Hydrolysis of lmidazole-2-ylidenes

Article abstract of DOI:10.1021/ja103578y

The direct reaction of an imidazole-2-ylidene in a predominantly aqueous environmentabout 0.1 M solution in a H₂O (>60%)/THF solvent system] was investigated for the first time. The reaction yielded a stable solution of the corresponding imidazolium-hydroxide of pH 13, which is in agreement with results from an ab initio molecular dynamics simulation. In contrast, hydrolysis of the carbene in a mainly aprotic environment (>80% THF) gives a hydrogen-bridged carbene-water complex which could be detected by NMR and IR spectroscopies for the first time. This complex converts slowly to two isomeric ring opened products and is at higher water concentration in dynamic equilibrium with the imidazolium hydroxide. A computational mechanistic study of the carbene hydrolysis with a gradually increasing number of water molecules revealed that the imidazolium-hydroxide structure can only be optimized with three or more water molecules as reactants, and with the increasing number of water molecules its stability is increasing with respect to the carbene-water complex. In agreement with the experimental results, these findings point out that solvent stabilization and basicity of the hydroxide ion plays a crucial role in the reaction. With increasing number of water molecules the barriers connecting the reaction intermediates are getting smaller, and the ring opened hydrolysis products can be derived from imidazolium-hydroxide type intermediates. Computational studies on the hydrolysis of a nonaromatic imidazolidine-2-ylidene analogue clearly indicated the analogous ring-opened product to be by 10-12 kcal/mol more stable than the appropriate ion pair and the carbene-water complex, in agreement with the known aromatic stabilization of imidazol-2-ylidenes. Accordingly, these molecules hydrolyze with exclusive formation of the ring-opened product.

Full text of DOI:10.1021/ja103578y

ARTICLE
pubs.acs.org/JACS
Hydrolysis of Imidazole-2-ylidenes
Oldamur Hollꢀoczki,†,‡ Pꢀeter Terleczky,† Dꢀenes Szieberth,† Georgios Mourgas,§ Dietrich Gudat,*,§ and
Lꢀaszlꢀo Nyulꢀaszi*,†,‡
†Department of Inorganic and Analytical Chemistry and ‡Materials Structure and Modeling Research Group of the Hungarian Academy
of Sciences, Budapest University of Technology and Economics, Szt. Gellꢀert tꢀer 4., Budapest, H-1111 Hungary
§Institut f€ur Anorganische Chemie, Universit€at Stuttgart, Pfaffenwaldring 55, 70550 Stuttgart, Germany
S Supporting Information
b
ABSTRACT: The direct reaction of an imidazole-2-ylidene in a
predominantly aqueous environment [about 0.1 M solution in a
H2O (>60%)/THF solvent system] was investigated for the first
time. The reaction yielded a stable solution of the corresponding
imidazolium-hydroxide of pH 13, which is in agreement with
results from an ab initio molecular dynamics simulation. In
contrast, hydrolysis of the carbene in a mainly aprotic environ-
ment (>80% THF) gives a hydrogen-bridged carbene-water
complex which could be detected by NMR and IR spectroscopies for the first time. This complex converts slowly to two isomeric
ring opened products and is at higher water concentration in dynamic equilibrium with the imidazolium hydroxide. A computational
mechanistic study of the carbene hydrolysis with a gradually increasing number of water molecules revealed that the
imidazolium-hydroxide structure can only be optimized with three or more water molecules as reactants, and with the increasing
number of water molecules its stability is increasing with respect to the carbene-water complex. In agreement with the experimental
results, these findings point out that solvent stabilization and basicity of the hydroxide ion plays a crucial role in the reaction. With
increasing number of water molecules the barriers connecting the reaction intermediates are getting smaller, and the ring opened
hydrolysis products can be derived from imidazolium-hydroxide type intermediates. Computational studies on the hydrolysis of a
nonaromatic imidazolidine-2-ylidene analogue clearly indicated the analogous ring-opened product to be by 10-12 kcal/mol more
stable than the appropriate ion pair and the carbene-water complex, in agreement with the known aromatic stabilization of
imidazol-2-ylidenes. Accordingly, these molecules hydrolyze with exclusive formation of the ring-opened product.
’ INTRODUCTION
reaction (for the full conversion 3 months were needed!) with an
equimolar amount of water in THF.8Compound 2a under the
same conditions hydrolyzes to 4a (Scheme 1) instantaneously.8
The sluggish reactivity of 1a is in clear contrast with the expected
high sensitivity of carbenes against even traces of humidity. The
proposed mechanism of this reaction was a concerted insertion
into the O-H bond,11 rather than a stepwise protonation-hydroxide
addition, since addition of catalytic amounts of OH- or Hþ sources
to the reaction mixture did not increase the rate of hydrolysis.
Furthermore, the imidazolium salt formed in the reaction with
the added acid aimed for catalysis was found to be resistant against
any further decomposition. The difference between the reaction
rate of 1 and 2 was rationalized by the known difference in their
stability.12,13
The proton/deuteron exchange of the imidazolium cation 5b
in the presence of large excess of water has also been investigated
in buffered solutions in the pH range 5-8.9 Even though in these
experiments no other product than the imidazolium cation 5b
could be detected,9 the presence of carbene 1b was concluded
from the proton/deuteron exchange reaction (Scheme 2) followed
In the last few decades stable singlet carbenes1 have become
one of the most widely examined groups of compounds in
chemistry. The interest is generated by their catalytic applic-
ability either as transition metal complexes2 or metal free organo-
catalysts,3 having often outstanding selectivity and stability.2e,3b
Derivatives of the remarkably stable imidazole-2-ylidenes4 are
perhaps the most frequently used species. Still, although their
transition metal complexes can be resistant to moisture, and some
reactions can even be performed in aqueous media,5 free carbenes
are usually considered to be particularly sensitive against hydro-
lysis.1,6 As this property makes their handling difficult and exp-
ensive,7 a better understanding and prevention of this reaction
could seriously improve their applicability. It is thus strange that
only a few attempts were made to investigate this hydrolysis, and
although it was noticed that different hydrolysis products were
obtained under different conditions,8,9 no explanation for this
behavior has been sought.
The hydrolysis of the (free) 1,3-ditert-butylimidazole-2-ylidene
1a differs from that of the saturated 1,3-ditert-butylimida-
zolidine-2-ylidene10 2a.8 In the presence of air or moisture, 1a
converts to 3a (Scheme 1),7 and it has been reported that the
same product (3a) was also deliberately formed in a very slow
Received: April 27, 2010
Published: December 21, 2010
r
2010 American Chemical Society
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Scheme 1. Hydrolysis of Imidazole-Derived Carbenes
(DIPP = 2,6-Diisopropylphenyl)
bond. Thus, the number of water molecules can indeed have a
significant effect on the mechanism and energetics of the hydrolysis.
