Process optimization of 1-cyanocyclohexaneacetic acid hydrogenation using response surface methodology

• Published in: Research on chemical intermediates 2024-11, Vol.50 (11), p.5283-5303
• Main Authors: Xiong, Neng, Jiang, Lin-Li, Chen, Jia-Yu, Lin, Lei, Huang, Jin-Rong, Shen, Qi, Xue, Ya-Ping, Zheng, Yu-Guo
• Format: Article
• Language: English
• Subjects: Biological activity; Biological effects; Catalysis; Catalysts; Chemical synthesis; Chemistry; Chemistry and Materials Science; Fine chemicals; Hydrogenation; Impurities; Inorganic Chemistry; Parameter identification; Physical Chemistry; Reaction time; Response surface methodology; Substrates
• ISSN: 0922-6168; 1568-5675
• DOI: 10.1007/s11164-024-05400-8

Hydrogenation plays an important role in the production of bulk and fine chemicals. In the present work, the hydrogenation process of 1-cyanocyclohexaneacetic acid (1-CA), a key intermediate in the chemo-enzymatic synthesis of the antiepileptic drug gabapentin, was investigated. The catalysts were screened, the operating parameters for the 1-CA hydrogenation were determined by response surface methodology, and the effects of biological impurities on the reaction and catalysts were investigated. The reaction temperature, reaction solution pH and reaction time were identified as the main factors for hydrogenation by single-factor experiments. Under the optimal reaction conditions: reaction temperature 110 °C, solution pH 12.33, reaction time 3.74 h, hydrogen pressure 2 MPa and stirring speed 500 rpm, the substrate conversion reached 100%, and the total product yield reached 96.40%, which was very close to the prediction (96.88%). It was demonstrated that biological impurities greatly affect the reaction rate of hydrogenation, as well as the activity and reusability of the catalyst, in which protein impurities lead to catalyst deactivation through cumulative deposition on the catalyst surface and within the pores.