Proximity effect, group contribution

Alternatives to Soave s approach and group contribution adaptations would be better focused on capabilities not offered by such approaches. For example, pure component properties like vapor pressure are assumed to be available when applying Soave s methodology. In the coming world of chemical product design, this assumption may not be satisfactory. Molecular simulation offers the prospect of being able to make these predictions for transport properties as well as equilibrium properties. Proximity effects would also be naturally included within molecular modeling. While the National Research Council has estimated that such predictive capability may not be available for a decade or two, viable preliminary versions may come much sooner than that. 

As an example of how this may be used, we return to the group contribution model for the octanol-water partition coefficient discussed above. As already shown, this model was quite good for monofunctional (i.e., only one nonalkyl group) solutes when applied to multiple functional solutes, the large deviations shown in Fig. 4a were found. The failure of the GCSKOW model is the result of strong proximity effects in multifunctional compounds. 

Dahmani, A. Ait Kaci, A. Jose, J. Vapour pressures and excess functions of N,N,N ,N -tetramethylaIkanediamine + cyclohexane. A group contribution study of the N-N proximity effect Fluid Phase Equilib. 1997,130,271-279... 

One further point is worthy of brief mention. While we have focused on lone pair/lone pair repulsive interactions that destabilize transition state C, it is conceivable that A is actually stabilized relative to C by a favorable charge-charge interaction between the ester carbonyl (5 ) and the aldehydic carbonyl carbon (5+) owing to the proximity of these groups in A. While it is not yet possible to resolve the relative contributions of these distinct stereoelectronic effects, it is clear that our mechanistic proposal e)mlains the experimental results only if the dioxaborolane and the C-COaiPr bonds exist in the conformations indicated in B. Any conformational infidelity at either site would be expected to lead to diminished enantioselectivity. 

---