Interestingly, no computational studies have been devoted to
understand this apparently complex behavior of the hydrolysis
properties of imidazole-2-ylidenes, despite the significance of this
reaction. Only the reaction of less stable12 H, Me, CN, Cl, and F
substituted carbenes with one and two water molecules provid-
ing the corresponding O-H inserted product alcohol has been
examined by Restrepo et al., showing a decrease in gaps by the
addition of the second molecule of water, due to its proton relay
behavior.21 Furthermore, the low rate of the reaction of imidazol-
2-ylidene with an equimolar amount of water raises the question
of how moist the solvent can be for the carbene to remain intact.
In the present work, the hydrolysis of 1,3-dimethylimidazole-2-
ylidene 1b, and 1,3-ditertbuthylimidazole-2-ylidene 1a, together
with that of the nonaromatic 1,3-dimethylimidazolidine-2-yli-
dene 2b will be discussed with different numbers of neighboring
water molecules, to model the reaction in the gas phase, in
nonpolar organic solvents containing traces of water, and in
aqueous solution. In addition, these studies will be backed by
experimental investigations of the hydrolysis of 1,3-bis(2,6-
diisopropyl-phenyl)imidazole-2-ylidene 1c.
Scheme 2. Hydrogen/Deuterium Exchange of Imidazolium
Cation
’ MODELS AND METHODS
Although the carbene to water molar ratio does not provide direct
information about the microenvironment of the carbene, increasing
concentration of water will result in larger water networks,22 containing
two, three, or more water molecules. Thus, to account for the different
amounts of water we have first computed the reaction between the
carbenes and one, two, and three water molecules.
To model the decomposition in the aqueous phase we used a
microsolvation approach, considering a water monolayer, with the
assumption that a primary solvate shell contains most of the favorable
(e.g., hydrogen bond with the solute) and unfavorable (such as between
an unpolar chain and a polar solvent) interactions.23 The explicit model
chosen consists of 30 water molecules in the primary shell, providing full
coverage for the solvated molecule, and one water molecule as a reactant.
The principles to form the starting geometries of the clusters were to
keep linear hydrogen bonds, and keep the tetrahedral structure around
the oxygen of each water molecule. This resulted in a shell consisting of
water pentamers and hexamers.23 To use a different approach for the
description of the aqueous phase reaction, ab initio molecular dynamic
simulations have also been performed for 1b surrounded by 102 water
molecules (equivalent to a ca. 0.5 M concentration).
Full geometry optimizations and the subsequent verification of the
Hessian have been performed by the Gaussian 03 program package.24a
For the reaction of one, two, and three water molecules with 1b the
intermediates and transition states have been optimized with different
DFT functionals (B3LYP, B3PW91, PW91PW91, B97-1, MPW1K,
MPWB1K, BMK, M05-2X, TPSSh) and also at the MP2 level with the
6-311þG** and 6-311þþG** basis sets. To further test the reliability of
the geometries and relative energies B3LYP/aug-cc-pVTZ, B3LYP/6-
311þG**//B3LYP/6-31þG*, RI-MP2/def2-TZVPP//B3LYP/6-
31þG*,24b RI-B97-D/def2-TZVPP,24b and, for certain systems, CCSD-
(T)/cc-pVTZ//B3LYP/6-31þG* and CCSD(T)/cc-pVTZ//MP2/6-
311þG** calculations have also been performed. To make coupled
cluster single point calculations accessible, the convergence criteria has
been set to 10-5 on the energy and 10-7 on the wave function in case of
these calculations. Since the relative energies of each point calculated at
the B3LYP/6-311þG** and B3LYP/6-311þG**//B3LYP/6-31þG*
level were found to be in reasonable agreement with those at all other
levels (for details see Supporting Information), we applied B3LYP/6-
311þG** for the reaction of 1a and 2b with one, two, and three water
by NMR spectroscopy.9,14,15 We note that similar exchange at
positions 4 and 5 has also been reported (Scheme 2).14b
Facile protonation of a carbene to give an imidazolium cation
is in accordance with the reported extremely strong basicity of
carbenes.16 Imidazolium cations as cationic components of “ionic
liquids” are used in a variety of applications in the presence of water
or air moisture without considerable decomposition.17 Neverthe-
less, while these findings suggest a reversible protonation/deproto-
nation reaction instead of a ring-opening in the presence of large
excess of water, it remains unclear at which water to carbene ratio,
and at which pH range, the mechanism of the hydrolytic reaction
will switch from ring-opening to protonation.
In this context it should be mentioned that water molecules
may play multiple roles in hydrolysis reactions. First, water can be
a proton donor; the result of this simple reaction would result in
formation of an imidazolium-hydroxide18 from a carbene. The
acidity of a water molecule is influenced by the environment, and it is
greatly increased if the resulting hydroxide ion is stabilized by several
hydrogen bonds (possibly from other water molecules).19 It has
been reported, for example, that in a dodecahedral water cluster an
autoprotonation reaction can take place with a very low barrier.19
Second, a series of water molecules may act as a relay channel to
transfer the proton from its original to the final position,19 giving a
possible explanation for the well-known high electric conductivity of
proton (and hydroxide ion). Such proton relay is also known to
greatly reduce the activation barrier for otherwise hindered bond
cleavage reactions.20-22 Third, water molecules may stabilize ionic
systems either as an electron pair donor or by forming a hydrogen
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molecules, and B3LYP/6-311þG**//B3LYP/6-31þG* for that of 1b
and 2b in the solvate shell. For the intermediates of the reaction of 1b in
the solvate shell, M05-2X/6-311þG**//M05-2X/6-31þG* energies
and further ωB97X-D/6-311þþG** and MOS(ω600)-RI-MP2/cc-
pVTZ single point energies24c at the B3LYP/6-31þG* level geometries
have been calculated. For the visualization of the optimized structures
the MOLDEN program has been used.25
Scheme 3. B3LYP/6-311þG** Energy Profilea,b of the
Reaction of 1b and One Water (Relative Energies in kcal mol-1
)
For the ab initio molecular dynamics calculations the VASP code has
been applied.26 Gamma point calculations were carried out using the
PW91PW91 GGA exchange-correlation functional and hard PAW
pseudopotentials provided with the VASP package. 500 eV was used
as cutoff energy for the plane wave basis set.
