Wheland complexes

It should be pointed out that the existence of stable structures of the intermediate-complex type (also known as a-complexes or Wheland complexes) is not of itself evidence for their being obligate intermediates in aromatic nucleophilic substitution. The lack of an element effect is suggested, but not established as in benzene derivatives (see Sections I,D,2 and II, D). The activated order of halogen reactivity F > Cl Br I has been observed in quantita-tivei36a,i37 Tables II, VII-XIII) and in many qualitative studies (see Section II, D). The reverse sequence applies to some less-activated compounds such as 3-halopyridines, but not in general.Bimolecular kinetics has been established by Chapman and others (Sections III, A and IV, A) for various reactions. 

In aromatic electrophilic substitutions, 60 corresponds to the Wheland complex. 

There is evidence for formation of a zwitterionic Meisenheimer-Wheland complex between superelectrophilic and supernucleophilic reagents. Thus, NMR spectra in CD2CI2 show the formation of (12) from 4,6-dinitrobenzofuroxan and l,3,5-lris(/V,/V-dialkylamino)benzenes. At temperatures above — 30 °C the spectra show the presence of a dynamic process interconverting the three equivalent ring positions of the nucleophile.51... 

The accepted reaction mechanism for the electrophilic aromatic nitration was postulated by Ingold in 1969[3] and involves several steps (Scheme 5.1). Firstly, the nitric acid is protonated by a stronger acid (sulfuric). The protonated nitric acid gives water and the nitronium ion (N02+) which is the electrophilic active species for nitration of aromatics. Nitric acid heterolysis is considered to be accelerated by the polarity of the solvent, and solvation of nitronium ion in different media affects its reactivity and the selectivity of the reaction. Combination of nitronium ion and an aromatic molecule form an intermediate named the Wheland complex or er-complex. The loss of a proton from the er-complex gives the aromatic nitrocompound (Scheme 5.1). 

The electrophilic aromatic substitution via sigma (Wheland) complexes, or the Ar-SE reaction, is the classical method for functionalizing aromatic compounds. In this section, we will focus on the mechanistic foundations as well as the preparative possibilities of this process. 

In the first step of the actual Ar-SE reaction, a substituted cyclohexadienyl cation is formed from the electrophile and the aromatic compound. This cation and its derivatives are generally referred to as a sigma or Wheland complex. Sigma complexes are described by at least three carbenium ion resonance forms (Figure 5.1). There is an additional resonance form for each substituent, which can stabilize the positive charge of the Wheland complex by a pi electron-donating (+M) effect (see Section 5.1.3). This resonance form is an all-octet formula. 

On the left side Figure 5.9 shows the primitive model of the charge distribution in the Wheland complex. Therein the positive charges only appear ortho and para to the reacting C atom, and in each case they equal +0.33. This charge distribution is obtained by superimposing the three resonance forms of Figure 5.1. 

There is also some debate over whether nitrations like the one in the last example may alternatively proceed via a nitrosyl cation (NO ) instead of a HN03 molecule as the electrophile. Small amounts of the nitrosyl cation occur in diluted nitric acid and would—via a Wheland complex intermediate—initially lead to a nitrosoaromatic compound (Ar-N=0) as the Ar-SE product. (Remember Figure 5.23 presented a different reaction mode between nitrosyl cations and—less electron-rich—aromatic compounds.) This nitrosoaromatic compound would subsequently undergo rapid oxidation by the diluted nitric acid to finally yield the nitroaromatic compound. 

Electrophilic Aromatic Substitutions via Wheland Complexes ( Ar-SE Reactions )... 

Wheland complexes are high-energy intermediates because they do not contain the conjugated aromatic electron sextet present in the product and in the starting material. Consequently, the formation of these complexes is the rate-determining step of... 

Ar-SE reactions (cf. Figure 5.1). This, in turn, means that Wheland complexes are also a good—even the best—model for the transition state of Ar-SE reactions. 

In a few cases, cations other than the proton are eliminated from the Wheland complex to reconstitute the aromatic system. The ferf-butyl cation (Figure 5.1, X=ferf-Bu) and protonated S03 (Figure 5.1, X=S03H) are suitable for such an elimination. When the latter groups are replaced in an Ar-SE reaction, we have the special case of an ipso substitution. Among other things, ipso substitutions play a role in the few Ar-SE reactions that are reversible (Section 5.1.2). 

