Thiourea and isothiocyanate - Two useful chromophores for stereochemical studies. A comparison of experiment and computation

Article abstract of DOI:10.1039/b821335f

Thioureas and isothiocyanates, compounds of high importance in organic synthesis, have not been considered so far as chiroptical probes that can provide structural information from the analysis of circular dichroism spectra. CD spectra of a set of molecul

Full text of DOI:10.1039/b821335f

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Thiourea and isothiocyanate – two useful chromophores for stereochemical
studies. A comparison of experiment and computation†
Jacek Gawronski,* Marcin Kwit and Pawel Skowronek
Received 28th November 2008, Accepted 26th January 2009
First published as an Advance Article on the web 25th February 2009
DOI: 10.1039/b821335f
Thioureas and isothiocyanates, compounds of high importance in organic synthesis, have not been
considered so far as chiroptical probes that can provide structural information from the analysis of
circular dichroism spectra. CD spectra of a set of molecules containing the thiourea, isothiocyanate and
phthalimide chromophores were obtained and analyzed on the grounds of the calculated populations
of conformers and their individual contributions to the CD spectra. It is shown that the thiourea and
isothiocyanate chromophores can provide useful structural information from the analysis of their
exciton-coupled CD spectra. Exciton-coupled CD spectra of thioureas were found to be sensitive to the
Z/E conformation of the chromophore. DFT calculations based on the B2LYP functional were shown
to provide a better match with the experimental spectra collected in the short wavelength region,
compared to the traditionally used B3LYP functional.
Many ab initio methods are now well established as useful
tools for predicting and understanding the chemical and physical
Thiourea and isothiocyanates are the two classes of organic sul-
phenomena, such as molecular structure, vibronic and electronic
Introduction
spectra with high accuracy.19 Nowadays there are two different
approaches for determination of absolute structure of chiral
molecules. X-ray crystallography is successful if a single crystal
is available and if the molecule contains at least one heavy atom to
allow reliable anomalous dispersion measurements.20 On the other
hand, a comparison of experimental and calculated chiroptical
data emerges now as a general and more convenient method,21
especially in the cases where simple empirical rules for various
types of chromophores do not provide correct stereochemical
predictions for a broad spectrum of investigated molecules.22
Among the methods offered currently by theoretical chemistry
for stereochemical investigations, those based on time-dependent
density functional theory (TDDFT) are most frequently used,
and again among the many functionals available, the B3LYP
hybrid functional in conjunction with basis sets ranging from
the relatively small (i.e. 6-31G(d)) to the very large (i.e. aug-CC-
pVXZ) finds the broadest applicability.23,24 Although the B3LYP
functional is the most frequently used for calculations of many
molecular properties, it may not provide satisfactory results for
calculations of properties dependent on long- and medium-range
noncovalent interactions25 and for transition metal chemistry. In
recent years, the development of new functional forms and their
validation against diverse databases have yielded new powerful
density functionals of broad applicability to many areas of
chemistry.26 For example, a few years ago Grimme proposed
a new functional, containing only two empirical parameters
and dubbed B2PLYP,27 which belongs to a general class of
double-hybrid density functionals (DHDFs). This virtual orbital-
dependent functional is based on a mixing of standard generalized
gradient approximations (GGA) for exchange by Becke (B) and
for correlation by Lee, Yang and Parr (LYP) with Hartree–Fock
(HF) exchange and a perturbative second-order correlation part
(PT2) that is obtained from hybrid-GGA–Kohn–Sham orbitals
fur/nitrogen compounds with numerous applications in synthetic
organic chemistry, materials chemistry, agriculture1–3 and crystal
engineering.4 Of particular interest are chiral compounds with
thiourea or isothiocyanate functional groups, which may serve as
chiral thiourea organocatalysts,5–12 chiral receptors13 and chiral
derivatizing agents.14 Despite the wide interest in such molecules,
very little is known of their chiroptical properties, electronic
circular dichroism (ECD) spectra in particular. Although isothio-
cyanates and thioureas are derived from amines they have not been
considered in the past as useful amine chromophoric derivatives.
This is in contrast to other amine chromophoric derivatives,
such as Schiff bases, benzamides or aromatic imides,15–17 which
have routinely been used in stereochemical studies.18 We wish
to report that isothiocyanates and thioureas, can serve as useful
chromophoric tags, allowing assignment of absolute configuration
or conformation from their ECD spectra. We used in this study
the derivatives of chiral trans-1,2-diaminocyclohexane (DACH)
of known conformational rigidity, which allows one to reduce the
number of significant conformers and to simplify the calculations
of low-energy structures and their ECD spectra. In addition, we
used the phthalimide chromophore as a reference for testing exci-
ton coupling power of the isothiocyanate and thiourea electronic
transitions. It is known from our previous studies that the principal
electronic transition of the phthalimide chromophore is located
on its C2 symmetry axis and therefore its position is insensitive to
chromophore rotation.15
Department of Chemistry, A. Mickiewicz University, Grunwaldzka 6, 60 780,
Poznan, Poland. E-mail: gawronsk@amu.edu.pl; Fax: +48 61 829 1505;
Tel: +48 61 829 1313
† Electronic supplementary information (ESI) available: Calculated struc-
tures and UV and CD spectra of compounds 1–10; experimental NMR
and MS spectra of compounds 5a, 5b, 7, 8a, 8b, 9 and 10. See DOI:
10.1039/b821335f
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and eigenvalues. Several studies have shown that DHDFs give
very accurate results for large molecules, thermodynamic data
and molecular structures comparable to those from CCSD(T).28
This and other new functionals are implemented in the latest
versions of TURBOMOLE29 package and they can also be run by
Gaussian0330 ground-state calculations, using the IOPs and extra-
overlays given in the original paper.27 The method was extended
recently by Grimme and Neese to electronically excited states
in the framework of TDDFT.31 This procedure is completely
analogous with a B2PLYP treatment of the electronic ground
state; however, for excited states the corrections to excitation
energies are calculated based on configuration interaction with
the perturbative double correction method CIS(D).32 It should be
noted that only the energy is corrected in this procedure, while all
other computed properties (oscillator and rotatory strengths and
transition moments for UV and CD) refer to the TD-hybrid-GGA
(in this case TD-B2LYP) level. One should bear in mind, however,
that using the IOPs and extra-overlays given in the original
paper27 for excited-state calculations with the use of Gaussian03
package, only the calculations with the hybrid part of the B2PLYP
functional can be carried out. For ECD spectroscopy, calculations
with the use of DHDFs, including perturbative corrections or
not, outperform other TDDFT approaches33 and therefore can be
used as a method of choice for reliable calculations of chiroptical
properties of chiral systems.
