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62-513: 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

124-411: A base that he named benzidam . In 1843, August Wilhelm von Hofmann showed that these were all the same substance, known thereafter as phenylamine or aniline . 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

186-466: A chiral imidazolidinone : Indole reacts with an enamide catalyzed by a chiral BINOL derived phosphoric acid : In the presence of 10–20 % chiral catalyst, 80–90% ee is achievable. Toluidine There are three isomers of toluidine , which are organic compounds discovered and named by James Sheridan Muspratt and August Wilhelm von Hofmann in 1845. These isomers are o -toluidine , m -toluidine , and p -toluidine , with

248-583: 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 . Aniline is toxic by inhalation of the vapour, ingestion, or percutaneous absorption. The IARC lists it in Group 2A ( Probably carcinogenic to humans ), and it has specifically been linked to bladder cancer. Aniline has been implicated as one possible cause of forest dieback . Many methods exist for

310-633: A member of the aromatic ring, which substantially stabilizes the cationic intermediate. Examples of electrophilic substitutions to pyrrole are the Pictet–Spengler reaction and the Bischler–Napieralski reaction . Electrophilic aromatic substitutions with prochiral carbon electrophiles have been adapted for asymmetric synthesis by switching to chiral Lewis acid catalysts especially in Friedel–Crafts type reactions . An early example concerns

372-402: A substance from coal tar that turned a beautiful blue color when treated with chloride of lime . 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, anil ( Indigofera suffruticosa ). In 1842, Nikolay Nikolaevich Zinin reduced nitrobenzene and obtained

434-411: A substituent group (other than hydrogen). The entering group may displace that substituent group but may also itself be expelled or migrate to another position in a subsequent step. The term ' ipso -substitution' is not used, since it is synonymous with substitution. A classic example is the reaction of salicylic acid with a mixture of nitric and sulfuric acid to form picric acid . The nitration of

496-453: A variety of polyanilines . These polymers exhibit rich redox and acid-base properties. 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 , H 2 NC 6 H 4 SO 3 H . If bromine water

558-425: Is acetanilide . At high temperatures aniline and carboxylic acids react to give the anilides. N -Methylation of aniline with methanol at elevated temperatures over acid catalysts gives N -methylaniline and N , N -dimethylaniline : 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

620-458: 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 NaNO 2 and phenol to produce a dye known as benzeneazophenol , in a process called coupling . The reaction of converting primary aromatic amine into diazonium salt

682-439: Is a flaky solid . This difference is related to the fact that the p -toluidine molecules are more symmetrical. p -Toluidine can be obtained from reduction of p -nitrotoluene . p -Toluidine reacts with formaldehyde to form Tröger's base . The ortho isomer is produced on the largest scale. Its primary application is as a precursor to the pesticides metolachlor and acetochlor . The other toluidine isomers are used in

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744-634: Is a positive charge on the carbon bearing the electron-withdrawing group (i.e., ortho or para attack) is less stable than the others. Therefore, these electron-withdrawing groups are meta directing because this is the position that does not have as much destabilization. The reaction is also much slower (a relative reaction rate of 6×10 compared to benzene) because the ring is less nucleophilic. Although discussions of directing groups usually focus on electronic effects (e.g. EWG vs EDGs), steric effect can prove influential. Thus, nitration of toluene gives approximately 2:1 ortho vs para-nitrotoluene . In

806-416: Is a special type of EAS with special ortho directors . Non-halogen groups with atoms that are more electronegative than carbon, such as a carboxylic acid group (-CO 2 H), withdraw substantial electron density from the pi system. These groups are strongly deactivating groups . Additionally, since the substituted carbon is already electron-poor, any structure having a resonance contributor in which there

868-454: 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: 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

930-476: Is both a base (p K aH = 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 . In aniline, the C−N bond length is 1.41 Å , compared to the C−N bond length of 1.47 Å for cyclohexylamine , indicating partial π-bonding between C(aryl) and N. The length of

992-399: 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 . It reacts with nitrobenzene to produce phenazine in

