H. S. Pereira, H. Santana, J.L. Silva
Jan 30, 2021
Citations
0
Influential Citations
3
Citations
Journal
Chemical Engineering and Processing
Abstract
Abstract The continuous production of the intermediate ortho-4-(2-fluoro-4-nitrophenyl)morpholine (o-FNM) was firstly explored in Microfluidic devices. The o-FNM is a key intermediate to synthesize Linezolid, a highly effective active pharmaceutical used against a wide class of Gram-positive pathogens. It is synthesized by eight consecutive reactions, taking about 60 hours. One of the most prolonged step, lasting about 11 h, is the reaction between morpholine and 2,4-difluoronitrobenzene to produce o-FNM. Despite these features, there is still a lack on researches approaching such process. The present paper evaluated for the first time the production of o-FNM in micro- and millireactors by CFD. An optimization of operating conditions (temperature, reactants molar ratio (MR) and residence time (τ)) was performed by a Central Composite Rotatable Design, evaluating its effects on the limiting reactant conversion, selectivity and production rate. The optimal production rate (157-195 mg/h in the microreactor) was noticed at 105 °C, MR = 4, τ = 50 s. The performance of different micromixer designs and scale-up effects was assessed. The devices exhibited o-FNM production rate about 1.5 - 7.5 g/h, equivalent to the reported in literature, keeping high levels of limiting reactant conversions (≈ 99%) and considerable selectivities (≥ 10).