Chemistry of thienopyridines. XIX. Further studies on chlorination and <i>S</i>‐oxidation in the thieno[2,3‐<i>b</i>] pyridine system

Abstract

Abstract Treatment of thieno [2,3‐ b ] pyridine (1a) with chlorine gas in chloroform (plus water) gave a mixture of two 2,3‐dichloro‐2,3‐dihydrothieno[2,3‐ b ] pyridine 1‐oxides [ trans‐syn (IIa), and cis‐anti (IIb)) [and 2,3,3‐trichloro‐2,3‐dihydrothieno[2,3‐ b ]pyridine syn ‐1‐oxide (IVa), as well as a non‐isolated fourth product (prohably the anti isomer of IVa) and sometimes a small amount of thieno[2,3‐ b ]pyridine 1,1‐dioxide (III). Treatment of Ia in a solvent (water, chloroform‐water, or THF‐water) with sulfuric acid and sodium hypochlorite gave a mixture of IIb and III. Effects of variations of reaction conditions on the composition of the product mixture were ascertained through chemical isolation and/or pmr analysis. Products formed were rationalized in terms of the chlorine‐water‐hypochlorous acid equilibrium, plus attack of chlorine variously at positions 1 ( S ‐atom), 2, and 3 of 1a, but of hypochlorous acid only at position 1. Thermal and chromatographic limitations on isolation procedures for some of the products were established. Stereochemistries of IIa, IIb, and IVa were assigned by means of pmr spectrometry with the aid of the shift reagent Eu(fod) 3 . Spin‐spin couplings between the proton at position 2 and those at positions 4 and 6 were observed at high resolution. In exploratory runs, 5‐ethyl‐la was converted into isolable 2,3‐dichloro‐5‐ethyl‐2,3‐dihydrothieno[2,3‐ b ]pyridine 1‐oxide, and 5‐acetyl‐Ia yielded 3‐chloro‐5‐acetylthieno] 2,3‐ b ]pyridine. Mass spectral fragmentation patterns for the various products are presented.