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Aniline
Aniline
Aniline
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Aniline
Structural formula of aniline
Structural formula of aniline
Aniline
Aniline
Names
Preferred IUPAC name
Aniline[1]
Systematic IUPAC name
Benzenamine
Other names
Phenylamine
Aminobenzene
Benzamine
Identifiers
3D model (JSmol)
605631
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.491 Edit this at Wikidata
EC Number
  • 200-539-3
2796
KEGG
RTECS number
  • BW6650000
UNII
UN number 1547
  • InChI=1S/C6H7N/c7-6-4-2-1-3-5-6/h1-5H,7H2 checkY
    Key: PAYRUJLWNCNPSJ-UHFFFAOYSA-N checkY
  • InChI=1/C6H7N/c7-6-4-2-1-3-5-6/h1-5H,7H2
    Key: PAYRUJLWNCNPSJ-UHFFFAOYAP
  • Nc1ccccc1
  • c1ccc(cc1)N
Properties
C6H5NH2
Molar mass 93.129 g·mol−1
Appearance Colorless liquid
Density 1.0297 g/mL
Melting point −6.30 °C (20.66 °F; 266.85 K)
Boiling point 184.13 °C (363.43 °F; 457.28 K)
3.6 g/(100 mL) at 20 °C
Vapor pressure 0.6 mmHg (20 °C)[2]
Acidity (pKa)
  • 4.63 (conjugate acid; H2O)[3]
−62.95·10−6 cm3/mol
1.58364
Viscosity 3.71 cP (3.71 mPa·s at 25 °C)
Thermochemistry
−3394 kJ/mol
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
 potential occupational carcinogen
GHS labelling:
GHS05: CorrosiveGHS06: ToxicGHS08: Health hazardGHS09: Environmental hazardGHS07: Exclamation mark
Danger
H301, H311, H317, H318, H331, H341, H351, H372, H400
P201, P202, P260, P261, P264, P270, P271, P272, P273, P280, P281, P301+P310, P302+P352, P304+P340, P305+P351+P338, P308+P313, P310, P311, P312, P314, P321, P322, P330, P333+P313, P361, P363, P391, P403+P233, P405, P501
NFPA 704 (fire diamond)
[5]
NFPA 704 four-colored diamondHealth 3: Short exposure could cause serious temporary or residual injury. E.g. chlorine gasFlammability 2: Must be moderately heated or exposed to relatively high ambient temperature before ignition can occur. Flash point between 38 and 93 °C (100 and 200 °F). E.g. diesel fuelInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
3
2
0
Flash point 70 °C (158 °F; 343 K)
770 °C (1,420 °F; 1,040 K)
Explosive limits 1.3–11%[2]
Lethal dose or concentration (LD, LC):
195 mg/kg (dog, oral)
250 mg/kg (rat, oral)
464 mg/kg (mouse, oral)
440 mg/kg (rat, oral)
400 mg/kg (guinea pig, oral)[4]
175 ppm (mouse, 7 h)[4]
250 ppm (rat, 4 h)
180 ppm (cat, 8 h)[4]
NIOSH (US health exposure limits):
PEL (Permissible)
 TWA 5 ppm (19 mg/m3) [skin][2]
REL (Recommended)
 Ca [potential occupational carcinogen][2]
IDLH (Immediate danger)
 100 ppm[2]
Related compounds
1-Naphthylamine
2-Naphthylamine
Related compounds
 Phenylhydrazine
Nitrosobenzene
Nitrobenzene
Supplementary data page
Aniline (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Aniline (From Portuguese: anil, meaning 'indigo shrub', and -ine indicating a derived substance)[6] is an organic compound with the formula C6H5NH2. Consisting of a phenyl group (−C6H5) attached to an amino group (−NH2), aniline is the simplest aromatic amine. It is an industrially significant commodity chemical, as well as a versatile starting material for fine chemical synthesis. Its main use is in the manufacture of precursors to polyurethane, dyes, and other industrial chemicals. Like most volatile amines, it has the odor of rotten fish. It ignites readily, burning with a smoky flame characteristic of aromatic compounds.[7] It is toxic to humans.

Relative to benzene, aniline is "electron-rich". It thus participates more rapidly in electrophilic aromatic substitution reactions. Likewise, it is also prone to oxidation: while freshly purified aniline is an almost colorless oil, exposure to air results in gradual darkening to yellow or red, due to the formation of strongly colored, oxidized impurities. Aniline can be diazotized to give a diazonium salt, which can then undergo various nucleophilic substitution reactions.

Like other amines, aniline is both a base (pKaH = 4.6) and a nucleophile, although less so than structurally similar aliphatic amines.

Because an early source of the benzene from which they are derived was coal tar, aniline dyes are also called coal tar dyes.

Structure

[edit]
Ball-and-stick model of aniline from the crystal structure at 252 K

Aryl-N distances

[edit]

In aniline, the C−N bond length is 1.41 Å,[8] compared to the C−N bond length of 1.47 Å for cyclohexylamine,[9] indicating partial π-bonding between C(aryl) and N.[10] The length of the chemical bond of C(aryl)−NH2 in anilines is highly sensitive to substituent effects. The C−N bond length is 1.34 Å in 2,4,6-trinitroaniline vs 1.44 Å in 3-methylaniline.[11]

Pyramidalization

[edit]

The amine group in anilines is a slightly pyramidalized molecule, with hybridization of the nitrogen somewhere between sp3 and sp2. The nitrogen is described as having high p character. The amino group in aniline is flatter (i.e., it is a "shallower pyramid") than that in an aliphatic amine, owing to conjugation of the lone pair with the aryl substituent. The observed geometry reflects a compromise between two competing factors: 1) stabilization of the N lone pair in an orbital with significant s character favors pyramidalization (orbitals with s character are lower in energy), while 2) delocalization of the N lone pair into the aryl ring favors planarity (a lone pair in a pure p orbital gives the best overlap with the orbitals of the benzene ring π system).[12][13]

Consistent with these factors, substituted anilines with electron donating groups are more pyramidalized, while those with electron withdrawing groups are more planar. In the parent aniline, the lone pair is approximately 12% s character, corresponding to sp7.3 hybridization.[12][clarification needed] (For comparison, alkylamines generally have lone pairs in orbitals that are close to sp3.)

