Roland Daniel, Haleegoah Jamin Nathaniel, Opoku Ernest, Tia Richard, Adei Evans
Theoretical and Computational Chemistry Laboratory, Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Theoretical and Computational Chemistry Laboratory, Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
J Mol Graph Model. 2019 Dec;93:107452. doi: 10.1016/j.jmgm.2019.107452. Epub 2019 Sep 13.
The mechanism of the reaction of 1,3,4-oxadiazoles with alkenes (ethylene) and cycloalkenes (cyclobutene, cyclopentene, cyclohexene and cycloocene) have been studied computationally at the DFT M06-2X/6-311G* level. The reaction is found to proceed via a concerted [4 + 2] addition followed by nitrogen extrusion and then [3 + 2] addition in a tandem cascade fashion, which in the case of cycloalkenes leads to exo-fused or endo-fused subframes, the exo of which is kinetically and thermodynamically favored. The [4 + 2] step is the rate-determining step of the reaction. CF as a substituent on the 1,3,4-oxadiazole decreases the activation barriers of the rate-determining step, while COMe on the oxadiazole increases the activation barriers of the rate-determining step, markedly in the case of the reaction with cyclopentene and only marginally in the reactions with ethylene. Increasing temperature decreases the barrier of the rate-determining step and stability of the products but increases the rate of the nitrogen extrusion step. The low barriers of the second and third steps of the reaction compared to the first step means that the intermediates will not be isolated in the reaction, confirming the experimental observations of earlier workers. Based on calculated activation barriers, the reactivity of the various cycloalkenes considered in this study follows the order: cyclooctene > cyclopentene > cyclohexene > cyclobutene which is consistent with the trends in product yields obtained in earlier experimental studies.
在DFT M06 - 2X/6 - 311G*水平上对1,3,4 - 恶二唑与烯烃（乙烯）和环烯烃（环丁烯、环戊烯、环己烯和环辛烯）的反应机理进行了计算研究。发现该反应通过协同的[4 + 2]加成，随后进行氮消除，然后以串联级联方式进行[3 + 2]加成，对于环烯烃而言，这会导致外向稠合或内向稠合的子框架，其中外向产物在动力学和热力学上更有利。[4 + 2]步骤是该反应的速率决定步骤。1,3,4 - 恶二唑上的CF作为取代基降低了速率决定步骤的活化能垒，而恶二唑上的COMe增加了速率决定步骤的活化能垒，在与环戊烯反应时显著增加，而在与乙烯反应时仅略有增加。升高温度会降低速率决定步骤的能垒和产物的稳定性，但会增加氮消除步骤的速率。与第一步相比，反应第二步和第三步的低能垒意味着反应中不会分离出中间体，这证实了早期研究人员的实验观察结果。基于计算得到的活化能垒，本研究中考虑的各种环烯烃的反应活性顺序为：环辛烯 > 环戊烯 > 环己烯 > 环丁烯，这与早期实验研究中获得的产物产率趋势一致。
