Quantum mechanical study and vibrational spectra of indazolium-3- carboxylate and its decarboxylation product, the N-heterocyclic carbene indazol-3-ylidene

Article abstract of DOI:10.1039/b812597j

Indazolium-3-carboxylate is a molecule that can be found as the nucleus of several pseudo-cross-conjugated mesomeric betaines, such as the alkaloid nigellicine. From a chemical point of view, one of the more interesting properties of this class of molecules is the possibility of forming an N-heterocyclic carbene by thermal decarboxylation. In this paper we have studied the carbene generation by decarboxylation of 1,2-dimethyl indazolium-3- carboxylate, using vibrational (infrared and Raman) spectroscopy and quantum chemistry calculations. Normal mode analysis allowed us to analyse the changes in the stretching force constants upon decarboxylation and to establish spectroscopic-structure relationships. We also investigate the effect of 5-halogen (fluoro, chloro) substitution on the carbene generation. Decarboxylation energy profiles of the three derivatives were calculated. Crossing of the energy paths when going from the transition state to the final product were obtained. The theoretical tendency found for the activation energies agrees with that observed for the decarboxylation temperatures and for the calculated NICS values of the benzene moieties. the Owner Societies.

Full text of DOI:10.1039/b812597j

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PAPER
www.rsc.org/pccp | Physical Chemistry Chemical Physics
Quantum mechanical study and vibrational spectra of indazolium-3-
carboxylate and its decarboxylation product, the N-heterocyclic carbene
indazol-3-ylidene
a
a
b
b
´
Andreas Schmidt, Bohdan Snovydovych, Juan Casado, Jose Joaquın Quirante,
Juan Teodomiro Lopez Navarrete and Francisco Javier Ramırez*
´
b
b
´
´
Received 22nd July 2008, Accepted 14th October 2008
First published as an Advance Article on the web 20th November 2008
DOI: 10.1039/b812597j
Indazolium-3-carboxylate is a molecule that can be found as the nucleus of several pseudo-cross-
conjugated mesomeric betaines, such as the alkaloid nigellicine. From a chemical point of view,
one of the more interesting properties of this class of molecules is the possibility of forming an
N-heterocyclic carbene by thermal decarboxylation. In this paper we have studied the carbene
generation by decarboxylation of 1,2-dimethyl indazolium-3-carboxylate, using vibrational
(infrared and Raman) spectroscopy and quantum chemistry calculations. Normal mode analysis
allowed us to analyse the changes in the stretching force constants upon decarboxylation and to
establish spectroscopic-structure relationships. We also investigate the effect of 5-halogen (fluoro,
chloro) substitution on the carbene generation. Decarboxylation energy profiles of the three
derivatives were calculated. Crossing of the energy paths when going from the transition state to
the final product were obtained. The theoretical tendency found for the activation energies agrees
with that observed for the decarboxylation temperatures and for the calculated NICS values of
the benzene moieties.
elegantissima.10 Indazolium-3-carboxylate is a recently syn-
Introduction
thetised analogue molecule11 of the alkaloid Nigellicine,
Fig. 1b. It is a PCCMB isolated from the herbaceous plant
Nigella sativa Linn.12 The seeds of this plant have been used for
thousands of years as a spice and for the treatment of various
diseases.13
Indazolium-3-carboxylate, Fig. 1a, is a representative case of
the class of alkaloids known as pseudo-cross-conjugated meso-
meric betaines (PCCMB). The mesomeric betaines (MB) are
neutral aromatic molecules that delocalize an even number of
charges within a common p-electron system.1,2 According to the
simple valence bond approach of classification, in a PCCMB
these charges are effectively, but not exclusively, delocalized in
separated parts of the molecule, as the positive charge can be
delocalized into the anionic moiety. Common atoms for the
delocalization of the negative and positive charges exist in
the canonical formulae, although these involve electron sextet
structures with a negligible contribution to the overall electronic
structure. Typically, in PCCMB and CCMB the charged
moieties are joined through an unstarred atom of the anionic
moiety. This atom is a nodal site of the highest occupied
molecular orbital (HOMO) and, consequently, the bond bet-
ween the two charged moieties, commonly named the union
bond, is always a weak single bond which ensures charge
separation within the molecule.
In spite of the fact that the chemistry of conjugated MB has
been widely studied, there is little information about PCCMB.14
Recently a series of halogen derivatives of 1,2-dimethyl
indazolium-3-carboxylate (hereafter MI3C) have been synthe-
sized as new representatives of PCCMB.15 With heating, these
molecules decarboxylate to yield the indazol-3-ylidene ana-
logues (hereafter MI3Y), Scheme 1. In a previous work, these
decarboxylations were studied by electrospray-ionization mass
spectrometry, NMR spectroscopy and differential scanning
calorimetry (DSC).15 The achieved data allowed to analyse
the influence the aggregation state and the halogen substitution
in the decarboxylation temperature.