The pyramidalization angle between the C–N bond and the bisector of the H–N–H angle is 142.5°.[14] For comparison, in more strongly pyramidal amine group in methylamine, this value is ~125°, while that of the amine group in formamide has an angle of 180°.

Production

[edit]

Industrial aniline production involves hydrogenation of nitrobenzene (typically at 200–300 °C) in the presence of metal catalysts:[15] Approximately 4 billion kilograms are produced annually. Catalysts include nickel, copper, palladium, and platinum,[7] and newer catalysts continue to be discovered.[16]

The reduction of nitrobenzene to aniline was first performed by Nikolay Zinin in 1842, using sulfide salts (Zinin reaction). The reduction of nitrobenzene to aniline was also performed as part of reductions by Antoine Béchamp in 1854, using iron as the reductant (Bechamp reduction). These stoichiometric routes remain useful for specialty anilines.[17]

Aniline can alternatively be prepared from ammonia and phenol derived from the cumene process.[7]

In commerce, three brands of aniline are distinguished: aniline oil for blue, which is pure aniline; aniline oil for red, a mixture of equimolecular quantities of aniline and ortho- and para-toluidines; and aniline oil for safranine, which contains aniline and ortho-toluidine and is obtained from the distillate (échappés) of the fuchsine fusion.[18]

[edit]

Many analogues and derivatives of aniline are known where the phenyl group is further substituted. These include toluidines, xylidines, chloroanilines, aminobenzoic acids, nitroanilines, and many others. They also are usually prepared by nitration of the substituted aromatic compounds followed by reduction. For example, this approach is used to convert toluene into toluidines and chlorobenzene into 4-chloroaniline.[7] Alternatively, using Buchwald-Hartwig coupling or Ullmann reaction approaches, aryl halides can be aminated with aqueous or gaseous ammonia.[19]

Reactions

[edit]

The chemistry of aniline is rich because the compound has been cheaply available for many years. Below are some classes of its reactions.

Oxidation

[edit]
Sample of 2,6-diisopropylaniline, a colorless liquid when pure, illustrating the tendency of anilines to air-oxidize to dark-colored products.

The oxidation of aniline has been heavily investigated, and can result in reactions localized at nitrogen or more commonly results in the formation of new C-N bonds. In alkaline solution, azobenzene results, whereas arsenic acid produces the violet-coloring matter violaniline. Chromic acid converts it into quinone, whereas chlorates, in the presence of certain metallic salts (especially of vanadium), give aniline black. Hydrochloric acid and potassium chlorate give chloranil. Potassium permanganate in neutral solution oxidizes it to nitrobenzene; in alkaline solution to azobenzene, ammonia, and oxalic acid; in acid solution to aniline black. Hypochlorous acid gives 4-aminophenol and para-amino diphenylamine.[18] Oxidation with persulfate affords a variety of polyanilines. These polymers exhibit rich redox and acid-base properties.

Polyanilines can form upon oxidation of aniline.

Electrophilic reactions at ortho- and para- positions

[edit]

Like phenols, aniline derivatives are highly susceptible to electrophilic substitution reactions. Its high reactivity reflects that it is an enamine, which enhances the electron-donating ability of the ring. For example, reaction of aniline with sulfuric acid at 180 °C produces sulfanilic acid, H2NC6H4SO3H.

If bromine water is added to aniline, the bromine water is decolourised and a white precipitate of 2,4,6-tribromoaniline is formed. To generate the mono-substituted product, a protection with acetyl chloride is required:

Aniline can react with bromine even in room temperatures in water. Acetyl chloride is added to prevent tribromination.

The reaction to form 4-bromoaniline is to protect the amine with acetyl chloride, then hydrolyse back to reform aniline.

The largest scale industrial reaction of aniline involves its alkylation with formaldehyde. An idealized equation is shown:

2 C6H5NH2 + CH2O → CH2(C6H4NH2)2 + H2O

The resulting diamine is the precursor to 4,4'-MDI and related diisocyanates.

Reactions at nitrogen

[edit]

Basicity

[edit]

Aniline is a weak base. Aromatic amines such as aniline are, in general, much weaker bases than aliphatic amines. Aniline reacts with strong acids to form the anilinium (or phenylammonium) ion (C6H5−NH+3).[20]

Traditionally, the weak basicity of aniline is attributed to a combination of inductive effect from the more electronegative sp2 carbon and resonance effects, as the lone pair on the nitrogen is partially delocalized into the pi system of the benzene ring. (see the picture below):

The lone electron pair on the nitrogen delocalizes into the pi system of the benzene ring. This is responsible for nitrogen's weaker basicity compared to other amines.

Missing in such an analysis is consideration of solvation. Aniline is, for example, more basic than ammonia in the gas phase, but ten thousand times less so in aqueous solution.[21]

Acylation

[edit]
Main article: Anilide

Aniline reacts with acyl chlorides such as acetyl chloride to give amides. The amides formed from aniline are sometimes called anilides, for example CH3−C(=O)−NH−C6H5 is acetanilide. At high temperatures aniline and carboxylic acids react to give the anilides.[22]

N-Alkylation

[edit]

N-Methylation of aniline with methanol at elevated temperatures over acid catalysts gives N-methylaniline and N,N-dimethylaniline:

C6H5NH2 + 2 CH3OH → C6H5N(CH3)2 + 2H2O

N-Methylaniline and N,N-dimethylaniline are colorless liquids with boiling points of 193–195 °C and 192 °C, respectively. These derivatives are of importance in the color industry.

