Solvophobic activation

Unhindered acrylic compounds afford high yields of Baylis-Hillman adducts at ambient pressure whereas substituted acrylic nitriles and esters require high pressure to lead to functionalized ethylenic derivatives in fair to excellent yields (Table 10.14). 

Optimization of chemical yields can also be achieved by physicochemical activation. It is meant as an activation mode resembling catalysis and involving physicochemical interactions between reactants and medium. The role of the solvent with respect to the course of organic reactions is of obvious importance. One of the first systematic studies reporting the kinetic effect is due to Menshutkin who determined rate constants for the addition of ethyl iodide to triethylamine [49]. This is a typical example of an ionogenic reaction in which the stability of the transition 

State is highly sensitive to the medium. There is a change of polarity of the reaction states from initial to transition state with a volume decrease known as electro-strictive shrinkage. Electrostriction can be critical to rate enhancement under pressure. In terms of kinetic parameters it is related to the pressure dependence of the dielectric constant (dins/dp). Some representative values of this quantity are listed in Table 10.15 [50]. 

In addition, reaction rates may be affected in other ways. It was reported, some 20 years ago, that the rate constants of Diels-Alder reactions were increased by several orders of magnitude when traditional organic solvents were replaced by water [51]. That an organic reaction proceeds faster in aqueous solution in which organic compounds are barely soluble is at first sight rather surprising. It is clear that specific interactions between transition state and water are manifested. 

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Lubineau A, Auge J, Scherrmann M-C (2005) State of the art organic chemistry in water. In Comils B (ed) Multiphase homogeneous catalysis. Wiley, Weinheim Scherrmann M-C, Norsikian S, Lubineau A (2005) Solvophobic activation in organic synthesis. In Atta-ur-Rahman (ed) Advances in organic synthesis, vol. 1. Bentham Science... 

Generalization of the biactivation method (combination of pressure and solvophobic activation) to the Diels-Alder reaction of furan with various dienophiles leads to the results listed in Table 10.29. The yields are modest to fair. The lower... 

In spite of the preceding observation that eluite retention in RPC with hydrocarbonaceous bonded phases may not occur by partitio ng of the eluite between two liquid phases, theoretical considerations based on the solvophobic treatment of solvent effects shows that it might be possible to relate the observed retention factors to partition coefficients between water and an organic solverit. Such a relationship would be quite useful in light of the scale developed by Hansch and his co-workers (2/12, 283) to characterize hydrophobic properties of drugs and other biologically active... 

The physical phenomena causing retention in HIC are basically the same as in solvophobic RPC. In HIC, the moderate binding power of the packing is complemented by the salting-out effect of the mobile phase. The mild conditions of HIC provide the best chance for recovering proteins of biological activity. 

Why does protein concentration exert such strong stabilizing influences on protein structure and, thereby, on enzymatic activity And why can a protein such as BSA affect the stability of an unrelated enzymatic protein like MDH To explain the effects shown in figure 6.21, another type of stabilizing influence must be introduced, one that differs from the mechanisms involving solvophobic (hydro-phobic and osmophobic) effects. The primary phenomenon involved in accounting for stabilization of macromolecular structure by other macromolecules is termed the excluded volume effect, which is one consequence of the molecu-... 

Ig k2 for the Menschutkin reaction of tri- -propylamine with iodomethane (Drougard and Decroocq) standard molar entropy change standard molar entropy of activation solvophobic power of a solvent (Abraham)... 

The IL effects can be explained with solvophobic interactions that generate an internal pressure, which promoted the association of the reactants in a solvent cavity during the activation process and showed an acceleration of the multicomponent reactions (MCRs) in comparison to conventional solvents. The reaction proceeded very efficiently with benzaldehyde and electron releasing and electron-withdrawing ortho-, meta-, and para-substituted benzaldehydes. IL was easily separated from the reaction medium by washing with water and distillation of the solvent nnder vacnnm and it can be reused for subsequent reactions and recycled. IL showed no loss of efficiency with regard to reaction time and yield after four successive runs. 

Chemical structure of the solute and its interactions with the solvent The structure (hydrocarbon chain length, branching, nature and location of polar functional groups) of the solute and its interactions with the solvent (solubility, complexation, micellization) have a marked effect on its adsorption. For example, it is well known from Traube s rule that for aqueous surfactant solutions the surface activity and hence the adsorption at the liquid-air interface increases with an increase in the chain length of the solute molecule. The solutes of interest, surfactants, are also capable of forming association structures in solution (micelles or reverse micelles depending on the solvent), which is a measure of their solvophobicity. 

By measuring the rate constant of the cycloaddition between cyclopentadiene and dimethylfumarate, Schneider [28] demonstrated the importance of solvophobic effects, quantified by solvophobic power (Sp) values [29], which originate from the standard free energy of transfer of alkanes from the gas phase to a given solvent. Such a sensitivity of Diels-Alder reactions to solvent hydrophobicity depends, however, on the nature of the reagents [ 30] and is more pronounced for the reactions with a more negative activation volume [31]. Evidence for presence of en-... 

In these cases the size of the activation volumes obviously depends not only on the effective packing probably caused by the restriction of vibrations and rotations in the transition state, but also on the transition-state polarization enhanced by the polar groups leading to a further decrease in volume which is not observed in the less polarized cycloadducts. Blake and Jorgensen [51] have assumed similar effects to explain the acceleration of Diels-Alder reactions in water. Catalytic and solvophobic promotion of high pressure addition reactions will be discussed in Chapter 11. 

From the whole body of results shown above, the pressure effect on solvophobic interactions will result in an additional activation volume term called AV. We suggest that the quantity AV = 1.AV be expressed as... 

The biactivation method (activation by pressure and solvophobic interactions) was applied to three types of bimolecular reactions [lOOj (i) [4 + 2] cycloadditions, AV range from -30 to —40 cm mol (ii) Michael-like reactions, AV range... 

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