Department Chemie und Biochemie, Ludwig-Maximilians-Universität München, Germany.
J Org Chem. 2009 Sep 18;74(18):7157-64. doi: 10.1021/jo901670w.
The cinchona alkaloids 1a-d react selectively at the quinuclidine ring with benzyl bromide and at the quinoline ring with benzhydrylium ions (diarylcarbenium ions). The kinetics of these reactions have been determined photometrically or conductimetrically and are compared with analogous reactions of quinuclidine and quinoline derivatives. Quantum chemical calculations [MP2/6-31+G(2d,p)//B3LYP/6-31G(d)] show that the products obtained by attack at the quinuclidine ring (N(sp3)) of quinine are thermodynamically more stable when small alkylating agents (primary alkyl) are used, while the products arising from attack at the quinoline ring (N(sp2)) are more stable for bulkier electrophiles (Ar(2)CH). In some cases, rate and equilibrium constants for their reactions with benzhydrylium ions could be determined. These data gave access to the Marcus intrinsic barriers, which are approximately 20 kJ mol(-1) lower for attack at the N(sp3)-center than at the N(sp2)-center.
金鸡纳生物碱 1a-d 可选择性地与苄基溴在奎宁啶环反应，与苯甲鎓离子（二芳基碳正离子）在喹啉环反应。这些反应的动力学已通过光度法或电导率法确定，并与类似的喹啉啶和喹啉衍生物的反应进行了比较。量子化学计算 [MP2/6-31+G(2d,p)//B3LYP/6-31G(d)] 表明，当使用小的烷基化剂（伯烷基）时，通过攻击奎宁的奎宁啶环（N(sp3)）获得的产物在热力学上更稳定，而对于更大的亲电试剂（Ar(2)CH），则由攻击喹啉环（N(sp2)）引起的产物更稳定。在某些情况下，可以确定它们与苯甲鎓离子反应的速率和平衡常数。这些数据提供了对马库斯内在障碍的了解，对于攻击 N(sp3)-中心，其内在障碍比攻击 N(sp2)-中心大约低 20 kJ mol(-1)。
