, a homocyclic 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). IUPAC Gold Book heterocyclic compounds 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 (cellulose and related materials), and many natural and synthetic dyes.
Although heterocyclic compound
s may be inorganic
, most contain at least one carbon
. While atoms that are neither carbon nor hydrogen are normally referred to in organic chemistry
s, this is usually in comparison to the all-carbon backbone. But this does not prevent a compound such as borazine
(which has no carbon atoms) 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
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 are fused to benzene rings, which for pyridine, thiophene, pyrrole, and furan are quinoline
, and benzofuran
, respectively. Fusion of two benzene rings gives rise to a third large family of compounds, respectively the acridine
, and dibenzofuran
. The unsaturated rings can be classified according to the participation of the heteroatom in the pi system
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 with one
Those with two
Compounds with one heteroatom:
Compounds with two heteroatoms:
With heterocycles containing five atoms, the unsaturated compound
s are frequently more stable because of aromaticity
Five-membered rings with one
The 5-membered ring compounds containing two
heteroatoms, at least one of which is nitrogen, are collectively called the azole
s and isothiazole
s contain a sulfur and a nitrogen atom in the ring. Dithiolane
s have two sulfur atoms.
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.
Five-member ring compounds with four
With 5-heteroatoms, the compound may be considered inorganic rather than heterocyclic.
Six-membered rings with a single
With three heteroatoms:
With four heteroatoms:
With five heteroatoms:
The hypothetical compound with six nitrogen heteroatoms would be hexazine
With 7-membered rings, the heteroatom must be able to provide an empty pi orbital (e.g., boron) for "normal" aromatic stabilization to be available; otherwise, homoaromaticity
may be possible. Compounds with one heteroatom include:
Those with two heteroatoms include:
Names in italics are retained by IUPAC and they do not follow the Hantzsch-Widman nomenclature
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
depending on the orientation. The pyridine analog is quinoline
. For azepine, benzazepine
is the preferred name. Likewise, the compounds with two benzene rings fused to the central heterocycle are carbazole
, and dibenzoazepine. Thienothiophene
are the fusion of two thiophene rings. Phosphaphenalene
s are a tricylic 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:E. Campaigne "Adrien Albert and the Rationalization of Heterocyclic Chemistry" J. Chemical Education 1986, Volume 6, 860.
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 dye
, allowing synthetic chemistry to displace a large agricultural industry
isolates chlorophyl derivatives from crude oil, explaining the biological origin of petroleum.
1951: Chargaff's rules
are described, highlighting the role of heterocyclic compounds ( purine
s and pyrimidine
s) in the genetic code.
Heterocyclic compounds are pervasive in many areas of life sciences and technology.Thomas L. Gilchrist "Heterocyclic Chemistry" 3rd ed. Addison Wesley: Essex, England,
1997. 414 pp. . Many drugs are heterocyclic compounds. Companies with the highest number of patents related to heterocyclic compounds.