Polarization direction substituent effect

In the El cb mechanism, the direction of elimination is governed by the kinetic acidity of the individual p protons, which, in turn, is determined by the polar and resonance effects of nearby substituents and by the degree of steric hindrance to approach of base to the proton. Alkyl substituents will tend to retard proton abstraction both electronically and sterically. Preferential proton abstraction from less substituted positions leads to the formation of the less substituted alkene. This regiochemistry is opposite to that of the El reaction. 

Similarly, carboxylic acid and ester groups tend to direct chlorination to the / and v positions, because attack at the a position is electronically disfavored. The polar effect is attributed to the fact that the chlorine atom is an electrophilic species, and the relatively electron-poor carbon atom adjacent to an electron-withdrawing group is avoided. The effect of an electron-withdrawing substituent is to decrease the electron density at the potential radical site. Because the chlorine atom is highly reactive, the reaction would be expected to have a very early transition state, and this electrostatic effect predominates over the stabilizing substituent effect on the intermediate. The substituent effect dominates the kinetic selectivity of the reaction, and the relative stability of the radical intermediate has relatively little influence. 

Evidence is provided by this analysis that (a) structural considerations discriminate among at least four practical classes of pi delocalization behavior, each of which has limited generality (b) the blend of polar and pi delocalization effect contributions to the observed effect of a substituent is widely variable among different reaction or data sets (the contributions may be opposite as well as alike in direction), depending upon structural considerations and the nature of the measurement (c) solvent may play an important role in determination of the observed blend of effects (d) it is the first three conditions which lead to the deterioration of the single substituent parameter treatment as a means of general and relatively precise description of observed electronic substituent effects in the benzene series. 

Based on the fundamental dipole moment concepts of mesomeric moment and interaction moment, models to explain the enhanced optical nonlinearities of polarized conjugated molecules have been devised. The equivalent internal field (EIF) model of Oudar and Chemla relates the j8 of a molecule to an equivalent electric field ER due to substituent R which biases the hyperpolarizabilities (28). In the case of donor-acceptor systems anomalously large nonlinearities result as a consequence of contributions from intramolecular charge-transfer interaction (related to /xjnt) and expressions to quantify this contribution have been obtained (29). Related treatments dealing with this problem have appeared one due to Levine and Bethea bearing directly on the EIF model (30), another due to Levine using spectroscopically derived substituent perturbations rather than dipole moment based data (31.) and yet another more empirical treatment by Dulcic and Sauteret involving reinforcement of substituent effects (32). 

The new treatment had its origins partly in ab initio molecular orbital calculations of substituent effects and partly in extensive studies of gas-phase proton transfer reactions from about 1980 (Section V.A). Various aspects of this work essentially drew attention to the importance of substituent polarizability. In 1986 Taft, Topsom and their colleagues252 developed a scale of directional substituent polarizability parameters , oa, by ab initio calculations of directional electrostatic polarization potentials at the 3-21G//3-31G level for a large set of CH3X molecules. The oa values were shown to be useful in the correlation analysis of gas-phase acidities of several series of substrates252, and such work has subsequently been extended by Taft and Topsom151. 

In view of the extensive documentation outlined above, the usefulness of the polarity alternation concept as a primary guide for evaluation of substituent effects can hardly be denied. The influence of a substituent on the ipso site has not been discussed in this article but an even more direct and important effect is implicit. Among the innumerable examples one may cite the preferential formation of geminal dimetallic species [5] in hydrometalation and carbometalation of vinylmetals and acetylenes. On the other hand, chemical systems are usually very complex, inter- and intramolecular forces including steric and stereoelectronic factors may dominate over polarity alternation. Thus, chelation by a proximal donor often directs metalation and stabilizes certain organometallic entities. In these instances the stability gaining from polarity alternation is overwhelmed. 

Anthracene absorbs at two wavelengths, at 360 nm and at 260 nm. The flat molecule is anisotropic and it has long axis along x coordinates and a short axis along y coordinate. The absorption at 360 nm is short axis polarized (La type). A substituent at 9,10 or 1, 4, S, and 8 positions may help rr retard the creation of dipole in this direction. Therefore, the intensity or position of this absorption region may be influenced by such substitutions. The absorption at 260 nm is long axis polarized (Lb type) and is perturbed by substitution at 2, 3, 6 and 7 positions. Such substituent effects are sometimes used to identify the polarization directions of a given electronic transition. 

M.O. calculations have predicted that all of the heterobenzenes have the same direction of polarization with negative end of the dipole towards the heteroatom67-70). This has been confirmed by substituent effects from pyridine, phos-phabenzene and arsabenzene 27). In each case the 4-methyl derivatives have dipole moments which exceed the parent compound since the electron donating methyl group reinforces the ring dipole. 

We are left with the problem of substituent effects that do not depend on direct mesomeric interactions between the substituent and the reaction center. Effects of this kind can arise in one of two ways. First, the bond between the substituent and the substrate may be polar, and there may also be polar bonds or charged atoms in the substituent itself the charges set up in this way can influence the reaction center either by altering the effective electronegativity of atoms connected with it (inductive effect) or by direct electrostatic interaction across space (field effect). Secondly, the substituent may be attached to a conjugated system which does not itself take part in the reaction, the case exemplified by the Hammett equation (Eq. (105)) here it... 

As seen from equation (3.2), in these benzimidazole systems the substituent effects are transmitted by the same mechanism but with different intensities. The degree of this transmission in the 2—>5(6) direction is approximately 20% lower than that in the opposite direction. The reason for this nonequivalence is likely to be due to the benzyl fragment polarization by electronegative nitrogen atoms of the five-membered heterocycle [689, 691],... 

The carbonyl-carbon kinetic isotope effect (KIE) and the substituent effects for the reaction of lithium pinacolone enolate (112) with benzaldehyde (equation 31) were analyzed by Yamataka, Mishima and coworkers ° and the results were compared with those for other lithium reagents such as MeLi, PhLi and AllLi. Ab initio (HF/6-31-I-G ) calculations were carried out to estimate the equilibrium isotope effect (EIE) on the addition to benzaldehyde. In general, a carbonyl addition reaction (equation 32) proceeds by way of either a direct one-step polar nucleophilic attack (PL) or a two-step process involving electron transfer (ET) and a radical ion intermediate. The carbonyl-carbon KIE was of primary nature for the PL or the radical coupling (RC) rate-determining ET mechanism, while it was considered to be less important for the ET rate-determining mechanism. The reaction of 112 with benzaldehyde gave a small positive KIE = 1.019),... 

The linear free energy equations (Chapter 2) do not directly give the charge characteristics of the reaction. The following discussion shows how the polar substituent effects can be treated to obtain a quantitative measure of relative charge. 

As we mentioned earlier, not all reaction series can be correlated by a Hammett equation. An underlying reason for the inability of Hammett and values to correlate all reaction series is that the substituent effects used to assign ct are a mixture of resonance and polar components. When direct resonance interaction with a reaction site is possible, the extent of the resonance increases and the substituent constants appropriate to the normal mix of resonance and polar effects fail. There have been various attempts to develop sets of a values that take extra resonance interactions into account. In addition to the and values used with the classical Hammett equation Table 3.27 lists substituent constants and ct . These are substituent constant sets that reflect enhanced resonance participation. The values are used for reactions in which there is direct resonance interaction between an electron donor substituent and a cationic reaction center, whereas the set pertains to reactions in which there is a direct resonance interaction between an electron acceptor and an anionic reaction site. In these cases, the resonance component of the substituent effect is particularly important. 

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