Aromatization

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Aromatization is a chemical reaction in which an aromatic system is formed from a single nonaromatic precursor. Typically aromatization is achieved by dehydrogenation of existing cyclic compounds, illustrated by the conversion of cyclohexane into benzene. Aromatization includes the formation of heterocyclic systems. [1]

Contents

The conversion of methylcyclohexane to toluene is a classic aromatization reaction. This platinum (Pt)-catalyzed process is practiced on scale in the production of gasoline from petroleum. MeC6H11toPhMe.png
The conversion of methylcyclohexane to toluene is a classic aromatization reaction. This platinum (Pt)-catalyzed process is practiced on scale in the production of gasoline from petroleum.

Industrial practice

Although not practiced under the name, aromatization is a cornerstone of oil refining. One of the major reforming reactions is the dehydrogenation of naphthenes into aromatics. The process, which is catalyzed by platinum, is exemplified in the conversion methylcyclohexane (a naphthene) into toluene (an aromatic). [2] Dehydrocyclization converts paraffins (acyclic hydrocarbons) into aromatics. [3] A related aromatization process includes dehydroisomerization of methylcyclopentane to benzene:

MeC5H9toPhH.png

Biochemical processes

Testosterone estradiol conversion.png

Aromatases are enzymes that aromatize rings within steroids. The specific conversions are testosterone to estradiol and androstenedione to estrone. [4] Each of these aromatizations involves the oxidation of the C-19 methyl group to allow for the elimination of formic acid concomitant with aromatization. Such conversions are relevant to estrogen tumorogenesis in the development of breast cancer and ovarian cancer in postmenopausal women and gynecomastia in men. [5] Aromatase inhibitors like exemestane (which forms a permanent and deactivating bond with the aromatase enzyme) [6] and anastrozole and letrozole (which compete for the enzyme) [7] have been shown to be more effective than anti-estrogen medications such as tamoxifen likely because they prevent the formation of estradiol. [5]

Aromatization pathways

Oxidative dehydrogenation

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 a redox 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]

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 a phenanthrene core by oxidation accompanied by a double methyl migration. [8] In the process, DDQ is itself reduced into an aromatic hydroquinone product.

DDQ aromatization rearrangement.png

Sulfur and selenium are traditionally used in aromatization, the leaving group being hydrogen sulfide. [9]

Soluble transition metal complexes can induce oxidative aromatization concomitant with complexation. α-Phellandrene (2-methyl-5-iso-propyl-1,3-cyclohexadiene) is oxidised to p-iso-propyltoluene with the reduction of ruthenium trichloride. [10]

Oxidative dehydrogenation of dihydropyridine results in aromatization, giving pyridine. [11]

Dehydration

240pxSemmler-Wolff synthesis of aniline Semmler-Wolff reaction.svg
240pxSemmler-Wolff synthesis of aniline

Non-aromatic rings can be aromatized in many ways. Dehydration allows the Semmler-Wolff reaction of 2-cyclohexenone oxime to aniline under acidic conditions. [12]

Tautomerization

1,4-Dioxotetralin and its aromatized tautomer 1,4-naphthalenediol coexist in equal abundance in solution. Tetrahydronaphthalenedione.png
1,4-Dioxotetralin and its aromatized tautomer 1,4-naphthalenediol coexist in equal abundance in solution.

The isomerization of cyclohexadienones gives the aromatic tautomer phenol. [13] [14] Isomerization of 1,4-naphthalenediol at 200 °C produces a 2:1 mixture with its keto form, 1,4-dioxotetralin. [15]

Hydride and proton abstraction

Classically, aromatization reactions involve changing the C:H ratio of a substrate. When applied to cyclopentadiene, proton removal gives the aromatic conjugate base cyclopentadienyl anion, isolable as sodium cyclopentadienide: [16]

2 Na + 2 C5H6 → 2 NaC5H5 + H2

Aromatization can entail removal of hydride. Tropylium, C
7H+
7 arises by the aromatization reaction of cycloheptatriene with hydride acceptors.

C
7H
8 + Br
2 → C
7H+
7 + Br−
 + HBr
Ciamician-Dennstedt rearrangement of a pyrrole to a pyridine. The first step involves dearomatization. The second step involves aromatization. Ciamician-Dennstedt Rearrangement.png
Ciamician-Dennstedt rearrangement of a pyrrole to a pyridine. The first step involves dearomatization. The second step involves aromatization.

From acyclic precursors

The aromatization of acyclic precursors is rarer in organic synthesis, although it is a significant component of the BTX production in refineries.

