With support of the Organic Dynamics Program in the Chemistry Division, Professor Peter de Lijser's proposed research will provide kinetic and mechanistic information on structure and reactivity of high-energy intermediates formed in the photooxidation of oximes and related compounds. These reactive intermediates, oxime radical cations, and other reactive oxygen or nitrogen species derived from these, such as iminoxyl and iminoyl radicals, will be studied in solution as well as in a confined environment (zeolites) in order to provide extra stabilization for the reactive intermediates. The proposal's primary research goals are:
1)To investigate the structure-reactivity relationships of oxime radical cations. This will require the PI and his research group to find conditions to observe these reactive intermediates directly. Both aldoxime and ketoximes will be studied and the formation of nitriles from aldoximes is of specific interest. 2)To probe the structure-reactivity relationships of oxime ethers, specifically the hypothesis that these species undergo nucleophilic addition or substitution at nitrogen. The PI's efforts will be focused on intramolecular reactions. 3)To selectively generate and study iminoxyl and iminoyl radicals, which are the proposed intermediates in the photooxidation of ketoximes and aldoximes, respectively.
Oximes and related compounds have found use as pesticides and drugs. Release of these chemicals into the environment (including cells and tissue of plants and higher animals) may result in photochemical (sensitized or direct) or enzymatic oxidations leading to the formation of reactive intermediates such as radical ions and radicals. The chemistry and potential dangers of these types of species are virtually unknown, and there exists a need for accurate kinetic and other reactivity data so that a general structure-reactivity pattern can be developed. The knowledge gained from these fundamental mechanistic and kinetic studies will establish a foundation for understanding experimental observations. The research will also provide much-needed tools to successfully utilize radical ions and other high-energy species for new chemical processes in synthesis and possibly in materials applications.
The proposed research will also provide an outstanding educational experience for students. Students will learn basic chemical laboratory principles such as how to synthesize, purify, and characterize compounds by means of spectroscopic techniques. Additionally, they will receive a solid education in learning mechanistic methodologies and advanced problem skills. Students will also receive training in less traditional techniques and areas such as electrochemistry, computational chemistry and nanosecond transient absorption spectroscopy; the last will be achieved by means of the newly purchased laser flash photolysis instrumentation with funds from this award. Professor de Lijser continues to build on his track record for increasing involvement of undergraduate students in scientific activities.
The Department of Chemistry and Biochemistry at California State University, Fullerton (CSUF) has long been recognized as offering a rigorous and contemporary curriculum that is responsive to future developments, reflects the interdisciplinary nature and diversity of the chemical science and enables students to become successful professionals, scholars, and scientifically literate citizens. Because the CSU provides a substantial percentage of the technical workforce, teachers and graduate student applicants in California, exposing students to modern research methods and environments will sustain regional, state-wide and national capabilities for education and training of undergraduates and Masters' students in the chemical sciences.
Oximes and oxime ethers are useful starting materials for synthetic transformations and are commonly used as drugs and pesticides, and also in a number of industrial processes. As such, oximes and their derivatives are likely to end up in the environment, which may lead to pollution issues as well as toxicological issues when taken up by organisms. A complete understanding of the behavior of these types of compounds under oxidative conditions is therefore essential. This NSF-funded research explores the structure and reactivity of the intermediates formed in the oxidative processes of oximes and their derivatives. This work has taught us about some of the fundamental reactivity of the reactive intermediates upon oxidation as described below. We have discovered that the radical species derived from benzylketoximes can undergo an unusual rearrangement that seems to be unique for this type of molecule. We aim to develop this into a probe that will allow us to prove the formation of the proposed reactive intermediates formed in certain enzyme-catalyzed processes and to monitor their reactivity. Our work has shown that beta-fragmentation reactions of N-alkoximinoyl radicals are very fast. These reactions therefore are useful methods for generating alkoxy radicals, for example as initiators for polymerization processes. Unlike transition-metal catalyzed cyclization reactions of o-alkynylaryl oximes, the photoinduced electron transfer reactions of these molecules give rise to a unique exo-cyclization pathway that is believed to involve iminoxyl radicals reacting with the alkyne moiety. This particular exo-cyclization pathway has not been observed before in these types of molecules and may provide a useful pathway to cyclic structures as synthetic targets. Some of the reactions we have discovered show the potential for generating novel heterocyclic aromatic molecules from simple starting materials that are easily prepared. The favorable cyclization reactions observed for these oxime ethers have guided us in the direction of heterocycle synthesis. These substrates and intermediates show promise for the preparation of more complicated ring structures present in natural products. Overall, our general understanding of the structure and reactivity of iminoxyl radical and oxime ether radical cation has increased dramatically and we expect to be able to take advantage of this knowledge when further pursuing potential applications. For example, the difference in reactivity observed when using the alkyne moiety or the aromatic ring will allow us to control the cyclization process based on the need for the presence of nitrogen only or both nitrogen and oxygen in the product. All of these findings, because of their fundamental nature, have contributed to a better understanding in the field of reaction dynamics and in a number of different chemistry fields, including organic synthesis. Beyond the discipline, this knowledge is eventually bound to impact studies and areas dealing with environmental issues as well as those of industrial processes, whether to avoid contamination, prevent toxicological issues, or to improve industrial processes. Having a better (public) knowledge about the behavior of reactive intermediates that can cause damage to the environment or living tissue may eventually lead to policy changes and improved environmental conditions. These combined research projects provided research training for 5 graduate students (MS) and 15 undergraduate students.
