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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 C<sub>6</sub>H<sub>4</sub>(OH)<sub>2</sub>. It has two hydroxyl groups bonded to a benzene ring in a para position. It is a white granular solid. Substituted derivatives of this parent compound are also referred to as hydroquinones. The name "hydroquinone" was coined by Friedrich Wöhler in 1843.

In 2023, it was the 274th most commonly prescribed medication in the United States, with more than 800,000 prescriptions.

Production

Hydroquinone is produced industrially in two main ways.

  • The most widely used route is similar to the cumene process in reaction mechanism and involves the dialkylation of benzene 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 and hydroquinone.
  • A second route involves hydroxylation of phenol over a catalyst. The conversion uses hydrogen peroxide and affords a mixture of hydroquinone and its ortho isomer catechol (benzene-1,2-diol):

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Other, less common methods include:

  • A potentially significant synthesis of hydroquinone from acetylene and iron pentacarbonyl has been proposed. Iron pentacarbonyl serves as a catalyst, rather than as a reagent, in the presence of free carbon monoxide gas. Rhodium or ruthenium can substitute for iron as the catalyst with favorable chemical yields, but are not typically used due to the cost of recovery from the reaction mixture. 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 of chlorophenol.

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 stoichiometry:

Hydroquinone can lose a hydrogen cation from both hydroxyl groups to form a diphenolate ion. The disodium diphenolate salt of hydroquinone is used as an alternating comonomer unit in the production of the polymer PEEK.

Skin depigmentation

Hydroquinone is used as a topical application in skin whitening to reduce the color of skin. It does not have the same predisposition to cause dermatitis 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 (FDA) revoked its previous approval of hydroquinone and proposed a ban on all over-the-counter 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. This conclusion was reached based on the extent of absorption in humans and the incidence of neoplasms in rats in several studies where adult rats were found to have increased rates of tumours, including thyroid follicular cell hyperplasias, anisokaryosis (variation in nuclei sizes), mononuclear cell leukemia, hepatocellular adenomas 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, 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). Additional studies under the National Toxicology Program (NTP) were suggested 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, questions raised about its safety profile by regulatory agencies in the EU, Japan, and the USA encourage the search for other agents with comparable efficacy. Several such agents are already available or under research, including azelaic acid, kojic acid, retinoids, cysteamine, topical steroids, glycolic acid, and other substances. One of these, 4-butylresorcinol, has been proven 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, substituted hydroquinones, typically anthrahydroquinone, are used to produce hydrogen peroxide, 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 beetles, along with hydrogen peroxide (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 catalases and peroxidases. When the contents of the reservoir are forced into the reaction chamber, the catalases and peroxidases rapidly break down the hydrogen peroxide and catalyze the oxidation 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.

Hydroquinone is thought to be the active toxin in Agaricus hondensis mushrooms.

Hydroquinone is one of the chemical constituents of the natural product propolis.

It is also one of the chemical compounds found in castoreum. This compound is gathered from the beaver's castor sacs.

References

  • International Chemical Safety Card 0166
  • NIOSH Pocket Guide to Chemical Hazards