Heterocyclic compound

A heterocyclic compound or ring structure is a hydrocarbon-based cyclic compound that contains at least one heteroatom as member(s) of its ring(s).IUPAC Gold Book heterocyclic compounds Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and applications of organic 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. More than half of known compounds are heterocycles. 59% of US FDA-approved drugs contain nitrogen heterocycles.

Classification The study of organic heterocyclic chemistry focuses especially on organic unsaturated derivatives, and the preponderance of work and applications involves unstrained organic 5- and 6-membered rings. Included are pyridine, thiophene, pyrrole, and furan. Another large class of organic heterocycles refers to those fused to benzene rings. For example, the fused benzene derivatives 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 organic compounds. Analogs of the previously mentioned heterocycles for this third family of compounds are acridine, dibenzothiophene, carbazole, and dibenzofuran, respectively.

Heterocyclic organic compounds can be usefully classified based on their electronic structure. The saturated organic heterocycles behave like the acyclic derivatives. Thus, piperidine and tetrahydrofuran are conventional amines and ethers, with modified steric profiles. Therefore, the study of organic heterocyclic chemistry focuses on organic unsaturated rings.

Inorganic rings Some heterocycles contain no carbon. Examples are borazine (B3N3 ring), hexachlorophosphazene (P3N3 ring), and trithiazyl trichloride (S3N3 ring). In comparison with organic heterocycles, which have numerous commercial applications, inorganic ring systems are mainly of theoretical interest. IUPAC recommends the Hantzsch-Widman nomenclature for naming heterocyclic compounds.

Notes on lists "Heteroatoms" are atoms in the ring other than carbon atoms. Names in italics are retained by IUPAC and do not follow the Hantzsch-Widman nomenclature. Some of the names refer to classes of compounds rather than individual compounds. Also no attempt is made to list isomers.

3-membered rings Although subject to ring strain, 3-membered heterocyclic rings are well characterized.

Three-membered rings with one heteroatom Heteroatom Saturated Unsaturated Boron Borirane Borirene Nitrogen Aziridine Azirine Oxygen Oxirane(ethylene oxide, epoxides) Oxirene Silicon Silirane Silirene Phosphorus Phosphirane Phosphirene Sulfur Thiirane(ethylene sulfide, episulfides) Thiirene Three-membered rings with two heteroatoms Heteroatoms Saturated Unsaturated 2 × Nitrogen Diaziridine Diazirine Nitrogen + Oxygen Oxaziridine Oxazirine Nitrogen + Sulfur Thiaziridine Thiazirine 2 × Oxygen Dioxirane (highly unstable) - - - - - - 2 × Sulfur Dithiirane (highly unstable) - - - - - -

4-membered rings Four-membered rings with one heteroatom Heteroatom Saturated Unsaturated Boron Boretane Borete Nitrogen Azetidine Azete Oxygen Oxetane Oxete Silicon Siletane Silete Phosphorus Phosphetane Phosphete Sulfur Thietane Thiete Four-membered rings with two heteroatoms Heteroatoms Saturated Unsaturated 2 × Nitrogen Diazetidine Diazete 2 × Oxygen Dioxetane Dioxete 2 × Sulfur Dithietane Dithiete Phosphorus + Oxygen Oxaphosphetane Oxaphosphete

5-membered rings 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. Dithioles have two sulfur atoms.

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 atom.

Five-membered rings with one heteroatom Heteroatom Saturated Unsaturated Boron Borolane Borole Nitrogen Pyrrolidine(Azolidine not used) Pyrrole(Azole not used)Pyrroline (partially unsaturated) Oxygen Oxolane Furan(Oxole not used) Silicon Silolane Silole Phosphorus Phospholane Phosphole Sulfur Thiolane Thiophene(Thiole not used) Germanium Germolane Germole Arsenic Arsolane Arsole Selenium Selenolane Selenophene Tin Stannolane Stannole Antimony Stibolane Stibole Tellurium Tellurolane Tellurophene Lead Plumbolane Plumbole Bismuth Bismolane Bismole Five-membered rings with two heteroatoms Heteroatoms Saturated Unsaturated (and partially unsaturated) 2 × Nitrogen Pyrazolidine Imidazolidine Pyrazole (Pyrazoline)Imidazole (Imidazoline) Nitrogen + Oxygen OxazolidineIsoxazolidine Oxazole (Oxazoline)Isoxazole (Isoxazoline) Nitrogen + Sulfur ThiazolidineIsothiazolidine Thiazole (Thiazoline)Isothiazole (Isothiazoline) Oxygen + Sulfur OxathiolaneIsoxathiolane OxathioleIsoxathiole 2 × Oxygen Dioxolane Dioxole 2 × Sulfur Dithiolane Dithiole Five-membered rings with three heteroatoms Heteroatoms Unsaturated 3 × Nitrogen Triazole 2 Nitrogen + Oxygen Oxadiazole 2 Nitrogen + Sulfur Thiadiazole Nitrogen + 2 Oxygen Dioxazole Nitrogen + 2 Sulfur Dithiazole Five-membered rings with four heteroatoms Heteroatoms Unsaturated 4 × Nitrogen Tetrazole 3 Nitrogen + Oxygen Oxatriazole 3 Nitrogen + Sulfur Thiatriazole Five-membered rings with five heteroatoms Heteroatoms Unsaturated 5 × Nitrogen Pentazole 4 Nitrogen + Oxygen Oxatetrazole 4 Nitrogen + Sulfur Thiatetrazole

6-membered rings The 6-membered ring compounds containing two heteroatoms, at least one of which is nitrogen, are collectively called the azines. Thiazines contain a sulfur and a nitrogen atom in the ring. Dithiines have two sulfur atoms.