In this paper we intend to show that thiourea and isothio-
cyanate molecules can act as chromophores for chiroptical studies.
The experimental CD/UV data are analysed on the grounds
of TDDFT computational results. We have chosen to use for
computations the newly developed functional B2LYP as well as
the most popular B3LYP functional for comparison. Due to the
size of the molecules used in the present study, we have chosen not
to apply the perturbative correction to the excitation energies at
the CIS(D) level.
Chart 1
the steric effects on the conformational equilibria. Both types of
molecules were synthesized and characterized by spectroscopic
methods as well as by TDDFT calculations of spectroscopic
properties.
Our computational studies were performed as follows: (i) con-
formational searches for simple achiral model molecules 1b, 2a, 2b
at the B3LYP/6-311++G(d,p) level, which allowed construction
of the PES for these molecules; (ii) full structure optimizations at
the B3LYP/6-311++G(2d,2p) level were performed for the energy
minima found on the PES; (iii) the results obtained for model com-
pounds were used as input parameters in conformational analyses
of more complex molecules 4–9; (iv) full structure optimizations
at the B3LYP/6-311++G(2d,2p) level were performed for low-
energy conformations of 4–9; (v) oscillator and rotatory strengths
for thermally accessible conformers of 1–10 were calculated; (vi)
for all optimized structures, frequency calculations were carried
out at the B3LYP/6-311++G(2d,2p) level of theory to confirm
that the conformers are stable; (vii) for the conformers having
relative energies ranging from 0.0 to 2.0 kcal mol-1, percentage
populations were calculated on the basis of the DG values, using
Boltzmann statistics and T = 298 K.
Results and discussion
Synthesis
Cyclohexyl isothiocyanate (1b) was commercial and was used
without additional purification. Compounds 2b,34 4,35 and 615
have been reported in the literature. The synthesis of 5a, 5b
and 7–10 is quite straightforward and described in the Ex-
perimental – it involves the reaction of N-phthaloyl-(R,R)-1,2-
diaminocyclohexane36 with thiophosgene to give 7 or with isothio-
cyanates 1a and 1b to give the thioureas 8a and 8b, respectively. The
reaction of 7 with N-phthaloyl-(R,R)-1,2-diaminocyclohexane
yields symmetrical thiourea 9 while the reaction of (R,R)-1,2-
diaminocyclohexane with thiophosgene yields cyclic thiourea 10
(Chart 1).
The results of our DFT calculations at the B3LYP/6-
311+G(2d,2p) level for molecules 1–10 are collected in Table 1
(see also Fig. A–C, ESI†).
Structure
Knowledge of the detailed structure of a molecule is a prerequisite
for calculation of its spectroscopic properties. Whereas structures
of isothiocyanates and thioureas are deceptively simple, their
conformations are not. For the present study we have chosen
molecules having different substituents – either small (methyl)
or bulky (cyclohexyl) – in order to determine the significance of
Methyl isothiocyanate (1a) has only one significant planar
structure (apart from rotamers due to the methyl substituent),
◦
=
having the calculated C–N C angle 149.2 . Cyclohexyl isothio-
cyanate molecule (1b) shows a more diverse conformational profile
(Fig. 1). Although the equatorial conformer with CS symmetry
◦
=
and torsion angle a (H–C–N C) equal to 180 is calculated as a
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Table 1 Structures of thermally accessible conformers of 2b, 4–10 calculated at the B3LYP/6-311++G(2d,2p) level, their relative energies (DG) and
populations
Compound
Symmetry
DG/kcal mol-1
Population (%)
Torsion angles a, a¢ (◦)
2b Z,Z
C2
C1
C1
C1
C1
C2
C2
C1
C2
C2
C2
C1
C2
C1
C2
C2
C1
C1
C1
C1
C1
C1
C1
C2
C2
0.00
0.51
0.0–0.6
0.8–1.1
0.8
1.0–1.1
1.5
71
29
56
22
6
8
2
-30a
2b E,Z
-35a, -30a
29–34b, 40–48b
5–48b, -16–91b
54b, 177b
56b
4 sp,sc (dieq.)
4 sp,sc (dieq.)
4 sc,ap (dieq.)
4 sc,sc (dieq.)
4 ap,ap (dieq.)
4 sc,sc (diax.)
4 ap,ap (diax.)
5a Zd,Zd,E,E
5a Zd,Zd,Z,Z
5a Zd,Zd,Z,E
5b Zd,Zd,E,E
5b Zd,Zd,Z, E
5b Zd,Zd,Z,Z
6
170b
1.1–1.6
1.9
5
1
46–64b, 60–65b
180b
0.00
0.11
0.19
0.00
0.25
0.98
—
39
33
28
55
35
10
>99
>99
37
34
29
76
24
94
6
-16b
-22b
-24b, -15b
40a, -18b
-27a, -9b, -25b, 40a
-30a, -18b
4c
7
—
62b, 5c
8a Zd,E
0.00
0.05
0.12
0.00
0.68
0.00
1.63
—
30b, -18c
32b, -19c
14b, 13c
8a Zd,Z
8a Ed,Z
8b Zd,Z
30a, 32b, -19c
-28a, 18b, 14c
-7c, 40b, 38b, -20c
32b, -20c
-81b
8b Ed,Z
9 E,Z
9 Z,Z
10
>99
d
a H–Ccyclohexane–N–C( S). b H–CDACH –N–C( S). c H–CDACH –N–C( O). CDACH –N–C S.
=
=
=
=
the molecule. In fact, single-point optimization of geometry of
conformer CS of 1b leads to the lowest energy structure C1, having
torsion angle a = 60◦.
Axial conformers of 1b are generally of higher energy (0.6–
0.7 kcal mol-1) compared to the lowest-energy equatorial con-
former, and the computation shows again a continuum of accessi-
ble conformers of C1 and CS symmetry due to the rotation around
the C–N bond (Fig. 1).
The conformations of thioureas were previously the subject of
study by NMR, IR and X-ray diffraction methods. Three distinct
conformers, Z,Z (trans,trans), Z,E (trans,cis) and E,E (cis,cis)
can be envisaged, as shown for N,N¢-dicyclohexylthiourea (2b)
(Fig. 2).
