98-95-3

A pale yellow to dark brown liquid. Flash point 190°F. Very slightly soluble in water. Toxic by inhalation and by skin absorption. Combustion give toxic oxides of nitrogen. Density 10.0 lb /gal.

Aluminum chloride added to NITROBENZENE(98-95-3) containing about 5% phenol caused a violent explosion [Chem. Eng. News 31:4915. 1953]. Heating a mixture of NITROBENZENE(98-95-3), flake sodium hydroxide and a little water led to an explosion, discussed in [Bretherick's 5th ed. 1995]. Mixed with oxidants, i.e. dinitrogen tetraoxide, fluorodinitromethane, nitric acid, peroxodisulfuric acid, sodium chlorate, tetranitromethane, uranium perchlorate, etc., forms highly sensitive explosive, [Bretherick 5th ed, 1995]. Heated mixtures of NITROBENZENE(98-95-3) and tin(IV) chloride produce exothermic decomposition with gas production [Bretherick, 5th Ed., 1995].

Very slightly soluble in water.

Toxic by ingestion, inhalation, and skin absorption. Methemoglobinemia. Possible carcinogen.

Can cause death due to respiratory failure. Classified as extremely toxic. The mean lethal oral dose is probably between 1 and 5 grams. Systemic effects may be delayed for a few hours. This compound is rapidly absorbed through the skin. It is a powerful methemoglobin former. Ethyl alcohol aggravates intoxication caused by nitrobenzene exposure.

Nitrobenzene is used in the manufacture of explosives and aniline dyes and as solvent and intermediate. It is also used in floor polishes; leather dressings and polished; and paint solvents, and to mask other unpleasant odors. Substitution reactions with nitrobenzene are used to form m-derivatives. Pregnant women may be especially at risk with respect to nitrobenzene as with many other chemical compounds, due to transplacental passage of the agent. Individuals with glucose-6-phosphate dehydrogenase deficiency may also be special risk groups. Additionally, because alcohol ingestion or chronic alcoholism can lower the lethal or toxic dose of nitrobenzene, individuals consuming alcoholic beverages may be at risk.

Moderate explosion hazard when exposed to heat or flame. Reacts violently with nitric acid, aluminum trichloride plus phenol, aniline plus glycerine, silver perchlorate and nitrogen tetroxide. Avoid aluminum trichloride; aniline; gycerol; sulfuric acid; oxidants; phosphorus pentachloride; potassium; potassium hydroxide. Avoid sunlight, physical damage to container, freezing, and intense heat.

If this chemical gets into the eyes, remove any contact lenses at once and irrigate immediately for at least 15 minutes, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts the skin, remove contaminated clothing and wash immediately with soap and water. Seek medical attention immediately. If this chemical has been inhaled, remove from exposure, begin rescue breathing (using universal precautions, including resuscitation mask) if breathing has stopped and CPR if heart action has stopped. Transfer promptly to a medical facility. When this chemical has been swallowed, get medical attention. Give large quantities of water and induce vomiting. Do not make an unconscious person vomit.

UN1662 Nitrobenzene, Hazard Class: 6.1; Labels: 6.1-Poisonous materials.

Concentrated nitric acid, nitrogen tetroxide; caustics; phosphorus pentachloride; chemically-active metals, such as tin or zinc. Violent reaction with strong oxidizers and reducing agents. Attacks many plastics. Forms thermally unstable compounds with many organic and inorganic compounds.

Incineration (982℃, 2.0 seconds minimum) with scrubbing for nitrogen oxides abatement . Consult with environmental regulatory agencies for guidance on acceptable disposal practices. Generators of waste containing this contaminant (≥100 kg/mo) must conform with EPA regulations governing storage, transportation, treatment, and waste disposal.

Clear, light yellow to brown, oily liquid with an almond-like or shoe polish odor. May darken on exposure to air. An experimentally determined odor threshold concentration of 4.7 ppb_v was reported by Leonardos et al. (1969). A detection odor threshold concentration of 9.6 mg/m³ (1.9 ppmv) was determined by Katz and Talbert (1930).

A yellow organic oil obtained by refluxing benzene with a mixture of concentrated nitric and sulfuric acids. The reaction is a typical electrophilic substitution on the benzene ring by the nitryl cation (NO₂⁺).

ChEBI: A nitroarene consisting of benzene carrying a single nitro substituent. An industrial chemical used widely in the production of aniline.

nitrobenzene: A yellow oily liquid,C₆H₅NO₂; r.d. 1.2; m.p. 6°C; b.p.211°C. It is made by the nitration ofbenzene using a mixture of nitricand sulphuric acids.

