View source for Aniline

{{Short description|Organic compound (C₆H₅NH₂); simplest aromatic amine}}
{{Other uses}}
{{Distinguish|text = the amino acid [[alanine]], or [[annulene]]}}
{{Chembox
| Verifiedfields = changed
| Watchedfields  = changed
| verifiedrevid  = 443390967
| Name           = Aniline
| ImageFile      =
| ImageFileL1    = Structural formula of aniline.svg
| ImageNameL1    = Structural formula of aniline
| ImageFileR1    = Aniline-3D-vdW.png
| ImageSizeR1    = 140px
| ImageNameR1    = Aniline
| PIN            = Aniline<ref name=iupac2013>{{cite book |title=Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 (Blue Book) |publisher=[[Royal Society of Chemistry|The Royal Society of Chemistry]] |date=2014 |location=Cambridge |pages=416, 668 |doi=10.1039/9781849733069-FP001 |isbn=978-0-85404-182-4 |quote=Aniline, for C<sub>6</sub>H<sub>5</sub>-NH<sub>2</sub>, is the only name for a primary amine retained as a preferred IUPAC name for which full substitution is permitted on the ring and the nitrogen atom. It is a Type 2a retained name; for the rules of substitution see P-15.1.8.2. Substitution is limited to substituent groups cited as prefixes in accordance with the seniority of functional groups explicitly expressed or implied in the functional parent compound name. The name benzenamine may be used in general nomenclature.}}</ref>
| SystematicName = Benzenamine
| OtherNames     = Phenylamine<br/>Aminobenzene<br/>Benzamine<br/>
| IUPACName      =
| Section1       = {{Chembox Identifiers
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB06728
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 17296
| SMILES = Nc1ccccc1
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 538
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5889
| PubChem = 6115
| PubChem1 = 8870
| PubChem1_Comment = ([[hydrochloride|HCl]])
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = SIR7XX2F1K
| UNII1_Ref = {{fdacite|correct|FDA}}
| UNII1 = 576R1193YL
| UNII1_Comment = ([[hydrochloride|HCl]])
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C00292
| EC_number = 200-539-3
| RTECS = BW6650000
| UNNumber = 1547
| Gmelin = 2796
| Beilstein = 605631
| 3DMet = B00082
| InChI = 1/C6H7N/c7-6-4-2-1-3-5-6/h1-5H,7H2
| InChIKey = PAYRUJLWNCNPSJ-UHFFFAOYAP
| SMILES1 = c1ccc(cc1)N
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C6H7N/c7-6-4-2-1-3-5-6/h1-5H,7H2
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = PAYRUJLWNCNPSJ-UHFFFAOYSA-N
| CASNo = 62-53-3
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo1 = 142-04-1
| CASNo1_Ref = {{cascite|correct|CAS}}
| CASNo1_Comment = ([[hydrochloride|HCl]])
}}
| Section2       = {{Chembox Properties
| Formula = {{chem2|C6H5NH2}}
| C=6|H=7|N=1
| Appearance = Colorless liquid
| Density = 1.0297 g/mL
| Solubility = 3.6 g/(100 mL) at 20 °C
| SolubleOther =
| Solvent = [[methanol]]
| MeltingPtC = −6.30
| BoilingPtC = 184.13
| pKa = {{unbulleted list
| 4.63 (conjugate acid; H<sub>2</sub>O)<ref name="VS">{{cite book |author1= Vollhardt, P. |author2= Schore, Neil |year=2018 |title=Organic Chemistry |edition=8th |publisher=W. H. Freeman |isbn=9781319079451 |page=1031}}</ref>
}}
| Viscosity = 3.71 [[poise (unit)|cP]] (3.71&nbsp;[[pascal second|mPa·s]] at 25&nbsp;°C)
| VaporPressure = 0.6 mmHg (20&nbsp;°C)<ref name=PGCH/>
| MagSus = −62.95·10<sup>−6</sup> cm<sup>3</sup>/mol
| RefractIndex = 1.58364
}}
| Section3       =
| Section4       = {{Chembox Thermochemistry
| DeltaHf =
| DeltaHc = −3394 kJ/mol
| Entropy =
}}
| Section5       =
| Section6       =
| Section7       = {{Chembox Hazards
| NFPA-H = 3
| NFPA-F = 2
| NFPA-R = 0
| NFPA_ref =<ref>{{cite web|url=https://cameochemicals.noaa.gov/chemical/2485|title=Aniline |publisher=US NOAA Office of Response and Restoration|website=cameochemicals.noaa.gov|access-date=2016-06-16}}</ref>
| GHSPictograms = {{GHS05}}{{GHS06}}{{GHS08}}{{GHS09}}{{GHS07}}
