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
Awarding Institution
SupervisorDavid H. Bremner (Supervisor)

Cite this

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

Student thesis: Doctoral Thesis