Heterocyclic compound

Pyridine, a heterocyclic compound
cyclo-octasulfur, a homocyclic compound

Heterocyclic compounds are cyclic compounds with at least two different elements as ring members atoms. [1] 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.[2] 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.

Contents

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 Struktur von Aziridin Struktur von Oxiran Struktur von Thiiran Struktur von Azirin Struktur von Oxiren Struktur von Thiiren
4-Ring
Name Azetidine Oxetane Thietane Azete Oxete Thiete
Structure Struktur von Azetidin Struktur von Oxetan Struktur von Thietan Struktur von Azet Struktur des Oxetiumions Struktur des Thietiumions
5-Ring
Name Pyrrolidine Tetrahydrofuran Tetrahydrothiophene Pyrrole Furan Thiophene
Structure Struktur von Pyrrolidin Struktur von Tetrahydrofuran Struktur von Tetrahydrothiophen Struktur von Pyrrol Struktur von Furan Struktur von Thiophen
6-Ring
Name Piperidine Tetrahydropyran Thiane Pyridine Pyrylium Thiopyran
Structure Struktur von Piperidin Struktur von Tetrahydropyran Struktur von Tetrahydrothiopyran Struktur von Pyridin Struktur des Pyryliumions Struktur des Thiopyryliumions
7-Ring
Name Azepane Oxepane Thiepane Azepine Oxepine Thiepine
Structure Struktur von Azepan Struktur von Oxepan Struktur von Thiepanan Struktur von Azepin Struktur von Oxepin Struktur von Thiepin

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:[3] 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

References

  1. ↑ IUPAC Gold Book heterocyclic compounds
  2. ↑ Eicher, T.; Hauptmann, S. (2nd ed. 2003). The Chemistry of Heterocycles: Structure, Reactions, Syntheses, and Applications. Wiley-VCH. ISBN 3527307206. 
  3. ↑ E. Campaigne "Adrien Albert and the Rationalization of Heterocyclic Chemistry" J. Chemical Education 1986, Volume 6, 860. doi:10.1021/ed063p860