Heterocyclic compound

Molecule with one or more rings composed of different elements

For other uses of "ring structure", see Ring structure.

"Heterocycles" redirects here. For the journal, see Heterocycles (journal).

Structures and names of common heterocyclic compounds Pyridine, a heterocyclic compound

A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s).[1] Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and applications of organic heterocycles.[2]

Examples of heterocyclic compounds include all of the nucleic acids, the majority of drugs, most biomass (cellulose and related materials), and many natural and synthetic dyes. More than half of known compounds are heterocycles.[3] 59% of US FDA-approved drugs contain nitrogen heterocycles.[4]

## Classification

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The study of organic heterocyclic chemistry focuses especially on organic unsaturated derivatives, and the preponderance of work and applications involves unstrained organic 5- and 6-membered rings. Included are pyridine, thiophene, pyrrole, and furan. Another large class of organic heterocycles refers to those fused to benzene rings. For example, the fused benzene derivatives of pyridine, thiophene, pyrrole, and furan are quinoline, benzothiophene, indole, and benzofuran, respectively. The fusion of two benzene rings gives rise to a third large family of organic compounds. Analogs of the previously mentioned heterocycles for this third family of compounds are acridine, dibenzothiophene, carbazole, and dibenzofuran, respectively.

Heterocyclic organic compounds can be usefully classified based on their electronic structure. The saturated organic heterocycles behave like the acyclic derivatives. Thus, piperidine and tetrahydrofuran are conventional amines and ethers, with modified steric profiles. Therefore, the study of organic heterocyclic chemistry focuses on organic unsaturated rings.

### Inorganic rings

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Some heterocycles contain no carbon. Examples are borazine (B3N3 ring), hexachlorophosphazene (P3N3 ring), and trithiazyl trichloride (S3N3 ring). In comparison with organic heterocycles, which have numerous commercial applications, inorganic ring systems are mainly of theoretical interest. IUPAC recommends the Hantzsch-Widman nomenclature for naming heterocyclic compounds.[5]

## Notes on lists

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* "Heteroatoms" are atoms in the ring other than carbon atoms.
* Names in italics are retained by IUPAC and do not follow the Hantzsch-Widman nomenclature.
* Some of the names refer to classes of compounds rather than individual compounds.
* Also no attempt is made to list isomers.

## 3-membered rings

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Although subject to ring strain, 3-membered heterocyclic rings are well characterized.[6]

Three-membered rings with one heteroatom

Heteroatom  | Saturated  | Unsaturated
Boron  | Borirane | Borirene
Nitrogen  | Aziridine | Azirine
Oxygen  | Oxirane
(ethylene oxide, epoxides)  | Oxirene
Phosphorus  | Phosphirane | Phosphirene
Sulfur  | Thiirane
(ethylene sulfide, episulfides)  | Thiirene
Three-membered rings with two heteroatoms
Heteroatoms  | Saturated  | Unsaturated
2 × Nitrogen  | Diaziridine | Diazirine
Nitrogen + Oxygen  | Oxaziridine | Oxazirine
Nitrogen + Sulfur  | Thiaziridine | Thiazirine
2 × Oxygen  | Dioxirane (highly unstable)  |
2 × Sulfur  | Dithiirane (highly unstable)  |

## 4-membered rings

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Four-membered rings with one heteroatom

Heteroatom  | Saturated  | Unsaturated
Boron  | Boretane | Borete
Nitrogen  | Azetidine | Azete
Oxygen  | Oxetane | Oxete
Phosphorus  | Phosphetane | Phosphete
Sulfur  | Thietane | Thiete
Four-membered rings with two heteroatoms
Heteroatoms  | Saturated  | Unsaturated
2 × Nitrogen  | Diazetidine | Diazete
2 × Oxygen  | Dioxetane | Dioxete
2 × Sulfur  | Dithietane | Dithiete

## 5-membered rings

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The 5-membered ring compounds containing two heteroatoms, at least one of which is nitrogen, are collectively called the azoles. Thiazoles and isothiazoles contain a sulfur and a nitrogen atom in the ring. Dithioles have two sulfur atoms.

