in a 47% yield irrespective of the amount of dichloroacetic acid used. Boiling aminodiol with an excess of acetic acid gives N, O-diacetylaminodiol, m.p. 170°, while heating with equimolar amount of acetic acid in toluene, or with 1-5 molar quantity of acetic acid in butanol gives N-acetylaminodiol, m.p. 162-163°, in 50-60% yield. Heating (I) in butanol with formic, menthoxyacetic and mandelic acids in butanol gives, respectively, N-formylaminodiol, m.p. 180°, in 80-90% yield, N-menthoxyacetylaminodiol, m.p. 138-140°, in 30% yield, and N-mandelylaminodiol, m.p. 182-184°, in 15% yield. Heating (I) with excess of benzoic acid at 130-140° gives N-benzoylaminodiol. From these results, it is seen that, although the yields vary according to the acid used, heating aminodiol with organic acid in butanol results in selective N-acylation, the reaction mechanism of which is assumed to be dehydration of organic salts of aminodiol.