Continuous-Flow Synthesis of syn-2-Amino-1,3-diol via Catalytic Hydrogenation: A Vital Intermediate of (+)-Thiamphenicol and (+)-Florfenicol

Abstract

In this paper, an expeditious and efficient continuous-flow process is reported for the synthesis of syn-2-amino-1,3diol. The starting material syn-2-nitro-1,3-diol reacts with hydrogen gas in a micro fixed-bed reactor packed with a Raney Ni catalyst to provide syn-2-amino-1,3-diol in 93% isolated yield. The reaction time in the flow system was markedly reduced (from 36 h in batch to 5 min in flow) due to enhanced mass transfer. The effects of the catalyst, solvent, reaction temperature, reaction time, pressure, and H 2 flow rate have been investigated successively. The optimum conditions for the continuous-flow reaction are described as follows when using Raney Ni as a catalyst at a reaction temperature of 25 °C, a reaction pressure of 10 bar, a reaction solvent of 3% AcOH in methanol, an H 2 flow rate of 25 sccm, and a liquid flow rate of 0.6 mL/min. The reaction kinetics in the temperature range of 10−40 °C were investigated. The reaction rate constants and activation energy were determined. The continuous flow system allows for an efficient hydrogenation of syn-2-nitro-1,3-diol on the hectogram scale, corresponding to an overall productivity of 73.6 g/d after continuous operation for over 240 h.