Cyclic compound#Ring-closing reactions

A cyclic compound or ring compound is a compound in which at least some its atoms are connected to form a ring.{{JerryMarch}}{{page needed|date=June 2015}} Rings vary in size from three to many tens or even hundreds of atoms. Examples of ring compounds readily include cases where:

• all the atoms are carbon (i.e., are carbocycles),
• none of the atoms are carbon (inorganic cyclic compounds),{{cite journal |doi=10.1007/BF01141802 |title=Classification of inorganic cyclic compounds |journal=Journal of Structural Chemistry |volume=2 |issue=3 |pages=350–8 |year=1961 |last1=Halduc |first1=I. |bibcode=1961JStCh...2..350H |s2cid=93804259 }} or where
• both carbon and non-carbon atoms are present (heterocyclic compounds with rings containing both carbon and non-carbon).

Common atoms can (as a result of their valences) form varying numbers of bonds, and many common atoms readily form rings. In addition, depending on the ring size, the bond order of the individual links between ring atoms, and their arrangements within the rings, cyclic compounds may be aromatic or non-aromatic; in the case of non-aromatic cyclic compounds, they may vary from being fully saturated to having varying numbers of multiple bonds. As a consequence of the constitutional variability that is thermodynamically possible in cyclic structures, the number of possible cyclic structures, even of small size (e.g., <17 atoms) numbers in the many billions.{{cite journal |doi=10.1021/ar500432k |pmid=25687211 |title=The Chemical Space Project |journal=Accounts of Chemical Research |volume=48 |issue=3 |pages=722–30 |year=2015 |last1=Reymond |first1=Jean-Louis |doi-access=free }}

Moreover, the closing of atoms into rings may lock particular functional group–substituted atoms into place, resulting in stereochemistry and chirality being associated with the compound, including some manifestations that are unique to rings (e.g., configurational isomers);{{cite book | author = William Reusch | date = 2010 | title = "Stereoisomers Part I" in Virtual Textbook of Organic Chemistry | publisher = Michigan State University | url = http://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/sterisom.htm#start | access-date = 7 April 2015 | archive-date = 10 March 2015 | archive-url = https://web.archive.org/web/20150310162343/http://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/sterisom.htm#start | url-status = live }} As well, depending on ring size, the three-dimensional shapes of particular cyclic structures — typically rings of five atoms and larger — can vary and interconvert such that conformational isomerism is displayed.

The vast majority of cyclic compounds are organic, and of these, a significant and conceptually important portion are composed of rings made only of carbon atoms (i.e., they are carbocycles).{{citation needed|date=April 2015}}

Inorganic atoms form cyclic compounds as well. Examples include sulfur and nitrogen (e.g. heptasulfur imide {{chem2|S7NH}}, trithiazyl trichloride {{chem2|(NSCl)3}}, tetrasulfur tetranitride {{chem2|S4N4}}), silicon (e.g., cyclopentasilane {{chem2|(SiH2)5}}), phosphorus and nitrogen (e.g., hexachlorophosphazene {{chem2|(NPCl2)3}}), phosphorus and oxygen (e.g., metaphosphates {{chem2|(PO3−)3}} and other cyclic phosphoric acid derivatives), boron and oxygen (e.g., sodium metaborate {{chem2|Na3(BO2)3}}, borax), boron and nitrogen (e.g. borazine {{chem2|(BN)3H6}}).{{citation needed|date=April 2015}} When carbon in benzene is "replaced" by other elements, e.g., as in borabenzene, silabenzene, germanabenzene, stannabenzene, and phosphorine, aromaticity is retained, and so aromatic inorganic cyclic compounds are also known and well-characterized.{{citation needed|date=April 2015}}

A heterocyclic compound is a cyclic compound that has atoms of at least two different elements as members of its ring(s).IUPAC Gold Book [http://goldbook.iupac.org/H02798.html heterocyclic compounds] Cyclic compounds that have both carbon and non-carbon atoms present are heterocyclic carbon compounds, and the name refers to inorganic cyclic compounds as well (e.g., siloxanes, which contain only silicon and oxygen in the rings, and borazines, which contain only boron and nitrogen in the rings). Hantzsch–Widman nomenclature is recommended by the IUPAC for naming heterocycles, but many common names remain in regular use.{{citation needed|date=April 2015}}