| GHSSignalWord = Danger
| HPhrases = {{H-phrases|301|311|317|318|331|341|351|372|400}}
| PPhrases = {{P-phrases|201|202|260|261|264|270|271|272|273|280|281|301+310|302+352|304+340|305+351+338|308+313|310|311|312|314|321|322|330|333+313|361|363|391|403+233|405|501}}
| FlashPtC = 70
| AutoignitionPtC = 770
| PEL = TWA 5 ppm (19 mg/m<sup>3</sup>) [skin]<ref name=PGCH>{{PGCH|0033}}</ref>
| MainHazards = potential occupational carcinogen
| REL = Ca [potential occupational carcinogen]<ref name=PGCH/>
| IDLH = 100 ppm<ref name=PGCH/>
| ExploLimits = 1.3–11%<ref name=PGCH/>
| LC50 = 175 ppm (mouse, 7 h)<ref name=IDLH>{{IDLH|62533|Aniline}}</ref>
| LCLo = 250 ppm (rat, 4 h)<br/>180 ppm (cat, 8 h)<ref name=IDLH/>
| LDLo = 195 mg/kg (dog, oral)<br/>250 mg/kg (rat, oral)<br/>464 mg/kg (mouse, oral)<br/>440 mg/kg (rat, oral)<br/>400 mg/kg (guinea pig, oral)<ref name=IDLH/>
}}
| Section8       = {{Chembox Related
| OtherFunction_label = [[aromatic amine]]s
| OtherFunction = [[1-Naphthylamine]]<br/>[[2-Naphthylamine]]
| OtherCompounds = [[Phenylhydrazine]]<br/>[[Nitrosobenzene]]<br/>[[Nitrobenzene]]
}}
}}
'''Aniline''' ({{ety|pt|anil|[[Indigofera tinctoria|indigo shrub]]}}, and ''-ine'' indicating a derived substance)<ref>{{Cite web|title=aniline {{!}} Etymology, origin and meaning of aniline by etymonline|url=https://www.etymonline.com/word/aniline|access-date=2022-02-15|website=www.etymonline.com|language=en}}</ref> is an [[organic compound]] with the [[chemical formula|formula]] {{chem2|C6H5NH2}}. Consisting of a [[phenyl group]] ({{chem2|\sC6H5}}) attached to an [[amino group]] ({{chem2|\sNH2}}), aniline is the simplest [[aromatic amine]]. It is an industrially significant [[Commodity chemicals|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 [[Combustion|ignites]] readily, burning with a smoky flame characteristic of aromatic compounds.<ref name=Ullmann/> 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 [[Redox|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 compound|diazonium]] salt, which can then undergo various nucleophilic substitution reactions.
Like other amines, aniline is both a [[Base (chemistry)|base]] (p''K''<sub>aH</sub> = 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==
[[File:Aniline-from-xtal-3D-balls.png|thumb|left|180px|[[Ball-and-stick model]] of aniline from the [[crystal structure]] at 252 K]]
===Aryl-N distances===
In aniline, the C−N bond length is 1.41 [[Angstrom|Å]],<ref>{{Cite journal|last1=Zhang|first1=Huaiyu|last2=Jiang|first2=Xiaoyu|last3=Wu|first3=Wei|last4=Mo|first4=Yirong|date=April 28, 2016|title=Electron conjugation versus π-π repulsion in substituted benzenes: why the carbon-nitrogen bond in nitrobenzene is longer than in aniline|url=https://pubmed.ncbi.nlm.nih.gov/26852720/|journal=Physical Chemistry Chemical Physics|volume=18|issue=17|pages=11821–11828|doi=10.1039/c6cp00471g|issn=1463-9084|pmid=26852720|bibcode=2016PCCP...1811821Z}}</ref> compared to the C−N bond length of 1.47 Å for [[cyclohexylamine]],<ref>{{Cite journal|last1=Raczyńska|first1=Ewa D.|last2=Hallman|first2=Małgorzata|last3=Kolczyńska|first3=Katarzyna|last4=Stępniewski|first4=Tomasz M.|date=2010-07-12|title=On the Harmonic Oscillator Model of Electron Delocalization (HOMED) Index and its Application to Heteroatomic π-Electron Systems|journal=Symmetry|language=en|volume=2|issue=3|pages=1485–1509|doi=10.3390/sym2031485|bibcode=2010Symm....2.1485R|issn=2073-8994|doi-access=free}}</ref> indicating partial [[Pi bond|π-bonding]] between C(aryl) and N.<ref>G. M. Wójcik "Structural Chemistry of Anilines" in Anilines (Patai's Chemistry of Functional Groups), S. Patai, Ed. 2007, Wiley-VCH, Weinheim. {{doi|10.1002/9780470682531.pat0385}}.</ref> The length of the [[chemical bond]] of {{chem2|C([[aryl]])\sNH2}} in anilines is highly sensitive to [[substituent effect]]s. The C−N bond length is 1.34 Å in [[2,4,6-Trinitroaniline|2,4,6-trinitroaniline]] vs 1.44 Å in [[3-Methylaniline|3-methylaniline]].<ref>{{cite book |doi=10.1002/9780470771662.ch1|chapter=Structural chemistry |title=Amino, Nitrosco and Nitro Compounds and Their Derivatives: Vol. 1 (1982) |year=1982 |last1=Sorriso |first1=S. |pages=1–51 |isbn=9780470771662 }}</ref>
