The synthesis and reactions of thienopyridines

Abstract

The synthesis of ortho-halogenated pyridine derivatives (A-D; R = CN, CO₂Et; R₁ = CN, CO₂Me, CO₂Et) containing methylene groups activated by the nitrile or ester functionality is described. Derivatives (A-D) are reacted with carbon disulfide in the presence of base, followed by alkylation with iodomethane, to afford novel thienopyridines (E-H; R = CN, CO₂Et; R₁ = CN, CO₂Me, CO₂Et; X = SMe).

Pyridine derivative (B; R = CN) also reacts with phenyl isothiocyanate to form thienopyridine (F; R = CN; X = NHPh). Reaction of the nitriles (A, C and D; R, R₁ = CN) under identical conditions, however, does not give the bicyclic compounds but ketene dithioacetals (I, J and K). Increasing the reaction temperature allows formation of thienopyridines (E, G and H; R, R₁ = CN; X = NHPh). Thienopyridines R = CO₂Et; R₁ = CO₂Me, CO₂Et; X = NHPh) are also synthesised from the ruction of the derivatives (A-D; R = CO₂Et; = CO₂Me; CO₂Et) with phenyl isothiocyanate.

Reaction of nitrile (A; R₁ = CN) with carbon disulfide in the presence of base, followed by quenching with ethyl chloroacetate affords thienopyridine (E; R1 = CN; X = SCH₂CO₂Et) which in turn cyclises with base to give tricyclic compound (L).

Thienopyridines (E; R₁ = NH₂; X = CN, Ph, CO₂Et, COMe, COPh, COCH₂CO₂Et) are synthesised from reactions of 3-cyanopyridine-2(lH)-thione with compounds containing a halogen atom adjacent to an active methylene group.

Nucleophilic reactions of thienopyridines (E; R₁ = CN; X = SMe, SOMe, SO₂Me) are investigated, in an attempt to prepare tricyclic compounds.

Date of Award	Jan 1992
Original language	English
Supervisor	David H. Bremner (Supervisor)