Conformational analysis of some N,N-diethyl-2-[(4′-substituted) phenylthio] acetamides

Article abstract of DOI:10.1016/j.saa.2013.06.118

The conformational analysis of some N,N-diethyl-2[(4′-substituted) phenylthio]acetamides bearing the substituents OMe 1, Me 2, H 3, Cl 4, Br 5 and NO₂ 6, was performed by v_CO IR analysis, along with B3LYP/6-311++G(d,p) and Polarisable Continuum Model (PCM) calculations, as well as NBO analysis for 1,3, and 6 and X-ray diffraction for 4. The results of the calculations indicated the existence of two stable conformation pairs, i.e. gauche (anti; syn) (most stable) and cis (anti; syn) in the gas phase. The gauche conformers were less polar with respect to the cis ones for 1 and 3, but more polar for 6. The most intense IR carbonyl doublet component observed at the lower frequency can be ascribed to the gauche conformers g(anti; syn) for 3-6 in n-C₆H₁₄, which is in agreement with the gauche and cis relative stabilities and frequencies resulting from the PCM calculations. Similarly, the single IR band for 1 and 2 in n-hexane may be attributed to the gauche conformers. The PCM calculations compared well with the IR data for the compounds in solution, showing that there is a progressive increase of the cis/gauche population ratio as the solvent polarity increases. The NBO analysis indicated that the gauche(anti; syn) conformation in the gas phase was stabilized by the relevant LP_S4 → π_C2=01 ^* π_C2=01 → σ^* _c3-s4, σ_C3-S4 → π_c2=01 ^*,π_c2=01^* → σ_c3-S4^*, and LP_O1 → σ _C11-H28 orbital interactions, which were absent in the cis(anti; syn) conformer. On the contrary, the cis conformer for derivatives 1, 3, and 6 were stabilized by the σ_C3-S4 → σ_C2-N5 ^* orbital interaction (through bond coupling), along with the additional LP_O1 → σ_S4-C10^* interaction for 6. Moreover, the electrostatic repulsion between the C ^δ+-S^δ- and C^δ+= O ^δ dipoles (Repulsive Field Effect) contributed to both the larger destabilization and increase of the v_CO frequency of the cis conformer with respect to the gauche conformer. X-ray single crystal analysis indicates that compound 4 assumes the c₂(anti) conformation in the solid state, which is the conformation obtained by compound 6 in the gas phase. To obtain the largest energy gain, the molecules were arranged in the crystal in a six-molecules synthon mediated by C-H···O and Cl-···Cl interactions, where the chlorine atoms were related by a crystallographic inversion center.

Full text of DOI:10.1016/j.saa.2013.06.118

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 115 (2013) 738–746
Contents lists available at SciVerse ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Conformational analysis of some N,N-diethyl-2-[(40-substituted)
phenylthio] acetamides
b
c
d
Elisângela Vinhato a, , Paulo R. Olivato , Julio Zukerman-Schpector , Maurizio Dal Colle
⇑
a Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, UNIFESP, Diadema, SP, Brazil
b Conformational Analysis and Electronic Interactions Laboratory, Instituto de Química, USP, CP 26077, 05513-970 São Paulo, SP, Brazil
c Departamento de Química, UFSCar, SP, Brazil
d Dipartimento di Chimica, Università di Ferrara, Ferrara, Italy
h i g h l i g h t s
g r a p h i c a l a b s t r a c t
ꢀ
Conformational analysis of
N,N-diethyl-2[(40-substituted)-
phenylthio]acetamides.
Y
Y
ꢀ
ꢀ
ꢀ
Solvent effect on the conformational
equilibrium through IR spectrocopy.
Theoretical calculations in the gas-
phase and in solvents (PCM).
Single crystal X-ray diffraction
analysis.
= H
= C
= N
= O
= S
Most stable conformers g(anti; syn)
Y = OMe 1, Me 2, H 3, Cl 4, Br 5, NO2 6
a r t i c l e i n f o
a b s t r a c t
The conformational analysis of some N,N-diethyl-2[(40-substituted)phenylthio]acetamides bearing the
substituents OMe 1, Me 2, H 3, Cl 4, Br 5 and NO2 6, was performed by mCO IR analysis, along with
B3LYP/6-311++G(d,p) and Polarisable Continuum Model (PCM) calculations, as well as NBO analysis for
1, 3, and 6 and X-ray diffraction for 4. The results of the calculations indicated the existence of two stable
conformation pairs, i.e. gauche (anti; syn) (most stable) and cis (anti; syn) in the gas phase. The gauche
conformers were less polar with respect to the cis ones for 1 and 3, but more polar for 6.
The most intense IR carbonyl doublet component observed at the lower frequency can be ascribed to
the gauche conformers g(anti; syn) for 3–6 in n-C6H14, which is in agreement with the gauche and cis rel-
ative stabilities and frequencies resulting from the PCM calculations. Similarly, the single IR band for 1
and 2 in n-hexane may be attributed to the gauche conformers. The PCM calculations compared well with
the IR data for the compounds in solution, showing that there is a progressive increase of the cis/gauche
population ratio as the solvent polarity increases. The NBO analysis indicated that the gauche(anti; syn)
Article history:
Received 23 May 2013
Accepted 28 June 2013
Available online 8 July 2013
Keywords:
Conformational analysis
Infrared spectroscopy
Theoretical calculations
X-ray diffraction analysis
N,N-diethyl-2[(40-substituted)-
phenylthio]acetamides
Solvent effect
conformation in the gas phase was stabilized by the relevant LPS4
rꢁC3AS4, and LPO1
orbital interactions, which were absent in the
cis(anti; syn) conformer. On the contrary, the cis conformer for derivatives 1, 3, and 6 were stabilized
by the rꢁC3ꢂS4
orbital interaction (through bond coupling), along with the additional
LPO1
! ; pC2@O1 ! ;
pꢁC2@O1 rꢁC3AS4
rC3AS4
!
pꢁC2@O1
;
pꢁC2@O1
rꢁ
!
!
rꢁ
C11AH28
!
S4AC10
C2AN5
!
rꢁ
interaction for 6. Moreover, the electrostatic repulsion between the CdþASdꢂ and Cd+-
@Odꢂ dipoles (Repulsive Field Effect) contributed to both the larger destabilization and increase of the
mCO frequency of the cis conformer with respect to the gauche conformer. X-ray single crystal analysis
indicates that compound
4 assumes the c2(anti) conformation in the solid state, which is the
⇑
Corresponding author. Address: Universidade Federal de São Paulo, UNIFESP, Instituto de Ciências Ambientais Químicas e Farmacêuticas, 09913-030 Diadema, SP, Brazil.
Tel.: +55 11 3319 3536.
E-mail address: evinhato@unifesp.br (E. Vinhato).
1386-1425/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.saa.2013.06.118

E. Vinhato et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 115 (2013) 738–746
739
conformation obtained by compound 6 in the gas phase. To obtain the largest energy gain, the molecules
were arranged in the crystal in a six-molecules synthon mediated by CAHꢃ ꢃ ꢃO and Clꢃ ꢃ ꢃCl interactions,
where the chlorine atoms were related by a crystallographic inversion center.
Ó 2013 Elsevier B.V. All rights reserved.
Introduction
acetamide 3 is a known compound [7]. The N,N-diethyl-2-[(40-
substituted) phenylthio] acetamides (1–2, 4–6) are new com-
Over the years, intramolecular nonbonded interactions, such as
Sꢃ ꢃ ꢃO, have been detected in a large number of organic sulfur com-
pounds [1]. Moreover, studies by Iwaoka et al. [2] have highlighted
the importance of this interaction in the stabilization of protein
folding. Our X-ray and ab initio (HF) studies [3] showed that the
intramolecular Sꢃ ꢃ ꢃO@C distance in the solid increased from
2-(4-nitrophenylthio)-cyclohexanone to 2-(4-nitrophenylsulfinyl)-
cyclohexanone and to 2-(4-nitrophenylsulfonyl)-cyclohexanone.
