Hydroquinone, also known as benzene-1,4-diol or quinol, is an
aromatic
In organic chemistry, aromaticity is a chemical property describing the way in which a conjugated system, conjugated ring of unsaturated bonds, lone pairs, or empty orbitals exhibits a stabilization stronger than would be expected from conjugati ...
organic compound
Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...
that is a type of
phenol
Phenol (also known as carbolic acid, phenolic acid, or benzenol) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile and can catch fire.
The molecule consists of a phenyl group () ...
, a derivative of
benzene
Benzene is an Organic compound, organic chemical compound with the Chemical formula#Molecular formula, molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar hexagonal Ring (chemistry), ring with one hyd ...
, having the
chemical formula
A chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, such as pare ...
C
6H
4(OH)
2. It has two
hydroxyl group
In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...
s
bonded to a
benzene ring in a
''para'' position. It is a white granular
solid
Solid is a state of matter where molecules are closely packed and can not slide past each other. Solids resist compression, expansion, or external forces that would alter its shape, with the degree to which they are resisted dependent upon the ...
. Substituted derivatives of this parent compound are also referred to as hydroquinones. The name "hydroquinone" was coined by
Friedrich Wöhler in 1843.
In 2022, it was the 268th most commonly prescribed medication in the United States, with more than 900,000 prescriptions.
Production
Hydroquinone is produced industrially in two main ways.
[Phillip M. Hudnall "Hydroquinone" in Ullmann's Encyclopedia of Industrial Chemistry 2002, Wiley-VCH, Weinheim. 2005 Wiley-VCH, Weinheim. .]
* The most widely used route is similar to the
cumene process in reaction mechanism and involves the dialkylation of
benzene
Benzene is an Organic compound, organic chemical compound with the Chemical formula#Molecular formula, molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar hexagonal Ring (chemistry), ring with one hyd ...
with
propene to give 1,4-diisopropylbenzene. This compound reacts with air to afford the bis(hydroperoxide), which is structurally similar to
cumene hydroperoxide and rearranges in acid to give
acetone
Acetone (2-propanone or dimethyl ketone) is an organic compound with the chemical formula, formula . It is the simplest and smallest ketone (). It is a colorless, highly Volatile organic compound, volatile, and flammable liquid with a charact ...
and hydroquinone.
* A second route involves
hydroxylation of
phenol
Phenol (also known as carbolic acid, phenolic acid, or benzenol) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile and can catch fire.
The molecule consists of a phenyl group () ...
over a catalyst. The conversion uses
hydrogen peroxide
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscosity, viscous than Properties of water, water. It is used as an oxidizer, bleaching agent, and antiseptic, usua ...
and affords a mixture of hydroquinone and its ortho isomer
catechol (benzene-1,2-diol):
::
Other, less common methods include:
* A potentially significant synthesis of hydroquinone from
acetylene
Acetylene (Chemical nomenclature, systematic name: ethyne) is a chemical compound with the formula and structure . It is a hydrocarbon and the simplest alkyne. This colorless gas is widely used as a fuel and a chemical building block. It is u ...
and
iron pentacarbonyl has been proposed.
Iron pentacarbonyl serves as a
catalyst, rather than as a
reagent, in the presence of free
carbon monoxide
Carbon monoxide (chemical formula CO) is a poisonous, flammable gas that is colorless, odorless, tasteless, and slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom connected by a triple bond. It is the si ...
gas.
Rhodium or
ruthenium can substitute for iron as the catalyst with favorable chemical yields but are not typically used due to their cost of recovery from the reaction mixture.
* Hydroquinone and its
derivatives can also be prepared by oxidation of various phenols, such as
aniline
Aniline (From , meaning ' indigo shrub', and ''-ine'' indicating a derived substance) is an organic compound with the formula . Consisting of a phenyl group () attached to an amino group (), aniline is the simplest aromatic amine. It is an in ...
and
DIPB.
Examples include
Elbs persulfate oxidation and
Dakin oxidation.
* Hydroquinone was first obtained in 1820 by the French chemists
Pelletier and
Caventou via the
dry distillation of
quinic acid.
*
Hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...
of
chlorophenol.
