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发表时间：2021-01-01

发表刊物：Huagong Xuebao/CIESC Journal

卷号：72

期号：3

页面范围：1465-1472

ISSN号：0438-1157

摘要：There are plenty of liquid-liquid homogeneous organic reactions in the drug research and development. A suitable reaction solvent can significantly increase the rate and selectivity for these reactions, thereby improve the synthesis efficiency and enhance the quality of drug synthesis. Taking the aromatic nucleophilic reaction (SNAr) of 2, 4-dichloro-5-nitropyrimidine and p-aminobenzonitrile as the research object, the computer-aided molecular design (CAMD) method was used to design the reaction solvent. First, the reaction rate constants for a small number of solvents are obtained using quantum mechanics (QM) method. Then, the obtained reaction rate constants are used to build a surrogate reaction kinetic model which correlates the solvent properties. Afterward, a mixed integer nonlinear programming (MINLP) multi-objective optimization model considering both selectivity and reaction rate is established. Finally, a decomposed algorithm is used to solve the established model, which achieves the objective of reaction solvent design in pharmaceutical reactions. © 2021, Editorial Board of CIESC Journal. All right reserved.

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