Carbon disulfide derivatives

[edit]

Boiled with carbon disulfide, it gives sulfocarbanilide (diphenylthiourea) (S=C(−NH−C6H5)2), which may be decomposed into phenyl isothiocyanate (C6H5−N=C=S), and triphenyl guanidine (C6H5−N=C(−NH−C6H5)2).[18]

Diazotization

[edit]

Aniline and its ring-substituted derivatives react with nitrous acid to form diazonium salts. One example is benzenediazonium tetrafluoroborate. Through these intermediates, the amine group can be converted to a hydroxyl (−OH), cyanide (−CN), or halide group (−X, where X is a halogen) via Sandmeyer reactions. This diazonium salt can also be reacted with NaNO2 and phenol to produce a dye known as benzeneazophenol, in a process called coupling. The reaction of converting primary aromatic amine into diazonium salt is called diazotisation. In this reaction primary aromatic amine is allowed to react with sodium nitrite and 2 moles of HCl, which is known as "ice cold mixture" because the temperature for the reaction was as low as 0.5 °C. The benzene diazonium salt is formed as major product alongside the byproducts water and sodium chloride.

Other reactions

[edit]

It reacts with nitrobenzene to produce phenazine in the Wohl–Aue reaction. Hydrogenation gives cyclohexylamine.

Being a standard reagent in laboratories, aniline is used for many niche reactions. Its acetate is used in the aniline acetate test for carbohydrates, identifying pentoses by conversion to furfural. It is used to stain neural RNA blue in the Nissl stain.[citation needed]

In addition, aniline is the starting component in the production of diglycidyl aniline.[23] Epichlorohydrin is the other main ingredient.[23][24]

Uses

[edit]

Aniline is predominantly used for the preparation of methylenedianiline and related compounds by condensation with formaldehyde. The diamines are condensed with phosgene to give methylene diphenyl diisocyanate, a precursor to urethane polymers.[7]

Most aniline is consumed in the production of methylenedianiline, a precursor to polyurethanes.

Other uses include rubber processing chemicals (9%), herbicides (2%), and dyes and pigments (2%).[25] As additives to rubber, aniline derivatives such as phenylenediamines and diphenylamine, are antioxidants. Illustrative of the drugs prepared from aniline is paracetamol (acetaminophen, Tylenol). The principal use of aniline in the dye industry is as a precursor to indigo, the blue of blue jeans.[7]

Cake of indigo dye, which is prepared from aniline.

Aniline oil is also used for mushroom identification. Kerrigan's 2016 Agaricus of North America P45: (Referring to Schaffer's reaction) "In fact I recommend switching to the following modified test. Frank (1988) developed an alternative formulation in which aniline oil is combined with glacial acetic acid (GAA, essentially distilled vinegar) in a 50:50 solution. GAA is a much safer, less reactive acid. This single combined reagent is relatively stable over time. A single spot or line applied to the pileus (or other surface). In my experience the newer formulation works as well as Schaffer's while being safer and more convenient."[26]

History

[edit]

Aniline was first isolated in 1826 by Otto Unverdorben by destructive distillation of indigo.[27] He called it Crystallin. In 1834, Friedlieb Runge isolated a substance from coal tar that turned a beautiful blue color when treated with chloride of lime. He named it kyanol or cyanol.[28] In 1840, Carl Julius Fritzsche (1808–1871) treated indigo with caustic potash and obtained an oil that he named aniline, after an indigo-yielding plant, anil (Indigofera suffruticosa).[29][30] In 1842, Nikolay Nikolaevich Zinin reduced nitrobenzene and obtained a base that he named benzidam.[31] In 1843, August Wilhelm von Hofmann showed that these were all the same substance, known thereafter as phenylamine or aniline.[32]

Synthetic dye industry

[edit]
Further information: Nigrosene

In 1856, while trying to synthesise quinine, von Hofmann's student William Henry Perkin discovered mauveine. Mauveine quickly became a commercial dye. Other synthetic dyes followed, such as fuchsin, safranin, and induline. At the time of mauveine's discovery, aniline was expensive. Soon thereafter, applying a method reported in 1854 by Antoine Béchamp,[33] it was prepared "by the ton".[34] The Béchamp reduction enabled the evolution of a massive dye industry in Germany. Today, the name of BASF, originally Badische Anilin- und Soda-Fabrik (English: Baden Aniline and Soda Factory), now the largest chemical supplier, echoes the legacy of the synthetic dye industry, built via aniline dyes and extended via the related azo dyes. The first azo dye was aniline yellow.[35]

Developments in medicine

[edit]

In the late 19th century, derivatives of aniline such as acetanilide and phenacetin emerged as analgesic drugs, with their cardiac-suppressive side effects often countered with caffeine.[36] Also in the late 19th century, Ehrlich found that the aniline dye methylene blue works as an antimalarial drug. He hypothesized that dyes that selectively stain pathogens over tissue would prefentially harm pathogens, leading to his "magic bullet" concept.[37]

During the first decade of the 20th century, while trying to modify synthetic dyes to treat African sleeping sickness, Paul Ehrlich – who had coined the term chemotherapy for his 'magic bullet' approach to medicine – failed and switched to modifying Béchamp's atoxyl, the first organic arsenical drug, and serendipitously obtained a treatment for syphilis – salvarsan – the first successful chemotherapy agent. Salvarsan's targeted microorganism, not yet recognized as a bacterium, was still thought to be a parasite, and medical bacteriologists, believing that bacteria were not susceptible to the chemotherapeutic approach, overlooked Alexander Fleming's report in 1928 on the effects of penicillin.[38]

