Alvarez E J, Brodbelt J S
Department of Chemistry and Biochemistry, University of Texas at Austin 78712, USA.
J Mass Spectrom. 1996 Aug;31(8):901-7. doi: 10.1002/(SICI)1096-9888(199608)31:8<901::AID-JMS366>3.0.CO;2-Z.
The gas-phase basicities and relative methylation nucleophilicities of a series of simple cyclic carbonyl-containing compounds were evaluated in order to understand the low reactivities of some barbiturates and anti-convulsants in the gas phase. The gas-phase basicities were determined by the bracketing method, and the relative methylation nucleophilicities were characterized by monitoring ion-molecule reactions with CH3OCH2+ ions from dimethyl ether. Heats of formation were calculated for the protonated and methylated structures in order to estimate the favored sites of protonation and methylation. As shown in this paper, the positions of the carbonyl groups have a striking effect on the relative gas-phase basicities and methylation rates within a related series of compounds. For those compounds with two carbonyl groups in 1,2 positions, the methylation efficiency is enhanced by a factor of 100 over those compounds with two carbonyl groups in the 1,3 or 1,4 positions. This large difference is attributed to the variation in molecular dipole moments of the three cyclohexanediones and the relative positions of the two carbonyl groups. Cyclohexane-1,2-dione has the greatest dipole moment, leading to the highest interaction energy with the CH3OCH2+ reactant, and has the capability for cooperative interaction during the attack on CH3OCH2+ and subsequent rapid methyl cation transfer between the two carbonyl groups, thus enhancing the reaction rate and product stability. The order of gas-phase basicities is also strongly influenced by the number and positions of the carbonyl groups and the presence of a nitrogen atom in the ring. For example, glutarimide, which has two carbonyl groups surrounding a nitrogen atom in the ring, has a gas-phase basicity that is about 10 kcal mol-1 less than that of cyclohexane-1,3-dione. This result is attributed to the restriction of partial hydrogen-bond formation between the two carbonyl groups in glutarimide because of increased planarity of the ring due to the nitrogen atom.
为了理解某些巴比妥类药物和抗惊厥药在气相中的低反应活性，对一系列含简单环状羰基的化合物的气相碱度和相对甲基化亲核性进行了评估。气相碱度通过括值法测定，相对甲基化亲核性通过监测与来自二甲醚的CH3OCH2+离子的离子 - 分子反应来表征。计算了质子化和甲基化结构的生成热，以估计质子化和甲基化的有利位点。如本文所示，羰基的位置对相关系列化合物中的相对气相碱度和甲基化速率有显著影响。对于那些在1,2位有两个羰基的化合物，其甲基化效率比在1,3或1,4位有两个羰基的化合物提高了100倍。这种巨大差异归因于三种环己二酮的分子偶极矩变化以及两个羰基的相对位置。环己烷 - 1,2 - 二酮具有最大的偶极矩，导致与CH3OCH2+反应物的相互作用能最高，并且在攻击CH3OCH2+以及随后两个羰基之间快速甲基阳离子转移过程中具有协同相互作用的能力，从而提高了反应速率和产物稳定性。气相碱度的顺序也受到羰基的数量和位置以及环中氮原子的存在的强烈影响。例如，环戊二酰亚胺在环中有一个被两个羰基包围的氮原子，其气相碱度比环己烷 - 1,3 - 二酮低约10 kcal mol-1。该结果归因于由于氮原子导致环平面性增加，限制了环戊二酰亚胺中两个羰基之间部分氢键的形成。
