Nitric acid reaction with aromatic compounds

More recently, chemiluminescence detectors based on redox reactions have made possible the detection of many classes of compounds not detected by flame ionization. In the redox chemiluminescence detector (RCD), the effluent from the column is mixed with nitrogen dioxide and passed across a catalyst containing elemental gold at 200-400°C. Responsive compounds reduce the nitrogen dioxide to nitric oxide. The nitric oxide is reacted with ozone to give the chemiluminescent emission. The RCD yields a response from compounds capable of undergoing dehydrogenation or oxidation and produces sensitive emissions from alcohols, aldehydes, ketones, acids, amines, olifins, aromatic compounds, sulfides, and thiols. 

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... 

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-... 

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... 

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). 

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). 

Nitric acid and especially fuming acid is a strong oxidant and nitrating agent, especially when it is combined with sulphuric acid (formation of an electrophilic species). The dangers of the reactions which involve this compound are linked to the exothermicity of the reactions and the eventual formation, particularly in an aromatic series, of nitrated species that can be very unstable in some cases. 

The NO + 03 chemiluminescent reaction [Reactions (1-3)] is utilized in two commercially available GC detectors, the TEA detector, manufactured by Thermal Electric Corporation (Saddle Brook, NJ), and two nitrogen-selective detectors, manufactured by Thermal Electric Corporation and Antek Instruments, respectively. The TEA detector provides a highly sensitive and selective means of analyzing samples for A-nitrosamines, many of which are known carcinogens. These compounds can be found in such diverse matrices as foods, cosmetics, tobacco products, and environmental samples of soil and water. The TEA detector can also be used to quantify nitroaromatics. This class of compounds includes many explosives and various reactive intermediates used in the chemical industry [121]. Several nitroaromatics are known carcinogens, and are found as environmental contaminants. They have been repeatedly identified in organic aerosol particles, formed from the reaction of polycyclic aromatic hydrocarbons with atmospheric nitric acid at the particle surface [122-124], The TEA detector is extremely selective, which aids analyses in complex matrices, but also severely limits the number of potential applications for the detector [125-127],... 

As mentioned already in CHEC-II(1996) <1996CHEC-II(8)411>, some tetrazolo[l,5- ]pyridines can react with their C(5)-C(6) and C(7)-C(8) double bonds as dienophiles in Diels-Alder reactions. A novel study again supported this recognition Goumont et al. described that 6,8-dinitrotetrazolo[l,5- ]pyridine 11 easily react with some 2,3-disub-stituted butadienes to give bis-cycloadducts 48 <2002T3249>. These products when treated with potassium /-butoxide undergo base catalyzed elimination of nitric acid followed by oxidation reaction to yield the fully aromatic tetracyclic compounds 49 (Scheme 14). 

The same reaction can be applied, not only to the aromatic parent substances, the hydrocarbons, but also to all their derivatives, such as phenols, amines, aldehydes, acids, and so on. The nitration does not, however, always proceed with the same ease, and therefore the most favourable experimental conditions must be determined for each substance. If a substance is very easily nitrated it may be done with nitric acid sufficiently diluted with water, or else the substance to be nitrated is dissolved in a resistant solvent and is then treated with nitric acid. Glacial acetic acid is frequently used as the solvent. Substances which are less easily nitrated are dissolved in concentrated or fuming nitric acid. If the nitration proceeds with difficulty the elimination of water is facilitated by the addition of concentrated sulphuric acid to ordinary or fuming nitric acid. When nitration is carried out in sulphuric acid solution, potassium or sodium nitrate is sometimes used instead of nitric acid. The methods of nitration described may be still further modified in two ways 1, the temperature or, 2, the amount of nitric acid used, may be varied. Thus nitration can be carried out at the temperature of a freezing mixture, at that of ice, at that of cold water, at a gentle heat, or, finally, at the boiling point. Moreover, we can either employ an excess of nitric acid or the theoretical amount. Small scale preliminary experiments will indicate which of these numerous modifications may be expected to yield the best results. Since nitro-compounds are usually insoluble or sparingly soluble in water they can be precipitated from the nitration mixture by dilution with water. 

These compounds are less common than indole (benzo[ ]pyrrole). In the case of benzo[i>]furan the aromaticity of the heterocycle is weaker than in indole, and this ring is easily cleaved by reduction or oxidation. Electrophilic reagents tend to react with benzo[Z ]furan at C-2 in preference to C-3 (Scheme 7.21), reflecting the reduced ability of the heteroatom to stabilize the intermediate for 3-substitution. Attack in the heterocycle is often accompanied by substitution in the benzenoid ring. Nitration with nitric acid in acetic acid gives mainly 2-nitrobenzo[Z ]furan, plus the 4-, 6- and 7-isomers. When the reagent is in benzene maintained at 10 °C, both 3- and 2-nitro[ ]furans are formed in the ratio 4 1. Under Vilsmeier reaction conditions (see Section 6.1.2), benzo[Z ]furan gives 2-formylbenzo[6]furan in ca. 40% yield. 

Hantzsch synthesis The reaction of 1,3-dicarbonyl compounds with aldehydes and NH3 provides a 1,4-dihydropyridine, which can be aromatized by oxidation with nitric acid or nitric oxide. Instead of NH3, primary amine can be used to give 1-substituted 1,4-dihydropyridines. 

TNT is the abbreviation of the aromatic nitrated aromatic compound 2,4,6-trinitrotoluene. It is a pale-yellow crystalline solid that was first synthesized in 1863 by the German chemist Joseph Wilbrand (1811—1894), but it was not immediately used as an explosive. TNT is made by nitrating toluene using nitric acid, sulfuric acid, and oleum (a mixture of sulfuric acid and S03). Nitration of toluene occurs in stages, with the nitro units added sequentially in a stepwise process as the reaction proceeds. The last nitro unit is accomplished by using oleum (SO, dissolved in sulfuric acid). After nitration, unused acids are recycled, and the product is washed with sodium sulfite and water to remove impurities. 

Similarly, primary aromatic amines undergo complex reactions when heated with nitric acid. The amine derivatives of anthraquinone, pyridine and thiazole are exceptions the amino group in these compounds is decomposed by the nitrating mixture. This was noticed by Scholl [27], who proposed the following method for nitrating / -aminoanthraquinone ... 

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