The latter three methods are generally less
atom-economical than oxidation with hydrogen peroxide, and their commercial practice in China produced serious
pollution
Pollution is the introduction of contaminants into the natural environment that cause harm. Pollution can take the form of any substance (solid, liquid, or gas) or energy (such as radioactivity, heat, sound, or light). Pollutants, the component ...
in 2022.
Reactions
The reactivity of hydroquinone's
hydroxyl groups resembles that of other
phenol
Phenol (also known as carbolic acid, phenolic acid, or benzenol) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile and can catch fire.
The molecule consists of a phenyl group () ...
s, being weakly acidic. The resulting
conjugate base easily undergoes ''O''-alkylation to give
mono- and diethers. Similarly, hydroquinone is highly susceptible to ring substitution via
Friedel–Crafts alkylation. This reaction is often used for the production of several popular antioxidants, namely 2-''tert''-butyl-4-methoxyphenol (
BHA). The useful dye
quinizarin is produced by
diacylation of hydroquinone with
phthalic anhydride.
[
]
Redox
Hydroquinone can be reversibly oxidised under mild conditions to give benzoquinone. Naturally occurring hydroquinone derivatives, such as coenzyme Q, exhibit similar reactivity, wherein one hydroxyl group is exchanged for an amino group. Given the conditional reversibility and relative ubiquity of reagents, oxidation reactions of hydroquinones and hydroquinone derivatives are of significant commercial use, often used at an industrial scale.
When colorless hydroquinone and benzoquinone - bright yellow in solid form - are cocrystallized at a 1:1 ratio, a dark-green crystalline charge-transfer complex (melting point
The melting point (or, rarely, liquefaction point) of a substance is the temperature at which it changes state of matter, state from solid to liquid. At the melting point the solid and liquid phase (matter), phase exist in Thermodynamic equilib ...
171 °C), known as quinhydrone (), is formed. This complex dissolves in hot water, dissociating both quinone molecules in solution.
Amination
An important reaction involves the conversion of hydroquinone to its mono- and di-amine derivatives. One such derivative, methylaminophenol, used in photography, is produced according to the stochiometry:[
: +
Diamines - used in the rubber industry as antiozone agents - aminated from ]aniline
Aniline (From , meaning ' indigo shrub', and ''-ine'' indicating a derived substance) is an organic compound with the formula . Consisting of a phenyl group () attached to an amino group (), aniline is the simplest aromatic amine. It is an in ...
, are formed via a similar pathway:
: + 2
Uses
Hydroquinone has a variety of uses principally associated with its action as a reducing agent that is soluble in water. It is a major component in most black and white photographic developer
In the Photographic processing, processing of photographic films, plates or papers, the photographic developer (or just developer) is one or more chemicals that convert the latent image to a visible image. Developing agents achieve this conversio ...
s for film and paper where, with the compound metol, it reduces silver halides to elemental silver
Silver is a chemical element; it has Symbol (chemistry), symbol Ag () and atomic number 47. A soft, whitish-gray, lustrous transition metal, it exhibits the highest electrical conductivity, thermal conductivity, and reflectivity of any metal. ...
.
There are various other uses associated with its reducing power. As a polymerisation inhibitor, exploiting its antioxidant
Antioxidants are Chemical compound, compounds that inhibit Redox, oxidation, a chemical reaction that can produce Radical (chemistry), free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants ...
properties, hydroquinone prevents polymerization of acrylic acid, methyl methacrylate, cyanoacrylate
Cyanoacrylates are a family of strong fast-acting adhesives with industrial, medical, and household uses. They are derived from ethyl cyanoacrylate and related esters. The cyanoacrylate group in the monomer rapidly polymerizes in the presence ...
, and other monomers that are susceptible to radical-initiated polymerization
In polymer chemistry, polymerization (American English), or polymerisation (British English), is a process of reacting monomer molecules together in a chemical reaction to form polymer chains or three-dimensional networks. There are many fo ...
. By acting as a free radical scavenger, hydroquinone serves to prolong the shelflife of light-sensitive resins such as preceramic polymers.
Hydroquinone can lose a hydrogen cation from both hydroxyl groups to form a diphenolate ion. The disodium
Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...
diphenolate salt
In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural crystalline mineral, salt is also known as r ...
of hydroquinone is used as an alternating comonomer
A monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or two- or three-dimensional network in a process called polymerization.
