Orientation in nucleophilic aromatic substitution

Our interpretation of reactivity and orientation in nucleophilic aromatic substitution has been based on one all-important assumption that we have not yet justified displacement involves two steps, of which the first one is much slower than the second. 

The significance of obtaining only the 1,3,5-trifluorotrichlorobenzene will become clear in later discussion of orientation of nucleophilic aromatic substitution. However, a higher temperature, permitted by the use of Sulpholan as solvent [44], gave perfluoro-naphthalene from the perchloro compound (Figure 9.18). 

These ideas have been expanded to predict and explain the orientation of nucleophilic aromatic substitution processes for a variety of perfluorinated heteroaromatic systems and the sites of nucleophilic substitution are indicated in Fig. 8.6 for a number of systems studied. Specific examples that confirm this mechanistic analysis are given in subsequent appropriate sections below. 

Chambers, R.D. Close, D. Musgrave, W.K.R. Waterhouse, J.S. Williams, D.L.H. Orienting effects of chlorine substituents in nucleophilic aromatic substitution. J. 

The preceding explanation would seem to explain most of the data in Table 8.21, but there is one apparent discrepancy. We might have expected the methoxy substituent to be electron-donating, but it gives the same product orientation as does trifluoromethyl. This intuitive expectation of the substituent effect of methoxy is based primarily on its influence on electrophilic aromatic substitution (SeAr) and on nucleophilic aromatic substitution (SwAr) reactions, both of which involve attachment of a species to an aromatic ring to form a cr complex. In contrast, the carbanionic intermediates presumed to be formed in the benzyne reaction have the nonbonded pair of electrons in... 

In the discussion of electrophilic aromatic substitution (Chapter 11) equal attention was paid to the effect of substrate structure on reactivity (activation or deactivation) and on orientation. The question of orientation was important because in a typical substitution there are four or five hydrogens that could serve as leaving groups. This type of question is much less important for aromatic nucleophilic substitution, since in most cases there is only one potential leaving group in a molecule. Therefore attention is largely focused on the reactivity of one molecule compared with another and not on the comparison of the reactivity of different positions within the same molecule. 

Not all radical aromatic substitutions are as immune to polar effects as is attack by phenyl. Some radicals reveal marked electrophilic or nucleophilic character. Oxygen-centered radicals, for example, are electrophilic, as would be expected if there is substantial polar contribution to the transition state. Table 9.13 lists partial rate factors for substitution by benzoyl radicals note that the orientation and activation trends found in typical electrophilic substitutions have begun to appear, but are still modest compared with the dramatic effects shown in Table 9.12 for a true heterolytic substitution.179... 

Photonucleophilic substitution may be preparatively useful in view of the peculiar orientation. In several cases direct attack of the nucleophile onto the excited state of the aromatic (SwAr ) occurs (and then orientation can be rationalized on the basis of the MO coefficients in the excited state), but when... 

However, the presence of certain groups at certain positions of the ring markedly activates the halogen of aryl halides toward displacement. We shall have a look at some of these activation effects, and thei. try to account for them on the basis of the chemical principles we have learned. We shall find a remarkable parallel between the two kinds of aromatic substitution, electrophilic and nucleophilic, with respect both to mechanism and to the ways in which substituent groups affect reactivity and orientation. 

When substitution occurs in polyhalogenated aromatic compounds, such as the pentafluorobenzene derivatives, QF5X, the extent of the replacement of F or X by the nucleophile and the product orientation must be determined. 

These systems nitrate aromatie eompounds by a proeess of electro-philie substitution, the eharacter of whieh is now understood in some detail ( 6.1). It should be noted, however, that some of them ean eause nitration and various other reactions by less well understood processes. Among sueh nitrations that of nitration via nitrosation is especially important when the aromatic substrate is a reactive one ( 4.3). In reaetion with lithium nitrate in aeetie anhydride, or with fuming nitrie aeid, quinoline gives a small yield of 3-nitroquinoline this untypieal orientation (ef. 10.4.2 ) may be a eonsequenee of nitration following nucleophilic addition. ... 

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