<!--Structural chemistry
S. Sorriso
Book Editor(s):Saul Patai
First published: 28 April 1982 https://doi-org.proxy2.library.illinois.edu/10.1002/9780470771662.ch1
Book Series:PATAI'S Chemistry of Functional Groups-->
===Pyramidalization===
The [[amine group]] in anilines is a slightly pyramidalized molecule, with hybridization of the nitrogen somewhere between [[Orbital hybridisation|sp<sup>3</sup> and sp<sup>2</sup>]]. 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) [[Delocalized bonding|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).<ref name=":0">{{Cite book|last=Alabugin, Igor V. |title=Stereoelectronic effects : a bridge between structure and reactivity|year=2016|isbn=978-1-118-90637-8|location=Chichester, UK|oclc=957525299}}</ref><ref>Alabugin I. V.; Manoharan, M.; Buck, M.; Clark, R. J. Substituted Anilines: The Tug-Of-War between Pyramidalization and Resonance Inside and Outside of Crystal Cavities. THEOCHEM, 2007, 813, 21-27. http://dx.doi.org/10.1016/j.theochem.2007.02.016.</ref>
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 sp<sup>7.3</sup> hybridization.<ref name=":0" />{{clarify|reason=Incorrect statement! The sp7.3 hybridization does not exist! What is this, a typo? Do you mean sp2.3 hybridization?|date=June 2023}} (For comparison, alkylamines generally have lone pairs in orbitals that are close to sp<sup>3</sup>.)
The pyramidalization angle between the C–N bond and the bisector of the H–N–H angle is 142.5°.<ref>{{cite book|title=Organic chemistry|last=Carey|first=Francis A.|date=2008|publisher=McGraw-Hill Higher Education|isbn=9780073047874|edition= 7th|location=Boston|oclc=71790138}}</ref> 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==
Industrial aniline production involves [[hydrogenation]] of [[nitrobenzene]] (typically at 200–300&nbsp;°C) in the presence of metal [[catalyst]]s:<ref>{{Cite patent|number=US3136818A|title=Production of aniline|gdate=1964-06-09|invent1=Heinrich|invent2=Guenter|invent3=Joachim|invent4=Anton|inventor1-first=Sperber|inventor2-first=Poehler|inventor3-first=Pistor Hans|inventor4-first=Wegerich|url=https://patents.google.com/patent/US3136818A/en}}</ref> Approximately 4 billion kilograms are produced annually.  Catalysts include nickel, copper, palladium, and platinum,<ref name=Ullmann/> and newer catalysts continue to be discovered.<ref>{{cite journal |doi=10.1038/nchem.1645 |title=Heterogenized Cobalt Oxide Catalysts for Nitroarene Reduction by Pyrolysis of Molecularly Defined Complexes |date=2013 |last1=Westerhaus |first1=Felix A. |last2=Jagadeesh |first2=Rajenahally V. |last3=Wienhöfer |first3=Gerrit |last4=Pohl |first4=Marga-Martina |last5=Radnik |first5=Jörg |last6=Surkus |first6=Annette-Enrica |last7=Rabeah |first7=Jabor |last8=Junge |first8=Kathrin |last9=Junge |first9=Henrik |last10=Nielsen |first10=Martin |last11=Brückner |first11=Angelika |last12=Beller |first12=Matthias |journal=Nature Chemistry |volume=5 |issue=6 |pages=537–543 |pmid=23695637 |bibcode=2013NatCh...5..537W |s2cid=3273484 }}</ref>
:[[File:Aniline from Nitrobenzene.svg|400px]]
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.<ref>{{Citation|last=Porter|first=H. K.|title=The Zinin Reduction of Nitroarenes|date=2011|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/0471264180.or020.04|work=Organic Reactions|pages=455–481|publisher=John Wiley & Sons, Ltd|language=en|doi=10.1002/0471264180.or020.04|isbn=978-0-471-26418-7|access-date=2022-02-01}}</ref>
Aniline can alternatively be prepared from ammonia and [[phenol]] derived from the [[cumene process]].<ref name="Ullmann"/>
