Continuous-flow nitration of o-xylene has been studied with different nitrating agents over a wide range of conditions for different parameters such as temperature, residence time, and concentrations. A nitrating mixture comprising sulfuric acid and fuming nitric acid was seen to yield higher selectivity for the isomer 1,2-dimethyl-3-nitrobenzene over the isomer 1,2-dimethyl-4-nitrobenzene and also a non-negligible quantity of dinitro derivatives of o-xylene. With only fuming nitric acid as the nitrating agent, the reaction was selective for 1,2-dimethyl-4-nitrobenzene over 1,2-dimethyl-3-nitrobenzene. Impurities mainly come from nitration of mononitro derivatives, and this occurs more from nitration of the 3-nitro isomer because of its higher reactivity with nitric acid. An economic analysis of the continuous-flow reactor for the production of 1,2-dimethyl-4-nitrobenzene at 100 and 500 kg/h in a jacketed tubular reactor showed that numbering-up is a more economical approach for higher production capacity. A combination of large-and small-sized tubes depending upon the relative rates of heat generation during a reaction will achieve more profit and a shorter payback period than having the entire reactor made of a single tube size.
A multistep sequential
flow synthesis of isopropyl phenol is demonstrated,
involving 4-step exothermic, endothermic, and temperature sensitive
reactions such as nitration, reduction, diazotization, and high temperature
hydrolysis. Nitration of cumene with fuming nitric acid produces 2-
and 4-nitrocumene which are converted into respective cumidines by
the hydrogenation using Pd/Ni catalyst in H-cube with gravity separation.
Hydrolysis of in situ generated diazonium salts in the boiling acidic
conditions is carried out using integration of flow and microwave-assisted
synthesis. 58% of 4-isopropyl phenol was obtained. The sequential
flow synthesis can be applied to synthesize other organic compounds
involving this specific sequence of reactions.
A 3-step continuous flow oxidation of alcohols is demonstrated with continuous generation of chlorine as the first step followed by its use for the flow synthesis of high strength sodium hypochlorite.
The continuous flow nitration of acetophenone followed by reduction of the meta isomer has been demonstrated using simple tubular reactors. Because of ease of separation of the desired isomer from the first step, both steps are made continuous, but separately. The continuous flow nitration was carried out in a safe manner in a shorter reaction time than the conventional approach. The choice of micromixer was seen to affect the performance of the nitration reaction. The effect of different parameters on the yield of the desired product was studied. The reduction step with sodium sulfide was found to be economical and could be carried out efficiently at 70°C using sodium sulfide in ethanol, using a silicone tube. Both steps were demonstrated for several hours, yielding a sufficiently large quantity (∼100 g) of m-aminoacetophenone at lab scale in a single day using simple tubular reactors.
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