Computational Study and Kinetic Analysis of the Aminolysis of Thiolactones

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• 作者：Gilles B. Desmet ; Dagmar R. D鈥檋ooge ; Maarten K. Sabbe ; Guy B. Marin ; Filip E. Du Prez ; Pieter Espeel ; Marie-Fran莽oise Reyniers
• 刊名：Journal of Organic Chemistry
• 出版年：2015
• 出版时间：September 4, 2015
• 年：2015
• 卷：80
• 期：17
• 页码：8520-8529
• 全文大小：632K
• ISSN：1520-6904

文摘

The aminolysis of three differently 伪-substituted 纬-thiolactones (Cb>4b>Hb>5b>OSX, X = H, NHb>2b>, and NH(CO)CHb>3b>) is modeled based on CBS-QB3 calculated free energies corrected for solvation using COSMO-RS. For the first time, quantitative kinetic and thermodynamic data are provided for the concerted path and the stepwise path over a neutral tetrahedral intermediate. These paths can take place via an unassisted, an amine-assisted, or a thiol-assisted mechanism. Amine assistance lowers the free energy barriers along both paths, while thiol assistance only lowers the formation of the neutral tetrahedral intermediate. Based on the ab initio calculated rate coefficients, a kinetic model is constructed that is able to reliably describe experimental observations for the aminolysis of N-acetyl-dl-homocysteine thiolactone with n-butylamine in THF and CHClb>3b>. Reaction path analysis shows that for all conditions relevant for applications in polymer synthesis and postpolymer modification, an assisted stepwise mechanism is operative in which the formation of the neutral tetrahedral intermediate is rate-determining and which is mainly amine-assisted at low conversions and thiol-assisted at high conversions.