As depicted in Scheme 1, the product of this reacction can
be described as the contributions of two relevant resonance
Surprisingly, MB are frequently present in nature.1 In fact
some PCCMB have been isolated from natural sources, such as
shihunine from Dendrobium sp.,3–5 flavocarpine from Pleiocarpa
mutica,6,7 aeroginosine A and B from Pseudomonas aeruginosa8,9
or vincarpine and its dihydro derivative from Vinca major
a Institute of Organic Chemistry, Clausthal University of Technology,
Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld, Germany
b
´
´
Departamento de Quımica Fısica, Facultad de Ciencias, Universidad
de Malaga, 29071 Malaga, Spain. E-mail: ramirez@uma.es;
Fig. 1 Chemical structures of the alkaloids indazolium-3-carboxylate
´
´
Fax: +34-952-132000; Tel: +34-952-132258
(a) and nigellicine (b).
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5-chloro indazol-3-carboxylic acids, respectively, using KOH
instead of H2SO4 in the saponification reaction. More details
of this synthesis are reported elsewhere.15
Vibrational spectroscopy
Scheme 1
Infrared spectra at room temperature were recorded from pure
solid samples, dispersed into a KBr pellet, using a Bruker
VERTEX 70 Fourier-transform (FT) spectrometer purged
with dry nitrogen. The KBr used was dried following the usual
routine for infrared measurements (110 1C, at least 24 h),
thus preventing H2O trapping during the decarboxylation).
Typically, 500 scans at a resolution better than 4 cmÀ1 were
accumulated to optimize the signal-to-noise ratio. Individual
scans were examined by the recording routine before aver-
aging, being automatically discarded when the mean intensity
deviations were greater than 10% over the full interferogram
length.
forms. One of these, an all-octet structure, preserves the
separation between the negative and positive charges, which
are now separated by the N2QC3 double bond of the
pyrazolium ring. The second form is an N-heterocyclic carbene
(NHC) in which the carbon atom attached to the carboxylate
group in MI3C possesses an electron sextet structure. In the
solid state, the carbene MI3Y cannot be stabilized after CO2
extrusion.15 On the contrary, in solution of methanol and
deuterated dimethyl sulfoxide the product is able to capture a
proton to give the 1,2 dimethyl indazolium cation. Evidence
has been achieved on the strong relationship between the
phenomenon of pseudo-cross-conjugation and NHC formation
by means of an extrusion reaction.11,16,17
Raman spectra were obtained using both the FRA106/S
module coupled to the VERTEX 70 FT system and the Bruker
Senterra dispersive Raman microscope. Excitation wavelengths
used were 1064 nm (from a Nd-YAG laser at 500 mw) for the
FT-Raman and 532 nm (from a high energy laser diodes at
20 mw) for the dispersive micro-Raman spectra. Spectra resolu-
tion were always better than 2 cmÀ1. Negligible differences were
observed when comparing FT and dispersive Raman spectra.
Spectral measurements were carried out by using the Bruker
OPUSr spectroscopic software.
In this paper we present a spectroscopic study of the genera-
tion of the carbene MI3Y by thermal decarboxylation of the
betaine MI3C in the solid state. We used infrared and Raman
spectroscopies, aided by quantum chemistry calculations in the
framework of density functional theory (DFT) calculations, to
get insight into the mechanistic aspects of this process as well as
characterizing the species involved in the reaction and the
dependency with the chemical structure and the 5-halogen
(fluoro, chloro) substitution. Vibrational spectroscopy is a very
advantageous technique for structural characterization. Com-
pared with other methods, infrared and Raman spectra offer
high sensitivity and a great number of experimental data
directly related with the atoms in the molecules and their bonds.
These techniques are able to be applied to any aggregation state
in a non-destructive form and can be used coupled with a wide
catalog of accessories (temperature, pressure, reflection. . .) and
complementary techniques (electrochemistry, microscopy. . .).
These make infrared and Raman spectroscopy greatly superior
to monitor chemical reactions and their reactants and products.
Decarboxylation reactions were monitorized by infrared
and Raman spectroscopy. A variable-temperature cell Specac
P/N 21525, with interchangeable pairs of KBr windows, was
used for infrared spectra. The variable temperature cell
consists of a surrounding vacuum jacket (0.5 Torr), and
combines a refrigerant Dewar and a heating block as the
sample holder. It is also equipped with a copper constantan
thermocouple for temperature monitoring purposes, so that
any temperature from À170 to 250 1C can be reached. Samples
were inserted into the heating block part or the Dewar/cell
holder assembly in the form of a KBr pellet. Temperature-
controlled Raman spectra were obtained using the heating/
freezing stage THMS600 of the Senterra Microscope. A
temperature controller (Eurotherm) allows us to reach
temperatures from ambient to 600 1C, while temperatures
below ambient were achieved by pumping liquid nitrogen
through the heating/cooling block of the stage.
