A novel and green synthesis of pentacyclic-fused pyrano[3,2-b:5,4-b']diquinoline-8-carboxylic acids using Pfitzinger reaction

Abstract

In this work, a novel and green synthesis of pentacyclic-fused pyrano[3,2-b:5,4-b']diquinoline-8-carboxylic acids (7a-q) has been developed via the Pfitzinger reaction of 5-methyl-1H-pyrano[3,4-b]quinolin-4(3H)-one (9) with various isatins (8a-q). The reaction employs the basic ionic liquid [BMIm]OH (0.5 equiv.) as an eco-friendly homogeneous catalyst in aqueous medium under ultrasonic irradiation at room temperature for 4–6 h, affording the desired products in 74–88% yields. This synthetic protocol offers several notable advantages, including experimental simplicity, mild and environmentally benign conditions (water as solvent, ultrasonic activation), elimination of conventional strong bases, easy work-up (filtration and recrystallization), and avoidance of hazardous organic solvents. The greenness of the method is further supported by Eco-scale scores (44–66), which fall within the range typical for pharmaceutical industry standards. This work provides a sustainable and practical approach to structurally novel pentacyclic quinoline derivatives of potential medicinal interest.