Chalmer Wren
December 2, 2008
Advanced Organic Chemistry
Introduction
Carbenes are a family of organic molecules composed of a neutral divalent carbon
atom with a sextet of electrons.2 The two primary categories that carbenes can be divided
into are singlets and triplets. Singlet carbenes are extremely reactive and, until recently,
their existence was thought too transitory to be directly observed.2 In fact, carbenes were
not even commercially available until 1995.
In 1954, Doering and Hoffman established dichlorocarbene as an intermediate in
the hydrolysis of chloroform under basic conditions, thereby introducing carbenes into
organic chemistry.3 In 1964, carbenes were introduced into organmetallic chemistry by
Fischer.3 Recently, in 2008, the existence of the simplest carbene, methlyene, was
observed directly using spectroscopy.1 Numerous examples of carbenes can be seen in
Table on page 7.
Spectroscopy
Due to the instability inherent to carbenes, studying them with spectroscopy, as in
general, is challenging. Time resolved absorption spectroscopy and matrix isolation
spectroscopy have been the most potent and rewarding means of studying carbenes.8 The
former of these means of study allows the for the observation of reaction kinetics, and has
allowed determination of carbene lifetimes and absolute reaction rates.8 In matrix
isolation spectroscopy, a carbene is trapped in a solid matrix at extremely low
temperatures. By performing the process at low temperatures, thereby minimizing
thermal energy, the carbene product is kinetically stabilized. Generally, a precursor to
the photochemical production of carbene, which are frequently diazo compounds such as
V-12 from Figure 12, is situated in the matrix and photochemically converted to the
carbene product.8 The matrix then immobilizes the carbene.
Two kinds of organic matrices can be used; organic glass or rare gas matrices.
For an organic glass, the photochemical precursor to a carbene is mixed with an organic
solvent and then frozen, forming an organic glass matrix. However, the high reactivity of
carbenes limits the use of all but the most inert organic solvents and, in for the more
reactive carbenes, organic glass matrices can’t be used at all. In such cases, the use of a
rare gas matrix is necessary.8 Developed by Whittle et al., a mixture of the carbene
precursor and an inert gas are sprayed onto a spectroscopic window at sufficiently cold
temperature to cause immediate condensation and formation of the matrix.9 Methylene
was observed using this method, with argon as the matrix.1
Diazomethane can also be reacted with acyl chloride, I-12, to produce a carbene.7
The reaction, depicted in Figure 12, begins with acylation, wherein the lone pair of the
carbon in diazomethane forms a bond to the electron deficient carbon of the carbonyl
group, replacing the chlorine and forming the diazonium compound II-12. Then, a
second diazomethane molecule acts as a base, taking a proton from the –carbon of II12. This results in the formation of III-12, a diazocarbonyl compound. Applying heat or
light causes III-12 to decompose into the nitrogen gas and the carbene IV-12. The
diazocarbonyl is an example of a photochemical precursor that could be used to produce
a carbene in matrix isolation spectroscopy.
Matrix isolation spectroscopy not only allows for characterization of carbenes, but
also serves as tool for investigating bimolecular reactions of carbenes. This is
accomplished by doping the matrix with some secondary reactant. After matrix
formation and carbene immobilization, the matrix can be heated to release the carbene
which subsequently reacts with the secondary reactant used to dope the matrix.8 The
products of this reaction can then be spectroscopically studied and characterized.
Carbene Structure
Carbenes can be sp-hybridized or sp2-hybridized. Carbenes that are sp-hybridized
have a linear geometry while sp2-hybridized carbenes have a bent geometry. An sp2hybridized carbene has a nonbonding  orbital and a nonbonding py orbital, hereafter
designated as the p orbital for an sp2-hybridized carbene. For an sp2-hibridized carbene
with bent geometry, the four possible electronic configurations are depicted in Figure 1.
Figure 1
A
B
C
D
Didier Bourissou, Olivier Guerret, François P. Gabbaï, and Guy Bertrand. Chem. Rev., December 22, 1999.100 (1), 39 –92.
Figure 1A depicts a triplet state with pconfiguration 3B1 statewherein the two
nonbonding electrons are in different orbitals, one in the p orbital and one in the s
orbital, while have parallel spins. Figure 1B depicts a singlet state with configuration
1A1 statewherein the two-nonbonding electrons are both in the  orbital. Figure 1C
depicts a singlet state with pconfiguration 1A1 statewherein the two-nonbonding
electrons are both in the porbital. Figure 1D depicts an excited singlet state with p
configuration (1B1 statewherein the two nonbonding electrons are in different orbitals
while having anti-parallel spins.3 Carbenes with a linear configuration are sp-hybridized,
having two nonbonding degenerate orbitals px and py, and are usually triplet carbenes.
With the exception of dihalogenocarbenes and carbenes with sulfur, nitrogen, or
oxygen bond directly the to divalent carbene, which likely exist as singlets, most
carbenes are non-linear triplets.10 The preferred singlet state for dihalogenocarbenes and
carbenes with nitrogen, oxygen, or sulfur substituents can be explained by resonance
stabilization, depicted in Figure 4 and Figure 7.
