Heterocyclic compound: Difference between revisions
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[[Image:Pyridine.svg|thumb|right|125px|[[Pyridine]], a heterocyclic compound]] |
[[Image:Pyridine.svg|thumb|right|125px|[[Pyridine]], a heterocyclic compound]] |
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A '''heterocyclic compound''' or '''ring structure''' is a [[cyclic compound]] that has atoms of at least two different [[chemical element|elements]] as members of its ring(s).<ref>[[IUPAC Gold Book]] [http://goldbook.iupac.org/H02798.html ''heterocyclic compounds'']</ref> '''Heterocyclic chemistry''' is the branch of [[organic chemistry]] dealing with the synthesis, properties, and applications of |
A '''heterocyclic compound''' or '''ring structure''' is a [[cyclic compound]] that has atoms of at least two different [[chemical element|elements]] as members of its ring(s).<ref>[[IUPAC Gold Book]] [http://goldbook.iupac.org/H02798.html ''heterocyclic compounds'']</ref> '''Heterocyclic organic chemistry''' is the branch of [[organic chemistry]] dealing with the synthesis, properties, and applications of '''organic heterocycles'''.<ref name=Gilchrist/> |
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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.<ref name=Rees>{{cite journal |doi=10.1002/jhet.5570290306|title=Polysulfur-Nitrogen Heterocyclic Chemistry|year=1992|last1=Rees|first1=Charles W.|journal=Journal of Heterocyclic Chemistry|volume=29|issue=3|pages=639–651}}</ref> 59% of US FDA-approved drugs contain nitrogen heterocycles.<ref>{{cite journal|author=Edon Vitaku, David T. Smith, Jon T. Njardarson|title=Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals|journal=J. Med. Chem.|volume=57|year=2014|issue=24|pages=10257–10274|doi=10.1021/jm501100b|pmid=25255204}}</ref> |
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.<ref name=Rees>{{cite journal |doi=10.1002/jhet.5570290306|title=Polysulfur-Nitrogen Heterocyclic Chemistry|year=1992|last1=Rees|first1=Charles W.|journal=Journal of Heterocyclic Chemistry|volume=29|issue=3|pages=639–651}}</ref> 59% of US [[FDA]]-approved drugs contain [[nitrogen]] heterocycles.<ref>{{cite journal|author=Edon Vitaku, David T. Smith, Jon T. Njardarson|title=Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals|journal=J. Med. Chem.|volume=57|year=2014|issue=24|pages=10257–10274|doi=10.1021/jm501100b|pmid=25255204}}</ref> |
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== Classification == |
== Classification == |
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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 ring]]s. 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 compounds. Analogs of the previously mentioned heterocycles for this third family of compounds are acridine, dibenzothiophene, carbazole, and dibenzofuran, respectively. |
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 ring]]s. 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. |
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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 on unsaturated rings. |
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. |
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===Inorganic rings=== |
===Inorganic rings=== |
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Some heterocycles contain no carbon. Examples are [[borazine]] (B<sub>3</sub>N<sub>3</sub> ring), [[hexachlorophosphazene]]s (P<sub>3</sub>N<sub>3</sub> rings), and S<sub>4</sub>N<sub>4</sub>. In comparison with organic heterocycles, which have numerous commercial applications, inorganic ring systems are mainly of theoretical interest. [[International Union of Pure and Applied Chemistry|IUPAC]] recommends the [[Hantzsch-Widman nomenclature]] for naming heterocyclic compounds.<ref>{{GoldBookRef|title=Hantzsch–Widman name|file=H02737}}</ref> |
Some heterocycles contain no carbon. Examples are [[borazine]] (B<sub>3</sub>N<sub>3</sub> ring), [[hexachlorophosphazene]]s (P<sub>3</sub>N<sub>3</sub> rings), and [[tetrasulfur tetranitride]] S<sub>4</sub>N<sub>4</sub>. In comparison with organic heterocycles, which have numerous commercial applications, inorganic ring systems are mainly of theoretical interest. [[International Union of Pure and Applied Chemistry|IUPAC]] recommends the [[Hantzsch-Widman nomenclature]] for naming heterocyclic compounds.<ref>{{GoldBookRef|title=Hantzsch–Widman name|file=H02737}}</ref> |
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==Notes on lists== |
==Notes on lists== |
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* "Heteroatoms" are atoms in the ring other than carbon atoms. |
* "Heteroatoms" are atoms in the ring other than [[carbon]] atoms. |
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⚫ | |||
* Some of the names refer to classes of compounds rather than individual compounds. |
* Some of the names refer to classes of compounds rather than individual compounds. |
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* Also no attempt is made to list isomers. |
* Also no attempt is made to list [[isomers]]. |
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== 3-membered rings == |
== 3-membered rings == |
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Although subject to [[ring strain]], 3-membered heterocyclic rings are well characterized.<ref>{{March6th}}</ref> |
Although subject to [[ring strain]], 3-membered heterocyclic rings are well characterized.<ref>{{March6th}}</ref> |
