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

Cacheux, Valérie M. Y.

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

dc.check.date	2023-05-20T11:37:21Z
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.check.entireThesis	Entire Thesis Restricted
dc.check.info	Restricted to everyone for five years	en
dc.check.opt-out	Not applicable	en
dc.check.reason	This thesis is due for publication or the author is actively seeking to publish this material	en
dc.contributor.advisor	Collins, Stuart G.	en
dc.contributor.advisor	Maguire, Anita R.	en
dc.contributor.author	Cacheux, Valérie M. Y.
dc.contributor.funder	SSPC	en
dc.contributor.funder	Science Foundation Ireland	en
dc.date.accessioned	2018-05-21T11:37:21Z
dc.date.issued	2018
dc.date.submitted	2018
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.description.status	Not peer reviewed	en
dc.description.version	Accepted Version
dc.format.mimetype	application/pdf	en
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.identifier.uri	https://hdl.handle.net/10468/6157
dc.language.iso	en	en
dc.publisher	University College Cork	en
dc.relation.project	info:eu-repo/grantAgreement/NSF//6930598/US/Synthetic Organic Chemistry/	en
dc.rights	© 2018, Valerie M.Y. Cacheux.	en
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/	en
dc.subject	Thiazine	en
dc.subject	α-Thio-β-chloroacrylamide	en
dc.subject	Organic chemistry	en
dc.subject	Flow chemistry	en
dc.thesis.opt-out	true
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