Nitration, of benzene

Helpful Hint i-, g benzene ring donates an electron pair to the terminal bromine, forming the An electrostatic potential arenium ion and neutralizing the formal positive charge on the other bromine. 

A proton is removed from the arenium ion to form bromobenzene and regenerate the catalyst. 

The mechanism of the chlorination of benzene in the presence of ferric chloride is analogous to the one for bromination. 

Fluorine reacts so rapidly with benzene that aromatic fluorination requires special conditions and special types of apparatus. Even then, it is difficult to limit the reaction to mono-fluorination. Fluorobenzene can be made, however, by an indirect method that we shall see in Section 20.7D. 

Iodine, on the other hand, is so unreactive that a special technique has to be used to effect direct iodination the reaction has to be carried out in the presence of an oxidizing agent such as nitric acid  

Controlled fluorination of benzene is difficult, but it can be accomplished by a two-step thallation procedure. Benzene reacts with thallium tris(trifluoroacetate), TI(0C0CF3)3, to give an organothallium intermediate. Further reaction with potassium fluoride and boron trifluoride gives the aryl fluoride. Propose a mechanism for the first step, the thallation of benzene. 

Thallation reactions are potentially useful, but organothallium compounds are highly 

Benzene reacts with hot, concentrated nitric acid to give nitrobenzene. This sluggish reaction is not convenient because a hot mixture of concentrated nitric acid with any oxidizable material might explode. A safer and more convenient procedure uses a mixture of nitric acid and sulfuric acid. Sulfuric acid is a catalyst, allowing nitration to take place more rapidly and at lower temperatures. 

The mechanism is shown next Sulfuric acid reacts with nitric acid to form the nitronium ion ( N02), a powerful electrophile. The mechanism is similar to other sulfuric acid-catalyzed dehydrations. Sulfuric acid protonates the hydroxyl group of nitric acid, allowing it to leave as water and form a nitronium ioa The nitronium ion reacts with benzene to form a sigma complex. Loss of a proton from the sigma complex gives nitrobenzene. 

Nitric acid has a hydroxyl group that can protonate and leave as water, similar to the dehydration of an alcohol. 

Similar to the alkylation and the chlorination of benzene, the nitration reaction is an electrophilic substitution of a benzene hydrogen (a proton) with a nitronium ion (NO ). The liquid-phase reaction occurs in presence of both concentrated nitric and sulfuric acids at approximately 50°C. Concentrated sulfuric acid has two functions it reacts with nitric acid to form the nitronium ion, and it absorbs the water formed during the reaction, which shifts the equilibrium to the formation of nitrobenzene  

Most of the nitrobenzene (=97%) produced is used to make aniline. Other uses include synthesis of quinoline, benzidine, and as a solvent for cellulose ethers. 

Aniline (aminobenzene) is an oily liquid that turns brown when exposed to air and light. The compound is an important dye precursor. 

The main process for producing aniline is the hydrogenation of nitrobenzene  

The hydrogenation reaction occurs at approximately 270°C and slightly above atmospheric over a Cu/Silica catalyst. About a 95% yield is obtained. 

Based on Hammond s postulate, does the structure of the transition state for formation of the carbocation intermediate more closely resemble benzene or cyclohexadienyl cation  

With this as background, we ll examine each of the electrophilic aromatic substitutions presented in Table 12.1 in more detail, especially with respect to the electrophile that reacts with benzene. 

Having outlined the general mechanism for electrophilic aromatic substitution, we need only identify the specific electrophile in the nitration of benzene to have a fairly clear idea of how the reaction occurs. 

The role of nitronium ion in the nitration of benzene was demonstrated by Sir Christopher Ingold—the same person who suggested the S l and 8 2 mechanisms of nucleophilic substitution and who collaborated with Cahn and Prelog on the R and S notational system. 

Electrostatic potential map of nitronium ion (NO2+). The positive charge is concentrated on nitrogen. 

The electrophile (E ) that reacts with benzene is nitronium ion ( NOi). The concentration of nitronium ion in nitric acid alone is too low to nitrate benzene at a convenient rate, but can be increased by adding sulfuric acid. 

CHAPTER TWELVE Reactions of Arenes Electrophilic Aromatic Substitution 

Nitration of the ring is not limited to benzene alone, but is a general reaction of compounds that contain a benzene ring. It would be a good idea to write out the answer to the following problem to ensure that you understand the relationship of starting materials to products in aromatic nitration before continuing to the next section. 

Nitroaromatic compounds are useful in synthesis because converting the nitro (-N02) group to an amino (-NH2) group is relatively easy. For example, the reaction of nitrobenzene with acidic tin(II) chloride (SnCl2) converts nitrobenzene to aniline, an important industrial chemical used in the production of medicines, plastics, and dyes, to name but a few. 

The electrophile (E ) in this reaction is nitronium ion ( O=N=O0. The charge distribution in nitronium ion is evident both in its Lewis structure and in the electrostatic potential map on page 479, which also shows the complementary relationship between the electron-poor region near nitrogen of N02 and the electron-rich region associated 

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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. 

