Reaction pathway of POCl₃-mediated Knoevenagel condensation of bisulfite adducts with 2,4-thiazolidinedione

GRAPHICAL ABSTRACT

Abstract

We investigated the POCl₃-mediated transformation of aromatic bisulfite adducts to the corresponding 5-arylidenethiazolidine-2,4-diones. The in situ transformation of an aromatic bisulfite adduct to the parent aldehyde in a non-aqueous non-polar solvent (toluene) was demonstrated using DoE (Design of experiment), offline ¹H NMR, online ReactIR, HPLC, LC-MS, and GC-MS. By means of these analytical tools, we determined, for the first time, the structure of the intermediate species (aldehyde) prior to the carbon–carbon double-bond formation. The carbon–sulfur bond undergoes a fast cleavage, immediately after the addition of POCl₃, which finally affords the corresponding 5-arylidenethiazolidine-2,4-diones.

KEYWORDS:

• Knoevenagel condensation
• statistical design of experiment
• ¹H NMR
• ReactIR
• LC-MS

Acknowledgment

We are grateful to the management of Dr. Reddy's Laboratories Limited for giving support to carry out this work.