A large group of 5-membered ring compounds with three or more heteroatoms also exists. One example is the class of dithiazoles, which contain two sulfur atoms and one nitrogen atom.

Five-membered rings with one heteroatom

Heteroatom  | Saturated  | Unsaturated
Antimony | Stibolane | Stibole
Arsenic | Arsolane | Arsole
Bismuth | Bismolane | Bismole
Boron | Borolane | Borole
Germanium | Germolane | Germole
Nitrogen | Pyrrolidine
(Azolidine not used)  | Pyrrole
(Azole not used)
Pyrroline (partially unsaturated)
Oxygen | Oxolane | Furan
(Oxole not used)
Phosphorus | Phospholane | Phosphole
Selenium | Selenolane | Selenophene
Silicon | Silolane | Silole
Sulfur | Thiolane | Thiophene
(Thiole not used)
Tellurium | Tellurolane | Tellurophene
Tin | Stannolane | Stannole
Five-membered rings with two heteroatoms
Heteroatoms  | Saturated  | Unsaturated (and partially unsaturated)
2 × Nitrogen  | Pyrazolidine
Imidazolidine | Pyrazole (Pyrazoline)
Imidazole (Imidazoline)
Nitrogen + Oxygen  | Oxazolidine
Isoxazolidine | Oxazole (Oxazoline)
Isoxazole (Isoxazoline)
Nitrogen + Sulfur  | Thiazolidine
Isothiazolidine | Thiazole (Thiazoline)
Isothiazole (Isothiazoline)
Oxygen + Sulfur  | Oxathiolane
Isoxathiolane | Oxathiole
Isoxathiole
2 × Oxygen  | Dioxolane | Dioxole
2 × Sulfur  | Dithiolane | Dithiole
Five-membered rings with three heteroatoms
Heteroatoms  | Saturated  | Unsaturated
3 × Nitrogen  |  | Triazole
2 Nitrogen + Oxygen  |  | Oxadiazole
2 Nitrogen + Sulfur  |  | Thiadiazole
Nitrogen + 2 Oxygen  |  | Dioxazole
Nitrogen + 2 Sulfur  |  | Dithiazole
Five-membered rings with four heteroatoms
Heteroatoms  | Saturated  | Unsaturated
4 × Nitrogen  |  | Tetrazole
3 Nitrogen + Oxygen  |  | Oxatriazole
3 Nitrogen + Sulfur  |  | Thiatriazole
Five-membered rings with five heteroatoms
Heteroatoms  | Saturated  | Unsaturated
5 × Nitrogen  |  | Pentazole
4 Nitrogen + Oxygen  |  | Oxatetrazole
4 Nitrogen + Sulfur  |  | Thiatetrazole

## 6-membered rings

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The 6-membered ring compounds containing two heteroatoms, at least one of which is nitrogen, are collectively called the azines. Thiazines contain a sulfur and a nitrogen atom in the ring. Dithiines have two sulfur atoms.

Six-membered rings with one heteroatom

Heteroatom  | Saturated  | Unsaturated  | Ions
Antimony | Stibinane | Stibinine | Stibatabenzene cation
Arsenic | Arsinane | Arsinine | Arsatabenzene cation
Bismuth | Bisminane | Bismine | Bismatabenzene cation
Boron | Borinane | Borinine | Boratabenzene anion
Germanium | Germinane | Germine |
Nitrogen | Piperidine
(Azinane not used)  | Pyridine
(Azine not used)  | Pyridinium cation
Oxygen | Oxane | Pyran
(Oxine not used)  | Pyrylium cation
Phosphorus | Phosphinane | Phosphinine | Phosphininium cation[7]
Selenium | Selenane | Selenopyran | Selenopyrylium cation
Silicon | Silinane | Siline |
Sulfur | Thiane | Thiopyran
(Thiine not used)  | Thiopyrylium cation
Tellurium | Tellurane | Telluropyran | Telluropyrylium cation
Tin | Stanninane | Stannine |
Six-membered rings with two heteroatoms
Heteroatoms  | Saturated  | Unsaturated
2 × Nitrogen  | Piperazine | Pyrazine
Pyrimidine
Pyridazine
Nitrogen + Oxygen  | Morpholine | Oxazine
Nitrogen + Sulfur  | Thiomorpholine | Thiazine
Oxygen + Sulfur  | Oxathiane | Oxathiin
2 × Oxygen  | Dioxane | Dioxin
2 × Sulfur  | Dithiane | Dithiin
Six-membered rings with three heteroatoms
Heteroatoms  | Saturated  | Unsaturated
3 × Nitrogen  | Triazinane | Triazine
3 × Oxygen  | Trioxane | Trioxin
3 × Sulfur  | Trithiane | Trithiin
Six-membered rings with four heteroatoms
Heteroatoms  | Saturated  | Unsaturated
4 × Nitrogen  |  | Tetrazine
2 Nitrogen + 2 Boron  |  | Carborazine

