Leveraging automation to elucidate reaction mechanisms
department or school: Science, Faculty of
department or school: Chemistry, Department of
data provider: DSpace
degree campus: UBCV
creator: Malig, Thomas
issued: 2020-09-22T18:28:36Z
issued: 2020
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Understanding chemical processes facilitates reaction optimization to make synthetic procedures more efficient while also enabling reaction discovery. Temporal profiling of chemical reactions provides the gold standard for increasing mechanistic understanding. Unfortunately, obtaining time-course information reproducibly, accurately, and also minimizing analyst intervention is a significant challenge. Combining in situ spectroscopic methods with automated sampling techniques provides a robust method to generate kinetic profiles enabling increased mechanistic understanding. This thesis explores the development and application of online HPLC as an analytical technique to obtain concentration data while minimizing workload for the analyst. By utilizing commercially available laboratory equipment and software we have created a sampling device capable of automatically monitoring both homogeneous and heterogeneous reactions, as well as those performed under an inert atmosphere. The ability of the platform to sample, dilute, mix, and analyze reaction aliquots reproducibly has been validated, thereby ensuring accuracy of acquired time-course data. This automated reaction monitoring device has been used to delineate reaction mechanisms for a series of chemically distinct transformations. The Kinugasa reaction for the synthesis of beta-lactams was investigated. A novel retrocycloaddition step accounts mechanistically for byproducts associated with the transformation. A telescoped synthesis yielding cyanoimidazoles via combining an imidazole forming condensation annulation with a functional group conversion was also investigated. A series of Buchwald-Hartwig aminations performed within a glovebox using various aryl halide components were explored. Lastly, the mechanism of a synthetic procedure to synthesize Spiro-OMeTAD, a state-of-the-art organic material used in modern solar cells, was probed. By leveraging automated reaction monitoring devices, mechanistic understanding for…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/76128
note: LEVERAGING AUTOMATION TO ELUCIDATE REACTION MECHANISMS by Thomas Malig B.Sc. Tech, University of Guelph, 2013 M.Sc., University of Calgary, 2016 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Chemistry) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) September 2020 © Thomas Malig, 2020 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Leveraging Automation to Elucidate Reaction Mechanisms submitted by Thomas Malig in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemistry Examining Committee: Jason E. Hein, Associate Professor, Chemistry, UBC Supervisor Glenn Sammis, Associate Professor, Chemistry, UBC Supervisory Committee Member Dan Bizzotto, Professor, Chemistry, UBC University Examiner John Sherman, Professor, Chemistry, UBC University Examiner Additional Supervisory Committee Members: David Perrin, Professor, Chemistry, UBC Supervisory Committee Member Parisa Mehrkhodavandi, Professor, Chemistry, UBC Supervisory Committee Member iii Abstract Understanding chemical processes facilitates reaction optimization to make synthetic procedures more efficient while also enabling reaction discovery. Temporal profiling of chemical reactions provides the gold standard for increasing mechanistic understanding. Unfortunately, obtaining time-course information reproducibly, accurately, and also minimizing analyst intervention is a significant challenge. Combining in situ spectroscopic methods with automated sampling techniques provides a robust method to generate kinetic profiles enabling increased mechanistic understanding. This thesis explores the development and application of online HPLC as an analytical technique to obtain concentration data while minimizing workload for the analyst. By utilizing commercially availa…
has type: Thesis/Dissertation
date issued: 2020-11
is shown at: 10.14288/1.0394472
language: eng
degree discipline: Chemistry
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/76128