Experimental methods
Samples
The 1,2-dimethyl indazolium-3-carboxylate, or MI3C, was
synthesized by esterification of indazol-3-carboxylic acid
with methanol, Scheme 2. The N,N-dimethyl derivative was
obtained by treating with dimethylsulfate in xylene and using
nitrobenzene as a catalyst. Final saponification with H2SO4
yielded MI3C. The 5-fluoro and 5-chloro derivatives of this
compound were obtained similarly from the 5-fluoro and
Theoretical calculations
The Gaussian’03 package of programs18 was used for DFT
quantum chemical calculations. The Becke’s three parameter
(B3) gradient-corrected exchange functional was used, and the
non-local correlation was provided by the Perdew–Wang’91
Scheme 2
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(PW91) expressions.19,20 All the electronic and vibrational
properties were calculated using the 6-311+G(2d,p) basis
set.21,22 It includes diffuse functions on heavy atoms and
polarization on heavy and hydrogen atoms, a requirement
necessary for calculations of charged-separated states. This is
also required for diradical structures where some atoms bear
very large electron densities. The open-shell methodology for
both singlet and triplet states was always used. Implicit solvent
was incorporated using a polarizable continuum model
(PCM),23,24 in which the solvent is assimilated to a continuum
characterized by its dielectric constant while the solute
molecule is placed into a size-adapted cavity formed from
overlapping atom-centered van der Waals spheres.
The minimum energy structures were achieved by allowing
all the geometrical parameters to vary independently. Harmonic
force constants, in Cartesian coordinates, were evaluated
at the ground state optimized geometry using analytical
second derivatives. Infrared absorption intensities were
analytically evaluated from the atomic polar tensors.25 The
Cartesian force constants were transformed into a set of non-
redundant locally symmetrized internal coordinates, defined
according to the Pulay methodology,26 which allowed for a
more useful description of the vibrational potential energy.
Wavenumbers and normal coordinates were calculated by the
Wilson FG matrix method.27 Obtained transition structures
(TS) were confirmed by frequency calculations. Subsequent
intrinsic reaction coordinate (IRC) calculations28 were
performed to unsure that the computed transition states
correlate with the minima depicted in Scheme 1. Isotropic
nucleus independent chemical shift (NICS) values were
evaluated by the gauge invariant atomic orbital (GIAO)
method.29 NICS scannings were performed over the optimized
structures at the geometric center of the benzene rings of
the decarboxylation product. NICS scanning over vertical
distances above of that point were also calculated.
Fig. 2 Comparison between the theoretical and the experimental
vibrational spectra of MI3C.
Table 1 summarizes the more intense infrared and Raman
bands and their assignments on the basis of the calculated
potential energy distribution (PED). As can be seen in Fig. 2,
the theoretical spectra exhibit a reasonably good correlation
with the experimental ones in both wavenumbers and inten-
sities. The PED values, together with the calculated intensities,
allow a reliable assignment of the carboxylate bands. Thus, the
two stretching modes are assigned to the two more intense
Results and discussion
Interpreting the vibrational spectra of MI3C
Prior to analyzing the decarboxylation, we have to achieve a
suitable knowledge of the vibrational spectra of MI3C,
especially concerning the region in which vibrations of the
carboxylate group appear. This task has not been reported to
date, so that we have proposed a general assignment of the
vibrational features of this molecule supported by quantum
chemistry and normal mode calculations. The experimental
infrared and Raman spectra of MI3C between 1700 and
700 cmÀ1 are shown in Fig. 2 together with the theoretical
spectra as predicted by B3PW91/6-311+G(2d,p) quantum
chemistry calculation. The quadratic force constants were
uniformly scaled by a factor of 0.96.30 This methodology does
not modify the calculated infrared intensities, which allowed us
to combine them with the scaled wavenumbers in order to
depict the theoretical spectrum. The only exception to this
general procedure was the correction of the low out-diagonal
force constant of the two C–O stretching vibrations, which does
not describe suitably the strong interaction of these two bonds
in the same carboxylate group.
infrared bands in this region, measured at 1657 and 1320 cmÀ1
,
while the corresponding bending vibrations are assigned to the
medium intensity bands at 816 and 748 cmÀ1. The aromatic
stretching vibrations of the benzene and of the pyrazolium rings
and the methyl bending modes are also quite well discriminated.
We would like to emphasize that most of the bands in this
region can be largely assigned, in a good approach, to a single
vibrational local coordinate, which is very useful to monitor the
decarboxylation reaction using vibrational tools.