In solution the presence of planar and non-planar conformers is
suggested, according to NMR and IR spectra, the Z,E conformer
being the main constituent of the equilibrium mixture.34,37,38
The conformational equilibria depend on the size of thiourea
substituents – planarity of the thiourea molecule is apparently
more pronounced for the dimethyl derivative than for other N,N¢-
disubstituted derivatives. In the solid state, X-ray diffraction
studies show39 that both low-energy types of conformers, Z,Z
and Z,E, can be encountered, each conformer type involved in a
different pattern of intermolecular hydrogen bonding.40
N,N¢-Dimethylthiourea (2a) has two low-energy conformers,
=
Z,E (planar, CS symmetry) and Z,Z (slightly twisted, H–N–C S
angle a = 177◦, C2 symmetry), in an equilibrium ratio 93 : 7.
This is in keeping with a general tendency for conformational
preferences of dialkyl thioureas and with the results of recent DFT
calculations at the B3LYP/6-31G(d) level of the relative energies
of conformers of N,N¢-dialkylthioureas.41 A much higher relative
energy has been calculated for the planar E,E conformer of 2a
as well as for non-planar conformers of 2a (0 < a, a¢ < 180), in
Fig. 1 PES for equatorial and axial conformers of 1b calculated at the
B3LYP/6-311++G(d,p) level.
low-energy structure, rotation of the isothiocyanate group around
the C–N bond does not significantly increase the total energy of
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the relationship between the total energy of the molecule and
the rotation of the isothiocyanate substituents, torsion angles
H–C*–N–C were changed at 30◦ steps to give 144 different
structures for each diequatorial and diaxial conformers of 4.
Then single-point energy calculations were performed for each
conformer and this allowed the construction of the PES for
4 (see Fig. D, ESI). The conformers which were found as the
energy minima on the PES were fully optimized at the B3LYP/6-
311++G(2d,2p) level of theory. As expected, in all conformers
of 4 the isothiocyanate moieties were bent◦, with the calculated
=
C–N C angle in a narrow range, 145–147 . The lowest-energy
conformers of both diequatorial and diaxial 4 are of C1 symmetry
(Table 1) and are grouped into families of conformers according
=
to the magnitudes of the H–CDACH –N–C( S) torsion angles. In the
family of C1 symmetry conformers one of the torsion angles is
sc; bis-sc structures are of the lowest energy among the diaxial
conformers of 4. Bis-ap structures are of C2 symmetry and are
of higher energy, hence their calculated population is only within
1–2%. The most stable conformers of 4, diequatorial sp,sc, count
for 78% of the entire conformer population. This is of importance
with respect to the discussion of the chiroptical properties of 4 (see
below). Note that torsion angles a and a¢ for conformers of 4 are
positive in the majority of cases.
Fig. 2 Definition of torsion angles a in basic conformers of compounds
1b–3b: 1b, a = H–C–N C; 2b, a, a¢ = H–C–N–C; 3b, a = H–C–N–C.
=
comparison to the energies of planar Z,Z and Z,E conformers (see
Fig. 3).
Low-energy structures of dithioureas 5a and 5b are uniform
=
in their tendency for Z configuration around the CDACH –N–X S
bond (Table 1). They also show a preference toward mixed Z/E
configuration around each thiourea moiety, although all-Z and
mixed Z,E/Z,Z structures do not differ much in their energies,
except the all-Z conformer of 5b. Torsion angles a and a¢ around
the C–N bonds of DACH molecules are uniformly negative, in the
range -9◦ to -25◦, as expected for the R,R configuration of the
DACH scaffold.
Bis-phthalimide 6 and isothiocyanate-phthalimide 7 derivatives
of DACH are conformationally restricted molecules, with little
rotational freedom around the C–N bonds. This is apparently due
to the steric constraints imposed by the phthalimide group(s).
Hence, the only accessible conformers are these with eclipsed
◦
=
H–CDACH –C O bonds (torsion angles a ca. 5 ). The isothiocyanate
substituent in 7 is turned away from the phthalimide moiety, hence
angle a is synclinal (62◦).
=
Fig. 3 PES for 2a as a function of torsion angles a and a¢ (H–N–C S)
Phthalimide-thiourea derivatives 8a and 8b display structural
diversity due to Z,E conformational changes of the thiourea
chromophore. For 8a three structures of nearly equal calculated
energy/population were found, differing in Z,E, Z,Z and E,Z
conformation of the thiourea chromophore (Table 1). In the case
of 8b, the analog of 8a with a more bulky cyclohexyl substituent
attached to the thiourea moiety, only two low-energy structures,
Z,Z and E,Z, were found, the former being the most stable
and accounting for 76% of the conformer population (Table 1).
This is in agreement with the data for 2b and 5b discussed
calculated at the B3LYP/6-311++G(d,p) level.
For N,N¢-dicyclohexylthiourea (2b), the calculation indicates
two thermally accessible conformers, Z,Z and Z,E, participating
in the equilibrium in the ratio 71 : 29. These conformers are
accordingly of C2 and C1 symmetry (see Table 1), with torsion
angles a ca. -30◦. Note that in the crystal structure of 2b the Z,E
conformer shows disorder due to rotation of one of the cyclohexyl
groups around the C–N bond.39a
=
Whereas the structure of N-methylphthalimide (3a) does not
require a detailed conformational analysis, the calculated lowest
energy structure of the N-cyclohexyl analogue (3b) was found to
have CS symmetry, conforming to the previously established pref-
erence for equatorial phthalimide substituent with the carbonyl
group eclipsing the (N)–C–H bond.15 Diisothiocyanate 4 is of
special interest since a rather complex conformational equilibrium
can be anticipated due to the small energy differences calculated
for the conformers of a related model compound 1b. To find
earlier. Torsion angle a H–CDACH –N–C( S) is positive for all
structures of 8a and 8b whereas the phthalimide torsion angles
a¢ are negative for Z,E and Z,Z structures and positive for
the E,Z structure. A more complex bis-phthalimide-thiourea
derivative 9 shows less conformational freedom compared to
8a and 8b. The lower-symmetry (C1) conformer (E,Z) is the
dominant one (94%) in the equilibrium mixture containing also
a C2 symmetry structure (Z,Z). As in the case of 8a and 8b,
=
torsion angles a H–CDACH –N–C( S) are positive, in the range
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32–40◦, whereas the phthalimide torsion angles a¢ are negative
(Table 1).
