Study on Continuous-Flow Process for Direct Synthesis of p-Aminophenol from Nitrobenzene

p-Aminophenol (PAP) is an important organic chemical raw material and a pharmaceutical intermediate. Catalytic hydrogenation of nitrobenzene (NB) is an environmentally friendly and economical production method. However, the one-pot method in a traditional batch reactor often leads to a low reaction rate and low PAP yield at low hydrogen pressure. In this work, a continuous-flow process for direct synthesis of PAP by the hydrogenation–rearrangement of NB was established, which provides a safe, green, and efficient method for the synthesis of PAP. The effects of various reaction conditions were investigated. Under the optimal reaction conditions, a 94.5% yield of phenylhydroxylamine (PHA) was achieved in the hydrogenation process under atmospheric pressure. The catalyst activity remained good for 50 h of continuous operation. Solvent tetrahydrofuran (THF) and additive 4-dimethylaminopyridine (DMAP) are more conducive to the synthesis of PHA than other solvents. For different acid catalysts in the Bamberger rearrangement with an equivalent concentration of 2 N, stronger acidity led to greater conversion of PHA. The Bamberger rearrangement is solvent-sensitive, and aprotic solvents will reduce the conversion of PHA. The full continuous process for direct synthesis of PAP from NB was studied by mixing sulfuric acid solution and PHA/THF solution with a microfluidic chip. The conversion of PHA was 100% with a low H₂SO₄ concentration of 1 wt % at a residence time of 13.6 min. The process was reduced from the hour level of the batch process to the minute level, and the H₂SO₄ concentration was reduced.