Electrochemical reduction of 5-benzylidene thiazolidine-2,4-diones: a greener approach to the preparation of glitazone APIs

Author(s)

de Castro, Pedro P. ; Martins, Guilherme M. ; Gomes, Ronewalber B. ; Simoso, Guilherme B. ; Amarante, Giovanni W. ; Brocksom, Timothy J. ; de Oliveira, Kleber T.

• Document type: Journal article
• Source: CHEMICAL COMMUNICATIONS; v. 59, n. 61, p. 4-pg., 2023-07-05.

Abstract

A transition-metal free methodology for the chemoselective reduction of benzylidene thiazolidine-2,4-diones and similar heterocycles is described, allowing the preparation of a broad scope of the corresponding reduced derivatives in up to 90% yield. The protocol has a simple and safe experimental setup, in which water was employed as the hydrogen source. To further demonstrate the synthetic utility of this transformation, the antidiabetic API Pioglitazone was prepared in 81% yield. To the best of our knowledge, this is the first hydride and transition-metal free protocol for the synthesis of Pioglitazone, highlighting its potential utility as a greener alternative in both academic and industrial synthesis. (AU)

• FAPESP's process: 20/06874-6 - Applications of technologies and synthetic methodologies developed under continuous flow conditions at LQBO-UFSCar for the preparation of molecules with biological activities and APIs
• Grantee: Kleber Thiago de Oliveira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/13924-2 - Development of novel continuous flow approaches towards the preparation of pharmaceuticals: Axitinib, Lacosamide, Pioglitazone and Rosiglitazone
• Grantee: Pedro Pôssa de Castro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 21/14446-7 - Multi-user equipment approved in grant 13/07276-1: Mass spectrometer with triple quadrupole analyzer and gas chromatography system coupled to the mass spectrometer
• Grantee: Vanderlei Salvador Bagnato
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 22/00074-3 - Regioselective fluorination of N-heterocycles using electrosynthesis and continuous flow conditions
• Grantee: Guilherme Ariel Machado Martins
• Support Opportunities: Scholarships in Brazil - Post-Doctoral