The Nitration of Benzene

The nitration of benzene with nitric acid requires sulfuric acid as a catalyst. 

To generate the necessary electrophile, sulfuric acid protonates nitric acid. Protonated nitric acid then loses water to form a nitronium ion, the electrophile required for nitration. 

The mechanism for the electrophilic aromatic substitution reaction is the same as the mechanisms for the electrophilic aromatic substitution reactions we looked at in Section 19.4. 

A base ( B) in the reaction mixture (for example, H2O, HS04, or the solvent) removes the proton from the carbon that formed the bond with the electrophile. 

Solution The only electrophile available is D . Therefore, adds to a ring carbon and H comes off the same ring carbon. The reaction can be repeated at each of the other five ring carbons. 

---

In the nitration of benzene, wj-dinilro- and sym-trinitrobenzenes are obtained under more vigorous conditions. With naphthalene, 1-nitronaphthalene is the first product and further nitration gives a mixture of 1,5- and 1,8-dinitronaphthalenes 2-nitronaphthalene is never obtained. 

Hji function. A better correlation, up to nearly 89% sulphuric acid, is obtained by comparing the results at 25 °C with the acidity function — (/f + log % q). si, 42a, 43a these comparisons a straight line of approximately unit slope is obtained (fig. 2.4), although for the nitration of benzene in acidities greater than 68% sulphuric acid, the slope becomes i-20 (fig. 2.5). 

Rates of nitration in perchloric acid of mesitylene, luphthalene and phenol (57 I-6i-i %), and benzene (57 i-64 4%) have been deter-mined. The activated compounds are considered below ( 2.5). A plot of the logarithms of the second-order rate coefficients for the nitration of benzene against — ( f + log over the range of acidity... 

This consideration prompted an investigation of the nitration of benzene and some more reactive compounds in aqueous sulphuric and perchloric acids, to establish to what extent the reactions of these compounds were affected by the speed of diffusion together of the active species. ... 

Nitration in organic solvents is strongly catalysed by small concentrations of strong acids typically a concentration of io mol 1 of sulphuric acid doubles the rate of reaction. Reaction under zeroth-order conditions is accelerated without disturbing the kinetic form, even under the influence of very strong catalysis. The effect of sulphuric acid on the nitration of benzene in nitromethane is tabulated in table 3.3. The catalysis is linear in the concentration of sulphuric acid. 

In experiments on the nitration of benzene in acetic acid, to which urea was added to remove nitrous acid (which anticatalyses nitration 4.3.1), the rate was found to be further depressed. The effect was ascribed to nitrate ions arising from the formation of urea nitrate. In the same way, urea depressed the rate of the zeroth-order nitration of mesitylene in sulpholan. ... 

TABLE 9.3 The nitration of benzene derivatives containing positively charged substituents ... 

The kinetics of the nitration of benzene, toluene and mesitylene in mixtures prepared from nitric acid and acetic anhydride have been studied by Hartshorn and Thompson. Under zeroth order conditions, the dependence of the rate of nitration of mesitylene on the stoichiometric concentrations of nitric acid, acetic acid and lithium nitrate were found to be as described in section 5.3.5. When the conditions were such that the rate depended upon the first power of the concentration of the aromatic substrate, the first order rate constant was found to vary with the stoichiometric concentration of nitric acid as shown on the graph below. An approximately third order dependence on this quantity was found with mesitylene and toluene, but with benzene, increasing the stoichiometric concentration of nitric acid caused a change to an approximately second order dependence. Relative reactivities, however, were found to be insensitive... 

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... 

Figure 12 3 adapts the general mechanism of electrophilic aromatic substitution to the nitration of benzene The first step is rate determining m it benzene reacts with nitro mum ion to give the cyclohexadienyl cation intermediate In the second step the aro maticity of the ring is restored by loss of a proton from the cyclohexadienyl cation... 

The role of nitronium ion in the nitration of benzene was demonstrated by Sir Christo pher Ingold—the same per son who suggested the SnI and Sn2 mechanisms of nu cleophilic substitution and who collaborated with Cahn and Prelog on the R and S notational system... 

To illustrate substituent effects on rate consider the nitration of benzene toluene and (trifluoromethyl)benzene... 

Nitration (Section 12 3) The active electro phile in the nitration of benzene and its... 