1054-532: 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." Aniline was first isolated in 1826 by Otto Unverdorben by destructive distillation of indigo . He called it Crystallin . In 1834, Friedlieb Runge isolated

1116-411: Is consistent with low yields of meta-substituted product. Other substituents, such as the alkyl and aryl substituents , may also donate electron density to the pi system; however, since they lack an available unshared pair of electrons, their ability to do this is rather limited. Thus, they only weakly activate the ring and do not strongly disfavor the meta position. Directed ortho metalation

1178-404: 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

1240-538: 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. 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

1302-431: Is replaced by an electrophile . Some of the most important electrophilic aromatic substitutions are aromatic nitration , aromatic halogenation , aromatic sulfonation , alkylation Friedel–Crafts reaction and acylation Friedel–Crafts reaction. The most widely practised example of this reaction is the ethylation of benzene. Approximately 24,700,000 tons were produced in 1999. (After dehydrogenation and polymerization,

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1364-430: Is shown: The resulting diamine is the precursor to 4,4'-MDI and related diisocyanates. 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 ( C 6 H 5 −NH + 3 ). Traditionally, the weak basicity of aniline is attributed to a combination of inductive effect from

1426-400: Is sometimes exploited synthetically, particularly the case of replacement of silyl by another functional group ( ipso attack). However, the loss of groups like iodo or alkyl is more often an undesired side reaction. Both the regioselectivity —the diverse arene substitution patterns —and the speed of an electrophilic aromatic substitution are affected by the substituents already attached to

1488-511: Is the other main ingredient. 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. 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

1550-492: The Hughes–Ingold mechanistic symbol S E Ar , begins with the aromatic ring attacking the electrophile E (2a). This step leads to the formation of a positively charged and delocalized cyclohexadienyl cation , also known as an arenium ion , Wheland intermediate, or arene σ-complex (2b). Many examples of this carbocation have been characterized, but under normal operating conditions these highly acidic species will donate

1612-538: 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 . In addition, aniline is the starting component in the production of diglycidyl aniline . Epichlorohydrin

1674-483: The amino group of aniline , are strongly activating (some time deactivating also in case of halides ) and ortho/para -directing by resonance. Such activating groups donate those unshared electrons to the pi system, creating a negative charge on the ortho and para positions. These positions are thus the most reactive towards an electron-poor electrophile. This increased reactivity might be offset by steric hindrance between activating group and electrophile but on

1736-408: The chemical bond of C( aryl )−NH 2 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 . The amine group in anilines is a slightly pyramidalized molecule, with hybridization of the nitrogen somewhere between sp and sp . The nitrogen is described as having high p character. The amino group in aniline

1798-425: The nitrogen atom can donate electron density to the pi system (forming an iminium ion ), giving four resonance structures (as opposed to three in the basic reaction). This substantially enhances the stability of the cationic intermediate. When the electrophile attacks the meta position, the nitrogen atom cannot donate electron density to the pi system, giving only three resonance contributors. This reasoning

1860-485: The 2 position involves the loss of CO 2 as the leaving group. Desulfonation in which a sulfonyl group is substituted by a proton is a common example. See also Hayashi rearrangement . In aromatics substituted by silicon, the silicon reacts by ipso substitution. Compared to benzene, furans , thiophenes , and pyrroles are more susceptible to electrophilic attack. These compounds all contain an atom with an unshared pair of electrons ( oxygen , sulfur , or nitrogen ) as

1922-665: The C–N bond and the bisector of the H–N–H angle is 142.5°. 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°. Industrial aniline production involves hydrogenation of nitrobenzene (typically at 200–300 °C) in the presence of metal catalysts : Approximately 4 billion kilograms are produced annually. Catalysts include nickel, copper, palladium, and platinum, and newer catalysts continue to be discovered. The reduction of nitrobenzene to aniline

Aniline - Misplaced Pages Continue

1984-559: 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). 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 hybridization. (For comparison, alkylamines generally have lone pairs in orbitals that are close to sp.) The pyramidalization angle between

