Aniline

Description

Aniline is the simplest primary aromatic amine and a compound formed by the substitution of a hydrogen atom in the benzene molecule with an amino group. It is colorless oil like flammable liquid with strong odor. When heated to 370 C, it is slightly soluble in water and soluble in ethanol, ether, chloroform and other organic solvents. It becomes brown in the air or under the sun. It can be distilled by steam. A small amount of zinc powder is added to prevent oxidation when it is distilled. The purified aniline can be added 10 ~ 15ppm NaBH4 to prevent oxidation deterioration. The solution of aniline is alkaline.
It is easy to produce salt when it reacts with acid. The hydrogen atoms on its amino groups can be substituted by alkyl or acyl groups to produce second or third grade aniline and acyl aniline. When substitution reaction occurs, the products of ortho and para substituted products are mainly produced. It reacts with nitrite to form diazonium salts, which can be used to produce a series of benzene derivatives and azo compounds.

Uses

Aniline is an important industrial chemical for many decades. Currently, it is most widely used for the manufacture of polyurethanes and rubber, with lesser amounts consumed in the production of pesticides (herbicides, fungicides, insecticides, animal repellants), defoliants, dyes, antioxidants, antidegradants, and vulcanization accelerators. It is also an ingredient of some household products, such as polishes (stove and shoe), paints, varnishes, and marking inks.

Reaction

A primary aromatic amine, aniline is a weak base and forms salts with mineral acids such as aniline hydrochloride. PKb = 9.30, 0.2mol aqueous solution PH value 8.1. In acidic solution, nitrous acid converts aniline into a diazonium salt that is an intermediate in the preparation of a great number of dyes and other organic compounds of commercial interest. When aniline is heated with organic acids, it gives amides, called anilides, such as acetanilide from aniline and acetic acid. Monomethylaniline and dimethylaniline can be prepared from aniline and methyl alcohol. Catalytic reduction of aniline yields cyclohexylamine.
Various oxidizing agents convert aniline to quinone, azobenzene, nitrosobenzene, p-aminophenol, and the phenazine dye aniline black. Amino groups can undergo acylation, halogenation, alkylation and diazotization, and the presence of amino groups makes it nucleophiles capable of many nucleophilic reactions, and at the same time activates the electrophilic substitution on aromatic rings.

Production

Aniline was first obtained in 1826 by the destructive distillation of indigo. It is named because of the specific indigo-yielding plant “Indigofera anil” (Indigofera suffruticosa); In 1857, W.H.Jr. Perkin made aniline from reduction of nitrobenzene with iron filings using hydrochloric acid as catalyst which is still being used. At present, the methods of aniline production include catalytic vapor phase reduction of nitrobenzene with hydrogen, catalytic reaction of chlorobenzene and ammonolysis of phenol (Japan).
Before 1960s, aniline production was based on coal tar benzene, and now petroleum benzene has been used. At the end of 1990s, the world's aniline production capacity was above 2.5 million t. 50% of the aniline is used in the production of dye intermediates. About 25% aniline is used to produce isocyanate and its copolymers. The remaining (25%) is used for pesticides, gasoline antiknock agents, and photographic materials etc.

Hazards

The toxicity of Aniline is LD50500mg/kg (dog oral administration), and is a common pollutant in the environment. Aniline has strong toxicity to blood and nerves. It can be absorbed by skin or by respiratory tract to cause toxicity.
The acute (short-term) and chronic (long-term) effects of aniline in humans consist mainly of effects on the lung, such as upper respiratory tract irritation and congestion. Chronic exposure may also result in effects on the blood. Human cancer data are insufficient to conclude that aniline is a cause of bladder tumors while animal studies indicate that aniline causes tumors of the spleen. EPA has classified aniline as a Group B2, probable human carcinogen.
Evidence reported by the National Institute for Occupational Safety and Health (NIOSH) clearly associates the occupational exposure to o-toluidine and aniline with an increased risk of bladder cancer among workers. The risk of bladder cancer is greatest among workers with possible and definite exposures to o-toluidine and aniline, and the risk increases with the duration of exposure.

Description

First produced in 1826 by Otto Unverdorben through destructive distillation of indigo, the first industrial use was as a purple dye, Mauveine, formulated by William Henry Perkin accidentally in an attempt to isolate quinone. The name aniline was given in deference to the indigoyielding plant, Indigofera suffruticosa, commonly named anil.

