MECHANISMS OF NUCLEOPHILIC SUBSTITUTION AT C-N BOND

C-N 键的亲核取代机制

• 批准号: 6107437
• 负责人: JAMES P JOHNSON
• 金额: --
• 依托单位: TEXAS WOMAN'S UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6107437
• 关键词: carbon; chemical binding; chemical bond; chemical cleavage; chemical group; chemical substitution; chemical synthesis; cyclic compound; imines; nitrogen; stereochemistry

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.

许多重要的酶催化反应涉及亲核性。 碳-氧双键上的取代。据信， 立体电子效应在这些酶催化的过程中起着重要的作用。 通过四面体进行的亲核取代反应 中间体。因为它与碳-氧关系密切 双键，我们建议评估立体电子的重要性 含a的化合物对亲核取代反应的影响 碳-氮双键。 我们研究计划的长期目标一直是合成 含碳氮双键的构型稳定的化合物 可用于动力学和立体化学研究的键[Ar(X)C=NOCH3] 关于这个纽带的反应。赤霉菌稳定的Z和E异构体的分离 羟甲基氯化物(X=C1)、烷基苯羟亚胺(X=OCH2CH3)、 胺酮[X=(CH2)3N]和羟基氰化物(X=CN)使我们能够 开展了C=N键的亲核攻击机理研究。我们 建议通过合成环状化合物来继续这项研究，其中 羟甲基氯或羟肟酸盐官能团被锁定在 平面E配置。我们建议研究亲核反应的动力学。 在这些环状化合物中进行取代，以便比较速率数据 与在开链化合物上得到的结果相同。这项研究应该删除 关于对E利率数据的解释的任何模棱两可的地方 苯基被扭曲的开链化合物的异构体 C=N键的平面。 该项目和其他相关项目将为MBRS学生提供 学习用于(1)合成有机材料的现代方法的机会 化学；(2)有机结构测定，包括核磁共振、红外光谱和红外光谱。 UV/Vis光谱；(3)动力学测量。