Heterocyclic compound

"Ring structure" redirects here. For the literary structure, see Chiastic structure.

Pyridine, a heterocyclic compound

cyclo-octasulfur, a homocyclic compound

Heterocyclic compounds are cyclic compounds with at least two different elements as ring members atoms. They are the counterparts of homocyclic compounds, which have only ring atoms from the same element.

Although heterocyclic compounds may be inorganic, most contain at least one carbon atom, and one or more atoms of elements other than carbon within the ring structure, such as sulfur, oxygen or nitrogen. Since in organic chemistry non-carbons usually are considered to replace carbon atoms, they are called heteroatoms (meaning 'different from carbon and hydrogen'). Nevertheless, a ring with only heteroatoms is homocyclic. The IUPAC recommends the Hantzsch-Widman nomenclature for naming heterocyclic compounds.

Heterocyclic chemistry is the branch of chemistry dealing with synthesis, properties, and applications of heterocycles.

Classification based on electronic structure

Heterocyclic compounds can be usefully classified based on their electronic structure. The saturated heterocycles behave like the acyclic derivatives. Thus, piperidine and tetrahydrofuran are conventional amines and ethers, with modified steric profiles. The study of heterocyclic chemistry therefore focuses especially on unsaturated derivatives, and the preponderance of work and applications involves unstrained 5- and 6-membered rings. Included are pyridine, thiophene, pyrrole, and furan. Another large class of heterocycles are fused to benzene rings, which for pyridine, thiophene, pyrrole, and furan are quinoline, benzothiophene, indole, and benzofuran, respectively. Fusion of two benzene rings gives rise to a third large family of compounds, respectively the acridine, dibenzothiophene, carbazole, and dibenzofuran. The unsaturated rings can be classified according to the participation of the heteroatom in the pi-system.

3-Membered rings

Heterocycles with three atoms in the ring are more reactive because of ring strain. Those containing one heteroatom are, in general, stable. Those with two heteroatoms are more likely to occur as reactive intermediates. Common 3-membered heterocycles are:

Heteroatom	Saturated	Unsaturated
Nitrogen	Aziridine	Azirine
Oxygen	Ethylene oxide (epoxides, oxiranes)
Sulfur	Thiirane (episulfides)	Thiirene

Those with two heteroatoms include:

Heteroatom	Saturated	Unsaturated
Oxygen	Dioxirane
Nitrogen		Diazirine

4-Membered rings

Compounds with one heteroatom:

Heteroatom	Saturated	Unsaturated
Nitrogen	Azetidine	Azete
Oxygen	Oxetane	Oxete
Sulfur	Thietane	Thiete

Compounds with two heteroatoms:

Heteroatom	Saturated	Unsaturated
Nitrogen	Diazetidine
Oxygen	Dioxetane	Dioxetene
Sulfur	Dithietane	Dithiete

5-Membered rings

With heterocycles containing five atoms, the unsaturated compounds are frequently more stable because of aromaticity.

Five-membered rings with a single heteroatom:

Heteroatom	Saturated	Unsaturated
Nitrogen	Azolidine	Pyrrole
Oxygen	Oxolane	Furan
Sulfur	Thiolane	Thiophene
Phosphorus	Phospholane	Phosphole
Silicon	Silolane	Silole
Arsenic	Arsolane	Arsole

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. Dithiolanes have two sulfur atoms.

Heteroatom	Saturated	Unsaturated
Nitrogen	Imidazolidine Pyrazolidine	Imidazole Imidazoline Pyrazole Pyrazoline
Nitrogen/oxygen	Oxazolidine Isoxazolidine	Oxazole Oxazoline Isoxazole Isoxazoline
Nitrogen/sulfur	Thiazolidine Isothiazolidine	Thiazole Thiazoline Isothiazole Isothiazoline
Oxygen	Dioxolane
Oxygen/sulfur	Oxathiolane
Sulfur	Dithiolane

A large group of 5-membered ring compounds with three heteroatoms also exists. One example is dithiazoles that contain two sulfur and a nitrogen atom.

Heteroatom	Saturated	Unsaturated
Nitrogen		Triazoles
Nitrogen/2-sulfur		Dithiazole
2-Nitrogen/oxygen		Furazan Oxadiazole
2-Nitrogen/sulfur		Thiadiazole

Five-member ring compounds with four heteroatoms:

Heteroatom	Saturated	Unsaturated
Nitrogen		Tetrazole

With 5-heteroatoms, the compound may be considered inorganic rather than heterocyclic. Pentazole is the all nitrogen heteroatom unsaturated compound.

6-Membered rings

Six membered rings with a single heteroatom:

Heteroatom	Saturated	Unsaturated
Nitrogen	Piperidine	Pyridine
Oxygen	Tetrahydropyran	Pyran
Sulfur	Thiane	Thiopyran

With two heteroatoms:

Heteroatom	Saturated	Unsaturated
Nitrogen	Piperazine	Diazines
Nitrogen / oxygen	Morpholine	Oxazine
Nitrogen / sulfur		Thiazine
Sulfur	Dithiane
Oxygen	Dioxane	Dioxin

With three heteroatoms:

Heteroatom	Saturated	Unsaturated
Nitrogen		Triazine
Oxygen	Trioxane

With four heteroatoms:

Heteroatom	Saturated	Unsaturated
Nitrogen		Tetrazine

The hypothetical compound with six nitrogen heteroatoms would be hexazine.

7-Membered rings

With 7-membered rings, the heteroatom must be able to provide an empty pi orbital (eg boron) for "normal" aromatic stabilization to be available; otherwise homoaromaticity may be possible. Compounds with one heteroatom include:

Heteroatom	Saturated	Unsaturated
Nitrogen	Azepane	Azepine
Oxygen	Oxepane	Oxepine
Sulfur	Thiepane	Thiepine

Those with two heteroatoms include:

Heteroatom	Saturated	Unsaturated
Nitrogen		Diazepine
Nitrogen/sulfur		Thiazepine

8-Membered rings

Compounds with one heteroatom include:

Heteroatom	Saturated	Unsaturated
Nitrogen	Azocane	Azocine
Oxygen	Oxecane
Sulfur	Thiocane

Images

	Saturated			Unsaturated
Heteroatom	Nitrogen	Oxygen	Sulfur	Nitrogen	Oxygen	Sulfur
3-Ring
Name	Aziridine	Oxirane	Thiirane	Azirine	Oxirene	Thiirene
Structure
4-Ring
Name	Azetidine	Oxetane	Thietane	Azete	Oxete	Thiete
Structure
5-Ring
Name	Pyrrolidine	Tetrahydrofuran	Tetrahydrothiophene	Pyrrole	Furan	Thiophene
Structure
6-Ring
Name	Piperidine	Tetrahydropyran	Thiane	Pyridine	Pyrylium	Thiopyran
Structure
7-Ring
Name	Azepane	Oxepane	Thiepane	Azepine	Oxepine	Thiepine
Structure

Fused 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. For azepine, benzazepine is the preferred name. Similarly, the compounds with two benzene rings fused to the central heterocycle are carbazole, acridine, and dibenzoazepine.

History of heterocyclic chemistry

The history of heterocyclic chemistry began in the 1800's, in step with the development of organic chemistry. Some noteworthy developments: 1818: Brugnatelli isolates 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, allowing synthetic chemistry to displace a large agricultural industry 1936: Treibs isolates chlorophyl 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.

External links

• Hantzsch-Widman nomenclature, IUPAC
• Heterocyclic amines in cooked meat, US CDC
• List of known and probable carcinogens, American Cancer Society
• List of known carcinogens by the State of California, Proposition 65 (more comprehensive)