Conformational preferences for some 3,3-bis[(4′-substituted phenylsulfanyl)]1-methyl-2-piperidinones through spectroscopic and theoretical studies

Article abstract of DOI:10.1080/17415993.2013.771359

The analysis of the IR carbonyl band of some 3,3-bis[(4′-substituted phenylsulfanyl)]1-methyl-2-piperidinones 1-5 bearing as substituents OMe 1, Me 2, H 3, Cl 4 and Br 5, supported by B3LYP/6-31G(d,p) calculations for 3, indicated the existence of three conformers in the gas phase and practically a single conformer in solution. In the gas phase, the c₁ conformer is less polar and slightly more stable than the most polar c₂ conformer. The c₃ conformer is the least polar and least stable conformer. The summing up of the selected natural bond orbital delocalization orbital energies is practically the same (ca.136 kcal mol^-1) for the c₁, c₂ and c₃ conformers of 3. Therefore, the trend of the [O ^δ--(CO)···H ^δ+ _o- Ph] (hydrogen bond) attractive electrostatic interactions along with the trend of the [O ^δ--(CO)···S ^δ-] repulsive electrostatic interactions are the main factors which determine the observed computed relative populations for the c₁ (44%), c₂ (31%) and c₃ (25%) conformers. Moreover, the IR single carbonyl stretching band found (for 1-5) in solvents of increasing relative permissivity (CCl₄, CHCl₃, CH₂Cl ₂, CH₃CN), in agreement with polarisable continuum model calculations (for 3), show that the most polar c₂ conformer is practically unique in the solution (for 1-5), and the geometry is very close to that of the c₂′ conformer in the solid state (for 1-4).

Full text of DOI:10.1080/17415993.2013.771359

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Conformational preferences for
some 3,3-bis[(4′-substituted
phenylsulfanyl)]1-methyl-2-
piperidinones through spectroscopic
and theoretical studies
Paulo R. Olivatoa, Carlos R. Cerqueira Jra, Bruna Contieria, Jean M.
M. Santosa & Julio Zukerman-Schpectorb
a Instituto de Química, Universidade de São Paulo-USP, CP 26077,
05513-970 São Paulo, SP, Brazil
b Departamento de Química, Universidade Federal de São Carlos,
UFSCAR, São Carlos, SP, Brazil
Published online: 03 Apr 2013.
To cite this article: Paulo R. Olivato, Carlos R. Cerqueira Jr, Bruna Contieri, Jean M. M. Santos
& Julio Zukerman-Schpector (2013) Conformational preferences for some 3,3-bis[(4′-substituted
phenylsulfanyl)]1-methyl-2-piperidinones through spectroscopic and theoretical studies, Journal of
Sulfur Chemistry, 34:6, 617-626, DOI: 10.1080/17415993.2013.771359
To link to this article: http://dx.doi.org/10.1080/17415993.2013.771359
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Journal of Sulfur Chemistry, 2013
Vol. 34, No. 6, 617–626, http://dx.doi.org/10.1080/17415993.2013.771359
Conformational preferences for some 3,3-bis[(4ꢀ-substituted
phenylsulfanyl)]1-methyl-2-piperidinones through spectroscopic
and theoretical studies
Paulo R. Olivatoa*, Carlos R. Cerqueira Jra, Bruna Contieria, Jean M. M. Santosa
and Julio Zukerman-Schpectorb
aInstituto de Química, Universidade de São Paulo-USP, CP 26077, 05513-970 São Paulo, SP, Brazil;
bDepartamento de Química, Universidade Federal de São Carlos, UFSCAR, São Carlos, SP, Brazil
(Received 1 November 2012; final version received 27 January 2013)
The analysis of the IR carbonyl band of some 3,3-bis[(4ꢀ-substituted phenylsulfanyl)]1-methyl-2-
piperidinones 1–5 bearing as substituents OMe 1, Me 2, H 3, Cl 4 and Br 5, supported by B3LYP/6-31G(d,p)
calculations for 3, indicated the existence of three conformers in the gas phase and practically a single
conformer in solution. In the gas phase, the c1 conformer is less polar and slightly more stable than the
most polar c2 conformer. The c3 conformer is the least polar and least stable conformer. The summing up of
the selected natural bond orbital delocalization orbital energies is practically the same (ca.136 kcal mol−1
)
for the c1, c2 and c3 conformers of 3. Therefore, the trend of the [Oδ−(CO) · · · Hδ+o−Ph] (hydrogen bond)
attractive electrostatic interactions along with the trend of the [Oδ−(CO) · · · Sδ−] repulsive electrostatic
interactions are the main factors which determine the observed computed relative populations for the c1
(44%), c2 (31%) and c3 (25%) conformers. Moreover, the IR single carbonyl stretching band found (for
1–5) in solvents of increasing relative permissivity (CCl4, CHCl3, CH2Cl2, CH3CN), in agreement with
polarisable continuum model calculations (for 3), show that the most polar c2 conformer is practically
ꢀ
unique in the solution (for 1–5), and the geometry is very close to that of the c2 conformer in the solid
state (for 1–4).
= H
Y
Y
= C
= N
= O
= S
Most polar conformer (c2)
Y= OMe 1, Me 2, H 3, Cl 4, Br 5
Keywords: 3,3-bis[(4ꢀ-substituted phenylsulfanyl)]-1-methyl-2-piperidinones; conformational analysis;
IR spectroscopy; theoretical calculations; X-ray crystal structure
1. Introduction
As part of our on-going research on the conformational and electronic interaction studies in
β-thio-carbonyl compounds (1, 2) utilizing IR spectroscopic and theoretical methods, the
*Corresponding author. Email: prolivat@iq.usp.br
© 2013 Taylor & Francis