Within the context of spectroscopic (IR, 13C NMR, UV, and UPS),
X-ray diffraction, and theoretical studies of the compounds contain-
ing the AC(O)CH2SA moiety, the results indicated that in the gas
phase and in solution they prefer the gauche conformation [4]. In
general, the stability of the gauche rotamers of b-carbonyl-sulfides
pounds and were prepared as described previously in the literature
[8].
General Procedure for the preparation of 1–6
Benzenethiol (10 mmol) was added to 10 mmol sodium in abso-
lute ethanol. After 5 min, the resulting solution of sodium thiolate
was added dropwise, with stirring to 2-bromo-N,N-diethylaceta-
mide (10 mmol) in ethanol at 0 °C. The reaction was stirred at
room temperature (r.t.). Water was then added to the reaction
mixture followed by extraction with CH2Cl2. The organic extract
was dried over MgSO4 and removal of the solvent yielded the
product.
N,N-diethyl-2-[(4-methoxyphenyl)thio]acetamide 1: colorless oil;
yield: 98%. Bp: 145 °C/0.05 mmHg. 1H NMR (300 MHz, CDCl3) d
(ppm) 7.46–7.43 (m, 2H), 6.85–6.82 (m, 2H), 3.79 (s, 3H), 3.61 (s,
2H), 3.35 (q, 2H, 3J = 7.2 Hz), 3.33 (q, 2H, 3J = 7.2 Hz), 1.16 (t, 3H,
3J = 7.2 Hz), 1.09 (t, 3H, 3J = 7.2 Hz). 13C NMR (75.5 MHz, CDCl3) d
(ppm) 167.8, 159.6, 134.5, 124.9, 114.5, 55.3, 42.4, 40.3, 38.6,
14.3, 12.9. Anal. calcd. for C13H19NO2S: C, 61.63; H, 7.56; N, 5.53.
Found: C, 61.59; H, 7.43; N, 5.75.
N,N-diethyl-2-[(4-methylphenyl)thio]acetamide 2: colorless oil;
yield: 55%. Bp: 115 °C/0.03 mmHg. 1H NMR (300 MHz, CDCl3) d
(ppm) 7.37–7.34 (m, 2H), 7.11–7.08 (m, 2H), 3.67 (s, 2H), 3.35 (q,
2H, 3J = 7.2 Hz), 3.30 (q, 2H, 3J = 7.2 Hz), 2.30 (s, 3H), 1.17 (t, 3H,
3J = 7.2 Hz), 1.09 (t, 3H, 3J = 7.2 Hz). 13C NMR (75.5 MHz, CDCl3) d
(ppm) 167.7, 137.2, 131.4, 131.3, 129.7, 42.5, 40.3, 37.7, 21.0,
14.3, 12.8. Anal. calcd for C13H19NOS: C, 65.78; H, 8.07; N, 5.90.
Found: C, 65.56; H, 7.78; N, 5.99.
N,N-diethyl-2-(phenylthio)acetamide 3: white solid; yield: 81%.
Mp: 43–45 °C. 1H NMR (300 MHz, CDCl3) d (ppm) 7.47–7.43 (m,
2H), 7.32–7.18 (m, 3H), 3.73 (s, 2H), 3.37 (q, 2H, 3J = 7.2 Hz), 3.33
(q, 2H, 3J = 7.2 Hz), 1.19 (t, 3H, 3J = 7.2 Hz), 1.10 (t, 3H,
3J = 7.2 Hz). 13C NMR (75.5 MHz, CDCl3) d (ppm) 167.5, 135.4,
130.4, 128.9, 126.8, 42.5, 40.4, 37.1, 14.4, 12.8. Anal. calcd, for C12-
H17NOS: C, 64.53; H, 7.67; N, 6.27. Found: C, 64.27; H, 7.51; N, 6.33.
2-[(4-chlorophenyl)thio]-N,N-diethylacetamide 4: white solid;
yield: 66%. Mp: 53–54 °C. 1H NMR (300 MHz, CDCl3) d (ppm)
7.41–7.37 (m, 2H), 7.28–7.24 (m, 2H), 3.70 (s, 2H), 3.37 (q, 2H,
3J = 7.2 Hz), 3.33 (q, 2H, 3J = 7.2 Hz), 1.20 (t, 3H, 3J = 7.2 Hz), 1.10
(t, 3H, 3J = 7.2 Hz). 13C NMR (75.5 MHz, CDCl3) d (ppm) 167.2,
133.8, 133.0, 131.7, 129.0, 42.5, 40.5, 14.4, 12.8. Anal. calcd. for C12-
H16ClNOS: C, 55.91; H, 6.26; N, 5.43. Found: C, 56.17; H, 6.38; N,
5.49.
has been attributed to pCꢁO
The
/
rCAS and pCO
/
rꢁ orbital interactions.
AS
C
mCO IR analysis along with ab initio computations and X-ray dif-
fraction studies of N,N-diethyl-2-[(40-substituted) phenylsulfinyl]
acetamides [5], revealed that the cis conformer in the gas phase
and in solution is more stable, but the quasi-gauche conformer is
preferred in the solid state. Recent IR and DFT studies of some N-
methoxy-N-methyl-2-[(40-substituted)phenylthio]-propanamides
[6] indicated that the gauche conformation is the most stable for
these compounds in the gas phase and in solution. As part of contin-
uing research on conformational studies, we turned our attention to
the N,N-diethyl-2-[(40-substituted) phenylthio]acetamides: OMe 1,
Me 2, H 3, Cl 4, Br 5, NO2 6 (Scheme 1). In this paper, we report the
combined application of IR spectroscopy in solution (solvents of dif-
ferent polarities), for 1–6, theoretical calculations (B3LYP/6-
311++Gꢁꢁ) in the gas phase and Polarisable Continuum Model
(PCM; solvents of different polarities) for 1, 3, and 6, and X-ray dif-
fraction analysis for compound 4.
Experimental
Materials
All solvents for IR measurements were spectrograde and used
without further purification. The N,N-diethyl-2-(phenylthio)-
2-[(4-bromophenyl)thio]-N,N-diethylacetamide 5: white solid;
yield: 63%. Mp: 39–40 °C. 1H NMR (300 MHz, CDCl3) d (ppm)
7.43–7.38 (m, 2H), 7.34–7.30 (m, 2H), 3.70 (s, 2H), 3.37 (q, 2H,
3J = 7.2 Hz), 3.33 (q, 2H, 3J = 7.2 Hz), 1.20 (t, 3H, 3J = 7.2 Hz), 1.10
(t, 3H, 3J = 7.2 Hz). 13C NMR (75.5 MHz, CDCl3) d (ppm) 167.2,
134.5, 132.0, 131.8, 120.8, 42.5, 40.5, 36.9, 14.4, 12.8. Anal. calcd.
for C12H16BrNOS: C, 47.69; H, 5.34; N, 4.63. Found: C, 47.65; H,
5.37; N, 4.55.
N,N-diethyl-2-[(4-nitrophenyl)thio]acetamide 6: yellow solid;
yield: 61%. Mp: 63–65 °C. 1H NMR (300 MHz, CDCl3) d (ppm)
8.15–8.10 (m, 2H), 7.52–7.47 (m, 2H), 3.87 (s, 2H), 3.41 (q, 4H,
3J = 7.2 Hz), 1.26 (t, 3H, 3J = 7.2 Hz), 1.13 (t, 3H, 3J = 7.2 Hz). 13C
NMR (75.5 MHz, CDCl3) d (ppm) 166.2, 146.2, 145.4, 127.1, 123.9,
42.7, 40.7, 35.1, 14.4, 12.8. Anal. calcd. for C12H16N2O3S: C, 53.71;
H, 6.01; N, 10.44. Found: C, 53.66; H, 5.87; N, 10.19.
Scheme 1. Atoms labeling of N,N-diethyl-2-[(40-substituted)phenylthio]aceta-
mides and definition of relevant dihedral angles.

