Thiophene systems. 10. The synthesis and chemistry of some thienopyridinols

Substituted thieno[2,3‐c]‐, thieno[3,2‐c]‐ and thieno[3,4‐c]pyridinols have not been described despite the fact that a few descriptions of the parent ring systems have appeared in the literature. As part of our ongoing program to investigate the synthesis of thiophene derivatives with potential biological activity, we became interested in the preparation of the various thienopyridinols. Syntheses of the title compounds 2a, 3 and 25 were achieved starting from thiophene‐3‐acetic acid and 3‐acetylthiophene. The two isomeric systems 2a and 3 were reacted with electrophiles to give products substituted at the position α to the hydroxy group on the pyridine ring (the 4‐ and 6‐positions, respectively). Lack of stability of 25 precluded studies on this system. Compounds 2a, 3 and 25 reacted with acetic anhydride to give O‐acetyl derivatives while reaction of the anion of 2a and 3 with methyl iodide gave mixtures of O‐ and N‐methylation. The N‐methylated products are the novel thienopyridones 45 and 47.