For rigid chiral C2-symmetric thiourea 10 the only available low-
energy structure is of E◦,E conformation with the torsion angle a
=
H–CDACH –N–C( S) -81 . Due to the cyclic E,E conformation this
structure is different from the structures of acyclic thioureas 2b, 5b,
8b and 9, and therefore is of interest with respect to the chiroptical
properties of the thiourea chromophore.
We note that thioureas 5a, 5b, 8a, and 8b undergo slow (on the
NMR timescale) conformational changes, resulting in broadening
of the NH signals (see ESI).
Absorption and circular dichroism spectra
Having established the structures of molecules 1–10, we were
able to calculate their electronic spectra (UV and CD) using the
TDDFT metod.
In order to test which combination of functional/basis set
performs better for calculation of the CD spectra of 1–10, two
different functionals, B3LYP and the double-hybrid functional
B2PLYP, recently introduced by Grimme and coworkers, have
been employed in combination with 6-311++G(2d,2p) basis
set.27,42 Due to the size of the molecules, we do not perform
additional CIS(D) perturbative corrections calculations, thus our
results refer to the TD-B2LYP method.33
Although each experimental spectrum was reproduced sat-
isfactorily by either B3LYP or B2LYP hybrid functionals in
conjunction with the basis sets augmented with diffuse functions,
better overall agreement was obtained with the use of the B2LYP
hybrid functional combined with 6-311++G(2d,2p) basis set. We
note that while B3LYP consistently underestimated the excitation
energy, the opposite was observed with the use of the B2LYP
functional.
There are five types of chromophores which are included
in molecules 1–10, i.e. the isothiocyanate, the Z,E-, Z,Z- and
E,E-thiourea, and the phthalimide. In order to determine the
nature of the electronic transitions involved in the absorption
spectra of these chromophores, the UV spectra of the minimalistic
structures 1a, 2a (E,Z and Z,Z), 3a and 10¢ were calculated
using the B2LYP/6-311++G(2d,2p) method. In these structures
the cyclohexyl substituents were replaced by the methyl groups
and the cyclohexane ring in 10 was removed to leave the chiral
structure intact in 10¢ (see Chart 1 and Fig. 4).
Fig. 4 shows the calculated electronic transitions of the five
chromophores as well as the directions of polarizations of the
identified electronic transitions. For methyl isothiocyanate (1a)
there are two n–p* transitions involving the sulfur atom of the
thiocarbonyl group at the longer-wavelength part of the spectrum.
The most intensive band, located at ca. 200 nm, is presumably
= =
of p–p* character and polarized along the S C N bond axis
(x–y).
The three thiourea chromophores in molecules 2a(E,Z),
2a(Z,Z) and 10¢(E,E) differ in configuration and in the energies
and intensities of their electronic transitions. In fact, the shapes
of the calculated UV spectra of configurational isomers of 2a
differ significantly (see Fig. E, ESI). A common feature of
these chromophores is the presence of a low intensity Rydberg
(n(S)–RY*) transition in the lowest energy part of the electronic
Fig. 4 Calculated at TDDFT/B2LYP/6-311++G(2d,2p) level of theory
UV spectra, oscillator strengths (vertical bars) and directions of polar-
izations of main electronic transitions for model compounds 1a, 2a, 3a
and 10¢. All calculated spectra were wavelength-corrected to match the
experimental UV spectra of 1b, 2b, 3b and 10 respectively.
=
spectrum (ca. 280 nm). This transition, polarized along the C S
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bond axis, is insignificant with respect to its contribution to
the CD spectra. For the conformers of 2a low intensity the
n(S)–p* transition is found in the region at ca. 250 nm. The
most intense electronic transition is of predominantly the p–p*
type in all three configurational isomers of the thiourea chro-
mophore. This transition is located in a 230–235 nm spectral
The experimental and calculated electronic absorption spectra
of compounds 1–10 and the electronic CD spectra of compounds
4–10 are shown in Fig. 5 and 6.
The calculated UV spectra are conformation-averaged. For the
UV and CD spectra of individual conformers see ESI, Fig. E–M.
In general, out of the two functionals used, B3LYP and B2LYP,
the latter provides UV and CD spectra with a better match
for the experimental spectra. Therefore, further discussion will
be limited to the results obtained with the use of the B2LYP
functional.
Except 10, all chiral molecules are bichromophoric or trichro-
mophoric, and one may expect that the CD spectra will be
dominated by exciton interactions between the electronically
allowed (p–p* type) transitions. Indeed, the shapes of the CD
spectra and significant magnitudes of the Cotton effects observed
support the exciton origin of the most intense Cotton effects.43
Bis-isothiocyanate 4 displays a strong negative Cotton effect
(De -94) located at 195 nm which is associated with a strong UV
=
range, polarized along the C S bond and involves the orbitals of
the thiourea molecule. In thiourea molecule of E,E conformation
(molecule 10¢) the p–p* transition is red-shifted to ca. 250 nm and
is more intense than that found for the E,Z and Z,Z isomers.
The electronic transitions of the phthalimide chromophore were
studied previously with the use of semiempirical calculations and
linear dichroism measurements.15 The present DFT study of the
electronic transitions in N-methylphthalimide (3a) confirms the
presence of a long-wavelength n–p* transition at ca. 310 nm and
of at least three electronic p–p* transitions below 290 nm, the most
intense (pAr–p*CO) located at ca. 220 nm and polarized along the
molecular symmetry axis (Fig. 4).
Fig. 5 Experimental (solid lines, left columns) and calculated at B2LYP/6-311++G(2d,2p) (solid lines, right columns) and B3LYP/6-311++G(2d,2p)
(dashed lines, right columns) UV spectra for compounds 1–10. All calculated spectra are scaled in oscillator strength (f ) and wavelength-corrected to
match the experimental UV spectra (see Experimental for details).
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Fig. 6 Experimental (solid lines, left columns) and calculated at B2PLYP/6-311++G(2d,2p) (solid lines, right columns) and B3LYP/6-311++G(2d,2p)
levels (dashed lines, right columns) CD spectra for compounds 4–10. All calculated spectra are scaled in rotatory strength (Rvel) and wavelength-corrected
as in Fig. 5.
maximum below 190 nm. The calculation shows the presence of a
negative exciton couplet (R = -63 at 199 nm; +98 at 187 nm) in
the CD spectrum of 4. A negative exciton couplet is obtained for
the calculated CD spectra of the most abundant (78% conformer
population) family of diequatorial 4ap,sc conformers (Fig. H,
ESI). These results are in full agreement with the model in which
the electric dipole transition moments for the p–p* transitions
of the two isothiocyanate chromophores form a negative-helicity
exciton system.