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-toluidine]]s; and aniline oil for [[safranine]], which contains aniline and ortho-[[toluidine]] and is obtained from the [[distillation|distillate]] (échappés) of the [[fuchsine]] fusion.{{sfn|Chisholm|1911|p=48}}
===Related aniline derivatives===
Many analogues and [[derivative (chemistry)|derivatives]] of aniline are known where the phenyl group is further substituted. These include [[toluidine]]s, [[xylidine]]s, [[chloroaniline]]s, [[aminobenzoic acid]]s, [[nitroaniline]]s, 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]].<ref name="Ullmann"/> Alternatively, using Buchwald-Hartwig coupling or Ullmann reaction approaches, aryl halides can be aminated with aqueous or gaseous ammonia.<ref>{{Cite web|url=https://www.organic-chemistry.org/synthesis/C1N/amines/anilines.shtm|title = Aniline synthesis by amination (Arylation)}}</ref>
==Reactions==
The chemistry of aniline is rich because the compound has been cheaply available for many years. Below are some classes of its reactions.
===Oxidation===
[[File:2,6-(iPr)2C6H3NH2sample.jpg|thumb|left|Sample of [[2,6-Diisopropylaniline|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 [[1,4-benzoquinone|quinone]], whereas [[chlorate]]s, 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]].{{sfn|Chisholm|1911|p=48}} Oxidation with [[persulfate]] affords a variety of [[polyaniline]]s. These polymers exhibit rich redox and acid-base properties.
[[File:Polyaniline structure.svg|thumb|left|400px|[[Polyaniline]]s can form upon oxidation of aniline.]]
===Electrophilic reactions at ortho- and para- positions===
Like [[phenol]]s, 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&nbsp;°C produces [[sulfanilic acid]], {{chem2|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 [[Protecting group|protection]] with acetyl chloride is required:
[[File:Aniline reaction with bromine .jpg|left|thumb|200x200px|Aniline can react with bromine even in room temperatures in water. Acetyl chloride is added to prevent tribromination.]]
The reaction to form [[4-Bromoaniline|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:
:{{chem2|2 C6H5NH2 + CH2O → CH2(C6H4NH2)2 + H2O}}
The resulting diamine is the precursor to [[4,4'-MDI]] and related diisocyanates.
===Reactions at nitrogen===
====Basicity====
Aniline is a weak [[base (chemistry)|base]]. [[Aromatic amine]]s such as aniline are, in general, much weaker bases than [[aliphatic]] amines. Aniline reacts with strong acids to form the [[Anilinium chloride|anilinium]] (or phenylammonium) ion ({{chem2|C6H5\sNH3+}}).<ref>{{McMurry3rd}}</ref>
Traditionally, the weak basicity of aniline is attributed to a combination of inductive effect from the more electronegative sp<sup>2</sup> 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):
[[File:Anilin delocalization.svg|none|thumb|394x394px|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.<ref>{{March6th}}</ref>
====Acylation====
{{Main|Anilide}}
Aniline reacts with [[acyl chloride]]s such as [[acetyl chloride]] to give [[amide]]s. The amides formed from aniline are sometimes called [[anilide]]s, for example {{chem2|CH3\sC(\dO)\sNH\sC6H5}} is [[acetanilide]]. At high temperatures aniline and carboxylic acids react to give the anilides.<ref>{{OrgSynth|author=Carl N. Webb|title= Benzanilide |collvol=1|collvolpages=82|year=1941|prep=cv1p0082}}</ref>
====''N''-Alkylation====
''N''-Methylation of aniline with [[methanol]] at elevated temperatures over [[Acid catalysis|acid catalysts]] gives [[N-methylaniline|''N''-methylaniline]] and [[N,N-dimethylaniline|''N'',''N''-dimethylaniline]]:
:{{chem2|C6H5NH2 + 2 CH3OH → C6H5N(CH3)2 + 2H2O}}
''N''-Methylaniline and ''N'',''N''-dimethylaniline are colorless liquids with [[boiling point]]s of 193–195&nbsp;°C and 192&nbsp;°C, respectively. These derivatives are of importance in the color industry.