Once a Cartesian force field is transformed to the space of
locally symmetrized vibrational coordinates, the diagonal force
constants for the stretching vibrations are available. They are
directly interpretable as a measure of the bond strength and can
be also compared with the calculated bond lengths of the
optimized structure. We have depicted in Fig. 3 the stretching
force constants (SFC) and the optimized bond lengths (OBL) of
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Table 1 Experimental and B3PW91/6-311+G(2d,p) wavenumbers and normal mode descriptions for the more intense infrared and Raman
bands of MI3C
Ira
Rama
Calc.b
I,ir
I,Ra
Potential energy distribution (PED)3
À
1657 vs
1607 s
1630 wm
1662
1638
1587
1523
1511
443
54
6
36
16
27
13
32
40
22
100 n (CO2
)
72 n (benzene), 23 n (pyraz)
81 n (benzene)
54 n (pyraz)
29 d(pyraz), 27 n (benzene),
23 n (pyraz)
56 d(CH3), 12 n (pyraz)
34 d(CH3), 23 d(CH),
22 n (benzene), 20 n (pyraz)
88 d(CH3)
1572 s
1517 sh
1508 m
1513 m
1474 w
1484 m
1476 sh
1478
1460
2
44
19
19
1443 m
1436 w
1409 m
1377 w
1363 s
1449
1438
1391
1384
1373
1355
1322
1234
1187
1155
1132
1125
1100
1084
1008
970
16
30
56
7
17
46
246
50
11
7
9
51
5
15
22
16
54
2
27
1
1
5
16
8
1434 w
1405 s
1379 w
1363 wm
1341 s
1320 vs
1246 m
1194 wm
1163 w
80 d(CH3)
74 d(CH3)
34 n (pyraz), 32 d(CH), 24 n (benzene)
90 n (benzene), 17 n (pyraz)
52 n (pyraÀz)
1342 s
1317 m
1247 w
1195 m
1168 w
1141 wm
1124 w
1103 w
71 n (CO2 )
30 d(CH), 24 n (pyraz)
27 d(N–CH3), 27 n (benzene)
59 d(CH)
0
7
3
92 r(CH3)
53 d(CH)
52 r(CH3)
1130 w
1102 w
991 wm
962 w
907 wm
860 vw
816 s
12
14
7
14
2
111
38
31
52 r(CH3), 24 n (pyraz)
60 n (benzene)
999 m
964 w
908 w
861 vw
808 w
762 w
743 m
23
7
8
1
5
62 d(benzene), 17 n (benzene)
27 n (benzene), 23 d(N–CH3), 22 n (pyraz)
92 g(benzene)
898
846
785
744
58 d(CO2À), 18 n (C–CO2À), 16 d(benzene)
761 s
748 sh
1
2
100 g(benzene)
À
741
40 g(benzene),17 g(CO2À), 13 d(CO2
)
a
b
Wavenumbers in cmÀ1. Used symbols for relative intensities are: s = strong, m = medium, w = weak, v = very, sh = shoulder. Potential
energy distribution (values greater than 10%). Symbols used in vibrational coordinates: n (bond stretching), d(aromatic in-plane bending),
g(aromatic out-of-plane bending), r(methyl rocking). Coordinates with the same characters were added to clarify.
MI3C. In our opinion, the most outstanding fact is the low value
obtained for the SFC of the union bond, 2.83 mdyn AÀ1, which
is appreciably lower than the usual values for a typical C–C
single bond (about 4.5–5.0 mdyn AÀ1). This result agrees
with the pseudo-cross-conjugation phenomenon and supports
the CO2 extrusion observed at relatively low temperatures. It
also correlates well with the optimized bond length of 1.559 A.
The six skeletal SFC of the benzene ring show a low dispersion,
namely 1.14 mdyn AÀ1 measured as the difference between the
maximum and the minimum value, being the averaged value
6.64 mdyn AÀ1. On the contrary, this difference is almost three
times higher, 3.12 mdyn AÀ1 within the pyrazolium ring. Here,
the weakest skeletal SFC was calculated for the N1–N2 bond,
6.16 mdyn AÀ1, while the highest one was predicted for the
N1–C5 bond, 9.28 mdyn AÀ1. Interestingly, the N1–C5 OBL is
0.034 A longer than the N2–C3 one, although its SFC is
0.89 mdyn AÀ1 greater, thus suggesting a stronger bond. On
the other hand, the N1–C5 stretching vibration is strongly
coupled with the benzene stretching vibrations in the light of
the PED data, and its contribution to the pyrazolium stretching
modes is small.