Chemical Properties

Aniline,C6H5NH2, is slightly soluble in water,miscible in alcohol and ether,and turns yellow to brown in air. Aniline may be made(1) by the reduction, with iron or tin in HCI, of nitrobenzene, and(2) by the amination of chlorobenzene by heating with ammonia to a high temperature corresponding to a pressure of over 200 atmospheres in the presence of a catalyst(a mixture of cuprous chlorideandoxide).Aniline is the end point of reduction of most mononitrogen substituted benzene nuclei,as nitro benzene beta-phenyl hydroxylamine, azoxybenzene, azobenzene, hydrazobenzene. Aniline is detected by the violet coloration produced by a small amountof sodium hypochlorite. Aniline is used as a solvent, in the preparation of compound in the manufacture of dyes and their intermediates, and in the manufacture of medicinal chemicals.

Physical properties

Colorless, oily liquid with a faint ammonia-like odor and burning taste. Gradually becomes yellow to reddish-brown on exposure to air or light. The lower and upper odor thresholds are 2 and 128 ppm, respectively (quoted, Keith and Walters, 1992). An odor threshold of 1.0 ppm_v was reported by Leonardos et al. (1969).

Uses

Aniline is used in the manufacture of dyes,pharmaceuticals, varnishes, resins, photo graphic chemicals, perfumes, shoe blacks,herbicides, and fungicides. It is also usedin vulcanizing rubber and as a solvent. Itoccurs in coal tar and is produced from thedry distillation of indigo. It is also producedfrom the biodegradation of many pesticides.Aniline is a metabolite of many toxic com pounds, such as nitrobenzene, phenacetin,and phenylhydroxylamine.

Uses

A thin, colorless oil prepared by reducing benzene with iron filings in the presence of hydrochloric or acetic acid and then separating the aniline formed by distillation. It is slightly soluble in water but dissolves easily in alcohol, ether, and benzene. Aniline is the base for many dyes used to increase the sensitivity of emulsions.

Uses

Rubber accelerators and antioxidants, dyes and intermediates, photographic chemicals (hydro- quinone), isocyanates for urethane foams, pharma- ceuticals, explosives, petroleum refining, dipheny- lamine, phenolics, herbicides, fungicides.

Definition

ChEBI: A primary arylamine in which an amino functional group is substituted for one of the benzene hydrogens.

Production Methods

Aniline was obtained in 1826 by Unverdorben from distillation of indigo and was given the name aniline in 1841 by Fritzsche (Windholz et al 1983). The chemical was manufactured in the U. S. by the Bechamp reaction involving reduction of nitrobenzene in the presence of either copper/silica or hydrochloric acid/ferrous chloride catalysts; but in 1966, amination of chlorobenzene with ammonia was introduced (IARC 1982; Northcott 1978). Currently, aniline is produced in the U.S., several European countries and Japan by the catalytic hydrogenation of nitrobenzene in either the vapor phase or solvent system. This chemical is also produced by reacting phenol with ammonia (HSDB 1989). Production in 1982 amounted to 331,000 tons (HSDB 1989).

Synthesis Reference(s)

Chemical and Pharmaceutical Bulletin, 29, p. 1159, 1981 DOI: 10.1248/cpb.29.1159
The Journal of Organic Chemistry, 58, p. 5620, 1993 DOI: 10.1021/jo00073a018

General Description

A yellowish to brownish oily liquid with a musty fishy odor. Melting point -6°C; boiling point 184°C; flash point 158°F. Denser than water (8.5 lb / gal) and slightly soluble in water. Vapors heavier than air. Toxic by skin absorption and inhalation. Produces toxic oxides of nitrogen during combustion. Used to manufacture other chemicals, especially dyes, photographic chemicals, agricultural chemicals and others.

Air & Water Reactions

Darkens on exposure to air and light. Polymerizes slowly to a resinous mass on exposure to air and light. Slightly soluble in water.

