Accidental discovery of a ‘longer-range’ vinylogous Pummerer-type lactonization: formation of sulindac sulfide lactone from sulindac

Unexpected formation of sulindac sulfide lactone occurred when sulindac was treated with oxalyl chloride and triethylamine. Structurally analogous sulindac sulfide and indomethacin did not undergo such lactonization under similar reaction conditions. We believe that the sulfoxide function in sulindac plays a pivotal role possibly via a ‘longer-range’ vinylogous Pummerer-type reaction as a driving force for the observed lactonization. The structure of the lactone was confirmed by single crystal X-ray analysis.

Unexpected formation of sulindac sulfide lactone (4) from sulindac (1) in presence of oxalyl chloride and Et3N has occurred probably via a thionium ion-assisted ‘longer-range’ vinylogous Pummerer-type lactonization.Figure optionsDownload as PowerPoint slide