Nitrobenzyl reduction

Today’s conventional offline techniques are challenged by the instability of reaction intermediates and products, as well as being labor intensive when tracking reaction progression and/or determining reaction kinetics. Accurate determination of the reaction endpoint(s) is often not possible by offline techniques.

Reaction components are easily detected and followed by the consumption of Ф-NO2 and the formation of Ф-NH2. Reaction progression starts without delay in the fast formation of Ф-NH2 and no evidence of solution phase intermediate formation or accumulation exists. An accurate and precise endpoint for Ф-NH2 production can be easily established. Through the shape of the component profiles, mechanism and kinetics information can be deduced from the graph indicating zero order kinetics for both consumption of Ф-NO2 and formation of Ф-NH2. Critical process parameters, such as a lack of catalyst modifier, are shown to be ideal for Ф-NH2 production, as well as direct and complete conversion Ф-NO2 to Ф-NH2 that results with an optimized process reaction endpoint.

Reaction components are easily detected and followed by the consumption of Ф-NO2 formation and accumulation of Ф-NHOH, and formation of Ф-NH2. Reaction progression starts with conversion of Ф-NO2 to the intermediate Ф-NHOH. A delay in the production of Ф-NH2 is observed during the formation and accumulation of Ф-NHOH. An accurate and precise endpoint for both Ф-NHOH intermediate and Ф-NH2 product can be easily determined. Mechanism and kinetics information can be deduced from the graph through the shape of the component profiles - indicating there are two kinetic regimes. Zero order kinetics is observed for both consumption of Ф-NO2 and formation of Ф-NHOH, whereas near first order kinetics (with respect to CФ-NHOH) is observed for the delayed Ф-NH2 formation. Critical process parameters, such as a lack of catalyst modifier, are ideal for Ф-NH2 production, whereas the DMSO modifier is ideal for Ф-NHOH production. Also, the intermediate Ф-NHOH formation and conversion lengthens the reaction endpoint for Ф-NH2.

Through the information rich and real-time results, shorter scaleup times result from a more comprehensive understanding of the process. Increased selectivity/yield can be achieved from the real-time results providing almost instantaneous feedback on reaction direction. Reduced step cycle time and better reaction control is a direct result of accurate endpoint determinations that allow chemists to stop a reaction at a specific time point and/or initiate a secondary reaction. Less batch failure results from being able to “see” the progression of the reaction in real time, which increases the flexibility of control over the batch quality.

Increased safety gained by having better knowledge of reaction kinetics and key control parameters (e.g., solvent, catalyst, heat transfer in reactor, step-wise heat of reaction, etc.) allows better control of reaction and rate to avoid undesirable issues (e.g., adiabatic temperature rise). In addition, the quantitative knowledge of Ф-NHOH accumulation during aniline production calls for precaution either not to expose the batch to air or O2 at high concentration of Ф-NHOH or operate under the conditions with minimum Ф-NHOH accumulation.

Real-time, in situ, operando analysis of O2 sensitive Ф-NHOH, unstable Ф-NHOH at high concentration (potential for explosion when Ф-NHOH is accumulated and the batch is exposed to O2) and under H2 pressure is ideally suited for ReactIR™, whereas it is more difficult or even impossible to analyze by offline techniques without sample preparation, perturbation, intrusion or material loss.