Electrophilic Nitration Mechanism

In a sulfuric-nitric mixture the protonation of nitric acid occurs at the expense of a stronger sulfuric acid. 

Except for nitric acid and the nitrated mixture, the nitration of aromatic compounds can be carried out with nitronium salts as well [12], 

Olah et al. have found out that the reaction rates on the nitration with nitronium salts are in good agreement with the stability of ir-complexes [6, 13-16], On this basis the authors have assumed that the nitronium salts serve as the nitrating agent the stage limiting the reaction rate is the formation of ir-complcx (Fig. 2) that is rather uncommon in aromatic substitution. 

These works have caused intensive polemic discussed in detail in a review [12] and a monograph [24], 

Ross et al. have reported some discrepancy between the experimental data and generally accepted mechanism of nitration [18-20], The authors paid special attention to the participation of the radical cation of the aromatic substrate during nitration. It has been shown [20] that in the gas phase the nitronium cation does not act as a nitrating 

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Figure 16.4 The mechanism of electrophilic nitration of an aromatic ring. An electrostatic potential map of the reactive electrophile N02+ shows that the nitrogen atom is most positive (blue).

Recently, nitration of organolithiums and Grignards with N204 has been developed for the preparation of certain kinds of nitro compounds (Eqs. 2.14 and 2.15).31 The success of this process depends on the reaction conditions (low temperature) and the structure of substrates. For example, 3-nitrothiophene can be obtained in 70% overall yield from 3-bromothiophene this is far superior to the older method. 3-Nitroveratrole cannot be prepared usefully by classical electrophilic nitration of veratrole, but it can now be prepared by direct o>7/ o-lithiation followed by low-temperature N204 nitration. The mechanism is believed to proceed by dinitrogen tetroxide oxidation of the anion to a radical, followed by the radical s combination. 

Thermal (electrophilic) and photochemical (charge-transfer) nitrations share in common the rapid, preequilibrium formation of the EDA complex [ArH, PyNO ]. Therefore let us consider how charge-transfer activation, as established by the kinetic behaviour of the reactive triad in Scheme 12, relates to a common mechanism for electrophilic nitration. Since the reactive intermediates pertinent to the thermal (electrophilic) process, unlike those in its photochemical counterpart, cannot be observed directly, we must rely initially on the unusual array of nonconventional nitration products (Hartshorn, 1974 Suzuki, 1977) and the unique isomeric distributions as follows. 

Finally, we ask, if the reactive triads in Schemes 1 and 19 are common to both electrophilic and charge-transfer nitration, why is the nucleophilic pathway (k 2) apparently not pertinent to the electrophilic activation of toluene and anisole One obvious answer is that the electrophilic nitration of these less reactive [class (ii)] arenes proceeds via a different mechanism, in which N02 is directly transferred from V-nitropyridinium ion in a single step, without the intermediacy of the reactive triad, since such an activation process relates to the more conventional view of electrophilic aromatic substitution. However, the concerted mechanism for toluene, anisole, mesitylene, t-butylbenzene, etc., does not readily accommodate the three unique facets that relate charge-transfer directly to electrophilic nitration, viz., the lutidine syndrome, the added N02 effect, and the TFA neutralization (of Py). Accordingly, let us return to Schemes 10 and 19, and inquire into the nature of thermal (adiabatic) electron transfer in (87) vis-a-vis the (vertical) charge-transfer in (62). 

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). 

Suzuki, H. and Mori, T. Unusual isomer distribution of dinitrobenzenes and nitrophenols formed as side products during the ozone-mediated nitration of benzene with nitrogen dioxide - further evidence for the alternative mechanism of electrophilic nitration of arenes. J. Chem. Soc., Perkin Trans. 2, 1995, 41 44. 

Abstract Synthesis methods of various C- and /V-nitroderivativcs of five-membered azoles - pyrazoles, imidazoles, 1,2,3-triazoles, 1,2,4-triazoles, oxazoles, oxadiazoles, isoxazoles, thiazoles, thiadiazoles, isothiazoles, selenazoles and tetrazoles - are summarized and critically discussed. The special attention focuses on the nitration reaction of azoles with nitric acid or sulfuric-nitric acid mixture, one of the main synthetic routes to nitroazoles. The nitration reactions with such nitrating agents as acetylnitrate, nitric acid/trifluoroacetic anhydride, nitrogen dioxide, nitrogen tetrox-ide, nitronium tetrafluoroborate, V-nitropicolinium tetrafluoroborate are reported. General information on the theory of electrophilic nitration of aromatic compounds is included in the chapter covering synthetic methods. The kinetics and mechanisms of nitration of five-membered azoles are considered. The nitroazole preparation from different cyclic systems or from aminoazoles or based on heterocyclization is the subject of wide speculation. The particular section is devoted to the chemistry of extraordinary class of nitroazoles - polynitroazoles. Vicarious nucleophilic substitution (VNS) reaction in nitroazoles is reviewed in detail. 