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{{div col begin}} |
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⚫ | |||
{| class="wikitable" |
{| class="wikitable" |
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⚫ | |||
!Heteroatom |
!Heteroatom |
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!Saturated |
!Saturated |
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| Boron |
| Boron |
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| [[Borirane]] |
| [[Borirane]] |
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| |
| Borirene |
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|- |
|- |
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| Nitrogen |
| Nitrogen |
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| [[Thiirene]] |
| [[Thiirene]] |
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|} |
|} |
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⚫ | |||
{| class="wikitable" |
{| class="wikitable" |
||
⚫ | |||
!Heteroatoms |
!Heteroatoms |
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!Saturated |
!Saturated |
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| Nitrogen + oxygen |
| Nitrogen + oxygen |
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| [[Oxaziridine]] |
| [[Oxaziridine]] |
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| Oxazirine |
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⚫ | |||
|- |
|- |
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| 2× Oxygen |
| 2× Oxygen |
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| |
| |
||
|} |
|} |
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{{div col end}} |
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== 4-membered rings == |
== 4-membered rings == |
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{{div col begin}} |
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⚫ | |||
{| class="wikitable" |
{| class="wikitable" |
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⚫ | |||
⚫ | |||
! Heteroatom |
! Heteroatom |
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! Saturated |
! Saturated |
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| [[Thiete]] |
| [[Thiete]] |
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|} |
|} |
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⚫ | |||
{| class="wikitable" |
{| class="wikitable" |
||
⚫ | |||
! Heteroatoms |
! Heteroatoms |
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! Saturated |
! Saturated |
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| [[Dithiete]] |
| [[Dithiete]] |
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|} |
|} |
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{{div col end}} |
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== 5-membered rings == |
== 5-membered rings == |
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⚫ | |||
⚫ | |||
⚫ | |||
{{div col begin}} |
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{| class="wikitable" |
{| class="wikitable" |
||
⚫ | |||
|- |
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! Heteroatom |
! Heteroatom |
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! Saturated |
! Saturated |
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|- |
|- |
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! [[Nitrogen]] |
! [[Nitrogen]] |
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| ''[[Pyrrolidine]]'' ("Azolidine" |
| ''[[Pyrrolidine]]'' ("Azolidine" not used) |
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| ''[[Pyrrole]]'' ("Azole" |
| ''[[Pyrrole]]'' ("Azole" not used) |
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|- |
|- |
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! [[Oxygen]] |
! [[Oxygen]] |
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| [[Stannole]] |
| [[Stannole]] |
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|} |
|} |
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⚫ | |||
⚫ | |||
{| class="wikitable" |
{| class="wikitable" |
||
⚫ | |||
! Heteroatoms |
! Heteroatoms |
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! Saturated |
! Saturated |
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|- valign=top |
|- valign=top |
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! Oxygen + sulfur |
! Oxygen + sulfur |
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| [[ |
| [[1,3-Oxathiolane]]<br>[[1,2-Oxathiolane]] |
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| [[Oxathiole]] ([[Oxathioline]])<br>[[Isoxathiole]] |
| [[Oxathiole]] ([[Oxathioline]])<br>[[Isoxathiole]] |
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|- valign=top |
|- valign=top |
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! 2× sulfur |
! 2× sulfur |
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| [[Dithiolane]] |
| [[Dithiolane]] |
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| [[Dithiole]] |
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|} |
|} |
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⚫ | |||
⚫ | |||
{| class="wikitable" |
{| class="wikitable" |
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⚫ | |||
|- |
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! Heteroatoms |
! Heteroatoms |
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! Saturated |
! Saturated |
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| [[Pentazole]] |
| [[Pentazole]] |
