spiro compound

{{Short description|Any chemical compound having one atom as the only common member of two rings}}

In organic chemistry, spiro compounds are compounds that have at least two molecular rings sharing one common atom. Simple spiro compounds are bicyclic (having just two rings).{{rp|SP-0}}{{cite book |author1=Clayden, Jonathan |author2=Greeves, Nick |author3=Warren, Stuart | year = 2012 | title = Organic Chemistry | edition = 2nd | pages = 319f, 432, 604, 653, 746, 803, 839, 846f | location = Oxford, UK | publisher = Oxford University Press | url = https://books.google.com/books?isbn=0199270295 | access-date = 2 February 2016 | isbn = 978-0-19-927029-3 }}{{rp|653,839}} The presence of only one common atom connecting the two rings distinguishes spiro compounds from other bicyclics.For all four categories, see {{cite book |author=Reusch, William |title=Virtual Text of Organic Chemistry |publisher=Michigan State University, Department of Chemistry |year=1999 |edition=Jan. 2016 |location=East Lansing, MI, USA |chapter=Saturated Hydrocarbons, Alkanes and Cycloalkanes: Cycloalkanes (Table: Examples of Isomeric C₈H₁₄ Bicycloalkanes) or Nomenclature: Cycloalkanes (same Table), and passim |access-date=3 February 2016 |chapter-url=https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/intro1.htm}} The specific chapters can be found at [https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/chapt5.htm] and [https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/nomen1.htm#nom2b], respectively, same access date. For the description featuring adjacent atoms for all but the isolated category, see Clayden, op. cit.{{rp|653ff}} {{rp|839ff}} Spiro compounds may be fully carbocyclic (all carbon) or heterocyclic (having one or more non-carbon atom). One common type of spiro compound encountered in educational settings is a heterocyclic one— the acetal formed by reaction of a diol with a cyclic ketone.

The common atom that connects the two (or sometimes three) rings is called the spiro atom.{{rp|SP-0}} In carbocyclic spiro compounds like spiro[5.5]undecane, the spiro-atom is a quaternary carbon, and as the -ane ending implies, these are the types of molecules to which the name spirane was first applied (though it is now used general of all spiro compounds).{{rp|1138ff}} The two rings sharing the spiro atom are most often different, although they can be identical [e.g., spiro[5.5]undecane and spiropentadiene, at right].{{rp|319f.846f}}

Selected spiro compounds

Elatol.png | 1. Elatol, isolated from Laurencia dendroidea (red algae){{cite journal |author1=Smith, Laura K. |author2=Baxendale, Ian R. |name-list-style=amp | year = 2015 | title = Total Syntheses of Natural Products Containing Spirocarbocycles | journal = Org. Biomol. Chem. | volume = 13 |issue=39 | pages = 9907–9933 | doi = 10.1039/C5OB01524C |pmid=26356301 | doi-access = free }}

Spironolactone.svg | 2. Spironolactone, a commercial diuretic medication

Spiro-C5H4.png | 3. Spiropentadiene, which is highly strained.{{cite web |date=13 July 1991 |title = Elusive bowtie pinned down |website=The Free Library |url=http://www.thefreelibrary.com/Elusive+bowtie+pinned+down.-a011134368 | access-date = 2 February 2016}}

Spiroverbindung Nomenklatur.svg | 4. (A) 1-Bromo-3-chlorospiro[4.5]decan-7-ol, and (B) '1-bromo-3-chlorospiro[3.6]decan-7-ol.

Carbocyclic spiro compounds

Bicyclic ring structures in organic chemistry that have two fully carbocyclic (all carbon) rings connected through a carbon atom are the usual focus of the topic of spirocycles. Simple parent spirocycles include spiropentane, spirohexane, etc. up to spiroundecane. Several exist as isomers. Lower members of the class are strained. The symmetric isomer of spiroundecane is not.

Some spirocyclic compounds occur as natural products.