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The term macrocycle is used for compounds having a rings of 8 or more atoms.{{cite journal |last1=Still |first1=W.Clark |last2=Galynker |first2=Igor |year=1981 |title=Chemical consequences of conformation in macrocyclic compounds |journal=Tetrahedron |volume=37 |issue=23 |pages=3981–96 |doi=10.1016/S0040-4020(01)93273-9}}{{cite book |author=J. D. Dunitz |title=Perspectives in Structural Chemistry |date=1968 |publisher=Wiley |editor=J. D. Dunitz and J. A. Ibers |volume=2 |location=New York |pages=1–70}} Macrocycles may be fully carbocyclic (rings containing only carbon atoms, e.g. cyclooctane), heterocyclic containing both carbon and non-carbon atoms (e.g. lactones and lactams containing rings of 8 or more atoms), or non-carbon (containing only non-carbon atoms in the rings, e.g. diselenium hexasulfide). Heterocycles with carbon in the rings may have limited non-carbon atoms in their rings (e.g., in lactones and lactams whose rings are rich in carbon but have limited number of non-carbon atoms), or be rich in non-carbon atoms and displaying significant symmetry (e.g., in the case of chelating macrocycles). Macrocycles can access a number of stable conformations, with preference to reside in conformations that minimize transannular nonbonded interactions within the ring (e.g., with the chair and chair-boat being more stable than the boat-boat conformation for cyclooctane, because of the interactions depicted by the arcs shown).{{citation needed|date=April 2015}} Medium rings (8-11 atoms) are the most strained, with between 9-13 (kcal/mol) strain energy, and analysis of factors important in the conformations of larger macrocycles can be modeled using medium ring conformations.Eliel, E.L., Wilen, S.H. and Mander, L.S. (1994) Stereochemistry of Organic Compounds, John Wiley and Sons, Inc., New York.{{page needed|date=April 2015}} Conformational analysis of odd-membered rings suggests they tend to reside in less symmetrical forms with smaller energy differences between stable conformations.{{cite journal |last1=Anet |first1=F.A.L. |last2=St. Jacques |first2=M. |last3=Henrichs |first3=P.M. |last4=Cheng |first4=A.K. |last5=Krane |first5=J. |last6=Wong |first6=L. |year=1974 |title=Conformational analysis of medium-ring ketones |journal=Tetrahedron |volume=30 |issue=12 |pages=1629–37 |doi=10.1016/S0040-4020(01)90685-4}}

File:Macrocycles 2revEnglUse.jpg, 18-crown-6; B, the simple tetra-aza chelator, cyclam; C, an example porphyrin, the unsubstituted porphine; D, a mixed amine/imine, the Curtis macrocycle; E, the related enamine/imine Jäger macrocycle, and F, the tetracarboxylate-derivative DOTA macrocycle.]]

IUPAC nomenclature has extensive rules to cover the naming of cyclic structures, both as core structures, and as substituents appended to alicyclic structures.{{citation needed|date=April 2015}} The term macrocycle is used when a ring-containing compound has a ring of 12 or more atoms. The term polycyclic is used when more than one ring appears in a single molecule. Naphthalene is formally a polycyclic compound, but is more specifically named as a bicyclic compound. Several examples of macrocyclic and polycyclic structures are given in the final gallery below.

{{anchor|annular atom}}The atoms that are part of the ring structure are called annular atoms.{{cite book |last1=Morris |first1=Christopher G. |url=https://books.google.com/books?id=nauWlPTBcjIC&pg=PA120 |title=Academic Press Dictionary of Science and Technology |last2=Press |first2=Academic |publisher=Gulf Professional Publishing |year=1992 |isbn=9780122004001 |page=120 |language=en |access-date=2020-09-14 |archive-url=https://web.archive.org/web/20210413203802/https://books.google.com/books?id=nauWlPTBcjIC&pg=PA120 |archive-date=2021-04-13 |url-status=live}}

The closing of atoms into rings may lock particular atoms with distinct substitution by functional groups such that the result is stereochemistry and chirality of the compound, including some manifestations that are unique to rings (e.g., configurational isomers).

