Nanocatalyst-enabled amide bond formation: advances, mechanistic insights, and future perspectives

Abstract

Amide bonds are among the most ubiquitous linkages in pharmaceuticals, agrochemicals, polymers, and natural products. Despite their importance, conventional methods for forming these linkages often suffer from drawbacks such as low atom economy, harsh reaction conditions, and the generation of considerable waste. In recent years, nanocatalyst-based approaches have gained increasing attention as a more efficient alternative. Their appeal lies in their unique physicochemical features, including large surface areas, tunable active sites, and adjustable electronic properties, all of which can enhance catalytic activity and selectivity. In this context, the present review examines recent progress in nanocatalytic strategies for amide bond formation. It brings together a variety of catalytic systems, ranging from metal and metal oxide nanoparticles to bimetallic and heterostructured materials, as well as single-atom catalysts and ligand-functionalized hybrid nanomaterials. Rather than listing developments alone, the discussion focuses on how these systems operate, with attention to mechanistic details and reaction pathways. Key transformations considered include the direct amidation of carboxylic acids, the coupling of amines with alcohols through dehydrogenation, decarbonylative processes involving acyl derivatives, and C–H activation routes. Challenges such as catalyst recovery, stability, and correlations between structure and performance are critically discussed. By articulating current advances alongside practical limitations, this review aims to guide future innovation toward greener, more efficient, and industrially viable nanocatalyst-assisted amide synthesis methodologies.