Kinetic solvent effects on 1,3-dipolar cycloadditions of benzonitrile oxide

The kinetics of 1,3-dipolar cycloadditions of benzonitrile oxide with a series of N-substituted maleimides and with cyclopentene are reported for water, a wide range of organic solvents and binary solvent mixtures. The results indicate the importance of both solvent polarity and specific hydrogen-bond interactions in governing the rates of the reactions. The aforementioned reactions are examples for which these factors often counteract, leading to a complex dependence of rate constants on the nature of the solvent. For the reactions of N-ethylmaleimide and N-n-butylmaleimide with benzonitrile oxide, isobaric activation parameters have been determined in several organic solvents, water, and water–1-propanol mixtures. Interestingly, the activation parameters reveal significant differences in solvation in different solvents that are not clearly reflected in the rate constants. In highly aqueous mixtures, enforced hydrophobic interactions lead to an increase in rate constant, relative to organic solvents. However, the overall rate enhancement in water is modest, if present at all, because the solvent polarity diminishes the rate constant. This pattern contrasts with common Diels–Alder reactions, where polarity, hydrogen-bond donor capacity and enforced hydrophobic interactions work together, which can result in impressive rate accelerations in water.