The synthesis and reactions of thienopyridines

  • Kenneth Wilson

    Student thesis: Doctoral Thesis

    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 AwardJan 1992
    Original languageEnglish
    SupervisorDavid H. Bremner (Supervisor)

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