Aniline, phenylamine or aminobenzene is an organic compound with the formula C6H5NH2. Consisting of a phenyl group attached to an amino group, aniline is the prototypical aromatic amine. Being a precursor to many industrial chemicals, its main use is in the manufacture of precursors to polyurethane. Like most volatile amines, it possesses the somewhat unpleasant odor of rotten fish. It ignites readily, burning with a smoky flame characteristic of aromatic compounds.
- 1 Production
- 2 Reactions
- 3 Uses
- 4 History
- 5 Toxicology and testing
- 6 References
- 7 External links
Aniline is mainly produced in industry in two steps from benzene. First, benzene is nitrated using a concentrated mixture of nitric acid and sulfuric acid at 50 to 60 °C, which gives nitrobenzene. In the second step, the nitrobenzene is hydrogenated, typically at 200–300 °C in presence of various metal catalysts:
Originally, the reduction was effected with a mixture of ferrous chloride and iron metal via the Bechamp reduction.
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.
Related aniline derivatives
Many derivatives of aniline can be prepared in similar fashion from nitrated aromatic compounds. Nitration followed by reduction of toluene affords toluidines. Nitration of chlorobenzene and related derivatives and reduction of the nitration products gives aniline derivatives, e.g. 4-chloroaniline.
The chemistry of aniline is rich because the compound has been cheaply available for many years. Below are some classes of its reactions.
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. Oxidation with persulfate affords a variety of polyanilines compounds. These polymers exhibit rich redox and acid-base properties.
Electrophilic reactions at carbon
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, which can be converted to sulfanilamide. Sulfanilamide is one of the sulfa drugs, which were widely used as antibacterials in the early 20th century. 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
Aniline is a weak base. Aromatic amines such as aniline are, in general, much weaker bases than aliphatic amines because of the electron-withdrawing effect of the phenyl group. Aniline reacts with strong acids to form anilinium (or phenylammonium) ion (C6H5-NH3+). Although aniline is weakly basic, it precipitates zinc, aluminium, and ferric salts, and, on warming, expels ammonia from its salts. The weak basicity is due to both an inductive effect from the more electronegative sp2 carbon and to a resonance effect, as the lone pair on the nitrogen is partially delocalized into the pi system of the benzene ring.
Aniline reacts with carboxylic acids or more readily with acyl chlorides such as acetyl chloride to give amides. The amides formed from aniline are sometimes called anilides, for example CH3-CO-NH-C6H5 is acetanilide. Antifebrin (acetanilide), an anti-pyretic and analgesic, is obtained by the reaction of acetic acid and aniline.
- C6H5NH2 + 2 CH3OH → C6H5N(CH3)2 + 2H2O
N-Methylaniline and dimethylaniline are colorless liquids with boiling points of 193–195 °C and 192 °C, respectively. These derivatives are of importance in the color industry. Aniline combines directly with alkyl iodides to form secondary and tertiary amines.
Carbon disulfide derivatives
Aniline and its ring-substituted derivatives react with nitrous acid to form diazonium salts. Through these intermediates, aniline can be conveniently converted to -OH, -CN, or a halide via Sandmeyer reactions. This diazonium salt can also be reacted with NaNO2 and phenol which produces a dye which is benzeneazophenol, this process is called coupling.
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.
The largest application of aniline is for the preparation of methylene dianiline and related compounds by condensation with formaldehyde as discussed above). The diamines are condensed with phosgene to give Methylene diphenyl diisocyanate, a precursor to urethane polymers. Other uses include rubber processing chemicals (9%), herbicides (2%), and dyes and pigments (2%). 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.
Aniline was first isolated by destructive distillation of indigo by Otto Unverdorben, who named it Crystallin. In 1834, Friedlieb Runge isolated from coal tar a substance that turned a beautiful blue color when treated with chloride of lime, and he named it kyanol or cyanol. 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, Añil (Indigofera suffruticosa). In 1842, Nikolay Nikolaevich Zinin reduced nitrobenzene and obtained a base that he named benzidam. In 1843, August Wilhelm von Hofmann showed that all of these substances are the same substance — thereafter known as phenylamine or aniline.
Synthetic dye industry
In 1856, von Hofmann's student William Henry Perkin discovered mauveine and went into industry producing the first synthetic dye. Other aniline dyes followed, such as fuchsine, safranine, and induline. At the time of mauveine's discovery, aniline was expensive. Soon thereafter, applying a method reported in 1854 by Antoine Béchamp, it was prepared "by the ton". The Béchamp reduction enabled the evolution of a massive dye industry in Germany. Today, the name of BASF, originally Badische Anilin- und Soda-Fabrik, now among the largest chemical suppliers, 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.
Developments in medicine
In the late 19th century, aniline emerged as an analgesic drug, its cardiac-suppressive side effects countered with caffeine. 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.
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. By the 1940s, over 500 related sulfa drugs were produced. Medications in high demand during World War II (1939–45), these first miracle drugs, chemotherapy of wide effectiveness, propelled the American pharmaceutics industry. 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.
Toxicology and testing
Aniline is toxic by inhalation of the vapour, ingestion, or percutaneous absorption. The IARC lists it in Group 3 (not classifiable as to its carcinogenicity to humans) due to the limited and contradictory data available. The early manufacture of aniline resulted in increased incidents of bladder cancer, but these effects are now attributed to naphthylamines, not anilines.
Many methods exist for detection of aniline. It is metabolized to p-aminophenol and p-acetamidophenol, which are excreted in urine as sulfate and glucuronide conjugates. On hydrolysis of urine, p-aminophenol is reformed, and can be detected using the o-cresol test.
- This article incorporates text from a publication now in the public domain: Chisholm, Hugh, ed. (1911). Encyclopædia Britannica (11th ed.). Cambridge University Press
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- No longer in common medicinal use.
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- Otto Unverdorben (1826). "Ueber das Verhalten der organischen Körper in höheren Temperaturen" [On the behaviour of organic substances at high temperatures]. Annalen der Physik und Chemie 8 (11): 397–410. Bibcode:1826AnP....84..397U. doi:10.1002/andp.18260841109.
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- 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 ; see pages 457–459.
- synonym I 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.)
- Perkin, William Henry. 1861-06-08. "Proceedings of Chemical Societies: Chemical Society, Thursday, May 16, 1861." The Chemical News and Journal of Industrial Science. Retrieved on 2007-09-24.
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- Wilcox RW, "The treatment of influenza in adults", Medical News, 1900 Dec 15;77():931-2, p 932.
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- John E Lesch, The First Miracle Drugs: How the Sulfa Drugs Transformed Medicine (New York: Oxford University Press, 2007), pp 202–3.
- "Medicine: Spoils of war", Time, 15 May 1950.
- Muir, GD (ed.) 1971, Hazards in the Chemical Laboratory, The Royal Institute of Chemistry, London.
- The Merck Index. 10th ed. (1983), p.96, Rahway: Merck & Co.
- 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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