Reactivity Profile

Aniline is a heat sensitive base. Combines with acids to form salts. Dissolves alkali metals or alkaline earth metals with evolution of hydrogen. Incompatible with albumin, solutions of iron, zinc and aluminum, and acids. Couples readily with phenols and aromatic amines. Easily acylated and alkylated. Corrosive to copper and copper alloys. Can react vigorously with oxidizing materials (including perchloric acid, fuming nitric acid, sodium peroxide and ozone). Reacts violently with BCl3. Mixtures with toluene diisocyanate may ignite. Undergoes explosive reactions with benzenediazonium-2-carboxylate, dibenzoyl peroxide, fluorine nitrate, nitrosyl perchlorate, peroxodisulfuric acid and tetranitromethane. Violent reactions may occur with peroxyformic acid, diisopropyl peroxydicarbonate, fluorine, trichloronitromethane (293° F), acetic anhydride, chlorosulfonic acid, hexachloromelamine, (HNO3 + N2O4 + H2SO4), (nitrobenzene + glycerin), oleum, (HCHO + HClO4), perchromates, K2O2, beta-propiolactone, AgClO4, Na2O2, H2SO4, trichloromelamine, acids, FO3Cl, diisopropyl peroxy-dicarbonate, n-haloimides and trichloronitromethane. Ignites on contact with sodium peroxide + water. Forms heat or shock sensitive explosive mixtures with anilinium chloride (detonates at 464° F/7.6 bar), nitromethane, hydrogen peroxide, 1-chloro-2,3-epoxypropane and peroxomonosulfuric acid. Reacts with perchloryl fluoride form explosive products.

Hazard

An allergen. Toxic if absorbed through the skin. Combustible. Skin irritant. Questionable car- cinogen.

Health Hazard

Aniline is a moderate skin irritant, a moderate to severe eye irritant, and a skin sensitizer in animals. Aniline is moderately toxic via inhalation and ingestion. Symptoms of exposure (which may be delayed up to 4 hours) include headache, weakness, dizziness, nausea, difficulty breathing, and unconsciousness. Exposure to aniline results in the formation of methemoglobin and can thus interfere with the ability of the blood to transport oxygen. Effects from exposure at levels near the lethal dose include hypoactivity, tremors, convulsions, liver and kidney effects, and cyanosis. Aniline has not been found to be a carcinogen or reproductive toxin in humans. Some tests in rats demonstrate carcinogenic activity. However, other tests in which mice, guinea pigs, and rabbits were treated by various routes of administration gave negative results. Aniline produced developmental toxicity only at maternally toxic dose levels but did not have a selective toxicity for the fetus. It produces genetic damage in animals and in mammalian cell cultures but not in bacterial cell cultures.

Fire Hazard

Combustion can produce toxic fumes including nitrogen oxides and carbon monoxide. Aniline vapor forms explosive mixtures with air. Aniline is incompatible with strong oxidizers and strong acids and a number of other materials. Avoid heating. Hazardous polymerization may occur. Polymerizes to a resinous mass.

Flammability and Explosibility

Aniline is a combustible liquid (NFPA rating = 2). Smoke from a fire involving aniline may contain toxic nitrogen oxides and aniline vapor. Toxic aniline vapors are given off at high temperatures and form explosive mixtures in air. Carbon dioxide or dry chemical extinguishers should be used to fight aniline fires.

Chemical Reactivity

Reactivity with Water No reaction; Reactivity with Common Materials: No reaction; Stability During Transport: Stable; Neutralizing Agents for Acids and Caustics: Flush with water and rinse with dilute acetic acid; Polymerization: Not pertinent; Inhibitor of Polymerization: Not pertinent.

Biochem/physiol Actions

The acute toxicity of aniline involves its activation in vivo to 4-hydroxyaniline and the formation of adducts with hemoglobin. In erythrocytes, this is associated with the release of iron and the accumulation of methemoglobin and the development of hemolytic anemia and inflammation of the spleen. Tumor formation is often observed in the spleen on prolonged administration.