The experimental UV and CD spectra of 5b are quite well
reproduced by the calculations, especially with the use of B2LYP
functional. Both experimental and calculated CD spectra show the
presence of a long-wavelength negative Cotton effect just below
300 nm, due to a formally forbidden n(S)–p* transition (Fig. 6).
The presence of the allowed p–p* transitions in the thiourea
chromophore makes possible interpretation of the CD spectrum of
bis-thiourea molecule 5b within the exciton coupling model. The
absorption bands of 5b at 249 nm and 215 nm (Fig. 5) correspond
to a positive exciton couplet (De +30 at 251 nm, -35 at 216 nm) in
the CD spectrum (Fig. 6).
the pattern of signs of the most intense Cotton effects (+ at ca.
250 nm, - at ca. 205 nm) similar to that in the experimental and in
calculated, population-weighted CD spectra (Fig. 6). The presence
of at least two orthogonal p–p* transitions in each thiourea
chromophore (cf. Fig. 4) is responsible for a complex pattern
of the Cotton effects observed in the calculated CD spectra of
structurally related bis-thiourea 5a (Fig. I, ESI). Nevertheless, the
characteristic +/- sequence of the Cotton effects is found in the
calculated CD spectra of 5a and 5b and also in the experimental
CD spectrum of 5b and can be considered as a diagnostic
feature of the bis-thiourea chromophoric system in a M helicity
arrangement, here imposed by the absolute configuration of (R,R)-
DACH molecule. In addition we note that the experimental
CD spectrum of 5a is very similar to that of 5b (Fig. N,
ESI).
Bis-phthalimide 6 is reported here as a reference molecule, and
the analysis of its CD spectrum within the exciton coupling model
has been described earlier.15,17 The DFT calculations reproduce
the experimental CD spectrum of 6 quite well with the use of
B2LYP functional. This is because molecule 6 is conformationally
restricted, having a single energy minimum (shown in Table 1).
Since the most intense p–p* phthalimide transition is polarized
along its C2 axis and its direction is rotation-independent, the
phthalimide can be used as a reference chromophore of choice for
determining the heterochromophoric coupling in derivatives 7–9.
According to calculations, the pattern of signs of the exciton
Cotton effects is quite complex and to some extent dependent on
the conformation of the thiourea chromophore. Thus, for the most
populated Z,Z,E,E and Z,Z,Z,E stereoisomers of 5b (Fig. J, ESI)
the calculations performed with the B2LYP functional provide
1568 | Org. Biomol. Chem., 2009, 7, 1562–1572
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Whereas the absorption spectra of derivatives of N-phthaloyl-1,2-
diaminocyclohexane 7–9 are dominated by a strong absorption
band at ca. 220 nm, the corresponding CD spectra display
distinct exciton Cotton effects due to coupling of phthalimide
and isothiocyanate transitions in 7 (De -26 at 219 nm, +28 at
201 nm), or phthalimide and thiourea transitions in 8b (De +4 at
238 nm, -25 at 221 nm) and 9 (De +30 at 231 nm, -65 at 218
nm). These spectral features can also be found in the calculated
CD spectra with the use of the B2LYP functional (Fig. 6).
Moreover, the experimental CD spectra of 8a and 8b, differing in
the substitution of the thiourea moiety, are very similar (see Fig.
N, ESI). The computed CD spectra for individual conformers of
8a (Fig. K, ESI) show significant differences, while the CD spectra
of individual conformers of 8b and 9 (Fig. L and M, ESI) all show
the characteristic pattern of the exciton Cotton effects, positive at
ca. 240 nm and negative at ca. 220 nm. Note, however, that the
results of calculations are sensitive to the functional used, i.e. for
E,Z and Z,Z conformers of 9 consistent results were obtained
with the B2LYP functional.
The CD spectrum of monothiourea 10 displays three Cotton
effects (Fig. 6). Long-wavelength negative Cotton effect at 287 nm
is presumably of n(S)–p* character whereas two positive p–p*
Cotton effects are located at 251 and 213 nm. We note that a
positive Cotton effect at 251 nm results from a negative helicity of
the thiourea chromophore (negative N–C–C–N torsion angle).
This is in accordance with a general helicity rule44 predicting
a positive rotational strength for the transition polarized in a
plane perpendicular to the C2 axis in a chromophore of M
helicity.
Fig. 7 Pattern of diagnostic exciton Cotton effects due to (a) homochro-
mophoric or (b) heterochromophoric coupling.
Whereas most of the features of the CD spectra in Fig. 7 are self-
explanatory, the complexity of the CD spectra of thioureas merits
a few comments. We note that their CD spectra are dependent
on the thiourea conformation at the point of attachment to the
chiral center (here DACH molecule). Thus, opposite-sign exciton
Cotton effects are calculated for Z and E conformers of 8a and
8b, the experimental spectra being dominated by the contribution
of Z conformers. On the other hand, the exciton Cotton effects of
9 are due to a dominant E,Z conformer and further sensitive to
the contribution due to homochromophoric exciton coupling of
the two phthalimide groups.
We anticipate that the results presented here will be useful
for structural studies of chiral molecules containing the thiourea
or isothiocyanate chromophores (homochromophoric coupling)
or in combination of these with other CD active groups (het-
erochromophoric coupling). Another important finding of the
present study is the observation that the B2LYP functional,
recently introduced by Grimme et al.,27,42 performs much better
than the commonly used B3LYP functional for the calculation
of CD spectra. It is recommended that the former be used for
the calculations of chiroptical data in a short-wavelength UV
absorption region.
Conclusions
The present study shows that synthetically important thioureas
and isothiocyanates can also be considered as chromophores for
stereochemical studies by electronic circular dichroism. Despite
rotational freedom around the carbon–nitrogen bonds, conforma-
tional constraints for model molecules could be determined by the
calculations at the DFT B3LYP/6-311++G(2d,2p) level. Whereas
a number of low-energy rotamers were found for isothiocyanates
1b and 4, the presence of a bulky vicinal phthalimide group in
7 significantly restricted the accessible conformers to just one.