Experimental manipulations were performed under an atmosphere of
dry argon using either Schlenk techniques or a glove box. For the
experimental studies, 1,3-bis-(2,6-diisopropylphenyl)imidazole-2-ylidene
1c was prepared according to the procedure previously described by
Dible and Sigman.27 The crude product was purified by recrystallization
from hexane and its purity checked by elemental analysis and 1H
NMR spectroscopy. Studies of the hydrolysis were carried out by either
adding a defined amount of deionized and degassed water with a
microliter syringe to solutions of the carbene (30 mg) in anhydrous
C6D6 or THF-d8 (0.5 mL) or, alternatively, treating a suspension of solid
1c (30 mg) in water (0.4 mL) with THF-d8 (0.1-0.2 mL) to ensure
formation of a homogeneous solution. The reactions were followed by
1H and 13C NMR spectroscopy. Products were identified and char-
acterized in the reaction mixtures by one-dimensional (1H, 13C{1H})
and two-dimensional (1H-gs-NOESY, 1H,13C-gsHSQC, 1H,13C-gsHMBC)
NMR spectra; no attempts toward isolation of any of the products was
made. For a titration of a carbene solution with water, specified amounts
of water were added by means of a microliter syringe to a precooled
(-35 °C) solution of 1c (30 mg) in THF-d8 (0.5 mL). The reaction was
monitored by recording 1H and 13C NMR spectra at -35 °C immedi-
ately after homogenization of the solution. All NMR spectra were
recorded on a Bruker AV400 spectrometer (1H 400.1 MHz, 13C 100.6
MHz) at 303 K. The WET technique was used to suppress the water
signal in aqueous solution. Chemical shifts are referenced to external
TMS (1H, 13C); i, o, m, p denote the positions in N-aryl rings. IR spectra
of reaction mixtures of 1c and H2O in C6D6 were measured on a Nicolet
6700 FT-IR spectrometer equipped with a diamond ATR unit. A
a M05-2X/6-311þG** relative energies are 10.4, 0.0, 27.5, -3.3; 33.6,
-10.6, 30.5, -14.1 kcal mol-1, respectively.
b MP2/6-311þG** relative energies are 10.3, 0.0, 28.2, -1.0, 33.8, -7.4,
30.2, -7.1 kcal mol-1, respectively. CCSD(T)/cc-pVTZ/6-311þG**
relative energies are 10.5, 0.0, 35.2, 2.9, 33.1, -10.3, 30.2, -12.6 kcal
mol-1, respectively.
Chart 1. Chemical Structures of the Molecules Involved in
the Hydrolysis of 1a-c (DIPP = 2,6-Diisopropylphenyl)
1
3JHH = 7 Hz, 2 H, CH), 1.31 (d, 3JHH = 7 Hz, 12 H, CH3), 1.12 (d, 3JHH
=
complete listing of available H and 13C NMR data including the
7 Hz, 6 H, CH3), 1.03 (d, 3JHH = 7 Hz, 6 H, CH3). 1H NMR (THF-d8;
signals of the aromatic protons in N-aryl substituents omitted as no
unambiguous assignment feasible): δ = 8.02 (d, 4JHH = 0.9 Hz, CHO),
6.39 (br d, 3JHH = 9 Hz, 1 H, NH), 5.63 (dd, 3JHH = 7.8, 9.1 Hz, 1 H,
CHdN), 4.84 (ddd, 3JHH = 7.8 Hz, 4JHH = 0.9, 0.9 Hz, 1 H, CHdN),
3.55 (sept, 3JHH = 7 Hz, 2 H, CH), 3.25 (sept, 3JHH = 7 Hz, 2 H, CH),
1.25 (d, 3JHH = 7 Hz, 12 H, CH3), 1.21 (d, 3JHH = 7 Hz, 12 H, CH3).
assignment of individual resonances is included in the Supporting
Information.
Spectroscopic data. Data for 1c - H2O follow. 1H NMR (C6D6):
δ = 7.27 (m, 2 H, p-CH), 7.17 (m, 4 H, m-CH), 6.57 (s, 2 H, C4/5H), 2.90
(sept, 3JHH = 7 Hz, 4 H, CH), 1.53 (s, 2 H, H2O), 1.28 (d, 3JHH = 7 Hz, 6 H,
CH3), 1.16 (d, 3JHH = 7 Hz, 6 H, CH3). 1H NMR (THF-d8): δ = 7.36 (m,
2 H, p-CH), 7.26 (m, 4 H, m-CH), 7.19 (s, 2 H, C4/5H), 2.81 (sept, 3JHH
=
1
Data for 5c follow. H NMR (H2O/THF-d8 4:1): δ = 7.98 (s, 2 H,
7 Hz, 4 H, CH), 2.59 (s, H2O), 1.20 (d, 3JHH = 7 Hz, 12 H, CH3), 1.17 (d,
3JHH = 7 Hz, 12 H, CH3).
C4/5H), 7.64(m, 2H, p-CH), 7.47(m, 4H, m-CH), 2.41 (sept, 3JHH =7Hz,
4 H, CH), 1.22 (d, 3JHH = 7 Hz, 6 H, CH3), 1.15 (d, 3JHH = 7 Hz, 6 H, CH3).
Data for for 3c follow. 1H NMR (C6D6; signals of aromatic protons in
N-aryl substituents omitted as no unambiguous assignment feasible):
δ = 8.20 (s, 1 H, CHO), 7.83 (t, 3JHH = 4 Hz, 1 H, CHdN), 4.50 (d,
3JHH = 4 Hz, 2 H, NCH2), 3.00 (sept, 3JHH = 7 Hz, 2 H, CH), 2.98 (sept,
’ RESULTS AND DISCUSSION
Reaction with One Water Molecule. The energy profile of
the proposed mechanism, with the relative energies of the
intermediates and transition states, is shown in Scheme 3, and
Chart 1 summarizes the chemical structures of the molecules
involved in the hydrolysis of 1a-c. The initial step of this
reaction is the formation of a hydrogen-bonded structure 6b,28
in which one of the hydrogen atoms of the water molecule is
coordinated to the hypovalent carbon atom.18 The oxygen is
3JHH = 7 Hz, 2 H, CH), 1.17 (d, 3JHH = 7 Hz, 12 H, CH3), 0.97 (d, 3JHH
=
7 Hz, 6 H, CH3), 0.93 (d, 3JHH = 7 Hz, 6 H, CH3). 1H NMR (THF-d8;
signals of aromatic protons in N-aryl substituents omitted as no
unambiguous assignment feasible): δ = 8.17 (s, 1 H, CHO), 7.76 (t,
3JHH = 3.9 Hz, 1 H, CHdN), 4.52 (d, 3JHH = 3.9 Hz, 2 H, NCH2), 3.23
(sept, 3JHH = 7 Hz, 2 H, CH), 2.87 (sept, 3JHH = 7 Hz, 2 H, CH), 1.26 (d,
3JHH = 7 Hz, 12 H, CH3), 1.11 (d, 3JHH = 7 Hz, 12 H, CH3).