Manufacture and Processing. Mononitrotoluenes are produced by the nitration of toluene in a manner similar to that described for nitrobenzene. The presence of the methyl group on the aromatic ring faciUtates the nitration of toluene, as compared to that of benzene, and increases the ease of oxidation which results in undesirable by-products. Thus the nitration of toluene generally is carried out at lower temperatures than the nitration of benzene to minimize oxidative side reactions. Because toluene nitrates at a faster rate than benzene, the milder conditions also reduce the formation of dinitrotoluenes. Toluene is less soluble than benzene in the acid phase, thus vigorous agitation of the reaction mixture is necessary to maximize the interfacial area of the two phases and the mass transfer of the reactants. The rate of a typical industrial nitration can be modeled in terms of a fast reaction taking place in a zone in the aqueous phase adjacent to the interface where the reaction is diffusion controlled. 

It is interesting to mention here that Dewar and Storch (1989) drew attention to the fact that ion-molecule reactions often lack a transition state barrier in theoretical calculations related to the gas phase, but are known to proceed with measurable activation energy in solution. Szabo et al. (1992) made separate calculations at the ab initio Hartree-Fock 3/21 G level for the geometry of the nitration of benzene with the protonated methyl nitrate by two mechanisms, not involving solvent molecules. Both calculations yielded values for the energy barriers. 

Documenting the lack of an effect can be just as important as the presence of one. Consider the nitration of benzene, an electrophilic substitution process. The use of... 

One of the most extensively studied examples of electrophilic substitution is the nitration of benzene. A mixture of nitric acid and concentrated sulfuric acid converts benzene slowly into nitrobenzene. The actual nitrating agent is the electrophile NQ2+ (the nitronium ion, ONO ), a linear triatomic ion ... 

Detection of an Intermediate. In many cases, an intermediate cannot be isolated but can be detected by IR, NMR, or other spectra. The detection by Raman spectra of NOj was regarded as strong evidence that this is an intermediate in the nitration of benzene (see 11-2). Free radical and triplet intermediates can often be detected by ESR and by CIDNP (see Chapter 5). Free radicals [as well as radical ions and EDA complexes] can also be detected by a method that does not rely on spectra. In this method, a doublebond compound is added to the reaction mixture, and its fate traced. One possible result is cis-trans conversion. For example, cis-stilbene is isomerized to the trans isomer in the presence of RS- radicals, by this mechanism ... 

Burns, J. R., Ramshaw, C., A microreactor for the nitration of benzene and toluene, in Proceedings of the 4th International Conference on Microreaction Technology, IMRET 4, pp. 133-140 (5-9 March 2000), AlChE Topical Conf Proc., Atlanta, USA. 

The nitration of benzene is a standard organic synthesis process, well described in the scientific and patent literature [31, 97],... 

For conventional stirred tank processing of the nitration of benzene, the dependence of conversion on impeller speed is given in [102]. 

Table 4.2 Comparison of conversion and by-product formation for the nitration of benzene in conventional reactors and micro reactor set-ups [31],...

Doku, G. N., Haswell, S. J., McCreedy, T, Greenway, G. M., Electric field-induced mobilisation of multiphase solution systems based on the nitration of benzene in a micro reactor. Analyst 126 (2001) 14-20. 

Nitration can be catalyzed by lanthanide salts. For example, the nitration of benzene, toluene, and naphthalene by aqueous nitric acid proceeds in good yield in the presence of Yb(03SCF3)3.5 The catalysis presumably results from an oxyphilic interaction of nitrate ion with the cation, which generates or transfers the N02+ ion.6 This catalytic procedure uses a stoichiometric amount of nitric acid and avoids the excess strong acidity associated with conventional nitration conditions. 

The presence of N02, the nitronium ion, both in this solution and in a number of salts (some of which, e.g. NOz C104e, have actually been isolated) has been confirmed spectroscopically there is a line in the Raman spectrum of each of them at 1400 cm"1 which can only originate from a species that is both linear and triatomic. Nitric acid itself is converted in concentrated sulphuric acid virtually entirely into N02, and there can be little doubt left that this is the effective electrophile in nitration under these conditions. If the purpose of the sulphuric acid is merely to function as a highly acid medium in which NOz can be released from HO—N02, it would be expected that other strong acids, e.g. HC104, would also promote nitration. This is indeed found to be the case, and HF plus BF3 are also effective. The poor performance of nitric acid by itself in the nitration of benzene is thus explained for it contains but little N02 the small amount that is present is obtained by the two-stage process... 

Doku GN, Haswell SJ, McCreedy T, Greenway GM (2001) Electric Field-Induced Mobilisation of Multiphase Solution Systems Based on the Nitration of Benzene in a Microreactor. Analyst 126 14-20... 

The difficulty of nitration increases progressively with the number of nitro-groups introduced. Already the introduction of a second nitro-group into nitrobenzene requires much more powerful reagents than the nitration of benzene itself. Symmetrical trinitrobenzene is formed only after several days boiling of the dinitro-compound with fuming nitric add and even then only in poor yield. 

---