Solvent effect microsolvation

In our studies, solvent effects were included in three different ways (i) by explicit inclusion of water molecules, (ii) by using a continuum solvation model and (iii) by the combination of models (i) and (ii). The first approach is called microsolvation,... 

For the Michael addition between 3-pentanone and nitrostyrene a report by Patil and Sunoj points out a key limitation of the standard enamine derived transition state model when a polar protic reaction medium is employed (Scheme 17.10) [42]. The unassisted transition state inclusive of continuum solvent effects failed to predict the correct stereochemical outcome of the reaction as compared to the experimental observations. The predicted lowest energy transition state has been identified as leading to an incorrect configuration of the newly formed chiral centers as well as the wrong diastereomer. Further refinements to the transition state models were carried out with inclusion of explicit solvent molecules in view of the fact that the reaction being modeled has been conducted in methanol as the solvent. After examining several microsolvated transition states with varying... 

The rate acceleration imposed by 0-cyclodextrin was explained in terms of a microsolvent effect 6> The inclusion of the substrate within the hydrophobic cavity of cyclodextrin simulates the changes in solvation which accompany the transfer of the substrate from water to an organic solvent. Uekama et al.109) have analyzed the substituent effect on the alkaline hydrolysis of 7-substituted coumarins (4) in the... 

Hydrolyses of p-nitrophenyl and 2,4-dinitrophenyl sulfate are accelerated fourfold and eightfold, respectively, by cycloheptaamylose at pH 9.98 and 50.3° (Congdon and Bender, 1972). These accelerations have been attributed to stabilization of the transition state by delocalization of charge in the activated complex and have been interpreted as evidence for the induction of strain into the substrates upon inclusion within the cycloheptaamylose cavity. Alternatively, accelerated rates of hydrolysis of aryl sulfates may be derived from a microsolvent effect. A comparison of the effect of cycloheptaamylose with the effect of mixed 2-propanol-water solvents may be of considerable value in distinguishing between these possibilities. 

Recently, an example of cycloamylose-induced catalysis has been presented which may be attributed, in part, to a favorable conformational effect. The rates of decarboxylation of several unionized /3-keto acids are accelerated approximately six-fold by cycloheptaamylose (Table XV) (Straub and Bender, 1972). Unlike anionic decarboxylations, the rates of acidic decarboxylations are not highly solvent dependent. Relative to water, for example, the rate of decarboxylation of benzoylacetic acid is accelerated by a maximum of 2.5-fold in mixed 2-propanol-water solutions.6 Thus, if it is assumed that 2-propanol-water solutions accurately simulate the properties of the cycloamylose cavity, the observed rate accelerations cannot be attributed solely to a microsolvent effect. Since decarboxylations of unionized /3-keto acids proceed through a cyclic transition state (Scheme X), Straub and Bender suggested that an additional rate acceleration may be derived from preferential inclusion of the cyclic ground state conformer. This process effectively freezes the substrate in a reactive conformation and, in this case, complements the microsolvent effect. 

The rate of decarboxylation of activated carboxylate anions [e.g. (10)], shows strong solvent dependence. It is not surprising, therefore, that these reactions have been used to probe the microsolvent effects of micelles and CDs (Fendler and Fendler, 1975). In particular, it was anticipated that complexation with a CD might result in catalysis by providing an environment for the reaction that is less polar than water. 

From these experiments on molecular clusters, a new aspect of ion-molecule reactions can be studied as a function of the cluster size and compared with results on the gas phase and in the liquid phase. The role of the solvent in bimolecular reactions has been evidenced and the catalytic effect depends on the number of molecules (which represents a new result compared with experiments in solution) and the nature of the solvent. These systems appear to be very good systems to study the chemistry under microsolvation. 

In addition to the microsolvation, the effect of solvation on the reaction has also been modeled by Re and Morokuma [111]. They demonstrated the significance of molecular solvation using the two-layered ONIOM method. The Sn2 pathway between CH3CI and OH ion in microsolvated clusters with one or two water molecules has been studied. This work highlighted the role of solvent in the chemical reaction and also the power of ONIOM model to predict complex systems. All these studies have undoubtedly brought out the significance of H-bonding in solute-solvent interaction, chemical reactivity, and molecular solvation phenomenon. 

---