Azaindole derivatives. 63. Effect of the solvating capacities of solvents on the pathways of reactions under the conditions of the Hofmann rearrangement

Abstract

It is shown that 1-benzyl-6-chloro-7-carbamoyl-5-azaindoline undergoes primarily normal skeletal rearrangement to give 1-benzyl-6-chloro-7-methoxycarbonylamino-5-azaindoline under the conditions of the Hofmann reaction in the presence of pyridine, whereas the primary process in aqueous methanol is splitting out of an isocyanate anion to give 1-benzyl-6-chloro-7-bromo-5-azaindoline. Under the same conditions 1-benzyl-6-chloro-7-carbamoyl-5-azaindole is converted to a mixture of 1-benzyl-6-chloro-7-methoxycarbonylamine-5-azaindole and products of electrophilic substitution of the hydrogen in the 3 position of the starting compound and the final reaction products by bromine, whereas 1-benzyl-7-carbamoyl-5-azaindoline forms 1-benzyl-7-methoxy-carbonylamino-5-azaindoline in ∼50% yield.