Six-membered rings with one heteroatom Heteroatom Saturated Unsaturated Ions Boron Borinane Borinine Boratabenzene anion Nitrogen Piperidine(Azinane not used) Pyridine(Azine not used) Pyridinium cation Oxygen Oxane Pyran(Oxine not used) Pyrylium cation Silicon Silinane Siline - - - - - - Phosphorus Phosphinane Phosphinine Phosphininium cation Sulfur Thiane Thiopyran(Thiine not used) Thiopyrylium cation Germanium Germinane Germine - - - - - - Arsenic Arsinane Arsinine Arsatabenzene cation Selenium Selenane Selenopyran Selenopyrylium cation Tin Stanninane Stannine - - - - - - Antimony Stibinane Stibinine Stibatabenzene cation Tellurium Tellurane Telluropyran Telluropyrylium cation Lead Plumbinane Plumbine - - - - - - Bismuth Bisminane Bismine Bismatabenzene cation Six-membered rings with two heteroatoms Heteroatoms Saturated Unsaturated 2 × Nitrogen Piperazine PyrazinePyrimidinePyridazine Nitrogen + Oxygen Morpholine Oxazine Nitrogen + Sulfur Thiomorpholine Thiazine Oxygen + Sulfur Oxathiane Oxathiin 2 × Oxygen Dioxane Dioxin 2 × Sulfur Dithiane Dithiin Nitrogen + Boron Azaborinane Azaborine Six-membered rings with three heteroatoms Heteroatoms Saturated Unsaturated 3 × Nitrogen Triazinane Triazine 3 × Oxygen Trioxane Trioxin 3 × Sulfur Trithiane Trithiin 2 Nitrogen + 1 Sulfur Thiadiazinane Thiadiazine Six-membered rings with four heteroatoms Heteroatoms Unsaturated 4 × Nitrogen Tetrazine 2 Nitrogen + 2 Boron Carborazine

Six-membered rings with five heteroatomsThe hypothetical chemical compound with five nitrogen heteroatoms would be pentazine.

Six-membered rings with six heteroatomsThe hypothetical chemical compound with six nitrogen heteroatoms would be hexazine. Borazine is a six-membered ring with three nitrogen heteroatoms and three boron heteroatoms.

7-membered rings In a 7-membered ring, the heteroatom must be able to provide an empty π-orbital (e.g. boron) for "normal" aromatic stabilization to be available; otherwise, homoaromaticity may be possible.

Seven-membered rings with one heteroatom Heteroatom Saturated Unsaturated Boron Borepane Borepine Nitrogen Azepane Azepine Oxygen Oxepane Oxepine Silicon Silepane Silepine Phosphorus Phosphepane Phosphepine Sulfur Thiepane Thiepine Seven-membered rings with two heteroatoms Heteroatoms Saturated Unsaturated 2 × Nitrogen Diazepane Diazepine Nitrogen + Oxygen Oxazepane Oxazepine Nitrogen + Sulfur Thiazepane Thiazepine

8-membered rings Heteroatom Saturated Unsaturated Nitrogen Azocane Azocine Oxygen Oxocane Oxocine Sulfur Thiocane Thiocine

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

9-membered rings Heteroatom Saturated Unsaturated Nitrogen Azonane Azonine Oxygen Oxonane Oxonine Sulfur Thionane Thionine

Images of rings with one heteroatom Saturated Unsaturated Heteroatom Nitrogen Oxygen Sulfur Nitrogen Oxygen Sulfur 3-atom ring Aziridine Oxirane Thiirane Azirine Oxirene Thiirene 4-atom ring Azetidine Oxetane Thietane Azete Oxete Thiete 5-atom ring Pyrrolidine Oxolane Thiolane Pyrrole Furan Thiophene 6-atom ring Piperidine Oxane Thiane Pyridine Pyran Thiopyran 7-atom ring Azepane Oxepane Thiepane Azepine Oxepine Thiepine 8-atom ring Azocane Oxocane Thiocane Azocine Oxocine Thiocine 9-atom ring Azonane Oxonane Thionane Azonine Oxonine Thionine

Fused/condensed 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 derivative is quinoline or isoquinoline, and the class of analogues with two nitrogen atoms is known as the benzodiazines. For the azepine derivative, benzazepine is the preferred name. Likewise, the compounds with two benzene rings fused to the central heterocycle are carbazole, acridine, and dibenzoazepine. Heptazine is a tricyclic nitrogen-containing heterocyclic system derived by fusion of three triazine rings, and analog of 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 makes alloxan from uric acid. 1832: Döbereiner 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 chlorophyll 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.

Uses 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. Among the modifications to the family of antitumor compounds, heterocyclic organic compounds have been extensively applied by many groups in order to modify the reactivity profile. Pyrrole, pyrimidine, indole, quinoline and purine are few classes of heterocycles which showed interesting cytotoxicity profiles, which can be highly beneficial when developing cancer drugs. Heterocyclic compounds play a central role in modern medicinal chemistry, with a large majority of newly approved drugs, containing at least one heterocyclic ring particularly nitrogen-containing systems. Their prevalence is attributed to their ability to modulate physicochemical properties such as solubility, lipophilicity, and binding affinity to biological targets.

Heterocyclic compound

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