Greener alternatives for synthesis of isoquinoline and its derivatives: a comparative review of eco-compatible synthetic routes

Abstract

Isoquinoline derivatives, a prominent class of nitrogen-containing heterocycles, serve a pivotal role in medicinal chemistry due to their broad spectrum of bioactivities. While traditional synthetic routes for these scaffolds are well-established, conventional methods often rely on transition-metal catalysts, harsh conditions, expensive reagents, and toxic solvents, raising environmental and economic concerns. In response to the pressing demand for sustainable practices, this review underscores the integration of green chemistry principles into modern synthetic design, offering environmentally acceptable methods for accessing isoquinoline frameworks. Despite extensive research on isoquinoline synthesis and its therapeutic relevance, a dedicated analysis of sustainable methodologies remains absent. This work bridges that gap by critically evaluating recent innovations in green synthesis, including the use of benign solvents, recyclable catalytic systems, atom-economical reactions, and energy-efficient processes.