====Carbon disulfide derivatives====
Boiled with [[carbon disulfide]], it gives sulfocarbanilide (diphenyl[[thiourea]]) ({{chem2|S\dC(\sNH\sC6H5)2}}), which may be decomposed into phenyl [[isothiocyanate]] ({{chem2|C6H5\sN\dC\dS}}), and triphenyl [[guanidine]] ({{chem2|C6H5\sN\dC(\sNH\sC6H5)2}}).{{sfn|Chisholm|1911|p=48}}
====Diazotization====
Aniline and its ring-substituted derivatives react with [[nitrous acid]] to form [[diazonium salt]]s.  One example is [[benzenediazonium tetrafluoroborate]]. Through these intermediates, the amine group can be converted to a [[hydroxyl]] ({{chem2|\sOH}}), [[cyanide]] ({{chem2|\sCN}}), or [[Halocarbon|halide]] group ({{chem2|\sX}}, where X is a [[halogen]]) via [[Sandmeyer reaction]]s. This diazonium salt can also be reacted with [[Sodium nitrite|{{chem2|NaNO2}}]] and [[phenol]] to produce a [[dye]] known as [[benzeneazophenol]], in a process called ''[[azo coupling|coupling]]''.
The reaction of converting [[Primary amine|primary]] [[Aromatic compound|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 [[Hydrogen chloride|HCl]], which is known as "ice cold mixture" because the temperature for the reaction was as low as 0.5&nbsp;°C. The benzene diazonium salt is formed as major product alongside the byproducts [[water]] and [[sodium chloride]].
===Other reactions===
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|date=May 2010}}
In addition, aniline is the starting component in the production of [[diglycidyl aniline]].<ref name="Panda 2019 38">{{Cite book |last=Panda |first=Dr H |title=Epoxy Resins Technology Handbook (Manufacturing Process, Synthesis, Epoxy Resin Adhesives and Epoxy Coatings |publisher=Asia Pacific Business Press Inc |year=2019 |isbn=978-8178331829 |edition=2nd |pages=38}}</ref> [[Epichlorohydrin]] is the other main ingredient.<ref name="Panda 2019 38"/><ref>{{Cite journal |last1=Jung |first1=Woo-Hyuk |last2=Ha |first2=Eun-Ju |last3=Chung |first3=Il doo |last4=Lee |first4=Jang-Oo |date=2008-08-01 |title=Synthesis of aniline-based azopolymers for surface relief grating |url=https://doi.org/10.1007/BF03218555 |journal=Macromolecular Research |language=en |volume=16 |issue=6 |pages=532–538 |doi=10.1007/BF03218555 |s2cid=94372490 |issn=2092-7673}}</ref>
==Uses==
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.<ref name="Ullmann">{{cite book |last1=Kahl |first1=Thomas |url=https://books.google.com/books?id=qGc2yQEACAAJ |title=Ullmann's encyclopedia of industrial chemistry |last2=Schröder |first2=K. W. |last3=Lawrence |first3=F. R. |last4=Elvers |first4=Barbara |last5=Höke |first5=Hartmut |last6=Pfefferkorn |first6=R. |last7=Marshall |first7=W. J. |publisher=Wiley: New York |year=2007 |isbn=978-3-527-20138-9 |editor-last=Ullmann |editor-first=Fritz |chapter=Aniline |doi=10.1002/14356007.a02_303 |oclc=11469727}}</ref>
:[[File:Synthesis of 4,4'-diaminodiphenylmethane.svg|thumb|400px|left|Most aniline is consumed in the production of [[methylenedianiline]], a precursor to polyurethanes.]]