1
Data for 8c follow. H NMR (C6D6): δ = 8.04 (s, 1 H, CHO),
apparently oriented to the methyl groups, indicating C-H
O
7.2-7.1 (m, 6 H, p,m-CH), 7.14 (m, 1 H, p-CH), 7.00 (m, 2 H, m-CH),
6.75 (br, 1 H, NH), 5.56 (d, 3JHH = 7 Hz, 1 H, dCH—N), 4.66 (d, 3JHH
= 7 Hz, 1 H, dCH—N), 3.73 (sept, 3JHH = 7 Hz, 2 H, CH), 3.20 (sept,
3 3 3
interaction that could be verified by localizing the corresponding
bondcriticalpoint.29 The electron densityatthatpoint (F = 0.008)
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Scheme 4. B3LYP/6-311þG** Energy Profilea for the
Reaction of 1b with Three Water Molecules (Relative
Energies in kcal mol-1
)
Figure 1. Relative energy of 5b and 7b with respect to 6b, in the presence
of 1-5 and 31 water molecules at the B3LYP/6-311þG** level.
a M05-2X/6-311þG** relative energies are 11.5, 0.0, 3.1, 2.2, 2.5, 2.4,
7.5, 1.9, 2.4, 0.3 kcal mol-1, respectively. RI-MP2/def2-TZVPP//
B3LYP/6-311þG**: 12.6, 0.0, 3.0, 2.8, 5.3, 4.5, 10.5, 6.5, 7.2, 3.1 kcal
mol-1, respectively.
the driving force of the reaction, which is, however, kinetically
hindered by the substantial barriers both for the insertion (25.7
kcal mol-1 at the B3LYP/6-311þG**level) andtheratedetermining
ring-opening step (32.3 kcal mol-1 at the B3LYP/6-311þG**
level).
was about 20% of that between two hydrogen bonded water
molecules, indicating a weak interaction only. It is noteworthy
that the Ccarbene-Owater bonded intermediate, which was reported21
to have a key role in the hydrolysis of the less stabilized11
carbenes, could not be located, in agreement with the stabilized
nature of imidazol-2-ylidenes. Similarly, no imidazolium-hydroxide
type structure could be optimized; attempts to locate such struc-
tures resulted in 6b, as had recently been shown for the 1,3-
dimethylimidazolium hydroxide ion pair.18
From the hydrogen bonded structure 6b the concerted
insertion of the carbene into the O-H bond is possible (as
suggested by Denk et al.8), yielding a nonaromatic 2,3-dihydro-
1,3-dimethylimidazole-2-ol 7b with a saturated carbon atom.30
The transition state of this step is quite polarized, as suggested by
the -0.95 Mulliken charge on the oxygen in comparison to the
corresponding values of -0.57 and -0.28 for 6b and 7b, and is
therefore destabilized, and the negatively charged OH moiety is
tilted away from the vertical symmetry plane of the ring due to
the aforementioned interaction with the hydrogen of the alkyl
group. This transition structure can also be considered as a close
contact imidazolium-hydroxide ion pair, based on the 1.079 Å
C(2)-H bond and the 1.864 Å O-H and 2.312 Å C-O
distances. Interestingly, the B3LYP/6-311þG** H-bonded
structure 6b is somewhat more stable than 7b (for results at
other levels of the theory see Table S1 in the Supporting
Information). It should be noted that in a recent computational
study18 a significantly (by ca. 3 kcal mol-1) larger energy
difference between 6b and 7b has been reported. The difference
is due to the fact that we have located an isomer of 7b which is
more stable than the previously reported18 one.
To have a better comparison with the experimental work of
Denk et al., the hydrolysis of the tert-butyl derivative has also
been examined. For the analogous reaction path, similar relative
energies were obtained for intermediate 7a (1.9 kcal mol-1),
products (-12.8 kcal mol-1 for both 8a and 3a33), and the ring-
opening transition state (30.9 kcal mol-1) compared to those for
the methyl analogue, but the barrier of the OH insertion is
considerably decreased (18.6 kcal mol-1), presumably due to
the increased number of the stabilizing nearby methyl groups.
Accordingly, for the more heavily substituted carbenes it is reason-
able to expect that the 6 and 7 type structures are in dynamic
equilibrium with each other, while the subsequent ring-opening
is hindered by the substantial, rate determining barrier.
Reaction with Two and Three Water Molecules. The
reaction of 1b with two water molecules exhibits a similar energy
profile as that with one water molecule (for the corresponding
scheme see Supporting Information), but the barrier of the
insertion of the carbene into the O-H bond is significantly
lower (14.5 kcal mol-1) due to the coordination of the second
water to the passing OH- moiety. Apparently, the second water
molecule alleviates the proton transfer also in the ring-opening step,
resulting in a barrier of 24.6 kcal mol .
-1 34 The reaction of 1b with
a water cluster of three water molecules (Scheme 4) results in a
hydrogen bonded assembly. Among these structures, 6bw3 was found
to be the most stable one, which can be attributed to the weak
hydrogen bonds between the methyl hydrogens and oxygen, as
shown by the presence of bond critical points.29 Most interestingly, in
the presence of three waters an imidazolium-hydroxide 5bw3
structure could also be optimized. 5bw3 is connected to the slightly
more stable 6bw3 by a low barrier proton shift. Expectedly, ionic 5b
can be stabilized with respect to 6b by the presence of more water.
(In the presence of four and five water molecules, the relative energy
of 5b decreases to 0.7 and -1.4 kcal mol-1, respectively, see
Figure 1.) Polar solvents also stabilize the imidazolium hydroxide,
type 5b structures, as shown by single point PCM energy calculations
in THF which predict 5bw3 to be more stable than 6bw3 by 1.6 kcal
mol-1. There are several 5bw3 structures with different hydrogen
The transition state of the direct rearrangement of 7b to 3b by
proton transfer could not be found; however, a rearrangement
yielding 8b (that is a Schiff base isomer of the experimentally
found product) could be obtained.31 The final isomerization
from 8b to the thermodynamically more stable 3b32 is apparently
aided by the formyl group, or alternatively by another water or
solvent molecule acting as a proton relay. The relative energies of
7b and 3b show that the stability of the products provides indeed
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bond arrangements, which are connected by low energy barriers.
7bw3 is formed from 5bw3-2. Thus, in the presence of three water
molecules a stepwise protonation/deprotonation mechanism is
operative rather than a concerted carbene insertion into the O-H
bond via a contact ion pair-like transition structure.
Scheme 5. Optimized Geometries for the Steps of Carbene
Hydrolysis in a Primary Solvate Shell with Their Relative
Energiesa (in kcal mol-1
)
The destabilization of the insertion products 7bw2 and 7bw3,
with respect to 6bw2 and 6bw3, is 4.7 and 8.4 kcal mol-1, respectively.