In 1932, Bayer sought medical applications of its dyes. Gerhard Domagk identified as an antibacterial a red azo dye, introduced in 1935 as the first antibacterial drug, prontosil, soon found at Pasteur Institute to be a prodrug degraded in vivo into sulfanilamide – a colorless intermediate for many, highly colorfast azo dyes – already with an expired patent, synthesized in 1908 in Vienna by the researcher Paul Gelmo for his doctoral research.[38] By the 1940s, over 500 related sulfa drugs were produced.[38] Medications in high demand during World War II (1939–45), these first miracle drugs, chemotherapy of wide effectiveness, propelled the American pharmaceutics industry.[39] In 1939, at Oxford University, seeking an alternative to sulfa drugs, Howard Florey developed Fleming's penicillin into the first systemic antibiotic drug, penicillin G. (Gramicidin, developed by René Dubos at Rockefeller Institute in 1939, was the first antibiotic, yet its toxicity restricted it to topical use.) After World War II, Cornelius P. Rhoads introduced the chemotherapeutic approach to cancer treatment.[40]

Rocket fuel

[edit]

Some early American rockets, such as the Aerobee and WAC Corporal, used a mixture of aniline and furfuryl alcohol as a fuel, with nitric acid as an oxidizer. The combination is hypergolic, igniting on contact between fuel and oxidizer. It is also dense, and can be stored for extended periods. Aniline was later replaced by hydrazine.[41]

Toxicology and testing

[edit]

Aniline is toxic by inhalation of the vapour, ingestion, or percutaneous absorption.[42][43] The IARC lists it in Group 2A (Probably carcinogenic to humans), and it has specifically been linked to bladder cancer.[44] Aniline has been implicated as one possible cause of forest dieback.[45]

Many methods exist for the detection of aniline.[46]

Oxidative DNA damage

[edit]

Exposure of rats to aniline can elicit a response that is toxic to the spleen, including a tumorigenic response.[47] Rats exposed to aniline in drinking water, showed a significant increase in oxidative DNA damage to the spleen, detected as a 2.8-fold increase in 8-hydroxy-2'-deoxyguanosine (8-OHdG) in their DNA.[47] Although the base excision repair pathway was also activated, its activity was not sufficient to prevent the accumulation of 8-OHdG. The accumulation of oxidative DNA damages in the spleen following exposure to aniline may increase mutagenic events that underlie tumorigenesis.

Notes

[edit]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Aniline

View on Grokipedia
from Grokipedia
Aniline is an with the molecular formula C₆H₅NH₂, serving as the prototypical and a fundamental building block in . It appears as a colorless to pale yellow oily liquid at , with a characteristic amine-like , though it darkens to brown upon exposure to air and light due to oxidation. Key physical properties include a of -6 °C, a of 184 °C, a of 1.022 g/mL at 25 °C, and limited in (approximately 3.6 g/100 mL at 25 °C) but high with most organic solvents. Chemically, aniline is a with a pKa of 4.6 for its conjugate acid, and it undergoes typical reactions of primary amines such as , , and diazotization, while its aromatic ring activates at ortho and para positions. First isolated in 1826 by German chemist Otto Unverdorben through the of , aniline derives its name from the Portuguese word "anil" for the indigo plant (). Its significance surged in the mid-19th century when, in 1856, 18-year-old accidentally synthesized —the first synthetic dye—from aniline derivatives while attempting to produce , sparking the aniline dye industry and the broader field of synthetic . Today, aniline is produced industrially on a massive scale, primarily via a two-step process: of to using a mixture of nitric and sulfuric acids, followed by catalytic of over metals like or . Global production reached approximately 10 million metric tons as of 2024, with major manufacturers including , Dow, and . Aniline's primary applications lie in its role as a versatile intermediate in , accounting for over 90% of its consumption. It is essential for producing polyurethane precursors like (MDI), which is used in foams, coatings, and adhesives; for synthesizing azo dyes, , and other colorants in the and industries; and for rubber accelerators, antioxidants, and pharmaceuticals such as and sulfonamides. Additionally, it finds use in agrochemicals like herbicides and in photographic chemicals. Despite its utility, aniline is toxic, causing upon exposure, and is classified as a probable by regulatory agencies, necessitating strict handling protocols in industrial settings.

Properties

Physical properties

Aniline is a colorless to pale yellow oily liquid at , with a characteristic often described as resembling rotten or musty. It has a molecular weight of 93.13 g/mol and appears denser than . Upon prolonged exposure to air and light, it gradually darkens to a reddish-brown color due to oxidation, forming colored impurities without significant loss in purity. Key thermodynamic properties include a of -6 °C and a of 184 °C at standard pressure. The is 1.022 g/mL at 25 °C, and the is 0.6 mmHg at 20 °C, with vapors heavier than air (vapor 3.22 relative to air). The is 1.586 at 20 °C, and the dynamic is 3.7 mPa·s at 25 °C.
PropertyValueConditions
Flash point70 °CClosed cup
Autoignition temperature615 °C-
Aniline exhibits limited solubility in water, with 3.6 g/100 mL at 20 °C, resulting in an aqueous solution pH of approximately 8.1 for a 1% solution due to its weak basicity. It is miscible with organic solvents such as ethanol, diethyl ether, and chloroform. The amino group contributes to its moderate polarity, influencing these solubility characteristics.

