Synthesis and reactions of some pyridines and thienopyridines

  • Keith Sturrock

    Student thesis: Doctoral Thesis

    Abstract

    The overall aim of this research project is to investigate nucleophilic substitution reactions of the thiomethyl group of 3-ethyloxycarbonyl-2-methylthiothieno[2,3-b]jpyridine. The multistep synthesis of this compound is reviewed and improvements described. The first step is the N-oxidation of ethyl 3- pyridylacetate, so reagents for the preparation of this and other 3-substituted pyridines were investigated and a novel workup procedure for oxidation with m-CPBA (m-chloroperbenzoic acid) is described. The preparation of ethyl 2-chloro-3-pyridylacetate and several polychlorinated pyridine derivatives are reported. Novel ketene dithioacetals were prepared from ethyl 5-chloro-3-pyridylacetate and 5-chloro-3-pyridylacetonitrile and some were converted to highly substituted thiophenes. Novel thieno[2,3-b]pyridines and [3,2-c]pyridines were prepared from ethyl 2-chloro-3-pyridylacetate, ethyl 4-chloro-3-pyridylacetate and their N-oxides. Preparation of the sulphoxide and sulphone of 3-ethyloxycarbonyl-2- methylthiothieno[2,3-b]pyridine was investigated and their relative susceptibility to substitution by some nitrogen nucleophiles examined. The conversion of benzylamine to benzaldehyde by the N-oxide group during the reaction of 3-ethyloxycarbonyl-2-methylthiothieno[2,3-b]pyridine N-oxide with benzylamine was studied in some detail. Attempts were made to develop a synthetic route to the potential agonist of serotonin, 3-(2-aminoethyl)-5-hydroxythieno[2,3-b]pyridine from 3-ethyloxycarbonyl-2-methylthiothieno[2,3-b]pyridine. Successful removal of the thiomethyl group at C-2 of 3-ethyloxycarbonyl-2-methylthiothieno[2,3- bjpyridine and progress made in development of the side chain at C-3 is reported. This thesis exhibits evidence of clear progress towards the development of a novel synthetic route to potential agonists of serotonin.
    Date of AwardAug 2005
    LanguageEnglish
    SupervisorDavid H. Bremner (Supervisor)

    Cite this

    Synthesis and reactions of some pyridines and thienopyridines
    Sturrock, K. (Author). Aug 2005

    Student thesis: Doctoral Thesis