# 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). Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and applications of organic heterocycles.
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. 59% of US FDA-approved drugs contain nitrogen heterocycles.

## Classification

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

Some heterocycles contain no carbon. Examples are borazine (B$_3$N$_3$ ring), hexachlorophosphazenes (P$_3$N$_3$ rings), and tetrasulfur tetranitride S$_4$N$_4$. 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.

## Notes on lists

* "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

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

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

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

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 |
| 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

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

| 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

| Heteroatom | Saturated | Unsaturated |
| Nitrogen | Azonane | Azonine |
| Oxygen | Oxonane | Oxonine |
| Sulfur | Thionane | Thionine |

## Images of rings with one heteroatom

| | Saturated | Saturated | Saturated | Unsaturated | Unsaturated | 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

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 analog is quinoline or isoquinoline, and the class of analogues with two nitrogen atoms is known as the benzodiazines. For azepine, benzazepine is the preferred name. Likewise, the compounds with two benzene rings fused to the central heterocycle are carbazole, acridine, and dibenzoazepine. Thienothiophene are the fusion of two thiophene rings. Phosphaphenalenes are a tricyclic phosphorus-containing heterocyclic system derived from the carbocycle phenalene.

## History of heterocyclic chemistry

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

Heterocyclic compounds are pervasive in many areas of life sciences and technology. Many drugs are heterocyclic compounds.