Molecular structure

Aniline has the \ceC6H5NH2\ce{C6H5NH2} and a molecular weight of 93.13 g/mol. The features a ring directly attached to an amino (\ce−NH2\ce{-NH2}) group, where the atom is bonded to the ipso carbon of the phenyl ring and two hydrogen atoms. Due to , the on the delocalizes into the π-electron system of the aromatic ring, contributing partial double-bond character to the C–N linkage and influencing the overall electronic distribution. This effect results in a C–N of 1.402 ± 0.002 Å, shorter than the 1.471 Å typical for aliphatic C–N bonds (as in methylamine) but comparable to the 1.397 Å C–C bond length in , reflecting the aryl nature of the connection. The atom in aniline exhibits , with an H–N–H bond angle of approximately 113°, intermediate between the tetrahedral ideal of 109.5° seen in and the planar 120° expected for full sp² hybridization. This pyramidalization is quantified by an out-of-plane angle of about 37.5° between the C–N bond and the plane of the \ceNH2\ce{NH2} group, arising from sp³ hybridization at modified by partial flattening toward planarity. The barrier to at is approximately 5.4 kcal/mol, lower than in simple alkylamines due to the conjugative stabilization in the . Aniline possesses a dipole moment of 1.53 D, attributable to the opposing electronic effects: the amino group acts as a donor, enriching on , while the phenyl ring exerts a modest inductive withdrawal, creating overall polarity with the negative end at the nitrogen.

Synthesis

Industrial production

The primary industrial method for aniline production is the catalytic of , which proceeds via the reaction C₆H₅NO₂ + 3H₂ → C₆H₅NH₂ + 2H₂O. This liquid-phase process typically employs or catalysts and operates at temperatures of 200–300 °C and pressures of 50–100 bar to achieve high conversion rates exceeding 99%. , the key feedstock, is obtained through the of with a of nitric and sulfuric acids. An alternative route, the Béchamp process, involves the reduction of using and , following the C₆H₅NO₂ + 3Fe + 6HCl → C₆H₅NH₂ + 3FeCl₂ + 3H₂O. Although historically significant, this method generates substantial waste and is now less common, primarily limited to facilities where the byproducts serve as pigments. Global aniline production reached approximately 10.4 million metric tons in 2024, driven by demand in and dye sectors, with major producers including SE, Dow Inc., and Covestro AG operating large-scale integrated plants. These facilities often employ continuous flow processes for to optimize throughput and energy use, followed by purification via at aniline's of 184 °C to remove , unreacted , and impurities like . Modern plants incorporate heat recovery systems and advanced catalysts to enhance energy efficiency, reducing consumption by up to 20% compared to older designs. Production of aniline derivatives, such as toluidines, is frequently integrated into the same facilities by hydrogenating nitrotoluenes derived from , allowing shared infrastructure for reactors and columns. Emerging sustainable methods include bio-based production. In February 2024, launched the world's first for bio-based aniline, using renewable feedstocks such as biomass-derived muconic acid via a biotechnological process, aiming to decarbonize production while maintaining compatibility with existing supply chains.

Laboratory methods

In laboratory settings, aniline is commonly prepared by the reduction of using tin and concentrated as the . The reaction proceeds as follows: C₆H₅NO₂ + 3Sn + 6HCl → C₆H₅NH₂ + 3SnCl₂ + 2H₂O. Typically, is added to granulated tin in a , followed by the slow addition of concentrated HCl while cooling in an to control the ; the mixture is then refluxed for several hours until the reduction is complete, as indicated by the cessation of . An alternative reducing system employs with HCl, which offers a cheaper option but requires similar conditions and generates more sludge. After reduction, the workup involves basification with to liberate the free aniline base from its salt, followed by to separate the volatile aniline from inorganic byproducts and unreacted materials. The distillate is then extracted multiple times with to isolate the organic layer, which is dried over solid pellets to remove residual water. Final purification is achieved by under reduced pressure (boiling point approximately 184°C at , but lowered to avoid ), yielding colorless aniline with typical laboratory yields of 70-85% when using excess tin and maintaining temperatures below 100°C during . Alternative methods include catalytic using (Pd/C) as the catalyst in solvent under hydrogen gas at and , which provides a cleaner procedure with minimal byproducts and yields exceeding 90% in small-scale setups equipped with a hydrogenator. Electrochemical reduction represents another option, employing a such as a cobalt phthalocyanine-modified electrode in an aqueous electrolyte, where nitrobenzene is selectively reduced to aniline at potentials around -0.8 V vs. SCE, suitable for controlled experiments in divided cells. For selective reduction in polynitro compounds, the Zinin reduction using aqueous sodium sulfide (Na₂S) is preferred, as it targets the ortho or para nitro group relative to activating substituents without affecting others, historically first applied to nitrobenzene itself. Safety considerations are paramount due to the corrosiveness of HCl and tin chlorides; reactions must be conducted in a with protective gloves, goggles, and avoiding direct contact, while optimizing yields involves precise of reducing agents and inert atmosphere to prevent side reactions.

Chemical reactions

Reactions of the amino group

The amino group in aniline exhibits basic properties, but it is significantly weaker than that of aliphatic amines or due to delocalization of the into the aromatic ring, which reduces its availability for . The pK_b of aniline is 9.40, corresponding to a pK_a of 4.60 for its conjugate acid (anilinium ion), making it a compared to (pK_a 9.25 for ammonium ion). This diminished basicity influences its reactivity in acid-base equilibria and -dependent transformations. Acylation of the amino group is a common protective strategy in , where aniline reacts with acylating agents like to form , an that moderates the amino group's reactivity. The reaction proceeds as follows: C6H5NH2+(CH3CO)2O→C6H5NHCOCH3+CH3COOH\mathrm{C_6H_5NH_2 + (CH_3CO)_2O \rightarrow C_6H_5NHCOCH_3 + CH_3COOH} This transformation is nucleophilic, with the amino group attacking the carbonyl carbon of the anhydride, and is often employed to prevent unwanted side reactions during multi-step syntheses. N-Alkylation involves the nucleophilic attack of aniline's amino group on alkyl halides, yielding secondary or tertiary amines such as N-methylaniline from methyl iodide. For example: C6H5NH2+CH3I→C6H5NHCH3+HI\mathrm{C_6H_5NH_2 + CH_3I \rightarrow C_6H_5NHCH_3 + HI} However, overalkylation to tertiary amines or salts is a frequent challenge due to the increased nucleophilicity of the products, which can be mitigated by using excess aniline or selective catalysts. Diazotization is a key transformation where the amino group is converted to a diazonium salt, serving as a versatile intermediate for further derivatization. Aniline reacts with in the presence of at 0–5 °C: C6H5NH2+NaNO2+2HCl→C6H5N2+Cl−+NaCl+2H2O\mathrm{C_6H_5NH_2 + NaNO_2 + 2HCl \rightarrow C_6H_5N_2^+ Cl^- + NaCl + 2H_2O} This low-temperature condition stabilizes the diazonium ion, preventing decomposition, and enables subsequent reactions like Sandmeyer coupling or formation. Additional reactions of the amino group include its interaction with (CS₂) in basic aqueous media to form phenyl dithiocarbamate salts, which are useful precursors in synthesis. Aniline also condenses with aldehydes to produce Schiff bases (imines), such as N-benzylideneaniline from , via and dehydration.

