Nitric acid reactions with aromatics

Nitration of strongly deactivated aromatics was carried out with nitric acid mixed with triflatoboric superacid.482 The method is characterized by high yields (penta-fluorobenzene, 99%, 1,2,3,5-tetrafluorobenzene, 89% 2,3,4-trifluoronitrobenzene, 96% methyl phenyl sulfone, 78%), usually high regioselectivity, and mild reaction conditions (room temperature), and it also tolerates many functional groups. 

Nitration. Add 0.4 mL of concentrated sulfuric acid to 100 mg of the aryl halide (or aromatic compound) and stir. Add 0.4 mL of concentrated nitric acid dropwise with stirring and shaking while cooling the reaction mixture in water. Then heat and shake the reaction mixture in a water bath at about 50°C for 15 min, pour into 2 mL of cold water, and collect the product by filtration. Recrystallize from methanol to constant melting point. 

Not only can the mother substances, the aromatic hydrocarbons, but all their derivatives, as phenols, amines, aldehydes, acids, etc., undergo similar reactions. But the nitration does not take place in every case with the same ease. In each case, therefore, the most favourable conditions for the experiment must be determined. If a compound is very easily nitrated, the nitration may be effected, according to the conditions, by nitric acid diluted with water, or the substance may be dissolved in a solvent which is not attacked by nitric acid glacial acetic acid is frequently used for this purpose, and then treated with nitric add. The reverse process may also be employed, i.e. the substance is added to a mixture of nitric acid and water, or nitric acid and glacial acetic acid. If a substance is moderately difficult to nitrate, it is added... 

Oxidation at Benzylic Position. Nitric acid oxidizes many aromatic alkyl substituents to the carboxylic acid group. Thus toluene is oxidized to benzoic acid in 85-90% yield. Oxidation of ethylbenzene with 15% nitric acid also gives benzoic acid in 80% yield. The reaction is general and has also been applied to the oxidation of pyridine derivatives. When 4-methylpyridine is treated with 10% nitric acid in phosphoric acid at elevated temperature and pressure, 4-pyridinecarboxylic acid is obtained in 93% yield. The reaction of p-isopropyltoluene can be controlled to give the partially oxidized product, p-methylbenzoic acid, in 56-59% yield. Additional examples of selective benzylic oxidations are shown in eqs 13 and... 

Pyridines can be made by condensation reactions of acyclic starting materials such as carbonyl compounds with ammonia. The most general of these methods is the Hantzsch pyridine synthesis. In this reaction, two molecules of a j8-dicarbonyl compound, an aldehyde, and ammonia combine in several steps (Worked Example 25-28) to give a substituted dihydropyridine, which is readily oxidized by nitric acid to the aromatic system. When the j8-dicarbonyl compound is a 3-ketoester, the resulting product is a 3,5-... 

Nitration introduces a nitro group (— NO ) onto an aromatic ring. Electrophilic aromatic substitution requires nitric acid (HNOj), with sulfuric acid as a catalyst. Nitronium ion, (NO ), is the electrophile. It forms in two steps by the reaction of nitric acid with sulfuric acid. 

A brief account of aromatic substitution may be usefully given here as it will assist the student in predicting the orientation of disubstituted benzene derivatives produced in the different substitution reactions. For the nitration of nitrobenzene the substance must be heated with a mixture of fuming nitric acid and concentrated sulphuric acid the product is largely ni-dinitrobenzene (about 90 per cent.), accompanied by a little o-dinitrobenzene (about 5 per cent.) which is eliminated in the recrystallisation process. On the other hand phenol can be easily nitrated with dilute nitric acid to yield a mixture of ortho and para nitrophenols. It may be said, therefore, that orientation is meta with the... 

The operation of the nitronium ion in these media was later proved conclusively. "- The rates of nitration of 2-phenylethanesulphonate anion ([Aromatic] < c. 0-5 mol l i), toluene-(U-sulphonate anion, p-nitrophenol, A(-methyl-2,4-dinitroaniline and A(-methyl-iV,2,4-trinitro-aniline in aqueous solutions of nitric acid depend on the first power of the concentration of the aromatic. The dependence on acidity of the rate of 0-exchange between nitric acid and water was measured, " and formal first-order rate constants for oxygen exchange were defined by dividing the rates of exchange by the concentration of water. Comparison of these constants with the corresponding results for the reactions of the aromatic compounds yielded the scale of relative reactivities sho-wn in table 2.1. 

