Spiro compound

Spiro compounds have at least two

molecular rings with only one
common atom. The simplest spiro
compounds are bicyclic (having just
two rings), or have a bicyclic portion
as part of the larger ring system, in
Preparation of a heterocyclic spiro compound. Each molecule
either case with the two rings
shown in line-angle representation, where each angle (vertex)
connected through the defining single represents a carbon atom, and each line a bond between atoms (and
common atom.[3]: SP-0 [4]: 653, 839 The where necessary hydrogen atoms to fulfill carbon's valence of four
one common atom connecting the are implied). The heterocyclic spiro product, at right of arrow, is a
participating rings distinguishes spiro common ketal (acetal) structure prepared from a monocyclic type of
compounds from other bicyclics: from ketone and a generally acyclic type of diol (both at left of arrow). The
isolated ring compounds like schematic is for the synthesis of the protected 1,4-
biphenyl that have no connecting dioxaspiro[4.5]decane[1] from cyclohexanone and the alcohol,
atoms, from fused ring compounds ethanediol. Note the apparent planarity, which masks the actual
like decalin having two rings linked orthogonal orientation of the two rings.
by two adjacent atoms, and from
bridged ring compounds like
norbornane with two rings linked by two non-adjacent atoms.[5][4]: 653ff : 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;[3]: SP-0 in carbocyclic spiro compounds like
spiro[5.5]undecane (see image at right), 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).[6]: 1138ff Likewise, a tetravalent neutral silicon or positively charged
quaternary nitrogen atom (ammonium cation) can be the spiro center in these compounds, and many of
these have been prepared and described.[6]: 1139f The 2-3 rings being joined are most often different in
nature, though they, on occasion, be identical [e.g., spiro[5.5]undecane, just shown, and spiropentadiene, at
right]. Although sketches of organic structures makes spiro compounds appear planar, they are not; for
instance, a spiro compound with a pair of three-membered cyclopropene rings connected in spiro fashion
(image below) has been given the popular misnomer of being a bow tie structure, when it is not flat or
planar like a bow tie. This can be stated another way, saying that the best-fit planes to each ring are often
perpendicular or are otherwise non-coplanar to one another.[4]: 319f.846f

Spiro compounds are present throughout the natural world, some cases of which have been exploited to
provide tool compounds for biomedical study and to serve as scaffolds for the design of therapeutic agents
with novel shapes. As well, the spiro motif is present in various practical compound types (such as dyes), as
well as in a wide variety of oligo- and polymeric materials designs, for the unique shapes and properties the
spiro center imparts, e.g., in the design of electronically active materials in particular. In both cases, the
presence of the spiro center, often with four distinct groups attached, and with its unique aspects of chirality,
adds unique challenges to the chemical synthesis of each compound type.