Toxicology

Aniline, a weakly alkaline liquid, is readily absorbed into the circulation after oral ingestion, inhalation and dermal contact. In human volunteers, more than 90 % of the inhaled aniline vapors (5 – 30 mg/m3) were absorbed in the state of rest . The percutaneous uptake from the vapor phase accounted for 25 – 30 % of the total incorporation in normally dressed individuals at 25 ?C and 35 % relative air humidity (estimated absorption rate: 0.2 – 0.4 μg cm?2h?1), but increased by 21 and 29 % when the temperature was elevated by 5 ?Cand the humidity from 35 to 75 %, respectively . Likewise, when applied as liquid to human skin from a drained gauze (concentration 10 mg/cm2), skin absorption of aniline was between 0.2 and 0.7 mg cm?2h?1 but could reach up to 3.5 mg cm?2h?1 on highly moistened skin , also temperature appeared to be a factor.
Aniline undergoes rapid oxidation, mainly in the liver, but also in other organs like the intestine and erythrocytes. Three primary transformation reactions compete with each other and are expressed to varying degree in different species and individuals:
1) N-Hydroxylation
2) (Ring) hydroxylation
3) N-Acetylation followed by p-(ring) hydroxylation
In secondary steps, the hydroxyl intermediates are rapidly conjugated, largely to sulfate and glucuronic acid and excreted, mainly in the urine . In humans, the half-life of aniline is ca. 3.5 h .
The primary conversion products, mainly phenylhydroxylamine and p-aminophenol as well as their oxidized forms nitrosobenzene and p-iminoquinone, resulting from reactions 1 and 2, are regarded as toxification steps to biologically active compounds (see below), whereas N-acetylation may be considered as a detoxification step, which is followed by phydroxylation to N-acetyl-p-aminophenol. NAcetyl transferase is congenitally expressed to varying extent in humans (“strong and weak acetylators”; see below); this is a reason for different individual susceptibilities.
Certain metabolites, such as nitrosobenzene, are coupled to thiols, especially glutathione; the quantities of aniline-protein conjugates, especially aniline-Hb adducts in blood, are diagnostic tools for the estimation of aniline exposure and body burden .

Safety Profile

Suspected carcinogen with experimental neoplastigenic data. A human poison by an unspecified route. Poison experimentally by most routes incluhng inhalation and ingestion. Experimental reproductive effects. A skin and severe eye irritant, and a rmld sensitizer. In the body, aniline causes formation of methemoglobin, resulting in prolonged anoxemia and depression of the central nervous system; less acute exposure causes hemolysis of the red blood cells, followed by stimulation of the bone marrow. The liver may be affected with resulting jaundice. Long-term exposure to a d n e dye manufacture has been associated with malignant bladder growths. A common air contaminant, A combustible liquid when exposed to heat or flame. To fight fire, use alcohol foam, CO2, dry chemical. It can react vigorously with oxidizing materials. When heated to decomposition it emits highly toxic fumes of NOx. Spontaneously explosive reactions occur with benzenediazonium-2-carboxylate, dibenzoyl peroxide, fluorine nitrate, nitrosyl perchlorate, red fuming nitric acid, peroxodisulfuric acid, and tetranitromethane. Violent reactions with boron trichloride, peroxyformic acid, dhsopropyl peroxydicarbonate, fluorine, trichloronitromethane (145℃), acetic anhydride, chlorosulfonic acid, hexachloromelamine, (HNO3 + N2O4 + H2SO4), (nitrobenzene + glycerin), oleum, (HCHO + HClO4), perchromates, K2O2, ppropiolactone, AgClO4, Na2On, H2SO4, trichloromelamine, acids, peroxydisulfuric acid, F03Cl, diisopropyl peroxy-dicarbonate, n-haloimides, and trichloronitromethane. Ignites on contact with sodium peroxide + water. Forms heator shock-sensitive explosive mixtures with anhnium chloride (detonates at 240°C/7.6 bar), nitromethane, hydrogen peroxide, 1 -chloro-2,3- epoxypropane, and peroxomonosulfuric acid. Reactions with perchloryl fluoride, perchloric acid, and ozone form explosive products.

Synthesis

The highly exothermic catalytic hydrogenation (ΔH =?544 kJ/mol at 200 ?C) of nitrobenzene is performed both in the vapor and in the liquid phase in commercially used processes .

Potential Exposure

Aniline is widely used as an intermediate in the synthesis of dyestuffs. It is also used in the manufacture of rubber accelerators and antioxidants, pharmaceuticals, marking inks; tetryl, optical whitening agents; photographic developers; resins, varnishes, perfumes, shoe polishes, and many organic chemicals.