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|} |
|} |
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{{div col end}} |
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== 6-membered rings == |
== 6-membered rings == |
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{{div col begin}} |
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⚫ | |||
{| class="wikitable" |
{| class="wikitable" |
||
⚫ | |||
! Heteroatom |
! Heteroatom |
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! Saturated |
! Saturated |
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|- |
|- |
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| Nitrogen |
| Nitrogen |
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| ''[[Piperidine]]''<br>(Azinane |
| ''[[Piperidine]]''<br>(Azinane not used) |
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| ''[[Pyridine]]''<br>([[Azine (heterocycle)|Azine]] |
| ''[[Pyridine]]''<br>([[Azine (heterocycle)|Azine]] not used) |
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| [[Pyridinium]] cation |
| [[Pyridinium]] cation |
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|- |
|- |
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| Oxygen |
| Oxygen |
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| [[Oxane]] |
| [[Oxane]] |
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| ''[[Pyran]]''<br>(2''H''-[[Oxine]] |
| ''[[Pyran]]''<br>(2''H''-[[Oxine]] not used) |
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| [[Pyrylium]] cation |
| [[Pyrylium]] cation |
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|- |
|- |
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| Sulfur |
| Sulfur |
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| [[Thiane]] |
| [[Thiane]] |
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| ''[[Thiopyran]]''<br>(2''H''-Thiine |
| ''[[Thiopyran]]''<br>(2''H''-Thiine not used) |
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| [[Thiopyrylium]] cation |
| [[Thiopyrylium]] cation |
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|- |
|- |
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|} |
|} |
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⚫ | |||
|+ Six-membered rings; ''two'' heteroatoms |
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⚫ | |||
|- |
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! Heteroatom |
! Heteroatom |
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! Saturated |
! Saturated |
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|} |
|} |
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⚫ | |||
|+ Six-membered rings; ''three'' heteroatoms |
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⚫ | |||
|- |
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! Heteroatom |
! Heteroatom |
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! Saturated |
! Saturated |
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|} |
|} |
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⚫ | |||
|+ Six-membered rings; ''four'' heteroatoms |
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⚫ | |||
|- |
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! Heteroatom |
! Heteroatom |
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! Saturated |
! Saturated |
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| |
| |
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| [[Tetrazine]] |
| [[Tetrazine]] |
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⚫ | |||
| 2 nitrogen, 2 [[boron]] || || [[Carborazine]] |
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|} |
|} |
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⚫ | |||
[[Carborazine]] is a six-membered ring with two nitrogen heteroatoms and two boron heteroatom. |
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⚫ | |||
⚫ | |||
⚫ | |||
|- |
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! Heteroatom |
! Heteroatom |
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! Saturated |
! Saturated |
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| [[Pentazine]] |
| [[Pentazine]] |
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|} |
|} |
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{{div col end}} |
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===Six-membered rings with six heteroatoms=== |
===Six-membered rings with six heteroatoms=== |
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The [[hypothetical chemical compound]] with six nitrogen heteroatoms would be [[hexazine]]. |
The [[hypothetical chemical compound]] with six nitrogen heteroatoms would be [[hexazine]]. [[Borazine]] is a six-membered ring with three nitrogen heteroatoms and three boron heteroatoms. |
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[[Borazine]] is a six-membered ring with three nitrogen heteroatoms and three boron heteroatoms. |
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== 7-membered rings == |
== 7-membered rings == |
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⚫ | |||
⚫ | |||
{{div col begin}} |
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{| class="wikitable" |
{| class="wikitable" |
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|+ Seven-membered rings; ''one'' heteroatom |
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! Heteroatom |
! Heteroatom |
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! Saturated |
! Saturated |
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| [[Thiepine]] |