These values are significantly larger than the 0.7 kcal mol-1 energy
difference in case of the single water molecule. Likewise, for 5bw3,
several 7bw3 type structures are conceivable; those in Scheme 4 are
obtained by IRC calculations started from the corresponding transi-
tion states. Nevertheless, the aforementioned trend still holds if we
compare the energy of our most stable isomers of 7b-like structures:
their energy rises from 0.7 to 3.5 and 5.2 kcal mol-1, respectively,
when one or two additional water molecules are added. These data
suggest that, with the increasing number of water molecules, the
barrier between the 5, 6, and 7 type structures is reduced, alleviating
their rearrangement to each other. On the other hand the 5 type
structures are simultaneously stabilized by excess of water, and
imidazolium hydroxide (stabilized by an appropriately large cluster
of water molecules) might be the only product of the reaction
(Figure 1). It should be noted here that by other functionals (such as
M05-2X, see footnote in Scheme 4 and Supporting Information)
somewhat smaller relative energies have been obtained for 7b
compounds. Nevertheless, the gradual destabilization of type 7b
structures compared to the analogue 5b by the increasing number of
water molecules could be observed with all applied methods.
The stability of the open chain products (3 and 8) provides
also the driving force for the reaction in the presence of two and
three water molecules. The barrier for the ring-opening step is
somewhat reduced to 21.6 kcal mol-1 (with respect to the
reactants) in the presence of three reactant water molecules
(see Schemes S2 and S3 in the Supporting Information), and is
still the rate limiting step. 8bw2 and 8bw3 are somewhat more
stable than 3bw2 and 3bw3 in the gas phase. Modeling the
presence of the THF solvent by PCM calculation of the t-Bu
analogues, both 3aw2 and 3aw3 are by 0.6 kcal mol-1 more stable
than 8aw2 and 8aw3, respectively, in agreement with Denk's
result,8 who observed only 3a as reaction product.
a The reacting water molecule/resulting OH- group is green. M05-2X/
6-311þG**//M05-2X/6-31þG* relative energies are (in kcal mol-1
6bw31, 6.4; 5bw31, 0.0; 8bw31, 3.6; 3bw31, 4.2.
)
the lack of OH- addition in the presence of an excess of water is that
although the possible open chain reaction products (8bw31 and
3bw31) have been obtained, their energy has been found to be
significantly higher than that of 5bw31-1 (4.7 and 5.4 kcal mol-1
,
respectively). It is worth mentioning here that all DB-RI-MP2/cc-
pVTZ//B3LYP/6-31þG*, ωB97X-D/6-311þþG**//B3LYP/6-
31þG*, DB-ωB97X-D/cc-pVTZ//B3LYP/6-31þG*, and M05-
2X/6-311þG**//M05-2X/6-31þG* single point energies have
been found to be in reasonable agreement with the B3LYP/6-
311þG**//B3LYP/6-31þG* ones, while MOS(ω600)-RI-MP2/
cc-pVTZ//B3LYP/6-31þG* relative energies are similar for 5bw31
and 3bw31 (for more information see Supporting Information).
Thus, it is apparent that solvation stabilizes 5b to such an extent that
the ring-opening process (yielding the nonionic, and thus not so well
solvated, 8bw31 and 3bw31) becomes unfavorable.
Employing a First Solvate Shell To Model the Effect of
Water as a Solvent. Thirty water molecules provide a full coverage
for the carbene and a “reactant” water molecule (Scheme 5, 6bw31
)
that forms a H-bond with the hypovalent carbon atom. Proton
transfer from the reactant to the carbene yields 1,3-dimethylimida-
zolium-hydroxide solvated by 30 water molecules (5bw31), being
more stable by 6.1 kcal mol-1. The migration of the hydroxide ion
within the solvate shell yields several minima, having similar energies
to 5bw31 (see Supporting Information). At this point it must be noted
that the hydrate shell may have numerous hydrogen-bond orienta-
tions, which have some influence on the shell's stability.35 Thus, all
structures have been optimized using starting geometries with the
same hydrogen bond orientations, which have remained unchanged
during the relaxed optimization, except for 5bw31-2 (see Supporting
Information), where the migration of the hydrogen bonds follows the
movement of the hydroxide ion.
In order to investigate the feasibility of the OH- addition in
more dilute aqueous solutions, ab initio molecular dynamic
calculations (using the PW91PW91 functional) were carried
out on a 1b-water system, using a cubic unit cell with 15 Å
edges containing one 1b and 102 water molecules. The unit cell
was constructed by placing the carbene in a box of water having the
appropriate density and removing the overlapping water molecules.
Geometry optimization was carried out keeping the unit cell para-
meters fixed, and then random velocities corresponding to the zero-
point vibrations were assigned to the individual atoms. The system
was warmed up to 300 K in 3000 steps using a 1 fs time step, then
kept at 300 K for 5000 time steps.
The possible adduct of the hydroxide ion and the imidazolium
cation (7bw31) could not be obtained; the C-O bond always
opened up during the optimization, despite our efforts to find a
minimum containing an intact 7b type structural unit.36 Conse-
quently, it is very likely that the elimination of a hydroxide anion
(stabilized by hydratation) from a 7b-like structure would take
place without any barrier in aqueous media. As a further indication for
Protonation of the carbene happened early in the simulation
(at 700 fs), and the carbene remained protonated during the
entire simulation process. The hydroxide ion formed was
tracked, and the distance of the O atom of the hydroxide ion
(identified by having only one proton within 1.3 Å) from the
C(2) atom of the imidazolium cation was plotted against time in
Figure 2. The plot displays a generally increasing trend (jumps on
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in good agreement with the planar, thus presumably aromatic,
structure of the imidazole ring in the O-H insertion TS of 1b.
However, with an increasing number of neighboring waters, the
barrier of the formation of the 2b-derived adducts drops faster
than that of the aromatic 1b derivatives; thus, in the case of three
involved water molecules the gap is ca. 10 kcal mol-1 lower for
the nonaromatic carbene, in good agreement with the observed
difference in reaction rates of 1a and 2a by Denk et al.8 This
finding indicates that, with this extended stabilization of the
polarized transition state, aromaticity contributes significantly to
the kinetic stabilization of 1b in the hydrolysis reaction.
The energy of the ring-opening TS (the rate determining step)
is apparently also influenced by the backbone, since in the case of
a single water it is considerably higher for 2b than for 1b with
respect to the corresponding water adduct. Since in this step the
initial rupture of the C-N bond results in a negatively charged
amide moiety which instantaneously rearranges to 8b by a proton
migration, this difference can be explained by the stabilizing effect
of conjugation in the TS between the backbone double bond and
the amide. However, an additional water molecule can also stabi-
lize the amide moiety with respect to 7b by hydrogen bond formation,
resulting in a reduced barrier.
2b has also been examined in a solvate shell using a water
monolayer consisting of 30 molecules, which provided full
coverage for 2b (Scheme 7). Interestingly, 9bw31 could not be
optimized; all attempts gave 11bw31 by a proton transfer from the
H-bonding water molecule to the carbene during optimization.
