Substituent effects on an inverse electron demand hetero Diels-Alder reaction in aqueous solution and organic solvents:Cycloaddition of substituted styrenes to di(2-pyridyl)-1,2,4,5-tetrazine

The kinetics of the Diels-Alder reactions of di(2-pyridyl)-1,2,4,5-tetrazine (1) with substituted styrenes 2 was investigated in aqueous media and in organic solvents. The second-order rate constants ofthis reaction increase dramatically in water-rich media. A decrease in pH accelerates the aqueous Diels-Alder reaction even more. The Hammett p-values and also the electronic demand eta-values of the reaction are solvent sensitive. In protic solvents the dipolar character of the activated complex is increased, but simultaneously hydrogen-bond interactions stabilize the activated complex. These effects are most pronounced in 2,2,2-trifluoroethanol, which shows that the aqueous accelerations cannot be solely attributed to solvent-induced changes of the reaction mechanism.