The value of the second-order rate constant for nitration of benzene-sulphonic acid in anhydrous sulphuric acid varies with the concentration of the aromatic substrate and with that of additives such as nitromethane and sulphuryl chloride. The effect seems to depend on the total concentration of non-electrolyte, moderate values of which (up to about 0-5 mol 1 ) depress the rate constant. More substantial concentrations of non-electrolytes can cause marked rate enhancements in this medium. Added hydrogen sulphate salts or bases such as pyridine... 

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. ... 

The rates of nitration of benzene, toluene, and ethylbenzene in solutions of nitric acid c. 3-7 mol 1 ) in nitromethane were independent... 

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. ... 

The kinetics of nitration of benzene in solutions at c. 20 °C in carbon tetrachloride have been investigated. In the presence of an excess of benzene (c. 2-4 mol 1 ) the rate was kinetically of the first order in the concentration of benzoyl nitrate. The rate of reaction was depressed by the addition of benzoic anhydride, provided that some benzoic acid was present. This result suggested that benzoyl nitrate itself was not responsible for the nitration, but generated dinitrogen pentoxide... 

First-order nitrations. The kinetics of nitrations in solutions of acetyl nitrate in acetic anhydride were first investigated by Wibaut. He obtained evidence for a second-order rate law, but this was subsequently disproved. A more detailed study was made using benzene, toluene, chloro- and bromo-benzene. The rate of nitration of benzene was found to be of the first order in the concentration of aromatic and third order in the concentration of acetyl nitrate the latter conclusion disagrees with later work (see below). Nitration in solutions containing similar concentrations of acetyl nitrate in acetic acid was too slow to measure, but was accelerated slightly by the addition of more acetic anhydride. Similar solutions in carbon tetrachloride nitrated benzene too quickly, and the concentration of acetyl nitrate had to be reduced from 0-7 to o-i mol 1 to permit the observation of a rate similar to that which the more concentrated solution yields in acetic anhydride. 

The rates of nitration of benzene in solutions at 25 °C containing 0-4-2-0 mol 1 of acetyl nitrate in acetic anhydride have been deter-mined.2 The rates accord with the following kinetic law ... 

The effects of added species. The rate of nitration of benzene, according to a rate law kinetically of the first order in the concentration of aromatic, was reduced by sodium nitrate, a concentration of io mol 1 of the latter retarding nitration by a factor of about Lithium nitrate... 

The addition of sulphuric acid increased the rate of nitration of benzene, and under the influence of this additive the rate became proportional to the first powers of the concentrations of aromatic, acetyl nitrate and sulphuric acid. Sulphuric acid markedly catalysed the zeroth-order nitration and acetoxylation of o-xylene without affecting the kinetic form of the reaction. ... 

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... 

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... 

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

Figure 12 11 compares the energy profile for nitration of benzene with those for attack at the ortho meta and para positions of (trifluoromethyl)benzene The presence of the electron withdrawing trifluoromethyl group raises the activation energy for attack at all the ring positions but the increase is least for attack at the meta position... 

Its rate is some 30 times slower than the corresponding nitration of benzene The major products are o chloromtrobenzene and p chloromtrobenzene... 

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

For the process step involving handling of spent sulfuric acid, several patents have been issued in which improvements in this step were a main claim. The azeotropic nitration of benzene essentially eliminates the need to reconcentrate sulfuric acid (10,11). The nitration step is carried out at higher than usual temperatures (120—160°C). Because excess benzene is used, the higher temperature allows water to be removed as a water—benzene azeotrope. The water is separated and the benzene phase, containing approximately 8% nitrobenzene, is recycled back into the reactor. The dry sulfuric acid is then reused continuously. 

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. 

Nitration of benzene yields nitrobenzene, which is reduced to aniline, an important intermediate for dyes and pharmaceuticals. Benzene is chlorinated to produce chlorobenzene, which finds use in the preparation of pesticides, solvents, and dyes. 

Example 10.1. The nitration of toluene is 23 times faster than nitration of benzene in nitric acid-acetic anhydride. The product ratio is 63% ortho, 34% para, and 3% meta. Calculate the partial rate factors. 

Because of Us high polarity and low nucleophilicity, a trifluoroacetic acid medium is usually used for the investigation of such carbocationic processes as solvolysis, protonation of alkenes, skeletal rearrangements, and hydride shifts [22-24] It also has been used for several synthetically useful reachons, such as electrophilic aromatic substitution [25], reductions [26, 27], and oxidations [28] Trifluoroacetic acid is a good medium for the nitration of aromatic compounds Nitration of benzene or toluene with sodium nitrate in trifluoroacetic acid is almost quantitative after 4 h at room temperature [25] Under these conditions, toluene gives the usual mixture of mononitrotoluenes in an o m p ratio of 61 6 2 6 35 8 A trifluoroacetic acid medium can be used for the reduction of acids, ketones, and alcohols with sodium borohydnde [26] or triethylsilane [27] Diary Iketones are smoothly reduced by sodium borohydnde in trifluoroacetic acid to diarylmethanes (equation 13)... 

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