Hydantoin, or glycolylurea, is a heterocyclic

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...

with the formula CH₂C(O)NHC(O)NH. It is a colorless solid that arises from the reaction of glycolic acid and

urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important ...

. It is an oxidized derivative of imidazolidine. In a more general sense, hydantoins can refer to a

groups A group is a number of persons or things that are located, gathered, or classed together. Groups of people * Cultural group, a group whose members share the same cultural identity * Ethnic group, a group whose members share the same ethnic ide ...

and a class of compounds with the same ring structure as the parent. For example,

phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The in ...

(mentioned below) has two phenyl groups substituted onto the number 5 carbon in a hydantoin molecule.

Synthesis

Hydantoin was first isolated in 1861 by

Adolf von Baeyer Johann Friedrich Wilhelm Adolf von Baeyer (; 31 October 1835 – 20 August 1917) was a German chemist who synthesised indigo and developed a nomenclature for cyclic compounds (that was subsequently extended and adopted as part of the IUPAC org ...

in the course of his study of uric acid. He obtained it by

hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic ...

of allantoin, hence the name. : Harnsäureabbau

Friedrich Urech synthesized 5-methylhydantoin in 1873 from alanine sulfate and potassium cyanate in what is now known as the Urech hydantoin synthesis. The method is very similar to the modern route using alkyl and arylcyanates. The 5,5-dimethyl compound can also be obtained from acetone cyanohydrin (also discovered by Urech: see

cyanohydrin reaction A cyanohydrin reaction is an organic chemical reaction in which an aldehyde or ketone reacts with a cyanide anion or a nitrile to form a cyanohydrin. This nucleophilic addition is a reversible reaction but with aliphatic carbonyl compounds equ ...

) and ammonium carbonate. This reaction type is called the Bucherer–Bergs reaction. Hydantoin can also be synthesized either by heating allantoin with hydroiodic acid or by "heating bromacetyl urea with alcoholic ammonia". The cyclic structure of hydantoins was confirmed by Dorothy Hahn 1913. Of practical importance, hydantoins are obtained by condensation of a

cyanohydrin In organic chemistry, a cyanohydrin or hydroxynitrile is a functional group found in organic compounds in which a cyano and a hydroxy group are attached to the same carbon atom. The general formula is , where R is H, alkyl, or aryl. Cyanohyd ...

with ammonium carbonate. Another useful route, which follows the work of Urech, involves the condensation of amino acids with cyanates and isocyanates: : AA+RNCO

Uses and occurrence

Pharmaceuticals

The hydantoin group can be found in several medicinally important compounds. In pharmaceuticals, hydantoin derivatives form a class of

anticonvulsants Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of ...

;

and fosphenytoin both contain hydantoin moieties and are both used as anticonvulsants in the treatment of seizure disorders. The hydantoin derivative dantrolene is used as a muscle relaxant to treat

malignant hyperthermia Malignant hyperthermia (MH) is a type of severe reaction that occurs in response to particular medications used during general anesthesia, among those who are susceptible. Symptoms include muscle rigidity, fever, and a fast heart rate. Complica ...

, neuroleptic malignant syndrome, spasticity, and ecstasy intoxication. Ropitoin is an example of an antiarrhythmic hydantoin.

Pesticides

The hydantoin derivative

Imiprothrin Imiprothrin is a synthetic pyrethroid insecticide. It is an ingredient in some commercial and consumer insecticide products for indoor use. It has low acute toxicity to humans through the inhalation and dermal routes, but to insects it acts as a n ...

is a pyrethroid insecticide. Iprodione is a popular fungicide containing the hydantoin group.

Synthesis of amino acids

Hydrolysis of hydantoins affords amino acids: :RCHC(O)NHC(O)NH + H₂O → RCHC(NH₂)CO₂H + NH₃ Hydantoin itself reacts with hot, dilute

hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid. It is a component of the gastric acid in the dige ...

to give glycine. Methionine is produced industrially via the hydantoin obtained from methional.

Methylation

Methylation In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These ...

of hydantoin yields a variety of derivatives. Dimethylhydantoin (DMH) may refer to any dimethyl derivative of hydantoin, but especially 5,5-dimethylhydantoin.

Halogenation

Some ''N''-halogenated derivatives of hydantoin are used as chlorinating or brominating agents in

disinfectant A disinfectant is a chemical substance or compound used to inactivate or destroy microorganisms on inert surfaces. Disinfection does not necessarily kill all microorganisms, especially resistant bacterial spores; it is less effective than s ...

/sanitizer or

biocide A biocide is defined in the European legislation as a chemical substance or microorganism intended to destroy, deter, render harmless, or exert a controlling effect on any harmful organism. The US Environmental Protection Agency (EPA) uses a sli ...

products. The three major ''N''-halogenated derivatives are dichlorodimethylhydantoin (DCDMH), bromochlorodimethylhydantoin (BCDMH), and dibromodimethylhydantoin (DBDMH). A mixed ethyl-methyl analogue, 1,3-dichloro-5-ethyl-5-methylimidazolidine-2,4-dione (bromochloroethylmethylhydantoin), is also used in mixtures with the above.

DNA oxidation to hydantoins after cell death

A high proportion of

cytosine Cytosine () ( symbol C or Cyt) is one of the four nucleobases found in DNA and RNA, along with adenine, guanine, and thymine ( uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached ( ...

and

thymine Thymine () ( symbol T or Thy) is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidin ...

bases in DNA are oxidized to hydantoins over time after the death of an organism. Such modifications block DNA polymerases and thus prevents PCR from working. Such damage is a problem when dealing with ancient DNA samples.

External links and further reading

*
Hazard DB: Hydantoin
*

English Translation of 1926 German review article on the Preparation of hydantoins by Heinrich Biltz and Karl Slotta

References

{{Anticonvulsants