Monitoring the decarboxylation of MI3C by infrared and
Raman spectroscopy
We depict in Fig. 4 the effect of increasing temperature on the
vibrational spectra of MI3C. It is worth pointing out that, in
the case of the infrared spectra, the carbon dioxide molecules
were trapped in the potassium bromide pellet, as evidenced by
the appearance of the band at 2335 cmÀ1 (see Fig. 4) which is
due to the antisymmetric stretching vibration of the CQO
bonds. At the same time we observed a noticeable intensity
reduction of the infrared and Raman bands assigned in the
precedent section to the stretching and bending vibrations of
the carboxylate group. The spectral features are also in agree-
ment with large changes in the electronic structure of the
aromatic moiety, especially the pyrazolium ring. This assess-
ment is supported by the fact that no clear correlation can be
Fig. 3 Optimized bond lengths (A) and stretching force constants
(mdyn AÀ1) for MI3C.
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Scheme 1. Subsequent elimination of CO2 generates a charge
separated state, MI3Y, consisting of the carbon atom pre-
viously connected to the carboxylate group charged negatively
and the adjacent nitrogen with positive charge. This structure
has a neutral or charge compensated resonance form, also
illustrated in Scheme 1, in which a carbene species is formed
on the relevant carbon atom while the charge over the nitrogen
is originated exclusively from its electronegativity and those of
the neighbour atoms.
Electronic and vibrational properties of the initial and final
products of this decarboxylation reaction have been compared.
OBL, SFC and Mulliken charges of MI3Y are shown in Fig. 5.
OBL and SFC exhibit similar values to those obtained
for MI3C (Fig. 3) for the benzene moitey. On the contrary,
significant deviations were found for the pyrazolium ring, which
suggests the weakening of the skeletal bonds. The greater
changes are localized in the N1–N2 bond, whose OBL and
SFC change by 3.6 and 31.2%, respectively. We must emphasize
that all the skeletal SFC of the pyrazolium ring decrease;
however, their associated OBL do not always enlarge. The
N2–C3 OBL varies from 1.331 to 1.320 A while its SFC
decreased by 14.0%. In addition, four C–C bonds of the benzene
moiety have shorter OBL and lower SCF values than the C3–C4
bond of the pyrazolium ring. This unusual result not only
evidences a significant change in the characteristics of this bond,
and more specially in the common atom C3, but the nature of
the bonds of the whole pyrazolium ring are modified. We have
summarized in Table 2 the calculated wavenumbers of both
MI3C and MI3Y in which the contribution of intrinsic stretch-
ing vibrations of the pyrazolium ring is greater than 10%. These
selected values in both molecules are well supported by experi-
mental wavenumbers. At a first glance, we observe two different
correlations of wavenumbers and assignments. However, we can
appreciate that the wavenumbers for MI3Y are lower, as a
whole, than those calculated for MI3C. Lower wavenumbers are
indicative of weaker bonds, which supports the contribution of
the carbene resonant form of MI3Y since it only presents single
bonds, while the charge-separated form displays pseudo-
aromaticity (see Scheme 2). A non-vanishing contribution of
the carbene form in the structure of MI3C is also supported by
the Mulliken charge distribution (Fig. 5). The charge over the
N2 atom is +0.44 a.u., or intermediate between +1 (charge-
separated form) and 0 (carbene form) and even lower than the
charge of the C4 atom, +0.71 a.u. In addition, the charge over
the C3 (the negative center in the first form) is only À0.09 a.u.
Fig. 4 Evolution of the infrared and Raman spectra of MI3C when
going from 20 to 170 1C. The arrows indicate the main spectral
features. The band of the insert belongs to the carbon dioxide
molecules trapped into the potassium bromide pellet.
found for most of the pyrazolium vibrational bands, while
those assigned to the benzene ring are easily correlated with
bands appearing at similar wavenumbers. In consequence,
information about the behaviour of the pyrazolium stretching
vibrations will help us to characterize the properties of the
final product of the decarboxylation.
Characterizing of the decarboxylation product
Quantum chemical modelling of the decarboxylation mecha-
nism has been carried out by assuming the reaction pathway in
Fig. 5 Optimized bond lengths (A), stretching force constants (mdyn AÀ1) and atomic charges (atomic unit) of MI3Y.
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Table 2 B3PW91/6-311+G(2d,p) wavenumbers of MI3C and MI3Y
in which the pyrazolium stretching modes have contributions greater
than 10%
MI3Ca
n (py)b Main assign.c MI3Ya
n (py)b Main assign.c
1638 (1607) 23
1523 (1517) 54
1511 (1513) 23
1478 (1484) 12
1460 (1474) 20
1384 (1377) 34
1373 (1363) 17
1355 (1341) 52
1234 (1247) 24
1084 (1102) 24
n (benz)
n (pyraz)
n (pyraz)
d(CH3)
d(CH3)
n (pyraz)
n (benz)
n (pyraz)
d(CH)
1628 (1624) 16
n (benz)
d(CH)
d(CH3)
1494 (1516) 19
1483 (1482) 24
1436 (1446) 28
1373 (1382) 32
1337 (1331) 24
1231 (1250) 67
1203 (1196) 30
1032 (1014) 33
889 (907) 25
834 (835) 46
711 (712) 38
d(CH3)
n (pyraz)
n (benz)
n (pyraz)
n (pyraz)
n (pyraz)
d(benz)
n (pyraz)
n (pyraz)
r(CH3)
n (benz)
898 (907)
22
Wavenumbers in cmÀ1. The values in parentheses are the observed
wavenumber, either infrared or Raman bands, having the highest
b
intensity. Contribution, in terms of PED, of the stretching modes
a
Fig. 7 Comparison between the theoretical B3PW91/6-311+G(2d,p)
and the experimental infrared spectra of MI3Y.