618 P.R. Olivato et al.
3-(4ꢀ-substituted phenylsulfanyl)]-1-methyl-2-piperidinones (3), which are the precursors of the
title compounds, were synthesized and studied. In the non-polar solvent n-hexane, there is a good
match between the νCO IR doublet relative intensities and the MP2/6-31G(d,p) calculations; that
is, there is a predominance of the population of the less polar axial (ca. 86%) conformer ove◦r
= − −
the more polar quasi-equatorial conformer whose [O C C S] dihedral angles are ca. −83
and ca. −41◦, respectively. As the relative permissivity increases, going from n-C6H14 to CCl4,
CHCl3 and CH2Cl2, the more polar quasi-equatorial conformer becomes the more stable and
unique conformer in the most polar solvent (CH3CN). The higher stabilization of the axial con-
former with respect to the quasi-equatorial conformer has been ascribed mainly by the large
contribution of the hyperconjugative (σC → π∗CO, πCO → σ∗
and nS → π∗CO) interac-
−
−
S
C
S
tions in comparison to the same interactions (almost absent) for the quasi-equatorial conformer.
As an extension of this research, we have studied the 1-methyl-2-piperidinones bearing two sulfur
Scheme 1. Atom labeling of 3,3-bis[(4ꢀ-substituted phenylsulfanyl)]-1-methyl-2-piperidinones
and definition of relevant dihedral angles.
Scheme 2. Synthetic route for compounds 1–5.