When large concentrations of water are added to the solutions, nitration according to a zeroth-order law is no longer observed. Under these circumstances, water competes successfully with the aromatic for the nitronium ions, and the necessary condition for zeroth-order reaction, namely that all the nitronium ions should react with the aromatic as quickly as they are formed, no longer holds. In these strongly aqueous solutions the rates depend on the concentrations and reactivities of the aromatic compound. This situation is reminiscent of nitration in aqueous nitric acid in which partial zeroth-order kinetics could be observed only in the reactions of some extremely reactive compounds, capable of being introduced into the solution in high concentrations ( 2.2.4). 

It has already been noted that, as well as alkylbenzenes, a wide range of other aromatic compounds has been nitrated with nitronium salts. In particular the case of nitrobenzene has been examined kinetically. Results are collected in table 4.4. The reaction was kinetically of the first order in the concentration of the aromatic and of the nitronium salt. There is agreement between the results for those cases in which the solvent induces the ionization of nitric acid to nitronium ion, and the corresponding results for solutions of preformed nitronium salts in the same solvent. 

Certain features of the addition of acetyl nitrate to olefins in acetic anhydride may be relevant to the mechanism of aromatic nitration by this reagent. The rapid reaction results in predominantly cw-addition to yield a mixture of the y -nitro-acetate and y5-nitro-nitrate. The reaction was facilitated by the addition of sulphuric acid, in which case the 3rield of / -nitro-nitrate was reduced, whereas the addition of sodium nitrate favoured the formation of this compound over that of the acetate. As already mentioned ( 5.3. i), a solution of nitric acid (c. i 6 mol 1 ) in acetic anhydride prepared at — 10 °C would yield 95-97 % of the nitric acid by precipitation with urea, whereas from a similar solution prepared at 20-25 °C and cooled rapidly to —10 °C only 30% of the acid could be recovered. The difference between these values was attributed to the formation of acetyl nitrate. A solution prepared at room... 

Recent experiments have shown that the concentration of aromatic compound needed to maintain zeroth-order kinetics (see below) was much greater than for nitrations with solutions of nitric acid in some inert organic solvents reactions which were first order in the concentration of the aromatic were obtained when [ArH] < c. 2 x io mol 1 . ... 

The evidence outlined strongly suggests that nitration via nitrosation accompanies the general mechanism of nitration in these media in the reactions of very reactive compounds.i Proof that phenol, even in solutions prepared from pure nitric acid, underwent nitration by a special mechanism came from examining rates of reaction of phenol and mesi-tylene under zeroth-order conditions. The variation in the initial rates with the concentration of aromatic (fig. 5.2) shows that mesitylene (o-2-0 4 mol 1 ) reacts at the zeroth-order rate, whereas phenol is nitrated considerably faster by a process which is first order in the concentration of aromatic. It is noteworthy that in these solutions the concentration of nitrous acid was below the level of detection (< c. 5 X mol... 

This qualification must be applied to the results of Dewar and his co-workers relating to the reaction of a series of polynuclear aromatic compounds with solutions of nitric acid in acetic anhydride at o °C... 

The limit to the significance of aromatic reactivity set by reaction at the encounter rate is reached at different levels of reactivity in different conditions. As already seen, for nitration with nitric acid in organic... 

More information has appeared concerning the nature of the side reactions, such as acetoxylation, which occur when certain methylated aromatic hydrocarbons are treated with mixtures prepared from nitric acid and acetic anhydride. Blackstock, Fischer, Richards, Vaughan and Wright have provided excellent evidence in support of a suggested ( 5.3.5) addition-elimination route towards 3,4-dimethylphenyl acetate in the reaction of o-xylene. Two intermediates were isolated, both of which gave rise to 3,4-dimethylphenyl acetate in aqueous acidic media and when subjected to vapour phase chromatography. One was positively identified, by ultraviolet, infra-red, n.m.r., and mass spectrometric studies, as the compound (l). The other was less stable and less well identified, but could be (ll). 

Nitrations can be performed in homogeneous media, using tetramethylene sulfone or nitromethane (nitroethane) as solvent. A large variety of aromatic compounds have been nitrated with nitronium salts in excellent yields in nonaqueous media. Sensitive compounds, otherwise easily hydroly2ed or oxidized by nitric acid, can be nitrated without secondary effects. Nitration of aromatic compounds is considered an irreversible reaction. However, the reversibihty of the reaction has been demonstrated in some cases, eg, 9-nitroanthracene, as well as pentamethylnitrobenzene transnitrate benzene, toluene, and mesitylene in the presence of superacids (158) (see Nitration). 

