Fundamental elements of process intensification were applied to generate efficient batch and continuous syntheses of the high-volume HIV drug nevirapine.

Numerous synthetic methods for the continuous preparation of fine chemicals and active pharmaceutical ingredients (API’s) have been reported in recent years resulting in a dramatic improvement in process efficiencies. Herein we report a highly efficient continuous synthesis of the antimalarial drug hydroxychloroquine (HCQ). Key improvements in the new process include the elimination of protecting groups with an overall yield improvement of 52% over the current commercial process. The continuous process employs a combination of packed bed reactors with continuous stirred tank reactors for the direct conversion of the starting materials to the product. This high-yielding, multigram-scale continuous synthesis provides an opportunity to achieve increase global access to hydroxychloroquine for treatment of malaria.

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Aromatic N-heterocycles have been used in electrochemical CO2 reduction, but their precise role is not yet fully understood. We used first-principles quantum chemistry to determine how the molecular sizes and substituent groups of these molecules affect their standard redox potentials involving various proton and electron transfers. We then use that data to generate molecular Pourbaix diagrams to find the electrochemical conditions at which the aromatic N-heterocycle molecules could participate in multiproton and electron shuttling in accordance with the Sabatier principle. While one-electron standard redox potentials for aromatic N-heterocycles can vary significantly with molecule size and the presence of substituent groups, the two-electron and two-proton standard redox potentials depend much less on structural modifications and substituent groups. This indicates that a wide variety of aromatic N-heterocycles can participate in proton, electron, and/or hydride shuttling under suitable electrochemical conditions.

The average operation time of residents was 116.47 min, which was significantly longer (p<0.0001) than that of the board-certified surgeon (average 81.07 min). It cost USD $40.36 more for each operation performed by residents in terms of operation room costs. The surgical success rate of residents was 81.82%, which was significantly lower (p=0.016) than that of the board-certified surgeon (96.43%).