Contents
 Carbocyclic spiro compounds
Heterocyclic spiro compounds
Polyspiro compounds
Nomenclature
Chirality
Preparation
Specific methods
Uses
Spiroaromaticity
Etymology
Further reading
References
A fully carbo-cyclic
External links
spiro compound.
Spiro[5.5]undecane,[2]
again shown in line-
Carbocyclic spiro compounds angle representation
and in apparent
Bicyclic ring structures in organic chemistry that have two fully carbocyclic (all planarity, masking
carbon) rings connected through just one atom are present both in natural the actual most
products,[7] as well as in esoteric targets of chemical synthesis. The two populated chair
carbocycles can be different in nature, or identical. In common targets derived conformation of
each ring, and their
from natural products, they are essentially always different.[7] In esoteric targets,
actual orthogonal
such as highly strained hydrocarbons like spiropentadiene, shown here, the rings
orientation to one
can be identical. The atom connecting the two rings is called the spiro-atom; in
another.
carbocyclic spiro compounds, the spiro-atom is a quaternary carbon. The 11-
carbon bicyclic structure shown above, spiro[5.5]undecane, is also a fully
carbocyclic spiro compound. While the presentation of this structure makes it
appear fully planar, it is not. The best-fit planes to each six-atom ring above is near
to perpendicular, and the best-fit planes to rings of spiro compounds are likewise
generally non-coplanar. For instance, the structure of faux bow tie spiropentadiene,
shown above, makes clear that the planes that are defined by the atoms of each
ring—i.e., the best-fit plane of each cyclopropene—are orthogonal (perpendicular)
to one another.[8] A fully carbocyclic
spiro compound.
Heterocyclic spiro compounds Spiropentadiene, an
esoteric
hydrocarbon, in a
Spiro compounds are considered heterocyclic if the spiro atom or any atom in representation where
either ring are not carbon atoms. Cases include the presence of a spiro heteroatom all carbons and
such silicon and nitrogen (but also other Group IVA [14] and other atom types) hydrogens are
connecting the rings that have been observed or are under theoretical shown explicitly. The
study;[6]: 1139f moreover, there are also many cases where one or more two cyclopropene
heteroatoms appear in one or more of the rings that are joined at a carbon spiro rings are each
atom (e.g., where 1 oxygen spironolactones and 2 oxygen/2 sulfur ketals/thioketals planar, but are
are very common).[9] perpendicular to
each other.
A common case is the presence of two atoms that are not carbon in one of
the rings, with those two rings both attached to the spiro atom; indeed,
often the earliest exposure of a chemist in training to a spiro compound is
to a heterocyclic form, the ketal (acetal) formed in the protection of ketones
by diols and dithiols. An example of this is shown above, in the synthesis
of the acetal 1,4-dioxaspiro[4.5]decane from cyclohexanone and
ethanediol. In this case, because the four atoms attached to the spiro atom
are not all carbons, the spiro atom is not a quaternary carbon. A further The Brazilian Laurencia
example of an acetal formed from a cyclic ketone, except with a dithiol, is dendroidea (red algae)
the spiro compound spirapril, which has a five-membered ring formed sesquiterpene and
from 1,2-ethanedithiol. Again, while the rings could be identical, in the halogenated carbocyclic
heterocyclic case they are, again, almost always non-identical. Once again, spiro compound elatol[7]
the best-fit planes to each ring are generally non-coplanar to one another
(i.e., the rings are not coplanar, despite appearing so in images).

Polyspiro compounds
A polyspiro compound is connected by two or more spiroatoms
making up three or more rings.

Nomenclature
A further example of a hetero-
Nomenclature for spiro cyclic spiro compound, the on-
compounds was first discussed market drug spironolactone,
by Adolf von Baeyer in where the two 5-membered rings
1900.[10] The prefix spiro ring in the upper right hand corner
denotes two rings with a spiro compose a spiro ring system.
junction. The main method of One of the rings is a lactone (i.e.,
systematic nomenclature is to contains as ester functional
Two examples of spiro compound follow with square brackets group).
nomenclature, A. 1-bromo-3- containing the number of atoms
chlorospiro[4.5]decan-7-ol, and B. in the smaller ring then the
1-bromo-3-chlorospiro[3.6]decan-7- number of atoms in the larger ring, separated by a period, in each
ol. 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.[11] For example, compound A in the image 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.

Chirality
Spiranes can be chiral, in three distinct ways.[6]: 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 substiuents, as
with alkylidenecycloalkanes, may make a spiro compound display
central chirality (rather than axial chirality resulting from the twist);
third, the substiuents 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.[6]: 1138ff, 1119ff [4]: 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).[6]: 1119f Assignment of
absolute configuration of spiro compounds has been challenging, but a number of each type have been
unequivocally assigned.[6]: 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.