Other uses include [[rubber]] processing chemicals (9%), [[herbicide]]s (2%), and dyes and pigments (2%).<ref name="CPoA">{{cite news|title=Aniline|publisher=The Chemical Market Reporter |url=http://www.the-innovation-group.com/ChemProfiles/Aniline.htm|access-date=2007-12-21 |url-status=dead |archive-url=https://archive.today/20020219104231/http://www.the-innovation-group.com/ChemProfiles/Aniline.htm|archive-date=2002-02-19}}</ref> As additives to rubber, aniline derivatives such as [[phenylenediamine]]s and [[diphenylamine]], are antioxidants. Illustrative of the drugs prepared from aniline is [[paracetamol]] (acetaminophen, [[Tylenol (brand)|Tylenol]]). The principal use of aniline in the dye industry is as a precursor to [[indigo dye|indigo]], the blue of [[jeans|blue jeans]].<ref name=Ullmann/>
[[File:Indigo cake.jpg|thumb|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."<ref>Kerrigan, Richard (2016). Agaricus of North America. NYBG Press. p. 45. ISBN 978-0-89327-536-5.</ref>
==History==
Aniline was first isolated in 1826 by [[Otto Unverdorben]] by [[destructive distillation]] of [[indigo dye|indigo]].<ref>{{cite journal
|title=Ueber das Verhalten der organischen Körper in höheren Temperaturen
|trans-title=On the behaviour of organic substances at high temperatures
|author=Otto Unverdorben
|journal=Annalen der Physik und Chemie
|volume=8
|pages=397–410
|year=1826
|url=https://books.google.com/books?id=zx0AAAAAMAAJ&pg=PA397
|doi=10.1002/andp.18260841109|bibcode=1826AnP....84..397U
|issue =11}}</ref> He called it ''Crystallin''. In 1834, [[Friedlieb Ferdinand Runge|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''.<ref>F. F. Runge (1834) "Ueber einige Produkte der Steinkohlendestillation" (On some products of coal distillation), ''Annalen der Physik und Chemie'', '''31''': [https://books.google.com/books?id=CWbkAAAAMAAJ&pg=PA65 65–77] (see page 65), [https://books.google.com/books?id=CWbkAAAAMAAJ&pg=PA513 513–524]; and '''32''': [https://books.google.com/books?id=CWbkAAAAMAAJ&pg=RA1-PA308 308–332] (see page 331).</ref> 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]]'').<ref>J. Fritzsche (1840) [https://books.google.com/books?id=VYI-AAAAcAAJ&pg=PA4 "Ueber das Anilin, ein neues Zersetzungsproduct des Indigo"] (On aniline, a new decomposition product of indigo), ''Bulletin Scientifique'' [publié par l'Académie Impériale des Sciences de Saint-Petersbourg], '''7''' (12): 161–165. Reprinted in:
*J. Fritzsche (1840) "Ueber das Anilin, ein neues Zersetzungsproduct des Indigo", ''Justus Liebigs Annalen der Chemie'', '''36''' (1): 84–90.
*J. Fritzsche (1840) [https://books.google.com/books?id=eBFLAAAAYAAJ&pg=PA453 "Ueber das Anilin, ein neues Zersetzungsproduct des Indigo"], ''Journal für praktische Chemie'', '''20''': 453–457. In a postscript to this article, Erdmann (one of the journal's editors) argues that aniline and the "cristallin", which was found by Unverdorben in 1826, are the same substance; see [https://books.google.com/books?id=eBFLAAAAYAAJ&pg=PA457 pages 457–459].</ref><ref>synonym [http://www.etymonline.com/index.php?term=aniline ''I anil''], ultimately from Sanskrit "nīla", dark-blue.</ref> In 1842, [[Nikolay Nikolaevich Zinin]] reduced [[nitrobenzene]] and obtained a base that he named ''benzidam''.<ref>N. Zinin (1842). "Beschreibung einiger neuer organischer Basen, dargestellt durch die Einwirkung des Schwefelwasserstoffes auf Verbindungen der Kohlenwasserstoffe mit Untersalpetersäure" (Description of some new organic bases, produced by the action of hydrogen sulfide on compounds of hydrocarbons and hyponitric acid [H<sub>2</sub>N<sub>2</sub>O<sub>3</sub>]), ''Bulletin Scientifique'' [publié par l'Académie Impériale des Sciences de Saint-Petersbourg], '''10''' (18): 272–285. Reprinted in: N. Zinin (1842) [https://books.google.com/books?id=dxJLAAAAYAAJ&pg=PA140 "Beschreibung einiger neuer organischer Basen, dargestellt durch die Einwirkung des Schwefelwasserstoffes auf Verbindungen der Kohlenwasserstoffe mit Untersalpetersäure"], ''Journal für praktische Chemie'', '''27''' (1): 140–153. Benzidam is named on page 150.
