A novel and facile synthesis of 3,5-Disubstituted isothiozoles under metal free conditions using acetophenones and dithioesters

Abstract

A facile and conveniently simple new protocol is devised for the synthesis of 3,5-disubstituted and annulated isothiozoles under transition metal and catalyst free conditions utilizing easily available acetophenones, dithioesters and NH₄OAc. This strategy involves C=O and C=S functionalization via sequential imine formation followed by intra molecular cyclization and aerial oxidation forming consecutive C−N and S−N bonds respectively in one pot. This protocol offers a low cost, user friendly, straight forward and widely applicable approach to 3,5-disubstituted isothiazoles.

Graphical Abstract

Keywords:

• Air oxidation
• C–N and N–S bond formation
• intramolecular cyclization
• isothiazoles
• metal and catalyst free

Acknowledgments

We thank NMR facility, Institute of Excellence, University of Mysore, Manasagangotri, Mysore, India for spectral data.

Additional information

Funding

The author (N.C) is thankful to UGC, New Delhi, for senior research fellowships and financial support from the DBT Glue grant [No. BT/PR23078/MED/29/1253/2017 dated-22/03/2018] and VGST [K-FIST (L1)] grant [No. KSTePS/VGST/K-FIST(L1)/2017-18/GRD-681/79/2018-2019 dated-17/09/2018] and PURSE grant (phase 2/27(C); dated: 13/09/2019 and phase 2/27(G); dated: 01/10/2019). UOM/IOE/Project fellow/687/2019-20 dated 01/01/2020.