The aHphatic iodine derivatives are usually prepared by reaction of an alcohol with hydroiodic acid or phosphoms trHodide by reaction of iodine, an alcohol, and red phosphoms addition of iodine monochloride, monobromide, or iodine to an olefin replacement reaction by heating the chlorine or bromine compound with an alkaH iodide ia a suitable solvent and the reaction of triphenyl phosphite with methyl iodide and an alcohol. The aromatic iodine derivatives are prepared by reacting iodine and the aromatic system with oxidising agents such as nitric acid, filming sulfuric acid, or mercuric oxide. 

Organic Reactions. Nitric acid is used extensively ia iadustry to nitrate aHphatic and aromatic compounds (21). In many iastances nitration requires the use of sulfuric acid as a dehydrating agent or catalyst the extent of nitration achieved depends on the concentration of nitric and sulfuric acids used. This is of iadustrial importance ia the manufacture of nitrobenzene and dinitrotoluene, which are iatermediates ia the manufacture of polyurethanes. Trinitrotoluene (TNT) is an explosive. Various isomers of mononitrotoluene are used to make optical brighteners, herbicides (qv), and iasecticides. Such nitrations are generally attributed to the presence of the nitronium ion, NO2, the concentration of which iacreases with acid strength (see Nitration). 

Miscellaneous Reactions. Aromatic sulfonic acid derivatives can be nitrated using nitric acid [52583-42-3] HNO, ia H2SO4 (19). Sultones may be treated with hydrazine derivatives to give the corresponding ring-opened sulfonic acid (20). 

Aromatic Ring Reactions. In the presence of an iodine catalyst chlorination of benzyl chloride yields a mixture consisting mostly of the ortho and para compounds. With strong Lewis acid catalysts such as ferric chloride, chlorination is accompanied by self-condensation. Nitration of benzyl chloride with nitric acid in acetic anhydride gives an isomeric mixture containing about 33% ortho, 15% meta, and 52% para isomers (27) with benzal chloride, a mixture containing 23% ortho, 34% meta, and 43% para nitrobenzal chlorides is obtained. 

Nitrobenzotrichloride is also obtained in high yield with no significant hydrolysis when nitration with a mixture of nitric and sulfuric acids is carried out below 30°C (31). 2,4-Dihydroxybenzophenone [131 -56-6] is formed in 90% yield by the uncatalyzed reaction of benzotrichloride with resorcinol in hydroxyHc solvents (32) or in benzene containing methanol or ethanol (33). Benzophenone derivatives are formed from a variety of aromatic compounds by reaction with benzotrichloride in aqueous or alcohoHc hydrofluoric acid (34). 

In an attempt to protect thiophenols during electrophilic substitution reactions on the aromatic ring, the three substituted thioethers were prepared. After acetylation of the aromatic ring (with moderate yields), the protective group was converted to the disulfide in moderate yields, 50-60%, by oxidation with hydrogen peroxide/boiling mineral acid, nitric acid, or acidic potassium permanganate. ... 

Aromatic rings can be nitrated by reaction with a mixture of concentrated nitric and sulfuric acids. The electrophile is the nitronium ion, N02+, which is generated from HNO3 by protonation and loss of water. The nitronium ion reacts with benzene to yield a carbocation intermediate, and loss of H+ from this intermediate gives the neutral substitution product, nitrobenzene (Figure 16.4). 

In aromatic compds, an amino group may be replaced by the nitro group by diazotization and reaction with nitric acid in the presence of cuprous salts (the Sandmeyer reaction). This method is used for lab work only and is described in standard textbooks on preparative organic chemistry... 

The rate of the reaction with most reagents is proportional to the concentration of NO2, not to that of other species. When the reagent produces this ion in small amounts, the attack is slow and only active substrates can be nitrated. In concentrated and aqueous mineral acids the kinetics are second order first order each in aromatic substrate and in nitric acid (unless pure nitric acid is used in which case there are pseudo-first-order kinetics). But in organic solvents, such as nitromethane, acetic acid, and CCI4, the kinetics are first order in nitric acid alone and zero order in aromatic substrate, because the rate-determining step is formation of NOj and the substrate does not take part in this. 

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