Fritzsche, Zinin's colleague, soon recognized that "benzidam" was actually aniline. See: Fritzsche (1842) ''Bulletin Scientifique'', '''10''': 352. Reprinted as a postscript to Zinin's article in: J. Fritzsche (1842) [https://books.google.com/books?id=dxJLAAAAYAAJ&pg=PA153 "Bemerkung zu vorstehender Abhandlung des Hrn. Zinin"] (Comment on the preceding article by Mr. Zinin), ''Journal für praktische Chemie'', '''27''' (1): 153.<br/>
See also: (Anon.) (1842) [https://books.google.com/books?id=Wz49AAAAcAAJ&pg=PA283 "Organische Salzbasen, aus Nitronaphtalose und Nitrobenzid mittelst Schwefelwasserstoff entstehend"] (Organic bases originating from nitronaphthalene and nitrobenzene via hydrogen sulfide), ''Annalen der Chemie und Pharmacie'', '''44''': 283–287.</ref> In 1843, [[August Wilhelm von Hofmann]] showed that these were all the same substance, known thereafter as ''phenylamine'' or ''aniline''.<ref>August Wilhelm Hofmann (1843) [https://archive.org/stream/annalenderchemi35liebgoog#page/n49/mode/2up "Chemische Untersuchung der organischen Basen im Steinkohlen-Theeröl"] (Chemical investigation of organic bases in coal tar oil), ''Annalen der Chemie und Pharmacie'', '''47''': 37–87. On page 48, Hofmann argues that krystallin, kyanol, benzidam, and aniline are identical.</ref>
===Synthetic dye industry===
In 1856, while trying to synthesise [[quinine]], [[August Wilhelm von Hofmann|von Hofmann]]'s student [[Sir William Henry Perkin|William Henry Perkin]] discovered [[mauveine]].  Mauveine quickly became a commercial dye.  Other [[chemical synthesis|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]],<ref>A. Béchamp (1854) [http://gallica.bnf.fr/ark:/12148/bpt6k347830.image.f185 "De l'action des protosels de fer sur la nitronaphtaline et la nitrobenzine. Nouvelle méthode de formation des bases organiques artificielles de Zinin"] (On the action of iron protosalts on nitronaphthaline and nitrobenzene. New method of forming Zinin's synthetic organic bases.), ''Annales de Chemie et de Physique'', 3rd series, '''42''': 186 – 196. (Note: In the case of a metal having two or more distinct oxides (e.g., iron), a "protosalt" is an obsolete term for a salt that is obtained from the oxide containing the lowest proportion of oxygen to metal; e.g., in the case of iron, which has two oxides – iron (II) oxide (FeO) and iron (III) oxide (Fe<sub>2</sub>O<sub>3</sub>) – FeO is the "protoxide" from which protosalts can be made. See: [[:wikt:protosalt|Wiktionary: protosalt]].)</ref> it was prepared "by the ton".<ref>Perkin, William Henry. 1861-06-08. [https://books.google.com/books?id=oKEEAAAAYAAJ&dq=roseine+fuchsine&pg=RA3-PA347 "Proceedings of Chemical Societies: Chemical Society, Thursday, May 16, 1861"]. ''The Chemical News and Journal of Industrial Science''. Retrieved on 2007-09-24.</ref> The [[Bechamp reduction|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 [[sodium carbonate|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 dye]]s. The first azo dye was [[aniline yellow]].<ref>Auerbach G, "Azo and naphthol dyes", ''Textile Colorist'', 1880 May;'''2'''(17):137-9, [https://books.google.com/books?id=pCExAQAAMAAJ&dq=oldest+known+azo+dye&pg=PA138 p 138].</ref>
{{Further|Nigrosene}}
===Developments in medicine===
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]].<ref>Wilcox RW, "The treatment of influenza in adults", ''Medical News'', 1900 Dec 15;'''77'''():931-2, [https://books.google.com/books?id=jAdYAAAAMAAJ&dq=great+temptation+to+relieve+that+headaches+and+the+muscular+pains+by+the+coal-tar+products+of+the+anilin+series&pg=PA932 p 932].</ref> During the first decade of the 20th century, while trying to modify synthetic dyes to treat [[African trypanosomiasis|African sleeping sickness]], [[Paul Ehrlich]] – who had coined the term ''[[chemotherapy]]'' for his ''[[magic bullet (medicine)|magic bullet]]'' approach to medicine – failed and switched to modifying [[Antoine Béchamp|Béchamp]]'s [[atoxyl]], the first organic [[arsenic]]al drug, and serendipitously obtained a treatment for [[syphilis]] – [[salvarsan]] – the first successful chemotherapy agent. [[treponema pallidum|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]].<ref name=Wagener>D J Th Wagener, ''The History of Oncology'' (Houten: Springer, 2009), [https://books.google.com/books?id=53fmwacXu44C&pg=PA150 pp 150–1].</ref>