Thioureas 2, 5, 8 and 9 showed a preference toward E,Z or
Z,Z conformation, with conformer distribution depending on the
substituents at the nitrogen atoms. Low-energy E,E conformers
were not observed for acyclic thioureas. TDDFT calculations at
B2LYP/6-311++G(2d,2p) level provided UV and CD spectra in
very good agreement with the experimental data. These results
could be rationalized within the exciton coupling model for the
allowed p–p* transitions. The main transitions of high oscillator
strengths which are responsible for the appearance of exciton
Experimental
= =
Cotton effects in the CD spectra are polarized along the N C S
General
=
bond system in isothiocyanates (ca. 190 nm) along the C S
bond axis (240–250 nm) and parallel to the N ◊ ◊ ◊ N direction
(ca. 210 nm) in thioureas. Using the phthalimide as an external
reference chromophore, whose most intensive transition (ca. 220
nm) is polarized along the chromophore symmetry axis, a simple
pattern of exciton Cotton effects in the range 250 to 185 nm can
be envisaged, on the basis of the experimental and calculated data
(Fig. 7).
NMR spectra were recorded in deuteriochloroform on a Varian
XL300 instrument and are reported in ppm with respect to
TMS as a reference. FAB MS were measured with a 604 AMD
Intectra spectrometer. FT-IR spectra were taken in KBr pellets
with a Bruker IFS 113v spectrometer. CD and UV spectra were
measured with a Jasco J-910 spectropolarimeter. Melting points
are uncorrected.
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Computational methods
one portion via syringe. After 10 min of stirring triethylamine
(0.14 mL, 101 mg, 1 mmol) was added in one portion. The
whole mixture was stirred at room temperature for additional
4 h. Next dichloromethane (2 mL) and water (5 mL) were added
to the mixture. The layers were separated, the organic layer was
washed with 1 N HCl (2 ¥ 5 mL), dried over magnesium sulfate
and evaporated to dryness. The crude product was purified by
flash chromatography on silica gel to give 115 mg of white solid
which was crystallized from diethyl ether–hexane. Yield after
crystallization 89 mg, (63%), mp 77–80 C; H NMR (CDCl3)
d 1.36–1.41 (2H, m), 1.56–1.69 (1H, m), 1.82–1.86 (3H, m), 2.09–
2.32 (2H, m), 4.12–4.21 (1H, m), 4.48–4.57 (1H, m), 7.73–7.77
(2H, m), 7.84–7.7.89 (2H, m); 13C NMR (CDCl3) d 23.9, 24.8,
28.9, 33.6, 54.8, 56.9, 76.6, 123.4, 131.6, 134.2, 168.0; IR (KBr)
n/cm-1: 3460, 2963, 2940, 2866, 2207, 2173, 2080, 1774, 1760,
1718, 1706, 1610, 1466, 1456, 1369, 1372, 1352, 1104, 1067, 1046,
1020, 1002, 952, 931, 901, 867, 837, 789, 711, 635, 528, 466; EI MS
(m/z) [M+] = 286.1; CD (acetonitrile) De (nm): -1.0 (300), 11.1
(238), -25.9 (219), 27.6 (201); UV (acetonitrile) e (nm): 1900 (294),
10200sh (236), 39100 (220).
In our computations all excited-state calculations have been
performed, based upon the ground-state geometries of single
molecules, with the use of a Gaussian program package.30 Op-
timization of structures were performed using tight convergence
criteria. Rotatory strengths were calculated using both length
and velocity representations. In the present study the differences
between the values of rotatory strengths calculated in length and
velocity representations were quite small, and for this reason only
velocity representations were taken into account. The computed
oscillator strengths and rotational strengths were converted to the
UV and CD spectra by broadening to Gaussian-shape absorption
curves, according to the procedure described by Grimme et al.45
The calculated spectra were either blue- or red-shifted by ca. 10–
20 nm in relation to the experimental data, depending on the
method used. For scaling the calculated spectra of 3b, 6, 8b and
9 the position of the most intense phthalimide absorption band
at ca. 220 nm was taken as a reference; in the remaining cases
the position of the longest-wavelength absorption band served the
purpose. The scaling factors were either smaller or greater than
one, depending on the applied either blue or red shift.
◦
1
8a. To a stirred solution of trans-N-phthaloyl-(1R,2R)-
diaminocyclohexane (122 mg, 0.5 mmol) in dichloromethane
(2 mL), methyl isothiocyanate (44 mg, 0.6 mmol) in 2 mL of
dichloromethane was added in one portion. The mixture was
stirred at room temperature overnight. After evaporation to
dryness the crude product was purified by chromatography (eluent:
3% MeOH–CH2Cl2) to give 95 mg (60% yield) of viscous oil; 1H
NMR (CDCl3) d 1.22–1.64 (3H, m), 1.81–1.92 (3H, m), 2.30–2.34
(1H, bs), 2.47 (1H, bs), 2.81–2.83 (3H, s), 3.97–4.06 (1H, m), 4.66
(1H, bs) 5.60 (1H, bs), 5.84 (1H, bs) 7.70–7.74 (2H, m), 7.80–7.84
(2H, m); 13C NMR (CDCl3) d 24.5, 25.0, 28.9, 30.6, 33.4, 54.8,
123.3, 131.6, 134.1, 152.1, 169.0, 182.1; IR (KBr) n/cm-1: 3455,
3357, 3309, 3110, 2934, 2656, 1767, 1700, 1613, 1573, 1539, 1402,
1372, 1284, 1257, 1107, 1068, 1034, 869, 724, 580, 530; FAB MS
(m/z) [M++1] = 318.1; CD (acetonitrile) De (nm): -1.6 (324), 2.1
(282), -1.0 (243), 9.2 (236), -28.0 (211), 8.5 (204); UV (acetonitrile)
e (nm): 2050 (292), 11100sh (250), 15790sh (240), 41430 (217).
Synthesis
5a. To a stirred solution of trans-(1R,2R)-diaminocyclo-
hexane (114 mg, 1 mmol) in dichloromethane (4 mL), methyl
isothiocyanate (160 mg, 2.2 mmol) in 2 mL dichloromethane
was slowly added via syringe. The solution was stirred at room
temperature for 5 h. Next the mixture was evaporated to dryness.