=Preparation=

File:FechtEster.svg.|320px]]

File:SpiroC11.svg

The spirocyclic core is usually prepared by dialkylation of an activated carbon center. The dialkylating group is often a 1,3-, 1,4-, etc. dihalide.{{cite journal |doi=10.15227/orgsyn.080.0144 |title=Synthesis and [3+2] Cycloaddition of a 2,2-Dialkoxy-1-methylenecyclopropane: 6,6-Dimethyl-1-methylene-4,8-Dioxaspiro[2.5]octane and cis-5-(5,5-Dimethyl-1,3-dioxan-2-ylidene)hexahydro-1(2H)-pentalen-2-one |journal=Organic Syntheses |date=2003 |volume=80 |page=144|first1=Masaharu |last1=Nakamura |first2=Xiao Qun |last2=Wang |first3=Masahiko |last3=Isaka |first4=Shigeru |last4=Yamago |first5=Eiichi |last5=Nakamura }} In some cases the dialkylating group is a dilithio reagent, such as 1,5-dilithiopentane.{{cite journal |doi=10.15227/orgsyn.070.0204 |title=Spiroannelation Via Organobis(Cuprates): 9,9-Dimethylspiro[4.5]Decan-7-One |journal=Organic Syntheses |date=1992 |volume=70 |page=204| first1=Paul A. |last1=Wender |first2=Alan W. |last2=White |first3=Frank E. |last3=McDonald

}} For generating spirocycles containing a cyclopropane ring, cyclopropanation with cyclic carbenoids has been demonstrated.{{cite journal |doi=10.15227/orgsyn.101.0061 |title=Preparation of a Radical Clocks Bearing Carbonyl Groups: Synthesis of N-Methoxy-N-methylspiro[cyclopropane-1,9'-fluorene]-2-carboxamide |date=2024 |last1=Bartolo |first1=Nicole D. |first2=Ryan N. |last2=Robson|first3=Collin H. |last3=Witt|first4=K. A. |last4=Woerpel|journal=Organic Syntheses |volume=101 |pages=61–80 |pmc=11326668 }}

Spiro compounds are often prepared by diverse rearrangement reactions. For example, the pinacol-pinacolone rearrangement is illustrated below.{{rp|985}} is employed in the preparation of aspiro[4.5]decane.{{cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/291783#section=Top|title=1,1'-Bicyclopentyl-1,1'-diol|author=Pubchem|work=nih.gov|access-date=7 March 2016}}].

File:The synthesis of a spiro-keto compound form a symmetrical diol.png

Heterocyclic spiro compounds

Image:Ketal Synthesis V.1.svg

Spiro compounds are considered heterocyclic if the spiro atom or any atom in either ring are not carbon atoms. Cases with a spiro heteroatom such as boron, silicon, and nitrogen (but also other Group IVA [14] are often trivial to prepare. Many borate esters derived from glycols illustrate this case.{{cite journal |doi=10.15227/orgsyn.087.0026 |title=Synthesis of Spiroborate Esters from 1,2-Aminoalcohols, Ethylene Glycol and Triisopropyl Borate: Preparation of (S)-1-(1,3,2-Dioxaborolan-2-Yloxy)-3-Methyl-1,1-Diphenylbutan-2-Amine |journal=Organic Syntheses |date=2010 |volume=87 |page=26|author=Viatcheslav Stepanenko, Kun Huang, Margarita Ortiz-Marciales |pmc=2915795 }} Likewise, a tetravalent neutral silicon and quaternary nitrogen atom (ammonium cation) can be the spiro center. Many such compounds have been described.{{rp|1139f}}

Particularly common spiro compounds are ketal (acetal) formed by condensation of cyclic ketones and diols and dithiols.{{cite journal |doi=10.15227/orgsyn.093.0210 |title=Preparation of 1,5-Dioxaspiro[5.5]undecan-3-one |date=2016 |last1=Craig |first1=Robert |last2=Smith |first2=R. C. |last3=Pritchett |first3=B. P. |last4=Estipona |first4=B. I. |last5=Stoltz |first5=B. M. |journal=Organic Syntheses |volume=93 |pages=210–227 |pmid=28729749 |pmc=5514842 }}{{cite journal |doi=10.15227/orgsyn.071.0063 |title=Stereocontrolled Preparation of 3-Acyltetrahydrofurans from Acid-Promoted Rearrangements of Allylic Ketals: (2S,3S)-3-Acetyl-8-Carboethoxy-2,3-Dimethyl-1-Oxa-8-Azaspiro[4.5]Decane |journal=Organic Syntheses |date=1993 |volume=71 |page=63 }}{{cite journal |doi=10.15227/orgsyn.064.0073 |title=Dichlorovinylation of an Enolate: 8-Ethynyl-8-Methyl-1,4-Dioxaspiro[4.5]Dec-6-Ene |journal=Organic Syntheses |date=1986 |volume=64 |page=73 }} A simple case is the acetal 1,4-dioxaspiro[4.5]decane from cyclohexanone and glycol. Cases of such ketals and dithioketals are common.