Preparation
Spiro compounds present unique preparative challenges, whether each ring contributing to its structure is
unique or identical, or whether they are carbocyclic or heterocyclic—owing to the practical implications of
tetra-functionalizing the central spiro atom (often with four different groups), and of the unique aspects of
chirality that apply to these compounds.[9]

Specific methods

Some spiro compounds can be synthesized using the Pinacol-pinacolone rearrangement;[4]: 985 for
example, spiro[4.5]decane (final compound in following two line scheme) can be synthesized from
symmetric 1,2-diols of the sort shown below [e.g., this route's starting material, (1,1′-bicyclopentyl)-1,1′-
diol[12]]. Initially, one of the carbinol moieties is protonated, allowing water to leave, and yielding the
corresponding carbocation (second structure, first row); this intermediate then undergoes a bond migration,
resulting in ring expansion of the adjacent ring, with deprotionation unmasking the ketone functional group
to complete the first line of the mechanism. This first product, a spirobicyclic ketone, is a spiro compound
in its own right, and yields the further spiro carbinol and the alicyclic spiro hydrocarbon after two further
reduction reactions. First, reduction of the carbonyl that ends the mechanism's first line provides the spiro
carbinol starting material of the second line, which is needed for reduction to the alkane (shown). This latter
reduction is accomplished using lithium aluminum hydride (LiAlH4 ), via the alcohol tosylate (formed using
tosyl chloride). Hence this three reaction sequence provides three spiro compounds (ketone, alcohol, and
alkane), of possible research or practical use.[4]: 985
Uses
Spiro forms of lactones and oxazines are frequently used as leuco dyes, frequently displaying chromism—
reversible structural change between forms giving rise to colorless and colored appearances, especially in
solution.

Spiroaromaticity
Spiroaromaticity in organic chemistry refers to a special case of aromaticity in which conjugation is
interrupted by a single spiroatom. Although this spiro center disrupts the continuous overlap of p-orbitals,
traditionally thought to be a requirement for aromaticity, considerable thermodynamic stability and many of
the spectroscopic, magnetic, and chemical properties associated with aromatic compounds are still observed
for such compounds.

Etymology
A spiro compound, or spirane, from the Latin spīra, meaning a twist or coil,[13][6]: 1138 [14] 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,[3]: SP-0 examples of which are
shown at right.

Further reading
Clayden, Jonathan ; Greeves, Nick & Warren, Stuart (2012). Organic Chemistry ([Link]
[Link]/books?isbn=0199270295) (2nd ed.). Oxford, UK: Oxford University Press.
pp. 319f, 432, 604np, 653, 746int, 803ketals, 839, 846f. ISBN 978-0199270293. Retrieved
2 February 2016.
Eliel, Ernest Ludwig; Wilen, Samuel H. & Mander, Lewis N. (1994). "Chirality in Molecules
Devoid of Chiral Centers (Chapter 14)" ([Link]
J). Stereochemistry of Organic Compounds (1st ed.). New York, NY, USA: Wiley & Sons.
pp. 1119–1190, esp. 1119ff, 1138ff, and passim. ISBN 978-0471016700. Retrieved
2 February 2016. For a further but less stable source of the same text that provides access to
the relevant material, see [4] ([Link]
s-Ernest-Eliel/dp/0471016705/ref=sr_1_1?s=books&ie=UTF8&qid=1454600262&sr=1-1&ke
ywords=Stereochemistry+of+Organic+Compounds+Eliel), same access date.
Examples of spiro natural products and their synthesis: Smith, Laura K. & Baxendale, Ian R.
(2015). "Total Syntheses of Natural Products Containing Spirocarbocycles" ([Link]
0.1039%2FC5OB01524C). Org. Biomol. Chem. 13 (39): 9907–9933.
doi:10.1039/C5OB01524C ([Link] PMID 26356301 (htt
ps://[Link]/26356301).
Rios, Ramon (2012). "Enantioselective Methodologies for the Synthesis of Spiro
Compounds". Chem. Soc. Rev. (print, online). 41 (3): 1060–1074.
 doi:10.1039/C1CS15156H ([Link] PMID 21975423 (htt
ps://[Link]/21975423). {{cite journal}}: |format= requires
|url= (help)
The IUPAC documents on naming of spiro compounds: Moss, G.P. and the Working Party of
the International Union of Pure and Applied Chemistry [IUPAC], Organic Chemistry Division,
Commission on Nomenclature of Organic Chemistry (III.1) (1999). "Extension and Revision
of the Nomenclature for Spiro Compounds (IUPAC Recommendations1999)" ([Link]
g/publications/pac/pdf/1999/pdf/[Link]) (PDF). Pure Appl. Chem. 71 (3): 531–558.
doi:10.1351/pac199971030531 ([Link] ISSN 1365-
3075 ([Link] S2CID 20131819 ([Link]
[Link]/CorpusID:20131819). Retrieved 3 February 2016. The full author (Working Party) list
and a link to a German translation are provided in a corresponding footnote. Also available
online at "Extension and Revision of the Nomenclature for Spiro Compounds" ([Link]
[Link]/iupac/spiro/). London, GBR: Queen Mary University of London., same access
date.

