Aniline (from Portuguese anil'indigo shrub', and-ine indicating a derived substance)[6] is anorganic compound with theformulaC6H5NH2. Consisting of aphenyl group (−C6H5) attached to anamino group (−NH2), aniline is the simplestaromatic amine. It is an industrially significantcommodity chemical, as well as a versatile starting material forfine chemical synthesis. Its main use is in the manufacture of precursors topolyurethane, dyes, and other industrial chemicals. Like most volatile amines, it has the odor of rottenfish. Itignites 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 inelectrophilic aromatic substitution reactions. Likewise, it is also prone tooxidation: 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 adiazonium salt, which can then undergo various nucleophilic substitution reactions.
Like other amines, aniline is both abase (pKaH = 4.6) and anucleophile, although less so than structurally similaraliphatic amines.
Because an early source of the benzene from which they are derived wascoal tar, aniline dyes are also calledcoal tar dyes.
Theamine group in anilines is a slightly pyramidalized molecule, with hybridization of the nitrogen somewhere betweensp3 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 thelone pair with thearyl 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 inmethylamine, this value is ~125°, while that of the amine group informamide has an angle of 180°.
Industrial aniline production involveshydrogenation ofnitrobenzene (typically at 200–300 °C) in the presence of metalcatalysts:[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 byNikolay Zinin in 1842, using sulfide salts (Zinin reaction). The reduction of nitrobenzene to aniline was also performed as part of reductions byAntoine 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 andphenol derived from thecumene 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- andpara-toluidines; and aniline oil forsafranine, which contains aniline and ortho-toluidine and is obtained from thedistillate (échappés) of thefuchsine fusion.[18]
Many analogues andderivatives of aniline are known where the phenyl group is further substituted. These includetoluidines,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 converttoluene into toluidines andchlorobenzene into4-chloroaniline.[7] Alternatively, using Buchwald-Hartwig coupling or Ullmann reaction approaches, aryl halides can be aminated with aqueous or gaseous ammonia.[19]
Sample of2,6-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, whereasarsenic acid produces the violet-coloring matter violaniline.Chromic acid converts it intoquinone, whereaschlorates, in the presence of certain metallic salts (especially ofvanadium), giveaniline black. Hydrochloric acid and potassium chlorate givechloranil.Potassium permanganate in neutral solution oxidizes it tonitrobenzene; in alkaline solution toazobenzene, ammonia, andoxalic acid; in acid solution to aniline black.Hypochlorous acid gives4-aminophenol and para-aminodiphenylamine.[18] Oxidation withpersulfate affords a variety ofpolyanilines. These polymers exhibit rich redox and acid-base properties.
Likephenols, aniline derivatives are highly susceptible toelectrophilic substitution reactions. Its high reactivity reflects that it is anenamine, which enhances the electron-donating ability of the ring. For example, reaction of aniline withsulfuric acid at 180 °C producessulfanilic acid,H2NC6H4SO3H.
Aniline is a weakbase.Aromatic amines such as aniline are, in general, much weaker bases thanaliphatic amines. Aniline reacts with strong acids to form theanilinium (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 ofsolvation. Aniline is, for example, more basic than ammonia in the gas phase, but ten thousand times less so in aqueous solution.[21]
Aniline reacts withacyl chlorides such asacetyl chloride to giveamides. The amides formed from aniline are sometimes calledanilides, for exampleCH3−C(=O)−NH−C6H5 isacetanilide. At high temperatures aniline and carboxylic acids react to give the anilides.[22]
N-Methylaniline andN,N-dimethylaniline are colorless liquids withboiling points of 193–195 °C and 192 °C, respectively. These derivatives are of importance in the color industry.
Boiled withcarbon disulfide, it gives sulfocarbanilide (diphenylthiourea) (S=C(−NH−C6H5)2), which may be decomposed into phenylisothiocyanate (C6H5−N=C=S), and triphenylguanidine (C6H5−N=C(−NH−C6H5)2).[18]
Aniline and its ring-substituted derivatives react withnitrous acid to formdiazonium salts. One example isbenzenediazonium tetrafluoroborate. Through these intermediates, the amine group can be converted to ahydroxyl (−OH),cyanide (−CN), orhalide group (−X, where X is ahalogen) viaSandmeyer reactions. This diazonium salt can also be reacted withNaNO2 andphenol to produce adye known asbenzeneazophenol, in a process calledcoupling.The reaction of convertingprimaryaromatic amine into diazonium salt is called diazotisation.In this reaction primary aromatic amine is allowed to react withsodium nitrite and 2 moles ofHCl, 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 byproductswater andsodium chloride.