2046-408: The addition of chloral to phenols catalyzed by aluminium chloride modified with (–)-menthol . A glyoxylate compound has been added to N,N-dimethylaniline with a chiral bisoxazoline ligand – copper(II) triflate catalyst system also in a Friedel–Crafts hydroxyalkylation : In another alkylation N-methylpyrrole reacts with crotonaldehyde catalyzed by trifluoroacetic acid modified with

2108-405: The benzene ring. In terms of regioselectivity, some groups promote substitution at the ortho or para positions, whereas other groups favor substitution at the meta position. These groups are called either ortho–para directing or meta directing , respectively. In addition, some groups will increase the rate of reaction ( activating ) while others will decrease the rate ( deactivating ). While

2170-453: The case of tert-butylbenzene, however, the selectivity is reversed:73% of the product is 4-nitro-tert-butybenzene]]. Compared to benzene, the rate of electrophilic substitution on pyridine is much slower, due to the higher electronegativity of the nitrogen atom. Additionally, the nitrogen in pyridine easily gets a positive charge either by protonation (from nitration or sulfonation ) or Lewis acids (such as AlCl 3 ) used to catalyze

2232-504: The chemical structures below. The chemical properties of the toluidines are quite similar to those of aniline , and toluidines have properties in common with other aromatic amines. Due to the amino group bonded to the aromatic ring, the toluidines are weakly basic . The toluidines are poorly soluble in pure water but dissolve well in acidic water due to formation of ammonium salts, as usual for organic amines. ortho - and meta -toluidines are viscous liquids , but para -toluidine

2294-579: 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

2356-399: The color industry. Boiled with carbon disulfide , it gives sulfocarbanilide (diphenyl thiourea ) ( S=C(−NH−C 6 H 5 ) 2 ), which may be decomposed into phenyl isothiocyanate ( C 6 H 5 −N=C=S ), and triphenyl guanidine ( C 6 H 5 −N=C(−NH−C 6 H 5 ) 2 ). Aniline and its ring-substituted derivatives react with nitrous acid to form diazonium salts . One example

2418-519: The commodity plastic polystyrene is produced.) In this process, acids are used as catalyst to generate the incipient carbocation. Many other electrophilic reactions of benzene are conducted, although on a much smaller scale; they are valuable routes to key intermediates. The nitration of benzene is achieved via the action of the nitronium ion as the electrophile. The sulfonation with fuming sulfuric acid gives benzenesulfonic acid . Aromatic halogenation with bromine , chlorine , or iodine gives

2480-443: The corresponding aryl halides. This reaction is typically catalyzed by the corresponding iron or aluminum trihalide. The Friedel–Crafts reaction can be performed either as an acylation or as an alkylation . Often, aluminium trichloride is used, but almost any strong Lewis acid can be applied. For the acylation reaction a stoichiometric amount of aluminum trichloride is required. The overall reaction mechanism, denoted by

2542-425: The detection of aniline. Exposure of rats to aniline can elicit a response that is toxic to the spleen , including a tumorigenic response. 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 . Although the base excision repair pathway was also activated, its activity

Aniline - Misplaced Pages Continue

2604-454: 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 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

2666-401: The electron density especially at positions 2, 4 and 6, leaving positions 3 and 5 as the ones with comparably higher reactivity, so these types of groups are meta directors (see below). Halogens are electronegative, so they are deactivating by induction, but they have lone pairs, so they are resonance donors and therefore ortho/para directors. Groups with unshared pairs of electrons, such as

2728-489: 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. Some early American rockets, such as the Aerobee and WAC Corporal , used a mixture of aniline and furfuryl alcohol as

2790-649: 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

2852-497: 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 . 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 . During the first decade of the 20th century, while trying to modify synthetic dyes to treat African sleeping sickness , Paul Ehrlich – who had coined

2914-553: The more electronegative sp 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): 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. Aniline reacts with acyl chlorides such as acetyl chloride to give amides . The amides formed from aniline are sometimes called anilides , for example CH 3 −C(=O)−NH−C 6 H 5

