Substitution, electrophilic Wheland intermediates

As the o-complexes in these azo coupling reactions are steady-state intermediates (Wheland intermediates, named after Wheland s suggestion in 1942), their stereochemistry cannot be determined directly. Bent structures like that in Figure 12-6 can, however, be isolated in electrophilic substitutions of 1,3,5-triaminobenzene... 

What we shall be doing in the discussion that follows is comparing the effect that a particular Y would be expected to have on the rate of attack on positions o-/p- and m-, respectively, to the substituent Y. This assumes that the proportions of isomers formed are determined entirely by their relative rates of formation, i.e. that the control is wholly kinetic (cf. p. 163). Strictly we should seek to compare the effect of Y on the different transition states for o-, m- and p-attack, but this is not usually possible. Instead we shall use Wheland intermediates as models for the transition states that immediately precede them in the rate-limiting step, just as we have done already in discussing the individual electrophilic substitution reactions (cf. p. 136). It will be convenient to discuss several different types of Y in turn. 

With naphthalene, electrophilic substitution (e.g. nitration) is found to take place preferentially at the 1- (a-), rather than the alternative 2- (/ -), position. This can be accounted for by the more effective delocalisation, and hence stabilisation, that can take place in the Wheland intermediate for 1 - attack (60a - 606) compared with that for 2-attack (61) ... 

Pyridine is thus referred to as a n-deficient heterocycle and, by analogy with a benzene ring that carries an electron-withdrawing substituent, e.g. N02 (p. 151), one would expect it to be deactivated towards electrophilic attack. Substitution takes place, with difficulty, at the 3-position because this leads to the most stable Wheland intermediate (63) the intermediates for 2- and 4-attack (64 and 65, respectively) each has a canonical state in which the charge is located on divalent N—a highly unstable, i.e. high energy, state ... 

Electrophilic substitution of pyrrole can, however, be carried out under specialised conditions (e.g. acylation with (MeC0)20/BF3, sulphonation with a pyridine/S03 complex, C5H5N-S03, cf. (67)) leading to preferential attack at the 2-, rather than the 3-, position. This reflects the slightly greater stabilisation of the Wheland intermediate for the former (70) compared with that for the latter (71) ... 

The arylstannanes undergo electrophilic substitution more readily than do the parent protic compounds, through a similar Wheland intermediate (Equation (52)). 

Protonated polymethylbenzenes281 and the chlorohexamethylbenzenium cation,282 intermediates in aromatic electrophilic substitutions known as Wheland intermediates, have been isolated as crystalline salts, allowing investigators to obtain their X-ray crystal structure. Nitrosoarenium a complexes of various arenes were directly observed by transient absorption spectroscopy.283 Kochi presented a method combining appropriate instrumental techniques (X-ray crystallography, NMR, time-resolved UV-vis spectroscopy) for the observation, identification, and structural characterization of reactive intermediates fa and n complexes) in electrophilic aromatic substitution.284... 

We consider as dihydro derivatives those rings which contain either one or two 5p3-hybridized carbon atoms. According to this definition, all reactions of the aromatic compounds with electrophiles, nucleophiles or free radicals involve dihydro intermediates. Such reactions with electrophiles afford Wheland intermediates which usually easily lose H+ to re-aromatize. However, nucleophilic substitution (in the absence of a leaving group such as halogen) gives an intermediate which must lose H and such intermediates often possess considerable stability. Radical attack at ring carbon affords another radical which usually reacts further rapidly. In this section we consider the reactions of isolable dihydro compounds it is obvious that much of the discussion on the aromatic heterocycles is concerned with dihydro derivatives as intermediates. 

For the trifluoroacetylation of 2-substituted thiophenes, furans, and pyrroles in C2H4C12, 75°, the p values are —7.4, —10.3, and ca. —4.5, respectively.259 The value for substituted benzenes is not known. In the gas phase ionization of substituted furans, thiophenes, selenophenes, and pyrroles,264 a reaction proceeding through a positively charged molecular ion taken to be analogous to the Wheland intermediate for electrophilic substitution, the p values are reported to be —20.2, —16.5,... 

Resonance stabilization is important in electrophilic aromatic substitution as well. While each of the canonical forms of the Wheland intermediate has a sextet carbon atom, the charge is distributed over the remaining five atoms of the ring by resonance and is thus greatly stabilized. 

Electrophilic aromatic substitution normally proceeds via a positively charged intermediate 71 (known as a Wheland intermediate or cr-complex) (equation 27)84. 

Strong differences in the reactivity of the aromatic C=C double bond compared to the reactivity of the C=C double bond of olefins are observed olefinic electrophilic additions are faster than aromatic electrophilic substitutions. For instance, the addition of molecular bromine to cyclohexene (in acetic acid) is about 1014 times faster than the formation of bromobenzene from benzene and bromine in acetic acid113,114. Nevertheless, the addition of halogens to olefins parallels the Wheland intermediate formation in the halogenation of aromatic substrates. 

Another class of gitonic superelectrophiles (based on the 1,3-carbodica-tion structure) are the Wheland intermediates or sigma complexes derived from electrophilic aromatic substitution of carbocationic systems (eq 8). 

Now consider electrophilic substitution in R at atom j. The Wheland intermediate T is derived from R by excision of atom j (Fig. 3). The -electron density at atom i in S is given by... 

This is the typical reaction undergone by thiophenes, i.e. electrophilic substitution at the carbon atom adjacent to the sulfur (positions 2 and 5). This immediately raises the question vhy does electrophilic substitution occur primarily at C-2 (or C-5) " Consideration of Wheland intermediates gives an easily understandable, simplified picture of what is happening. In the case of... 

Figure 3. Consideration of Wheland intermediates for electrophilic substitution of thiophene at (i) C-2, (ii) C-3.

Electrophilic attack occurs more readily at the a than at the )8 position in all five-membered rings. The preference for a substitution may be rationalized by comparing the energies of the transition states leading to a- and -substituted products. Taking the Wheland intermediates as models for the transition states, it is possible to see that, while for a attack, three limiting resonance structures (17-19)... 

---