Chirality

File:Spiroverbindung Chiralität.svg

Spiranes can be chiral,{{cite journal | author = Rios, Ramon | year = 2012 | title = Enantioselective Methodologies for the Synthesis of Spiro Compounds | journal = Chemical Society Reviews | volume = 41 | issue = 3 | pages = 1060–1074 | doi = 10.1039/C1CS15156H | pmid = 21975423 }} in various ways.{{rp|1138ff}} First, while nevertheless appearing to be twisted, they yet may have a chiral center making them analogous to any simple chiral compound, and second, while again appearing twisted, the specific location of substituents, as with alkylidenecycloalkanes, may make a spiro compound display central chirality (rather than axial chirality resulting from the twist); third, the substituents of the rings of the spiro compound may be such that the only reason they are chiral arises solely from the twist of their rings, e.g., in the simplest bicyclic case, where two structurally identical rings are attached via their spiro atom, resulting in a twisted presentation of the two rings.{{rp|1138ff,1119ff}}{{rp|319f.846f}} Hence, in the third case, the lack of planarity described above gives rise to what is termed axial chirality in otherwise identical isomeric pair of spiro compounds, because they differ only in the right- versus left-handed "twist" of structurally identical rings (as seen in allenes, sterically hindered biaryls, and alkylidenecycloalkanes as well).{{rp|1119f}} Assignment of absolute configuration of spiro compounds has been challenging, but a number of each type have been unequivocally assigned.{{rp|1139ff}}

Some spiro compounds exhibit axial chirality. Spiroatoms can be the origin of chirality even when they lack the required four different substituents normally observed in chirality. When two rings are identical the priority is determined by a slight modification of the CIP system assigning a higher priority to one ring extension and a lower priority to an extension in the other ring. When rings are dissimilar the regular rules apply.{{clarify|date=February 2016}}

Nomenclature and etymology

Nomenclature for spiro compounds was first discussed by Adolf von Baeyer in 1900.{{Cite journal|doi=10.1002/cber.190003303187|first=Adolf |last=von Baeyer|author1-link=Adolf von Baeyer|title=Systematik und Nomenclatur Bicyclischer Kohlenwasserstoffe|volume= 33|pages= 3771–3775|year=1900|journal=Berichte der Deutschen Chemischen Gesellschaft|issue=3|url=https://zenodo.org/record/1425984 }}

IUPAC provides advice on naming of spiro compounds.{{cite journal |author=Moss, G.P. |title=Extension and Revision of the Nomenclature for Spiro Compounds |journal=Pure Appl. Chem. | volume = 71 | issue = 3 | pages = 531–558 | year = 1999 | doi = 10.1351/pac199971030531 | s2cid = 20131819 | issn = 1365-3075| doi-access = free }} The full author (Working Party) list and a link to a German translation are provided in a corresponding footnote. Also available online at {{cite web |url= http://www.chem.qmul.ac.uk/iupac/spiro/ |title= Extension and Revision of the Nomenclature for Spiro Compounds | publisher= Queen Mary University of London | location= London, GBR }}

The prefix spiro denotes two rings with a spiro junction. The main method of systematic nomenclature is to follow with square brackets containing the number of atoms in the smaller ring then the number of atoms in the larger ring, separated by a period, in each case excluding the spiroatom (the atom by which the two rings are bonded) itself. Position-numbering starts with an atom of the smaller ring adjacent to the spiroatom around the atoms of that ring, then the spiroatom itself, then around the atoms of the larger ring.{{cite web |url= https://www.acdlabs.com/iupac/nomenclature/79/r79_197.htm |title= Spiro Hydrocarbons. Rule A-41. Compounds: Method 1 }} For example, compound A in Image #4 above (Selected Spiro Compounds) is called 1-bromo-3-chlorospiro[4.5]decan-7-ol, and compound B is called 1-bromo-3-chlorospiro[3.6]decan-7-ol.

