Different paths lead to the same destination: a highly efficient TMSOTf/HFIP catalytic system for large-scale synthesis of fluoroalkyl-containing 4,4′-methylenedianiline (MDA) monomers

Abstract

A facile and scalable synthesis route to fluoroalkyl-containing 4,4′-methylenedianiline (MDA) monomers was developed with more user-friendly fluoral hydrate that hinges on the beneficial combination of a catalytic amount of TMSOTf and easily recyclable HFIP as the solvent. The use of minimal amounts of acid in HFIP with strong hydrogen bond-donating ability and cation-stabilizing ability not only reduces the risk of the reaction and simplifies product isolation but also significantly suppresses the side reactions, ensuring that all the possible intermediates (at least more than 6) generated in the whole reaction process lead to the same target diamine. Furthermore, the trace amount of water in the solvent plays a key role in promoting the challenging conversion, which provides a more practical pathway for the utilization of the highly moisture-sensitive TMSOTf catalytic system. This protocol exhibits a broad substrate scope (>50 examples) and exceptional scalability, as demonstrated by the successful kilogram-scale synthesis.