Rates and Equilibria Intermolecular Steric Effects

In this section, we concentrate on the influence of steric effects on heterocyclic reactivity, but we do not treat reactions of substituents bonded to heteroaromatics, except in special cases of ambident reactivity (ring vs. substituent) modified by steric effects. 

One of the simplest methods to evaluate the steric effect of a substituent, in a position ortho to a reactive center, is to compare results for the same group at a 

For heteroaromatics having a basicity which can be measured precisely by conventional potentiometric or spectrophotometric methods, a pKa value is easily obtained. Owing to the very small size of the proton, the pKa is considered free from steric effects. Thus, the nucleophilicity of a series of heteroaromatic molecules, say in quaternization reactions, may be compared to the pKa within the same series this is a Bronsted relation  

Remark a. Since nucleophilicity corresponds to rate constants and is kinetically controlled and basicity corresponds to equilibria and is thermody- 

Remark b. Because nucleophilicity is usually recorded in organic solvents and pKa in water (or water/methanol mixtures), this can make a large difference. Answer The nucleophilicities of a series of molecules in different organic solvents are correlated with excellent correlation coefficients (r). Furthermore, correlations of each series with pKa in the case of non-ortho substituents is also very good. That the slope, a, of the Bronsted relation is an estimate of transition state location may be questioned (78T2331). Deviations from the Bronsted a seem to be well established as a measure of steric effects. 

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