740
E. Vinhato et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 115 (2013) 738–746
IR measurements
Theoretical calculations
The IR spectra were recorded with a FT-IR Nicolet Magna 550
spectrometer with 1.0 cmꢂ1 resolution. The carbonyl region
(1800–1600 cmꢂ1) was recorded for n-hexane, carbon tetrachlo-
ride, chloroform, and acetonitrile solutions at a concentration of
2.0 ꢄ 10ꢂ2 mol/dm3 using a 0.519 mm sodium chloride cell. The
carbonyl first overtone region (3600–3100 cmꢂ1) was recorded
for a carbon tetrachloride solution (2.0 ꢄ 10ꢂ2 mol/dm3) using a
1.00 quartz cell. The overlapped carbonyl bands (fundamental
and first overtone) were deconvoluted by means of the Grams/32
curve fitting program (version 4.04 Level II) [9]. The populations
of the cis and gauche conformers were estimated from the maxi-
mum of each component of the resolved carbonyl doublet ex-
pressed as percentage of absorbance, assuming equal molar
absorptivity coefficients for the studied compounds 1–6.
All calculations were carried out using methods and basis sets
implemented in the Gaussian package of programs (G03.E01)
[12]. Geometry optimizations were performed by the use of
Becke’s three-parameter hybrid functional combined with the
Lee, Yang, and Parr (LYP) correlation functional, denoted as
B3LYP [13]. The 6-311++G(d,p) basis set was employed for all in-
volved atoms. Harmonic vibrational frequencies were computed
and zero-point energy corrections were determined and included
in all relative energy calculations. The polarizable continuum mod-
el (PCM) [14] approach was used for a full geometry optimization
in n-heptane, carbon tetrachloride, chloroform, and acetonitrile,
employing the same functional and basis set as in the gas-phase
study. The NBO 3.1 program [15] was used as implemented in
the GAUSSIAN 03 package, and the reported NBO delocalization
energies (E2) were those given by second-order perturbation
theory.
NMR measurements
Results and discussion
1H NMR spectra were recorded on a Varian Inova 1 spectrome-
ter operating at 299.947 MHz for 0.1 mol/dm3 solutions in chloro-
form-d. H chemical shifts are reported in ppm relative to TMS
(internal standard).
Table 2 summarizes the stretching frequencies and absorbance
percentage resulting from fitting the carbonyl IR band curve for the
N,N-diethyl-2-[(40-substituted)phenylthio] acetamides 1–6 in sol-
vents with increasing relative permittivity [16], i.e. n-hexane
(e = 1.9), carbon tetrachloride (e = 2.2), chloroform (e = 4.9), and
acetonitrile (e = 38). Compounds 3–6 showed a carbonyl doublet
in n-hexane, carbon tetrachloride, and chloroform, while com-
pounds 1–2 displayed only a singlet in n-hexane, and behave sim-
ilarly to 3–6 in the other solvents. In acetonitrile all compounds
present a single, symmetrical band.
The lower carbonyl frequency component was approximately
2–5 times more intense than the higher frequency one in
n-C6H14 for compounds 3–6 and in CCl4 for 1–6. The enhancement
of the solvent relative permittivity increases the intensity of the
higher carbonyl frequency component for compounds 3–6 going
from n-C6H14 to CH3CN and also for compounds 1–2 going from
CCl4 to CH3CN. The solvent effect on the carbonyl band compo-
nents for compound 3 is illustrated in Fig. 1. Moreover, Table 2
shows that, in the non-polar solvents, n-C6H14 and CCl4, there is
a discrete increase in the intensity ratio of the low frequency com-
ponent with respect to the high frequency component, going from
nitro 6 to methoxy 1 derivatives. For example, for n-C6H14, it in-
creased from 76%/24% to 100%/0%, and for CCl4 it increased from
69%/31% to 85%/15%.
X-ray measurements
X-ray crystallographic data were collected with a CAD4-Mach3
diffractometer using graphite-monochromated Mo K
a radiation
(k = 0.71073 Å). Data were collected at 290 K and the structure
was solved by direct methods with SIR92 [10] and refined by
full-matrix least-squares on F2 with SHELXL-97 [11]. All non-
hydrogen atoms were refined anisotropically and hydrogen atoms
were geometrically placed (CAH = 0.93–0.98 Å) and refined riding
with Uiso (H) = 1.2Ueq (C) and Uiso (H) = 1.5 Ueq (methyl-C). The
key crystallographic data are given in Table 1. CCDC 936152 con-
tains the supplementary crystallographic data for this paper. These
data can be obtained free of charge from the Cambridge Crystallo-
graphic Data Centre (CCDC), 12 Union Road, Cambridge CB2 1EZ,
UK; fax: +44 1223 336 33; e-mail: deposit@ccdc.cam.ac.uk.
Table 1
Crystal data and structure refinement.
The occurrence of two carbonyl band components in the first
overtone region (CCl4) for 1–6 at frequencies about twice of those
in the fundamental region minus approximately 15 cmꢂ1 (which
corresponds to two times the mechanical anharmonicity) and with
nearly the same intensity ratios, indicates that compounds 1–6
were present, in carbon tetrachloride, as two conformers
[17a,17b]. The observed IR solvent effect suggests the existence
of one conformer for 1–2 and two conformers for 3–6 in n-hexane,
and two conformers in chloroform, and one conformer for 1–6 in
acetonitrile.
In order to evaluate the geometry of the minimum energy con-
formations in the gas phase, B3LYP/6-311++G(d,p) calculations
were performed for the N,N-diethyl-2-[(40-substituted)phenylthio]
acetamides 1, 3, and 6. The calculated geometrical parameters, car-
bonyl frequencies (mCO), relative energies (Boltzmann distribution),
and dipole moments for the conformers, along with the X-ray dihe-
Color/dimensions (mm)
Chemical formula
Formula weight
Crystal system
Space group
Unit cell dimensions
a (Å)
b (Å)
Colorless/0.12 ꢄ 0.08 ꢄ 0.04
C12 H16 Cl N O S
257.77
Monoclinic
P21/n
12.950(1)
8.6036(9)
13.069(1)
112.401(9)
1346.2(2)
4
c (Å)
ꢀ(ꢅ)
Volume (Å3)
Z
Density (calculated) (g/cm3)
Absorption coefficient (mmꢂ1
_ range for data collection (ꢅ)
Reflections measured
1.272
0.419
)
2.81–28.50
3417
3417/1665 (Rint = 0.048)
3417/0/147
1.003
R1 = 0.0465
wR2 = 0.1160
R1 = 0.1369
wR2 = 0.1481
0.338/ꢂ0.277
Independent/observed reflections
Data/restraints/parameters
Goodness of fit on F2
dral angles of 4 are listed in Table 3.
Final R indices [I > 2_(I)]
Calculations indicated the existence of one pair of syn-clinal
(gauche) conformers and one pair of syn-periplanar (cis) conform-
ers, such as g and c1 for 1 and 3 and g and c2 for 6. Additionally,
each one of the g, c1, and c2 conformers existed in an anti-syn
R indices (all data)
Dq max, min, (e Åꢂ3
)

E. Vinhato et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 115 (2013) 738–746
741
Table 2
Frequencies (m
, cmꢂ1) and intensities of the carbonyl stretching bands in the IR spectra of N,N-diethyl-2-[(40-substituted) phenylthio] acetamides, Et2NC(O)CH2S-C6H4-Y 1–6.
Compd.
Y
n-C6H14
CCl4
CHCl3
CH3CN
m
Pa
m
P
mb
P
m
P
m
P
1
2
3
4
5
6
OMe
Me
H
–
–
100
–
1657.7
1646.5
1657.4
1647.0
1657.4
1647.0
1657.0
1646.9
1657.0
1646.6
1657.5
1646.6
15
85
16
84
17
83
25
75
27
73
31
69
3304.2
3278.5
3300.0
3278.1
3300.7
3279.4
3302.1
3279.0
3301.9
3278.6
3304.1
3279.8
15
85
16
84
19
81
21
79
23
77
28
72
1638.5
1628.7
1638.0
1630.4
1639.4
1631.5
1639.9
1632.5
1641.7
1632.0
1641.8
1633.4
38
62
40
60
40
60
42
58
43
57
66
34
1639.7
100
–
100
–
100
–
100
–
100
–
100
–
1657.4
–
–
1640.6
–
1640.3
–
1641.6
–
1641.5
–
1657.9
1663.8
1655.7
1664.0
1655.2
1664.9
1655.8
1666.3
1655.2
100
21
79
28
72
29
71
24
76
Cl
Br
NO2
1643.3
–
a
Intensity of each component of the carbonyl band expressed in percentage of absorbance.