| [[Thiepine]] |
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|} |
|} |
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Those with two heteroatoms include: |
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{| class="wikitable" |
{| class="wikitable" |
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|+ Seven-membered rings; ''two'' heteroatoms |
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|- |
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! Heteroatom |
! Heteroatom |
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! Saturated |
! Saturated |
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| [[Thiazepine]] |
| [[Thiazepine]] |
||
|} |
|} |
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{{div col end}} |
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== 8-membered rings == |
== 8-membered rings == |
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{{div col begin}} |
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{| class="wikitable" |
{| class="wikitable" |
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|- |
|- |
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| [[Thiocane]] |
| [[Thiocane]] |
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| [[Thiocine]] |
| [[Thiocine]] |
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⚫ | |||
| 4 nitrogen, 4 boron || || [[Borazocine]] |
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|} |
|} |
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{{div col end}} |
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[[Borazocine]] is an eight-membered ring with four nitrogen heteroatoms and four boron heteroatoms. |
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== 9-membered rings == |
== 9-membered rings == |
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{| class="wikitable" |
{| class="wikitable" |
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|- |
|- |
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== Images of rings with one heteroatom== |
== Images of rings with one heteroatom== |
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⚫ | |||
{| class="wikitable" |
{| class="wikitable" |
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|- |
|- |
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! align="left" | Heteroatom !![[Nitrogen]] !![[Oxygen]] !![[Sulfur]] !!Nitrogen !!Oxygen !!Sulfur |
! align="left" | Heteroatom !![[Nitrogen]] !![[Oxygen]] !![[Sulfur]] !!Nitrogen !!Oxygen !!Sulfur |
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|- |
|- |
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! rowspan="2" | 3- |
! rowspan="2" | 3-atom ring |
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| [[Aziridine]] || [[Oxirane]] || [[Thiirane]] || [[Azirine]] || [[Oxirene]] || [[Thiirene]] |
| [[Aziridine]] || [[Oxirane]] || [[Thiirane]] || [[Azirine]] || [[Oxirene]] || [[Thiirene]] |
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|- |
|- |
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| [[File:Aziridin.svg|60px|Structure of |
| [[File:Aziridin.svg|60px|Structure of aziridine]] || [[File:Ethylene oxide.svg|60px|Structure of oxirane]] || [[File:Thiiran.svg|60px|Structure of thiirane]] || [[File:Azirin.svg|60px|Structure of azirine]] || [[File:Oxiren.svg|60px|Structure of oxirene]] || [[File:Thiiren.svg|60px|Structure of thiirene]] |
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|- |
|- |
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! rowspan="2" | 4- |
! rowspan="2" | 4-atom ring |
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| [[Azetidine]] || [[Oxetane]] || [[Thietane]] || [[Azete]] || [[Oxete]]|| [[Thiete]] |
| [[Azetidine]] || [[Oxetane]] || [[Thietane]] || [[Azete]] || [[Oxete]]|| [[Thiete]] |
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|- |
|- |
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| [[File:Azetidine structure.svg|70px|Structure of |
| [[File:Azetidine structure.svg|70px|Structure of acetidine]] || [[File:Oxetan.png|60px|Structure of oxetane]] || [[File:Thietan.png|60px|Structure of thietane]] || [[File:Azete structure.svg|60px|Structure of azete]] || [[File:Oxetene.svg|64px|Structure of oxete]] || [[File:Thietene.png|74px|Structure of thiete]] |
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|- |
|- |
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! rowspan="2" | 5- |
! rowspan="2" | 5-atom ring |
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| ''[[Pyrrolidine]]'' || [[Oxolane]] || [[Thiolane]] || ''[[Pyrrole]]'' || ''[[Furan]]'' || ''[[Thiophene]]'' |
| ''[[Pyrrolidine]]'' || [[Oxolane]] || [[Thiolane]] || ''[[Pyrrole]]'' || ''[[Furan]]'' || ''[[Thiophene]]'' |
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|- valign="top" |
|- valign="top" |
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|| [[File:Pyrrolidine-Structural Formula V.1.svg|60px|Structure of |
|| [[File:Pyrrolidine-Structural Formula V.1.svg|60px|Structure of pyrrolidine]] || [[File:Tetrahydrofuran acsv.svg|70px|Structure of oxolane]] || [[File:Tetrahydrothiophen.png|70px|Structure of thiolane]] |
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|| [[File:Pyrrol2.svg|70px|Structure of |
|| [[File:Pyrrol2.svg|70px|Structure of pyrrole]] || [[File:Furan.svg|70px|Structure of furan]] || [[File:Thiophen.svg|70px|Structure of thiophene]] |
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|- |
|- |