Evidence Of Existence
In 1954, Doering and Hoffman established dichlorocarbene as an intermediate in
the hydrolysis of chloroform under basic conditions.5 They reacted cyclohexene with
chloroform in the presence of the strong base potassium t-butoxide.5 In the mechanism
they proposed t-butoxide first removes the proton from chloroform, resulting in the
formation of t-butyl alcohol and the conjugate base of chloroform. The conjugate base of
chloroform, a trichloromethide anion, forms chloride ion and a carbene known as
dichlorocarbene. The mechanism for the formation of dichlorocarbene is shown in
Figure 2.
Figure 2
Cl
Cl
Cl
H
+ O
-
Cl
-
+
HO
Cl
Cl
chloroform
Cl
C
t-butoxide
trichloromethide ion
t-butyl alcohol
C
Cl
dichlorocarbene
Then, as shown in Figure 3, dichlorocarbene goes on to react with cyclohexene,
forming 1,1-dichloro-2,2-dimethylcyclopropane in what is referred to as a cycloaddition.
The reaction is likely a concerted process.
Figure 3
Cl
C
Cl
Cl
+
Cl
dichlorocarbene
cyclohexene
1,1-dichloro-2,2-dimethychyclopropane
Doering and Hoffman did not observe dichlorocarbene directly but, rather,
trapped the carbene as a stable adduct and then deduced its existence as the best possible
explanation for the observed results. Cycloaddition reactions can occur for both triplet
and singlet carbenes.10 As discussed in Spectroscopy, such carbenes have since been
observed directly.
Carbene Reactivity
Because singlet usually carbenes have an unoccupied orbital and an orbital
occupied by a lone pair of electrons, some should display ambiphilic character.3
Ambiphilic species are those that are stabilized by both electron-donating and electronwithdrawing species and therefore have the potential to react with both electrophilic and
nucleophilic species.4 The unoccupied orbital gives the carbene carbon its electrophilic
character, while the lone pair imparts the carbene carbon with the potential for
nucleophilic character. The ground state multiplicity of a carbene is influenced by
inductive, mesomeric, and steric effects.4
Inductive Effects
The electronegativity of a carbene substituent influences whether the ground state
is a triplet or singlet state. -electron withdrawing substituents increase the s character of
the occupied nonbonding orbital, thereby inductively stabilizing the carbene in the
singlet state depicted in Figure 1B.3 electron donating substituents favor the triplet
state by destabilizing nonbonding orbital.3
Mesomeric Effects
Another primary contributor to the structure and stability of a carbene is the
mesomeric effect, which is also known as the resonance effect. The stability of a carbene
substituent Substituents that donate electron density are designated with an X, while
substituents that withdrawal electron density are designated with a Z. (X,X)-Carbenes,
i.e., carbenes for which both substituents donate electron density, should be sp2hybridized singlets.3 Donating electron density to the empty p orbital increases its
energy, thereby increasing the magnitude of energy required for an electron to move from
the orbital to the p orbital, thereby favoring the carbene configuration depicted in
Figure 1B.3 Through resonance, the p orbital and the adjacent p orbitals the substituents
interact to form partial double bond character. The resonance structures of (X,X)-carbene
is depicted in Figure 4.
Figure 4
X
C
X
+
X
C
X
X
C
X+
(Z,Z)-Carbenes, i.e., carbenes whose substituents withdrawal electron density,
should be sp-hybridized singlet carbenes.3 The unoccupied substituent p orbitals interact
mesomerically with the py orbital to form a 2-electron 3-center  system .3 1999, (Z,Z)carbenes have not been isolated .3 The resonance structures of a (Z,Z)-carbene is
depicted in Figure 5.
Figure 5
Z
C
Z
+
Z
C
+
Z
Z
C
Z
(X,Z)-Carbenes are neither linear or nonlinear, but instead are classified as quasilinear. The X substituent lone pair interacts with the py orbital, while the Z substituent
interacts with the px orbital .3 The singlet state for (X,Z)-carbenes is favored .3 Bulky
substituents kinetically stabilize all types of carbenes, and steric effects may even dictate
the ground state multiplicity if mesomeric and inductive effects are negligible .3
Carbene Synthesis
In addition the reaction of chloroform with strong base, discussed earlier and
shown in Figure 2, several other means of producing carbenes exist. For example, the
carbene know as methylene can be produced by subjecting diazomethane to photolysis,
which is depicted in Figure 6.7
Figure 6
H
-
C
+
N
N
hv
N
N
H
+ C
H
H
Synthesis of Stable Singlet (X,X)-Carbenes
Aminocarbenes
The stability of singlet carbenes is largely dictated by substituents associated with
it. For example, the stability of carbenes can be increased using amino substituents. This
is because the adjacent nitrogen atoms decrease the electron deficiency of p orbital by
donating electron density through resonance, while stabilizing the lone pair of the
orbital of carbon by inductively withdrawing electron density.3 The resonance of
diamniocarbene is shown in Figure 7.