Six-membered rings with five heteroatoms
The hypothetical chemical compound with five nitrogen heteroatoms would be pentazine.

Six-membered rings with six heteroatoms
The hypothetical chemical compound with six nitrogen heteroatoms would be hexazine. Borazine is a six-membered ring with three nitrogen heteroatoms and three boron heteroatoms.

## 7-membered rings

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In a 7-membered ring, the heteroatom must be able to provide an empty π-orbital (e.g. boron) for "normal" aromatic stabilization to be available; otherwise, homoaromaticity may be possible.

Seven-membered rings with one heteroatom

Heteroatom  | Saturated  | Unsaturated
Boron  | Borepane | Borepine
Nitrogen  | Azepane | Azepine
Oxygen  | Oxepane | Oxepine
Phosphorus  | Phosphepane | Phosphepine
Sulfur  | Thiepane | Thiepine
Seven-membered rings with two heteroatoms
Heteroatoms  | Saturated  | Unsaturated
2 × Nitrogen  | Diazepane | Diazepine
Nitrogen + Oxygen  | Oxazepane | Oxazepine
Nitrogen + Sulfur  | Thiazepane | Thiazepine

## 8-membered rings

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Heteroatom  | Saturated  | Unsaturated

|
|

Nitrogen  | Azocane | Azocine
Oxygen  | Oxocane | Oxocine
Sulfur  | Thiocane | Thiocine

Borazocine is an eight-membered ring with four nitrogen heteroatoms and four boron heteroatoms.

## 9-membered rings

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Heteroatom  | Saturated  | Unsaturated

|
|

Nitrogen  | Azonane | Azonine
Oxygen  | Oxonane | Oxonine
Sulfur  | Thionane | Thionine

## Images of rings with one heteroatom

[edit]

| Saturated | Unsaturated

|
|

Heteroatom | Nitrogen | Oxygen | Sulfur | Nitrogen | Oxygen | Sulfur
3-atom ring  | Aziridine | Oxirane | Thiirane | Azirine | Oxirene | Thiirene
|  |  |  |  |
4-atom ring  | Azetidine | Oxetane | Thietane | Azete | Oxete | Thiete
|  |  |  |  |
5-atom ring  | Pyrrolidine | Oxolane | Thiolane | Pyrrole | Furan | Thiophene
|  |  |  |  |
6-atom ring  | Piperidine | Oxane | Thiane | Pyridine | Pyran | Thiopyran
|  |  |  |  |
7-atom ring  | Azepane | Oxepane | Thiepane | Azepine | Oxepine | Thiepine
|  |  |  |  |
8-atom ring  | Azocane | Oxocane | Thiocane | Azocine | Oxocine | Thiocine
|  |  |  |  |
9-atom ring  | Azonane | Oxonane | Thionane | Azonine | Oxonine | Thionine
|  |  |  |  |

## Fused/condensed rings

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Heterocyclic rings systems that are formally derived by fusion with other rings, either carbocyclic or heterocyclic, have a variety of common and systematic names. For example, with the benzo-fused unsaturated nitrogen heterocycles, pyrrole provides indole or isoindole depending on the orientation. The pyridine derivative is quinoline or isoquinoline, and the class of analogues with two nitrogen atoms is known as the benzodiazines. For the azepine derivative, benzazepine is the preferred name. Likewise, the compounds with two benzene rings fused to the central heterocycle are carbazole, acridine, and dibenzoazepine. Heptazine is a tricyclic nitrogen-containing heterocyclic system derived by fusion of three triazine rings, and analog of the carbocycle phenalene.