Electrophilic aromatic substitution

The amino group (-NH₂) in aniline serves as a strong activating and ortho/para director in (EAS) reactions, primarily due to its +R ( donating) effect. This donation delocalizes the of electrons from into the aromatic ring, significantly increasing the at the ortho and para positions relative to the -NH₂ group. As a result, electrophilic attack is favored at these sites, making the ring highly nucleophilic. This activation leads to a dramatic enhancement in reactivity, with the overall rate of EAS for aniline being approximately 10⁷ times faster than that for under comparable conditions. However, the high reactivity often results in polysubstitution, necessitating protective strategies for controlled monosubstitution. For instance, in , treatment of aniline with three equivalents of Br₂ in acetic acid or aqueous medium rapidly yields 2,4,6-tribromoaniline along with the anilinium hydrobromide salt (C₆H₅NH₂ + 3 Br₂ → C₆H₂Br₃NH₂ + 3 HBr, where the product is typically isolated as C₆H₅NH₂·2HBr + C₆H₂Br₃NH₂). shows a strong preference for the para position in initial substitution steps due to lower steric hindrance compared to ortho sites, though the ortho positions are also activated and lead to trisubstitution under mild conditions. Nitration of aniline similarly proceeds at ortho and para positions but is complicated by oxidation and polysubstitution when using mixed HNO₃/H₂SO₄; thus, the amino group is commonly protected by to form (C₆H₅NHCOCH₃), which moderates the activation while retaining ortho/para directionality. of yields predominantly the para isomer (about 70-80% para-nitro), which can be hydrolyzed back to p-nitroaniline. Sulfonation also favors the para position, with heating aniline (formed from aniline and H₂SO₄) at 180-200°C producing (4-aminobenzenesulfonic acid) as the major product, attributed to the greater thermodynamic stability of the para isomer and steric factors disfavoring ortho substitution; the reaction is reversible, further driving selectivity toward the more stable para-sulfonated product.

Other reactions

Aniline undergoes oxidation reactions that vary depending on the oxidizing agent employed. Mild oxidants such as or air can lead to the formation of , also known as aniline black, a conducting polymer resulting from the oxidative of aniline monomers. Stronger oxidants like (KMnO₄) promote the formation of imines through further oxidation of the aromatic ring, often involving radical intermediates and leading to colored products. Additionally, aerial oxidation under catalytic conditions can selectively convert aniline to via intermediate coupling. In reactions, aniline derivatives participate in formation following diazotization of another aniline molecule, where the resulting diazonium ion (e.g., C₆H₅N₂⁺) acts as an coupling with the electron-rich aniline ring to yield derivatives, typically in acidic media to stabilize the diazonium species. This process is a cornerstone for synthesizing symmetric azo dyes, with yields often exceeding 80% under optimized conditions. Aniline serves as a in metal complexation with transition metals, forming coordination compounds that facilitate catalytic processes. For instance, aniline coordinates to Cu²⁺ ions via the , enabling applications in C–H reactions where air serves as the oxidant. Similarly, complexes with aniline derivatives, such as 2-(methylthio)aniline-Pd(II), exhibit high efficiency in –Miyaura cross-coupling reactions conducted in aqueous media, achieving turnover numbers up to 10⁵. Photochemical reactions of aniline under UV lead to and , particularly at wavelengths around 193 nm, where the molecule fragments into phenyl and NH₂ radicals or undergoes ring distortion. Specific conditions, such as photocatalytic setups with complexes, can induce dimerization of aniline derivatives, forming stable π-dimers that contribute to initiation. Thermal decomposition of aniline occurs above 300 °C, primarily yielding and gas through homolytic cleavage of the C–N bond and subsequent radical rearrangements, with minor byproducts like hydrogen and depending on the atmosphere. This process highlights aniline's thermal stability relative to , with decomposition rates increasing exponentially beyond 350 °C.