First overtone.
b
.8
(a)
(d)
.8
.7
.6
.5
.4
.3
.2
.1
0
.7
.6
.5
.4
.3
.2
.1
0
1700 1680 1660 1640 1620 1600 1580 1560
1720 1700 1680 1660 1640 1620 1600
Wavenumber (cm-1)
Wavenumber (cm-1)
.8
(b)
(e)
.7
.6
.5
.4
.3
.2
.1
0
.4
.3
.2
.1
0
1700 1680 1660 1640 1620 1600 1580
1700 1680 1660 1640 1620 1600
Wavenumber (cm-1)
Wavenumber (cm-1)
(c)
.08
.07
.06
.05
.04
.03
3340 3320 3300 3280 3260 3240
Wavenumber (cm-1)
Fig. 1. IR spectra of N,N-diethyl-2-(phenylthio)-acetamide (3) showing the analytically resolved carbonyl stretching bands in n-hexane (a), carbon tetrachloride [fundamental
(b) and first overtone (c)], chloroform (d), and acetonitrile (e).
equilibrium, as the [AC(O)ANEt2] group was almost planar (with d
and d0 dihedral angles of approximately 0.5° and 177°, respec-
tively). The g(anti; syn) conformers of 1, 3, and 6 were the most sta-
minima on the ground state potential energy surface at a of
approximately 6° of the c1(anti; syn) conformations for 1 and 3
and c2(anti; syn) conformations for 6. For 1 and 3, the g(anti; syn)
conformers were less polar than the c1(anti; syn) conformers.
However, we observed the opposite for 6, wherein the g(anti;
ble and possessed a
a dihedral angle (O1@C2AC3AS4) of about
95°. Rotation around this internal coordinate lead to the remaining

742
E. Vinhato et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 115 (2013) 738–746
Table 3
Relative energies (E, kJ molꢂ1), Boltzmann populations (P, %), dipole moments (
l
, D), carbonyl harmonic frequencies (
m
, cmꢂ1), and selected dihedral angles (°) optimized for
different cis(c) and gauche(g) conformers of 1, 3 and 6 at the B3LYP/6-311++G(d,p) level and the X-ray geometrical data for 4-Cl-C6H4-SCH2C(O)NEt2 (4).
Compd.
Y
Conf.a
Eb
Pc
l
mC@O
Dihedral anglesd
a
b
c
d
d0
e
e0
1
OMe
g(anti)
g(syn)
c1(anti)
c1(syn)
0
69.5
19.6
8.6
2.23
2.17
4.45
4.29
1694.6
1692.0
1714.4
1713.8
95.6
97.6
ꢂ7.6
ꢂ3.3
ꢂ94.3
ꢂ93.7
ꢂ74.9
ꢂ76.1
43.4
42.4
85.5
87.1
ꢂ0.4
ꢂ0.8
0.1
ꢂ0.4
ꢂ177.0
ꢂ175.7
ꢂ178.5
ꢂ178.9
ꢂ88.1
78.4
ꢂ97.1
3.14
5.16
8.46
ꢂ105.8
ꢂ96.6
ꢂ88.4
2.3
78.5
ꢂ101.9
3
6
4
H
g(anti)
g(syn)
c1(anti)
c1(syn)
0
76.3
19.7
3.3
3.08
3.00
4.74
4.66
1696.1
1693.5
1715.3
1714.8
97.8
99.6
ꢂ8.3
ꢂ5.2
ꢂ90.3
ꢂ90.0
ꢂ75.7
ꢂ76.2
30.4
30.9
82.7
83.5
ꢂ0.8
ꢂ0.6
0.5
ꢂ177.8
ꢂ176.8
ꢂ178.2
ꢂ177.9
ꢂ178.9
ꢂ177.9
ꢂ179.3
ꢂ177.9
ꢂ88.6
78.5
ꢂ96.1
3.35
7.78
11.44
ꢂ104.1
ꢂ96.4
ꢂ88.2
0.8
0.1
78.3
ꢂ102.4
NO2
Cl
g(anti)
g(syn)
c2(anti)
c2(syn)
0
74.9
20.6
3.5
9.18
9.15
7.87
7.82
1696.0
1694.2
1713.0
1710.7
99.9
ꢂ81.5
16.1
16.9
176.5
176.9
ꢂ0.6
ꢂ0.5
0.2
ꢂ0.1
ꢂ87.6
78.1
ꢂ95.5
3.19
7.59
10.78
100.6
ꢂ9.2
ꢂ8.2
ꢂ82.2
ꢂ102.6
ꢂ96.8
ꢂ176.7
ꢂ177.5
ꢂ88.7
1.0
77.5
ꢂ105.0
X-ray
c2(anti)
–
–
–
2.5(5)
175.1(2)
ꢂ155.0(3)
5.4(6)
ꢂ174.8(4)
ꢂ89.6(6)
ꢂ97.8(5)
a
Conformer designation; (g) and (c) refers to the gauche and cis conformers, respectively; syn refers to both N,N-diethyl methyl groups in the same half-space defined by
the [AC(O)N] plane and anti refers to the methyl groups above and the other bellow the referred plane.
b
Relative energies.
Molar fraction in percentage..
See Scheme 1.
c
d
(a)
g(anti)
g(syn)
c1(anti)
c1(syn)
(b)
g(anti)
g(syn)
c1(anti)
c1(syn)
(c)
c2(anti)
c2(syn)
g(anti)
g(syn)
Fig. 2. Gauche and cis conformers obtained at B3LYP/6-311++G(d,p) level for 1 (a), 3 (b) and 6 (c).
syn) conformers were more polar than the c2(anti; syn) ones. The
structures of the computed g(anti; syn), c1(anti; syn), and c2(anti;
syn) conformers for 1, 3 and 6 are illustrated in Fig. 2 [18].
each pair of conformers for 1, 3, and 6 g(anti)/g(syn), c1(anti)/
c1(syn), and c2(anti)/c2(syn) of ca. 3.7 is very close to the previously
computed (anti)/(syn) ratio for the N,N-diethylacetamide [5]. The
larger population of the anti (g, c1 and c2) conformers of 1, 3, and
6 relative to the syn ones may be justified by the same factors
which stabilize the anti conformer to a larger extent relative to
the syn one for the parent N,N-diethylacetamide. Furthermore,
each anti-syn pair for the (g, c1, and c2) conformers of 1, 3, and 6
The
e
and e0 dihedral angles define the anti and syn conformers.
That is, both methyls of the N,N-diethylcarboxamide group are at
the same half-space defined by the [AC(O)AN] plane (for the syn
conformer) or one methyl is in each half-space relative to the
referred plane (for the anti conformer). The population ratio for

E. Vinhato et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 115 (2013) 738–746
743
exhibits almost the same dipole moment values along with very
close computed carbonyl frequencies (Table 3).
energy ordering of conformers in acetonitrile compared to that of
the isolated molecule (gas phase) for compounds 1, 3, and 6.
The comparison between experimental IR (Table 2) and PCM
(Table 4) data provides further support of the fact that the most in-
tense carbonyl doublet component for 3–6 (Table 2) in n-hexane
may be attributed to the gauche conformers g(anti; syn), which
are more stable and have a lower frequency than the cis ones.
The single band for 1 and 2 in n-hexane (Table 2) may be attributed
to the gauche conformer in the same way. For 6, the dipole mo-
ments of the c2 conformers are smaller than those of the g con-
formers. However, the calculated frequencies and the solvent
effect are in agreement with the experimental results.