A spiro compound, or spirane, from the Latin spīra, meaning a twist or coil,Eliel, et al., op. cit., introduces the synonym spirane and the Latin and translation as twist or whorl; Lewis' dictionary, op. cit., speaking to basic definitions in ancient use, and provides the vowel marking and definitions of coil, fold, twist, or spiral.{{cite book |author1=Eliel, Ernest Ludwig |title=Stereochemistry of Organic Compounds |author2=Wilen, Samuel H. |author3=Mander, Lewis N. |publisher=Wiley & Sons |year=1994 |isbn=978-0-471-01670-0 |edition=1st |location=New York, NY, USA |pages=1119–1190, esp. 1119ff, 1138ff; and passim |chapter=Chirality in Molecules Devoid of Chiral Centers (Chapter 14) |access-date=2 February 2016 |chapter-url=https://books.google.com/books?id=IyfwAAAAMAAJ}} For a further but less stable source of the same text that provides access to the relevant material, see [https://www.amazon.com/Stereochemistry-Organic-Compounds-Ernest-Eliel/dp/0471016705/ref=sr_1_1?s=books&ie=UTF8&qid=1454600262&sr=1-1&keywords=Stereochemistry+of+Organic+Compounds+Eliel], same access date.{{rp|1138}}{{cite book |author=Lewis, Charlton T. | year = 1890 | title = An Elementary Latin Dictionary | chapter = spīra [dictionary entry] | location = New York, NY, USA | publisher = American Book Company | chapter-url = https://www.perseus.tufts.edu/hopper/text?doc=Perseus%3Atext%3A1999.04.0060%3Aalphabetic+letter%3DS%3Aentry+group%3D20%3Aentry%3Dspira | access-date = 3 February 2016 | quote = "Quoting: 'spīra ae, f, σπεῖρα, a coil, fold, twist, spiral: in spirain se conligit anguis, V., O.: longo iactetur spira galero, i. e. tie, Iu.'" }} The Greek transcription, σπεῖρα, reflects the use of this cognate as one ancient Greek term to refer to a coil or related fold, see {{cite book |author=Woodhouse, S.C. | year = 1910 | title = English-Greek Dictionary: A Vocabulary of the Attic Language | chapter = Fold, subs. [dictionary entry] | location = Ludgate Hill [London, ENG] | publisher = George Routledge & Sons | chapter-url = http://artflsrv02.uchicago.edu/cgi-bin/efts/dicos/woodhouse_test.pl?keyword=^Fold,%20subs. | access-date = 3 February 2016 | quote = "Quoting: 'Fold, subs. … Coil : V. σπεῖρα… see coil.' "}} is a chemical compound, typically an organic compound, that presents a twisted structure of two or more rings (a ring system), in which 2 or 3 rings are linked together by one common atom,{{cite journal |author=Moss, G.P. |title=Extension and Revision of the Nomenclature for Spiro Compounds |journal=Pure Appl. Chem. | volume = 71 | issue = 3 | pages = 531–558 | year = 1999 | doi = 10.1351/pac199971030531 | s2cid = 20131819 | issn = 1365-3075| doi-access = free }} Note, the article co-authors, the Working Party of the IUPAC (1992-1998), were P. M. Giles, Jr., E. W. Godly, K.-H. Hellwich, A. K. Ikizler, M. V. Kisakürek, A. D. McNaught, G. P. Moss, J. Nyitrai, W. H. Powell, O. Weissbach, and A. Yerin. Also available online at {{cite web |url= http://www.chem.qmul.ac.uk/iupac/spiro/ |title= Extension and Revision of the Nomenclature for Spiro Compounds |publisher= Queen Mary University of London |location= London, GBR |access-date= 3 February 2016 }} Also available in German, with et al. indicating the same working party, at {{cite journal |author=Hellwich, Karl-Heinz | title = Erweiterung und Revision der Nomenklatur der Spiroverbindungen | journal = Angewandte Chemie | volume = 114 | issue = 20 | pages = 4073–4089 | date = 18 October 2002 | doi = 10.1002/1521-3757(20021018)114:20<4073::AID-ANGE4073>3.0.CO;2-T | bibcode = 2002AngCh.114.4073H | quote = Die Übersetzung basiert auf der "Extension and Revision of the Nomenclature for Spiro Compounds" der Commission on Nomenclature of Organic Chemistry (III.1) der Organic Chemistry Division der International Union of Pure and Applied Chemistry, veröffentlicht in Pure Appl. Chem. 1999, 71, 531–558.|display-authors=etal}}{{rp|SP-0}}