Among acyclic precursors, alkynes are relatively prone to aromatizations since they are partially dehydrogenated. The Bergman cyclization is converts an enediyne to a dehydrobenzene intermediate diradical, which abstracts hydrogen to aromatize. [17] The enediyne moiety can be included within an existing ring, allowing access to a bicyclic system under mild conditions as a consequence of the ring strain in the reactant. Cyclodeca-3-en-1,5-diyne reacts with 1,3-cyclohexadiene to produce benzene and tetralin at 37 °C, the reaction being highly favorable owing to the formation of two new aromatic rings:

Scheme 1. Bergman cyclization Bergman cyclization.svg
Scheme 1. Bergman cyclization

See also

Related Research Articles

<span class="mw-page-title-main">Aromatic compound</span> Compound containing rings with delocalized pi electrons

Aromatic compounds or arenes usually refers to organic compounds "with a chemistry typified by benzene" and "cyclically conjugated." The word "aromatic" originates from the past grouping of molecules based on odor, before their general chemical properties were understood. The current definition of aromatic compounds does not have any relation to their odor. Aromatic compounds are now defined as cyclic compounds satisfying Hückel's Rule. Aromatic compounds have the following general properties:

The quinones are a class of organic compounds that are formally "derived from aromatic compounds [such as benzene or naphthalene] by conversion of an even number of –CH= groups into –C(=O)– groups with any necessary rearrangement of double bonds", resulting in "a fully conjugated cyclic dione structure". The archetypical member of the class is 1,4-benzoquinone or cyclohexadienedione, often called simply "quinone". Other important examples are 1,2-benzoquinone (ortho-quinone), 1,4-naphthoquinone and 9,10-anthraquinone.

Cyclohexane is a cycloalkane with the molecular formula C6H12. Cyclohexane is non-polar. Cyclohexane is a colourless, flammable liquid with a distinctive detergent-like odor, reminiscent of cleaning products. Cyclohexane is mainly used for the industrial production of adipic acid and caprolactam, which are precursors to nylon.

<span class="mw-page-title-main">Phenanthrene</span> Polycyclic aromatic hydrocarbon composed of three fused benzene rings

Phenanthrene is a polycyclic aromatic hydrocarbon (PAH) with formula C14H10, consisting of three fused benzene rings. It is a colorless, crystal-like solid, but can also appear yellow. Phenanthrene is used to make dyes, plastics, pesticides, explosives, and drugs. It has also been used to make bile acids, cholesterol and steroids.

<span class="mw-page-title-main">Hückel's rule</span> Method of determining aromaticity in organic molecules

In organic chemistry, Hückel's rule predicts that a planar ring molecule will have aromatic properties if it has 4n + 2 π electrons, where n is a non-negative integer. The quantum mechanical basis for its formulation was first worked out by physical chemist Erich Hückel in 1931. The succinct expression as the 4n + 2 rule has been attributed to W. v. E. Doering (1951), although several authors were using this form at around the same time.

In chemistry, dehydrogenation is a chemical reaction that involves the removal of hydrogen, usually from an organic molecule. It is the reverse of hydrogenation. Dehydrogenation is important, both as a useful reaction and a serious problem. At its simplest, it's a useful way of converting alkanes, which are relatively inert and thus low-valued, to olefins, which are reactive and thus more valuable. Alkenes are precursors to aldehydes, alcohols, polymers, and aromatics. As a problematic reaction, the fouling and inactivation of many catalysts arises via coking, which is the dehydrogenative polymerization of organic substrates.

Cyclohexa-1,3-diene (also known as Benzane) is an organic compound with the formula (C2H4)(CH)4. It is a colorless, flammable liquid. Its refractive index is 1.475 (20 °C, D). It is one of two isomers of cyclohexadiene, the other being 1,4-cyclohexadiene.

<span class="mw-page-title-main">Cyclohexa-1,4-diene</span> Chemical compound

1,4-Cyclohexadiene is an organic compound with the formula C6H8. It is a colourless, flammable liquid that is of academic interest as a prototype of a large class of related compounds called terpenoids, an example being γ-terpinene. An isomer of this compound is 1,3-cyclohexadiene.

<span class="mw-page-title-main">Catalytic reforming</span> Chemical process used in oil refining

Catalytic reforming is a chemical process used to convert petroleum refinery naphthas distilled from crude oil into high-octane liquid products called reformates, which are premium blending stocks for high-octane gasoline. The process converts low-octane linear hydrocarbons (paraffins) into branched alkanes (isoparaffins) and cyclic naphthenes, which are then partially dehydrogenated to produce high-octane aromatic hydrocarbons. The dehydrogenation also produces significant amounts of byproduct hydrogen gas, which is fed into other refinery processes such as hydrocracking. A side reaction is hydrogenolysis, which produces light hydrocarbons of lower value, such as methane, ethane, propane and butanes.