The distribution of gauche rotamers for compounds 1–6, which
was estimated from experimental carbonyl band intensities in
n-hexane, are not the same, but they are comparable to those
obtained by B3LYP(PCM) calculations for 3 and 6. In addition, the
calculated frequencies trend compares well with the IR data.
To evaluate the energies of the donor–acceptor orbital interac-
tions, we performed the natural bond orbital (NBO) analysis for the
four conformers of 1, 3, and 6 (Table 5). The three strongest orbital
The analysis of the gas phase-calculated g(anti; syn) populations
for compounds 1 (89.1%), 2 (96%), and 6 (95.5%) do not indicate any
substituent effect. However, the electron-withdrawing group
(EWG) nitro leads to a cis [c2(anti; syn)] conformer whose geometry
differs from that of the cis (c1) conformers for 1 and 3. For instance,
for the c2(anti; syn) conformers of 6, the S(4)AC(10) bond becomes
coplanar with the carbonyl group (with
c dihedral angles, of about
176°).
It should be noted that there is a reasonably good match be-
tween the theoretical (gas phase) gauche/cis population ratio and
IR data in solution for non-polar solvents. In fact, the similarity
of the carbonyl frequencies in the gas phase for the anti and syn
pairs of the cis and gauche conformers originates a carbonyl dou-
blet in solution for which the less intense, higher frequency com-
ponent corresponds to the pair of the cis conformers and the
lower frequency component corresponds to the more stable pair
of the gauche conformers. In solutions of n-C6H14 and CCl4, which
are the least polar, gauche conformers (ca. 85%) are predominant
with respect to the most polar cis ones. In the polar solvent, CHCl3,
we observed a decrease in the gauche/cis population ratio for 1–5
from 60%/40%, except for 6, where the ratio remained at 34%/
66%. Moreover, in the highly polar solvent, CH3CN, the most polar
cis conformer is the only one present.
interactions were LPN5
!
pꢁC2@O1 (ca. 65.5 kcal molꢂ1; conjugative),
rꢁC2AC3 (ca.
LPO1
!
rꢁC2AN5 (ca. 23.5 kcal molꢂ1), and LPO1
!
18.6 kcal molꢂ1; through bond coupling). They were observed for
all the studied conformations, and were quite similar for 1, 3,
and 6. These results indicate that these orbital delocalizations are
not responsible for the gauche preference since both gauche and
cis conformers exhibit very similar NBO delocalization values.
The g(anti; syn) conformers preference in the gas phase may be
To get further information on the conformational preferences in
solution, the geometries found in the gas phase were optimized at
B3LYP/6-311++G(d,p) using the PCM (Polarisable Continuum Mod-
el) method. The solvent effect was computed in n_heptane, carbon
tetrachloride, chloroform, and acetonitrile, and selected parame-
ters are summarized in Table 4.
ascribed to the occurrence of: LPS4
!
pꢁC2@O1
;
pC2@O1
!
rꢁC3AS4
;
rC3AS4
!
pꢁC2@O1
;
pꢁC2@O1
!
rꢁC3AS4
,
and LPO1
!
rꢁC11AH28 orbital
interactions. The unusual pCꢁ@O
!
rꢁCꢂX interaction was observed
The optimized geometries for 1, 3, and 6 taking into account the
solvent effect are almost the same as in the gas phase. Only the
for some N,N-dimethyl-2-haloacetamides by NBO analysis [19],
and through electron spectroscopy for the N,N-diethyl-2-meth-
c1(anti; syn) conformations for 1 presented a distortion in the
a
ylthioacetamide
LPS4
[20].
Moreover,
the
sum
of
the
!
!
pꢁC2@O1
;
pC2@O1
!
rꢁC3@S4
;
rC3@S4
!
pꢁC2@O1
;
and pꢁC2@O1
dihedral angle, which changed from ꢂ7.6° (gas phase) to 24.5°
rꢁC3AS4 interactions of approximately 13.7 kcal molꢂ1 stabilizes the
g(anti; syn) conformers for 1, 3, and 6 by almost the same amount.
In addition to the interactions mentioned above, the g(anti; syn)
conformers are also stabilized by an intramolecular hydrogen bond
between the carbonyl oxygen and the ortho-hydrogen atoms:
(acetonitrile).
Analysis of the population data presented in Table 4 indicates
that the more polar cis conformers become more stable as the polar-
ity of the solvent increases. While solvents of low polarity yield
comparable results to those found in the gas phase, the strongly po-
lar solvent (acetonitrile) is found to substantially lower the energy
of the cis (c1; c2) conformers that possess larger permanent electric
moments. This differential stabilization is sufficient to change the
LPO1
!
rꢁC11AH28. Its value increases progressively going from elec-
tron donating group (EDG) [OMe; 0.9 kcal molꢂ1], to hydrogen [H;
1.4 kcal molꢂ1], and then to EWG [NO2; 1.7 kcal molꢂ1].
Table 4
Relative energies (E, kJ molꢂ1), Molar fraction in percentage (P, %), dipole moments (
l
, D) and carbonyl harmonic frequencies (
m
C@O, cmꢂ1) optimized for different cis(c) and
CH3CN (e = 38)
gauche(g) conformers of 1, 3 and 6 at the B3LYP/6-311++G(d,p) level including the solvent effect PCM method.
Compd.
Conf.a
Heptane (e = 1.9)
CCl4 (e = 2.2)
CHCl3 (e = 4.9)
Eb
Pc
mC@O
l
E
P
mC@O
l
E
P
mC@O
l
E
P
mC@O
l
1 (OMe)
g(anti)
g(syn)
c1(anti)
c1(syn)
0
65.2
17.5
13.8
3.5
1679.4
1677.8
1699.3
1699.5
2.49
0
66.4
15.2
14.6
3.8
1676.2
1675.6
1696.6
1694.5
2.50
0
54.5
11.8
26.2
7.5
1661.3
1660.3
1681.7
1682.1
2.73
2.46
6.32
0
23.6
5.0
63.7
7.7
1645.9
1644.6
1660.3
1661.2
3.03
3.25
3.84
7.20
2.43
5.04
4.89
3.65
3.74
7.08
2.49
5.20
4.99
3.78
1.81
4.90
2.79
5.67
5.56
2.99
6.45
6.27
5.24
3 (H)
g(anti)
g(syn)
c1(anti)
c1(syn)
0
75.6
18.3
4.8
1679.3
1679.4
1698.6
1700.0
3.41
3.33
5.42
5.31
0
75.7
17.2
5.6
1677.3
1676.0
1695.2
1695.2
3.49
3.39
5.55
5.48
0
70.6
13.9
12.5
3.0
1662.6
1662.5
1680.4
1680.6
3.84
3.72
6.33
6.14
0
49.3
11.0
32.4
7.3
1646.4
1646.4
1663.0
1663.5
4.22
4.12
7.10
7.10
3.50
6.84
10.04
3.67
6.42
9.75
4.01
4.28
7.80
3.71
1.04
4.73
1.3
1.5
6 (NO2)
g(anti)
g(syn)
c2(anti)
c2(syn)
0
69.4
18.0
10.0
2.6
1681.7
1681.0
1694.8
1692.8
10.25
10.24
8.69
0
70.9
14.2
11.8
3.1
1678.4
1677.5
1690.5
1688.5
10.44
10.41
8.86
0
50.4
11.1
30.7
7.8
1665.1
1664.7
1671.8
1671.6
11.42
11.34
9.53
2.30
6.14
0
22.8
4.8
58.0
14.4
1650.1
1649.4
1653.7
1651.4
12.33
12.34
10.25
10.28
3.35
4.79
8.15
3.98
4.42
7.77
3.74
1.22
4.62
8.67
8.83
9.33
3.44
a
Conformer designation; (g) and (c) refers to the gauche and cis conformers, respectively; syn refers to both N,N-diethyl methyl groups in the same half-space defined by
the [AC(O)N] plane and anti refers to the methyl groups above and the other bellow the referred plane.
b
Relative energies.