Classification
Chemis ...
unit in the production of the polymer
A polymer () is a chemical substance, substance or material that consists of very large molecules, or macromolecules, that are constituted by many repeat unit, repeating subunits derived from one or more species of monomers. Due to their br ...
PEEK
Polyether ether ketone (PEEK) is a beige coloured organic thermoplastic polymer in the polyaryletherketone (PAEK) family, used in engineering applications. It was invented in November 1978 and brought to market in the early 1980s by part of I ...
.
Skin depigmentation
Hydroquinone is used as a topical application in skin whitening
Skin whitening, also known as skin lightening and skin bleaching, is the practice of using chemical substances in an attempt to lighten the skin or provide an even skin color by reducing the melanin concentration in the skin. Several chemicals h ...
to reduce the color
Color (or colour in English in the Commonwealth of Nations, Commonwealth English; American and British English spelling differences#-our, -or, see spelling differences) is the visual perception based on the electromagnetic spectrum. Though co ...
of skin. It does not have the same predisposition to cause dermatitis
Dermatitis is a term used for different types of skin inflammation, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened ...
as metol does. This is a prescription-only ingredient in some countries, including the member states of the European Union under Directives 76/768/EEC:1976.
In 2006, United States Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
revoked its previous approval of hydroquinone and proposed a ban on all over-the-counter
Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid pres ...
preparations. The FDA officially banned hydroquinone in 2020 as part of a larger reform of the over-the-counter drug review process. The FDA stated that hydroquinone cannot be ruled out as a potential carcinogen
A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruse ...
. This conclusion was reached based on the extent of absorption
Absorption may refer to:
Chemistry and biology
*Absorption (biology), digestion
**Absorption (small intestine)
*Absorption (chemistry), diffusion of particles of gas or liquid into liquid or solid materials
*Absorption (skin), a route by which su ...
in humans and the incidence of neoplasm
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s in rats in several studies where adult rats were found to have increased rates of tumours, including thyroid follicular cell hyperplasia
The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by ...
s, anisokaryosis (variation in nuclei sizes), mononuclear cell leukemia, hepatocellular adenoma
Hepatocellular adenoma (also known as hepatic adenoma or hepadenoma) is a rare, benign liver tumor. It most commonly occurs in people with elevated systemic levels of estrogen, classically in women taking estrogen-containing oral contraceptive me ...
s and renal tubule cell adenomas. The Campaign for Safe Cosmetics has also highlighted concerns.
Numerous studies have revealed that hydroquinone, if taken orally, can cause exogenous ochronosis
Ochronosis is a syndrome caused by the accumulation of homogentisic acid in connective tissues. The condition was named after the yellowish (ocher-like) discoloration of the tissue seen on microscopic examination. Macroscopically, though, the af ...
, a disfiguring disease in which blue-black pigments are deposited onto the skin; however, skin preparations containing the ingredient are administered topically. The FDA had classified hydroquinone in 1982 as a safe product - generally recognized as safe and effective (GRASE), however additional studies under the National Toxicology Program (NTP) were suggested in order to determine whether there is a risk to humans from the use of hydroquinone. NTP evaluation showed some evidence of long-term carcinogenic and genotoxic effects.
While hydroquinone remains widely prescribed for treatment of hyperpigmentation
Hyperpigmentation, also known as the dark spots or circles on the skin, is the darkening of an area of Human skin, skin or nail (anatomy), nails caused by increased melanin.
Causes
Hyperpigmentation can be caused by sun damage, inflammation, or ...
, questions raised about its safety profile by regulatory agencies in the EU, Japan, and USA encourage the search for other agents with comparable efficacy. Several such agents are already available or under research, including azelaic acid
Azelaic acid (AzA), or nonanedioic acid, is an organic compound with the formula HOOC(CH2)7carboxylic acid, COOH. This saturated dicarboxylic acid exists as a white powder. It is found in wheat, rye, and barley. It is a precursor to diverse ind ...
, kojic acid
Kojic acid is an organic compound with the formula . It is a derivative of 4-Pyrone, 4-pyrone that functions in nature as a chelation agent produced by several species of fungus, especially ''Aspergillus oryzae'', which has the Japanese common na ...
