A versatile new synthesis of quinolines and related fused pyridines. Part 7. The conversion of acetamidothiophens into thienopyridines

Abstract

5-Substituted-2-acetamidothiophens are converted into 2-acetamidothiophen-3-carbaldehydes in good yield with equimolar amounts of dimethylformamide and phosphoryl chloride in hot dichloroethane. However, undersimilar conditions but with three mol of phosphoryl chloride, 6-chlorothieno[2,3-b]pyridines are obtained. Use of phosphoryl chloride as solvent (7 mol) with three mol of dimethylformamide gives good yields of 6-chlorothieno-[2,3-b]pyridine-5-carbaldehydes. Similarly, thieno[3,2-b]-and thieno[3,4-b]-pyridines are obtained from 3-acetamidothiophen and 2,5-dimethyl-3-acetamidothiophen respectively. The mechanisms of these reactions are explored and compared with those involved in the formation of related quinolines from acetanilides and shown to involve initial ring formylation. The analogous formation of 2-chloroquinolines is shown to have limited potential.