The O-H adduct 10bw31, however, could be optimized, having
somewhat higher energy (3.9 kcal mol-1) than 11bw31. This is in
Figure 2. Distance of the OH- ion from the C(2) atom of the imidazo-
lium moiety plotted against time in the molecular dynamics simulation.
the graph are caused by proton transfer from the nearby water to
the hydroxide ion) from the point of protonation until the
distance of the OH- ion reaches the 7-9 Å interval where it
oscillates until the end of the simulation. Apparently the solva-
tion of the protonated carbene and the hydroxide ion keeps the
hydroxide well apart from the carbene, thus preventing further
reaction, in agreement with the aforementioned relative energies
of 5bw31-2 and the possible open chain derivatives.
Hydrolysis of Imidazolidine-2-ylidene. Since aromaticity
has an effect on the stability of imidazole-2-ylidenes,13 the energy
profile of the hydrolysis is presumably also influenced signifi-
cantly by aromatic properties, in agreement with the experimen-
tally found differences in the rate of decomposition. To explore
the extent of this effect we investigated the hydrolysis of 2b. The
reaction paths were found to be analogous to that of 1b. For the
energy profile of the reaction with one and two water molecules
see Supporting Information; for the one with three waters, see
Scheme 6. Chart 2 summarizes the chemical structures of the
molecules involved in the hydrolysis of 2b.
The interaction energy between the carbene and the water or
water cluster is 9.4, 13.4, and 14.8 kcal mol-1 in 9b, 9bw2, and
9bw3, respectively. The analogous values for 1b, 1bw2, and 1bw3
are 9.6, 13.9, and 11.2 kcal mol-1, respectively, showing that the
strength of the hydrogen bond is only slightly influenced by the
change in aromatic properties. Furthermore, 11bw3, the hydro-
xide salt derivable from the carbene, could also be optimized in
the case of at least three interacting water molecules. The water
adduct intermediates 10b, 10bw2, 10bw3 and the reaction products
4b, 4bw2, 4bw3, however, are by about 10 kcal mol-1 more stabi-
lized with respect to the corresponding 9b structure than the
analogous intermediates (7b, 7bw2, 7bw3) and products (3b, 3bw2,
3bw3) with respect to the corresponding 6b, 6bw2, and 6bw3,
respectively. This energy difference, which compares favorably with
the 13-15 kcal mol-1 aromatic stabilization energy of 1b,13c,d
makes the insertion into the O-H bond (yielding intermediate
10b) exothermic in the presence of both two or three water
molecules.
clear contrast with the unsuccessful attempts to optimize 7bw31
,
the analogous derivative of the aromatic 1b. Furthermore, the
energy of the open chain product 4bw31 was found to be lower
than that of 11bw31 by 10.4 kcal mol-1, indicating that 2b in
water can decompose by ring-opening. Thus, solvation alone
does not provide enough stability for the ionic azolium salt
11bw31, while for the stability of 5bw31 aromaticity contributes
significantly. Consequently, the integrity of the ring of imidazole
derived carbenes in the presence of water, and also that of
imidazolium salts in basic aqueous solution, is attributable to
both aromatic properties and solvation.
Experimental Studies of Carbene Hydrolysis. NMR spec-
troscopic monitoring of the hydrolysis of carbene 1c in both
C6D6 and THF-d8 with different amounts of water ranging from
a substoichiometric quantity (0.5 equiv of water) to a slight excess
(4 equiv) allowed us to identify as the first directly detectable
products the formyl derivative 8c and its Schiff base tautomer 3c,
respectively. The ratio of both products depended on the solvent
used; whereas in C6D6 only traces of 3c were observed, it
constituted the major isomer in the more polar THF (the isomer
ratio varied with the amount of water present but ratios of 3c:8c of
up to 2:1 were observed). Although no ene-diamine tautomer (8a)
had been observed by Denk and co-workers during the hydrolysis of
carbene 1a,8 a similar tautomerization had also been reported for
N-t-butyl and N-aryl substituted R-amino-imines37 and was assumed
to reflect the different electron releasing properties of the substit-
uents present. The formyl derivatives 3c and 8c were found to be
stable in C6D6 solution whereas in THF a further partial hydrolysis
to give small amounts of formic acid and 1,2-bis(2,6-diisopro-
pylphenyl)ethane37 was observed. NMR spectroscopic monitoring
of the progress of the reaction indicated that carbene 1c was in both
solvents hydrolyzed at a much higher rate as had been reported for
1a8 since small amounts of the hydrolysis products were detectable
Interestingly, the barrier of the water addition was found to be
similar for 1b and 2b (25.7 and 23.3 kcal mol-1, respectively),
indicating that this TS is for both molecules destabilized by the
same effect, which is apparently the cleavage of the O-H bond of
the water molecule rather than the change in aromaticity. This is
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Scheme 6. B3LYP/6-311þG** Energy Profile of the Reaction of 2b with Three Water Molecules (Relative Energies in kcal mol-1
)
Chart 2. Chemical Structures of the Molecules Involved in
the Hydrolysis of 2b
concentration of approximately 0.15 mmol mL-1 (as calculated
from the relative signal intensities and the known initial carbene
concentration) is far larger than the maximum concentration of
water in pure benzene at the same temperature (0.042 mmol mL-1
at 30 °C39). Comparison of the NMR data of 1c in anhydrous
solvents or in the presence of water disclosed further small but
significant changes in chemical shifts of all signals, with the largest
deviation being observed for the 13C NMR resonance of the divalent
carbon atom which moved from a value of 220.4 ppm in anhydrous
C6D6 to 217.2 ppm in a carbene-H2O 1:1 mixture.
1
Scheme 7. Optimized Geometries for the Steps of Carbene
Hydrolysis in a Primary Solvate Shell and Their Relative
Inspection of 2D H EXSY spectra of the reaction mixtures
indicated the presence of reversible dynamic exchange between
the protons in H2O and the hydrogen atoms on the imidazole
ring. Similar isotope scrambling had previously been noted to
occur between carbene 1a and solvents with kinetically acidic
protons like DMSO, methanol, or water.40 Although the ex-
change mechanism was not satisfactorily established, it had been
suggested that the H/D-exchange may proceed via a stepwise
protonation-deprotonation involving both an imidazolium ca-
tion and an “abnormal” (4-deprotonated) carbene isomer41 as
key intermediates. NMR signals of imidazolium cations are not
directly detectable in the presence of carbenes as both species
interconvert rapidly by exchange of the acidic proton at C2,42 and
the spectra of mixtures display thus only a single set of NMR signals
which represents the population weighted average of the true NMR
spectra of both components. However, due to the large shift
difference for the ring protons at C4(5) in both species,42 the
position of the averaged signal can still serve as sensitive probe of
the composition of a given solution. In this regard, the observation
that addition of small amounts of water to solutions of carbene 1c in
anhydrous solvents produces only very small displacements (-0.04
ppm in C6D6 and þ0.02 ppm in THF-d8) allows us to rule out that a
significant amount of the carbene was converted into the corre-
sponding imidazolium cation. Therefore, the presence of consider-
able amounts of a bis(carbene)-proton complex42 may also be
ruled out under these circumstances. Instead, we prefer to explain
the observed NMR spectral changes by assuming the presence of a
carbene-water complex in which both components are connected
by hydrogen bonding. The formation of such a complex has
precedence in the characterization of an isolable H-bridged adduct
of a carbene with diphenylamine,28b and is also supported by IR
studies of a solution of 1c:H2O (1:1) in C6D6. The spectrum
Energies (in kcal mol-1 a
)
a The OH- ion formed in the reaction is green.
