Aromatization is achemical reaction in which anaromatic system is formed from a single nonaromatic precursor. Typically aromatization is achieved by dehydrogenation of existing cyclic compounds, illustrated by the conversion ofcyclohexane intobenzene. Aromatization includes the formation of heterocyclic systems.[1]
Although not practiced under the name, aromatization is a cornerstone ofoil refining. One of the major reforming reactions is thedehydrogenation ofparaffins andnaphthenes into aromatics.
The process, which is catalyzed by platinum supported by aluminium oxide, is exemplified in the conversionmethylcyclohexane (a naphthene) intotoluene (an aromatic).[2]Dehydrocyclization converts paraffins (acyclic hydrocarbons) into aromatics.[3] A related aromatization process includesdehydroisomerization ofmethylcyclopentane to benzene:
As of alkanes, they first dehydrogenate to olefins, thenform rings at the place of the double bond, becoming cycloalkanes, and finally gradually lose hydrogen to become aromatic hydrocarbons.[4]
For cyclohexane, cyclohexene, and cyclohexadiene, dehydrogenation is the conceptually simplest pathway for aromatization. The activation barrier decreases with the degree of unsaturation. Thus, cyclohexadienes are especially prone to aromatization. Formally, dehydrogenation is aredox process. Dehydrogenative aromatization is the reverse of arene hydrogenation. As such, hydrogenation catalysts are effective for the reverse reaction. Platinum-catalyzed dehydrogenations of cyclohexanes and related feedstocks are the largest scale applications of this reaction (see above).[1]
Aromatases areenzymes that aromatize rings within steroids. The specific conversions aretestosterone toestradiol andandrostenedione toestrone.[5] Each of these aromatizations involves the oxidation of the C-19methyl group to allow for the elimination offormic acid concomitant with aromatization. Such conversions are relevant to estrogentumorogenesis in the development ofbreast cancer andovarian cancer inpostmenopausal women andgynecomastia in men.[6]Aromatase inhibitors likeexemestane (which forms a permanent and deactivating bond with the aromatase enzyme)[7] andanastrozole andletrozole (whichcompete for the enzyme)[8] have been shown to be more effective than anti-estrogen medications such astamoxifen likely because they prevent the formation of estradiol.[6]
Although practiced on a very small scale compared to the petrochemical routes, diverse methods have been developed for fine chemical syntheses.
2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is often the reagent of choice. DDQ and an acid catalyst has been used to synthesise a steroid with aphenanthrene core by oxidation accompanied by a doublemethyl migration.[9] In the process, DDQ is itself reduced into an aromatichydroquinone product.
Sulfur and selenium are traditionally used in aromatization, the leaving group beinghydrogen sulfide.[10]
Soluble transition metal complexes can induce oxidative aromatization concomitant with complexation.α-Phellandrene (2-methyl-5-iso-propyl-1,3-cyclohexadiene) is oxidised top-iso-propyltoluene with the reduction ofruthenium trichloride.[11]
Oxidative dehydrogenation of dihydropyridine results in aromatization, givingpyridine.[12]
Non-aromatic rings can be aromatized in many ways.Dehydration allows theSemmler-Wolff reaction of2-cyclohexenoneoxime toaniline under acidic conditions.[13]
Theisomerization of cyclohexadienones gives the aromatic tautomerphenol.[14][15] Isomerization of 1,4-naphthalenediol at 200 °C produces a 2:1 mixture with its keto form, 1,4-dioxotetralin.[16]
Classically, aromatization reactions involve changing the C:H ratio of a substrate. When applied tocyclopentadiene, proton removal gives the aromatic conjugate basecyclopentadienyl anion, isolable assodium cyclopentadienide:[17]
Aromatization can entail removal of hydride. Tropylium,C
7H+
7 arises by the aromatization reaction of cycloheptatriene with hydride acceptors.
The aromatization of acyclic precursors is rarer in organic synthesis, although it is a significant component of theBTX production in refineries.
Among acyclic precursors, alkynes are relatively prone to aromatizations since they are partially dehydrogenated. TheBergman cyclization converts anenediyne to a dehydrobenzene intermediate diradical, which abstracts hydrogen to aromatize.[18] The enediyne moiety can be included within an existing ring, allowing access to a bicyclic system under mild conditions as a consequence of thering strain in the reactant. Cyclodeca-3-en-1,5-diyne reacts with1,3-cyclohexadiene to produce benzene andtetralin at 37 °C, the reaction being highly favorable owing to the formation of two new aromatic rings:
