For electrophilic aromatic

If the Lewis base ( Y ) had acted as a nucleophile and bonded to carbon the prod uct would have been a nonaromatic cyclohexadiene derivative Addition and substitution products arise by alternative reaction paths of a cyclohexadienyl cation Substitution occurs preferentially because there is a substantial driving force favoring rearomatization Figure 12 1 is a potential energy diagram describing the general mechanism of electrophilic aromatic substitution For electrophilic aromatic substitution reactions to... 

Now that we ve outlined the general mechanism for electrophilic aromatic substitution we need only identify the specific electrophile m the nitration of benzene to have a fairly clear idea of how the reaction occurs... 

Scheme 10.2. Generalized Mechanism for Electrophilic Aromatic Substitution...

At this point, attention can be given to specific electrophilic substitution reactions. The kinds of data that have been especially useful for determining mechanistic details include linear ffee-energy relationships, kinetic studies, isotope effects, and selectivity patterns. In general, the basic questions that need to be asked about each mechanism are (1) What is the active electrophile (2) Which step in the general mechanism for electrophilic aromatic substitution is rate-determining (3) What are the orientation and selectivity patterns ... 

Figure 12.1 is a potential energy diagram describing the general mechanism of electrophilic aromatic substitution. For electrophilic aromatic substitution reactions to... 

FIGURE 12.1 Potential energy diagram for electrophilic aromatic substitution. 

Resole syntheses entail substitution of formaldehyde (or formaldehyde derivatives) on phenolic ortho and para positions followed by methylol condensation reactions which form dimers and oligomers. Under basic conditions, pheno-late rings are the reactive species for electrophilic aromatic substitution reactions. A simplified mechanism is generally used to depict the formaldehyde substitution on the phenol rings (Fig. 7.21). It should be noted that this mechanism does not account for pH effects, the type of catalyst, or the formation of hemiformals. Mixtures of mono-, di-, and trihydroxymethyl-substituted phenols are produced. 

The frontier orbital theory was developed for electrophilic aromatic substitution (Chapter Elements of a Chemical Orbital Theory by Inagaki in this volume). Application is successful to the ortho-para orientation (Scheme 23a) for the benzenes substituted with electron donating groups. The ortho and para positions have larger HOMO amplitudes. The meta orientation (Scheme 23b) for the electron accepting groups is under control of both HOMO and the next HOMO [25]. 

A second group of aromatic substitution reactions involves aryl diazonium ions. As for electrophilic aromatic substitution, many of the reactions of aromatic diazonium ions date to the nineteenth century. There have continued to be methodological developments for substitution reactions of diazonium intermediates. These reactions provide routes to aryl halides, cyanides, and azides, phenols, and in some cases to alkenyl derivatives. 

The mechanism for electrophilic aromatic substitution is addition-elimination. Using these working hypotheses, Mills and Nixon explained the regioselectivity of electrophilic substitution in 5-hydroxyindan versus 6-hydroxytetralin. 

The X-ray structure of the dibromine complex with toluene (measured at 123 K) is more complicated, and shows multiple crystallographically independent donor/acceptor moieties [68]. Most important, however, is the fact that in all cases the acceptor shows an over-the-rim location that is similar to that in the benzene complex. In both systems, the acceptor is shifted by 1.4 A from the main symmetry axis, the shortest Br C distances of 3.1 A being significantly less than the sum of the van der Waals radii of 3.55 A [20]. Furthermore, the calculated hapticity in the benzene/Br2 complex (x] = 1.52) is midway between the over-atom (rj = 1.0) and over-bond (rj = 2.0) coordination. In the toluene complex, the latter varies from rj = 1.70 to 1.86 (in four non-equivalent coordination modes) and thus lies closer to the over-bond coordination model. Moreover, the over-bond bromine is remarkably shifted toward the ortho- and para-carbons that correspond to the positions of highest electron density (and lead to the transition states for electrophilic aromatic bromination [12]). Such an experimental location of bromine is in good agreement with the results of high level theoretical... 

More than just a few parameters have to be considered when modelling chemical reactivity in a broader perspective than for the well-defined but restricted reaction sets of the preceding section. Here, however, not enough statistically well-balanced, quantitative, experimental data are available to allow multilinear regression analysis (MLRA). An additional complicating factor derives from comparison of various reactions, where data of quite different types are encountered. For example, how can product distributions for electrophilic aromatic substitutions be compared with acidity constants of aliphatic carboxylic acids And on the side of the parameters how can the influence on chemical reactivity of both bond dissociation energies and bond polarities be simultaneously handled when only limited data are available ... 