## History of heterocyclic chemistry

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The history of heterocyclic chemistry began in the 1800s, in step with the development of organic chemistry. Some noteworthy developments:[8]

* 1818: Brugnatelli makes alloxan from uric acid.
* 1832: Dobereiner produces furfural (a furan) by treating starch with sulfuric acid.
* 1834: Runge obtains pyrrole ("fiery oil") by dry distillation of bones.
* 1906: Friedlander synthesizes indigo dye, allowing synthetic chemistry to displace a large agricultural industry.
* 1936: Treibs isolates chlorophyll derivatives from crude oil, explaining the biological origin of petroleum.
* 1951: Chargaff's rules are described, highlighting the role of heterocyclic compounds (purines and pyrimidines) in the genetic code.

## Uses

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Heterocyclic compounds are pervasive in many areas of life sciences and technology.[2] Many drugs are heterocyclic compounds.[9] Among the modifications to the family of antitumor compounds, heterocyclic organic compounds have been extensively applied by many groups in order to modify the reactivity profile. Pyrrole, pyrimidine, indole, quinoline and purine are few classes of heterocycles which showed interesting cytotoxicity profiles, which can be highly beneficial when developing cancer drugs. [10]

## See also

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* Spiroketals

## References

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1. ^ IUPAC Gold Book heterocyclic compounds
2. ^ a b Thomas L. Gilchrist "Heterocyclic Chemistry" 3rd ed. Addison Wesley: Essex, England, 1997\. 414 pp. ISBN 0-582-27843-0.
3. ^ Rees, Charles W. (1992). "Polysulfur-Nitrogen Heterocyclic Chemistry". Journal of Heterocyclic Chemistry. 29 (3): 639–651\. doi:10.1002/jhet.5570290306.
4. ^ Edon Vitaku, David T. Smith, Jon T. Njardarson (2014). "Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals". J. Med. Chem. 57 (24): 10257–10274\. doi:10.1021/jm501100b. PMID 25255204.`{{cite journal}}`: CS1 maint: multiple names: authors list (link)
5. ^ IUPAC, Compendium of Chemical Terminology, 5th ed. (the "Gold Book") (2025). Online version: (2006-) "Hantzsch–Widman name". doi:10.1351/goldbook.H02737
6. ^ 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
7. ^ Fischer, Lukas; Wossidlo, Friedrich; Frost, Daniel; Coles, Nathan T.; Steinhauer, Simon; Riedel, Sebastian; Müller, Christian (6 August 2021) [19th July 2021]. "One-step methylation of aromatic phosphorus heterocycles: synthesis and crystallographic characterization of a 1-methyl-phosphininium salt". Chemical Communications. 57 (2021, 57). Royal Society of Chemistry: 9522–9525\. doi:10.1039/D1CC03892C. PMID 34546255.
8. ^ Campaigne, E. (1986). "Adrien Albert and the rationalization of heterocyclic chemistry". Journal of Chemical Education. 63 (10): 860. Bibcode:1986JChEd..63..860C. doi:10.1021/ed063p860.
9. ^ "IPEXL.com Multilingual Patent Search, Patent Ranking". www.ipexl.com. Archived from the original on 24 September 2015. Retrieved 8 September 2010.
10. ^ Kidwai, M.; Venktaramanan, R.; Mohan, R.; Sapra, P. (1 June 2002). "Cancer Chemotherapy and Heterocyclic Compounds". Current Medicinal Chemistry. 9 (12): 1209–1228\. doi:10.2174/0929867023370059. ISSN 0929-8673. PMID 12052173. Archived from the original on 20 June 2024.

## External links

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Wikimedia Commons has media related to heterocyclic compounds.

Wikiquote has quotations related to Heterocyclic compound.

* Hantzsch-Widman nomenclature, IUPAC
* Heterocyclic amines in cooked meat, US CDC
* List of known and probable carcinogens, American Cancer Society Archived 13 December 2003 at the Wayback Machine
* List of known carcinogens by the State of California, Proposition 65 (more comprehensive)

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