Applications

Dyes and pigments

Aniline played a pivotal role in the development of the synthetic industry as the key precursor to , the first commercially successful synthetic , discovered in 1856 by through the oxidation of impure aniline containing toluidine impurities. This accidental discovery during attempts to synthesize marked the birth of the modern color chemistry field, enabling vibrant, stable dyes for textiles that surpassed natural alternatives in consistency and scalability. Azo dyes, which constitute the largest class of synthetic colorants, are commonly synthesized from aniline via diazotization to form benzenediazonium chloride, followed by coupling with electron-rich aromatic compounds such as or naphthols to yield intensely colored products. Representative examples include , produced by coupling diazotized aniline with aniline itself, resulting in a bright yellow hue suitable for textiles and inks, and , derived from the diazotization of (an aniline sulfonate) coupled with N,N-dimethylaniline, widely used as a and in analytical applications due to its sharp color change. These reactions highlight aniline's versatility as a component, enabling a vast array of shades from yellow to red and brown. Aniline derivatives also serve as intermediates in the production of , notably synthetic , which is manufactured via the Heumann process involving the condensation of aniline with to form N-phenylglycine, followed by cyclization and oxidation. This method revolutionized the of and , providing a deep blue color with excellent fastness properties that natural could not match, and it remains a cornerstone for vat applications in textiles. In contemporary applications, approximately 7% of aniline production (based on 1990s US data) is directed toward dyes and pigments, supporting the creation of acid dyes such as acid blue 45 (from aniline-based azo structures) for and , and direct dyes like direct blue 1 for cellulosic fibers in apparel and paper industries. These colorants leverage aniline's reactivity to achieve high tinctorial strength and affinity for substrates, contributing to the estimated 1 million tons of synthetic dyes produced annually worldwide. Effluents from aniline-based dye production pose environmental challenges due to the persistence and toxicity of residual aniline and azo compounds, necessitating advanced treatment methods like (AOPs), which effectively mineralize these pollutants into harmless byproducts such as CO₂ and water. Regulatory frameworks, including those from the U.S. Environmental Protection Agency, classify certain aniline-derived wastes as hazardous, mandating or physicochemical treatments to mitigate aquatic and prevent in ecosystems.

Pharmaceuticals and agrochemicals

Aniline derivatives play a crucial role in the synthesis of various pharmaceuticals and agrochemicals, primarily through and reduction reactions that protect the amino group and introduce functional moieties for . In the United States, approximately 4% of aniline production is directed toward pharmaceuticals (based on data), with additional usage in agrochemicals contributing to broader applications in bioactive compounds. These derivatives often involve the reduction of nitroaniline intermediates using catalytic methods, such as ferrite nanoparticles for selective , to yield the corresponding anilines essential for therapeutic and pesticidal . A prominent example in pharmaceuticals is (acetaminophen), synthesized industrially from aniline via to , followed by to p-nitroacetanilide, and subsequent reduction of the nitro group to afford directly. This route leverages the reduction step to maintain the acetamido group, enabling 's role as a widely used and . received regulatory approval from the U.S. (FDA) and holds a significant in the global analgesics sector, with the paracetamol market valued at approximately USD 922 million in 2024 and projected to reach USD 1,460 million by 2034. Sulfonamide antibiotics, such as , are another key class derived from aniline through protection as , followed by sulfonation with chlorosulfonic acid to form p-acetamidobenzenesulfonyl chloride, , and to the free . was historically approved by the FDA in the 1930s for treating bacterial infections, though its market has diminished due to newer antibiotics; it remains available in topical formulations like vaginal creams for use, with global pricing around USD 30,780 per metric ton in the U.S. as of 2022. Antimalarials like are synthesized via a starting from 4-methoxy-2-nitroaniline—a nitroaniline derivative of aniline—condensed with and reduced to the aminoquinoline structure. phosphate is FDA-approved for the radical cure of and prevention of relapses, with the global primaquine market valued at USD 150 million in 2024 and expected to reach USD 250 million by 2033. In agrochemicals, herbicides such as propanil are produced from 3,4-dichloroaniline—an aniline derivative obtained via of 1,2-dichloro-4-nitrobenzene—acylated with to form the active . This reduction of the nitroaniline precursor is critical for generating the arylamine backbone. Propanil is registered by the U.S. Environmental Protection Agency (EPA) for selective post-emergence in , with an interim registration review decision issued in 2020 confirming its eligibility under the Federal Insecticide, Fungicide, and Rodenticide Act. The global propanil market is projected to reach USD 310 million by 2032, driven by demand in rice cultivation in and .

Other industrial uses

A significant portion of aniline production serves as a precursor to (MDI), which is essential for manufacturing foams used in insulation, furniture, and automotive applications. Worldwide, 73% to 85% of aniline is directed toward MDI synthesis, highlighting its central role in the . Major chemical producers like and integrate aniline production with MDI facilities to streamline operations and reduce costs in this vertically aligned industry. Aniline derivatives are also employed in the rubber industry as and accelerators to enhance and prevent degradation from oxidation and heat. For instance, N-phenyl-β-naphthylamine, synthesized from aniline, acts as a key in and other rubber products, extending service life in demanding conditions. In the explosives sector, aniline functions as an intermediate and stabilizer in the production of various high-energy materials, contributing to formulations that require components for stability and performance. Specific derivatives like hydrazobenzene are utilized in explosive compositions, while , derived through processes involving aniline intermediates, serves as a component in propellants. Aniline contributes to photographic chemicals, where it is used in the synthesis of developers and sensitizers that facilitate in traditional . Global aniline consumption reached approximately 10.4 million tons in 2024, with projections to grow at a of 4.48% to 16.14 million tons by 2033, driven largely by demand in and rubber sectors. This growth underscores aniline's integration into major supply chains, where production is often co-located with downstream users to optimize and efficiency in hubs.

History

Discovery and early development

Aniline was first isolated in by German chemist Otto Unverdorben through the of , a process involving heating the plant-derived dye in the presence of lime to yield a crystalline substance he named "." This marked the initial recognition of the compound, though its chemical identity remained unclear at the time. In 1834, Friedlieb Runge isolated a similar substance from , the byproduct of coal coking, and named it "kyanol" after observing its reaction with to produce a striking color. Runge's work highlighted as a potential natural source for the compound, distinct from . Seven years later, in , Russian chemist Carl Julius Fritzsche prepared the substance by heating with caustic potash, yielding an oily liquid he termed "aniline," derived from the word anil for . That same period saw further experimentation, including Fritzsche's attempts at reduction methods, though the definitive reduction came shortly after. A pivotal advancement occurred in 1842 when Russian chemist Nikolay Zinin achieved the partial reduction of using ammonium sulfide, producing a base he called "benzidam." This key experiment demonstrated a synthetic route from , establishing a foundational method for preparation and underscoring aniline's relation to derivatives. In 1843, August Wilhelm Hofmann elucidated the structural identity of these substances, confirming through comparative analysis that "crystallin," "kyanol," "aniline," and "benzidam" were the same compound, which he recognized early as phenylamine (C₆H₅NH₂). Hofmann's work, including degradative studies on related dyes, laid the groundwork for understanding aniline's phenylamine structure, resolving prior confusions and standardizing the name "aniline."