immediately after mixing all reagents, and cleavage of the imidazole
ring was completed within a few hours. Although no quantitative
kinetic measurements were made, the reaction became faster at
increased water concentrations. Even if the presence of any reaction
intermediates preceding the formation of 3c and 8c was not directly
detectable, thorough analysis of the observed spectral data allowed
us to derive some further information on the initial stages of the
1
reaction. Thus, H NMR spectra of reaction mixtures in both
solvents showed beside the resonances of carbene 1c and hydrolysis
products 3c and 8c a signal attributable to unreacted water. The
chemical shift of this signal differed from the known value of the
water signal in the pure solvent38 and moved to increasingly lower
field when the molar ratio of 1c:H2O increased. The spectra of
solutions in C6D6 were special as in this case a second water signal
appeared when more than 1 equiv of water (with respect to 1c) was
present. As we also observed in these cases the formation of a two
phase system, we attribute one signal (δ = 1.53) to water dissolved
in the organic phase and the second one (δ = 4.7) to the aqueous
phase.38 Integration of the spectra confirmed that the organic phase
contained approximately equal molar amounts of carbene and
water, and allowed us thus to deduce that the absolute water
showed weak absorption bands at 3660, 3151, and 3121 cm-1
,
respectively, which are in reasonable agreement with the scaled43
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B3LYP/6-311þG** values (3737 and 3300 cm-1). These bands are
absent in both a solution of 1c in anhydrous C6D6 and in H2O-
saturated C6D6, respectively, and have similar frequencies as had
been established for the vibrational modes of water-clusters in
benzene (C6H6) where individual water molecules may exhibit
hydrogen-bridging interactions with either the π-system of the
solvent or other water molecules in the cluster.44 The presence of
three bands in the investigated region suggests that more than one
complex might be involved (possibly an equilibrating mixture of free
carbene and assemblies of a carbene with different numbers of water
molecules), which might also explain that the observed upfield shift
of the 13C NMR signal of C2 upon addition of 1 equiv of water
(Δδ -3.2 ppm) is much lower than the difference in B3LYP/IGLO-
III NMR shifts for 1b and 6b (1b, 243.6 ppm; 6b, 228.9 ppm).
In contrast to the results discussed so far, studies of the
hydrolysis of 1c in H2O-THF-d8 mixtures (containing <40%
THF and >290 equiv of H2O) produced a totally different picture.
1H and 13C NMR studies of the strongly alkaline solutions (pH
12-13) indicated that the hydrolysis of the starting material was
complete immediately after mixing. The spectra showed a single set
of signals which were attributable to the imidazolium cation 5c
whereas no indication for the formation of the ring cleaved products
3c and 8c was obtained. Unequivocal identification of 5c was
straightforward from the observed 13C chemical shifts of 126.1
(C2) and 132.3 (C4,5) ppm for the carbon atoms, and the strong
deshielding of the signal of the 4,5-protons in the imidazole ring (δ=
8.0-8.1 as compared to δ = 7.19 in THF-d8). Quite remarkably, a
signal for the proton at C2 was not detectable, which we explain as a
consequence of dynamic exchange with the solvent that is known to
occur at a high rate45 and is considered to induce merging of the
signal of this proton with the H2O signal. Monitoring the reaction
for an extended time indicated that 5c was stable and gave no
evidence for the occurrence of ring cleavage, suggesting that
conversion of the imidazolium salt to the formyl derivatives 3c or
8c, respectively, is under these conditions indeed unfavorable, as it
was predicted for 5b in the microsolvation study and by our
molecular dynamics investigation.
Having verified that hydrolysis of 1c in predominantly aque-
ous or predominantly organic solvent systems (THF, benzene,
<4 equiv of H2O) follows obviously different pathways, we
reckoned that monitoring the reaction in solvent mixtures with
intermediate amounts of water (between 4 and 300 equiv) might
allow us to observe at which point the change in reaction
pathways occurs. To this end, we performed a stepwise titration
of a solution of 1c with water under NMR control. Starting with a
solution of the carbene in anhydrous THF-d8, a specified amount
of water was added at each step and the resulting mixture
analyzed by 1H and 13C NMR. The experiment was carried out
at -35 °C in order to slow down the hydrolysis process and allow
sufficient time for the NMR characterization, and covered
solvent mixtures containing from 0 up to 20% of water.
Inspection of the NMR spectra recorded during the initial
stages of the titration revealed that the solution contained
unreacted 1c as major species beside small amounts of the ring
opened products 3c and 8c which were formed from the very
beginning. During the progress of the titration the signals
attributable to 3c and 8c grew slowly in intensity with increasing
reaction time but showed hardly any variation in chemical shift.
In contrast, the signals of 1c showed very pronounced displace-
ments after each addition of H2O which were largest for the H4,5
protons and the hypovalent carbon C2. Analysis of the titration
curves (Figure 3) reveals that the change in δ1H and δ13C
Figure 3. Titration curves showing the evolution of the chemical shifts
for the H4,5 protons (top) and the C2 carbon atom (bottom) during
titration of a THF solution of carbene 1c with water at -35 °C.
following the addition of the first equivalent of H2O is first cut
back when more water (up to approximately 10 equiv) is added.
A second, substantially larger jump is observed when the ratio of
H2O:1c is further raised from about 20:1 to 60:1, and finally the
curve flattens out when the excess of water grows still larger. Con-
sidering that the final chemical shifts come close to those of the
imidazolium cation 5c, the signal displacement during the later stages
of the titration is readily explained by assuming that the solution
contains a rapidly exchanging mixture of free carbene 1c, its pro-
tonated product 5c, and probably the corresponding bis-(carbene)-
proton complex,42 respectively. The observed resonances represent
then the population weighted average of all species, and the observed
trends imply that the relative population of 5c increases with the
water content of the solution, and that 5c represents the dominant
species during the last stages of the titration. The curvature of the
titration curves during the initial titration steps cannot be explained
by a simple equilibrium between 1c and 5c [probably also a bis-
(carbene)-proton complex42 is involved] but indicates that one (or
more) further species must be involved in the exchange process. As
the rather small absolute chemical shift changes in this regime suggest
that this species exhibits presumably similar spectral characteristics as
1c, we interpret these findings as further experimental evidence in
support of the presence of a hydrogen-bridged carbene-water
complex.
