Abstract

Eaton's reagent is a unique mixture of phosphorus pentoxide and methanesulfonic acid and has emerged as a versatile and potent catalyst in modern synthetic chemistry. This review provides a comprehensive overview of Eaton's reagent, detailing its preparation, mechanistic pathways, and diverse applications in organic synthesis. Since its introduction, Eaton's reagent has become invaluable, promoting a wide range of transformations, including Friedel–Crafts reactions, cyclodehydration, Beckmann rearrangement, aminolysis, and multi-component reactions. The reagent's distinct advantages over traditional catalysts, such as higher reactivity, milder reaction conditions, and improved yields, make it particularly effective for synthesizing heterocyclic compounds, pharmaceuticals, natural products, polymers, and advanced materials. Eaton's reagent has also been shown to facilitate solvent-free and eco-friendly synthetic methodologies, aligning with the increasing demand for sustainable chemical processes. This review consolidates recent advancements and applications of Eaton's reagent, underscoring its critical role in advancing synthetic methodologies and providing a foundation for future research to explore innovative reactions, mechanisms, and broader applications in organic synthesis. © 2025 Wiley-VCH GmbH.