HOME

TheInfoList



OR:

Aromatization is a
chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and break ...
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 Cyclohexane is a cycloalkane with the molecular formula . Cyclohexane is non-polar. Cyclohexane is a colorless, flammable liquid with a distinctive detergent-like odor, reminiscent of cleaning products (in which it is sometimes used). Cyclohex ...
into
benzene Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen ato ...
. Aromatization includes the formation of heterocyclic systems. :


Industrial practice

Although not practiced under the name, aromatization is a cornerstone of oil refining. One of the major reforming reactions is the
dehydrogenation 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. A ...
of
naphthene In organic chemistry, the cycloalkanes (also called naphthenes, but distinct from naphthalene) are the monocyclic saturated hydrocarbons. In other words, a cycloalkane consists only of hydrogen and carbon atoms arranged in a structure containing ...
s into aromatics. The process, which is catalyzed by platinum, is exemplified in the conversion
methylcyclohexane Methylcyclohexane (cyclohexylmethane) is an organic compound with the molecular formula is CH3C6H11. Classified as saturated hydrocarbon, it is a colourless liquid with a faint odor. Methylcyclohexane is used as a solvent. It is mainly converted ...
(a naphthene) into
toluene Toluene (), also known as toluol (), is a substituted aromatic hydrocarbon. It is a colorless, water-insoluble liquid with the smell associated with paint thinners. It is a mono-substituted benzene derivative, consisting of a methyl group (CH3) ...
(an aromatic). Dehydrocyclization converts paraffins (acyclic hydrocarbons) into aromatics. A related aromatization process includes dehydroisomerization of
methylcyclopentane Methylcyclopentane is an organic compound with the chemical formula CH3C5 H9. It is a colourless, flammable liquid with a faint odor. It is a component of the naphthene fraction of petroleum. It usually is obtained as a mixture with cyclohexan ...
to benzene: :


Biochemical processes

:
Aromatase Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze ma ...
s are
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
s that aromatize rings within steroids. The specific conversions are
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteris ...
to
estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development o ...
and
androstenedione Androstenedione, or 4-androstenedione (abbreviated as A4 or Δ4-dione), also known as androst-4-ene-3,17-dione, is an endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehy ...
to
estrone Estrone (E1), also spelled oestrone, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estriol. Estrone, as well as the other estrogens, are synthesized ...
. Each of these aromatizations involves the oxidation of the C-19 methyl group to allow for the elimination of
formic acid Formic acid (), systematically named methanoic acid, is the simplest carboxylic acid, and has the chemical formula HCOOH and structure . It is an important intermediate in chemical synthesis and occurs naturally, most notably in some ants. Est ...
concomitant with aromatization. Such conversions are relevant to estrogen tumorogenesis in the development of
breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...
and
ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different ...
in
postmenopausal Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
women and
gynecomastia Gynecomastia (also spelled gynaecomastia) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse ...
in men.
Aromatase inhibitors Aromatase inhibitors (AIs) are a class of drugs used in the treatment of breast cancer in postmenopausal women and in men, and gynecomastia in men. They may also be used off-label to reduce estrogen conversion when supplementing testosterone e ...
like
exemestane Exemestane, sold under the brand name Aromasin among others, is a medication used to treat breast cancer. It is a member of the class of antiestrogens known as aromatase inhibitors. Some breast cancers require estrogen to grow. Those cancers hav ...
(which forms a permanent and deactivating bond with the aromatase enzyme) and
anastrozole Anastrozole, sold under the brand name Arimidex among others, is a medication used in addition to other treatments for breast cancer. Specifically it is used for hormone receptor-positive breast cancer. It has also been used to prevent breast ca ...
and
letrozole Letrozole, sold under the brand name Femara among others, is an aromatase inhibitor medication that is used in the treatment of breast cancer. It was patented in 1986 and approved for medical use in 1996. In 2020, it was the 257th most commo ...
(which
compete Competition is a rivalry where two or more parties strive for a common goal which cannot be shared: where one's gain is the other's loss (an example of which is a zero-sum game). Competition can arise between entities such as organisms, indivi ...
for the enzyme) have been shown to be more effective than anti-estrogen medications such as
tamoxifen Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and treat breast cancer in women and men. It is also being studied for other types of cancer. It has b ...
likely because they prevent the formation of estradiol.


