Amphiphilic nano-assembly for dehydrative amination reactions of alcohols in aqueous medium

Abstract

Nano-assemblies such as surfactant micelles and vesicles are widely used in drug carriers, bioreactors, and gene delivery, but can also be used as catalytic systems for chemical transformations. In the current study, we introduce nano-assemblies formed by a novel sulfonate-based amphiphilic catalyst, designated Cat-2, which are responsive to acid catalyst (HBF4) and metal catalyst (Fe(BF4)2). When the amphiphilic assemblies of Cat-2 were applied for dehydrative aminations of allylic or benzylic alcohols, we obtained the desired sulfonamide or carboxamide products with reasonable to good yields (58-92%). This methodology was also applied for gram-scale synthesis of the FDA-approved drug naftifine. Cat-2 formed small micelles (similar to 20 nm) in water, which were transformed into large nano-assemblies (similar to 550 nm) upon the addition of HBF4 and Fe(BF4)2. This morphological change mainly originates from the coordination of the sulfonate group to Fe2+. The resulting Cat-2-Fe2+ assemblies contain amide groups at the hydrophilic-hydrophobic interfaces, which act as mediators for an effective proton transfer from HBF4 in a bulk solution to the alcoholic substrate in the assembly interior. As a result, the protonated alcoholic substrate undergoes dehydration to initiate a catalytic cycle for the dehydrative amination reaction. The present methodology is favorable due to its facile and green setup, cost effectiveness, and use of easily accessible and non-toxic catalysts. In addition, the current study provides insight into the design of nano-assemblies for catalyzing organic transformations. New nano-assemblies were developed for organic transformation in an aqueous medium. This assembly acts as a proton transfer mediator and thus facilitated dehydrative amination reactions of various alcohols with sulfonamides, amides or arylamines.