Reactivity effects Wheland intermediates

The formation of the Wheland intermediate from the ion-radical pair as the critical reactive intermediate is common in both nitration and nitrosation processes. However, the contrasting reactivity trend in various nitrosation reactions with NO + (as well as the observation of substantial kinetic deuterium isotope effects) is ascribed to a rate-limiting deprotonation of the reversibly formed Wheland intermediate. In the case of aromatic nitration with NO, deprotonation is fast and occurs with no kinetic (deuterium) isotope effect. However, the nitrosoarenes (unlike their nitro counterparts) are excellent electron donors as judged by their low oxidation potentials as compared to parent arene.246 As a result, nitrosoarenes are also much better Bronsted bases249 than the corresponding nitro derivatives, and this marked distinction readily accounts for the large differentiation in the deprotonation rates of their respective conjugate acids (i.e., Wheland intermediates). 

A review of methods of synthesis of aromatic iodo compounds has appeared offering considerable information of potential value to research chemists wishing to prepare iodoheterocycles (84RCR343). Iodination differs from chlorination and bromination in that a much less reactive electrophile (and a much larger one) is involved. The second step of the reaction is usually at least partially rate-determining. Isotope effects are noted in the iodination of indole [68AC(R) 1435], and the transition state resembles the Wheland intermediate more than in chlorination and bromination. 

Many reasons may be responsible for the different a )3 ratios observed in the four rings. In particular, the small ar.fi ratios for pyrrole [as well as the low sensitivity of this ring to substituent effects (Section IV, B)] may be due to the fact that in this case the Wheland intermediate is not a good model for the transition state. This hypothesis is in keeping with the Hammond postulate,183 according to which the transition state approaches closer to the unperturbed starting molecule as its reactivity increases. 

The existence of polarizability thus renders impossible any unique scale of electrophilic reactivity. The two most common theoretical measures, namely ir-electron densities and localization energies, correspond to transition states approximating the ground state and the Wheland intermediate, respectively, whereas the transition state (the precise structure of which is unknown), lies somewhere in between, it Densities, which relate to a situation where inductive effects are dominant, will tend to predict a relatively low 2- 3-rate ratio since all of the heteroatoms are inductive acceptors (-/). By contrast, since it electrons are delocalized from the heteroatoms more to the 2- than to the 3-position, localization energies will predict a high 2- 3-rate ratio. The importance of these factors becomes particularly evident in consideration of the substitution of benzo derivatives of these molecules (Chapter 8). 

In contrast to the heteroatom in five-membered heterocycles (Chapter 6), a pyridine nitrogen atom should be able to transmit electronic effects in a manner similar to a CH group in benzene. Difficulty attends assessment of such transmission abilities by comparison of the reactivities of pyridines and benzenes because the Hammett p factor obtained will be a measure of both the transmission ability (64JCS627) and the transition-state charge. Because pyridine is less reactive, the transition state for its reactions should be nearer to the Wheland intermediate than the corresponding transition states for reactions of the corresponding benzene... 

The Wheland intermediates that are formed in reaction 3-36 are important as their pentadienyl cation LUMO (3-10) has the appropriate symmetry for (Whiffen) enhanced hyperconjugation, which is in large part responsible for the high ipso reactivity, and the relative reactivities of compounds C6H5MEt3, compared with benzene, towards electrophiles, as M varies, are approximately (benzene 1), Si, 5 x 104, Ge 106, Sn 5 x 1011, Pb 1020.25 The 4-stannylbenzyltin compounds should further benefit from both the Whiffen effect at the ipso position and the simple C-Sn hyperconjugation at the 4-position (3-11). 

An interesting difference between the homoaryl and heteroaryl compounds is found in the reaction of 2-(tributylstannyl)-furan and -thiophene towards benzyhydryl cations.115 Whereas homoarylstannanes appear always to undergo ipso attack by electrophiles, the relative reactivities at the 2 (ipso) and 5 position in these two hetero-arenes are shown in Scheme 7-2 at both positions the reactivity is increased, but the effect is much larger at the 5-position. If C-Sn hyperconjugation is important in stabilising the Wheland intermediate, this unusual regioselectivity might be taken to imply that here there is an early transition state in which such an effect would be less important. 

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. 

The obtained l3C and 29Si NMR data do not vary significantly with the solvent as long as aromatic hydrocarbons are used. That is the maximum solvent effect on l3C NMR chemical shift, AS l3C w/v, for cation 9a is AS I3C w/v = 0.5 when the solvent is changed from benzene to toluene and the position of the 29Si resonance remains even unchanged. This indicates negligible interaction between the cation and solvent molecules, in particular no Wheland-type intermediates are formed. (38) Solvents other than aromatic hydrocarbons are however reactive towards vinyl cations 8-10 (see below). 

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