The electron-transfer mechanism for electrophilic aromatic nitration as presented in Scheme 19 is consistent with the CIDNP observation in related systems, in which the life-time of the radical pair [cf. (87)] is of particular concern (Kaptein, 1975 Clemens et al., 1984, 1985 Keumi et al., 1988 Morkovnik, 1988 Olah et al., 1989 Johnston et al., 1991 Ridd, 1991 Rudakov and Lobachev, 1991). As such, other types of experimental evidence for aromatic cation radicals as intermediates in electrophilic aromatic nitration are to be found only when there is significant competition from rate processes on the timescale of r<10 los. For example, the characteristic C-C bond scission of labile cation radicals is observed only during the electrophilic nitration of aromatic donors such as the dianthracenes and bicumene analogues which produce ArH+- with fragmentation rates of kf> 1010s-1 (Kim et al., 1992a,b). 

The nitration reagents (NO2 Y) for electrophilic aromatic nitration span a wide range and contain anions Y such as nitric acid (Y = OH-), acetyl nitrate (Y = OAc-), dinitrogen pentoxide (Y = NO3-), nitryl chloride (Y = Cl-), TV-nitropyridinium (Y = pyridine) and tetranitromethane [Y = C(N02)3-]. All reagents contain electron-deficient species which can serve as effective electron acceptors and form electron donor-acceptor (EDA) complexes with electron-rich donors including aromatic hydrocarbons107 (ArH, equation 86). Excitation of the EDA complexes by irradiation of the charge-transfer (CT) absorption band results in full electron transfer (equation 87) to form radical ion... 

Because the initial electrophilic attack and carbocation formation results in loss of aromatic stabilization, the electrophiles necessary for electrophilic aromatic substitution must be more reactive than those that typically react with alkenes. Thus, chlorination or... 

The empirical data for electrophilic aromatic substitution on benzocycloalkenes over a variety of reactions and conditions show a consistent trend of increased Cp selectivity due primarily to C deactivation, with some indication that Cp activation occurs in benzobicycloalkenes. Acidity work on the benzocycloalkenes and related pyridines demonstrates clearly the extent of deactivation. The rehybridization model of Finnegan and Streitweiser has been postulated to account for the deactivation. Thummel s correlation of C y -H P a provided the necessary link between rehybridization and deactivation. Theories involving bond fixation in the Wheland intmnediate deserve some further consideration but are not essential to an understanding of the present empirical data. 

For example, we recall discussions of o- and p-directing vs m-directing groups for electrophilic aromatic substitution, the importance of o- andp-quinonoid resonance structures vs the irrelevance of m-quinonoid long bonded resonance structures for stabilization of push-pull disubstituted benzenes. 

A priori, the two most likely mechanisms for electrophilic aromatic substitution on benzene, in the absence of strong base,156 are (1) direct displacement, the transition state for which is shown in 65, and (2) a two-step reaction in which... 

Nitronium Ion (N02+). Nitration is one of the most studied and best understood organic reactions.510-512 The species responsible for electrophilic aromatic nitration was shown to be the nitronium ion (N02+) 219. Since the early 1900s, extensive efforts have been directed toward the identification of this ion, whose existence was first shown by Hantzsch and later firmly established by Ingold and Hughes.510... 

With respect to iron catalysts, iron(III) chloride is one of the most common catalysts known for electrophilic aromatic substitutions and has been widely used in the past. In genera], it is an inexpensive and eco-friendly reagent featuring a higher catalytic activity than other metal chlorides [5, 6]. 

Reference should also be made to a superdelocalizability index Sp derived within the frame of the simple FEMO model [35], Goodness of fit of correlations of SfE values with relative rate constants for electrophilic aromatic substitution was found to be comparable with those based on CNDO/2 calculations. 

Chloromethylation.1 Chloromethyl methyl ether has been generally used for electrophilic aromatic chloromethylation, but it is highly toxic and now considered a carcinogen. Chloromethylation can be effected by use of a trimethylsilyl ether (1) of a chlorohydrin prepared as shown from trioxane and chlorotrimethylsilane in the presence of stannic chloride in chloroform. This reagent, generated in situ, is effective for chloromethylation of styrene in the presence of SnCl4 any excess is easily decomposed by hydrolysis. Bromomethylation is possible by replacement of ClSi(CH3)3 by BrSi(CH3)3. 

The most widely accepted mechanism for electrophilic aromatic substitution involves a change from sp2 to sps hybridization of the carbon under attack, with formation of a species (the Wheland or a complex) which is a real intermediate, i.e., a minimum in the energy-reaction coordinate diagram. In most of cases the rate-determining step is the formation of the a intermediate in other cases, depending on the structure of the substrate, the nature of the electrophile, and the reaction conditions, the decomposition of such an intermediate is kinetically significant. In such cases a positive primary kinetic isotope effect and a base catalysis are expected (as Melander43 first pointed out). 

The same workers590,591 also showed that, in the Pd(II)-catalyzed acetoxylation of substituted arenes, a complete reversal of the usual pattern of isomer distribution for electrophilic aromatic substitution or anodic oxidation of aromatics is observed. To explain these results it was suggested that acetoxylation by Pd(OAc)2 takes place via the following addition-elimination sequence ... 

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