Being a standard reagent in laboratories, aniline is used for many niche reactions. Its acetate is used in theaniline acetate test for carbohydrates, identifying pentoses by conversion tofurfural. It is used to stain neuralRNA blue in theNissl stain.[citation needed]
Aniline is predominantly used for the preparation of methylenedianiline and related compounds by condensation with formaldehyde. The diamines are condensed withphosgene to givemethylene diphenyl diisocyanate, a precursor to urethane polymers.[7]
Most aniline is consumed in the production ofmethylenedianiline, a precursor to polyurethanes.
Other uses includerubber processing chemicals (9%),herbicides (2%), and dyes and pigments (2%).[25] As additives to rubber, aniline derivatives such asphenylenediamines anddiphenylamine, are antioxidants. Illustrative of the drugs prepared from aniline isparacetamol (acetaminophen,Tylenol). The principal use of aniline in the dye industry is as a precursor toindigo, the blue ofblue jeans.[7]
Cake ofindigo 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]
In 1856, while trying to synthesisequinine,von Hofmann's studentWilliam Henry Perkin discoveredmauveine. Mauveine quickly became a commercial dye. Othersynthetic dyes followed, such asfuchsin,safranin, andinduline. At the time of mauveine's discovery, aniline was expensive. Soon thereafter, applying a method reported in 1854 byAntoine Béchamp,[33] it was prepared "by the ton".[34] TheBéchamp reduction enabled the evolution of a massive dye industry in Germany. Today, the name ofBASF, originallyBadische Anilin- und Soda-Fabrik (English:Baden Aniline andSoda Factory), now the largest chemical supplier, echoes the legacy of the synthetic dye industry, built via aniline dyes and extended via the relatedazo dyes. The first azo dye wasaniline yellow.[35]
In the late 19th century, derivatives of aniline such asacetanilide andphenacetin emerged asanalgesic drugs, with their cardiac-suppressiveside effects often countered withcaffeine.[36] Also in the late 19th century, Ehrlich found that the aniline dyemethylene 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 treatAfrican sleeping sickness,Paul Ehrlich – who had coined the termchemotherapy for hismagic bullet approach to medicine – failed and switched to modifyingBéchamp'satoxyl, the first organicarsenical drug, and serendipitously obtained a treatment forsyphilis –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, overlookedAlexander Fleming's report in 1928 on the effects ofpenicillin.[38]
In 1932,Bayer sought medical applications of its dyes.Gerhard Domagk identified as anantibacterial a red azo dye, introduced in 1935 as the first antibacterial drug,prontosil, soon found atPasteur Institute to be aprodrug degradedin vivo intosulfanilamide – a colorless intermediate for many, highlycolorfast azo dyes – already with an expired patent, synthesized in 1908 in Vienna by the researcherPaul Gelmo for his doctoral research.[38] By the 1940s, over 500 relatedsulfa drugs were produced.[38] Medications in high demand duringWorld War II (1939–45), these firstmiracle drugs, chemotherapy of wide effectiveness, propelled the American pharmaceutics industry.[39] In 1939, atOxford University, seeking an alternative to sulfa drugs,Howard Florey developed Fleming's penicillin into the first systemicantibiotic drug,penicillin G. (Gramicidin, developed byRené Dubos atRockefeller Institute in 1939, was the first antibiotic, yet its toxicity restricted it totopical use.) After World War II,Cornelius P. Rhoads introduced the chemotherapeutic approach to cancer treatment.[40]
Some early American rockets, such as theAerobee andWAC Corporal, used a mixture of aniline andfurfuryl alcohol as a fuel, withnitric acid as an oxidizer. The combination ishypergolic, igniting on contact between fuel and oxidizer. It is also dense, and can be stored for extended periods. Aniline was later replaced byhydrazine.[41]
Aniline is toxic by inhalation of the vapour, ingestion, or percutaneous absorption.[42][43] TheIARC lists it inGroup 2A (Probably carcinogenic to humans), and it has specifically been linked to bladder cancer.[44]Aniline has been implicated as one possible cause offorest dieback.[45]
Many methods exist for the detection of aniline.[46]
Exposure of rats to aniline can elicit a response that is toxic to thespleen, including atumorigenic response.[47] Rats exposed to aniline in drinking water, showed a significant increase in oxidativeDNA damage to the spleen, detected as a 2.8-fold increase in8-hydroxy-2'-deoxyguanosine (8-OHdG) in theirDNA.[47] Although thebase 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.
^Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge:The Royal Society of Chemistry. 2014. pp. 416, 668.doi:10.1039/9781849733069-FP001.ISBN978-0-85404-182-4.Aniline, for C6H5-NH2, 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.
^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.
^abAlabugin, Igor V. (2016).Stereoelectronic effects : a bridge between structure and reactivity. Chichester, UK.ISBN978-1-118-90637-8.OCLC957525299.{{cite book}}: CS1 maint: location missing publisher (link)
^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.
^Carey, Francis A. (2008).Organic chemistry (7th ed.). Boston: McGraw-Hill Higher Education.ISBN9780073047874.OCLC71790138.
^US3136818A, Heinrich, Sperber; Guenter, Poehler & Joachim, Pistor Hans et al., "Production of aniline", issued 1964-06-09
^Westerhaus, Felix A.; Jagadeesh, Rajenahally V.; Wienhöfer, Gerrit; Pohl, Marga-Martina; Radnik, Jörg; Surkus, Annette-Enrica; Rabeah, Jabor; Junge, Kathrin; Junge, Henrik; Nielsen, Martin; Brückner, Angelika; Beller, Matthias (2013). "Heterogenized Cobalt Oxide Catalysts for Nitroarene Reduction by Pyrolysis of Molecularly Defined Complexes".Nature Chemistry.5 (6):537–543.Bibcode:2013NatCh...5..537W.doi:10.1038/nchem.1645.PMID23695637.S2CID3273484.
^abPanda, Dr H (2019).Epoxy Resins Technology Handbook (Manufacturing Process, Synthesis, Epoxy Resin Adhesives and Epoxy Coatings (2nd ed.). Asia Pacific Business Press Inc. p. 38.ISBN978-8178331829.
^F. F. Runge (1834) "Ueber einige Produkte der Steinkohlendestillation" (On some products of coal distillation),Annalen der Physik und Chemie,31:65–77 (see page 65),513–524; and32:308–332 (see page 331).
^J. Fritzsche (1840)"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)"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; seepages 457–459.
^synonymI anil, ultimately from Sanskrit "nīla", dark-blue.
^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 [H2N2O3]),Bulletin Scientifique [publié par l'Académie Impériale des Sciences de Saint-Petersbourg],10 (18): 272–285. Reprinted in: N. Zinin (1842)"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)"Bemerkung zu vorstehender Abhandlung des Hrn. Zinin" (Comment on the preceding article by Mr. Zinin),Journal für praktische Chemie,27 (1): 153. See also: (Anon.) (1842)"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.
^August Wilhelm Hofmann (1843)"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.
^A. Béchamp (1854)"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 (Fe2O3) – FeO is the "protoxide" from which protosalts can be made. See:Wiktionary: protosalt.)
^Auerbach G, "Azo and naphthol dyes",Textile Colorist, 1880 May;2(17):137-9,p 138.
^Wilcox RW, "The treatment of influenza in adults",Medical News, 1900 Dec 15;77():931-2,p 932.
^Wainwright, Mark (January 2008). "Dyes in the development of drugs and pharmaceuticals".Dyes and Pigments.76 (3):582–589.doi:10.1016/j.dyepig.2007.01.015.
^abcD J Th Wagener,The History of Oncology (Houten: Springer, 2009),pp 150–1.
^John E Lesch,The First Miracle Drugs: How the Sulfa Drugs Transformed Medicine (New York: Oxford University Press, 2007),pp 202–3.
^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.
^Basic Analytical Toxicology (1995), R. J. Flanagan, S. S. Brown, F. A. de Wolff, R. A. Braithwaite, B. Widdop: World Health Organization
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