Mononitration of N-(4-Methoxyphenyl)acetamide in continuous-flow: Kinetics study and process optimization

Abstract

Mononitration products of N-(4-Methoxyphenyl)acetamide (NMA) are intermediates of various mature products. However, for the nitration of NMA, N-(4-methoxy-2-nitrophenyl)acetamide (2-NMA) and N-(4-methoxy-3-nitrophenyl) acetamide (3-NMA) will be produced at the same time, making it difficult to control the selectivity of single nitration product, and no kinetics study has ever been reported before. To comprehend the high regioselectivity nitration of NMA more deeply, a microfluidic system was developed to evaluate the reaction kinetics of NMA nitration. At first, two different systems for nitration were identified. Then, the kinetics parameters for these two systems were determined. Next, a series of validation experiments were designed to show the accuracy of the kinetic model. In the end, to obtain a controlled selectivity, the effects of reaction temperature, initial concentration and molar ratio were investigated through the model simulation. Under the conditions optimized by the kinetic model, the selectivity for both 2-NMA and 3-NMA could achieve above 99.5 %, but due to the changes in the properties of the reaction solution, it was extremely difficult to achieve in practice. Ultimately, within the feasibility range of the kinetic model, 98.4 % selectivity of 2-NMA and 96.1 % selectivity of 3-NMA were obtained in the microreactor, respectively.