MECHANISMS OF NUCLEOPHILIC SUBSTITUTION AT C-N BOND

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Many important enzyme-catalyzed reactions involve nucleophilic substitutions at the carbon-oxygen double bond. It is believed that stereoelectronic effects play an important role in those enzyme-catalyzed nucleophilic substitution reactions that proceed through tetrahedral intermediates. Because of its close relationship to the carbon-oxygen double bond, we propose to evaluate the importance of stereoelectronic effects on nucleophilic substitution reactions of compounds containing a carbon-nitrogen double bond. The long-term objective of our research program has been to synthesize configurationally stable compounds containing the carbon-nitrogen double bond [Ar(X)C=NOCH3] that can be used for kinetic and stereochemical studies on reactions at this bond. The isolation of stable Z and E isomers of hydroximoyl chlorides (X=C1), alkyl benzohydroximates (X=OCH2CH3), amidoximes [X=(CH2)3N], and hydroximoyl cyanides (X=CN) has enabled us to carry out mechanism studies on nucleophilic attack at the C=N bond. We propose to continue this research by synthesizing cyclic compounds in which the hydroximoyl chloride or hydroximate functional group is locked into a planar E configuration. We propose to study the kinetics of nucleophilic substitution in these cyclic compounds in order to compare the rate data with that obtained on the open-chain compounds. This study should remove any ambiguity concerning the interpretation of the rate data on the E isomers of the open-chain compounds where the phenyl group is twisted from the plane of the C=N bond. This project and other related projects will give MBRS students the opportunity to learn modern methods used in (1) synthetic organic chemistry; (2) organic structure determination including NMR, IR, and UV/VIS spectroscopy; and (3) kinetic measurements.