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
    Original languageEnglish
    SupervisorDavid H. Bremner (Supervisor)

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