Acid Catalyzed Transfer Hydrogenation - METTLER TOLEDO
Application Editorial

Acid Catalyzed Transfer Hydrogenation

Application Editorial

Continuous-flow Catalytic Asymmetric Hydrogenations: Reaction Optimization Using FTIR Inline Analysis

Optimizing Reaction Kinetics
The majority of enantioselective reductions depend on various transition-metal-catalyzed high-pressure hydrogenations. However, the drawbacks of these method conditions are often tolerated due to the excellent enantio selectivities and activity they obtain.

Rueping et. al studied the asymmetric organocatalytic hydrogenation of benzoxazines in continuous-flow microreactors as a metal-free alternative. Coupling inline mid-infrared spectroscopy for real-time reaction monitoring enabled the group to quickly, optimize the reaction for duration (kinetics) and yield (product quality) while minimizing the volume of material needed.

By studying the effects of a select set of parameters (temperature, flow rate, and residence time) the optimum set of conditions were determined as based on overall product yield. Inline mid-infrared provided the instantaneous feedback as each of these parameters were examined for their beneficial or negative contribution to the chemistry.

In situ conversion, as measured by ReactIR FTIR spectroscopy, tracks changes to the substrate and product over the course of the experiment. This allows researchers to determine key parameters for control and optimization. For example, by varying the temperature from 5 °C to 60 °C (5 °C increments), the ideal reaction temperature was identified to be 60 °C in a single eight-hour reaction. Additionally, ReactIR trends provided time-resolved reaction conversion data measuring the relative concentration of both product and substrate.

In this study, ReactIR demonstrated the ability to detect and monitor the substrate and product kinetic behavior leading to the optimized reactions conditions: temperature 60 °C, flow rate 0.1 mL/min, and 98 % yield (confirmed by column chromatography).

 

Acid Catalyzed Transfer Hydrogenation

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