Molar fraction in percentage.
c

744
E. Vinhato et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 115 (2013) 738–746
Table 5
LPS4
lar for the g(anti; syn) conformers, the progressive increase in the
dihedral angles going from approximately 16° for 6 to about
30° for 3 and to 42° for 1 leads to a decrease in the LPS4
interaction whose delocalization energies are approximately
18 kcal molꢂ1, 13 kcal molꢂ1 and 9 kcal molꢂ1, respectively.
The cis [c1 and c2(anti; syn)] conformers are stabilized by the
=
pꢁC10AC11 interaction from occurring (ca. 4.9 kcal molꢂ1). Simi-
Comparison of significant NBO energies (kcal molꢂ1) of the interacting orbitals for the
anti and syn, gauche (g) and cis (c1, c2) conformers of 1, 3 and 6 calculated at the
B3LYP/6-311++G(d,p) level.
c
=
pꢁC10AC11
Compd.
Y
Orbitals
Conformations
g(anti)
g(syn)
c1(anti)
c1(syn)
1
OMe
LPN5
LPO1
LPO1
LPO1
LPO1
LPO30
!
!
!
!
!
pꢁC2@O1
65.3
23.6
18.5
0.9
–
29.4
9.0
1.6
2.4
–
61.0
23.5
18.4
0.9
–
29.3
9.1
1.6
2.4
–
65.6
24.3
20.8
–
65.2
24.2
20.8
–
rꢁC2AN5
rꢁC2AC3
rꢁC11AH28
rꢁS4AC10
rC3AS4
!
rꢁC2AN5 interaction (through bond coupling) by ca.
3.1 kcal molꢂ1. Moreover, the near-planarity of the [O@CACASPh]
moiety (b dihedral angle ca. 177°) of the c2(anti; syn) conformers
–
–
for 6 allows the occurrence of the LPO1
!
rꢁS4AC10 interaction (ca.
!
rꢁC13AC12
pꢁC10AC11
pꢁC2@O1
30.0
5.0
–
–
3.2
–
30.0
5.1
–
–
3.2
–
1.4 kcal molꢂ1) which is not possible for the c1(anti; syn) conform-
ers of 1 and 3, due to their unfavorable b dihedral angles of ca. 75°.
The CHELPG [21] charges for 1, 3 and 6 are summarized in
Table 6, while Table 7 displays the interatomic distances between
some selected atoms and the difference between these contacts
LPS4
LPS4
pC2@O1
rC3AS4
rC3AS4
pꢁC2@O1
!
!
!
!
!
!
rꢁC3AS4
rꢁC2AN5
pꢁC2@O1
rꢁC3AS4
4.6
5.5
4.6
6.0
–
–
and the sum of the van der Waals (RvdW) radii (Dl) for 1, 3 and 6.
3
H
LPN5
LPO1
LPO1
LPO1
LPO1
LPS4
LPS4
pC2@O1
rC3AS4
rC3AS4
pꢁC2@O1
!
pꢁC2@O1
rꢁC2AN5
rꢁC2AC3
rꢁC11AH28
rꢁS4AC10
pꢁC10AC11
pꢁC2@O1
rꢁC3AS4
rꢁC2AN5
pꢁC2@O1
rꢁC3@
65.6
23.6
18.6
1.4
–
13.1
1.5
2.4
–
61.9
23.5
18.6
1.3
–
13.0
1.5
2.5
–
65.9
24.3
20.3
–
–
4.65
–
–
3.0
–
65.2
24.2
20.9
–
–
4.7
-
–
3.1
–
The 1, 3, 6 g(anti; syn) and the 1, 3 c1(anti; syn) conformers are
electrostatically stabilized by the close proximity of the positively
charged ortho hydrogen atom (H28) and the negatively charged
carbonyl oxygen atom (O1). In fact, the Oꢃ ꢃ ꢃH mean value for the
!
!
!
!
!
!
interatomic distance is shorter than the
RvdW radii by about
ꢂ0.41 Å for the 1, 3, and 6 g(anti; syn) conformers and ꢂ0.20 Å
for the 1 and 3 c1(anti; syn) ones. The negatively charged O(1)
and S(4) atoms of the cis conformers show interatomic distances
!
!
!
!
4.3
5.5
4.3
5.8
shorter than the
R
vdW radii by ca. ꢂ0.27 Å for 1 and 3 and ca.
–
–
S4
ꢂ0.51 Å for 6. The electron-withdrawing nitro-group is responsible
for the smaller negative charges for both the sulfur (ꢂ0.224e) and
oxygen (ꢂ0.506e) atoms for 6, as compared to those for 1 and 3,
whose values are (ꢂ0.297e; ꢂ0.563e) and (ꢂ0.288e; ꢂ0.556e),
respectively. This justifies the smaller Sꢃ ꢃ ꢃO calculated short con-
tact for 6.
c2(anti)
c2(syn)
6
NO2
LPN5
LPO1
LPO1
!
pꢁC2@O1
66.9
23.3
18.9
63.6
23.2
18.8
67.3
24.0
20.3
68.1
23.9
20.5
!
rꢁC2AN5
!
rꢁC2@
C
3
LPO1
LPO1
!
!
rꢁC11AH28
1.7
–
1.7
–
–
1.4
–
1.5
rꢁS4@
C
10
LPS4
LPS4
pC2@O1
rC3AS4
rC3AS4
pꢁC2@O1
!
pꢁC10AC11
18.3
1.3
2.5
–
3.9
5.8
18.2
1.3
2.6
–
3.9
6.1
23.2
–
–
3.9
–
–
23.2
–
–
3.9
–
–
The shorter Oꢃ ꢃ ꢃS contacts of the cis conformers cause a strong
Repulsive Field Effect [17a,22] between the Cd+@Odꢂ and Cd+ASdꢂ
dipoles, which contributes to the larger destabilization of these
conformers relative to the gauche ones, and to their higher mCO fre-
quencies observed in the gas phase (Table 3).
!
pꢁC2@O1
!
!
!
!
rꢁC3AS4
rꢁC2AN5
pꢁC2@O1
rꢁC3AS4
Additionally the short contacts [O1ꢃ ꢃ ꢃH18(NCH2) and O1ꢃ ꢃ ꢃH20(CH3)
(Table 7)] are in agreement with the large electrostatic stabiliza-
tion of the anti relative to the syn conformer [6]. The distance be-
tween the oppositely charged O1ꢃ ꢃ ꢃH18(NCH2) atoms is shorter
than the
R
vdW radii by ca. ꢂ0.34 Å for the anti conformer and only
As expected, due to the strong electron-withdrawing effect of
the 40-nitro group, the largest contribution of LPS4 pCꢁ10AC11 delo-
by ca. ꢂ0.26 Å for the syn conformer. On the other hand, the O1-
ꢃ ꢃ ꢃH20(CH3) contacts for the syn and anti conformers do not contrib-
ute to the stabilization of either conformers.
!
calization (conjugation) is observed for derivative 6 in both c2(anti;
syn, ca. 23 kcal molꢂ1) and g(anti; syn, ca. 18 kcal molꢂ1) conform-
The sum of the delocalization energies of the selected interac-
tions has maximum mean values of ca. 159 kcal molꢂ1 and
134 kcal molꢂ1 for the gauche (anti; syn) conformers for 1 and 2,
respectively. The energies significantly decrease to ca.
149 kcal molꢂ1 and ca. 118 kcal molꢂ1 for the corresponding cis
ers. In fact, due to its appropriate geometry the
(177°), compound 6 assumes the c2(anti; syn) conformations. This
differs from the c1(anti; syn) conformations for 1 and 3, whose
c dihedral angle
unfavorable
c dihedral angles of ca. 84° almost hinders the
Table 6
CHELPG charges (e) at selected atoms in 1, 3 and 6 obtained at the B3LYP/6-311++G(d,p) level.
Compd.
Conf.
O(1)[CO]
C(2)[CO]
S(4)
N(5)
H(28)
H(18)
H(20)
1
g(anti)
g(syn)
c1(anti)
c1(syn)
ꢂ0.583
ꢂ0.569
ꢂ0.563
ꢂ0.558
0.629
0.693
0.705
0.694
ꢂ0.288
ꢂ0.291
ꢂ0.297
ꢂ0.301
ꢂ0.377
ꢂ0.421
ꢂ0.556
ꢂ0.584
0.163
0.147
0.136
0.132
0.005
0
0.013
ꢂ0.013
0.042
0.044
0.059
0.066
3
6
g(anti)
g(syn)
c1(anti)
c1(syn)
ꢂ0.566
ꢂ0.552
ꢂ0.556
ꢂ0.554
ꢂ0.557
ꢂ0.546
ꢂ0.506
ꢂ0.503
0.671
0.658
0.678
0.658
ꢂ0.288
ꢂ0.302
ꢂ0.308
ꢂ0.314
ꢂ0.253
ꢂ0.257
ꢂ0.224
ꢂ0.228
ꢂ0.375
ꢂ0.410
ꢂ0.537
ꢂ0.557
ꢂ0.365
ꢂ0.403
ꢂ0.480
ꢂ0.522
0.127
0.121
0.125
0.126
ꢂ0.001
ꢂ0.008
0.016
ꢂ0.012
0.018
0.043
0.033
0.064
g(anti)
g(syn)
c2(anti)
c2(syn)
0.639
0.635
0.675
0.659
0.127
0.122
0.159
0.160
0.018
0.043
0.050
0.050
0.051
ꢂ0.006
0.008
ꢂ0.021

E. Vinhato et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 115 (2013) 738–746
745
Table 7
Selected interatomic distances (Å) for the conformations of compounds 1, 3 and 6 at the B3LYP/6-311++G(d,p) level, and the corresponding X-ray distances for 4.
Compd.
1
Conf.a
O(1)ꢃ ꢃ ꢃS(4)b
3.552
3.574
3.045
3.041
D
lc
O(1)ꢃ ꢃ ꢃH(18)d,e
2.371
2.451
2.369
2.448
D
l
O(1)ꢃ ꢃ ꢃH(20)d,e
2.937
2.670
2.938
2.681
D
l
O(1)ꢃ ꢃ ꢃH(28)d,e
2.354
2.362
2.526
2.545
Dl
g(anti)
g(syn)
c1(anti)
c1(syn)
0.23
0.25
ꢂ0.34
ꢂ0.26
ꢂ0.35
ꢂ0.27
0.22
ꢂ0.36
ꢂ0.35
ꢂ0.19
ꢂ0.17
ꢂ0.05
ꢂ0.27
0.22
ꢂ0.27
ꢂ0.04
3
6
4
g(anti)
g(syn)
c1(anti)
c1(syn)
3.583
3.604
3.049
3.047
0.26
0.28
2.366
2.450
2.374
2.450
ꢂ0.35
ꢂ0.27
ꢂ0.34
ꢂ0.27
ꢂ0.34
ꢂ0.26
ꢂ0.34
ꢂ0.24
2.955
2.670
2.925
2.680
0.24
ꢂ0.05
0.21
ꢂ0.04
0.21
ꢂ0.05
0.24
ꢂ0.05
2.296
2.313
2.492
2.488
ꢂ0.42
ꢂ0.40
ꢂ0.22
ꢂ0.23
ꢂ0.47
ꢂ0.46
–
ꢂ0.27
ꢂ0.27
g(anti)
g(syn)
c2(anti)
c2(syn)
3.613
3.621
2.808
2.802
0.29
0.30
2.378
2.456
2.380
2.471
2.927
2.670
2.957
2.667
2.245
2.255
f
ꢂ0.51
–
ꢂ0.51
–
–
f
X-ray
2.714(3)
ꢂ0.60
2.417(97°)
ꢂ0.31
–
–
–
–
a
b
c
d
e
f
Conformer designation.
Sum of the van der Waals (
R
vdW) radii = 3.32 Å.
Difference between nonbonded atoms distance and the
vdW radii = 2.72 Å.
Refers to the contact between the carbonyl oxygen and the nearest, phenyl, methylene or methyl hydrogen atom.
Interatomic distances significantly larger than the vdW radii.
RvdW radii.
R
R
The NBO analysis and the trend of the electrostatic interactions
are in agreement with the higher relative abundance of the gauche
(anti; syn) conformers found in the gas phase of ca. 93% with re-
spect to that of the cis (anti; syn) conformers.
The molecular structure of 4, determined by X-ray analysis, is
shown in Fig. 3. The geometry observed in the solid state is very
similar to the c2(anti) conformation obtained in the gas phase for
compound 6 (Table 3). The orientation of the phenyl ring is away
and coplanar with the carbonyl group resulting in an intramolecu-
lar Sꢃ ꢃ ꢃO distance of 2.714 Å that is significantly shorter than
R
vdW radii by ꢂ0.60 Å. This short distance contributes to the sta-
bilization of this conformation in the crystal.
The most prominent feature of the crystal packing is the forma-
tion of six-molecules synthon mediated by the CAHꢃ ꢃ ꢃO
(C1ꢃ ꢃ ꢃOi = 3.179(3) Å; C1AH1Bꢃ ꢃ ꢃOi = 151°; symmetry operation:
i = 3/2 ꢂ x, y ꢂ 1/2, ½ ꢂ z) and Clꢃ ꢃ ꢃCl interaction, as shown in
Fig. 3. The molecular structure of compound 4 showing the atom labeling and
displacement ellipsoids at the 30% probability level for non-H atoms.
Fig. 4. The Clꢃ ꢃ ꢃCl distance of 3.287(2) Å is less than the
RvdW radii
of 3.50 Å [23]. The geometry of this interaction is called Type I
[24,25]: both CAClꢃ ꢃ ꢃClii and CiiACliiꢃ ꢃ ꢃCl angles (154.6(1)°;
ii = 2 ꢂ x, ꢂy, 2 ꢂ z) are equal, as the chlorine atoms are related
by a crystallographic inversion centre. It is worth noting that calcu-
lations made by Awwadi et al. [26] determined that the strongest
halogenꢃ ꢃ ꢃhalogen interaction occurs when the halogens are
attached to an sp2-hybridized carbon atom.
(anti; syn) conformers. However, due to the almost planar geome-
try of the [O@CACASAPh] moiety for the cis (anti; syn) conformers
of 6, along with the smaller electrostatic repulsion between the
C@O and CAS dipoles with respect to 1 and 3, the sum of the delo-
calization energies for the gauche (syn, anti) conformers of 6 is only
slightly higher (ca. 143 kcal molꢂ1) than that of the cis conformers
(ca. 141 kcal molꢂ1).
Fig. 4. A view in projection showing the supramolecular array sustained by CAHꢃꢃꢃO and ClꢃꢃꢃCl interactions.

746
E. Vinhato et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 115 (2013) 738–746
Nível Superior CAPES (808/2009) to J.Z.-S. The Italian author would
Conclusions
like to thank MIUR (PRIN 2009) for financial support. The assis-
tance of Professor A. Rodrigues in revising this manuscript is also
greatly appreciated.
The conformational analysis of N,N-diethyl-2-[(40-substi-
tuted)phenylthio] acetamides 1–6 (OMe 1, Me 2, H 3, Cl 4, Br 5,
NO2 6) was performed by mCO IR analysis, B3LYP/6-311++G(d,p)
gas phase and PCM calculations (for 1, 3 and 6), and X-ray diffrac-
tion (for 4).
Calculations for 1, 3, and 6 indicated the existence of two stable
conformation pairs, gauche (anti; syn; most stable) and cis (anti;
syn) in the gas phase. The comparison of experimental (IR) and the-
oretical (PCM) data allows the attribution of the most intense car-
bonyl doublet component to the more stable and lower calculated
frequency gauche conformers g(anti; syn) for 3–6 in n-hexane and
1–6 in carbon tetrachloride. Analogously, the single band for 1
and 2 in n-hexane (IR) may be assigned to the gauche conformers.
Additionally, the PCM data show that there is a progressive in-
crease of cis/gauche population ratio as the solvent polarity in-
creases (from n-C6H14 to CCl4, to CHCl3, and to CH3CN), which is
in agreement with the progressive increase of the intensity of the
References
[1] (a) A. Kucsman, I. Kapovits, Organic Sulfur Chemistry, Theoretical and
Experimental Advances, Elsevier, Amsterdam, 1985;
(b) Y. Nagao, T. Hirata, S. Goto, S. Sano, A. Kakehi, K. Iizuka, M. Shiro, J. Am.
Chem. Soc. 120 (1998) 3104–3110;
(c) R. Tanaka, Y. Oyama, S. Imajo, S. Matsuki, M. Ishiguro, Bioorg. Med. Chem. 5
(1997) 1389–1399;
(d) M. Iwaoka, S. Takemoto, S. Tomoda, J. Am. Chem. Soc. 124 (2002) 10613–
10620;
(e) Y. Nagao, S. Miyamoto, M. Miyamoto, H. Takeshige, K. Hayashi, S. Sano, M.
Shiro, K. Yamaguchi, Y. Sei, J. Am. Chem. Soc. 128 (2006) 9722–9729.
[2] (a) M. Iwaoka, N. Isozumi, Molecules 17 (2012) 7266–7283;
(b) M. Iwaoka, S. Takemoto, M. Okada, S. Tomoda, Chem. Lett. (2001) 132–133;
(c) M. Iwaoka, S. Takemoto, M. Okada, S. Tomoda, Bull. Chem. Soc. Jpn. 75
(2002) 1611–1625.
[3] J. Zukerman-Schpector, E. Vinhato, P.R. Olivato, A. Rodrigues, M. Dal Colle, C.R.
Cerqueira Jr., H.D. Arman, E.R. Tiekink, Z. Kristallogr. 224 (2009) 484–492.
[4] P.R. Olivato, R. Rittner, Rev. Heteroat. Chem. 15 (1996) 115–159.
[5] P.R. Olivato, E. Vinhato, A. Rodrigues, J. Zukerman-Schpector, R. Rittner, M. Dal
Colle, J. Mol. Struct. 827 (2007) 25–34.
higher
quency one.
In the gas phase, the gauche conformers are stabilized by relevant
mCO frequency component with respect to the lower mCO fre-
[6] P.R. Olivato, N.L.C. Domingues, M.G. Mondino, C.F. Tormena, R. Rittner, M. Dal
Colle, J. Mol. Struct. 920 (2009) 393–400.
orbital interactions, namely LPS4
!
pCꢁ
,
pC2@
!
rꢁC3AS4
;
O
1
@
!
O
2
[7] S. Ceard, M. Vivier, D. Roche, M. Madesclaire, Sulfur Lett. 25 (2002) 15–20.
[8] C.K. Bradsher, F.C. Brown, R.J. Grantham, J. Am. Chem. Soc. 76 (1954) 114–115.
[9] Galactic Industries Corporation, 1991–1998, Salem, USA.
[10] A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, J. Appl. Crystallogr. 26
(1993) 343–350.
rC3AS4
!
pꢁC2@
;
1 pꢁC2@
1
!
rꢁC3AS4, and LPO1
1rCꢁ11AH28, which are
O
O
absent in the cis (anti; syn) conformers. In contrast, the cis rotamers
are destabilized via enhanced electrostatic repulsion imposed by
small torsional angles between the Cd+ASdꢂ and Cd+@Odꢂ dipoles.
[11] G.M. Sheldrick, Acta Crystallogr. A64 (2008) 112–122.
[12] 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.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, J.A.
Pople, Gaussian 03, Revision E.01, Gaussian Inc., Wallingford, CT, 2004.
[13] (a) A.D. Becke, J. Chem. Phys. 98 (1993) 5648–5652;
(b) A.D. Becke, J. Chem. Phys. 98 (1993) 1372–1377;
(c) C. Lee, W. Yang, R.G. Parr, Phys. Rev. B 37 (1988) 785–789.
[14] (a) M. Cossi, G. Scalmani, N. Rega, V. Barone, J. Chem. Phys. 117 (2002) 43–54;
(b) J. Tomasi, B. Mennucci, R. Cammi, Chem. Rev. 105 (2005) 2999–3093.
[15] E.D. Glendening, A.E. Reed, J.E. Carpenter, F. Weinhold, NBO Version 3.1 (2003).
[16] D.R. Lide (Ed.), CRC Handbook of Chemistry and Physics, CRC Press, Boca Raton,
2005.
[17] (a) L.J. Bellamy, Advances in Infrared Group Frequencies, Chapman and Hall,
London, 1975. pp. 141–142;
(b) A. Gaset, L. Lafaille, A. Verdier, A. Lattes, Bull. Soc. Chim. Fr. 10 (1968)
4108–4112.
[18] Figures were made using: CYLview, 1.0b; Legault, C.Y., Université de
Sherbrooke, 2009 <http://www.cylview.org>.
This Repulsive Field Effect is also responsible for their higher
mCO fre-
quency in the whole series. In addition, the rC3AS4
!
rꢁC2AN5 orbital
interaction (though bond coupling) contributes to the stabilization
of the cis conformers for derivatives 1, 3, and 6. In 6, the near planar-
ity of the O@CACASAPh moiety allows for an additional stabilizing
orbital interaction, LPO1
!
rꢁS4AC10. This interaction is absent in 1
and 3 derivatives as a consequence of the unfavorable geometry.
The sum of the energy contribution of the orbital interactions
(NBO analysis) and the electrostatic interactions correlates well
with the populations and the mCO frequencies of both pairs of the
cis and gauche conformers in the gas phase and in low-polarity
solvents.
X-ray single crystal analysis indicates that compound 4 as-
sumes the c2(anti) conformation in the solid state, which is the
conformation obtained by compound 6 in the gas phase. The orien-
tation of the phenyl ring is away and coplanar with the carbonyl
group resulting in an intramolecular Sꢃ ꢃ ꢃO distance that is signifi-
cantly shorter than
RvdW radii. This short contact contributes to
the stabilization of this conformation in the solid. The most prom-
inent feature in the crystal packing is the formation of a six-mole-
cules synthon mediated by CAHꢃ ꢃ ꢃO and Clꢃ ꢃ ꢃCl interactions. The
Clꢃ ꢃ ꢃCl distance is less than the
RvdW radii, and the chlorine atoms
are related by a crystallographic inversion center.
[19] C. Martins, R. Rittner, C.F. Tormena, J. Mol. Struct.: Theochem. 728 (2005) 79–
84.
[20] D. Jones, A. Modelli, P.R. Olivato, M. Dal Colle, M. Palo, G. Distefano, J. Chem.
Soc. Perkin Trans. 2 (1994) 1651–1656.
[21] C.M. Breneman, K.B. Wiberg, J. Compos. Chem. 11 (1990) 361–373.
[22] A.R. Katritzky, R.D. Topsom, Chem. Rev. 77 (1977) 639–658.
[23] A. Bondi, J. Phys. Chem. 68 (1964) 441–452.
[24] T. Sakurai, M. Sundaralingam, G.A. Jeffrey, Acta Crystallogr. 16 (1963) 354–
363.
[25] S.K. Nayak, M.K. Reddy, T.N. Guru Row, D. Chopra, Cryst. Growth Des. 11
(2011) 1578–1596.
Acknowledgements
The Brazilian authors wish to thank the Fundação de Amparo à
Pesquisa do Estado de São Paulo (FAPESP) for financial support for
this research and for a fellowship to E.V. They would also like to
thank the Conselho Nacional de Desenvolvimento Científico e Tec-
nológico (CNPq) for scholarships to E.V. and fellowships to P.R.O
and J.Z.-S., and Coordenação de Aperfeiçoamento de Pessoal de
[26] F.F. Awwadi, R.D. Willett, K.A. Peterson, B. Twamley, Chem. Eur. J. 12 (2006)
8952–8960.