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! rowspan="2" | 6- |
! rowspan="2" | 6-atom ring |
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| ''[[Piperidine]]'' || [[Oxane]] || [[Thiane]] || ''[[Pyridine]]'' || ''[[Pyran]]'' || ''[[Thiopyran]]'' |
| ''[[Piperidine]]'' || [[Oxane]] || [[Thiane]] || ''[[Pyridine]]'' || ''[[Pyran]]'' || ''[[Thiopyran]]'' |
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|- valign="top" |
|- valign="top" |
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|| [[File:Piperidin.svg|70px|Structure of |
|| [[File:Piperidin.svg|70px|Structure of piperidine]] || [[File:Tetrahydropyran (vzorec).svg|70px|Structure of oxane]] || [[File:Thiane3.svg|70px|Structure of thiane]] |
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|| [[File:Pyridin.svg|70px|Structure of |
|| [[File:Pyridin.svg|70px|Structure of pyridine]] || [[File:2H-Pyran.svg|70px|Structure of pyran]] || [[File:1,2-Thiapyran.svg|70px|Structure of thiopyran]] |
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|- |
|- |
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! rowspan="2" | 7- |
! rowspan="2" | 7-atom ring |
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| [[Azepane]] || [[Oxepane]] || [[Thiepane]] || [[Azepine]] || [[Oxepine]] || [[Thiepine]] |
| [[Azepane]] || [[Oxepane]] || [[Thiepane]] || [[Azepine]] || [[Oxepine]] || [[Thiepine]] |
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|- valign="bottom" |
|- valign="bottom" |
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| [[File:Azepane.svg|70px|Structure of |
| [[File:Azepane.svg|70px|Structure of azepane]] || [[File:Oxepan.png|70px|Structure of oxepane]] || [[File:Thiepan.svg|70px|Structure of thiepane]] || [[File:Azepine-2D-skeletal.png|70px|Structure of azepine]] || [[File:Oxepine.svg|70px|Structure of oxepine]] || [[File:Thiepine.png|70px|Structure of thiepine]] |
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|- |
|- |
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! rowspan="2" | 8- |
! rowspan="2" | 8-atom ring |
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| [[Azocane]] || [[Oxocane]] || [[Thiocane]] || [[Azocine]] || [[Oxocine]] || [[Thiocine]] |
| [[Azocane]] || [[Oxocane]] || [[Thiocane]] || [[Azocine]] || [[Oxocine]] || [[Thiocine]] |
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|- valign="bottom" |
|- valign="bottom" |
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| [[File:Azocane.png|70px|Structure of |
| [[File:Azocane.png|70px|Structure of azocane]] || [[File:Oxocano.png|70px|Structure of oxocane]] || [[File:Tiocano.png|70px|Structure of thiocane]] || [[File:Azocine.png|70px|Structure of azocine]] || [[File:Oxocinio.png|70px|Structure of oxocine]] || [[File:Tiocinio.png|70px|Structure of thiocine]] |
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|- |
|- |
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! rowspan="2" | 9- |
! rowspan="2" | 9-atom ring |
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| [[Azonane]] || [[Oxonane]] || [[Thionane]] || [[Azonine]] || [[Oxonine]] || [[(2Z,4Z,6Z,8Z)-Thionine|Thionine]] |
| [[Azonane]] || [[Oxonane]] || [[Thionane]] || [[Azonine]] || [[Oxonine]] || [[(2Z,4Z,6Z,8Z)-Thionine|Thionine]] |
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|- valign="bottom" |
|- valign="bottom" |
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| [[File:Azonano.png|66px|Structure of |
| [[File:Azonano.png|66px|Structure of azonane]] || [[File:Oxonano.png|70px|Structure of oxonane]] || [[File:Tionano.png|70px|Structure of thionane]] || [[File:Azonina.png|70px|Structure of azonine]] || [[File:Oxonina.png|70px|Structure of oxonine]] || [[File:Tionina.png|70px|Structure of thionine]] |
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== History of heterocyclic chemistry == |
== History of heterocyclic chemistry == |
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The history of heterocyclic chemistry began in the 1800s, in step with the development of [[organic chemistry]]. Some noteworthy developments:<ref>{{Cite journal |doi=10.1021/ed063p860|title=Adrien Albert and the rationalization of heterocyclic chemistry|journal=Journal of Chemical Education|volume=63|issue=10|pages=860|year=1986|last1=Campaigne|first1=E.|bibcode=1986JChEd..63..860C}}</ref> |
The history of heterocyclic chemistry began in the 1800s, in step with the development of [[organic chemistry]]. Some noteworthy developments:<ref>{{Cite journal |doi=10.1021/ed063p860|title=Adrien Albert and the rationalization of heterocyclic chemistry|journal=Journal of Chemical Education|volume=63|issue=10|pages=860|year=1986|last1=Campaigne|first1=E.|bibcode=1986JChEd..63..860C}}</ref> |
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* 1818: Brugnatelli |
* 1818: Brugnatelli makes [[alloxan]] from [[uric acid]] |
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* 1832: Dobereiner produces [[furfural]] (a furan) by treating [[starch]] with [[sulfuric acid]] |
* 1832: Dobereiner produces [[furfural]] (a furan) by treating [[starch]] with [[sulfuric acid]] |
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* 1834: Runge obtains [[pyrrole]] ("fiery oil") by dry distillation of bones |
* 1834: Runge obtains [[pyrrole]] ("fiery oil") by dry distillation of bones |
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* 1906: Friedlander synthesizes [[indigo dye]], allowing synthetic chemistry to displace a large agricultural industry |
