Electrophilic aromatic substitution transition state

The general validity of these equations is supported by a great deal of experimental data on aromatic substitution reactions of toluene. Examples of values for some reactions obtained from these equations are given in Table 11.4.78 For other substituents, the treatment works well with groups that, like methyl, are not very polarizable. For more polarizable groups the correlations are sometimes satisfactory and sometimes not, probably because each electrophile in the transition state makes a different demand on the electrons of the substituent group. 

In a chemical reaction, a more stable transition state, measured by the magnitude of the activation energy, implies an easier chemical reaction. Aromatic transition states are also known to facilitate the chemical reaction. Zhou and Parr defined the activation hardness as the hardness difference of the products and the transition state and found, in the case of electrophilic aromatic substitution, that the smaller the activation hardness, the faster the reaction is. For this specific reaction they also found a correlation of the activation hardness and Wheland s cation localization energy, also proposed as an indicator of aromaticity. This finding can indeed be interpreted as a manifestation of the maximum hardness principle. A transition state with a high hardness is more stable than one with a smaller hardness and is therefore easier to reach energetically. The same can be said about two transition states with different aromaticity. Again, hardness and aromaticity parallel each other. The activation hardness has been used in numerous applications for the prediction of site selectivity in chemical reac-... 

For electrophilic substitutions in general, and leaving aside theories which have only historical interest, two general processes have to be considered. In the first, the 5 3 process, a transition state is involved which is formed from the aromatic compound, the electrophile (E+), and the base (B) needed to remove the proton ... 

The best-known equation of the type mentioned is, of course, Hammett s equation. It correlates, with considerable precision, rate and equilibrium constants for a large number of reactions occurring in the side chains of m- and p-substituted aromatic compounds, but fails badly for electrophilic substitution into the aromatic ring (except at wi-positions) and for certain reactions in side chains in which there is considerable mesomeric interaction between the side chain and the ring during the course of reaction. This failure arises because Hammett s original model reaction (the ionization of substituted benzoic acids) does not take account of the direct resonance interactions between a substituent and the site of reaction. This sort of interaction in the electrophilic substitutions of anisole is depicted in the following resonance structures, which show the transition state to be stabilized by direct resonance with the substituent ... 

Rate data are also available for the solvolysis of l-(2-heteroaryl)ethyl acetates in aqueous ethanol. Side-chain reactions such as this, in which a delocalizable positive charge is developed in the transition state, are frequently regarded as analogous to electrophilic aromatic substitution reactions. In solvolysis the relative order of reactivity is tellurienyl> furyl > selenienyl > thienyl whereas in electrophilic substitutions the reactivity sequence is furan > tellurophene > selenophene > thiophene. This discrepancy has been explained in terms of different charge distributions in the transition states of these two classes of reaction (77AHC(21)119>. 

The substituent effects in aromatic electrophilic substitution are dominated by resonance effects. In other systems, stereoelectronic effects or steric effects might be more important. Whatever the nature of the substituent effects, the Hammond postulate insists diat structural discussion of transition states in terms of reactants, intermediates, or products is valid only when their structures and energies are similar. 

Ipso substitution, in which the electrophile attacks a position already carrying a substituent, is relatively rare in electrophilic aromatic substitution and was not explicitly covered in Section 10.2 in the discussion of substituent effects on reactivity and selectivity Using qualitative MO cOTicepts, discuss the effect of the following types of substituents on the energy of the transition state for ipso substitution. 

Probably the most important development of the past decade was the introduction by Brown and co-workers of a set of substituent constants,ct+, derived from the solvolysis of cumyl chlorides and presumably applicable to reaction series in which a delocalization of a positive charge from the reaction site into the aromatic nucleus is important in the transition state or, in other words, where the importance of resonance structures placing a positive charge on the substituent - -M effect) changes substantially between the initial and transition (or final) states. These ct+-values have found wide application, not only in the particular side-chain reactions for which they were designed, but equally in electrophilic nuclear substitution reactions. Although such a scale was first proposed by Pearson et al. under the label of and by Deno et Brown s systematic work made the scale definitive. 

Bifunctional catalysis in nucleophilic aromatic substitution was first observed by Bitter and Zollinger34, who studied the reaction of cyanuric chloride with aniline in benzene. This reaction was not accelerated by phenols or y-pyridone but was catalyzed by triethylamine and pyridine and by bifunctional catalysts such as a-pyridone and carboxylic acids. The carboxylic acids did not function as purely electrophilic reagents, since there was no relationship between catalytic efficiency and acid strength, acetic acid being more effective than chloracetic acid, which in turn was a more efficient catalyst than trichloroacetic acid. For catalysis by the carboxylic acids Bitter and Zollinger proposed the transition state depicted by H. 

Reactions that take place through dipolar transition states Menschutkin reaction (10-44), electrophilic aromatic substitution. 

We may ask How does Y know which side will give the more stable carbocation As in the similar case of electrophilic aromatic substitution (p. 681), we invoke the Hanunond postulate and say that the lower energy carbocation is preceded by the lower energy transition state. Markovnikov s rule also applies for halogen substituents because the halogen stabilizes the carbocation by resonance ... 

In aromatic substitution of the electrophilic type, a cation or potential cation attacks the benzene ring. The transition state or intermediate, whichever it may be, has largely covalent bonds holding... 

To provide an example of a reaction that is very different to electrophilic aromatic substitution, the oxidation of formic acid by bromine was also studied. This reaction, which involves electrophilic attack on the formate anion (15) (Cox and McTigue, 1964 Smith, 1972 Herbine et al., 1980 Brusa and Colussi, 1980), is catalysed by a-CD (/c /k2u = 11) (Tee et al., 1990a), and the degree of transition state stabilization (Xts = 0.18 mM) is similar to that for phenols (Table A4.2) and most of the other substrates (Table A4.4). 

A reaction in which an electrophile participates in het-erolytic substitution of another molecular entity that supplies both of the bonding electrons. In the case of aromatic electrophilic substitution (AES), one electrophile (typically a proton) is substituted by another electron-deficient species. AES reactions include halogenation (which is often catalyzed by the presence of a Lewis acid salt such as ferric chloride or aluminum chloride), nitration, and so-called Friedel-Crafts acylation and alkylation reactions. On the basis of the extensive literature on AES reactions, one can readily rationalize how this process leads to the synthesis of many substituted aromatic compounds. This is accomplished by considering how the transition states structurally resemble the carbonium ion intermediates in an AES reaction. 

Problem 11.25 Compare addition-elimination aromatic nucleophilic and electrophilic substitution reactions with aliphatic 5 2 reactions in terms of (a) number of steps and transition states, (b) character of intermediates. 

---