First aid

If this chemical gets into the eyes, remove anycontact lenses at once and irrigate immediately for at least15 min, occasionally lifting upper and lower lids. Seekmedical attention immediately. If this chemical contactsthe skin, remove contaminated clothing and wash immediately with soap and water. Seek medical attention immediately. If this chemical has been inhaled, remove fromexposure, begin rescue breathing (using universal precautions, including resuscitation mask) if breathing hasstopped and CPR if heart action has stopped. Transferpromptly to a medical facility. When this chemical hasbeen swallowed, get medical attention. Give large quantities of water and induce vomiting. Do not make an unconscious person vomit.Note to physician: Treat for methemoglobinemia.Spectrophotometry may be required for precise determination of levels of methemoglobinemia in urine.

Carcinogenicity

The IARC has classified aniline as a Group 3 carcinogen, that is, not classifiable as to its carcinogenicity. However, NIOSH has determined that there is sufficient evidence to recommend that OSHA require labeling this substance a potential occupational carcinogen. This position followed an evaluation of a high-dose feeding study of aniline hydrochloride in F344 rats and B6C3F1 mice (3000 or 6000 ppm and 6000 or 12,000 ppm, respectively). The test was negative in both sexes of mice; however, hemangiosarcomas of the spleen and combined incidence of fibrosarcomas and sarcomas of the spleen were statistically significant in the male rats; the number of female rats having fibrosarcomas of the spleen was also significant.

Source

Detected in distilled water-soluble fractions of regular gasoline (87 octane) and Gasohol at concentrations of 0.55 and 0.20 mg/L, respectively (Potter, 1996). Aniline was also detected in 82% of 65 gasoline (regular and premium) samples (62 from Switzerland, 3 from Boston, MA). At 25 °C, concentrations ranged from 70 to 16,000 μg/L in gasoline and 20 to 3,800 μg/L in watersoluble fractions. Average concentrations were 5.8 mg/L in gasoline and 1.4 mg/L in watersoluble fractions (Schmidt et al., 2002).
Based on laboratory analysis of 7 coal tar samples, aniline concentrations ranged from ND to 13 ppm (EPRI, 1990).
Aniline in the environment may originate from the anaerobic biodegradation of nitrobenzene (Razo-Flores et al., 1999).

storage

Color Code—Blue: Health Hazard/Poison: Store ina secure poison location. Prior to working with this chemicalyou should be trained on its proper handling and storage.Before entering confined space where aniline may be present, check to make sure that an explosive concentration doesnot exist. Store in tightly closed containers in a cool, dry,dark, well-ventilated area. Metal containers involving thetransfer of this chemical should be grounded and bonded.Where possible, automatically pump liquid from drums orother storage containers to process containers. Drums mustbe equipped with self-closing valves, pressure vacuumbungs, and flame arresters. Use only nonsparking tools andequipment, especially when opening and closing containersof this chemical. Where this chemical is used, handled, manufactured, or stored, use explosion-proof electrical equipment and fittings. Sources of ignition, such as smoking andopen flames, are prohibited where this chemical is used,handled, or stored in a manner that could create a potentialfire or explosion hazard. A regulated, marked area should beestablished where this chemical is handled, used, or storedin compliance with OSHA Standard 1910.1045.

Shipping

Aninline requires a shipping label of“POISONOUS/TOXIC MATERIALS.” It falls in HazardClass 6.1 and the Packing Group is II.[19, 20] Aniline carriesa plus sign ( 1 ), indicating that the designated proper shipping name and hazard class of the material must always beshown whether or not the material or its mixtures or solutions meet the definitions of the class. The hydrochloriderequires a “POISONOUS/TOXIC MATERIALS” label. Itfalls in Hazard Class 6.1 and Packing Group III.

Incompatibilities

May form explosive mixture with air. Unless inhibited (usually methanol), aniline is readily able to polymerize. Fires and explosions may result from contact with halogens, strong acids; oxidizers, strong base organic anhydrides; acetic anhydride, isocyanates, aldehydes, sodium peroxide. Strong reaction with toluene diisocyanate. Reacts with alkali metals and alkali earth metals. Attacks some plastics, rubber and coatings; copper and copper alloys.

Waste Disposal

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. Incineration with provision for nitrogen oxides removal from flue gases by scrubber, catalytic or thermal device.