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.<ref name=Wagener/> By the 1940s, over 500 related [[sulfa drug]]s were produced.<ref name=Wagener/> Medications in high demand during [[World War II]] (1939–45), these first ''miracle drugs'', chemotherapy of wide effectiveness, propelled the American pharmaceutics industry.<ref>John E Lesch, ''The First Miracle Drugs: How the Sulfa Drugs Transformed Medicine'' (New York: Oxford University Press, 2007), [https://books.google.com/books?id=dFgZRlRy5ScC&pg=PA202 pp 202–3].</ref> 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 University|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.<ref>{{cite magazine | title=Medicine: Spoils of War | magazine=[[Time (magazine)|Time]] | date=15 May 1950 | url=http://www.time.com/time/magazine/article/0,9171,820604,00.html | archive-url=https://web.archive.org/web/20130624131223/http://www.time.com/time/magazine/article/0,9171,820604,00.html | archive-date=24 June 2013 | url-status=dead | access-date=20 November 2020}}</ref>
===Rocket fuel===
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 propellant|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]].<ref name="Corporal">Brian Burnell. 2016. http://www.nuclear-weapons.info/cde.htm#Corporal SSM</ref>
==Toxicology and testing==
Aniline is toxic by inhalation of the vapour, ingestion, or percutaneous absorption.<ref name="HitCL">Muir, GD (ed.) 1971, ''Hazards in the Chemical Laboratory'', The Royal Institute of Chemistry, London.</ref><ref>''The Merck Index''. 10th ed. (1983), p.96, Rahway: Merck & Co.</ref> The [[International Agency for Research on Cancer|IARC]] lists it in [[list of IARC Group 2A carcinogens|Group 2A]] (''Probably carcinogenic to humans''), and it has specifically been linked to bladder cancer.<ref>{{Cite journal |doi=10.1155/2011/528353|title=Pathobiology and Chemoprevention of Bladder Cancer|year=2011|last1=Tanaka|first1=Takuji|last2=Miyazawa|first2=Katsuhito|last3=Tsukamoto|first3=Testuya|last4=Kuno|first4=Toshiya|last5=Suzuki|first5=Koji |journal=Journal of Oncology|volume=2011|pages=1–23 |doi-access=free |pmid=21941546 }}</ref>
Aniline has been implicated as one possible cause of [[forest dieback]].<ref name="Krahl1988">Krahl-Urban, B., Papke, H.E., Peters, K. (1988) ''Forest Decline: Cause-Effect Research in the United States of North America and Federal Republic of Germany''. Germany: Assessment Group for Biology, Ecology and Energy of the Julich Nuclear Research Center.</ref>
Many methods exist for the detection of aniline.<ref>''Basic Analytical Toxicology'' (1995), R. J. Flanagan, S. S. Brown, F. A. de Wolff, R. A. Braithwaite, B. Widdop: World Health Organization</ref>
===Oxidative DNA damage===
Exposure of rats to aniline can elicit a response that is toxic to the [[spleen]], including a [[carcinogenic|tumorigenic]] response.<ref name="Ma2008">{{Cite journal |doi=10.1016/j.taap.2008.08.010 |pmc=2614128 |pmid=18793663|title=Oxidative DNA damage and its repair in rat spleen following subchronic exposure to aniline |year=2008 |last1=Ma |first1=Huaxian |last2=Wang |first2=Jianling |last3=Abdel-Rahman |first3=Sherif Z. |last4=Boor |first4=Paul J. |last5=Khan |first5=M. Firoze |journal=Toxicology and Applied Pharmacology |volume=233 |issue=2 |pages=247–253 }}</ref> Rats exposed to aniline in drinking water, showed a significant increase in oxidative [[DNA damage (naturally occurring)|DNA damage]] to the spleen, detected as a 2.8-fold increase in [[8-oxo-2'-deoxyguanosine|8-hydroxy-2'-deoxyguanosine (8-OHdG)]] in their [[DNA]].<ref name = Ma2008/> 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==
{{Reflist|30em}}
==References==
*{{EB1911 |mode=cs2 |wstitle=Aniline |volume=2 |pages=47–48}}
==External links==
{{Wiktionary}}
{{Commons}}
*{{cite EB9 |mode=cs2 |wstitle=Aniline |volume=2 |pages=47–48 short=x}}
*[http://www.inchem.org/documents/icsc/icsc/eics0011.htm International Chemical Safety Card 0011]
*[https://www.cdc.gov/niosh/npg/npgd0033.html CDC - NIOSH Pocket Guide to Chemical Hazrds]
*[http://www.abc.chemistry.bsu.by/vi/aniline_electropolymerisation.htm Aniline electropolymerisation]
{{Authority control}}
[[Category:Anilines| ]]
[[Category:Dyes]]
[[Category:German inventions]]
[[Category:Hazardous air pollutants]]
[[Category:IARC Group 2A carcinogens]]
[[Category:Phenyl compounds]]