Charge substituent effects

Significantly low r values have been observed in the protonation equilibria (p i BH values) of benzoyl compounds (Mishima et al., 1988, 1990c, 1996c). ITie trend in the r values mentioned above predicts that a stabilized carbocation will not require a large ir-delocalization of the positive charge. Substituent effects on Ae gas-phase basicities (AG(co>h+) of the aromatic carbonyl compounds [30(R)], ArCOR (30) have been studied. 

The relative extent to which dipolar and charged substituent effects decrease with increasing distance from an acidic functional group can be obtained by dividing Equation (5) into Equation (6) ... 

Consideration of (i), as in the work of Ridd and his co-workers, would constitute a transition state theory of the substituent effects. (2) alone would give an isolated molecule description, and (3), in so far as the charge on the electrophile was considered to modify those on the... 

Field effects can be determined by calculating the effect of a bond dipole on a molecular probe at a specifted distance. One system that has been examined is H2 aligned with an H—X molecule. The substituent effect is related to the charge which develops at Ha, relative to the case where X = H. 

The relatively large p shows that the reaction is very sensitive to substituent effects and implies that there is a relatively large redistribution of charge in the transition state. 

This would disperse the positive charge over several atoms and diminish the sensitivity of the reaction to substituent effects. The p values that are observed are consistent with this interpretation. Whereas p is —3.25 for acetal hydrolysis, it is only —1.9 for hemiacetal hydrolysis. ... 

Because the substituent groups have a direct resonance interaction with the charge that develops in the a-complex, quantitative substituent effects exhibit a high resonance component. Hammett equations usually correlate best with the substituent constants (see Section 4.3). ... 

The position selectivity for electrophilic substitution in the simple five-membered heteroaromatic rings is usually 2 > 3. This reflects the more favorable conjugation in intermediate A than in intermediate B. In structure A the remaining C=C bond can delocalize the positive charge more effectively than in B. Substituents on the ring can easily override this directive influence, however. 

Next we turn to the magnitudes of the p constants. Evidently if p = 0, there is no substituent effect on reactivity. Moreover because p = -I-1.000 by definition for the aqueous ionization of benzoic acids, we have a scale calibration of sorts. Wiberg gives examples of p as a measure of the extent of charge development in the transition state. McLennan" has pointed out that p values must first be adjusted for the transmission factor before they can be taken as measures of charge devel-... 

To obtain qualitative information about a molecule, such as its moleculip orbitals, atomic charges or vibrational normal modes. In some cast semi-empirical methods may also be successfully used to predict energy-trends arising from alternate conformations or substituent effects in qualitative or semi-quantitative way (but care must be taken in this area). 

Decide if ion-dipole interactions are responsible for the observed substituent effects. Obtain the charge on carbon and nitrogen in each cyano group. What evidence is there for a polar CN bond Should the ion (O )-dipole (CN) interaction be stabilizing or destabilizing Can these interactions explain the trends in electrostatic potential (Hint Focus on changes in O—CN distance and in orientation of the cyano group.)... 

When a positively charged substituent such as the trimethylam-monio group is anywhere on the ring, but most effectively when it is ortho to the leaving group, it can favorably affect the entropy of activation with anionic nucleophiles and accelerate reaction. A recent example of reagent-substituent interaction is the electrophilic substitution of 2-carboxybiphenyl, nitration (non-polar solvent) of which occurs only at the 2 -position and not the 4 -position and has been postulated to be due to the interaction of the nitronium ion with the carboxyl group. 

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