Breaking Base Dependency: EDC·HCl-Promoted Henry Reaction under Solvent-Free Mild Acidic Conditions

A sustainable, efficient, and scalable protocol for the Henry reaction between various aldehydes and nitroalkanes is presented, utilizing 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl) as an organoacid. The reaction proceeds under solvent-free, room temperature conditions at acidic pH, delivering β-nitro alcohols in excellent yields of up to 99%. The methodology demonstrates a broad substrate scope, accommodating both electron-rich and electron-deficient aldehydes. Notably, the protocol operates under base-free conditions, suppresses elimination of byproducts, and is readily scalable to the gram level without loss in efficiency. These features make the process a valuable contribution to the green and practical pharmaceutical industry.