+
N
N
C
N
N
C
C
N
+
N
Figure 7
Realizing the potential for amino groups to stabilize carbenes, Wanzlick
attempted to synthesize the aminocarbene species II, depicted in Figure 8, in 1962.3 This
was accomplished the thermal elimination of chloroform.3 Only the product, III, was
isolated and subsequent cross-coupling experiments failed to verify the existence of an
equilibrium between III and the carbene intermediate.3
Figure 8
Ph
Ph
N
N
Cl
N
Ph
Ph
Cl
N
N
C
Cl
N
Ph
Ph
Ph
Ph
II
I
N
N
III
Despite Wanzlick’s failure, the isolation of stable aminocarbenes was eventually
achieved. In 1990, Arduengo, Harlow, and Kline reported the synthesis, structure, and
characterization of the first stable crystalline carbene. The crystalline carbene they
isolated was 1,3-di-1-adamantylimidazol-2-ylidene. They produced the carbene at room
temperature by deprotonating 1,3-di-1-adamantylimidazolium chloride with sodium
hydroxide in tetrahydrofuran. Dimsyl anion was used as a catalyst. The same carbene
can be produced using potassium t-butoxide. 1,3-di-1-adamantylimidazol-2-ylidene is a
clear colorless crystalline species and is stable in the absence of moisture and oxygen.6
In 1995 it was reported that the carbene known as 1,2,4-triazol-5-ylidene,
designated as I-9 in Figure 9, could be produced from a corresponding 5-methoxy-1,3,4triphenyl-4,5-dihydro-1H-1,2,4-triazole, designated as II-9 in Figure 9, in quantitatively
useful yields, making it the first commercially available carbene. The process, depicted
in Figure 9, was accomplished via thermal elimination of methanol at 80C and 0.1
millibars.3 Additional examples of amino stabilized carbenesinclude II, III, IV, V from
Table 1.
Figure 9
Ph
N
Ph
N
N
Ph
I-9
Ph
O
Ph
N
C
N
N
Ph
II-9
+
OH
Table 1
Didier Bourissou, Olivier Guerret, François P. Gabbaï, and Guy Bertrand. Chem. Rev., December 22, 1999.100 (1), 39 –92.
Figure 10
H3C
H
O
C
-
+
C N N
Cl
Cl
H
-
H
O
+
C C N N
H3C
I-12
-
C
C
CH3
V-12
H
-
H
heat or uv
N
O
C
C
C
+
N
NH
III-12
H
+
O
CH3
II-12
N
+
C N N
H
H
O
H
C
CH3
IV-12
+
N
N
Citations
1) Phantom Parent Molecule Of Important Class Of Chemical Compounds Isolated For
First Time. Science Daily [Online] June 17, 2008.
http://www.sciencedaily.com/releases/2008/06/080611135106.htmhttp://www.scienc
edaily.com/releases/2008/06/080611135106.htm (accessed November 1, 2008).
2) Peter R. Schreiner, Hans Peter Reisenauer, Frank C. Pickard IV, Andrew C.
Simmonett, Wesley D. Allen, Mátyus & Attila G. Császár. Nature. June 12,
2008. 453, 906-909.
3) Bourissou D., Guerret O., Gabbaï F., and Bertrand G. Chem. Rev., December 22,
1999.100 (1), 39 –92.
4) By Samir Z. Zard. Oxford University Press. 2003. pp 11.
http://books.google.com/books?id=BspMJ-hN_pgC&pg=RA1-PA4IA7&lpg=RA1-PA4IA7&dq=what+does+ambiphilic+mean&source=web&ots=tdUKcXaTMz&sig=u
RdUfYxS7rM0qC5CgvatXatkj_U. (accessed November 1, 2008).
5) W. von E. Doering, A. Kentaro Hoffman. J. Am. Chem. Soc. 1954, 76, 6162.
6). Anthony J. Arduengo III. Richard L. Harlow, Michael Kline. J. Am. Chem. Soc. 1995,
117, 11027.
7) Nick Greeves, Alex Lawrenson, Kirsty Barnes. (2007) University of Liverpool.
ChemTube3D – Interactive 3D Organic Reaction Mechanism. Carbenes.
http://osxs.ch.liv.ac.uk/~ng/external/CarbenesPhotolysisDiazomethaneCarbene.html (accessed November 9, 2008).
8) http://0scitation.aip.org.skyline.cudenver.edu/getpdf/servlet/GetPDFServlet?filetype=pdf
&id=JCPSA6000022000011001943000001&idtype=cvips (accessed November
11, 2008).
9) Whittle, E.; Dows, D.A.; Pimentel, G.C. J. Chem. Phys. 1954, 22, 1943.
10) Gilchrist, T. L.; Rees C.W. (1969) Appleton-Century-Crofts. p. 1-8