Aqueous acceleration

Tire importance of hydrophobic interactions in the aqueous acceleration is further demonstrated by a qualitative study described by Jenner on the effect of pressure on Diels-Alder reactions in water and a number of organic solvents. Invariably, the reactions in water were less accelerated by pressure than those in organic solvents, which is in line with the notion that pressure diminishes hydrophobic interactions. 

Comparison of the water-induced acceleration of the reaction of 2.4a with the corresponding effect on 2.4g is interesting, since 2.4g contains an ionic group remote from the reaction centre. The question arises whether this group has an influence on the acceleration of the Diels-Alder reaction by water. Comparison of the data in Table 2.1 demonstrates that this is not the case. The acceleration upon going from ethanol to water amounts a factor 105 ( 10) for 2.4a versus 110 ( 11) for 2.4g. Apparently, the introduction of a hydrophilic group remote from the reaction centre has no effect on the aqueous acceleration of the Diels-Alder reaction. 

The SMK2/AM1 model was used to elucidate the source ofthe aqueous acceleration of the Claisen rearrangement. The calculations allowed to state that this acceleration is caused by electronic polarization and first-shell hydration hydro-phillic effects, with the relative magnitudes and even the signs of these effects being quite sensitive to the substitution pattern [120]. 

In the retro-Diels-Alder reaction of anthracenedione [42], the volume of activation is small. Acceleration in water cannot come from a change in the hydration shell of the molecule. Hydrophobic interactions are negligible and aqueous acceleration is caused by the hydrogen-bond donating ability of water, which stabilizes the polarized activated complex. The Gibbs energy of activation displays a fair linear correlation with the Ej parameter. Hexafluoroisopropanol with an Ej value of 65.3 is even more efficient as a solvent than water Ej= 63.1) which appears to be less polar [41]. 

In aqueous solution, the PCM method computes an activation enthalpy of 15.3 kcal/mol, which is 46% [3.8 kcal/mol (computed)/8.2 kcal/mol (expected)] of the estimated reduction to a 10.9 kcal/mol activation barrier. In a second comparison, the second-order rate constants between cyclopentadiene and alkyl vinyl ketones have been reported to be 740 times larger in water than in ra-octane [82], Overall, the PCM model lowers the Gibbs activation energies of the NC reaction from benzene to water by 2.0 kcal/mol, which correspond to an aqueous rate increase of ca. 30 times. Therefore despite mirroring the experimental trend in activation barrier reduction with increasing solvent polarity, the PCM method does not fully account for the observed rate of aqueous acceleration. 

The kinetics of the Diels-Alder reactions of di(2-pyridyl)-l,2,4,5-tetrazine with substituted styrenes have been investigated in aqueous media and in organic solvents. The second-order rate constants of this reaction increase dramatically in water-rich media. A decrease in pH accelerates the aqueous Diels-Alder reaction even more. The Hammer p-values and also the electronic demand 77-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 attributed solely to solvent-induced changes of the reaction mechanism <1996JOC2001>. 

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