Diffusion mixing with a volatile tertiary amine as a very efficient technique for 1,3-dipolar cycloaddition reactions proceeding via dehydrohalogenation of stable precursors of reactive dipoles

Abstract

Spontaneous diffusion of volatile reagent vapors into a solution, containing a stable precursor of an unstable reactive intermediate, may be the simplest method for carrying out some organic reactions, including 1,3-dipolar cycloaddition. In the present work, this technique was applied to generate nitrile imines and nitrile oxides for the subsequent reactions with dipolarophiles from hydrazonyl halogenides or N-hydroxyimidoyl halogenides by the action of volatile tertiary amines (Et₃N, as well as Me₃N or DIPEA). Generation of highly reactive intermediates as a result of tertiary amine vapor diffusion into the reaction mixture makes it possible to obtain the products of 1,3-dipolar cycloaddition reactions in high yields and without the side product formation due to the created conditions of “dipole starvation”. The proposed method of diffusion reagent mixing allows us to carry out 1,3-dipolar cycloaddition reactions with low-stability and easily dimerizing nitrile oxides and nitrile imines in high yields and is incredibly easy experimentally. In fact, 1,3-dipoles are obtained by this method “molecule-by-molecule”, which prevents their unwanted dimerization.