Heterocycle Synthesis via One-Electron Oxidation of Nucleophile-Containing Oxime Derivatives
Authors:Neha Ansari, Brittany Grassbaugh, Aneta Jelowicki
Mentor:Peter de Lijser, Professor of Chemistry, California State University, Fullerton
Oximes and oxime ethers have found widespread use as drugs, additives, pesticides and other materials. Enzymatic metabolism of these substrates may lead to reactive intermediates such as radicals and radical ions, which may damage DNA or lead to disease. As such, a fundamental understanding of the structure and reactivity of these types of intermediates must be established. Our previous studies have shown that oxidation of oxime ethers in the presence of a nucleophile leads to nucleophilic attack at the oxidized nitrogen; therefore, oxime ethers with built-in nucleophiles may react to give cyclized products. Our current studies focus on oxime ethers with carbonyls acting as the built-in nucleophile. The purpose of these studies is to 1) understand the reactive intermediates formed and involved in the photosensitized electron transfer reactions of these substrates and 2) to investigate the possible cyclization pathways of the reactive intermediates formed by photosensitization. The focus of this study has been on the preparation and photooxidation of the mono t-butyl oxime ether derivative of 1-phenyl-1,3-butanedione. Previous work on the O-benzyl ether showed changes occurred in the aromatic region of the NMR spectrum, however, because of the presence of the benzyl group, it was not clear what these changes were caused by. The photolysis of the t-butyl ether derivative also shows clear changes in the aromatic region. The use of the solvent (benzene or acetonitrile) and the sensitizer was investigated and showed that the best results were obtained when using 2,3,5,6-tetrachloro-1,4-benzoquinone (CA) or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as the sensitizer and acetonitrile as the solvent. GC/MS analysis of the reaction mixtures shows the formation of two products with similar masses and mass spectra. On the basis of the mass spectra, it is possible that an unusual rearrangement may have taken place. The results of these studies will be discussed.