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. Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and applications of these heterocycles.
Examples of heterocyclic compounds include all of the nucleic acids, the majority of drugs, most biomass, and many natural and synthetic dyes. 59% of US FDA-approved drugs contain nitrogen heterocycles.

Classification

Although heterocyclic chemical compounds may be inorganic compounds or organic compounds, most contain at least one carbon. While atoms that are neither carbon nor hydrogen are normally referred to in organic chemistry as heteroatoms, this is usually in comparison to the all-carbon backbone. But this does not prevent a compound such as borazine from being labelled "heterocyclic". IUPAC recommends the Hantzsch-Widman nomenclature for naming heterocyclic compounds.
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. Therefore, the study of heterocyclic chemistry 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 refers to those fused to benzene rings. For example, the fused benzene analogs 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 compounds. Analogs of the previously mentioned heterocycles for this third family of compounds are acridine, dibenzothiophene, carbazole, and dibenzofuran, respectively. The unsaturated rings can be classified according to the participation of the heteroatom in the conjugated pi system.

3-membered rings

Heterocycles with three atoms in the ring are higher in energy and 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. The C-X-C bond angles in oxiranes and aziridines are very close to 60° and the peripheral H-C-H bond angles are near to 180°.

Three-membered rings with ''one'' heteroatom

Three-membered rings with ''two'' heteroatoms

HeteroatomSaturatedUnsaturated
NitrogenDiaziridineDiazirine
Nitrogen/oxygenOxaziridine
OxygenDioxirane

4-membered rings

Four-membered rings with ''one'' heteroatom

HeteroatomSaturatedUnsaturated
NitrogenAzetidineAzete
OxygenOxetaneOxete
SulfurThietaneThiete

Four-membered rings with ''two'' heteroatoms

5-membered rings

Five-membered rings with ''one'' heteroatom

HeteroatomSaturatedUnsaturated
AntimonyStibolaneStibole
ArsenicArsolaneArsole
BismuthBismolaneBismole
BoronBorolaneBorole
NitrogenPyrrolidine Pyrrole
OxygenTetrahydrofuranFuran
PhosphorusPhospholanePhosphole
SeleniumSelenolaneSelenophene
SiliconSilacyclopentaneSilole
SulfurTetrahydrothiopheneThiophene
TelluriumTellurophene
TinStannolaneStannole

Five-membered rings with ''two'' heteroatoms

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.
HeteroatomSaturatedUnsaturated
Nitrogen/nitrogenImidazolidine
Pyrazolidine		Imidazole
Pyrazole
Nitrogen/oxygenOxazolidine
Isoxazolidine		Oxazole
Isoxazole
Nitrogen/sulfurThiazolidine
Isothiazolidine		Thiazole
Isothiazole
Oxygen/oxygenDioxolane
Sulfur/sulfurDithiolane

Five-membered rings with at least ''three'' heteroatoms

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 atoms.
HeteroatomSaturatedUnsaturated
3 × NitrogenTriazoles
2 × Nitrogen / 1 × oxygenFurazan
Oxadiazole
2 × Nitrogen / 1 × sulfurThiadiazole
1 × Nitrogen / 2 × oxygenDioxazole
1 × Nitrogen / 2 × sulfurDithiazole
4 × NitrogenTetrazole
4 × Nitrogen/1 × OxygenOxatetrazole
4 × Nitrogen/1 × SulfurThiatetrazole
5 × NitrogenPentazole

6-membered rings

Six-membered rings with ''one'' heteroatom

HeteroatomSaturatedUnsaturatedIons
AntimonyStibinin-
ArsenicArsinaneArsinine-
BismuthBismin-
BoronBorinaneBorinineBoratabenzene anion
GermaniumGerminaneGermine-
NitrogenPiperidine Pyridine Pyridinium cation
OxygenTetrahydropyranPyran Pyrylium cation
PhosphorusPhosphinanePhosphinine-
SeleniumSelenopyrylium cation
SiliconSilinaneSiline-
SulfurThianeThiopyran Thiopyrylium cation
TinStanninaneStannine-

Six-membered rings with ''two'' heteroatoms

HeteroatomSaturatedUnsaturated
Nitrogen / nitrogenDiazinaneDiazine
Oxygen / nitrogenMorpholineOxazine
Sulfur / nitrogenThiomorpholineThiazine
Oxygen / oxygenDioxaneDioxine
Sulfur / sulfurDithianeDithiin
Boron / nitrogen1,2-Dihydro-1,2-azaborine

Six-membered rings with ''three'' heteroatoms

HeteroatomSaturatedUnsaturated
NitrogenTriazinaneTriazine
OxygenTrioxane
SulfurTrithiane

Six-membered rings with ''four'' heteroatoms

HeteroatomSaturatedUnsaturated
NitrogenTetrazine

Carborazine is a six-membered ring with two nitrogen heteroatoms and two boron heteroatom.

Six-membered rings with five heteroatoms

HeteroatomSaturatedUnsaturated
NitrogenPentazine

Six-membered rings with six heteroatoms

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

7-membered rings

With 7-membered rings, the heteroatom must be able to provide an empty pi orbital for "normal" aromatic stabilization to be available; otherwise, homoaromaticity may be possible. Compounds with one heteroatom include:
HeteroatomSaturatedUnsaturated
BoronBorepin
NitrogenAzepaneAzepine
OxygenOxepaneOxepine
SulfurThiepaneThiepine

Those with two heteroatoms include:
HeteroatomSaturatedUnsaturated
NitrogenDiazepaneDiazepine
Nitrogen/sulfurThiazepine

8-membered rings

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

9-membered rings

Images

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. 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 isolates alloxan from uric acid

1832: Dobereiner produces furfural by treating starch with sulfuric acid

1834: Runge obtains pyrrole by dry distillation of bones

1906: Friedlander synthesizes indigo dye, 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 in the genetic code.

Uses

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