{{Image frame|width=200|content=200px

|caption=Two conformers of cyclohexane, the chair at left, and the boat at right. Axial and equatorial hydrogen atoms are denoted with an a and e, respectively.}}

Depending on ring size, the three-dimensional shapes of particular cyclic structures—typically rings of 5-atoms and larger—can vary and interconvert such that conformational isomerism is displayed. Indeed, the development of this important chemical concept arose, historically, in reference to cyclic compounds. For instance, cyclohexanes—six membered carbocycles with no double bonds, to which various substituents might be attached, see image—display an equilibrium between two conformations, the chair and the boat, as shown in the image.

The chair conformation is the favored configuration, because in this conformation, the steric strain, eclipsing strain, and angle strain that are otherwise possible are minimized. Which of the possible chair conformations predominate in cyclohexanes bearing one or more substituents depends on the substituents, and where they are located on the ring; generally, "bulky" substituents—those groups with large volumes, or groups that are otherwise repulsive in their interactions{{citation needed|date=June 2015}}—prefer to occupy an equatorial location. An example of interactions within a molecule that would lead to steric strain, leading to a shift in equilibrium from boat to chair, is the interaction between the two methyl groups in cis-1,4-dimethylcyclohexane. In this molecule, the two methyl groups are in opposing positions of the ring (1,4-), and their cis stereochemistry projects both of these groups toward the same side of the ring. Hence, if forced into the higher energy boat form, these methyl groups are in steric contact, repel one another, and drive the equilibrium toward the chair conformation.

Because of the unique shapes, reactivities, properties, and bioactivities that they engender, cyclic compounds are the largest majority of all molecules involved in the biochemistry, structure, and function of living organisms, and in the man-made molecules (e.g., drugs, herbicides, etc.) through which man attempts to exert control over nature and biological systems.

Image:Dieckmann condensation scheme.svg

There are a variety of specialized reactions whose use is solely the formation of rings, and these will be discussed below. In addition to those, there are a wide variety of general organic reactions that historically have been crucial in the development, first, of understanding the concepts of ring chemistry, and second, of reliable procedures for preparing ring structures in high yield, and with defined orientation of ring substituents (i.e., defined stereochemistry). These general reactions include:

• Acyloin condensation;
• Anodic oxidations; and
• the Dieckmann condensation as applied to ring formation.

In organic chemistry, a variety of synthetic procedures are particularly useful in closing carbocyclic and other rings; these are termed ring-closing reactions. Examples include:

• alkyne trimerisation;
• the Bergman cyclization of an enediyne;
• the Diels–Alder, between a conjugated diene and a substituted alkene, and other cycloaddition reactions;
• the Nazarov cyclization reaction, originally being the cyclization of a divinyl ketone;
• various radical cyclizations;
• ring-closing metathesis reactions, which also can be used to accomplish a specific type of polymerization;
• the Ruzicka large ring synthesis, in which two carboxyl groups combine to form a carbonyl group with loss of {{chem2|CO2}} and {{chem2|H2O}};
• the Wenker synthesis converting a beta amino alcohol to an aziridine

A variety of further synthetic procedures are particularly useful in opening carbocyclic and other rings, generally which contain a double bond or other functional group "handle" to facilitate chemistry; these are termed ring-opening reactions. Examples include:

• ring opening metathesis, which can also be used to accomplish a specific type of polymerization.

{{Main|Ring expansion and ring contraction}}

Ring expansion and contraction reactions are common in organic synthesis, and are frequently encountered in pericyclic reactions. Ring expansions and contractions can involve the insertion of a functional group such as the case with Baeyer–Villiger oxidation of cyclic ketones, rearrangements of cyclic carbocycles as seen in intramolecular Diels-Alder reactions, or collapse or rearrangement of bicyclic compounds as several examples.

The following are examples of simple and aromatic carbocycles, inorganic cyclic compounds, and heterocycles:

Image:Benzene-6H-delocalized.svg | Benzene, a 6-membered carbocyclic organic compound, methine hydrogens shown, and 6 electrons shown as delocalized through drawing of circle (aromatic).

Image:Cycloheptane.png | Cycloheptane, a simple 7-membered carbocyclic compound, methylene hydrogens shown (non-aromatic).

Image:Cyclooctasulfur_structural_formula_3D.svg | Cyclo-octasulfur, an 8-membered inorganic cyclic compound (non-aromatic).

Image:1,3-Selenium hexasulfide.png|Diselenium hexasulfide, an 8-membered inorganic heterocyclic compound (non-aromatic).