of the pyrazolium bonds C4–C3, C3–N2, N2–N1 and N1–C5.
c
Vibrational coordinates which have the greater contribution to the
PED. See footnotes of Table 1 for symbols.
by the intensities. The largest deviations are observed in the
methyl bending region (1300–1450 cmÀ1) of both the infrared
and the Raman spectra. Methyl group polarization, and a
consequent enhancement of its bending infrared bands, can
not be excluded, especially for the N1-attached CH3 group.
For the remaining regions, the profiles of the calculated and
experimental spectra present a better similarity.
Theoretical study of MI3Y
Fig. 6 shows the calculated dipole moments (DM) and the
electronic density surfaces (EDS) of the two molecules. As
observed, decarboxylation gives rise to a dramatic reduction of
the DM, which goes from 11.85 D in MI3C to 4.50 D in
MI3Y, and to an appreciable change of its direction. The
normalized EDS explain these changes, as the highest electron
density moves from the oxygen to the nitrogen atoms and the
peripheral hydrogen atoms withdraw electron density from the
inner regions of the molecule. It is worthy to comment that, in
spite of the fact the C3 position does not have any attached
hydrogen atom, an considerable electronic density toward the
outer region of the molecule was obtained. This result is
compatible with the presence of two non-bonded electrons
on this position.
In the gas phase, where the previous discussed calculations
were made, the charge separated form could contribute less than
the carbene form. This fact might be solvent dependent, so that
the whole theoretical treatment of MI3Y was also performed
using a water-like PCM model. By comparing with the results
for the isolated molecule, minimal differences were obtained
for OBL and SFC values. The most noticeable deviation was
found for the charges over the bonded atoms C3 and N2, which
are now À0.34 and +0.32 a.u. This balances the charge separation
around this bond and, simultaneously, increases the contribu-
tion of the first resonant form in MI3Y. The calculated PCM
infrared and Raman spectra, included in Fig. 7 and 8, introduce
subtle improvements with respect to those obtained in gas phase,
which are largely due to minor changes in the calculated
We calculated the infrared and Raman spectra of MI3Y,
which are depicted in Fig. 7 and 8 together with the observed
ones of the decarboxylation product. In this case, the good fitting
when comparing the wavenumbers is not always accompanied
Fig. 6 Electrostatic potential surfaces and dipole moments of MI3C
Fig. 8 Comparison between the theoretical B3PW91/6-311+G(2d,p)
and MI3Y.
and the experimental Raman spectra of MI3Y.
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Scheme 3
intensities. The wavenumbers listed in Table 2 for MI3Y are
similar for PCM and gas phase. A noticeable improvement was
only obtained for the observed band at 1250 cmÀ1, which was
now calculated at 1254 cmÀ1. For the rest of experimental
Fig. 9 Energy profile diagram of the decarboxylation of 5-H (blue),
5-F (green) and 5-Cl (red) derivatives of MI3Y.
wavenumbers deviations are within Æ5 cmÀ1
.
Taking into account the presence of two non-bonding
electrons in MI3Y, we have investigated the first triplet state
of this molecule. We calculated a S0–T1 gap resulting to be
47.3 kcal molÀ1, which is similar to the reported value using the
B3LYP functional and the 6-31G(p) basis.11 This relatively high
exchange energy is justified taking into account the stabilization
energy that aryl groups add to the electronic states of carbenes,
which is greater by several kcal molÀ1 for singlet than for triplet
states.31 On the other hand, calculated open-shell spin densities
of MI3Y indicate that the contribution of resonant forms in
which the non-bonding electrons are unpaired, Scheme 3, are
negligible. We are therefore confident that the ground state of
this molecule is a singlet. The T1 state will have, therefore, a
very low population even at the decarboxylation temperatures
higher than 400 K. In addition, no appreciable contamination
by states of higher spin multiplicity was predicted for the S0
(open shell) state, while a very low spin contamination of 2.029
was calculated for the T1 state. No significant distortions are
therefore expected for the predicted potential energy surfaces
of this molecule, thus supporting the reliability of further
calculations of reaction energy profiles.32
energy ordering relative to the substituted atom is reversed
when going from activation energies to reaction energies. In
other words, the same atom (Cl) induces the more stable TS and
the less stable final product.
