Expeditious one-pot synthesis of highly substituted thiazolo[3,2-a]pyridines involving chromones

The 1,4-zwitterion derived from 4,5-dimethylthiazole and acetylenedicarboxylates has been shown to react at low temperature readily with 3-formylchromones (chromone-3-carboxaldehydes) resulting, after an unusual rearrangement, in the facile synthesis of thiazolo[3,2-a]pyridine derivatives; in the case of electron-donating substituents in the chromone ring tetracyclic chromenothiazolopyridines are isolated as the main reaction products. However, at higher temperature after an unexpected 1,2-aroyl migration 8-formyl-5H-[1,3]thiazolo[3,2-a]pyridines are formed as a mixture of two rotamers. Structural assignments of the new compounds as well as complete assignment of 1H and 13C NMR signals were based on the analysis of their 1H and 13C NMR (1D and 2D), IR, MS and elemental analysis data. Plausible mechanisms are proposed.

Graphical abstract4,5-Dimethylthiazole and acetylene react at low temperature with 3-formylchromones 1 resulting in thiazolo[3,2-a]pyridine derivatives 5 and in tetracyclic chromenothiaolopyridines 6. At higher temperature, after 1,2-aroyl migration, 8-formyl-5H-[1,3]thiazolo[3,2-a]pyridines 4 are formed as a mixture of two rotamers.Figure optionsDownload full-size imageDownload as PowerPoint slide