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.date.accessioned2008-08-28T22:43:06Zen
dc.date.available2008-08-28T22:43:06Zen
dc.date.issued2005en
dc.descriptiontexten
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.format.mediumelectronicen
dc.identifierb61143261en
dc.identifier.oclc71036003en
dc.identifier.urihttp://hdl.handle.net/2152/2322en
dc.language.isoengen
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
thesis.degree.departmentPharmacyen
thesis.degree.disciplinePharmacyen
thesis.degree.grantorThe University of Texas at Austinen
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

Access full-text files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
nadipurama07055.pdf
Size:
15.1 MB
Format:
Adobe Portable Document Format

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.65 KB
Format:
Plain Text
Description: