Methoxycarbonyl trifluoromethyl disulfide, CH3OC(O)SSCF 3: Synthesis, structure and conformational properties

Article abstract of DOI:10.1039/b9nj00382g

Pure methoxycarbonyl trifluoromethyl disulfide, CH₃OC(O) SSCF₃, has been prepared quantitatively by the reaction of CH ₃OC(O)SCl and Hg(SCF₃)₂. The conformational properties of the novel molecule have been studied by vibrational spectroscopy [IR(gas) and Raman(liquid)] and quantum chemical calculations (B3LYP and MP2 methods). The gaseous compound exhibits a conformational equilibrium at room temperature where the most stable form has C₁ symmetry with a synperiplanar (syn) orientation of the CO double bond with respect to the S-S disulfide bond. A second form is observed in the gaseous IR spectra corresponding to a conformer with the carbonyl bond CO in antiperiplanar (anti) position with respect to the S-S single bond. The structure of a single crystal of CH₃OC(O)SSCF₃ has been determined by X-ray diffraction analysis at low temperature using a miniature zone melting procedure. The crystalline solid (triclinic, P1, a = 6.4698(5) A, b = 9.0499(8) A, c = 12.5700(11) A, α = 97.219(6)°, β = 93.131(5)°, γ = 96.888(5)°and Z = 4) consists exclusively of molecules with the synperiplanar conformation and the usual gauche orientation around the disulfide bond [(CS-SC) = 91.06(15)°] is adopted. The geometrical parameters agree with those obtained from quantum chemical calculations.

Full text of DOI:10.1039/b9nj00382g

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Methoxycarbonyl trifluoromethyl disulfide, CH3OC(O)SSCF3: synthesis,
structure and conformational propertieswz
Sonia Torrico-Vallejos,a Mauricio F. Erben,*a Roland Boeseb and
ac
´
Carlos O. Della Vedova*
Received (in Victoria, Australia) 31st July 2009, Accepted 28th February 2010
First published as an Advance Article on the web 9th April 2010
DOI: 10.1039/b9nj00382g
Pure methoxycarbonyl trifluoromethyl disulfide, CH3OC(O)SSCF3, has been prepared
quantitatively by the reaction of CH3OC(O)SCl and Hg(SCF3)2. The conformational properties of
the novel molecule have been studied by vibrational spectroscopy [IR(gas) and Raman(liquid)]
and quantum chemical calculations (B3LYP and MP2 methods). The gaseous compound exhibits
a conformational equilibrium at room temperature where the most stable form has C1 symmetry
with a synperiplanar (syn) orientation of the CQO double bond with respect to the S–S disulfide
bond. A second form is observed in the gaseous IR spectra corresponding to a conformer with
the carbonyl bond CQO in antiperiplanar (anti) position with respect to the S–S single bond. The
structure of a single crystal of CH3OC(O)SSCF3 has been determined by X-ray diffraction
analysis at low temperature using a miniature zone melting procedure. The crystalline solid
ꢀ
(triclinic, P1, a = 6.4698(5) A, b = 9.0499(8) A, c = 12.5700(11) A, a = 97.219(6)1,
b = 93.131(5)1, g = 96.888(5)1 and Z = 4) consists exclusively of molecules with the
synperiplanar conformation and the usual gauche orientation around the disulfide bond
[f(CS–SC) = 91.06(15)1] is adopted. The geometrical parameters agree with those obtained from
quantum chemical calculations.
their evolution. Catalytic roles have been also attributed to
Introduction
disulfide bonds through mediating thiol–disulfide interchange
reactions in substrate proteins. There is rising evidence
for a third type of disulfide bond, referred as allosteric
disulfides, which can control protein functions by triggering
a conformational change when it breaks and/or forms.3
The synthesis of symmetrical (RSSR) and unsymmetrical
(RSSR0) disulfides has attracted much attention and several
outstanding reviews can be found in the chemical literature.4
Of central interest are efficient methods for the formation of
disulfide bonds required for the synthesis of many biologically
active compounds, such as peptides and peptide mimetics.5 A
number of disulfide-bridged peptides are of current and
potential interest as therapeutic drugs, including oxytocin
(childbirth), somatostatin and analogs (anticancer), calcitonin
(osteoporosis) and integrelin (anticlotting).6,7 This may
be due to the fact that pairing of cysteine residues to form
disulfide bridges represents the principal way for nature to
establish covalent crosslinks that can ‘lock’ conformations,
with concomitant effects on structural stabilities2 and biological
activities.8,9
The tertiary structure of many biological compounds is
determined by the structural properties of disulfide bridges.1
Since a significant fraction of the proteins made in the nature
contain disulfide bonds, the molecular structure of disulfides
has also attracted much attention. Very recently, Khakshoor
and Nowick2 report the use of disulfide linkages to stabilize a
cyclic b-sheet dimer with a well-defined structure. Indeed,
changes over time of the structural motifs associated with this
bond in different protein folds have been considered to explain
a CEQUINOR (UNLP-CONICET CCT La Plata), Departamento de
´
Quımica, Facultad de Ciencias Exactas, Universidad Nacional de La
Plata, 47 esq. 115 (B1900AJL), C.C. 962, La Plata, Buenos Aires,
Repu´blica Argentina. E-mail: carlosdv@quimica.unlp.edu.ar,
erben@quimica.unlp.edu.ar; Fax: ++54-(221)-425-9485;
Tel: ++54-(221)-425-9485
b Institut fur Anorganische Chemie, Universitat Duisburg-Essen,
¨
¨
¨
Universitatsstr., 5–7, D-45117 Essen, Germany
c
´
Laboratorio de Servicios a la Industria y al Sistema Cientıfico
(UNLP-CIC-CONICET) Camino Centenario, Gonnet,
Buenos Aires, Repu´blica Argentina
w This work is part of the postdoctoral work of STV, who is a
postdoctoral fellow of CONICET. CODV and MFE are members of
the Carrera del Investigador of CONICET, Repu´ blica Argentina.
z Electronic supplementary information (ESI) available: Experimental
and calculated (B3LYP/6-311++G**) vibrational data (cmꢀ1) are
given in Table S1. Crystal data and structure refinement for
CH3OC(O)SSCF3 are given in Table S2 and crystallographic details,
Moreover, the knowledge of the structural properties and
conformational preference of simple molecules containing
disulfide bonds is of prime interest.10 One of their most
important structural properties of symmetric disulfides XSSX
is represented by the dihedral angle around the S–S bond
[f(X–S–S–X)], with typical values close to 901. Thus, geometric
structures of non-cyclic symmetrical disulfides, XSSX, are
characterized by a gauche orientation around the S–S bond
and S–S bond lengths varying between 1.890(2) A in FSSF to
whole molecular parameters and
a list of atomic coordinates
and equivalent isotropic displacement coefficients and anisotropic
displacement parameters for CH3OC(O)SSCF3 are given in Tables
S3–S7. CCDC reference number 734324. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/b9nj00382g
ꢁc
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2.061(3) A in HSSH. Recent theoretical calculations predict
the strength of the sulfur–sulfur bond energy between
77.7 kcal molꢀ1 for FSSF and only 41.8 kcal molꢀ1 for
tetrasulfane, HSS–SSH.11 The p-shaped lone pairs of the
two sulfur atoms are perpendicular to each other with this
orientation favored by the anomeric effect, that is, an orbital
interaction between these lone pairs and the opposite empty
s* orbital of the S–X bond.12,13 This effect depends strongly
on the relative energies of the two orbitals involved, and can
explain the short S–S and long S–F bonds in FSSF14 with a
dihedral angle of 85.2(2)1. Other representative compounds
with f(XS–SX) dihedral angle values close to 901 are HSSH15
(90.76(6)1), ClSSCl16 (85.2(2)1), FC(O)SSC(O)F17 (82.2(19)1)
carbon atoms of the CH3, CF3 and CQO groups, respectively.
An extra resonance with very low intensity is observed at
d = 131.6 ppm, possibly due to decomposition products
(unidentified). For comparison, the 13C NMR spectrum of
the related CF3C(O)SCF325 molecule shows signals at d = 126.3
and 176.9 ppm attributed to the CF3 and CQO groups,
respectively.
In order to corroborate the purity of the sample, a further
GC-MS analysis was carried out. The gas chromatogram of
the compound measured in solution of diethyl ether shows a
single peak with a retention time of 5.8 min and a purity better
than 99%. The molecular ion peak is observed in the mass
spectrum as a very low intensity signal at m/z = 192 and
several fragments of CH3OC(O)SSCF3 are assigned. Thus,
peaks at m/z = 15 (65, CH3+), 59 (100, CH3OC(O)+), 69
(35, CF3+), 79 (35, CH3SS+), 133 (20, CF3SS+), 148
(15, CH3SSCF3+) and 161 (5, CF3SSC(O)+) are observed in
the mass spectrum (relative abundance in parentheses).
Additional evidence for the identity of CH3OC(O)SSCF3
comes from the analysis of its IR(gas) and Raman(liquid)
spectra (see Fig. 1 and Table S1 in the ESIz). An intense band
centered at 1782 cmꢀ1 is characteristic for the n(CQO) group,
and the strongest band in the IR(gas) spectrum, centered at
1180 cmꢀ1, is assigned to the nas(C–O–C) stretching mode.
The characteristic disulfide stretching mode26 is observed in
the Raman (liquid) spectrum as a medium intensity signal at
18
and CH3SSCH3 (85.3(37)1). However, steric repulsions
between bulky substituents may lead to larger dihedral angles,
such as in CF3SSCF319 and ButSSBut20 having dihedral angles
of 104.4(40) and 128.3(27)1, respectively.
Herein the preparation and characterization of a novel
disulfide compound, methoxycarbonyl trifluoromethyl disulfide,
CH3OC(O)SSCF3, are presented. As far as we know, no
previous report for this compound exists in the literature. In
this study we present an experimental investigation of the
structure and vibrational properties of the title compound,
which includes the use of vibrational [IR (gas) and Raman
(liquid)] and NMR (1H, 19F and 13C) spectroscopies. Its
crystal structure has been also determined at 190 K by X-ray
diffraction using an in situ crystallization method. The experi-
mental data have been supplemented by using quantum
chemical calculations.
541 cmꢀ1
.
Quantum chemical calculations
Several rotamers are possible for CH3OC(O)SSCF3, mainly
depending on the conformations adopted around each of the
three O–C, C–S and S–S single bonds in the molecule. Taking
into consideration structural studies previously reported for
CH3OC(O)X compounds, the syn orientation of the
f(CO–CQO) dihedral angle is preferred.23 Thus, special
attention was paid to the f(OQC–CS) and f(CS–SC) dihedral
angles. In a first step, the potential function for the internal
rotation around the S–S bond was derived by structure
Results
Synthesis and characterization
CH3OC(O)SSCF3 can be synthesized by reacting methoxy-
carbonylsulfenyl chloride, CH3OC(O)SCl, with bis(trifluoro-
methylthio)-mercury salt, Hg(SCF3)2, according the following
equation:
2CH3OC(O)SCl + Hg(SCF3)2 - 2CH3OC(O)SSCF3 + HgCl2
This method is adapted from that reported by Haas et al.21,22
used for synthesizing haloformyl(perhaloalkyl)-sulfanes and
disulfanes. The new compound is a colorless liquid, with
the characteristic overpowering sulfenylcarbonyl odor. The
compound is stable at room temperature in vacuum or in an
inert atmosphere for a couple of days in the liquid or
gaseous state.
1
The H NMR spectrum only shows a singlet signal located
at d = 3.96 ppm that corresponds to the CH3O group of the
molecule. A similar value of d = 3.48 ppm was reported for
related CH3OC(O)SNCO molecule.23 In the 19F NMR spectrum
one singlet located at d = ꢀ46.8 ppm is observed. For the
trifluoromethyldisulfide group (CF3SS–) the 19F NMR spectra
typically show a resonance at approximately d = ꢀ45 ppm.24
Besides, the 19F NMR spectrum of CF3C(O)SCF3 has been
recently reported showing a similar singlet at d = ꢀ41.8 ppm
assigned to the SCF3 group. In addition, the uncoupled
13C NMR spectrum of the title compound shows three singlet
signals at d = 56.7, 125.3 and 166.3 ppm, assigned to the
Fig. 1 Gaseous IR spectrum (top) at 7.2 mbar (glass cell, 100 mm
optical path length, Si windows, 0.5 mm thick) and liquid Raman
spectrum for CH3OC(O)SSCF3.
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Fig. 2 Calculated (B3LYP and MP2 methods with the 6-31G* basis
sets) potential function for internal rotation around the S–S single
bond in CH3OC(O)SSCF3 (MP2 curve is shifted by 1 kcal molꢀ1).
optimizations at fixed f(CS–SC) dihedral angles (syn orienta-
tions were supposed around both C–O and C–S single bonds).
Potential functions obtained with the B3LYP and MP2 methods
and 6-31G* basis sets are shown in Fig. 2. Minima occur at
dihedral angles around ꢂ901, whereas maxima in the region of
syn and anti orientation of the C–S–S–C skeleton are
observed, with imaginary frequencies at f(CS–SC) = 0 and 1801.
In addition to the enantiomeric forms that are related by
rotation around the disulfide bond, two conformations may
occur around the C(O)–S single bond depending on the
mutual orientation of the CQO double bond with respect
to the S–S single bond. The potential functions for the
internal rotation around the CS single bond was calculated
(B3LYP/6-31G*) by full geometry optimizations at fixed
[f(SS–CQO) in Fig. 3] dihedral angle, supposing syn and
gauche orientations around C(O)–O and S–S single bonds,
respectively (see Fig. 3). As expected, two structures correspond
to minima in the potential energy curve, the most stable one
having syn orientation of the CQO with respect to the S–S bond
Fig.
4
Molecular models for the two main conformers of
CH3OC(O)SSCF3.
[f(SS–CQO) = 01] while the anti form [f(SS–CQO) = 1801]
is located higher in energy by ca. 1 kcal molꢀ1
.
This analysis suggests that two main forms are expected to
determine the conformational properties of CH3OC(O)SSCF3,
syn-syn-gauche and syn-anti-gauche, depending to the orientation
around the O–C, C–S and S–S single bonds, respectively.
Thus, full geometry optimizations and frequency calculations
were performed for each of the most stable structures with the
B3LYP method using the 6-31G* and 6-311++G** basis sets
as well as with the MP2/6-31G* level of approximation.
Structural results obtained from DFT-based methods are
often as good as those derived from MP2 calculations.27 It is
well documented that hybrid functionals with large basis
sets yield reliable structures and vibrational frequencies for
inorganic compounds.28
Calculated relative energies (corrected by zero-point energy)
and frequencies of the CQO stretching vibrational modes with
their IR intensities are collected in Table 1. The optimized
molecular structures for the two main conformers of the title
molecule are shown in Fig. 4.
Vibrational analysis
The gas phase FTIR spectrum and the Raman spectrum
of liquid CH3OC(O)SSCF3 are shown in Fig. 1.
A
tentative assignment of the observed bands is performed
by comparison with the calculated spectrum, and the
approximate description of modes is based on the calculated
displacement vectors for the fundamental modes of vibration,
and also by comparison with spectra of related molecules,
CH3OC(O)SNCO,23 CH3OC(O)SCl,29 CF3C(O)SCF325and
30
XC(O)SSCF3 (X = Cl, F). Experimental and calculated
Fig. 3 Calculated potential function (B3LYP/6-31G*) for internal
rotation around the C–S single bond in CH3OC(O)SSCF3.
(B3LYP/6-311++G**) frequencies for the syn-syn-gauche
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Table 1 Calculated relative energies (corrected by zero-point energy;
kcal molꢀ1) and vibrational frequency of the CQO stretching mode
this mode between the two conformers is +33 cmꢀ1 (Table 1),
a value in good agreement with the experimentally observed
value of +35 cmꢀ1 in the gas-phase spectrum. Moreover, the
conformational composition was derived from the integrated
intensity of both 1782 and 1747 cmꢀ1 bands in the vapor IR
spectrum and taking into account the computed intensities
with the B3LYP/6-311++G** method (Table 1). A composition
of 81(5)% of the more stable syn-syn-gauche form at room
temperature was obtained (the estimated error limit includes
uncertainties in the measured areas).
(cmꢀ1
CH3OC(O)SSCF3
) , in parentheses) for
with IR intensities (Km molꢀ1
Conformers
Method of calculation
DE1
n(CQO)
syn-syn-gauche
B3LYP/6-31G*
B3LYP/6-311++G**
MP2/6-31G*
B3LYP/6-31G*
B3LYP/6-311++G**
MP2/6-31G*
0.00a
0.00b
0.00c
1.01
0.78
1.08
6.46
6.44
1853 (201)
1821 (251)
1839 (160)
1823 (265)
1788 (354)
1813 (219)
1878 (293)
1847 (355)
syn-anti-gauche
anti-syn-gauche
B3LYP/6-31G*
B3LYP/6-311++G**
Additional to the CQO normal mode of vibration, it is also
important to describe other absorptions. Thus, the most
intense gas-phase IR band at 1115 cmꢀ1 is assigned to the
symmetric stretching mode of the CF3 group, a value that is in
agreement with those reported for related species such as
a
b
E1
=
ꢀ1362.401432 hartrees. E1
=
ꢀ1362.644828 hartrees.
c
E1 = ꢀ1359.835513 hartrees.
25
30
CF3C(O)SCF3 and XC(O)SSCF3 (XQCl, F) with experi-
mental values of 1120, 1116 and 1119 cmꢀ1, respectively. A
weak absorption in the IR spectrum observed at 671 cmꢀ1 is
assigned to the out-of-plane deformation of the –OC(O)S–
group, whereas the values reported for this mode in related
molecules CH3OC(O)SNCO23 and FC(O)SSCF330 are 681 and
636 cmꢀ1, respectively. It is well-known that the n(S–S)
stretching mode is clearly observed in the Raman spectrum
and can be used to characterize disulfide containing
compounds. For CH3OC(O)SSCF3 the medium intensity
signal appearing at 541 cmꢀ1 is assigned to n(S–S), in coincidence
with reported values for other disulfide compounds
[FC(O)SSCF3 (567 cmꢀ1),30 FC(O)SSC(O)F (555 cmꢀ1),17
FC(O)SSC(O)CF3 (549 cm1)31 and FC(O)SSC(O)CF2Cl
(535 cmꢀ1)32].
and syn-anti-gauche conformers, together with the tentative
assignments are given in the ESI (Table S1).z
As mentioned, quantum chemical calculations reproduce
the presence of two conformers of CH3OC(O)SSCF3 at room
temperature, the syn-syn-gauche being the most stable form.
The presence of two bands in the region of the CQO group
in both the IR(gas) and Raman(liquid) spectra is evident.
Particularly, as observed in Fig. 5, two intense bands centered
at 1782 and 1747 cmꢀ1 are observed in the vapor IR spectrum
of CH3OC(O)SSCF3.
The most intense band, located at the higher wavenumber, is
assigned to the CQO stretching mode of the most stable
syn-syn-gauche conformer. A second band centered at 1747 cmꢀ1
can be attributed to the CQO stretching mode of the second
stable syn-anti-gauche form. The well-defined rotational contour
observed for this band gives confidence to this assignment. In
effect, because of the almost parallel orientation of the carbonyl
oscillator with respect to the principal axis of inertia A, an
A-type band is expected for the n(CQO) normal mode of
the syn-anti-gauche conformer (see Fig. 5). Additionally, the
calculated wavenumber difference [B3LYP/6-311++G**] for
Crystal structure
By using the in situ crystallization technique,33 an appropriate
single crystal of CH3OC(O)SSCF3 was grown at 190 K with a
miniature melting procedure using focused infrared laser
radiation. Methoxycarbonyl trifluoromethyl disulfide crystallizes
ꢀ
in the triclinic P1 spatial group with unit cell dimensions of
a = 6.4698(5) A, b = 9.0499(8) A, c = 12.5700(11) A, a =
97.219(6)1, b = 93.131(5)1, g = 96.888(5)1, and Z = 4. The
crystal structure has two molecules of CH3OC(O)SSCF3 in the
asymmetric unit. Table 2 includes the main geometric parameters
for both independent molecules (named as molecule 1 and
molecule 2) derived from the structure refinement, as well as
those obtained from quantum chemical calculations. As
expected, geometrical parameters for both molecules are quite
similar; therefore only the molecular structure of molecule 1 is
shown in Fig. 6. In the following discussion, averaged values
will be presented.
Only the most stable syn-syn-gauche conformer is observed
in the single crystal at 190 K, with dihedral angle values for the
CH3OC(O)S– group slightly deviating from planarity
[f(CO–CQO) = ꢀ2.1(4)1 and f(SS–CQO) = ꢀ0.2(3)1].
The structure adopted for the title compound around the
disulfide single bond is definitely gauche, with a dihedral angle
of f(CS–SC) = 91.06(15)1.
Fig. 5 IR spectrum in the carbonyl stretching region for gaseous
CH3OC(O)SSCF3 at 7.2 mbar. Principal moments of inertia (A and B in
the sheet plane) are shown for both syn-syn-gauche and syn-anti-gauche
conformers.
In general, the main geometric parameters obtained by
X-ray diffraction analysis are well reproduced by quantum
chemical calculations. The main deviations are observed for
ꢁc
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Fig. 6 Molecular model for the single-crystal structure of syn-syn-gauche
CH3OC(O)SSCF3 (only molecule 1 in the asymmetric unit is shown).
the bond distances around the disulfide group, which are
overestimated especially with the B3LYP method. Thus, even
with quite large basis sets (6-311++G**), the B3LYP method
predicts the S1–S2, S1–C1 and S2–C2 bonds to be too long by
ca. 0.06, 0.04 and 0.02 A, respectively. These parameters are
better described by the MP2/6-311++G** method, being the
S1–S2 bond length too long by 0.045 A.
Fig. 7 Packing of molecules in crystalline CH3OC(O)SSCF3 at 190 K
along the bc plane.
The overall crystal packing of CH3OC(O)SSCF3 as viewed
along the bc plane is shown in Fig. 7. Intermolecular inter-
actions dominated by FꢃꢃꢃF contacts are common for fluorinated
molecules where this type of interaction plays an important
role in the stabilization of the packing. According to quantum
chemical calculations, Fꢃ ꢃ ꢃF contacts in aromatic systems can
contribute up to 14 kcal molꢀ1 of local stabilization energy.34
Packing motifs identified in structural studies of perfluorated
compounds are characterized by C–Fꢃ ꢃ ꢃF–C non-bonded
distances of 2.777 and 2.868 A.35,36 For the title molecule,
the trifluoromethyl group interacts through C–FꢃꢃꢃF–C contacts
with average Fꢃ ꢃ ꢃF distances of 2.897 A. Intermolecular Sꢃ ꢃ ꢃO
interactions between the disulfide and carbonyl groups are
also observed, as can be seen in Fig. 8. The intermolecular
non-bonded S1_2ꢃ ꢃ ꢃO1_2 distances for molecules 2 (symmetry
code (1 ꢀ x, 2 ꢀ y, ꢀz)) are 3.169 A, a value that is shorter
than the sum of the van der Waals radii for sulfur and oxygen
atoms (3.3 A).37
atoms has attracted much attention because short Sꢃ ꢃ ꢃO
distances (typically in the range 2.77–3.16 A) have been
observed in solid phase studies.38 We have identified such
short 1,4 Sꢃ ꢃ ꢃO contacts in a series of acyl disulfides, where
intramolecular interactions between the CQO and S–S groups
may be present.31,32 For the title compound a 1,4 Sꢃ ꢃ ꢃO
intramolecular average distance of 3.116 A defined by the
sulfur atom attached to the CF3 group and the oxygen atom of
the carbonyl group is observed (see Fig. 8). Following the
study of Burling and Goldstein39 on non-bonded interactions,
the nearly planar conformation of the CH3OC(O)SS– moiety
favors the electronic delocalization of non-bonded p electrons
of the sulfur atoms, which may result in an increased attractive
interaction between the sulfur and oxygen atoms.
Discussion
The conformational properties of sulfenylcarbonyl compounds—
with general formula XC(O)SY—have been extensively studied
and the preference of a synperiplanar conformation around
The investigation of short non-bonded intramolecular 1,4
Sꢃ ꢃ ꢃO contacts in compounds containing sulfur and oxygen
Table 2 Experimental and calculated geometric parameters for the syn-syn-gauche conformer of CH3OC(O)SSCF3
X-rayb,c
B3LYP
MP2
Parametersa
Molecule 1
Molecule 2
6-311++G**
6-311++G**
S1–C1
S1–S2
S2–C2
1.801(3)
2.0110(15)
1.806(3)
1.193(4)
1.316(4)
1.321(5)
100.26(15)
101.71(14)
113.1(3)
125.9(3)
92.74(15)
177.4(2)
0.5(3)
1.803(3)
2.0116(14)
1.808(3)
1.185(4)
1.326(4)
1.326(4)
100.59(13)
102.39(15)
112.8(2)
126.6(3)
89.37(14)
51.1(3)
1.841
2.076
1.831
1.193
1.335
1.342
101.13
101.41
113.35
126.93
91.67
178.80
0.26
1.814
2.056
1.804
1.201
1.340
1.338
98.90
100.11
113.02
127.25
88.64
178.70
0.03
O1QC2
O2–C2
C1–Fd
C1–S1–S2
C2–S2–S1
F2–C1–S1
O1QC2–S2
f(C1S1–S2C2)
f(S2S1–C1F3)
f(S1S2–C2QO1)
f(C3O2–C2QO1)
ꢀ0.9(3)
ꢀ2.4(4)
ꢀ1.5(4)
0.07
0.17
a
b
c
d
For atom numbering see Fig. 6. Distance values in A and bond angles in degrees. Uncertainties are s values. Average values of the C–F
bond distances.
ꢁc
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Conclusions
According its vibrational spectra, CH3OC(O)SSCF3 exists in
the gas phase as a mixture of two conformers. At room
temperature the most stable syn-syn-gauche form is present
in a concentration of 81(5)%. This form is present as two
independent and similar molecules in a single crystal of
CH3OC(O)SSCF3 at 190(2) K, as deduced form the low
temperature X-ray diffraction analysis.
The molecular structure of CH3OC(O)SSCF3 is characterized
by a f(CS–SC) dihedral angle of 91.06(15)1. Previous studies
reported for disulfide containing compounds of the type RSSR
reveal that dihedral angles smaller than 901 are observed in
disulfides attached to two carbon atoms with sp2 hybridization;
if both carbon substituents are sp3-hybridized, the dihedral
angle is larger than 1201.30–32 An intermediate angle has been
observed in CH3OC(O)SSCF3, which contains both sp3- and
sp2-hybridized carbon atoms bonded to the disulfide bond.
Fig. 8 Illustration of the intermolecular non-bonded S1ꢃ ꢃ ꢃOQC
distances (3.169 A) [symmetry code (1 ꢀ x, 2 ꢀ y, ꢀz)] and
1,4 intramolecular SS1ꢃ ꢃ ꢃOQC interaction (3.116 A) for one
of the molecules of CH3OC(O)SSCF3 observed in the asymmetric
unit.
Experimental section
Hazards. The toxicological activity of CH3OC(O)SSCF3 has
not been investigated so far, but it is know that serious skin
burns result from contact with the adduct Hg(SCF3)2.45
Conventional vacuum techniques were used to condense
5.61 mmol of CH3OC(O)SCl over 2.88 mmol of Hg(SCF3)2
previously dried in vacuum at low temperatures (near 0 1C).
The reaction proceeds at ꢀ30 1C with stirring for 15 min, as
observed by the vanishing of the pale yellow color (due to
CH3OC(O)SCl). Subsequently the products were separated by
repeatedly ‘‘trap-to-trap’’ condensation through traps held at
ꢀ45, ꢀ80 and ꢀ196 1C. Pure CH3OC(O)SSCF3 (0.96 g, 89%)
was retained as a colorless liquid in the ꢀ45 1C trap. The yield
was nearly quantitative and only minor quantities of OCS and
CO2 were observed as by-products in the U-trap at ꢀ196 1C.
Hg(SCF3)2 was synthesized by reaction of HgF2 (97% Fluka)
with CS2 (98%, Aldrich) in a metal reactor according to the
literature procedure.45
the C–S single bond was well-established.23,29,40,41 Further-
more, in a few cases, it has been experimentally established
that the antiperiplanar conformation appears as a second
stable form at ambient temperature.42,43 In the case that Y is
an –SR group, the preferred mutual orientation of the CQO
bond with respect to the S–S bond is also synperiplanar.13,17,30
The presence of an acyl group attached to the disulfide bond,
as in FC(O)SSC(O)F,17 FC(O)SSCH3,30 FC(O)SSCF3,44
FC(O)SSC(O)CF3,31 and FC(O)SSC(O)CF2Cl32 may lead
to the conformational syn-anti equilibria. For the title
species, CH3OC(O)SSCF3, the interpretation of the vibra-
tional spectroscopy data suggests that the molecule exists in
the gas phase at room temperature as a mixture of two
conformers that differ in the relative orientation of the
carbonyl group with respect to the S–S single bond, with a
prevalence of the syn conformer [81(5)%], over the anti
form. This value is well reproduced by the computational
methods, which compute 80(5)% of the molecules in the
most stable syn-syn-gauche form [DG1 = 0.83 kcal molꢀ1
(B3LYP/6-311++G**)].
Instrumentation
(A) General procedure. Volatile materials were manipulated
in a glass vacuum line equipped with PTFE valves (Young,
London, UK) and capacitance pressure gauge (680 A, Setra
System) for the control of the pressure. The vacuum line had a
connection to an IR cell (optical path length 10 cm, Si windows
0.5 mm thick). This arrangement allowed us to observe the
course of the reaction by FTIR spectroscopy (EQUINOX 55,
Bruker). The pure compound was stored in flame-sealed glass
ampoules under liquid nitrogen in a long-term Dewar vessel. The
ampoules were opened with an ampoule key on the vacuum line,
an appropriate amount was taken out for the experiments and
then they were flame-sealed again.46
The
non-symmetrically
30
substituted
44
disulfides
FC(O)SSCF3 and FC(O)SSCH3 have been studied in
the gas phase and possess [f(CS–SC)] dihedral angles
of 95.0(27) and 83.5(15)1, respectively. Recently, the molecular
structure of two acyldisulfides has been experimentally
determined, resulting in dihedral angles [f(CS–SC)] lower
than 901: 84.2(2)1 in FC(O)SSC(O)CF2Cl32 (X-ray) and
31
77.7(21)1 in FC(O)SSC(O)CF3
(GED). The last value
corresponds to the smallest dihedral angle measured for non-
cyclic disulfides in the gas phase so far. Following this
trend, the S–S bond length and the [f(CS–SC)] torsion
angle in crystalline CH3OC(O)SSCF3 are 2.0113(15) A and
91.06(15)1, respectively.
(B) X-Ray diffraction at low temperature. An appropriate
crystal of ca. 0.3 mm diameter of CH3OC(O)SSCF3 was
obtained on the diffractometer at a temperature of 190(2) K
with a miniature zone melting procedure using focused
infrared laser radiation.33 The diffraction intensities were
ꢁc
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1370 | New J. Chem., 2010, 34, 1365–1372

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measured at low temperatures on a Nicolet R3m Vꢀ1 four-circle
diffractometer. Intensities were collected with graphite-
monochromatized Mo-Ka radiation using the o-scan technique.
The crystallographic data, conditions and some features of the
structure are listed in Table S2 (ESIz). The structure was
solved by Patterson syntheses and refined by full-matrix
least-squares method on F with the SHELXTL-Plus program.47
Absorption correction details are given elsewhere. All atoms
were assigned to anisotropic thermal parameters. Atomic
coordinates and equivalent isotropic displacement coefficients
are given in Table S3, and anisotropic displacement para-
meters for CH3OC(O)SSCF3 are given in Table S4 (ESIz).
X-Ray crystallographic data in CIF format is given as ESI.
Crystal structure data have been deposited at the Cambridge
Crystallographic Data Centre (CCDC). CCDC reference
number 734324. For crystallographic data in CIF or other
electronic format see DOI: 10.1039/b9nj00382g
German-Argentinean cooperation Awards (PROALAR) and
the DAAD Regional Program of Chemistry for Argentina.
They also thank Consejo Nacional de Investigaciones
Cientı
Investigaciones Cientı
(CIC), Republica Argentina. They are indebted to the
´
ficas
y
Te
´
cnicas (CONICET), the Comisio
´
n de
´
ficas de la Provincia de Buenos Aires
´
Facultad de Ciencias Exactas, Universidad Nacional de La
Plata for financial support. STV and CODV especially
acknowledge the DAAD, which generously sponsors the
DAAD Regional Program of Chemistry for the Repu´ blica
Argentina supporting Latin-American students studying for
their PhD in La Plata.
References
1 W. J. Wedemeyer, E. Welker, M. Narayan and H. A. Scheraga,
Biochemistry, 2000, 39, 4207–4216.
2 O. Khakshoor and J. S. Nowick, Org. Lett., 2009, 11, 3000–3003.
3 B. Schmidt, L. Ho and P. J. Hogg, Biochemistry, 2006, 45,
7429–7433.
4 See for example, D. Witt, R. Klajn, P. Barski and
B. A. Grzybowski, Curr. Org. Chem., 2004, 8, 1763–1795.
5 J. M. Fletcher and R. A. Hughes, Tetrahedron Lett., 2004, 45,
6999–7001.
6 L. Andersen, L. Blomberg, M. Flegel, L. Lepsa, B. Nillson and
M. Verlander, Biopolymers, 2000, 55, 227–250.
7 M. Verlander, Chim. Oggi-Chem. Today, 2002, 20, 62–66.
8 A. Obreza and S. Gobec, Curr. Med. Chem., 2004, 11, 3263–3278.
9 S. A. Kates, N. A. Sole, F. Albericio and G. Barany, in Peptides:
´
(C) Vibrational spectroscopy. Gas phase infrared spectra
were recorded with a resolution of 2 cmꢀ1 in the range of
4000–400 cmꢀ1 on a Bruker EQUINOX 55 FTIR spectro-
meter. An FT-Raman spectrum of liquid CH3OC(O)SSCF3
was run with a Bruker 66 with FRA 106 Raman accessory at a
resolution of 2 cmꢀ1; the sample in a 3 mm glass capillary was
excited with 100 mW of a 1064 nm Nd:YAG laser.
(D) NMR spectroscopy. For the 1H, 13C and 19F NMR
measurements, neat samples were flame-sealed in thin-walled
3 mm o.d. tubes and placed into 5 mm NMR tubes. The
spectra were recorded with a Varian Mercury Plus spectro-
meter operating at 200, 50.3 and 188.2 MHz, respectively.
Samples were measured at room temperature using CDCl3 as
an external lock and reference.
Design, Synthesis and Biological Activity, ed. C. Basava and
G. M. Anantharamaiah, Berlin, 1994, pp. 39–58.
10 V. Aquilanti, M. Ragni, A. C. P. Bitencourt, G. S. Maciel and
F. V. Prudente, J. Phys. Chem. A, 2009, 113, 3804–3813.
11 M. K. Denk, Eur. J. Inorg. Chem., 2009, 1358–1368.
12 D. R. Alleres, D. L. Cooper, T. P. Cunningham, J. Gerratt,
P. B. Karadakov and M. Raimondi, J. Chem. Soc., Faraday Trans.,
1995, 91, 3357–3362.
13 M. F. Erben and C. O. Della Ve
2379–2395.
´
dova, Helv. Chim. Acta, 2003, 86,
(E) GC-MS determination. The GC-MS measurements
were recorded in a GCMS-QP2010 SHIMADZU instrument
using gaseous helium as the mobile phase with the pressure in
the column head equal to 100 kPa. The column used was a
19091J-433 HP-5 of 30 m ꢄ 0.32 mm ꢄ 0.25 mm film
thickness. Approximately 1 mL volume of the compound
dissolved in C2H5OC2H5 was chromatographed under the
following conditions: the injection temperature was 200 1C,
the initial column temperature (70 1C) was held for 2 min, then
increased to 200 1C at 7 1C minꢀ1 and held for 2 min after
elevated to 300 1C at 5 1C minꢀ1 and held for 2 min more. In
the spectrometer the source was kept at 200 1C.
14 C. J. Marsden, H. Oberhammer, O. Losking and H. Willner,
J. Mol. Struct., 1989, 193, 233–245.
15 C. J. Marsden and B. J. Smith, J. Phys. Chem., 1988, 92, 347–353.
16 C. J. Marsden, R. D. Brown and P. D. Godfrey, J. Chem. Soc.,
Chem. Commun., 1979, 399–401.
´
17 H.-G. Mack, C. O. Della Vedova and H. Oberhammer, J. Phys.
Chem., 1992, 96, 9215–9217.
18 A. Yokozeki and S. H. Bauer, J. Phys. Chem., 1976, 80, 618–625.
19 C. J. Marsden and B. Beagley, J. Chem. Soc., Faraday Trans. 2,
1981, 77, 2213–2221.
20 H. Oberhammer, private communication, 1981.
21 A. Haas, H. Reinke and J. Sommerhoff, Angew. Chem., Int. Ed.
Engl., 1970, 9, 466–467.
22 A. Haas, J. Helmbrecht, W. Klug, B. Koch, H. Reinke and
J. Sommerhoff, J. Fluorine Chem., 1974, 3, 383–395.
23 S. Torrico-Vallejos, M. F. Erben, H. Willner, R. Boese and
(F) Theoretical calculations. All quantum chemical
calculations were performed with the GAUSSIAN03 program
package.48 Full geometry optimizations were done applying
ab initio (MP2) and DFT (B3LYP) methods using 6-31G* and
6-311++G** basis set. The calculated vibrational properties
corresponded in all cases to potential energy minima for which
no imaginary frequency was found.
C. O. Della Vedova, J. Org. Chem., 2007, 72, 9074–9080.
´
24 C. A. Burton and J. M. Shreeve, J. Am. Chem. Soc., 1976, 98,
6545–6547.
25 S. E. Ulic, C. O. Della Ve
´
dova, A. Hermann, H.-G. Mack and
H. Oberhammer, J. Phys. Chem. A, 2008, 112, 6211–6216.
26 K. R. Ackermann, J. Koster and S. Schlucker, Chem. Phys., 2009,
355, 81–84.
¨
27 W. Koch and M. C. Holthausen, A Chemist’s Guide to Density
Functional Theory, Wiley-VCH, Weinheim, 2nd edn, 2001, pp. 300.
28 M. W. Wong, Top. Curr. Chem., 2003, 231, 1–29.
´
29 M. F. Erben, C. O. Della Vedova, R. M. Romano, R. Boese,
H. Oberhammer, H. Willner and O. Sala, Inorg. Chem., 2002, 41,
Acknowledgements
Financial support by the Volkswagen-Stiftung and the
Deutsche Forschungsgemeinschaft is gratefully acknowledged.
The Argentinean authors thank the ANPCYT-DAAD for the
1064–1071.
30 A. Hermann, S. E. Ulic, C. O. Della Ve
H. Oberhammer, J. Fluorine Chem., 2001, 112, 297–305.
´
dova, H. G. Mack and
ꢁc
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2010 New J. Chem., 2010, 34, 1365–1372 | 1371

View Article Online
31 M. F. Erben, C. O. Della Ve
H. Oberhammer and R. Boese, Inorg. Chem., 2005, 44, 7070–7077.
32 M. F. Erben, C. O. Della Vedova, H. Willner and R. Boese, Eur. J.
´
dova, H. Willner, F. Trautner,
45 E. H. Man, D. D. Coffman and E. L. Muetterties, J. Am. Chem.
Soc., 1959, 81, 3575–3577.
46 W. Gombler and H. Willner, J. Phys. E: Sci. Instrum., 1987, 20,
1286–1288.
´
Inorg. Chem., 2006, 4418–4425.
33 R. Boese and M. Nussbaumer, in Organic Crystal Chem., ed.
D. W. Jones, Oxford University Press, Oxford, 1994, vol. 7, pp. 20–37.
34 C. F. Matta, N. Castillo and R. J. Boyd, J. Phys. Chem. A, 2005,
109, 3669–3681.
35 A. R. Choudhury, U. K. Urs, T. N. Guru Row and K. Nagarajan,
J. Mol. Struct., 2002, 605, 71–77.
36 D. Chopra, K. Nagarajan and T. N. Guru Row, Cryst. Growth
Des., 2005, 5, 1035–1039.
37 A. Bondi, J. Phys. Chem., 1964, 68, 441–451.
38 F. T. Burling and B. M. Goldstein, Acta Crystallogr., Sect. B:
Struct. Sci., 1993, 49, 738–744.
47 G. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr., 2008,
64, 112–122.
48 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr.,
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. 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. G. Johnson, W. Chen, M. W. Wong, C. Gonzalez and
J. A. Pople, GAUSSIAN 03 (Revision B.04), Gaussian, Inc.,
Wallingford, CT, 2004.
39 F. T. Burling and B. M. Goldstein, J. Am. Chem. Soc., 1992, 114,
2313–2320.
40 M. F. Erben and C. O. Della Ve
3740–3748.
41 M. F. Erben, R. Boese, C. O. Della Ve
H. Willner, J. Org. Chem., 2006, 71, 616–622.
42 C. O. Della Vedova, Spectrochim. Acta, Part A, 1991, 47, 1619–1626.
43 H.-G. Mack, H. Oberhammer and C. O. Della Ve
Chem., 1991, 95, 4238–4241.
´
dova, Inorg. Chem., 2002, 41,
´
dova, H. Oberhammer and
´
´
dova, J. Phys.
44 A. C. Fantoni and C. O. Della Ve
´
154, 240–245.
dova, J. Mol. Spectrosc., 1992,
ꢁc
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2010
1372 | New J. Chem., 2010, 34, 1365–1372