Synthesis of α-thio-β-chloroacrylamides including continuous processing and application to the formation of sulfur containing heterocycles

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dc.contributor.advisor Collins, Stuart G. en
dc.contributor.advisor Maguire, Anita R. en Cacheux, Valérie M. Y. 2018-05-21T11:37:21Z 2018 2018
dc.identifier.citation Cacheux, V. M. Y. 2018. Synthesis of α-thio-β-chloroacrylamides including continuous processing and application to the formation of sulfur containing heterocycles. PhD Thesis, University College Cork. en
dc.identifier.endpage 361 en
dc.description.abstract α-Thio-β-chloroacrylamides are formed from the analogous α-thioamides through an oxidative reaction cascade. In this work, enhanced insight into the mechanistic pathway leading to these highly functionalised compounds has been achieved, in addition to demonstration of their potential as intermediates in the synthesis of pharmaceutically significant heterocycles. The first chapter is an extensive literature review of the synthesis of sulfur containing heterocycles including 1,4-oxathiin, 1,4-dithiin, 1,4-thiazine and 1,4- benzothiazine derivatives. After an initial brief discussion of the importance of these compounds as therapeutic agents, common synthetic strategies and more exotic approaches are described. In some instances, the mechanisms involved in these transformations are outlined. The second chapter focuses on a detailed investigation of a series of α-thio-β- chloroacrylamides and of the intermediates involved in the reaction cascade leading to their formations. A previously unseen pathway leading to the β- chlorosulfide has been revealed. The advantages associated with used of a continuous flow process enabled for the first time the scale up of the α-thio-β- chloroacrylamide transformation. Notably, the reaction cascade can be controlled through this continuous system, leading to selective recovery of individual components from the reaction. Efficient rapid quantification of reaction products, intermediates, starting material and by-products within the process through HPLC underpinned the development of an efficient flow process. The third chapter discusses the synthesis of a range of functionalised α-thio-β- chloroacrylamides. The stereoselectivity and the efficiency of the transformation involved were seen to be highly sensitive to the precursor substituents and the solvent system employed. These novel derivatives enabled formation of 1,4- oxathiin, 1,4-thiazine and 1,4-benzothiazine derivatives via intramolecular cyclisation processes. Extension of the strategy to dithiin synthesis has also been investigated. The novel thiazine synthesised in this project was subsequently derivatised providing a broad range of new thiomorpholines. Investigation into the potential of these sulfur containing heterocycles as anti-cancer agents is described. en
dc.description.sponsorship R17051 SFI 12/RC/2275 SSPC2 LT1 en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2018, Valerie M.Y. Cacheux. en
dc.rights.uri en
dc.subject Thiazine en
dc.subject α-Thio-β-chloroacrylamide en
dc.subject Organic chemistry en
dc.subject Flow chemistry en
dc.title Synthesis of α-thio-β-chloroacrylamides including continuous processing and application to the formation of sulfur containing heterocycles en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD en
dc.internal.availability Full text not available en Restricted to everyone for five years en 2023-05-20T11:37:21Z
dc.description.version Accepted Version
dc.contributor.funder SSPC en
dc.contributor.funder Science Foundation Ireland en
dc.description.status Not peer reviewed en Chemistry en
dc.check.reason This thesis is due for publication or the author is actively seeking to publish this material en
dc.check.opt-out Not applicable en
dc.thesis.opt-out true
dc.check.entireThesis Entire Thesis Restricted
dc.check.embargoformat Apply the embargo to both hard bound copy and e-thesis (If you have submitted an e-thesis and a hard bound thesis and want to embargo both) en
dc.internal.conferring Summer 2018 en
dc.relation.project info:eu-repo/grantAgreement/NSF//6930598/US/Synthetic Organic Chemistry/ en

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© 2018, Valerie M.Y. Cacheux. Except where otherwise noted, this item's license is described as © 2018, Valerie M.Y. Cacheux.
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