References
1. "1,4-Dioxaspiro[4.5]decane" ([Link]
m/[Link]?rid=aa6e1001-5ee2-45
0c-9d26-e6b222c54f46). [Link]. Retrieved
3 February 2016.
2. "spiro[5.5]undecane" ([Link]
An example of the spiro-type
[Link]). [Link]. Retrieved
substructure found in polyphenols—
3 February 2016.
where two rings are joined at a single
shared point—with illustration of the
two stereoisomers that can arise,
here labeled R (rectus) and S
(sinister) based on the CIP system
to describe stereochemistry.
3. Moss, G.P. and the Working Party of the International
Union of Pure and Applied Chemistry (IUPAC), Organic
Chemistry Division, Commission on Nomenclature of
Organic Chemistry (III.1) (1999). "Extension and
Revision of the Nomenclature for Spiro Compounds
(IUPAC Recommendations1999)" ([Link]
ublications/pac/pdf/1999/pdf/[Link]) (PDF).
Pure Appl. Chem. 71 (3): 531–558.
doi:10.1351/pac199971030531 ([Link]
1%2Fpac199971030531). ISSN 1365-3075 ([Link]
[Link]/issn/1365-3075). S2CID 20131819 (http
s://[Link]/CorpusID:20131819).
Retrieved 3 February 2016. 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 "Extension and Revision of the Nomenclature
for Spiro Compounds" ([Link]
c/spiro/). London, GBR: Queen Mary University of
London. Retrieved 3 February 2016. Also available in
German, with et al. indicating the same working party, at
Hellwich, Karl-Heinz et al. (18 October 2002).
"Erweiterung und Revision der Nomenklatur der
Spiroverbindungen". Angewandte Chemie. 114 (20):
4073–4089. doi:10.1002/1521-
3757(20021018)114:20<4073::AID-
ANGE4073>[Link];2-T ([Link]
1-3757%2820021018%29114%3A20%3C4073%3A%3
AAID-ANGE4073%[Link]%3B2-T). "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."
4. Clayden, Jonathan ; Greeves, Nick & Warren, Stuart
(2012). Organic Chemistry ([Link]
oks?isbn=0199270295) (2nd ed.). Oxford, UK: Oxford
University Press. pp. 319f, 432, 604, 653, 746, 803, 839,
846f. ISBN 978-0199270293. Retrieved 2 February
2016.
5. For all four categories, see Reusch, William (1999).
"Saturated Hydrocarbons, Alkanes and Cycloalkanes:
Cycloalkanes (Table: Examples of Isomeric C8H14
Bicycloalkanes) or Nomenclature: Cycloalkanes (same
Table), and passim" ([Link]
ulty/reusch/virttxtjml/[Link]). Virtual Text of Organic
Chemistry (Jan. 2016 ed.). East Lansing, MI, USA:
Michigan State University, Department of Chemistry.
Retrieved 3 February 2016. The specific chapters can be
found at [1] ([Link]
ch/virttxtjml/[Link]) and [2] ([Link]
[Link]/faculty/reusch/virttxtjml/[Link]#nom2b),
respectively, same access date. For the description
featuring adjacent atoms for all but the isolated category,
see Clayden, op. cit.
6. Eliel, Ernest Ludwig; Wilen, Samuel H. & Mander, Lewis
N. (1994). "Chirality in Molecules Devoid of Chiral
Centers (Chapter 14)" ([Link]
