Chemistry of Thienopyridines. III. Syntheses of the Thieno[2,3-b]-and Thieno[3,2-b]pyridine Systems. Direct Substitution into the Former System

Abstract

Condensation-cyclization reactions of 2- and 3-thienylammonium hexachlorostannates were used in practical syntheses of thieno[2,3-b]pyridine (1), thieno[3,2-6]pyridine (2), and their derivatives. Malondialdehyde tetraethyl acetal (MDTA) reacted with these salts to give 1 and 2 (44 and 77% yields, respectively). Acetoacetaldehyde dimethyl acetal reacted (with attendant loss of acetone) to form monoacetyl derivatives, wherein the substituent is located β to the nitrogen atom. Methyl vinyl ketone led to mixed (α and γ) monomethyl compounds. Some 1,3-diketones and 1,3-ketoaldehydes also reacted. Structures of the monomethyl derivatives were established by direct comparison with the products of reaction of vmylmethylpyridines and methylethylpyridines with hydrogen sulfide at 630°. The salts of 4- and 5-amino-2-acetylthiophene also reacted with MDTA to form 2-acetyl derivatives of 1 and 2. Nmr data are reported and correlated with structures of the various thienopyridine compounds. Bromination of 1 gave the 2,3-dibromo derivative, while reaction of 1 with deuteriosulfuric acid gave fastest D-H exchange at C-3 and slower exchange at C-2. Reaction of 1 with methyllithium led to products expected from lithiation at C-2 and from addition to the C═N moiety. These results are consistent with calculated reactivity indices and expectations as based on data for the quinoline and benzo[b]thiophene systems. © 1969, American Chemical Society. All rights reserved.