* 1906: Friedlander synthesizes [[indigo dye]], allowing synthetic chemistry to displace a large agricultural industry |
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* 1936: [[Alfred E. Treibs|Treibs]] isolates |
* 1936: [[Alfred E. Treibs|Treibs]] isolates chlorophyll derivatives from crude oil, explaining the biological origin of petroleum. |
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* 1951: [[Chargaff's rules]] are described, highlighting the role of heterocyclic compounds ([[purine]]s and [[pyrimidine]]s) in the genetic code. |
* 1951: [[Chargaff's rules]] are described, highlighting the role of heterocyclic compounds ([[purine]]s and [[pyrimidine]]s) in the genetic code. |
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== Uses == |
== Uses == |
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Heterocyclic compounds are pervasive in many areas of life sciences and technology.<ref name=Gilchrist>Thomas L. Gilchrist "Heterocyclic Chemistry" 3rd ed. Addison Wesley: Essex, England, |
Heterocyclic compounds are pervasive in many areas of life sciences and technology.<ref name=Gilchrist>Thomas L. Gilchrist "Heterocyclic Chemistry" 3rd ed. Addison Wesley: Essex, England, |
||
1997. 414 pp. {{ISBN|0-582-27843-0}}.</ref> Many drugs are heterocyclic compounds.<ref>{{Cite web|url=http://www.ipexl.com/share/f593e64bc3679cb669d02c007efdca17|title=IPEXL.com Multilingual Patent Search, Patent Ranking|website=www.ipexl.com}}</ref> |
1997. 414 pp. {{ISBN|0-582-27843-0}}.</ref> Many drugs are heterocyclic compounds.<ref>{{Cite web|url=http://www.ipexl.com/share/f593e64bc3679cb669d02c007efdca17|title=IPEXL.com Multilingual Patent Search, Patent Ranking|website=www.ipexl.com|access-date=8 September 2010|archive-date=24 September 2015|archive-url=https://web.archive.org/web/20150924035914/http://www.ipexl.com/share/f593e64bc3679cb669d02c007efdca17|url-status=dead}}</ref> |
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==See also== |
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*[[Spiroketals]] |
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== References == |
== References == |
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* [http://www.chem.qmul.ac.uk/iupac/hetero/HW.html Hantzsch-Widman nomenclature, IUPAC] |
* [http://www.chem.qmul.ac.uk/iupac/hetero/HW.html Hantzsch-Widman nomenclature, IUPAC] |
||
* [http://www.cancer.gov/cancertopics/factsheet/Risk/heterocyclic-amines Heterocyclic amines in cooked meat, US CDC] |
* [http://www.cancer.gov/cancertopics/factsheet/Risk/heterocyclic-amines Heterocyclic amines in cooked meat, US CDC] |
||
* [http://www.cancer.org/docroot/PED/content/PED_1_3x_Known_and_Probable_Carcinogens.asp List of known and probable carcinogens, American Cancer Society] |
* [http://www.cancer.org/docroot/PED/content/PED_1_3x_Known_and_Probable_Carcinogens.asp List of known and probable carcinogens, American Cancer Society] {{Webarchive|url=https://web.archive.org/web/20031213030702/http://www.cancer.org/docroot/PED/content/PED_1_3x_Known_and_Probable_Carcinogens.asp |date=13 December 2003 }} |
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* [http://www.scorecard.org/chemical-groups/one-list.tcl?short_list_name=p65 List of known carcinogens by the State of California], [[Proposition 65]] (more comprehensive) |
* [http://www.scorecard.org/chemical-groups/one-list.tcl?short_list_name=p65 List of known carcinogens by the State of California], [[Proposition 65]] (more comprehensive) |
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Latest revision as of 15:52, 25 June 2024
![](http://upload.wikimedia.org/wikipedia/commons/thumb/a/a8/Heterocycle_compounds.jpg/280px-Heterocycle_compounds.jpg)
![](http://upload.wikimedia.org/wikipedia/commons/thumb/5/55/Pyridine.svg/125px-Pyridine.svg.png)
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 organic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and applications of organic heterocycles.[2]
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.[3] 59% of US FDA-approved drugs contain nitrogen heterocycles.[4]
Classification
[edit]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
[edit]Some heterocycles contain no carbon. Examples are borazine (B3N3 ring), hexachlorophosphazenes (P3N3 rings), and tetrasulfur tetranitride S4N4. 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.[5]
Notes on lists
[edit]- "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
[edit]Although subject to ring strain, 3-membered heterocyclic rings are well characterized.[6]
Heteroatom | Saturated | Unsaturated |
---|---|---|
Boron | Borirane | Borirene |
Nitrogen | Aziridine | Azirine |
Oxygen | Oxirane (ethylene oxide, epoxides) | Oxirene |
Phosphorus | Phosphirane | Phosphirene |
Sulfur | Thiirane (episulfides) | Thiirene |
Heteroatoms | Saturated | Unsaturated |
---|---|---|
2× Nitrogen | Diaziridine | Diazirine |
Nitrogen + oxygen | Oxaziridine | Oxazirine |
2× Oxygen | Dioxirane (highly unstable) |
4-membered rings
[edit]Heteroatom | Saturated | Unsaturated |
---|---|---|
Nitrogen | Azetidine | Azete |
Oxygen | Oxetane | Oxete |
Phosphorus | Phosphetane | Phosphete |
Sulfur | Thietane | Thiete |
Heteroatoms | Saturated | Unsaturated |
---|---|---|
2× Nitrogen | Diazetidine | Diazete |
2× Oxygen | Dioxetane | Dioxete |
2× Sulfur | Dithietane | Dithiete |
5-membered rings
[edit]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.