In order to give an explanation of these energies we
calculated NICS over the benzene moiety of the three molecules.
A negative NICS value is a measure of local aromaticity in
polycyclic systems,29 and they are being widely used to evaluate
this property.33–35 Initially, NICS are refered at the geometric
center of the cycle. It has been demonstrated that in this point
the NICS values can be contaminated by contributions from
electrons other than p (s, lone pairs, core. . .).29 In consequence,
we have scanned over a perpendicular height above the center of
the benzene ring to obtain a better evaluation of the p effect.
Typically, the values calculated near 1.0 A are recommended as
suitable indicators of aromaticity.36 The results obtained for
MI3Y and its 5-fluoro and 5-chloro derivatives are depicted in
Fig. 10. The NICS(1.25) values support the relative energies
shown in Fig. 9. The order 5H o 5F o 5Cl is reached for the
NICS(1.00), although the 5H-5F difference is too small when
comparing with its energy difference. NICS(1.00) was also the
more negative value for MI3Y-5H, in accord with previous
studies on five and six membered rings of condensed aromatic
systems.34 The presence of the halogen changes this behavior,
as the 5F and 5Cl derivatives have their minima at 0.5 A above
the center. This result indicates that the lone-electron pairs of the
Influence of 5-halogen substitution on the decarboxylation of
MI3C
The above experimental–theoretical comparison supports the
pathway proposed for the decarboxylation reaction and permits
further insight on the dependence of the reaction energetics with
the substitution of the phenyl group. Fig. 9 shows the energy
profiles obtained for the three compounds from the IRC
calculations. Activation energies around 11–12 kcal molÀ1 are
rather low in line with the low temperatures, around 100 1C,
measured in the TGA experiments. This finding is also in
agreement with the low values for the SFC of the union bond
and that breaks down in the reaction under study (i.e., lower
than 3 mdyn AÀ1). Furthermore the theoretical tendency found
for the activation energies (i.e., 5H 4 5F 4 5Cl) correlates
well with the starting temperatures for the CO2 extrusion (i.e.,
116 1C 4 100 1C 4 94 1C), such as previously reported,15 and
Fig. 10 NICS values of the benzene ring in 5-H (blue), 5-F (green)
and 5-Cl (red) derivatives of MI3Y calculated as a function of the
vertical height over the geometrical center of the cycle.
with the SFC provided in this study (i.e., 2.83 mdyn AÀ1
2.82 mdyn AÀ1 4 2.80 mdyn AÀ1). Fig. 9 also shows that the
4
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Phys. Chem. Chem. Phys., 2009, 11, 341–348 | 347

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halogen, that do not contribute to the p system, have a non-
vanishing effect at this height. In consequence, the NICS values
undergo a noticeable increase when increasing the distance, an
effect not observed for the 5H derivative.
4 M. Elander, L. Gawell and K. Lander, Acta Chem. Scand., 1971,
25, 721.
5 E. Breuer and S. Zbaida, Tetrahedron, 1975, 31, 499.
6 G. W. Gribble and E. A. Johnson, Tetrahedron Lett., 1987, 28,
5259.
7 G. Buchi, R. E. Manning and F. A. Hochstein, J. Am. Chem. Soc.,
¨
1962, 84, 3393.
Typically two main effects have to be considered associated
to the halogen substitution in this molecule: the inductive
(electronegativity) and the resonant (lone pairs) or mesomeric
effects. The first one is the predominant; however it largely
involves the s bond of the attached carbon atom. The Mulliken
charges calculated for the three molecules confirm that the
charges on the C5 and C4 atoms (the common atoms between
benzene and pyrazolium rings) are invariant with respect to the
substitution. On the contrary, the mesomeric effect acts on
the p system. In consequence it has the possibility of reaching
the C3 position through the conjugated p bonds, thus account-
ing for the obtained parameters since there is a large distance
between the breaking bond and the substituted position.
8 F. G. Holliman, J. Chem. Soc. C, 1969, 2514.
9 R. B. Herbert and F. G. Holliman, South African Ind. Chem., 1961,
15, 233.
10 E. Ali, V. S. Giri and S. C. Pakrashi, Tetrahedron Lett., 1976, 17,
4887.
11 A. Schmidt, L. Merkel and W. Eisfeld, Eur. J. Org. Chem., 2005,
36, 2124.
12 Atta-ur-Rahman, S. Malik, H. J. Cun-heng and Clardy, Tetrahe-
dron Lett., 1985, 26, 2759.
13 cf. Matthaeus, The Holy Bible, New Testament, Math. 23:23.
14 A. Schmidt, Curr. Org. Chem., 2004, 8, 653.
15 A. Schmidt, B. Snovydovych, T. Habeck, P. Drottboom, M. Gjikaj
¨
and A. Adam, Eur. J. Org. Chem., 2007, 38, 4909.
