Application of continuous-flow process for the efficient synthesis of 4-nitroaniline under high T/P

4-nitroaniline has been widely used in the production of antioxidants, dyes and pharmaceuticals. A continuous-flow strategy was exploited for the efficient synthesis of 4-nitroaniline through the noncatalytic amination of 4-chloronitrobenzene with aqueous ammonia in a highly controlled and safe manner, in which N-methyl-2-pyrrolidone was selected as the appropriate solvent. Various conditions (reaction temperature, residence time, 4-chloronitrobenzene concentration, molar ratio of ammonia to 4-chloronitrobenzene, presence of base catalyst) were investigated to improve the synthesis of 4-nitroaniline. The Box-Behnken design in response surface methodology was employed for the optimization of reaction conditions, and over 91% yield of 4-nitroaniline could be achieved. Furthermore, a kinetic model was proposed to guide the design and optimization of the synthesis of 4-nitroaniline.