Electrophilic substitution mechanism

As we ve seen, aromatic substitution reactions usually occur by an electrophilic mechanism. Aryl halides that have electron-withdrawing substituents, however, can also undergo nucleophilic aromatic substitution. For example. 2,4,6-trinitrochlorobenzene reacts with aqueous NaOH at room temperature to give 2,4,6-trinitrophenol. The nucleophile OH- has substituted for Cl-. 

The mechanism of substitution on an electron-rich benzene ring is electrophilic substitution, electrophilic attack on an atom and the replacement of one atom by another or by a group of atoms. The fact that substitution occurs rather than addition to the double bonds can be traced to the stability of the delocalized 7T-electrons in the ring. Delocalization gives the electrons such low energy—that is, they are bound so tightly—that they are unavailable for forming new cr-bonds (see Sections 2.7 and 3.12). 

The Sgl mechanism substitution electrophilic unimolecular) is rare, being found only in certain cases in which carbon is the leaving atom (see 11-37,11-38) or when a very strong base is present (see 11-1,11-11, and 11-42). It consists of two steps with an intermediate carbanion. The lUPAC designation is Dg + Ag. 

With respect to R this is of course electrophilic substitution. The mechanism is usually Sgl. 

The first product is derived from a normal electrophilic aromatic substitution reaction of the kind described in the text. The second product is derived from ipso electrophilic aromatic substitution. The mechanism is exactly the same, but in the last step z-Pr+ is lost instead of H+. 

This chapter is concerned with reactions that introduce or replace substituent groups on aromatic rings. The most important group of reactions is electrophilic aromatic substitution. The mechanism of electrophile aromatic substitution has been studied in great detail, and much information is available about structure-reactivity relationships. There are also important reactions which occur by nucleophilic substitution, including reactions of diazonium ion intermediates and metal-catalyzed substitution. The mechanistic aspects of these reactions were discussed in Chapter 10 of Part A. In this chapter, the synthetic aspects of aromatic substitution will be emphasized. 

Bromination and chlorination of alkanes and cycloalkanes can also take place by an electrophilic mechanism if the reaction is catalyzed by AgSbF. "2 Direct chlorination at a vinylic position by an electrophilic mechanism has been achieved with benzenescleninyl chloride PhSe(0)Cl and AIC13 or AIBr3. n However, while some substituted alkenes give high yields of chloro substitution products, others (such as styrene) undergo addition of Cl2 to the double bond (5-26).113 Electrophilic fluorination has already been mentioned (p. 690). 

In analogy to the traditional terms SW1 and Sw2, which refer to the extreme aliphatic substitution mechanisms, workers in the field of electrophilic substitution refer to S 1 (for substitution-electrophilic-unimolecular) and SE2 (substitution-electrophilic-bimolecular) mechanisms. Equations 4.40 and 4.41... 

The nomenclature used to describe this mechanism is not a subject of controversy, and all workers3-6 have used the symbol SE1 that is substitution, electrophilic, unimolecular. The unimolecular process referred to is the elementary reaction (1). 

Even now, there are two further limiting cases, for if k equilibrium constant for complex formation. Experimentally it will be a matter of extreme difficulty to distinguish either of these possibilities from mechanism SE2(open) or SE2 (cyclic), since all of these mechanisms require the reaction to follow second-order kinetics. Indeed, Reutov4 appears to include a situation such as (7), if the complex is present but in very low concentration, under the mechanistic title of SE2. This is also the nomenclature used by Traylor and co-workers11, but Abraham and Hill5 refer to such a situation as SEC (substitution, electrophilic, via co-ordination). 

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. 

Because metal ions are electrophiles, a reaction of this type is known as electrophilic substitution (the mechanism may be described as SE1 or SE2). In this reaction, the ligands are transferred from one metal to another, which is equivalent to one metal replacing the other. This type of reaction is much less common than the nucleophilic substitution reactions that will be considered in this section. 

Both acid and base catalysis have been used extensively to catalyze exchange in aromatic, and to a lesser extent, heterocyclic molecules. In acid exchange, the most widely used catalysts are sulfuric acid,122,129, 131 phosphoric acid,132 trifluoroacetic acid5133 perchloric acid,134 aluminum chloride,135 and the phosphoric acid-boron trifluoride complex.132 These reactions constitute the simplest electrophilic substitution. The mechanism for such substitution in benzenoid compounds is now comparatively well understood 122 however, the problem of heteroaromatic electrophilic substitution is still being clarified and has led to renewed interest in acid-catalyzed exchange in heterocyclic compounds.122... 

The orientation of addition of iodine chloride to butadiyne, however, corresponds to an electrophilic attack. A study of the kinetics of bromination of various mono- and dialkyl-substituted butadiynes has been interpreted in terms of an electrophilic mechanism . The observed rates increased with increasing inductive electron-releasing power of the substituents. However, the effects are small, and under the conditions used (two-fold excess of hydrocarbon) it seems likely that significant polybromination occurred . Marked catalysis by bromide ion was observed and interpreted in terms of electrophilic attack by bromine on a complex of acetylene with Br ... 

It is interesting to compare the reaetion schemes for the titanium derivatives with these proposed for eyclopentadienyliron dicarbonyls. In both cases C5H5 transfer occurs. In the former case the electron-deficient compound is the substrate, in the latter case the substrate is the electron donor. Thus ligand transfer from the titanium is a nucleophilic substitution, whereas the similar reaction for the iron derivatives can be described in terms of electrophilic substitution. The latter conclusion is in agreement with the results of Cramer (S5), w ho has suggested that CO substitution by halogens in the above-mentioned iron eomplexes follows an electrophilic mechanism 218, 219). 

The mechanism of these substitution reactions can be readily rationalized in a manner which completely parallels the accepted electrophilic mechanism of benzene and other aromatic systems. The electrophile, R", adds to the cyclobutadiene ligand to produce the 7r-allyl-Fe(CO)3 cationic intermediate (XVI) loss of a proton from this intermediate generates the substituted cyclobutadiene -Fe(CO)3 complex. We have previously isolated salts of the 7r-allyl-iron tricarbonyl cation (XVII), as well... 

For a discussion of the mechanism, see Taylor, R. Electrophilic Aromatic Substitution, Electrophilic Aromatic Substitution, Wiley, NY, 1990, pp. 188-213. 

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. 

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