The application of continuous methods in the synthesis of active pharmaceutical ingredients continues to receive significant attention in the academic as well as the industrial research communities. One of the major advantages of continuous methods is the ability to safely access kinetic synthons as well as highly reactive reagents that are typically unavailable through traditional batch methods. In this work, we report the high‐yielding, clean formation of an aryl‐turbo Grignard and its selective addition to a highly‐enolizable 1,3‐dichloroacetone, for the continuous synthesis of a key intermediate for fluconazole, a widely‐prescribed anti‐fungal agent. In addition, process optimization of the final API was also carried out to arrive at a semi‐continuous method to this essential medicine.

ABSTRACT.The current studies were designed to prepare tin(II) complexes of various Schiff base derivatives of 2-hydroxy-1-naphthaldehyde (HN) with L-histidine and sulfamethazine have been prepared and characterized by different physiochemical studies such as elemental analysis, atomic absorption, UV-Vis spectra, FTIR spectra, 1 H-NMR, 13 C-NMR and conductance studies. Antimicrobial and antioxidant activities were also calculated. Antibacterial activity was evaluated by the agar-well diffusion method. Two Gram-negative (Klebsiella pneumoniae and Escherichia coli) and three Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilis) bacterial strains were used. Antifungal activity was resolute against three fungal strains (Aspergillus niger, Aspergillus flavus and Alternaria solani) by using the agar tube dilution method. The antioxidant activity of ligands and their complexes was measured on the basis of the radical scavenging effect of 1,1-diphenyl-2-picryl-hydrazyl (DPPH)-free radical activity. Ligand HNSM exhibited excellent activities as antibacterial activity (22 mm), antifungal activity (55%) and antioxidant activity (119 ppm).