Industrial applications

The synthesis of by in 1856 marked a pivotal moment in the commercialization of aniline, igniting the synthetic industry as the first viable artificial colorant derived from aniline. and subsequent factory establishment in 1857 enabled large-scale production, transforming textile coloring from expensive natural sources to affordable synthetics and spurring global . By 1900, the synthetic dye sector had expanded dramatically, driven by innovations in aniline derivatives like and aniline black. Key milestones in the late 19th century included BASF's development of efficient industrial processes for aniline in the 1880s, which optimized reduction methods from and scaled output for dyes such as and eosins, solidifying Germany's dominance in the sector. In , aniline's role extended to pharmaceuticals through the development of sulfanilamide, a derivative from azo dye research, which became a groundbreaking antibacterial agent and paved the way for sulfa drugs treating infections like streptococcal . During , aniline served as a critical component in rocket fuels, such as in the German missile's /aniline propellant system, enabling hypergolic ignition for military applications. Post-war, the witnessed a polyurethane boom, with aniline used to produce (MDI), fueling the rapid growth of flexible and rigid foams for consumer goods, coatings, and adhesives amid economic recovery. Production methods shifted in the toward catalytic of , replacing older iron-based reductions for higher efficiency and purity, which supported this expansion. By the mid-2000s, global aniline output had reached approximately 5 million tons annually, reflecting diversified uses beyond s. As of , global production exceeded 10 million tons annually, driven by demand in polyurethanes and other sectors. However, the introduced environmental regulations, such as the U.S. , which imposed strict effluent controls on dye manufacturing, leading to plant closures and process overhauls to mitigate from aniline residues.

Health and safety

Toxicity

Aniline exposure poses significant health risks, primarily through its ability to induce , a condition where is oxidized to , impairing oxygen transport in the blood. Acute effects manifest rapidly following exposure, with symptoms including (bluish discoloration of the skin and mucous membranes), , , , and ; in severe cases, it can lead to convulsions, , or death due to . This oxidation occurs via aniline's metabolites interacting with , and it is particularly dangerous in infants, where it can mimic . The oral LD50 in rats is 250 mg/kg, indicating moderate . Chronic exposure to aniline is associated with carcinogenic potential, with the International Agency for Research on Cancer (IARC) classifying it as probably carcinogenic to humans (Group 2A) based on sufficient evidence in experimental animals and limited evidence in humans, particularly linking occupational exposure to increased bladder cancer risk. Studies of workers in industries handling aniline, such as dye and rubber production, have shown elevated incidences of bladder tumors, though confounding factors like co-exposure to other aromatic amines complicate attribution. Mechanisms of carcinogenicity involve oxidative DNA damage, where aniline is metabolized to reactive species such as quinone imines that generate reactive oxygen species (ROS), leading to adducts with DNA bases like guanine and promoting mutations. Aniline enters the body primarily through , dermal absorption, and , with being a major route due to its lipophilic allowing rapid penetration even through intact . The American Conference of Governmental Industrial Hygienists (ACGIH) recommends a (TLV) of 2 ppm for airborne exposure (8-hour time-weighted average), with a skin notation emphasizing the dermal . Common symptoms from these routes include those of , as well as potential . Biomonitoring of aniline exposure relies on measuring urinary p-aminophenol (also known as ), a primary excreted mainly as conjugates, with levels above 50 mg/g indicating significant exposure. Animal studies further reveal spleen toxicity as a key chronic effect, characterized by , , , and increased risk in rats, attributed to and hemolysis-induced congestion.

Environmental impact

Aniline exhibits moderate persistence in aquatic environments, with reported half-lives ranging from 2.3 days in industrial rivers to 10-14 days in surface waters during summer conditions under aerobic conditions. It is classified as readily biodegradable, primarily through aerobic bacterial degradation pathways that convert aniline to as a key intermediate, followed by ring cleavage. Ecotoxicological data indicate low bioaccumulation potential for aniline, with a log Kow of 0.90 and a of 2.6 in fish such as Danio rerio, suggesting limited uptake in organisms. Despite this, aniline is acutely toxic to aquatic species; for example, the 96-hour LC50 for fish like fathead minnows (Pimephales promelas) is approximately 1-10 mg/L, while exhibit growth inhibition with a 72-hour of 19 mg/L, and certain invertebrates such as show sensitivity with LC50 values as low as 0.1 mg/L. Primary sources of aniline release into the environment stem from industrial effluents, particularly from and plants, where concentrations in untreated can reach up to 100 mg/L. Detection in municipal and plant effluents has been reported at levels up to 0.48 mg/L in some cases, contributing to broader aquatic contamination. Regulatory frameworks address aniline's environmental risks; under the EU REACH regulation, registrants must implement measures to limit emissions and ensure safe use, including exposure assessments and risk management options to prevent releases into water. In the United States, the EPA designates aniline as a hazardous substance under CERCLA, with a reportable quantity of 5000 pounds (2270 kg) for spills or releases requiring notification. Remediation of aniline-contaminated wastewater commonly employs activated carbon adsorption, which effectively removes aniline through physical sorption, often achieving high efficiency in batch or continuous systems. Advanced oxidation processes (AOPs), such as ozonation or Fenton-based methods enhanced by catalysts like CuFe2O4 on activated carbon, provide oxidative degradation, mineralizing aniline to less harmful byproducts like CO2 and water. These techniques are particularly suited for refractory concentrations in industrial effluents.

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