A further aspect worth mentioning is the fact that we found
that the solution which is obtained at the end of the titration and
contains approximately 20% water is not stable, but that conver-
sion of the equilibrium mixture of carbene 1c and its conjugate
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acid 5c into the ring opened products 3c and 8c continues upon
prolonged storage at ambient temperature even if no more water
was added. This behavior is in marked contrast to the long-term
stability of the imidazolium hydroxide solutions obtained by
hydrolysis of 1c in a predominantly aqueous solvent system with
<40% THF.
A further important aspect of our study is the difference between
the reactivity of the aromatic imidazolium-derived system and its
saturated nonaromatic counterpart which yielded exclusively ring-
opened products, independent from the amount of the reacting
water. This underlines the importance of aromatic stabilization
for the robustness of imidazolium derived carbenes and also their
salts. Altogether, our investigations show clearly that imidazo-
lium-based carbenes are much less sensitive against humidity
(i.e., traces of water) than is generally considered.
’ SUMMARY AND CONCLUSION
The experimental and computational study of the hydrolysis
of imidazol-ylidenes at different carbene/water ratios reveals a
complex mechanistic picture. The first step of the hydrolysis of 1c
is the immediate formation of a dynamic mixture of water
-carbene complexes (e.g., 6c). The next reaction step is
determined by the amount of water present, which affects the
basicity of the hydroxide ion in the solution: at low water content,
the isolated OH- is a stronger base (the pKa of water in DMSO is
32)46 than the carbene (pKa of imidazolium ions is approximately
22 in DMSO16), thus preventing the formation of an ionic
imidazolium hydroxide, whereas in the presence of a large
amount of water the basicity of the hydroxide ion is significantly
reduced (pK ca. 16) but the basicity of the carbene remains
unchanged.9,16 As a consequence, under these conditions the
carbene is protonated, and the imidazolium (5c) hydroxide
solvated ion pair is the sole reaction product, in agreement with
results from the microsolvation model calculations and the
molecular dynamics study for 1b. At intermediate water content,
the imidazolium hydroxide 5c[OH] is in dynamic equilibrium
with the carbene 1c and probably an imidazolium-carbene
complex.42 The ratio 1c:5c is controlled by the solvent environ-
ment and increases strongly with decreasing water content,
reflecting presumably both the concentration dependence of
the equilibrium 1c þ H2O / 5c þ OH- and the stabilizing
effect of a more and more hydrophilic environment on the
imidazolium hydroxide. Under these circumstances, also a slow
and irreversible transformation to the ring opened products 3c
and 8c is observed. Apparently, decreasing water concentration
imposes a destabilizing effect on the hydroxide ion so that the
ring opened products may now provide the thermodynamic sink
for the reaction. This is in agreement with the results of the
computational study of the reaction between 1b and 3 mol of
water which shows that although an imidazolium hydroxide
structure indeed exists, the imidazolium ion can be attacked by
the (solvated) OH- to give the ring opened products 3c and 8c
via an energetically accessible transition structure. Finally, the
reaction mixtures with the smallest water concentrations clearly
showed the presence of a 1c-water complex, which was
experimentally detected for the first time. In agreement with
this observation, calculations depicted complexes of carbene 1b
with one or two water molecules as stable compounds whereas a
tautomer 5b(OH-) could not be located as a local minimum but
rather as a transition state connecting the carbene-water com-
plex with 7. These findings led us to conclude that in the presence
of the smallest water concentrations the imidazolium-hydroxide
ion pair does not play a role in the conversion to the ring opened
products 3 and 8, in full agreement with the report of Denk et al.8
who did not observe an appreciable change in the rate of the
hydrolysis of 1a upon addition of acid or base. A quantitative
understanding of the energetics and kinetics of the individual
interconnected reactions would require a still more precise model-
ing of the solvation effects that includes also the possibility of mixed
solvation of the carbene and solvent-water interactions.
’ ASSOCIATED CONTENT
S
Supporting Information. Complete refs 24a and 24c,
b
Schemes S1-S6, geometries (in Cartesian coordinates), total
energies of the optimized structures, and relative energies of the
structures involved in the reaction of 1b with 1-3 and 31 water
molecules at different levels of theory, as well as comprehensive
listings of 1H and 13C NMR data including signal assignments.
This material is available free of charge via the Internet at http://
pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
nyulaszi@mail.bme.hu
’ ACKNOWLEDGMENT
Financial support from the DFG-HAS travel grant, calcula-
tions of Tibor H€oltzl by the Q-Chem 3.2 program package, and
the comments of an anonymous referee are gratefully acknowl-
edged. This work is supported by the New Hungary Development
ꢀ
Plan (Project ID: TAMOP-4.2.1/B-09/1/KMR-2010-0002).
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Journal of the American Chemical Society
ARTICLE
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(31) It should also be mentioned that the ring opening OH inserted
product can proceed via a different, less favorable path (35.8 kcal mol-1
barrier), yielding a zwitterionic structure [Me—N—CHdCH—N-
(Me)—C(H)dOH] that can isomerize to a rotamer of the same Schiff
base in a multistep reaction. The last step of this mechanism having a
61.9 kcal mol-1 barrier is likely to proceed via a bimolecular process and
with a small barrier. For more information, also see Supporting
Information.
(32) Although the isomerization of 8b to 3b provides only 0.2 kcal
mol-1 energy in gas phase calculations, single point PCM calculations
with THF as solvent showed 1.5 kcal mol-1 energy benefits, in better
agreement with the experiments. We also note that there are many
possible isomeric structures of both 8b and 3b; those in the schemes are
the most stable ones.
(33) Although 8a and 3a have identical energy in gas phase calcula-
tions, single point PCM calculations with THF as solvent indicated 3a to
be more stable by 0.8 kcal mol-1, in better agreement with the
experiments.
(34) Although in the case of two and three waters the TS of the
direct 7bw2-1 to 3bw2 and 7bw3-1 to 3bw3 rearrangement has also
been found (37.4 and 36.6 kcal mol-1 B3LYP/6-311þG** barriers,
respectively), the formation of 8b is easier (the 7bw2-2 to 8bw2 and
7bw3-2 to 8bw3 barriers being 24.5 and 21.6 kcal mol-1, respectively,
at the same level). Thus, the reaction presumably proceeds via 8bw2
and 8bw3
.
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