1/29/2016 Heterocyclic compound - Wikipedia, the free encyclopedia Heterocyclic compound From Wikipedia, the free encyclopedia 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).[1] Heterocyclic chemistry is the branch of chemistry dealing with the synthesis, properties and applications of these heterocycles. In contrast, the rings of homocyclic compounds consist entirely of atoms of the same element. Although heterocyclic compounds may be inorganic, 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 (which has no Pyridine, a carbon atoms) from being labelled "heterocyclic". IUPAC recommends the Hantzsch- heterocyclic Widman nomenclature for naming heterocyclic compounds. compound Contents 1 Classification based on electronic structure cyclo-octasulfur, a 2 3-membered rings homocyclic compound 3 4-membered rings 4 5-membered rings 5 6-membered rings 6 7-membered rings 7 8-membered rings 8 9-membered rings 9 Images 10 Fused rings 11 History of heterocyclic chemistry 12 Commercial use 13 References 14 External links https://en.wikipedia.org/wiki/Heterocyclic_compound 1/8 1/29/2016 Heterocyclic compound - Wikipedia, the free encyclopedia 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. 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, 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 with one heteroatom are: Heteroatom Saturated Unsaturated Nitrogen Aziridine Azirine Oxirane (ethylene oxide, Oxygen Oxirene epoxides) Sulfur Thiirane (episulfides) Thiirene Those with two heteroatoms include: Heteroatom Saturated Unsaturated Nitrogen Diazirine Nitrogen/oxygen Oxaziridine Oxygen Dioxirane 4-membered rings Compounds with one heteroatom: Heteroatom Saturated Unsaturated Nitrogen Azetidine Azete Oxygen Oxetane Oxete Sulfur Thietane Thiete Compounds with two heteroatoms: https://en.wikipedia.org/wiki/Heterocyclic_compound 2/8 1/29/2016 Heterocyclic compound - Wikipedia, the free encyclopedia Heteroatom Saturated Unsaturated Nitrogen Diazetidine Oxygen Dioxetane Dioxete 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 one heteroatom: Heteroatom Saturated Unsaturated Nitrogen Pyrrolidine (Azolidine is not used) Pyrrole (Azole is not used) Oxygen Tetrahydrofuran (Oxolane is rare) Furan (Oxole is not used) Sulfur Thiolane Thiophene (Thiole is not used) Boron Borolane Borole Phosphorus Phospholane Phosphole Arsenic Arsolane Arsole Antimony Stibolane Stibole Bismuth Bismolane Bismole Silicon Silolane Silole Tin Stannolane Stannole 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. Unsaturated (and partially Heteroatom Saturated unsaturated) Nitrogen/nitrogen Imidazolidine Imidazole (Imidazoline) Pyrazolidine Pyrazole (Pyrazoline) Nitrogen/oxygen Oxazolidine Oxazole (Oxazoline) Isoxazolidine Isoxazole Nitrogen/sulfur Thiazolidine Thiazole (Thiazoline) Isothiazolidine Isothiazole Oxygen/oxygen Dioxolane Sulfur/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. https://en.wikipedia.org/wiki/Heterocyclic_compound 3/8 1/29/2016 Heterocyclic compound - Wikipedia, the free encyclopedia Heteroatom Saturated Unsaturated 3 × Nitrogen Triazoles Furazan 2 × Nitrogen / 1 × oxygen Oxadiazole 2 × Nitrogen / 1 × sulfur Thiadiazole 1 × Nitrogen / 2 × sulfur Dithiazole Five-member ring compounds with four heteroatoms: Heteroatom Saturated Unsaturated 4 × 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 Piperidine (Azinane is not Nitrogen Pyridine (Azine is not used) used) Oxygen Oxane Pyran (2H-Oxine is not used) Thiopyran (2H-Thiine is not Sulfur Thiane used) Silicon Salinane Siline Germanium Germinane Germine Tin Stanninane Stannine Boron Borinane Borinine Phosphorus Phosphinane Phosphinine Arsenic Arsinane Arsinine With two heteroatoms: Heteroatom Saturated Unsaturated Nitrogen / nitrogen Piperazine Diazines Oxygen / nitrogen Morpholine Oxazine Sulfur / nitrogen Thiomorpholine Thiazine Oxygen / oxygen Dioxane Dioxine Sulfur / sulfur Dithiane Dithiine With three heteroatoms: https://en.wikipedia.org/wiki/Heterocyclic_compound 4/8 1/29/2016 Heterocyclic compound - Wikipedia, the free encyclopedia Heteroatom Saturated Unsaturated Nitrogen Triazine Oxygen Trioxane Sulfur Trithiane 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 (e.g., 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 Homopiperazine Diazepine Nitrogen/sulfur Thiazepine 8-membered rings Heteroatom Saturated Unsaturated Nitrogen Azocane Azocine Sulfur 9-membered rings Heteroatom Saturated Unsaturated Nitrogen Azonane Azonine Oxygen Oxonane Oxonine Sulfur Thionane Thionine https://en.wikipedia.org/wiki/Heterocyclic_compound 5/8 1/29/2016 Heterocyclic compound - Wikipedia, the free encyclopedia Images Names in italics are retained by IUPAC and they do not follow the Hantzsch-Widman nomenclature Saturated Unsaturated Heteroatom Nitrogen Oxygen Sulfur Nitrogen Oxygen Sulfur Aziridine Oxirane Thiirane Azirine Oxirene Thiirene 3-Atom Ring Azetidine Oxetane Thietane Azete Oxete Thiete 4-Atom Ring Pyrrolidine Oxolane Thiolane Pyrrole Furan Thiophene 5-Atom Ring Piperidine Oxane Thiane Pyridine Pyran Thiopyran 6-Atom Ring Azepane Oxepane Thiepane Azepine Oxepine Thiepine 7-Atom Ring 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. https://en.wikipedia.org/wiki/Heterocyclic_compound 6/8 1/29/2016 Heterocyclic compound - Wikipedia, the free encyclopedia History of heterocyclic chemistry The history of heterocyclic chemistry began in the 1800s, in step with the development of organic chemistry. Some noteworthy developments:[2] 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 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. Commercial use Leading companies with a vast number of patents related to heterocyclic compounds are Bayer, Merck, Ciba- Geigy, Pfizer, Eli Lily, BASF, Hoffmann La Roche, ER Sqibb, Warner Lambert and Hoechst.[3] References 1. IUPAC Gold Book heterocyclic compounds (http://goldbook.iupac.org/H02798.html) 2. E. Campaigne "Adrien Albert and the Rationalization of Heterocyclic Chemistry" J. Chemical Education 1986, Volume 6, 860. doi:10.1021/ed063p860 (https://dx.doi.org/10.1021%2Fed063p860) 3. Companies with the highest number of patents related to heterocyclic compounds. (http://www.ipexl.com/share/f593e64bc3679cb669d02c007efdca17)