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.
Heteroatom | Saturated | Unsaturated |
---|---|---|
Antimony | Stibolane | Stibole |
Arsenic | Arsolane | Arsole |
Bismuth | Bismolane | Bismole |
Boron | Borolane | Borole |
Nitrogen | Pyrrolidine ("Azolidine" not used) | Pyrrole ("Azole" not used) |
Oxygen | Tetrahydrofuran | Furan |
Phosphorus | Phospholane | Phosphole |
Selenium | Selenolane | Selenophene |
Silicon | Silacyclopentane | Silole |
Sulfur | Tetrahydrothiophene | Thiophene |
Tellurium | Tellurophene | |
Tin | Stannolane | Stannole |
Heteroatoms | Saturated | Unsaturated (and partially unsaturated) |
---|---|---|
2× nitrogen | Imidazolidine Pyrazolidine |
Imidazole (Imidazoline) Pyrazole (Pyrazoline) |
Oxygen + sulfur | 1,3-Oxathiolane 1,2-Oxathiolane |
Oxathiole (Oxathioline) Isoxathiole |
Nitrogen + Oxygen | Oxazolidine Isoxazolidine |
Oxazole (Oxazoline) Isoxazole |
Nitrogen + sulfur | Thiazolidine Isothiazolidine |
Thiazole (Thiazoline) Isothiazole |
2× oxygen | Dioxolane | |
2× sulfur | Dithiolane | Dithiole |
Heteroatoms | Saturated | Unsaturated |
---|---|---|
N N N | Triazoles | |
N N O | Furazan Oxadiazole | |
N N S | Thiadiazole | |
N O O | Dioxazole | |
N S S | Dithiazole | |
N N N N | Tetrazole | |
N N N N O | Oxatetrazole | |
N N N N S | Thiatetrazole | |
N N N N N | Pentazole |
6-membered rings
[edit]Heteroatom | Saturated | Unsaturated | Ions |
---|---|---|---|
Antimony | Stibinin[7] | ||
Arsenic | Arsinane | Arsinine | |
Bismuth | Bismin[8] | ||
Boron | Borinane | Borinine | Boratabenzene anion |
Germanium | Germinane | Germine | |
Nitrogen | Piperidine (Azinane not used) |
Pyridine (Azine not used) |
Pyridinium cation |
Oxygen | Oxane | Pyran (2H-Oxine not used) |
Pyrylium cation |
Phosphorus | Phosphinane | Phosphinine | |
Selenium | Selenane | Selenopyran[9] | Selenopyrylium cation |
Silicon | Silinane | Siline | |
Sulfur | Thiane | Thiopyran (2H-Thiine not used) |
Thiopyrylium cation |
Tellurium | Tellurane | Telluropyran | Telluropyrylium cation |
Tin | Stanninane | Stannine |
Heteroatom | Saturated | Unsaturated |
---|---|---|
Nitrogen / nitrogen | Diazinane | Diazine |
Oxygen / nitrogen | Morpholine | Oxazine |
Sulfur / nitrogen | Thiomorpholine | Thiazine |
Oxygen / Sulfur | Oxathiane | Oxathiin |
Oxygen / oxygen | Dioxane | Dioxine |
Sulfur / sulfur | Dithiane | Dithiin |
Boron / nitrogen | 1,2-Dihydro-1,2-azaborine |
Heteroatom | Saturated | Unsaturated |
---|---|---|
Nitrogen | Triazinane | Triazine |
Oxygen | Trioxane | |
Sulfur | Trithiane |
Heteroatom | Saturated | Unsaturated |
---|---|---|
Nitrogen | Tetrazine | |
2 nitrogen, 2 boron | Carborazine |
Heteroatom | Saturated | Unsaturated |
---|---|---|
Nitrogen | Pentazine |
Six-membered rings with six heteroatoms
[edit]The 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
[edit]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.