According to Section 5.1.1 electrophilic ipso substitutions via Wheland complexes occur, for example, when a proton attacks at the substructure Csp2—ferf-Bu or Csp2—S03H of appropriately substituted aromatic compounds. After expulsion of a ferf-butyl cation or an HSO3 ion, an aromatic compound is obtained, which has been defunctionalized in the respective position. 

Stabilization and Destabilization of Wheland Complexes through Substituent Effects... 

Which Wheland complexes are the most stable This is determined to a small extent by steric effects and to a considerably greater extent by electronic effects As a car-bocation, a substituted Wheland complex is considerably more stable than an unsubstituted one only when it carries one or more donor substituents, and unsubstituted Wheland complexes E—C6Hj are still considerably more stable than Wheland complexes that contain one or more acceptor substituents. Therefore, donor-substituted benzenes are attacked by electrophiles more rapidly than benzene, and acceptor-substituted benzenes are attacked more slowly. 

A more detailed analysis of the stabilizing effect of donor substituents and the destabilizing effect of acceptor substituents (both are referred to as Subst in the following) on Wheland complexes E-QH5 -Subst explains, moreover, the regioselectivity of an Ar-SE attack on a monosubstituted benzene. Isomeric donor-containing Wheland complexes and acceptor-containing Wheland complexes have different stabilities. This follows from the uneven charge distributions in the Wheland complexes. 

Fig. 5.7. Charge distribution in Wheland complexes E-C6H6+ (refined model, on the right calculation for...

Because of completely analogous considerations, every acceptor-substituted Wheland complex E—C6H5—EWG+ is less stable than the reference compound E—C6Hg (Figure 5.9). From this analysis, one derives the following expectations for Ar-SE reactions of acceptor-substituted benzenes ... 

The regioselectivity and reactivity of Ar-SE reactions of naphthalene are explained correctly by comparing the free activation enthalpies for the formation of the Whe-land complexes 1-E—C10Hi"0 and 2-E—C10H 0 from the electrophile and naphthalene and for the formation of the Wheland complex E—C6Hg from the electrophile and benzene, respectively. 

With respect to the reactivitiesthe decisive effect is the following in the formation of either of the two isomeric Wheland complexes from naphthalene, the difference between the naphthalene resonance energy (66 kcal/mol)—which is uplifted—and the benzene resonance energy (36 kcal/mol)—which is maintained—is lost, that is, an amount of only 30 kcal/mol. By contrast, the formation of a Wheland complex from benzene costs the full 36 kcal/mol of the benzene resonance energy. This explains why... 

The regioselectivity of Ar-SE reactions with naphthalene follows from the different stabilities of the Wheland complex intermediate of the 1-attack (Figure 5.10, top) compared with that of the 2-attack (Figure 5.10, bottom). For the Wheland complex with the electrophile at Cl these are five sextet resonance forms. In two of them the aromaticity of one ring is retained. The latter forms are thus considerably more stable than the other three. The Wheland complex with the electrophile at C2 can also be described with five sextet resonance forms. However, only one of them represents an aromatic species. The first Wheland complex is thus more stable than the second. The 1-attack is consequently preferred over the 2-attack. 

In this example the phenyl substituent with its +M effect determines the structure of the most stable Wheland complex intermediate and thus the regioselectivity. The competing +1 effect of the alkyl substituent cannot prevail. This is understandable because it is not as effective at stabilizing an adjacent positive change as the phenyl group (cf. Table 5.3). 

Aryldiazonium salts are weak electrophiles. Consequently, they undergo Ar-SE reactions via Wheland complexes (azo couplings) only with the most strongly activated aromatic compounds. Phenolates and secondary as well as tertiary aromatic amines are therefore solely attacked. Primary aromatic amines react with diazonium salts, too, but via their N atom. Thus, triazenes, that is, compounds with the structure Ar—N=N—NH—Ar are produced. Phenol ethers or nondeprotonated phenols can be attacked by aryldiazonium salts only when the latter are especially good electrophiles, for example, when they are activated by nitro groups in the ortho or para position. 

The reason for both trends is the same the benzyl cations that attack the toluene or the benzene have different stabilities depending on the nature of their para substituent X. When X is the electron acceptor NOz, we have the most electron-deficient cation, whereas when X is the electron donor MeO, we have the most electron-rich cation. The formation of Wheland complexes from p-02N—C6H4—CHj should therefore be exothermic and exergonic. Conversely, the formation of Wheland complexes... 

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