2-Chloroaroylthioamides in the Synthesis of Thiochromeno[2,3-b]pyridines

Significance

Tricyclic thiochromeno[2,3-b]pyridine derivatives are shown to be synthesized in a one-pot multicomponent cascade reaction from ortho-halo-β-aroylthioamides, Meldrum’s acid and aromatic aldehydes. The aroylthioamides are easily prepared from the corresponding acetophenone and phenylisothiocyanate. Interestingly, only fluoro and chloro derivatives were used, possibly the reaction fails with the more reactive bromo and iodo derivatives. Further, more variety on the substituent on the thioamide nitrogen would have been desirable. In terms of aldehyde, the substrate scope was well studied. Aliphatic aldehydes gave complex mixtures in the reaction. The yields range from moderate to good and it is assumed that the mechanism involves a Knoevenagel condensation-Michael addition-cyclocondensation-decarboxylation- rearrangement-intramolecular S_NAr reaction sequence, but no evidence was provided to support this theory.