Chemistry of 1,2-dialkynylimidazoles: rearrangements to cyclopentapyrazines and imidazo[1,2-a]pyridines

dc.contributor.advisorKerwin, Sean M.en
dc.creatorNadipuram, Asha Krishnaen
dc.description.abstractA series of 1,2-dialkynylimidazoles (1,2-DAIs) intended as azaenediynes wherein the nitrogen is part of a heterocyclic imidazole ring were synthesized and their chemistry studied. The key N-alkynyl group was introduced using iodonium salts followed by a palladium coupling to add the 2-alkynyl side chain. Upon thermolysis in neat 1,4- cyclohexadiene, all of the 1,2-DAIs underwent an unprecedented molecular rearrangement to cyclopentapyrazine carbenes. These carbenes participated in hydrogen atom abstraction, cyclopropanation and C-H insertion. In benzene, all of the cyclopentapyrazine carbenes react with benzene, by presumably first forming a ix norcaradiene intermediate that rearranges to the phenyl adduct without any detection of cycloheptatriene intermediates. The carbene was also found to perform intramolecular olefin addition and C-H insertion forming interesting three- and four-membered ring pyrazines, yields of which were were maximized upon thermolysis in hexafluorobenzene. The rearrangement mechanisms of 1,2-DAIs were transformed in halogenated solvents. When compound 2.12 with an N-phyenylethynyl group was thermolyzed in chlorobenzene, a chloroimidazopyridine product derived from the 2,3-didehydropyridine intermediate was isolated. N-Ethynylated 1,2-DAIs, however, underwent a rearrangement to chlorinated imidazo[1,2-a]pyridines via a electrocyclic rearrangement of an α- chloroenamine intermediate. This rearrangement also occurred when an amine was the nucleophile while compounds in which the 2-alkynyl side chain is sterically demanding do not cyclize. Inclusion of the ynamine into an imidazole ring reversed the electronics of the N-alkynyl group in a few cases, with nucleophilic attack occurring at the β carbon of the ynamine.
dc.description.departmentPharmaceutical Sciencesen
dc.rightsCopyright is held by the author. Presentation of this material on the Libraries' web site by University Libraries, The University of Texas at Austin was made possible under a limited license grant from the author who has retained all copyrights in the works.en
dc.subject.lcshAntineoplastic antibioticsen
dc.titleChemistry of 1,2-dialkynylimidazoles: rearrangements to cyclopentapyrazines and imidazo[1,2-a]pyridinesen
dc.type.genreThesisen University of Texas at Austinen of Philosophyen

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