Chemistry of thienopyridines. XXXV. Synthesis, tautomerism, and reactions of quinoline and thienopyridine systems which bear a 1‐carboethoxy‐1‐cyanomethyl substituent in the pyridine ring, part 2

Abstract

AbstractA comparison is made amongst the isosteric Systems quinoline, thieno[2,3,‐b]pyridine, and thieno[3,2‐b]‐pyridine which bear the 1‐carboethoxy‐1‐cyanomethyl substituent (R) alpha or gamma to the heterocyclic nitrogen atom. Treatment of thieno[3,2‐b]pyridine 4‐oxide with ethyl cyanoacetate and acetic anhydride at room temperature (Hamana reaction) gives the alpha R‐derivative 6 (27%), formulated as an intramolecular H‐bonded structure. Neither 6 nor its quinoline alpha analog reacts with refluxing acetic anhydride, while the quinoline gamma isomer 8, existing as NH and CH tautomers, yields an N‐acetyl derivative 10 (70%) under similar conditions. For each of 6 and 8 one can isolate two crystalline forms which differ considerably in color. Compound 10 and its gamma analog in the thieno[2,3‐6]pyridine series (previously obtained directly from a Hamana reaction) serve as acetylating agents for aniline, 1‐aminobutane, morpholine, and cholesterol. Correlations and contrasts in the three Systems are presented.