Understanding “On-Water” Catalysis of Organic Reactions. Effects of H⁺ and Li⁺ Ions in the Aqueous Phase and Nonreacting Competitor H-Bond Acceptors in the Organic Phase: On H₂O versus on D₂O for Huisgen Cycloadditions

Abstract

For a typical Huisgen cycloaddition, carried out on water, the behavior of water molecules at the oil-water interface depended on the properties of the reactants. With weakly basic reactants, a small quantity of added H(+) (HClO4, 0.0001-0.01 M) present in the aqueous phase had negligible effects, but larger quantities of H(+) (HClO4, 0.1-3.0 M) increased the catalytic effect and caused protons to cross the water-organic interface and affect the products. Added Li(+) ions (LiClO4, 0.1-3.0 M) had no effect for on-water reactions but enhanced the rates and endo products for in-water reactions. For these cycloaddition reactions, the product endo:exo ratios, when compared to those in organic solvents, can be used to distinguish between the on-water and in-water modes. Comparisons of organic reactions on H2O and on D2O indicate that on-water catalysis ranges from weak to strong trans-phase H-bonding for reactants with basic pK(a) < ca. -6 and to interfacial proton transfer for reactants with higher basic pK(a) > ca. 2 (pKa of conjugate acid). Water shows a chameleon-type response to organic molecules at hydrophobic surfaces.

Spectacular Rate Enhancement of the Diels–Alder Reaction at the Ionic Liquid/n‐Hexane Interface

“…For the Diels–Alder reaction of methyl acrylate ( A ) with cyclopentadiene ( B ), this novel reaction medium provides large rate enhancements of up to 10 6 to 10 8 times with the values of the rate constants ranging from 80.6 to 1990 s −1 , and high endo / exo values ranging from 2.8 to 8.0, as compared to homogeneous media (Scheme ). Both the rate constants as well as the stereoselectivity for interfacial reactions were noted to be exceedingly larger than previously reported values for the same reaction at the given concentrations, in conventional solvent media, including water …”

“…The importance of heterogeneous reaction media to achieve large rate enhancements for Diels–Alder reaction under ′on water′ conditions was further highlighted by Klijn and Engberts . Butler and Coyne have reported that reactants with different solubilities in water display different rates for Huisgen cycloadditions reactions . A theoretical study from Jung and Marcus described the catalyzing effects of trans ‐phase dangling of OH groups to increase the rates of ′on water′ organic reactions .…”

“…A theoretical study from Jung and Marcus described the catalyzing effects of trans ‐phase dangling of OH groups to increase the rates of ′on water′ organic reactions . Subsequently, a number of reports describing the importance of heterogeneous reaction media to catalyze organic reactions have appeared in the literature …”

“…Both the rate constants as well as the stereoselectivity for interfacial reactions weren oted to be exceedingly larger than previously reported values for the same reactiona tt he given concentrations, in conventional solvent media, including water. [1][2][3][4] Our work on the ionic liquid interface as ar eactionm edium has been motivated by the recent findings citing the application of heterogeneous reactionm edia to perform organic synthesis. [2][3][4] Sharpless and co-workersh ave reported that the reaction time for av ariety of organicr eactions is dramatically shorter for heterogeneous 'on water' conditions than that for homogeneous in water conditions.…”

“…[1][2][3][4] Our work on the ionic liquid interface as ar eactionm edium has been motivated by the recent findings citing the application of heterogeneous reactionm edia to perform organic synthesis. [2][3][4] Sharpless and co-workersh ave reported that the reaction time for av ariety of organicr eactions is dramatically shorter for heterogeneous 'on water' conditions than that for homogeneous in water conditions. [5] An earlier report by Rideout and Breslow described ah ydrophobic rate enhancement of Diels Alder reactions in aqueous solutions.…”