The crude product was purified by flash chromatography (eluent:
3% MeOH–CH2Cl2) to give 109 mg (42% yield) of viscous oil;
1H NMR (CDCl3) d 1.36 (4H, bs), 1.79 (2H, bs), 2.28 (2H, bs),
2.96–3.03 (6H, m), 4.27 (2H, bs), 6.76 (2H, bs), 7.22 (2H, bs); 13
C
NMR (CDCl3) d 15.3, 21.3, 22.2, 22.5, 25.2, 31.5, 34.4, 45.2, 50.1,
73.8, 127.7, 129.7, 135.2, 135.6; IR (KBr) n/cm-1: 3247, 3064,
2934, 2855, 2215, 1565, 1511, 1500, 1468, 1386, 1343, 1263, 1233,
1178, 1108, 1035, 950, 914, 867, 849, 764, 730, 645; FAB MS (m/z)
[M++1] = 261,1; CD (acetonitrile) De (nm): 21.7 (247), -21.2 (212);
UV (acetonitrile) e (nm): 18600 (245), 17400 (210).
8b. To a stirred solution of trans-N-phthaloyl-(1R,2R)-
diaminocyclohexane (122 mg, 0.5 mmol) in dichloromethane
(2 mL), cyclohexyl isothiocyanate (85 mg, 0.08 mL, 0.6 mmol) was
added in one portion. The mixture was stirred at room temperature
overnight and then was heated to reflux for an additional hour.
After evaporation to dryness the crude◦product was crystallized
5b. To a stirred solution of trans-(1R,2R)-diaminocyclo-
hexane (114 mg, 1 mmol) in dichloromethane (4 mL), cyclohexyl
isothiocyanate (311 mg, 0.301 mL, 2.2 mmol) was slowly added via
syringe. The solution was stirred at room temperature for 5 h. Next
the mixture was filtered to remove the precipitate and the filtrate
was evaporated to dryness. The crude product was crystallized
from benzene to give 268 mg (67% yield) of white crystals; mp
1
from chloroform–hexane; mp 196–200 C; H NMR (CDCl3) d
◦
1
0.99–1.71 (12H, m), 1.82–1.91 (4H, m), 2.32 (1H, bs), 2.40 (1H,
bs), 3.64 (1H, bs), 4.03 (1H, t, J = 12.4 Hz), 4.61 (1H, bs) 5.49
(1H, bs), 5.64 (1H, d, J = 8.0 Hz) 7.70–7.74 (2H, m), 7.80–7.82
(2H, m); 13C NMR (CDCl3) d 24.6, 24.7, 25.3, 29.0, 32.4, 32.7,
33.5, 53.0, 54.9, 76.6, 123.3, 131.7, 134.1, 169.0, 179.9; IR (KBr)
n/cm-1: 3451, 3346, 32,81 3095, 2934, 2920, 2854, 2664, 1762,
1696, 1610, 1567, 1466, 1452, 1395,1320, 1238, 1152, 1132, 1085,
1067, 1017, 1000, 953, 870, 842, 739, 719, 639, 584, 530, 419; EI
MS (m/z) [M+] = 385.2; CD (acetonitrile) De (nm): -2.1 (323), 1.7
(286), -0.3 (264), 0.1 (255), -3.8 (243), 3.8 (238), -24.9 (221), 6.4
(202); UV (acetonitrile) e (nm): 1900 (292), 10800 (250), 15400sh
(239), 42900 (216).
219–223 C; H NMR (CDCl3) d 1.16–1.97 (26H, m), 2.30 (2H,
bs), 3.76 (2H, bs), 4.31 (2H, bs), 5.95 (2H, bs), 6.75 (2H, bs); 13
C
NMR (CDCl3) d 24.6, 25.3, 32.4, 32.7, 33.0, 42.6 (bs), 52.3 (bs),
60.2 (bs), 128.3, 179.6 (bs); IR (KBr) n/cm-1: 3233, 3057, 2929,
2853, 1561, 1549, 1510, 1448, 1335, 1284, 1229, 1083, 980, 944,
888, 867,848, 771, 737, 666, 631, 585; EI MS (m/z) [M+] = 396.3;
CD (acetonitrile) De (nm): 3.8 (278), 29.8 (251), -35.2 (216), 4.8
(196); UV (acetonitrile) e (nm): 24700 (248), 23200 (212).
7. To
a stirred solution of trans-N-phthaloyl-(1R,2R)-
diaminocyclohexane36 (122 mg, 0.5 mmol) in dichloromethane
(2 mL), thiophosgene (58 mg, 0.04 mL, 0.6 mmol) was added in
1570 | Org. Biomol. Chem., 2009, 7, 1562–1572
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9. To
a
stirred solution of trans-N-phthaloyl-(1R,2R)-
11 A. Berkessel and H. Gro¨ger, Asymmetric Organocatalysis, Wiley-VCh,
Weinheim, 2005, Chapter 5.
diaminocyclohexane (73 mg, 0.3 mmol) in dichloromethane
(2 mL), compound 7 (86 mg, 0.3 mmol) was added in one portion.
The mixture was stirred at room temperature overnight. After
evaporation of the solvent the crude product was crystallized from
methanol to give 64 mg (37% yield) of white crystals; mp 258–
12 C. Palomo, M. Oiarbide and A. Mielgo, Angew. Chem. Int. Ed., 2004,
43, 5442–5444.
13 F. Wu, Z. Wen and Y. Jiang, Y., Progress, in Chemistry, 2004, 16, 776–
784.
14 L. Ilisz, R. Berkecz and A. Pe´ter, J. Pharm. Biomed. Anal., 2008, 47,
1–15.
◦
1
260 C; H NMR (CDCl3) d 1.04–1.13 (2H, m), 1.21–1.46 (4H,
m), 1.66–1.78 (2H, m), 1.82–1.86 (4H, m), 2.03 (2H, d, J = 11.5
Hz), 2.46–2.53 (2H, m), 3.86–3.95 (2H, m), 4.63 (2H, d, J = 9.0
Hz), 5.43 (2H, d, J = 9.0 Hz), 7.66 (4H, m); 13C NMR (CDCl3) d
24.3, 25.3, 28.7, 29.9, 32.9, 54.5, 123.1, 131.8, 133.7, 168.7, 181.7;
IR (KBr) n/cm-1: 1773, 1714, 1706, 1612, 1553, 1514, 1468, 1420,
1391, 1373 1257, 1226, 1164, 1118, 1067, 1015, 724, 713, 637, 530,
482; EI MS (m/z) [M+] = 530.2; CD (acetonitrile) De (nm): -4.7
(323), 2.9 (286), 4.4 (253), -7.3 (243), 30.1 (231), -67.9 (218), 3.0
(207), 6.2 (193); UV (acetonitrile) e (nm): 292 (3600), 9100 (250),
22500sh (239), 75300 (216).