In organic chemistry, a cyclophane is a hydrocarbon consisting of an aromatic unit and a chain that forms a bridge between two non-adjacent positions of the aromatic ring. More complex derivatives with multiple aromatic units and bridges forming cagelike structures are also known. Cyclophanes are well-studied examples of strained organic compounds.

<span class="mw-page-title-main">1,4-Benzoquinone</span> Chemical compound

1,4-Benzoquinone, commonly known as para-quinone, is a chemical compound with the formula C6H4O2. In a pure state, it forms bright-yellow crystals with a characteristic irritating odor, resembling that of chlorine, bleach, and hot plastic or formaldehyde. This six-membered ring compound is the oxidized derivative of 1,4-hydroquinone. The molecule is multifunctional: it exhibits properties of a ketone, being able to form oximes; an oxidant, forming the dihydroxy derivative; and an alkene, undergoing addition reactions, especially those typical for α,β-unsaturated ketones. 1,4-Benzoquinone is sensitive toward both strong mineral acids and alkali, which cause condensation and decomposition of the compound.

<span class="mw-page-title-main">Cyclic compound</span> Molecule with a ring of bonded atoms

A cyclic compound is a term for a compound in the field of chemistry in which one or more series of atoms in the compound is connected to form a ring. Rings may vary in size from three to many atoms, and include examples where all the atoms are carbon, none of the atoms are carbon, or where both carbon and non-carbon atoms are present. Depending on the ring size, the bond order of the individual links between ring atoms, and their arrangements within the rings, carbocyclic and heterocyclic compounds may be aromatic or non-aromatic; in the latter case, they may vary from being fully saturated to having varying numbers of multiple bonds between the ring atoms. Because of the tremendous diversity allowed, in combination, by the valences of common atoms and their ability to form rings, the number of possible cyclic structures, even of small size numbers in the many billions.

<span class="mw-page-title-main">Bergman cyclization</span>

The Masamune-Bergman cyclization or Masamune-Bergman reaction or Masamune-Bergman cycloaromatization is an organic reaction and more specifically a rearrangement reaction taking place when an enediyne is heated in presence of a suitable hydrogen donor. It is the most famous and well-studied member of the general class of cycloaromatization reactions. It is named for Japanese-American chemist Satoru Masamune and American chemist Robert G. Bergman. The reaction product is a derivative of benzene.

Pyrylium is a cation with formula C5H5O+, consisting of a six-membered ring of five carbon atoms, each with one hydrogen atom, and one positively charged oxygen atom. The bonds in the ring are conjugated as in benzene, giving it an aromatic character. In particular, because of the positive charge, the oxygen atom is trivalent. Pyrilium is a mono-cyclic and heterocyclic compound, one of the oxonium ions.

<span class="mw-page-title-main">Tetraphenylcyclopentadienone</span> Chemical compound

Tetraphenylcyclopentadienone is an organic compound with the formula (C6H5)4C4CO. It is a dark purple to black crystalline solid that is soluble in organic solvents. It is an easily made building block for many organic and organometallic compounds.

<span class="mw-page-title-main">Chloranil</span> Chemical compound

Chloranil is a quinone with the molecular formula C6Cl4O2. Also known as tetrachloro-1,4-benzoquinone, it is a yellow solid. Like the parent benzoquinone, chloranil is a planar molecule that functions as a mild oxidant.

<span class="mw-page-title-main">2,3-Dichloro-5,6-dicyano-1,4-benzoquinone</span> Chemical compound

2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (or DDQ) is the chemical reagent with formula C6Cl2(CN)2O2. This oxidant is useful for the dehydrogenation of alcohols, phenols, and steroid ketones. DDQ decomposes in water, but is stable in aqueous mineral acid.

<span class="mw-page-title-main">Half sandwich compound</span> Class of coordination compounds

Half sandwich compounds, also known as piano stool complexes, are organometallic complexes that feature a cyclic polyhapto ligand bound to an MLn center, where L is a unidentate ligand. Thousands of such complexes are known. Well-known examples include cyclobutadieneiron tricarbonyl and (C5H5)TiCl3. Commercially useful examples include (C5H5)Co(CO)2, which is used in the synthesis of substituted pyridines, and methylcyclopentadienyl manganese tricarbonyl, an antiknock agent in petrol.

<span class="mw-page-title-main">1-Tetralone</span> Chemical compound

1-Tetralone is a bicyclic aromatic hydrocarbon and a ketone. In terms of its structure, it can also be regarded as benzo-fused cyclohexanone. It is a colorless oil with a faint odor. It is used as starting material for agricultural and pharmaceutical agents. The carbon skeleton of 1-tetralone is found in natural products such as Aristelegone A (4,7-dimethyl-6-methoxy-1-tetralone) from the family of Aristolochiaceae used in traditional Chinese medicine.