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 Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate (chemistry), substrate change. Oxidation is the loss of Electron, electrons or an increase in the oxidation state, while reduction ...
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).
2,3-Dichloro-5,6-dicyano-1,4-benzoquinone 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 min ...
(DDQ) is often the reagent of choice. DDQ and an acid catalyst has been used to synthesise a steroid with a
phenanthrene 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 and pesticides, ...
core by oxidation accompanied by a double
methyl migration In organic chemistry, a rearrangement reaction is a broad class of organic reactions where the carbon skeleton of a molecule is rearranged to give a structural isomer of the original molecule. Often a substituent moves from one atom to another ato ...
. In the process, DDQ is itself reduced into an aromatic
hydroquinone Hydroquinone, also known as benzene-1,4-diol or quinol, is an aromatic organic compound that is a type of phenol, a derivative of benzene, having the chemical formula C6H4(OH)2. It has two hydroxyl groups bonded to a benzene ring in a ''para'' ...
product. : Sulfur and selenium are traditionally used in aromatization, the leaving group being
hydrogen sulfide Hydrogen sulfide is a chemical compound with the formula . It is a colorless chalcogen-hydride gas, and is poisonous, corrosive, and flammable, with trace amounts in ambient atmosphere having a characteristic foul odor of rotten eggs. The und ...
. 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 Ruthenium(III) chloride is the chemical compound with the formula RuCl3. "Ruthenium(III) chloride" more commonly refers to the hydrate RuCl3·''x''H2O. Both the anhydrous and hydrated species are dark brown or black solids. The hydrate, with a va ...
. Oxidative dehydrogenation of dihydropyridine results in aromatization, giving
pyridine Pyridine is a basic (chemistry), basic heterocyclic compound, heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom. It is a highly flammable, weakl ...
.


Dehydration

Non-aromatic rings can be aromatized in many ways.
Dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mi ...
allows the Semmler-Wolff transformation of
2-cyclohexenone Cyclohexenone is an organic compound which is a versatile intermediate used in the synthesis of a variety of chemical products such as pharmaceuticals and fragrances. It is colorless liquid, but commercial samples are often yellow. Industrially, ...
oxime In organic chemistry, an oxime is a organic compound belonging to the imines, with the general formula , where R is an organic side-chain and R’ may be hydrogen, forming an aldoxime, or another organic group, forming a ketoxime. O-substitu ...
to
aniline Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine. It is an industrially significant commodity chemical, as well as a versatile start ...
under acidic conditions.


Tautomerization

The
isomerization In chemistry, isomerization or isomerisation is the process in which a molecule, polyatomic ion or molecular fragment is transformed into an isomer with a different chemical structure. Enolization is an example of isomerization, as is tautome ...
of cyclohexadienones gives the aromatic tautomer
phenol Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it ...
. Isomerization of 1,4-naphthalenediol at 200 °C produces a 2:1 mixture with its keto form, 1,4-dioxotetralin.


Hydride and proton abstraction

Classically, aromatization reactions involve changing the C:H ratio of a substrate. When applied to
cyclopentadiene Cyclopentadiene is an organic compound with the formula C5H6.LeRoy H. Scharpen and Victor W. Laurie (1965): "Structure of cyclopentadiene". ''The Journal of Chemical Physics'', volume 43, issue 8, pages 2765-2766. It is often abbreviated CpH beca ...
, proton removal gives the aromatic conjugate base
cyclopentadienyl anion In chemistry, the cyclopentadienyl anion or cyclopentadienide is an aromatic species with a formula of and abbreviated as Cp−. It is formed from the deprotonation of the molecule cyclopentadiene. Properties The cyclopentadienyl anion ...
, isolable as
sodium cyclopentadienide Sodium cyclopentadienide is an organosodium compound with the formula C5H5Na. The compound is often abbreviated as NaCp, where Cp− is the cyclopentadienide anion. Sodium cyclopentadienide is a colorless solid, although samples often are p ...
: :2 Na + 2 C5H6 → 2 NaC5H5 + H2 Aromatization can entail removal of hydride. Tropylium, arises by the aromatization reaction of cycloheptatriene with hydride acceptors. : + → + +


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 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 ...
is converts an
enediyne In organic chemistry, enediynes are organic compounds containing two triple bonds and one double bond. Enediynes are most notable for their limited use as antitumor antibiotics (known as enediyne anticancer antibiotics). They are efficient at ...
to a dehydrobenzene intermediate diradical, which abstracts hydrogen to aromatize. 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 organic chemistry, ring strain is a type of instability that exists when bonds in a molecule form angles that are abnormal. Strain is most commonly discussed for small rings such as cyclopropanes and cyclobutanes, whose internal angles are s ...
in the reactant. Cyclodeca-3-en-1,5-diyne reacts with
1,3-cyclohexadiene Cyclohexa-1,3-diene 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). A naturally occurring derivative of 1,3-cyclohexadiene is terpinene, a component of pine oi ...
to produce benzene and
tetralin Tetralin (1,2,3,4-tetrahydronaphthalene) is a hydrocarbon having the chemical formula C10H12. It is a partially hydrogenated derivative of naphthalene. It is a colorless liquid that is used as a hydrogen-donor solvent. Production Tetralin is pro ...
at 37 °C, the reaction being highly favorable owing to the formation of two new aromatic rings: :


See also

*
Aromatase Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze ma ...
*
Aromatic hydrocarbon Aromatic compounds, also known as "mono- and polycyclic aromatic hydrocarbons", are organic compounds containing one or more aromatic rings. The parent member of aromatic compounds is benzene. The word "aromatic" originates from the past grou ...


References

{{Reflist, 30em Hydrogen Oil refining Organic redox reactions