Cycloadditions in mixed aqueous solvents: the role of the water concentration

We examined the kinetics of a series of cycloaddition reactions in mixtures of water with methanol, acetonitrile and poly(ethylene glycol) (MW 1000). The reactions include the Diels–Alder (DA) reaction between cyclopentadiene and N ‐ n ‐butylmaleimide or acridizinium bromide, the retro‐Diels‐Alder (RDA) reaction of 1,4,4a,9a‐tetrahydro‐4a‐methyl‐(1α,4α,4aα,9aα)‐1,4‐methaneanthracene‐9,10‐dione and the 1,3‐dipolar cycloaddition of benzonitrile oxide with N ‐ n ‐butylmaleimide. Plots of log k vs the molar concentration or volume fraction of water are approximately linear, but with a characteristic break around 40 M water. This break, absent for the RDA reaction, is ascribed to hydrophobic effects. Comparison with aqueous mixtures of the more hydrophobic 1‐propanol shows that these mixtures induce qualitatively similar effects on the rate, but that preferential solvation effects cause the mixtures of 1‐propanol to exhibit a more complex behavior of log k on composition. The results are analyzed using the Abraham–Kamlett–Taft model. The solvent effects in aqueous mixtures are not satisfactorily described by this model. For some cycloadditions, small maxima in rate are observed in highly aqueous mixtures of alcohols. The origin of these maxima and the aforementioned breaks is most likely the same.