16 A. Schmidt, A. Beutler, T. Habeck, T. Mordhorst and
B. Snovydovych, Synthesis, 2006, 1882.
17 A. Schmidt, T. Habeck, L. Merkel, M. Makinen and P. Vainiotalo,
¨
Rapid Commun. Mass Spectrom., 2005, 19, 2211.
Conclusions
18 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, J. J. A. Montgomery, T. Vreven,
K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi,
V. Barone, B. Mennucci, M. Cossi,G. Scalmani, N. Rega,
G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota,
R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda,
O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian,
J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts,
R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli,
J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth,
P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich,
A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick,
A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz,
Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov,
G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin,
D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng,
A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson,
W. Chen, M. W. Wong, C. Gonzalez and J. A. Pople, GAUSSIAN
03, Gaussian, Inc., Wallingford, CT, 2004.
The vibrational spectra of indazolium-3-carboxylate and its
decarboxylated derivative have been interpreted using normal
coordinate analysis based on quantum chemistry calculations.
The CO2 extrusion was monitored by infrared and Raman
spectroscopy. A wide set of structural properties (stretching
force constants, optimized bond lengths, atomic charges,
electrostatic potential surfaces, dipole moments) was calculated
for the decarboxylation product. The influence of the medium
was also investigated. In summary, our results indicate that
both the charge-separated and the N-heterocycle carbene forms
noticeably contribute to the chemical properties of this product.
The effect of Cl and F substitution in the 5-position of the
benzene moiety was also investigated. The decarboxylation
temperatures correlated well with the stretching force
constants of the breaking bond and with the calculated
activation energies for the three derivatives. The analysis of
the NICS also agrees with the experimental results and
allowed us to interpret the observed trend in terms of the
contribution of the halogen lone-pairs to the aromaticity.
19 A. D. Becke, J. Chem. Phys., 1993, 98, 5648.
20 J. P. Perdew and Y. Wang, Phys. Rev. B, 1992, 45, 13244.
21 P. C. Hriharan and J. A. Pople, Theor. Chim. Acta, 1973, 28, 213.
22 T. Clark, J. Chandrasekhar, G. W. Spitznagel and P. V.
R. Schleyer, J. Comput. Chem., 1983, 4, 294.
23 S. Miertus, E. Scrocco and J. Tomasi, Chem. Phys., 1981, 55, 117.
24 S. Miertus and J. Tomasi, Chem. Phys., 1982, 65, 239.
25 S. J. Hickling and R. G. Wooleey, Chem. Phys. Lett., 1990, 166, 43.
26 P. Pulay, G. Fogarasi, F. Pang and J. E. Boggs, J. Am. Chem. Soc.,
1979, 101, 2550.
Acknowledgements
27 E. B. J. Wilson, Chem. Phys., 1939, 7, 1047.
28 K. Fukui, Acc. Chem. Res., 1981, 14, 363.
29 P. V. R. Schleyer, C. Maerker, A. Dransfeld, H. Jiao and
V. E. Hommes, J. Am. Chem. Soc., 1996, 118, 6317.
30 A. P. Scott and L. Radom, J. Phys. Chem., 1996, 100, 16502.
31 H. L. Woodcock, D. Moran, B. R. Brooks, P. V. R. Schleyer and
H. F. Schaefer III, J. Am. Chem. Soc., 2007, 129, 3763.
32 C. Sosa and H. B. Schlegel, Int. J. Quantum Chem., 1986, 29, 1001.
33 D. Moran, F. Stahl, H. F. Bettinger, H. F. Schaefer III and P. V.
R. Schleyer, J. Am. Chem. Soc., 2003, 125, 6746.
This work was supported by the Spanish Ministry of Science
and Technology, grant CTQ2006-14987-C02-01. We would
also like to thank to P.A.I., grant P06-FQM-01678, for
financial support. J.C. is grateful to the MEC of Spain for
an I3 position of Chemistry at the University of Malaga.
´
References
1 A. Schmidt, Adv. Heterocycl. Chem., 2003, 85, 67.
2 W. D. Ollis, S. P. Stanforth and C. A. Ramsden, Tetrahedron,
1985, 41, 2239.
3 Y. Inobishi, Y. Tsuda, T. Konita and S. Matsumoto, Chem.
Pharm. Bull., 1964, 12, 749.
34 S. Suzuki, Y. Morita, K. Fukui, K. Sato, D. Shiomi, T. Takui and
K. Nakasuji, J. Am. Chem. Soc., 2006, 128, 2530.
35 J. Poater, J. M. Bofill, P. Alemany and M. Sola, J. Org. Chem.,
2006, 71, 1700.
36 A. Stanger, J. Org. Chem., 2006, 71, 883.
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348 | Phys. Chem. Chem. Phys., 2009, 11, 341–348