15 J. Gawronski, F. Kazmierczak, K. Gawronska, U. Rychlewska, B.
Norde´n and A. Holme´n, J. Am. Chem. Soc., 1998, 120, 12083–12091.
16 J. Gawronski, K. Gawronska, P. Skowronek and A. Holme´n, J. Org.
Chem., 1999, 64, 234–241.
17 J. Gawronski, M. Brzostowska, K. Kacprzak, H. Kołbon and P.
Skowronek, Chirality, 2000, 12, 263–268.
18 J. Gawronski and P. Skowronek, Curr. Org. Chem., 2004, 8, 65–
82.
19 (a) T. Helgaker, T. A. Ruden, P. Jørgensen, J. Olsen and W. Klopper,
J. Phys. Org. Chem., 2004, 17, 913; (b) V. Barone, R. Improta and N.
Rega, Acc. Chem. Res., 2008, 41, 605–616.
20 M. F. C. Ladd and R. A. Palmer, Structure Determination by X-ray
Crystallography, 2nd edn, Plenum Press, New York, 1985.
21 see for example: B. C. Rinderspacher and P. R. Schreiner, J. Phys.
Chem. A, 2004, 108, 2867–2870.
10. To a stirred solution of trans-(1R,2R)-diaminocyclo-
hexane (57 mg, 0.5 mmol) in dichloromethane (2 mL) thiophos-
gene (57 mg, 0.5 mmol, 0.2 ml of 2.5 M soln. in dichloromethane)
was added slowly via syringe. After 10 min of stirring, triethy-
lamine (121 mg, 0.167 mL, 1.2 mmol) was added in one portion
and the mixture was stirred at room temperature for 2 h. Next
dichloromethane (2 mL) and water (3 mL) were added to the
mixture. The layers were separated, the organic layer was washed
with 1 N HCl (2 ¥ 3 mL), dried over magnesium sulfate and
evaporated to dryness. The crude product was purified by flash
chromatography on silica gel to give white solid (54 mg, 69%
yield); mp 168–171, 203–205 ◦C (lit.46 for rac-10, mp 148–150 ◦C);
1H NMR (CDCl3) d 1.29–1.60 (4H, m), 1.78–1.86 (2H, m), 2.04–
2.08 (2H, m), 3.28–3.33 (2H, m) 6.34 (2H, bs); 13C NMR (CDCl3)
d 23.8, 28.9, 64.8, 187.8; IR (KBr) cm-1 3210, 2953, 2933, 2663,
1506, 1457, 1353, 1304, 1254, 1219, 1171, 1139, 1102, 943, 924,
830, 702, 651, 620, 596, 484, 426; EI MS (m/z) [M+] = 156.2;
CD (acetonitrile) De (nm): -6.2 (286), 13.3 (251), 7.1 (213); UV
(acetonitrile) e (nm): 17450 (252), 9400 (210).
22 (a) T. D. Crawford, Theor. Chem. Acc., 2006, 115, 227–245; (b) T. D.
Crawford and P. J. Stephens, J. Phys. Chem. A, 2008, 112, 1339–1345;
(c) T. D. Crawford, M. C. Tam and M. L. Abrams, J. Phys. Chem. A,
2007, 111, 12057–12068 and literature cited therein.
23 K. Burke, J. Werschnik and E. K. U. Gross, J. Chem. Phys., 2005, 123,
062206.
24 (a) J. Tirado-Rives and W. L. Jorgensen, J. Chem. Theory Comput, 2008,
4, 297–306; (b) Y. Zhao and D. G. Truhlar, Acc. Chem. Res., 2008, 41,
157–167.
25 (a) P. R. Schreiner, Angew. Chem. Int. Ed, 2007, 46, 4217–4219;(b) M. D.
Wodrich, C. Corminboeuf, P. R. Schreiner, A. A. Fokin and P. van Ragu
Schleyer, Org. Lett, 2007, 9, 1851–1854; (c) P. R. Schreiner, A. A. Fokin,
R. A. Pascal and A. de Meijere, Org. Lett, 2006, 8, 3635–3638; (d) Y.
Zhao and D. G. Truhlar, Org. Lett, 2006, 8, 5753–5755; (e) C. E. Check
and T. M. Gilbert, J. Org. Chem., 2005, 70, 9828–9834.
26 (a) R. J. Bartlett, V. F. Lotrich and I. V. Schweigert, J. Chem. Phys, 2005,
123, 062205; (b) P. Mori-Sa´nchez, Q. Wu and W. Yang, J. Chem. Phys.,
2005, 123, 062204; (c) E. J. Baerends and O. V. Gritsenko, J. Chem.
Phys., 2005, 123, 062202; (d) A. Go¨rling, J. Chem. Phys, 2005, 123,
062203 and literature cited therein.
27 S. Grimme, J. Chem. Phys, 2006, 124, 034108.
28 F. Neese, T. Schwabe and S. Grimme, J. Chem. Phys., 2007, 126,
124115.
29 R. Ahlichrs, M. Ba¨r, M. Ha¨ser, H. Horn and C. Ko¨lmel, Chem. Phys.
Lett., 1989, 162, 165–169 (see also www.turbomole-gmbh.com for an
overview of the TURBOMOLE program).
30 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A.
Robb, J. R. Cheeseman, V. G. Zakrzewski, J. A. Montgomery, Jr., R. E.
Stratmann, J. C. Burant, S. Dapprich, J. M. Millam, A. D. Daniels,
K. N. Kudin, M. C. Strain, O. Farkas, J. Tomasi, V. Barone, M.
Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. Adamo, S. Clifford,
J. Ochterski, G. A. Petersson, P. Y. Ayala, Q. Cui, K. Morokuma,
P. Salvador, J. J. Dannenberg, D. K. Malick, A. D. Rabuck, K.
Raghavachari, J. B. Foresman, J. Cioslowski, J. V. Ortiz, A. G. Baboul,
B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.
Gomperts, 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, J. L. Andres, C. Gonzalez, M. Head-Gordon,
E. S. Replogle and J. A. Pople, Gaussian 03, Gaussian, Inc., Pittsburgh
PA, 2001.
Acknowledgements
This work was supported by a grant no. PBZ-KBN-126/T09/10
from the Ministry of Science. All calculations have been performed
at the Poznan´ Supercomputing and Networking Centre, Poland.
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