Nitrobenzene is produced commercially by the exothermic nitration of benzene with fuming nitric acid in the presence of a sulfuric acid catalyst at 50 to 65℃. The crude nitrobenzene is passed through washer-separators to remove residual acid and is then distilled to remove benzene and water.

Nitrobenzene is produced by the direct nitration of benzene with a mixture of sulfuric and nitric acids. U.S. capacity for nitrobenzene production is approximately 1.5 billion pounds . The most important use for nitrobenzene is in the production of aniline. Nearly 98% of the nitrobenzene produced in the U.S. is converted to aniline.

Journal of the American Chemical Society, 95, p. 5198, 1973 DOI: 10.1021/ja00797a017
Tetrahedron Letters, 27, p. 2335, 1986 DOI: 10.1016/S0040-4039(00)84522-0

Nitrobenzene is mainly utilized for aniline production. The aniline is used primarily for the manufacture of 4,4'-methylenebis (phenyl isocyanate) and polymers thereof (50%). The second largest use of aniline is in the manufacture of chemicals for rubber production (30%). Dyes and dye intermediates, hydroquinone and drugs account for about 8% of the aniline produced, while 10% of the aniline is converted to agricultural products such as pesticides and defoliants (Northcott 1978). It also is used as a solvent for cellulose ethers and an ingredient in polishes for metals and shoes (HSDB 1988).

Nitrobenzene is reasonably anticipated to be a human carcinogenbased on sufficient evidence of carcinogenicity from studies in experimental animals.

Biological. In activated sludge, 0.4% of the applied nitrobenzene mineralized to carbon dioxide after 5 d (Freitag et al., 1985). Under anaerobic conditions using a sewage inoculum, nitrobenzene degraded to aniline (Hallas and Alexander, 1983). When nitrobenzene (5 and 10 mg/L) was statically incubated in the dark at 25 °C with yeast extract and settled domestic wastewater inoculum, complete biodegradation with rapid acclimation was observed after 7 to 14 d (Tabak et al., 1981). In activated sludge inoculum, 98.0% COD removal was achieved in 5 d. The average rate of biodegradation was 14.0 mg COD/g?h (Pitter, 1976).
Razo-Flores et al. (1999) studied the fate of nitrobenzene (50 mg/L) in an upward-flow anaerobic sludge bed reactor containing a mixture of volatile fatty acids and/or glucose as electron donors. The nitrobenzene loading rate and hydraulic retention time for this experiment were 43 mg/L?d and 28 h, respectively. Nitrobenzene was effectively reduced (>99.9%) to aniline (92% molar yield) in stoichiometric amounts for the 100-d experiment.
Photolytic. Irradiation of nitrobenzene in the vapor phase produced nitrosobenzene and 4- nitrophenol (HSDB, 1989). Titanium dioxide suspended in an aqueous solution and irradiated with UV light (λ = 365 nm) converted nitrobenzene to carbon dioxide at a significant rate (Matthews, 1986). A carbon dioxide yield of 6.7% was achieved when nitrobenzene adsorbed on silica gel was irradiated with light (λ >290 nm) for 17 h (Freitag et al., 1985).
Chemical/Physical. In an aqueous solution, nitrobenzene (100 μM) reacted with Fenton’s reagent (35 μM). After 15 min, 2-, 3-, and 4-nitrophenol were identified as products. After 6 h, about 50% of the nitrobenzene was destroyed. The pH of the solution decreased due to the formation of nitric acid (Lipczynska-Kochany, 1991). Augusti et al. (1998) conducted kinetic studies for the reaction of nitrobenzene (0.2 mM) and other monocyclic aromatics with Fenton’s reagent (8 mM hydrogen peroxide; [Fe⁺²] = 0.1 mM) at 25 °C. They reported a reaction rate constant of 0.0260/min.

