Water and Organic Synthesis: A Focus on the In-Water and On-Water Border. Reversal of the In-Water Breslow Hydrophobic Enhancement of the Normal <i>endo</i>-Effect on Crossing to On-Water Conditions for Huisgen Cycloadditions with Increasingly Insoluble Organic Liquid and Solid 2π-Dipolarophiles

Abstract

Measurements of the endo/exo product ratios for Huisgen cycloadditions with a series of vinyl ketones, alkyl acrylates, and substituted styrenes as dipolarophiles with phthalazinium and pyridazinium dicyanomethanide 1,3-dipoles in acetonitrile and water show that as the reactions change from in-water (large hydrophobic enhancement of endo-products) to on-water, the hydrophobic enhancement of the endo-products is reduced and partially reversed (relative to acetonitrile). An expected increase of the endo-effect with increasing hydrophobic character of the dipolarophile is overcome by decreasing water solubility causing changeover to on-water conditions. On-water reactions do not show increased cycloaddition endo-effects (relative to organic solvents) as do in-water reactions.