2976-437: The nitrogen atom, being electronegative, can hold the negative charge by itself. Another way is to do an oxidation before the electrophilic substitution. This makes pyridine N -oxide , which due to the negative oxygen atom, makes the reaction faster than pyridine, and even benzene. The oxide then can be reduced to the substituted pyridine. The attachment of an entering group to a position in an aromatic compound already carrying

3038-438: The other hand there are two ortho positions for reaction but only one para position. Hence the final outcome of the electrophilic aromatic substitution is difficult to predict, and it is usually only established by doing the reaction and observing the ratio of ortho versus para substitution. In addition to the increased nucleophilic nature of the original ring, when the electrophile attacks the ortho and para positions of aniline,

3100-416: The other hand, deactivating substituents destabilize the intermediate cation and thus decrease the reaction rate by either inductive or resonance effects. They do so by withdrawing electron density from the aromatic ring. The deactivation of the aromatic system means that generally harsher conditions are required to drive the reaction to completion. An example of this is the nitration of toluene during

3162-432: The patterns of regioselectivity can be explained with resonance structures , the influence on kinetics can be explained by both resonance structures and the inductive effect . Substituents can generally be divided into two classes regarding electrophilic substitution: activating and deactivating towards the aromatic ring. Activating substituents or activating groups stabilize the cationic intermediate formed during

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3224-416: The prefixed letter abbreviating, respectively, ortho ; meta ; and para . All three are aryl amines whose chemical structures are similar to aniline except that a methyl group is substituted onto the benzene ring. The difference between these three isomers is the position where the methyl group (–CH 3 ) is bonded to the ring relative to the amino functional group (–NH 2 ); see illustration of

3286-448: The production of trinitrotoluene (TNT). While the first nitration, on the activated toluene ring, can be done at room temperature and with dilute acid, the second one, on the deactivated nitrotoluene ring, already needs prolonged heating and more concentrated acid, and the third one, on very strongly deactivated dinitrotoluene, has to be done in boiling concentrated sulfuric acid . Groups that are electron-withdrawing by resonance decrease

3348-525: The proton attached to the sp carbon to the solvent (or any other weak base) to reestablish aromaticity. The net result is the replacement of H by E in the aryl ring (3). Occasionally, other electrofuges (groups that can leave without their electron pair ) beside H will depart to reestablish aromaticity; these species include silyl groups (as SiR 3 ), the carboxy group (as CO 2 + H ), the iodo group (as I ), and tertiary alkyl groups like t -butyl (as R ). The capacity of these types of substituents to leave

3410-439: The reaction. This makes the reaction even slower by having adjacent formal charges on carbon and nitrogen or 2 formal charges on a localised atom. Doing an electrophilic substitution directly in pyridine is nearly impossible. In order to do the reaction, they can be made by 2 possible reactions, which are both indirect. One possible way to do a substitution on pyridine is nucleophilic aromatic substitution. Even with no catalysts,

3472-466: 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

3534-590: The substituted aromatic compounds followed by reduction. For example, this approach is used to convert toluene into toluidines and chlorobenzene into 4-chloroaniline . Alternatively, using Buchwald-Hartwig coupling or Ullmann reaction approaches, aryl halides can be aminated with aqueous or gaseous ammonia. 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

3596-425: The substitution by donating electrons into the ring system, by either inductive effect or resonance effects . Examples of activated aromatic rings are toluene , aniline and phenol . The extra electron density delivered into the ring by the substituent is not distributed evenly over the entire ring but is concentrated on atoms 2, 4 and 6, so activating substituents are also ortho/para directors (see below). On

3658-463: 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

3720-461: 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 (English: Baden Aniline and Soda Factory), now the largest chemical supplier, echoes

3782-504: 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. Aniline can alternatively be prepared from ammonia and phenol derived from the cumene process . In commerce, three brands of aniline are distinguished: aniline oil for blue, which

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3844-403: 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. Electrophilic aromatic substitution Electrophilic aromatic substitution ( S E Ar ) is an organic reaction in which an atom that is attached to an aromatic system (usually hydrogen)

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