, retinoids, cysteamine, topical steroids, glycolic acid
Glycolic acid (or hydroxyacetic acid; chemical formula ) is a colorless, odorless and hygroscopic crystal, crystalline solid, highly solubility, soluble in water. It is used in various skin care, skin-care products. Glycolic acid is widespread in ...
, and other substances. One of these, 4-butylresorcinol
4-Butylresorcinol, sometimes called 4-n-butylresorcinol, is a chemical used to treat hyperpigmentation of the epidermis. Hyperpigmentation is believed to be related to the enzyme tyrosinase which produces melanin. Among several chemicals known to ...
, has been proved to be more effective at treating melanin-related skin disorders by a wide margin, as well as safe enough to be made available over the counter.
In the anthraquinone process
The anthraquinone process, also called the Riedl–Pfleiderer process, is a process for the production of hydrogen peroxide, which was developed by IG Farben in the 1940s. The industrial production of hydrogen peroxide is based on the reduction o ...
substituted hydroquinones, typically anthrahydroquinone are used to produce hydrogen peroxide
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscosity, viscous than Properties of water, water. It is used as an oxidizer, bleaching agent, and antiseptic, usua ...
which forms spontaneously on reaction with oxygen. The type of substituted hydroquinone is selected depending on reactivity and recyclability.
Natural occurrences
Hydroquinones are one of the two primary reagents in the defensive glands of bombardier beetle
Bombardier beetles are adephagan ground beetles (Carabidae) in the tribes Brachinini, Paussini, Ozaenini, or Metriini—more than 500 species altogether—which are most notable for the defense mechanism that gives them their name: when disturbe ...
s, along with hydrogen peroxide
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscosity, viscous than Properties of water, water. It is used as an oxidizer, bleaching agent, and antiseptic, usua ...
(and perhaps other compounds, depending on the species), which collect in a reservoir. The reservoir opens through a muscle-controlled valve onto a thick-walled reaction chamber. This chamber is lined with cells that secrete catalase
Catalase is a common enzyme found in nearly all living organisms exposed to oxygen (such as bacteria, plants, and animals) which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting ...
s and peroxidase
Peroxidases or peroxide reductases ( EC numberbr>1.11.1.x are a large group of enzymes which play a role in various biological processes. They are named after the fact that they commonly break up peroxides, and should not be confused with other ...
s. When the contents of the reservoir are forced into the reaction chamber, the catalases and peroxidases rapidly break down the hydrogen peroxide and catalyze
Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...
the oxidation
Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...
of the hydroquinones into ''p''-quinones. These reactions release free oxygen and generate enough heat to bring the mixture to the boiling point and vaporize about a fifth of it, producing a hot spray from the beetle's abdomen
The abdomen (colloquially called the gut, belly, tummy, midriff, tucky, or stomach) is the front part of the torso between the thorax (chest) and pelvis in humans and in other vertebrates. The area occupied by the abdomen is called the abdominal ...
.[Organic Chemistry, Solomon and Fryhle, 10th edition, Wiley Publishing, 2010.]
Hydroquinone is thought to be the active toxin in ''Agaricus hondensis
''Agaricus hondensis'', commonly known as the felt-ringed agaricus, is a species of fungus in the family Agaricaceae. The species was officially described in 1912 by mycologist William Alphonso Murrill, along with three other ''Agaricus'' specie ...
'' mushrooms.
Hydroquinone has been shown to be one of the chemical constituents of the natural product propolis
Propolis or bee glue is a resinous mixture that honey bees produce by mixing saliva and beeswax with exudate gathered from tree buds, sap flows, or other botanical sources. It is used as a sealant for unwanted open spaces in the beehive. Pro ...
.
It is also one of the chemical compounds found in castoreum
Castoreum is a yellowish exudate from the castor sacs of mature beavers used in combination with urine to territorial marking, scent mark their territory.
Both beaver sexes have a pair of castor sacs and a pair of anal glands, located in two c ...
. This compound is gathered from the beaver
Beavers (genus ''Castor'') are large, semiaquatic rodents of the Northern Hemisphere. There are two existing species: the North American beaver (''Castor canadensis'') and the Eurasian beaver (''C. fiber''). Beavers are the second-large ...
's castor sacs.[The Beaver: Its Life and Impact. Dietland Muller-Schwarze, 2003, page 43]
book at google books
References
External links
{{Authority control
Photographic chemicals
IARC Group 3 carcinogens
Reducing agents