Ipso carbon substitution

The general mechanism for electrophilic substitution suggests that groups other than hydrogen could be displaced, provided the electrophile attacked at the substituted carbon. Substitution at a site already having a substituent is called ipso substitution and has been observed in a number of circumstances. The ease of removal of a substituent depends on its ability to accommodate a positive charge. This fector determines whether the newly attached electrophile or the substituent is eliminated from the [Pg.588]

In the solid state NMR study, uncomplexed phenyllithium, assumed to be a tetramer, as well as the TMEDA complexed dimer and the PMDTA complexed monomer were investigated. Both Li and Li isotopes were used in the preparations. The C spectra of the complexes are presented in Figure 12. It is evident that the substitution of Li with Li has profound effects on the Unewidths, especially of the ipso-carbon at ca 180 ppm in the aggregated uncomplexed system (Figure 12a and 12b, respectively). This is in accordance with the previously mentioned study of methyllithium. However, even the other positions are affected by the dipolar couplings to the four quadrupolar lithium cations, but to a lesser extent due to the larger C-Li distances. 

In the case of insertion toward fluorine (41), there is an even greater amount of positive-positive charge repulsion between the ortho and ipso carbons than in the transition state and this effect is responsible, in part, for a higher activation barrier for insertion toward F to form 41 than away from fluorine to form 40. Therefore, the origin of the pronounced influence of ortho,ortho-difluoro substitution on the lifetime of singlet arylnitrene and the increased activation energy of its cyclization is the result of combination of the steric effect and the extraordinary electronegativity of fluorine atom. 

Attack at the substituted (ipso) carbon evidently does occur, but it does not lead directly to substitution products because demethylation, unlike deprotonation, does not occur ... 

Hydroxylation of arylamines with persulfate ion, or Boyland-Sims oxidation, gives ortho-substituted aminophenols in good yields [29]. As with the Elbs oxidation, the procedure is also carried out in two steps - first, treatment with the oxidant to obtain an aminophenyl sulfate ester and, second, hydrolysis to obtain the final product. Primary, secondary and tertiary amines can all be used in this reaction. The ortho product is formed, except when no ortho-positions are available, which leads to para-substitution. Electrophilic attack on the ipso-carbon is believed to be the most likely mechanism, although minor radical pathways also seem to be present. 

The chemistry involved in nucleophilic aromatic substitution is well reflected in the reactions of a variety of nucleophiles with methyl penta-fluorophenyl ether (Ingemann et al 1982a). For most of the nucleophiles such as alkoxide, thiolate, enolate and (un)substituted allyl anions, the dominant reaction channel is the attack upon the fluoro-substituted carbon atoms, as is the case for OH-. The latter ion reacts approximately 75% by attack upon the fluoro-substituted carbon atoms and the remaining 25% by Sn2 (20%) and ipso (5%) substitution as summarized in (41). In the attack upon the fluorinated carbon atoms, the interesting observation is made that a F- ion is displaced via an anionic o-complex to form a F- ion/molecule complex, which is not observed to dissociate into F- as a free ionic product. 

Now the charge is delocalized to the three carbon atoms that do not include the ipso carbon and no G conjugation from the alkyl group is possible. The situation is no worse than that of benzene, but toluene reacts some 103 faster than benzene at the ortho and para positions. The stability of the transition states for electrophilic attack on toluene can again be modelled on these intermediates, so they follow the same pattern. The transition states for ortho and para attack have some positive charge at the ipso carbon but that for mefa substitution does not. 

Some differences in the change of 13C NMR chemical shifts of nitrobenzothiazoles compared with nitrobenzimidazoles and nitrobenzoxazoles have been discussed. In Table 3.30 the 13C NMR chemical shifts of nitrobenzothiazoles are presented. The nitro group introduction into position 2 leads to a 10 ppm down field shift of the ipso-carbon resonance, whereas a similar effect of the ipso-substitution in the phenylene fragment of benzothiazoles is 20 ppm [778-781], The results of regression analysis of the 13C NMR chemical shifts of benzothiazoles in terms of the inductive and resonance constants of substituents (F and R, c, and cR, c, and aR°) provide evidence for the fact that the substituent effect transmission from positions 2-6 is approximately 30% weaker than in the opposite direction [779], As stated previously, an analogous picture is observed for benzimidazoles. 

Aromatics. Alkyl substitution, as in toluene (3-35), has its major (a) effect on the ipso carbon. Because this carbon has no attached proton, its relaxation time is much longer than... 

The propensity for C-N vs. N-H activation correlates well with substituent Hammet parameters groups that increase the basicity of aniline increase the relative rate of N-H activation, suggesting that nucleophilic attack by the amine at an empty d /dy orbital of Ta(silox)3 preceeds oxidative addition. On the other hand, electron-withdrawing substituents decrease the rate of N-H activation and increase the rate of C-N activation, similarly to the effects observed on electrophilic aromatic substitution. Nucleophilic attack by the filled d a orbital of Ta(silox)3 is expected to occur at the arylamine ipso carbon preceding C-N oxidative addition. The carbon-heteroatom cleavages can be accomodated by mechanisms using both electrophilic and nucleophilic sites on the metal center. 

The same type of reactivity patterns was observed in the case of the 0-phenylation of alcohols by tetraphenylbismuthonium trifluoroacetate under neutral or acidic conditions. These observations led to the conclusion that these reactions of 0-phenylation of alcohols and phenols are better explained by an aromatic Sn2 substitution, involving nucleophilic attack of the bismuth-bearing aromatic carbon by the hydroxyl function of the substrate. The electron-withdrawing trifluoroacetoxy substituent induces a partial positive charge on the ipso carbon, which facilitates the substitution.24,51... 

The oxazoline-substituted bismuthine imide has a distorted trigonal bipyr-amidal structure, bearing three ipso carbon atoms at equatorial sites and two nitrogen atoms at apical sites with a Bi-N(imide) bond length of 2.13( 1) A and... 

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