In this work, an efficient synthesis of 2-imino-1,3,4-oxadiazolines from acylhydrazides and isothiocyanates is described. In the presence of 4-dimethylaminopyridine (DMAP) and molecular oxygen, various 2-imino-1,3,4-oxadiazolines were produced in good to high yields. The developed method showed a broad substrate scope and was effective on the gram scale. On the basis of the mechanistic studies and previous literature, it was proposed that the mechanism consists of an aerobic oxidation of acylhydrazides facilitated by DMAP and isothiocyanates, followed by a DMAP-mediated annulation of the in situ generated acyldiazenes with isothiocyanates.

A one-pot synthesis of 2-imino-1,3,4-thiadiazolines was successfully achieved under mild conditions. The developed synthesis involves Fe(Pc)-catalyzed aerobic oxidation of acylhydrazides followed by P(NMe 2 ) 3 -mediated annulation of the in situ generated N-acyldiazene with isothiocyanates. The present annulation showed broad substrate scope with good functional group tolerance, and was effective on gram scale.aerobic oxidation, heterocycle, one-pot synthesis, organic synthesis S C H E M E 1 Previously reported preparations of 2-imino-1,3,4-thiadiazoline scaffold and the developed one-pot process for 2-imino-1,3,4-thiadiazoline. (a) Traditional methods. (b) Chang's 7 work. (c) This work. Su Been Kim and Sang Eun Baek contributed equally to this study. Dedicated to Professor Sukbok Chang on the occasion of his 60th birthday