Nitrobenzene vapor is readily absorbed through the skin and lungs. At an airborne nitrobenzene concentration of 10 mg/m³ humans may absorb 18 to 25 mg in 6 h through the lungs and from 8 to 19 mg through the skin in the same length of time .
Urine is the major route of excretion of nitrobenzene metabolites in rabbits , rats and mice . The most abundant metabolite in earlier studies in rabbits and rats was p-aminophenol. This compound, or its glucuronide or sulfate conjugates, accounted for 19% to 31% of the dose. In a later study in rats in which the acid hydrolysis step employed by earlier workers to cleave conjugates was replaced by enzyme hydrolysis, no p-aminophenol was found in the urine of male Fischer-344 or CD rats .
About 9% of a nitrobenzene dose was excreted by B₆C₃F₁ mice as the sulfate conjugate. The major metabolites found in Fischer-344 rat urine were p-hydroxyacetanilide sulfate (19% of the dose), p-nitrophenol sulfate (20% of the dose) and m-nitrophenol sulfate (10% of the dose) .
In addition, an unidentified metabolite accounted for about 10% of the dose .
Male CD rats excreted the same metabolites after an oral dose of nitrobenzene, but in slightly different proportions. They excreted about half as much of the dose as the glucuronide or sulfate conjugates of P-hydroxyacetanilide (9% of the dose) and P-nitrophenol (13% of the dose), approximately the same amount of m-nitrophenol (8% of the dose), and about twice as much as the unidentified metabolite. Interestingly, whereas Fischer-344 rats excreted the phenolic metabolites of nitrobenzene exclusively as sulfates, CD rats excreted the same metabolites in the free form (15-17% of the total metabolite) and as glucuronides (4-20% of the total metabolite).
Approximately 4% of the dose also was excreted as p-hydroxyacetanilide by B₆C₃F₁ mice and as p- and m-nitrophenol (7% and 6% of the dose, respectively) sulfates, glucuronides and free metabolites .
Clearly, ring hydroxylation and reduction are important metabolic steps in the biotransformation of nitrobenzene in rabbits, rats, mice and humans . Since no significant isotope effect was found in the metabolism of deuterated nitrobenzene to these products in rats in vivo , the o- and p-nitrophenols may be formed through an arene oxide intermediate. A significant isotope effect was noted in the formation of m-nitrophenol from deuterated nitrobenzene in the same rats, leading to the conclusion that m-nitrophenol is formed by a direct oxygen insertion mechanism or by some other mechanism which does not involve an arene oxide intermediate. The reduction of nitrobenzene in vivo is largely, if not exclusively, due to the action of anaerobic intestinal microflora. Treatment with antibiotics totally eliminated the ability of cecal contents of Fischer-344 rats to reduce nitrobenzene in vitro, and rats treated with antibiotics eliminated p-hydroxyacetanilide as 0.9% of an oral dose of nitro-benzene. Normal rats excreted 16.2% of an oral dose of nitrobenzene as that metabolite .
The reduction of most nitro compounds by hepatic microsomes is not detectable under aerobic conditions, but is readily observable under anaerobic conditions. Mason and Holtzman proposed that the first intermediate in the microsomal reduction of nitroaromatic compounds is the nitro anion radical, the product of a one electron transfer to nitrobenzene or other nitroaromatic compound. Oxygen would rapidly oxidize the radical to yield the parent nitro compound and Superoxide anion. Both the nitro anion radical and Superoxide anion are potentially toxic compounds.
Both P-nitrophenol and P-aminophenol have been detected in human urine after exposure to nitrobenzene. p-Aminophenol has been found only after large accidental exposures and acid hydrolysis of urine. Since acid conditions convert p-acetamidophenol to P-aminophenol, the identity of the metabolite actually excreted is in doubt. P-Nitrophenol has been found in the urine of volunteers exposed to low inhalation doses of nitrobenzene, and Kuzelova and Popler have suggested that urinary P-nitrophenol be used to monitor exposure to nitrobenzene.

Common impurities include nitrotoluene, dinitrothiophene, dinitrobenzene and aniline. Most impurities can be removed by steam distillation in the presence of dilute H2SO4, followed by drying with CaCl2, and shaking with, then distilling at low pressure from BaO, P2O5, AlCl3 or activated alumina. It can also be purified by fractional crystallisation from absolute EtOH (by refrigeration). Another purification process includes extraction with aqueous 2M NaOH, then water, dilute HCl, and water, followed by drying (CaCl2, MgSO4 or CaSO4) and fractional distillation under reduced pressure. The pure material is stored in a brown bottle, in contact with silica gel or CaH2. It is very hygroscopic. [Beilstein 5 H 233, 5 I 124, 5 II 171, 5 III 591, 5 IV 708.]

The intermediates and products of nitrobenzene reduction can cause methemoglobinemia (a condition in which the blood’s ability to carry oxygen is reduced) by accelerating the oxidation of hemoglobin to methemoglobin. Three primary metabolic mechanisms have been identified: reduction of nitrobenzene to aniline by intestinal microflora, its reduction to aniline occurring in hepatic microsomes and erythrocytes, and nitrobenzene oxidative metabolism to the nitrophenols by hepatic microsomes. Many of the toxicological effects are likely triggered by metabolites of nitrobenzene. For example, methemoglobinemia is caused by the interaction of hemoglobin with the products of nitrobenzene reduction (i.e., nitrosobenzene, phenylhydroxylamine, and aniline). The anaerobic metabolism occurring in the gastrointestinal track is much faster than reduction by the hepatic microsomal fraction; therefore, the action of bacteria normally present in the small intestine is an important element in the formation of methemoglobin.