Heteroatom | Saturated | Unsaturated |
---|---|---|
Boron | Borepin | |
Nitrogen | Azepane | Azepine |
Oxygen | Oxepane | Oxepine |
Sulfur | Thiepane | Thiepine |
Heteroatom | Saturated | Unsaturated |
---|---|---|
Nitrogen | Diazepane | Diazepine |
Nitrogen/sulfur | Thiazepine |
8-membered rings
[edit]Heteroatom | Saturated | Unsaturated |
---|---|---|
Nitrogen | Azocane | Azocine |
Oxygen | Oxocane | Oxocine |
Sulfur | Thiocane | Thiocine |
4 nitrogen, 4 boron | Borazocine |
9-membered rings
[edit]Heteroatom | Saturated | Unsaturated |
---|---|---|
Nitrogen | Azonane | Azonine |
Oxygen | Oxonane | Oxonine |
Sulfur | Thionane | Thionine |
Images of rings with one heteroatom
[edit]Saturated | Unsaturated | ||||||
---|---|---|---|---|---|---|---|
Heteroatom | Nitrogen | Oxygen | Sulfur | Nitrogen | Oxygen | Sulfur | |
3-atom ring | Aziridine | Oxirane | Thiirane | Azirine | Oxirene | Thiirene | |
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4-atom ring | Azetidine | Oxetane | Thietane | Azete | Oxete | Thiete | |
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5-atom ring | Pyrrolidine | Oxolane | Thiolane | Pyrrole | Furan | Thiophene | |
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6-atom ring | Piperidine | Oxane | Thiane | Pyridine | Pyran | Thiopyran | |
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7-atom ring | Azepane | Oxepane | Thiepane | Azepine | Oxepine | Thiepine | |
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8-atom ring | Azocane | Oxocane | Thiocane | Azocine | Oxocine | Thiocine | |
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9-atom ring | Azonane | Oxonane | Thionane | Azonine | Oxonine | Thionine | |
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Fused/condensed rings
[edit]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
[edit]The history of heterocyclic chemistry began in the 1800s, in step with the development of organic chemistry. Some noteworthy developments:[10]
- 1818: Brugnatelli makes 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 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
[edit]Heterocyclic compounds are pervasive in many areas of life sciences and technology.[2] Many drugs are heterocyclic compounds.[11]
See also
[edit]References
[edit]- ^ IUPAC Gold Book heterocyclic compounds
- ^ a b Thomas L. Gilchrist "Heterocyclic Chemistry" 3rd ed. Addison Wesley: Essex, England, 1997. 414 pp. ISBN 0-582-27843-0.
- ^ Rees, Charles W. (1992). "Polysulfur-Nitrogen Heterocyclic Chemistry". Journal of Heterocyclic Chemistry. 29 (3): 639–651. doi:10.1002/jhet.5570290306.
- ^ Edon Vitaku, David T. Smith, Jon T. Njardarson (2014). "Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals". J. Med. Chem. 57 (24): 10257–10274. doi:10.1021/jm501100b. PMID 25255204.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "Hantzsch–Widman name". doi:10.1351/goldbook.H02737
- ^ Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York: Wiley-Interscience, ISBN 978-0-471-72091-1
- ^ "Stibinin". chemspider. Royal Society of Chemistry. Retrieved 11 June 2018.
- ^ "Bismin". ChemSpider. Royal Society of Chemistry. Retrieved 11 June 2018.
- ^ "Selenopyranium". ChemSpider. Royal Society of Chemistry. Retrieved 11 June 2018.
- ^ Campaigne, E. (1986). "Adrien Albert and the rationalization of heterocyclic chemistry". Journal of Chemical Education. 63 (10): 860. Bibcode:1986JChEd..63..860C. doi:10.1021/ed063p860.
- ^ "IPEXL.com Multilingual Patent Search, Patent Ranking". www.ipexl.com. Archived from the original on 24 September 2015. Retrieved 8 September 2010.
External links
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