Image:Pentasilolane.svg|Cyclopentasilane, a 5-membered inorganic cyclic compound (non-aromatic).

Image:Hexamethylcyclotrisiloxan.svg|Hexamethylcyclotrisiloxane, a 6-membered organic heterocyclic compound (non-aromatic).

Image:Hexachlorotriphosphazene-2D-dimensions.png|Hexachlorophosphazene, a 6-membered inorganic heterocyclic compound (aromatic).

Image:Borazine-dimensions-2D.svg|Borazine, a 6-membered inorganic heterocyclic compound (may be aromatic).

Image:Pentazole.svg | Pentazole, a 5-membered inorganic cyclic compound (aromatic).

Image:Azetidine structure.svg| Azetidine, a 4-membered nitrogen (aza) heterocyclic compound, methylene hydrogen atoms implied, not shown (non-aromatic).

Image:Pyridine.svg|Pyridine, a 6 membered heterocyclic compound, methine hydrogen atoms implied, not shown, and delocalized π-electrons shown as discrete bonds (aromatic).

Image:Azepine-2D-skeletal.png|Azepine, a 7-membered heterocyclic organic compound (non-aromatic).

The following are examples of cyclic compounds exhibiting more complex ring systems and stereochemical features:

Image:Naphtalene topo.svg | Naphthalene, technically a polycyclic, more specifically a bicyclic compound, with circles showing delocalization of π-electrons (aromatic).

Image:Cis-trans isomerism of decahydronaphthalene.svg | Decalin (decahydronaphthalene), the fully saturated derivative of naphthalene, showing the two stereochemistries possible for "fusing" the two rings together, and how this impacts the shapes available to this bicyclic compound (non-aromatic).

Image:Longifolene plus acsv.svg|Longifolene, a terpene natural product, and an example of a tricyclic molecule (non-aromatic).

Image:TaxolNumberingScheme.svg | Paclitaxel, a polycyclic natural product with a tricyclic core: with a heterocyclic, 4-membered D ring, fused to further 6- and 8-membered carbocyclic (A/C and B) rings (non-aromatic), and with three further pendant phenyl-rings on its "tail", and attached to C-2 (abbrev. Ph, C₆H₅; aromatics).

Image:Paclitaxel_JMolBiol_2001_1045.jpg | A representative three-dimensional shape adopted by paclitaxel, as a result of its unique cyclic structure.{{cite journal |doi=10.1006/jmbi.2001.5077 |pmid=11700061 |title=Refined structure of αβ-tubulin at 3.5 Å resolution |journal=Journal of Molecular Biology |volume=313 |issue=5 |pages=1045–57 |year=2001 |last1=Löwe |first1=J |last2=Li |first2=H |last3=Downing |first3=K.H |last4=Nogales |first4=E |url=https://zenodo.org/record/1229896 |access-date=2020-09-14 |archive-date=2021-01-22 |archive-url=https://web.archive.org/web/20210122161041/https://zenodo.org/record/1229896 |url-status=live }}

Image:Cholesterol.svg|Cholesterol, another terpene natural product, in particular, a steroid, a class of tetracyclic molecules (non-aromatic).

Image:Benzo-a-pyrene.svg|Benzo[a]pyrene, a pentacyclic compound both natural and man-made, and delocalized π-electrons shown as discrete bonds (aromatic).

Image:Pagodane.svg|Pagodane, a complex, highly symmetric, man-made polycyclic compound (non-aromatic).

Image:Brevetoxin A.svg|Brevetoxin A, a natural product with ten rings, all fused, and all heterocyclic, and a toxic component associated with the organisms responsible for red tides. The R group at right refers to one of several possible four-carbon side chains (see main Brevetoxin article; non-aromatic).

• Effective molarity
• Lactone
• Open-chain compound

• Jürgen-Hinrich Fuhrhop & Gustav Penzlin, 1986, "Organic synthesis: concepts, methods, starting materials," Weinheim, BW, DEU:VCH, {{ISBN|0895732467}}, see [https://books.google.com/books?id=lJbgAAAAMAAJ], accessed 19 June 2015.
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• {{MeshName|Polycyclic+Compounds}}
• {{MeshName|Macrocyclic+Compounds}}

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Category:Molecular geometry