Aromatic oxidations nitric acid

There is a synthesis, which is supposed to be safe and consists in using very small quantities of reagents and closely monitoring the temperature. However, the thermai control of the aromatic hydrocarbons/nitric acid reaction usually proves to be very difficult. Indeed, the temperature is either too high and the reaction is out of controi and can lead to detonation, or too low and the nitration or oxidation takes place too slowly causing the compounds to accumulate and the reaction to be delayed. The consequences are the same as before. 

Aniline also cannot be nitrated because nitric acid is an oxidizing agent and primary amines are easily oxidized. (Nitric acid and aniline can be an explosive combination.) Tertiary aromatic amines, however, can be nitrated. Because the tertiary amino group is a strong activator, nitration is carried out with nitric acid in acetic acid, a milder combination than nitric acid in sulfuric acid. About twice as much para isomer is formed as ortho isomer. 

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. 

Nitration. Direct nitration of aromatic amines with nitric acid is not a satisfactory method, because the amino group is susceptible to oxidation. The amino group can be protected by acetylation, and the acetylamino derivative is then used in the nitration step. Nitration of acetanilide in sulfuric acid yields the 4-nitro compound that is hydroly2ed to -rutroaruline [100-01-6]. 

Benzoic acid [65-85-0] C H COOH, the simplest member of the aromatic carboxyHc acid family, was first described in 1618 by a French physician, but it was not until 1832 that its stmcture was deterrnined by Wn b1er and Liebig. In the nineteenth century benzoic acid was used extensively as a medicinal substance and was prepared from gum benzoin. Benzoic acid was first produced synthetically by the hydrolysis of benzotrichloride. Various other processes such as the nitric acid oxidation of toluene were used until the 1930s when the decarboxylation of phthaUc acid became the dominant commercial process. During World War II in Germany the batchwise Hquid-phase air oxidation of toluene became an important process. 

Surface oxidation short of combustion, or using nitric acid or potassium permanganate solutions, produces regenerated humic acids similar to those extracted from peat or soil. Further oxidation produces aromatic acids and oxaUc acid, but at least half of the carbon forms carbon dioxide. 

Hypalon, chlorosulfated polyethylene, is particularly noted for its resistance to strong oxidizing materials such as sodium hypochlorite, chromic and nitric acids. It has good resistance to mineral and vegetable oils but is not recommended for use with aromatic and chlorinated hydrocarbons. 

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. ... 

Titov claims that the free radical mechanism applies for nitration of aliphatic hydrocarbons, of aromatic side chains, of olefins, and of aromatic ring carbons, if irf the latter case the nitrating agent is ca 60—70% nitric acid that is free of nitrous acid, or even more dil acid if oxides of nitrogen are present... 

The various methods that are used for the production of aromatic acids from the corresponding substituted toluenes are outlined in Figure 1. The first two methods -chlorination/hydrolysis and nitric acid oxidation - have the disadvantage of relatively low atom utilization (ref. 13) with the concomitant inorganic salt production. Catalytic autoxidation, in contrast, has an atom utilization of 87% (for Ar=Ph) and produces no inorganic salts and no chlorinated or nitrated byproducts. It consumes only the cheap raw material, oxygen, and produces water as the only byproduct. 

Consequently, as a result of increasing environmental pressure many chlorine and nitric acid based processes for the manufacture of substituted aromatic acids are currently being replaced by cleaner, catalytic autoxidation processes. Benzoic acid is traditionally manufactured (ref. 14) via cobalt-catalyzed autoxidation of toluene in the absence of solvent (Fig. 2). The selectivity is ca. 90% at 30% toluene conversion. As noted earlier, oxidation of p-xylene under these conditions gives p-toluic acid in high yield. For further oxidation to terephthalic acid the stronger bromide/cobalt/manganese cocktail is needed. 

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 nitrosophenol (10), which may be isolated, is oxidised very rapidly by nitric acid to yield the p-nitrophenol (11) and nitrous acid more nitrous acid is produced thereby and the process is progressively speeded up. No nitrous acid need be present initially in the nitric acid for a little of the latter attacks phenol oxidatively to yield HN02. The rate-determining step is again believed to be the formation of the intermediate (9). Some direct nitration of such reactive aromatic compounds by N02 also takes place simultaneously, the relative amount by the two routes depending on the conditions. 

A novel, mild system for the direct nitration of calixarenes has been developed using potassium nitrate and aluminum chloride at low temperature. The side products of decomposition formed under conventional conditions are not observed in this system, and the p-nitro-calixarenes are isolated in 75-89% yields.17 Such Friedel-Crafts-type nitration using nitryl chloride and aluminum chloride affords a convenient system for aromatic nitration.18 Nitryl chloride was previously prepared either by the oxidation of nitrosyl chloride or by the reaction of chlorosulfonic acid with nitric acid. However, these procedures are inconvenient and dangerous. Recently, a mixture of sodium nitrate and trimethysilyl chloride (TMSC1) has been developed as a convenient method for the in situ generation of nitryl chloride (Eq. 2.6). 

Dinitrogen pentoxide (prepared by the oxidation of N204 with 03) in nitric acid is a potent nitration system. It can be used for nitrating aromatic compounds at lower temperatures than conventional system. It is also convenient for preparing explosives that are unstable in nitrating media containing sulfuric acid (Eq. 2.7).20... 

Attempts of further nitration of dinitro derivative 83 under usual conditions failed. Using 100% nitric acid in fluorosulfonic acid or trifluoromethanesulfonic acid, reagents useful for nitration of deactivated aromatic systems led to the formation of moisture-sensitive nitration products, which undergo further oxidation to give o-quinone-like species 84 and 85. Using the latter conditions, compound 86 can be isolated in 20% yield and converted into the tetraoxo derivative 85 by heating at 220°C (Scheme 4) <1996JOC1898>. 

The naphthalene-like, aromatic stmcture of 1,2,3-benzothiadiazole imparts stability to the system that survives exposure to 20% potassium hydroxide at 150°C or 27% sulfuric acid at 200 °C. It is not oxidized by potassium permanganate, potassium ferricyanide, chromic acid, or dilute nitric acid <1996CHEC-II(4)289>. Electrophilic substitution occurs in the benzo ring, predominantly at the 4-position. Chlorine in the 6-position is displaced by a variety of nucleophiles <1975SST670>. 

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). 

---