Metal arene complexes are organometallic compounds of the formula (C6R6)xMLy. Common classes are of the type (C6R6)ML3 and (C6R6)2M. These compounds are reagents in inorganic and organic synthesis. The principles that describe arene complexes extend to related organic ligands such as many heterocycles (e.g. thiophene) and polycyclic aromatic compounds (e.g. naphthalene).

References

  1. 1 2 Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York: Wiley-Interscience, ISBN   978-0-471-72091-1
  2. ↑ Gary, J.H.; Handwerk, G.E. (1984). Petroleum Refining Technology and Economics (2nd ed.). Marcel Dekker, Inc. ISBN   0-8247-7150-8.
  3. ↑ Ono, Y. (1992). "Transformation of Lower Alkanes into Aromatic Hydrocarbons over ZSM-5 Zeolites". Catal. Rev. - Sci. Eng. 34 (3): 179–226. doi:10.1080/01614949208020306.
  4. ↑ Lephart, E. D. (1996). "A Review of Brain Aromatase Cytochrome P450". Brain Res. Rev. 22 (1): 1–26. doi:10.1016/0165-0173(96)00002-1. PMID   8871783. S2CID   11987113.
  5. 1 2 Avendaño, C.; Menéndez, J. C. (2008). "Aromatase Inhibitors". Medicinal Chemistry of Anticancer Drugs. Elsevier. pp. 65–73. doi:10.1016/B978-0-444-52824-7.00003-2. ISBN   9780080559629.
  6. ↑ Jasek, W., ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. pp. 656–660. ISBN   9783852001814.
  7. ↑ Dinnendahl, V.; Fricke, U., eds. (2007). Arzneistoff-Profile (in German). Vol. 4 (21st ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN   9783774198463.
  8. ↑ Brown, W.; Turner, A. B. (1971). "Applications of High-Potential Quinones. Part VII. The Synthesis of Steroidal Phenanthrenes by Double Methyl Migration". Journal of the Chemical Society C: Organic . 14: 2566–2572. doi:10.1039/J39710002566. PMID   5167256.
  9. ↑ Bergmann, F.; Szmuszkowicz, J.; Fawaz, G. (1947). "The Condensation of 1,1-Diarylethylenes with Maleic Anhydride". Journal of the American Chemical Society . 69 (7): 1773–1777. doi:10.1021/ja01199a055. PMID   20251415.
  10. ↑ Bennett, M. A.; Huang, T. N.; Matheson, T. W.; Smith, A. K. (1982). (η6-Hexamethylbenzene)ruthenium Complexes. Inorganic Syntheses. Vol. 21. pp. 74–78. doi:10.1002/9780470132524.ch16. ISBN   9780470132524.
  11. ↑ Shimizu, S.; Watanabe, N.; Kataoka, T.; Shoji, T.; Abe, N.; Morishita, S.; Ichimura, H. (2005). "Pyridine and Pyridine Derivatives". Ullmann's Encyclopedia of Industrial Chemistry. Wiley-VCH. doi:10.1002/14356007.a22_399. ISBN   3527306730.
  12. ↑ Horning, E. C.; Stromberg, V. L.; Lloyd, H. A. (1952). "Beckmann Rearrangements. An Investigation of Special Cases". Journal of the American Chemical Society . 74 (20): 5153–5155. doi:10.1021/ja01140a048.
  13. ↑ Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. (2001). Organic Chemistry (1st ed.). Oxford University Press. p.  531. ISBN   9780198503460.
  14. ↑ Capponi, M.; Gut, I. G.; Hellrung, B.; Persy, G.; Wirz, J. (1999). "Ketonization Equilibria of Phenol in Aqueous Solution". Canadian Journal of Chemistry . 77 (5–6): 605–613. doi:10.1139/cjc-77-5-6-605.
  15. ↑ Kündig, E. P.; Garcia, A. E.; Lomberget, T.; Bernardinelli, G. (2005). "Rediscovery, Isolation, and Asymmetric Reduction of 1,2,3,4-Tetrahydronaphthalene-1,4-dione and Studies of its [Cr(CO)3] Complex". Angewandte Chemie International Edition . 45 (1): 98–101. doi:10.1002/anie.200502588. PMID   16304647.
  16. ↑ Cotton, F. A.; Wilkinson, G. (1999). Advanced Inorganic Chemistry (6th ed.). John Wiley and Sons. ISBN   9780471199571.
  17. ↑ Mohamed, R. K.; Peterson, P. W.; Alabugin, I. V. (2013). "Concerted Reactions that Produce Diradicals and Zwitterions: Electronic, Steric, Conformational and Kinetic Control of Cycloaromatization Processes". Chemical Reviews . 113 (9): 7089–7129. doi:10.1021/cr4000682. PMID   23600723.
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