Electrophilic aromatic substitution directing effects

Example 22.4 Electrophilic Aromatic Substitution Directing Effects... 

There were two schools of thought concerning attempts to extend Hammett s treatment of substituent effects to electrophilic substitutions. It was felt by some that the effects of substituents in electrophilic aromatic substitutions were particularly susceptible to the specific demands of the reagent, and that the variability of the polarizibility effects, or direct resonance interactions, would render impossible any attempted correlation using a two-parameter equation. - o This view was not universally accepted, for Pearson, Baxter and Martin suggested that, by choosing a different model reaction, in which the direct resonance effects of substituents participated, an equation, formally similar to Hammett s equation, might be devised to correlate the rates of electrophilic aromatic and electrophilic side chain reactions. We shall now consider attempts which have been made to do this. 

Section 12 15 When two or more substituents are present on a nng the regioselectiv ity of electrophilic aromatic substitution is generally controlled by the directing effect of the more powerful activating substituent... 

Resonance effects are the primary influence on orientation and reactivity in electrophilic substitution. The common activating groups in electrophilic aromatic substitution, in approximate order of decreasing effectiveness, are —NR2, —NHR, —NH2, —OH, —OR, —NO, —NHCOR, —OCOR, alkyls, —F, —Cl, —Br, —1, aryls, —CH2COOH, and —CH=CH—COOH. Activating groups are ortho- and para-directing. Mixtures of ortho- and para-isomers are frequently produced the exact proportions are usually a function of steric effects and reaction conditions. 

Trialkyltin substituents are also powerful ipso-directing groups. The overall electronic effects are similar to those in silanes, but the tin substituent is a better electron donor. The electron density at carbon is increased, as is the stabilization of /S-carbocation character. Acidic cleavage of arylstannanes is formulated as an electrophilic aromatic substitution proceeding through an ipso-oriented c-complex. ... 

A Summary of Substituent Effects in Aromatic Substitution A summary of the activating and directing effects of substituents in electrophilic aromatic substitution is shown in Table 16.2. 

As a result of these substituent-induced polarizations, the complementary conjugative interactions at each ring site become somewhat imbalanced (so that, e.g., the donor-acceptor interaction from C3—C4 to C5—C(, is 23.1 kcal mol-1, but that in the opposite direction is only 16.4 kcal mol-1). From the polarization pattern in (3.133) one can recognize that excess pi density is accumulated at the ortho (C2, C6) and para (C4) positions, and thus that the reactivity of these sites should increase with respect to electrophilic attack. This is in accord with the well-known o, /(-directing effect of amino substitution in electrophilic aromatic substitution reactions. Although the localized NBO analysis has been carried out for the specific Kckule structure of aniline shown in Fig. 3.40, it is easy to verify that exactly the same physical conclusions are drawn if one starts from the alternative Kekule structure. 

These polarizations are seen to be in the opposite direction to those in aniline (3.133), so that higher pi density remains at the Ci (junction) and C3 and C5 (meta) positions. These polarity shifts are again consistent with the well-known m-directing effect of nitro substituents in electrophilic aromatic substitution reactions, and the results are again quite independent of which starting Kekule structure is selected for the localized analysis.63... 

Finally, we ask, if the reactive triads in Schemes 1 and 19 are common to both electrophilic and charge-transfer nitration, why is the nucleophilic pathway (k 2) apparently not pertinent to the electrophilic activation of toluene and anisole One obvious answer is that the electrophilic nitration of these less reactive [class (ii)] arenes proceeds via a different mechanism, in which N02 is directly transferred from V-nitropyridinium ion in a single step, without the intermediacy of the reactive triad, since such an activation process relates to the more conventional view of electrophilic aromatic substitution. However, the concerted mechanism for toluene, anisole, mesitylene, t-butylbenzene, etc., does not readily accommodate the three unique facets that relate charge-transfer directly to electrophilic nitration, viz., the lutidine syndrome, the added N02 effect, and the TFA neutralization (of Py). Accordingly, let us return to Schemes 10 and 19, and inquire into the nature of thermal (adiabatic) electron transfer in (87) vis-a-vis the (vertical) charge-transfer in (62). 

The structural theory of organic chemistry was developed in the last half of the nineteenth century. It led to the concept that chemical, physical and biological properties of all kinds must be a function of structural change. The earliest structure-property relationships (SPR) were qualitative. Examples are the directional effect of substituents on the benzene ring with respect to electrophilic aromatic substitution and orientation in... 

The observed effects of structure on rate and on orientation, confirmed by the Brown selectivity relationship, show that there is no basic difference between heterogeneous catalytic alkylation of aromatic compounds and homogeneous electrophilic aromatic substitution, cf. nitration, sul-phonation etc. This agreement allows the formulation of the alkylation mechanism as an electrophilic attack by carbonium ion-like species formed on the surface from the alkene on Br0nsted acidic sites. The state of the aromatic compound attacked is not clear it may react directly from the gas phase (Rideal mechanism ) [348] or be adsorbed weakly on the surface [359]. 

Two of three nitrofluorobenzene isomers react with methoxide, but the third is unreactive. Obtain energies of methoxide anion (at left), ortho, meta and para-nitrofluorobenzene, and the corresponding ortho, meta and para-methoxide anion adducts (so-called Meisenheimer complexes). Calculate the energy of methoxide addition to each of the three substrates. Which substrate is probably unreactive What is the apparent directing effect of a nitro group Does a nitro group have the same effect on nucleophilic aromatic substitution that it has on electrophilic aromatic substitution (see Chapter 13, Problem 4) Examine the structures and electrostatic potential maps of the Meisenheimer complexes. Use resonance arguments to rationalize what you observe. 

IV. ACTIVATING AND DIRECTIVE EFFECTS OF SILICON IN ELECTROPHILIC AROMATIC SUBSTITUTION... 

The isopropyl group is ortho, para-directing, and the nitro group is meta-directing. In this case their orientation effects reinforce each other. Electrophilic aromatic substitution takes place ... 

If the other reactant is an electrophile and a strong Lewis acid or proton acid is present, then the aromatic ring acts as the nucleophile and the reaction is one of the electrophilic aromatic substitution reactions listed in Table 17.2. Do not forget to consider the directive and rate effects of substituents on the aromatic ring. 

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