Analytical techniques for reaction monitoring, mechanistic investigations, and metal complex discovery
| dc.contributor.author | Thomas, Gilian T. | |
| dc.contributor.supervisor | McIndoe, J. Scott | |
| dc.date.accessioned | 2021-11-19T21:18:36Z | |
| dc.date.available | 2021-11-19T21:18:36Z | |
| dc.date.copyright | 2021 | en_US |
| dc.date.issued | 2021-11-19 | |
| dc.degree.department | Department of Chemistry | en_US |
| dc.degree.level | Doctor of Philosophy Ph.D. | en_US |
| dc.description.abstract | A variety of analytical techniques are showcased for their ability to provide insights into reaction mechanisms as well as active intermediate speciation. Pressurized Sample Infusion-Mass Spectrometry (PSI-ESI-MS), ion mobility-mass spectrometry (IMS-MS), and Nuclear Magnetic Resonance (NMR) spectroscopy are powerful analytical techniques capable of reaction monitoring. Contamination from vulcanized rubber was an issue with the PSI-ESI-MS technique as ions unrelated to the reaction were convoluting the mass spectrum. This was resolved by re-designing the PSI flask such that the septum was positioned above a condenser, preventing heat degradation of the septum and subsequent leaching of contam- inants into the reaction solution. The technique was then used to analyze the Buchwald-Hartwig amination reaction in real-time. The innovative use of Multiple Reaction Monitoring (MRM) scans facilitated observation of all catalytic intermediates, and elucidation of relative reaction rates for each step of the catalytic cycle. PSI-ESI-MS and NMR are complementary methods whereby catalytic intermediates are monitored via PSI-ESI-MS, and the rate of product formation is monitored via NMR spectroscopy. This combination of analytical methods was employed in the investigation of the Barluenga cross-coupling reaction between N-tosylhydrazones and aryl halides. A reaction screen revealed optimized homogeneous conditions, and the turnover limiting step was found to be off-cycle. IMS separates gaseous ions based on their size and shape immediately prior to MS analysis. Upon investigation of [PtCl3(C2H4)], and [PtCl3(CO)], it was found that residual [PtCl3] was forming [PtCl3(N2)] in the source of the instrument. Ion mobility was able to separate these isobaric ions, and DFT calculations and collision-induced dissociation experiments confirmed the existence of the gaseous [PtCl3(N2)] complex. NMR spectroscopy may also be employed as a strong reaction monitoring technique. The mechanism of C–H silylation by trimethyl(trifluoromethyl)silane and tetrabutylammonium difluorotriphenylsilicate was investigated using 19F-NMR. All intermediates and reaction byproducts were quantitatively observed, and the reaction conditions were optimized. A stopped-flow NMR system was used to gather data points in the first 0.2 seconds of the reaction. | en_US |
| dc.description.scholarlevel | Graduate | en_US |
| dc.identifier.bibliographicCitation | Thomas, G. T.; MacGillivray, L.; Dean, N. L.; Stoddard, R. L.; Yunker, L. P. E.; McIndoe, J. S. Confounding Contaminants in Mass Spectrometric Reaction Monitoring. Int. J. Mass Spectrom. 2019, 441, 14–18. https://doi.org/10.1016/J.IJMS.2019.04.001. | en_US |
| dc.identifier.bibliographicCitation | Thomas, G. T.; Janusson, E.; Zijlstra, H. S.; McIndoe, J. S. Step-by-Step Real Time Monitoring of a Catalytic Amination Reaction. Chem. Commun. 2019, 55 (78), 11727–11730. https://doi.org/10.1039/C9CC05076K. | en_US |
| dc.identifier.bibliographicCitation | Thomas, G. T.; Donnecke, S.; Paci, I.; McIndoe, J. S. Trichloro(Dinitrogen)Platinate(II). Chem. – A Eur. J. 2020, 26 (54), 12359–12362. https://doi.org/10.1002/chem.202003057. | en_US |
| dc.identifier.bibliographicCitation | García-Domínguez, A.; Helou De Oliveira, P. H.; Thomas, G. T.; Sugranyes, A. R.; Lloyd-Jones, G. C. Mechanism of Anion-Catalyzed C-H Silylation Using TMSCF3: Kinetically-Controlled CF3-Anionoid Partitioning As a Key Parameter. ACS Catal. 2021, 11 (5), 3017–3025. https://doi.org/10.1021/acscatal.1c00033. | en_US |
| dc.identifier.bibliographicCitation | Thomas, G. T.; Ronda, K.; McIndoe, J. S. A Mechanistic Investigation of the Pd-Catalyzed Cross-Coupling between N-Tosylhydrazones and Aryl Halides. Dalt. Trans. 2021, 50 (43), 15533–15537. https://doi.org/10.1039/D1DT03161A. | en_US |
| dc.identifier.uri | http://hdl.handle.net/1828/13525 | |
| dc.language | English | eng |
| dc.language.iso | en | en_US |
| dc.rights | Available to the World Wide Web | en_US |
| dc.subject | Mass Spectrometry | en_US |
| dc.subject | Reaction Monitoring | en_US |
| dc.subject | Catalysis | en_US |
| dc.subject | Pressurized Sample Infusion (PSI) | en_US |
| dc.subject | Ion Mobility Spectrometry | en_US |
| dc.title | Analytical techniques for reaction monitoring, mechanistic investigations, and metal complex discovery | en_US |
| dc.type | Thesis | en_US |