Previous work from the North group has resulted in the development of highly active catalysts for the addition of CO2 to epoxides resulting in the formation of cyclic carbonates. Some of these catalysts have been shown to be active in related reactions such as the addition of CS2 or isocyanates to epoxides. In this project, the use of these catalysts to catalyse the reaction between carbon dioxide and aziridines will be investigated, giving access to commercially important oxazolidinones. Recent work has shown that a catalyst is active for this reaction provided that the group on the nitrogen atom of the aziridine (R3) is electron donating such as an alkyl group. This project will build on this discovery.
Screening of catalysts:To determine the optimal catalyst lead class for the synthesis of oxazolidinones from aziridines and CO2 and to discover any differences between the catalyst classes in terms of regiochemistry and substrate specificity. Using a multipoint reactor, each catalyst will first be screened against a single aziridine (R1 = Ph, R2 = H, R3 = PhCH2) under a range of temperatures and pressures, using various solvents and with and without cocatalysts such as ammonium and phosphonium salts or DMAP. Then, under its optimized conditions, active catalysts will be screened against a range of aziridines differing in the structure of R1, R2 and R3.
Catalyst structure optimisation: To prepare one or more highly active optimized catalysts. The optimal lead catalyst(s) will then undergo structural optimization by varying the substituents present, especially those on the aromatic rings of the catalyst which can have powerful electronic and steric influences on catalyst activity. Each catalyst variant will be screened against a small number of aziridines rather than just one to ensure that a catalyst with generally high activity is being discovered.
Mechanistic studies on the optimal catalyst(s): To fully understand the mode of action of the most active catalysts. The stereochemical consequences (cis/trans) of converting 1,2-disubstitued (including 1-D-2-alkyl) aziridines into oxazolidinones with the optimized catalyst(s) will be determined and the secondary kinetic isotope effect associated with reaction of a 1,1-di-deuterated aziridine measured. Enantiomerically pure aziridines will also be prepared and the retention, inversion or loss of absolute stereochemistry during conversion to oxazolidinone determined. The reaction kinetics will be determined under a range of conditions and used to deduce the order with respect to aziridine, CO2 and catalyst. A Hammett analysis will be carried out using substituted aromatic rings on C or N to determine the degree of bond breaking in the TS. These data will allow a mechanism and catalytic cycle to be proposed.
DFT calculations (optional): To complement the experimental work, DFT calculations will be carried out on both the uncatalysed and catalysed conversion of aziridines to oxazolidinones. The DFT calculations will confirm the validity of the experimental mechanistic study, allow the rate determining step to be determined and be used iteratively to facilitate further optimization of the catalyst structure.
All research students follow our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills. All research students take the core training package which provides both a grounding in the skills required for their research, and transferable skills to enhance employability opportunities following graduation.
Project specific training will focus on synthetic chemistry, high pressure reactions and use of various analytical techniques (NMR, IR, mass spectrometry, X-ray crystallography, HPLC, GC etc) to characterise catalysts and reaction products. The student will also receive training in the synthesis of isotopically labelled compounds and various physical organic chemistry techniques including reaction kinetics, isotope effects and Hammett plots. There is also scope for the student to be trained in DFT calculations and their application to catalytic cycles. Presentation skills will be enhanced by presentations at weekly group meetings and at green chemistry meetings.
The Department of Chemistry holds an Athena SWAN Gold Award and is committed to supporting equality and diversity for all staff and students. The Department strives to provide a working environment which allows all staff and students to contribute fully, to flourish, and to excel: https://www.york.ac.uk/chemistry/ed/
. This PhD project is available to study full-time or part-time (50%).
This PhD will formally start on 1 October 2019. Induction activities will start on 30 September.