Electron-transfer mechanism in electrophilic nitration of activated heteroaromatic compounds 87ACR53 88UK254. 

Isotope Effects. If the hydrogen ion departs before the arrival of the electrophile (Sgl mechanism) or if the arrival and departure are simultaneous, there should be a substantial isotope effect (i.e., deuterated substrates should undergo substitution more slowly than non-deuterated compounds) because, in each case, the C—H bond is broken in the rate-determining step. However, in the arenium ion mechanism, the C—H bond is not broken in the ratedetermining step, so no isotope effect should be found. Many such studies have been carried out and, in most cases, especially in the case of nitrations, there is no isotope effect. This result is incompatible with either the SeI or the simultaneous mechanism. 

Electrophilic nitration and nitrosation of aromatics are fundamental synthetic organic reactions and are well understood in terms of mechanism/ On the other hand, similar nitration and nitrosation of alkanes were only studied in the 1970s and 1980s. 

The ease and predominant formation of the tertiary bridgehead 1-nitroadamantane in the electrophilic nitration of the rigid cage hydrocarbon clearly Indicates the suggested mechanism since no "backside" attack is possible through the cage con iound. 

Annulene undergoes addition reactions with bromine or with maleic anhydride thus its simple chemistry differs markedly from that of benzene [16]. Under special conditions it gives reactions which provide products typical of electrophilic substitution, but these reactions may not proceed by straightforward electrophilic substitution mechanisms. Thus it may be acetylated with acetic anhydride - boron trifluoride [52], and nitrated with copper(ll) nitrate in acetic anhydride, giving a mixture of dinitro-isomers [52,53]. Pyridinium bromide perbromide provided either monobromo-... 

The mechanism of aromatic aulphonation may be similar to that previously described for nitration and halogenation, involving attack of the electrophilic... 

Nitration can be effected under a wide variety of conditions, as already indicated. The characteristics and kinetics exhibited by the reactions depend on the reagents used, but, as the mechanisms have been elucidated, the surprising fact has emerged that the nitronium ion is preeminently effective as the electrophilic species. The evidence for the operation of other electrophiles will be discussed, but it can be said that the supremacy of one electrophile is uncharacteristic of electrophilic substitutions, and bestows on nitration great utility as a model reaction. 

Another reason for discussing the mechanism of nitration in these media separately from that in inert organic solvents is that, as indicated above, the nature of the electrophile is not established, and has been the subject of controversy. The cases for the involvement of acetyl nitrate, protonated acetyl nitrate, dinitrogen pentoxide and the nitronium ion have been advocated. 

Despite the fact that solutions of acetyl nitrate prepared from purified nitric acid contained no detectable nitrous acid, the sensitivity of the rates of nitration of very reactive compounds to nitrous acid demonstrated in this work is so great that concentrations of nitrous acid below the detectable level could produce considerable catalytic effects. However, because the concentration of nitrous acid in these solutions is unknown the possibility cannot absolutely be excluded that the special mechanism is nitration by a relatively unreactive electrophile. Whatever the nature of the supervenient reaction, it is clear that there is at least a dichotomy in the mechanism of nitration for very reactive compounds, and that, unless the contributions of the separate mechanisms can be distinguished, quantitative comparisons of reactivity are meaningless. 

If acetoxylation were a conventional electrophilic substitution it is hard to understand why it is not more generally observed in nitration in acetic anhydride. The acetoxylating species is supposed to be very much more selective than the nitrating species, and therefore compared with the situation in (say) toluene in which the ratio of acetoxylation to nitration is small, the introduction of activating substituents into the aromatic nucleus should lead to an increase in the importance of acetoxylation relative to nitration. This is, in fact, observed in the limited range of the alkylbenzenes, although the apparently severe steric requirement of the acetoxylation species is a complicating feature. The failure to observe acetoxylation in the reactions of compounds more reactive than 2-xylene has been attributed to the incursion of another mechan-104... 

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