d=IyfwAAAAMAAJ). Stereochemistry of Organic
Compounds (1st ed.). New York, NY, USA: Wiley &
Sons. pp. 1119–1190, esp. 1119ff, 1138ff, and passim.
ISBN 978-0471016700. Retrieved 2 February 2016. For
a further but less stable source of the same text that
provides access to the relevant material, see [3] (https://
[Link]/Stereochemistry-Organic-Compound
s-Ernest-Eliel/dp/0471016705/ref=sr_1_1?s=books&ie=
UTF8&qid=1454600262&sr=1-1&keywords=Stereoche
mistry+of+Organic+Compounds+Eliel), same access
date.
7. Smith, Laura K. & Baxendale, Ian R. (2015). "Total
Syntheses of Natural Products Containing
Spirocarbocycles" ([Link]
24C). Org. Biomol. Chem. 13 (39): 9907–9933.
doi:10.1039/C5OB01524C ([Link]
5OB01524C). PMID 26356301 ([Link]
[Link]/26356301).
8. Science News Staff (1991). "Elusive bowtie pinned
down" ([Link]
ned+down.-a011134368) (online). Science News (July
13). Retrieved 2 February 2016. "Quoting: 'W.E. Billups
and Michael M. Haley of Rice University in Houston
accepted the challenge… in the June 19 Journal of the
American Chemical Society, they report producing the
molecule… / The molecule, which resembles a bowtie
with one side bent perpendicular to the other, belongs to
a chemical family called the spiroalkenes, whose
members possess a single carbon at their cores.' "
9. Rios, Ramon (2012). "Enantioselective Methodologies
for the Synthesis of Spiro Compounds". Chem. Soc. Rev.
(print, online). 41 (3): 1060–1074.
doi:10.1039/C1CS15156H ([Link]
1CS15156H). PMID 21975423 ([Link]
[Link]/21975423). {{cite journal}}: |format=
requires |url= (help)
10. von Baeyer, Adolf (1900). "Systematik und Nomenclatur
Bicyclischer Kohlenwasserstoffe" ([Link]
ord/1425984). Berichte der Deutschen Chemischen
Gesellschaft. 33 (3): 3771–3775.
doi:10.1002/cber.190003303187 ([Link]
2%2Fcber.190003303187).
11. "Spiro Hydrocarbons. Rule A-41. Compounds: Method
1" ([Link]
[Link]).
12. Pubchem. "1,1'-Bicyclopentyl-1,1'-diol" ([Link]
[Link]/compound/291783#section=Top).
[Link]. Retrieved 7 March 2016.
13. 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.
14. Lewis, Charlton, T. (1890). "spīra [dictionary entry]" (http
s://[Link]/hopper/text?doc=Perseus%3A
text%3A1999.04.0060%3Aalphabetic+letter%3DS%3Ae
ntry+group%3D20%3Aentry%3Dspira). An Elementary
Latin Dictionary. New York, NY, USA: American Book
Company. Retrieved 3 February 2016. "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 Woodhouse, S.C. (1910). "Fold,
subs. [dictionary entry]" ([Link]
-bin/efts/dicos/woodhouse_test.pl?keyword=^Fold,%20s
ubs.). English-Greek Dictionary: A Vocabulary of the
Attic Language. Ludgate Hill [London, ENG]: George
Routledge & Sons. Retrieved 3 February 2016.
"Quoting: 'Fold, subs. … Coil : V. σπεῖρα… see coil.' "

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