Substrate-Specific Amidation of Carboxylic Acids in a Liquid−Liquid Two-Phase System Using Cyclodextrins as Inverse Phase-Transfer Catalysts

A novel system for substrate‐specific activation of carboxylic acids leading to the formation of carboxamides has been developed in our laboratory. A combination of a water‐soluble dehydrocondensing agent, 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methylmorpholinium chloride (DMT‐MM), and an inverse phase‐transfer catalyst (IPTC) (hydroxypropyl)cyclodextrin (HP‐β‐CD), in a water/ether biphasic solvent system was found to be most effective. A lipophilic carboxylic acid with a strong affinity for the cavity of HP‐β‐CD can be selectively transferred to the aqueous phase and predominantly reacts with DMT‐MM, dissolving in the aqueous phase. The substrate specificity was similar to that observed with a complex artificial enzyme based on CD. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)