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dc.contributor.advisorTimothy F. Jamison.en_US
dc.contributor.authorHeckman, Laurel Millikanen_US
dc.contributor.otherMassachusetts Institute of Technology. Department of Chemistry.en_US
dc.date.accessioned2018-09-28T20:59:27Z
dc.date.available2018-09-28T20:59:27Z
dc.date.copyright2018en_US
dc.date.issued2018en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/118267
dc.descriptionThesis: Ph. D. in Organic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2018.en_US
dc.descriptionCataloged from PDF version of thesis. Page 300 blank.en_US
dc.descriptionIncludes bibliographical references.en_US
dc.description.abstract[chemical formula] Highly functionalized 2-arylindoles were synthesized from 2-alkenylarylisocyanides and arylboronic acids using a simple, inexpensive copper catalyst. The reaction exhibits excellent functional group tolerance for both the arylisocyanide and boronic acid coupling partners. To avoid the direct handling of the pungent arylisocyanide starting materials, continuous flow chemistry is further demonstrated to provide safe and effective access to 2-arylindoles through in situ dehydration and cyclization of easy-to-handle 2-alkenyl-N-formylanilines. Laurel M. Heckman and Dr. Zhi He contributed equally to initial reaction investigation. Z.H. carried out the arylboronic acid scope. L. M. H. carried out reaction optimization, isocyanide scope and reactions in continuous flow. [chemical formula] Despite its utility, monochloramine (NH₂Cl) has not achieved widespread use as a nitrogen transfer reagent due to its unstable and hazardous nature. We developed a continuous flow platform for the safe, reliable, and inexpensive on-demand synthesis of NH₂Cl. Additionally we demonstrate the synthetic utility of NH2Cl by converting it to valuable NH aziridne and nitrile products in good to excellent yield in exceedingly short reaction times. Dr. Evan Styduhar developed continuous flow synthesis of NH₂Cl. E.S. also developed the reaction of NH2 Cl to form aziridines and nitriles in batch and continuous flow. Laurel M. Heckman helped optimize the continuous flow setup, performed the reaction scope in continuous flow, and explored additional substrates in batch. [chemical formula] A rapid, operationally simple synthesis of 6-TAMRA, an important probe for labeling biomolecules, from 2-carboxycarbonylterephthalic acid and 3-dimethylaminophenol is described herein. The intermediate ketoacid was synthesized in a single step from commercially available dimethylacetophenone. Additionally, progress was made towards a facile scalable synthesis in continuous flow. Dr. Justin A. M. Lummiss carried out the oxidation batch synthesis. Laurel M. Heckman carried out reaction screening and optimization of step 2 of the batch synthesis. L.M.H and J.A.M.L contributed equally to the experiments in continuous flow. Dale Thomas (graduate student, Jensen Research Group, MIT Department of Chemical Engineering) developed the fully automated platform. Bruce Adams (Staff, DCIF of MIT Department of Chemistry) helped with low temperature and 2-D NMR experiments. Peter MUller (Director, Diffraction Facility of MIT Department of Chemistry) carried out the single-crystal X-ray diffraction experiments.en_US
dc.description.statementofresponsibilityby Laurel Millikan Heckman.en_US
dc.format.extent300 pagesen_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsMIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectChemistry.en_US
dc.titleEnabling the use of unstable, hazardous reagents with continuous flow synthesisen_US
dc.typeThesisen_US
dc.description.degreePh. D. in Organic Chemistryen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistry.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistry
dc.identifier.oclc1054181451en_US


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