Synthesis of 2-Imino-1,3,4-oxadiazolines from Acylhydrazides and Isothiocyanates via Aerobic Oxidation and a DMAP-Mediated Annulation Sequence

Abstract

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.

Elemental Sulfur Promoted Cyclization of Aryl Hydrazones and Aryl Isothiocyanates Yielding 2-Imino-1,3,4-thiadiazoles

“…Some control experiments were next carried out (Scheme ). First, the reaction of hydrazide 5 and 2a was investigated (eq 1), as in the presence of organophosphorus catalyst 5 could be the precursor to undergo a cyclization with aryl isothiocyanate affording 2-imino-1,3,4-thiadiazoles . Yet, we did not detect the formation of 3aa , somewhat indicating that an oxidation of 1a was minor if possible.…”

“…In 2020, Yu, Chang, and co-workers developed a more general, direct tactic to afford 2-imino-1,3,4-thiadiazoles from a two-step method (Scheme ). Hydrazines were oxidized in the presence of molecular iodine to furnish N -acyldiazenes, which then underwent a P­(NMe 2 ) 3 -promoted cyclization with aryl isothiocyanates. A nearly identical approach could be used to afford 2-imino-1,3,4-selenadiazoles, using P­( n Bu) 3 .…”

Synthesis, in vitro α‐Glucosidase Inhibition, DFT Calculations, and Molecular Docking Studies of Some New Substituted 2,5‐Bis(pyrazolyl)‐1,3,4‐oxadiazoles

“…[25] Another two-steps strategy is refluxing of a mixture of carbohydrazide with acid chloride and later cyclized via cyclodehydration process. [26] Other miscellaneous documented strategies have involved: the reaction of carbohydrazide and its derivatives with; CS 2 in pyridine, [27] 1,1'-carbonyldiimidazole in DMF, [28] triethyl orthoformate, [29] a mixture of isobutyraldehyde and p-anisolyl iodide, [30] phenylisothiocyanate with tert-butyl hydroperoxide as oxidant [31] or via aerobic oxidation, [32] cyanogen bromide followed by dehydration with Eaton's reagent. [33] Nevertheless, the treatment of various aromatic acids with carbohydrazide is considered as a simple and a convergent synthetic approach to generate 2,5-disubstituted-1,3,4-oxadiazole molecules.…”