Journal of Sulfur Chemistry 619
atoms in the α-position, that is, 3,3-bis[(4ꢀ-substituted phenylsulfanyl)]-1-methyl-2-piperidinones
[Y = OMe 1, Me 2, H 3, Cl 4] (4–7) (Scheme 1) through single-crystal X-ray diffraction analysis.
The piperidone ring in these compounds has a half-chair distorted to a twisted-boat conforma-
tion. The phenylsulfanyl groups display synclinal geometries with respect to the [Ph–S–C=O]
◦
◦
−
−
dihedral angles of ca. 63 and ca. 47 . In general, the C H · · · O and C H · · · π intermolecular
interactions are responsible for the crystal packing (4–7).
In order to throw more light on the nature of the electronic and electrostatic interactions
which stabilize the possible stable conformations of the 3,3-bis[(4ꢀ-substituted phenylsulfanyl)]-
1-methyl-2-piperidinones bearing in the 4ꢀ positions electron-donating and electron-attracting
substituents (i.e. Y = OMe 1, Me 2, H 3, Cl 4, Br 5 (Scheme 1)), in the gas phase and in solvents
of increasing relative permissivity, this paper reports the IR study (for 1–5) along with the density
functional theory, polarisable continuum model (PCM) and natural bond orbital (NBO) (for 3).
2. Results and discussion
Table 1 shows the stretching frequencies of the unique carbonyl band component present for com-
pounds 1–5, in solvents of increasing relative permissivity, that is, carbon tetrachloride (ε = 2.2)
(8) (fundamental and first overtone), chloroform (ε = 4.8), dichloromethane (ε = 9.0) and ace-
tonitrile (ε = 37). The occurrence of a single carbonyl band in the first overtone region for 1–5,
in carbon tetrachloride, at frequencies twice those of the fundamental minus ca. 15 cm−1 (which
corresponds to twice the mechanical anharmonicity) (9), indicates the occurrence of at least one
conformer in the referred solvent and precludes the occurrence of any vibrational effect in the
fundamental transition of the νCO stretching mode (10, 11). The IR data also suggest the occur-
rence of at least one conformer in the remaining solvents for compounds 1–5. Similar to the
2-thio-substituted amides (1–3), going from the non-polar solvent, carbon tetrachloride, to the
most polar solvent, acetonitrile, there is a decrease of the νCO frequency by ca. 11 cm−1. Moreover,
practically no variation of the νCO frequency for compounds 1–5 is noticed for each solvent, going
in the 4ꢀ-position from electron-donating to electron-attracting substituents.
Aiming to estimate the geometries of the minimum energy conformations in the gas phase,
B3LYP/6-31G(d,p) calculations for compound 3, taken as the representative compound for
the whole series (1–5), were performed. Table 2 presents the relevant data for compound 3.
The calculations for 3 indicate the existence of three stable conformations: c1, c2 and c3. The pla-
−
−
−
narity of the [ C(O) N(1) C(2)] carboxamide moiety (2, 3) (Scheme 1) induces the piperidone
ring to assume a slightly distorted half-chair geometry, with δ and δꢀ dihedral angles being ca. 25◦
and ca. 44◦, respectively (Table 2 and Figure 1(a)–(c)). With respect to the carbonyl group, the
two 3-phenylsulfanyl substituents display geometries for conformers c1, c2 and c3 whose α and
Table 1. Frequencies (ν, cm−1) of the carbonyl stretching bands in the IR spectra of 3,3-bis[(4ꢀ-substituted
phenylsulfanyl)]1-methyl-2-piperidinones 1–5.
CCl4
CHCl3
CH2Cl2
CH3CN
Compound
Y
ν
νa
ν
ν
ν
1
2
3
4
5
OMe
Me
H
Cl
Br
1654
1655
1655
1655
1655
3292
3294
3295
3294
3295
1639
1640
1641
1642
1642
1641
1642
1643
1644
1644
1643
1644
1645
1644
1645
Note: aFirst overtone.

620 P.R. Olivato et al.
Table 2. Relative energies (E, kJ mol−1), dipole moments (μ, D), carbonyl frequencies (ν, cm−1) and selected torsion
angles (◦) calculated for the minimum energy conformations of 3,3-bis[(phenylsulfanyl)]-1-methyl-2-piperidinone 3 at
the B3LYP/6-31G(d,p) level.
Dihedral angles (◦)e
Conf.a
Eb
Pc
μ
νCdO
α
β
γ
δ
αꢀ
βꢀ
γ ꢀ
δꢀ
c1
c2
c3
0
0.21
0.33
44.0
30.6
25.4
3.74 1654.4
5.80 1654.7
3.43 1656.1
36.8
68.5
37.6
59.0
−82.3 −27.6 −79.5
46.8
88.8
44.0
157.2 −113.1
22.4 −42.4 −65.3
79.4 −42.3
163.3 −108.7 −26.8 −83.4
49.8
84.5 45.9
Notes: aConformer designation.
bRelative energy.
cMolar fraction in percentage.
dScaling factor of 0.951.
eSee Scheme 1.
Figure 1. Conformers for 3: c1 (a), c2 (b) and c3 (c) obtained at the B3LYP/6-31G(d,p) level and the ORTEP view of
ꢀ
c2 (d) (from (6)).
αꢀ dihedral angles are (ca. 37◦; −80◦), (ca. 69◦; −43◦) and (ca. 38◦; −83◦), respectively. These
geometries are quite similar to those of the quasi-equatorial and axial conformers previously
found in the mono-substituted phenylsulfanyl-1-methyl-2-piperidinones (3) (see above). For 3,
the c1 conformer (ca. 44%) is slightly more stable than the c2 and c3 conformers, whose popula-
tions are very close between them, that is, ca. 31% and ca. 25%, respectively. At first sight, the
relative stability for the c1, c2 and c3 conformers should be almost the same as one of the phenyl-
sulfanyl substituents has a quasi-equatorial geometry (ca. 39◦), while the other phenylsulfanyl
substituent displays an axial geometry (ca. 77◦) with respect to the carbonyl group. This should
=
−
cause almost the same repulsive field effect (10) between the C O and C S dipoles (for the

Journal of Sulfur Chemistry 621
Table 3. CHELPEG charge (e) at selected atoms obtained at the B3LYP/6-31G(d,p) level for the
3,3-bis(phenylsulfanyl)1-methyl-2-piperidinones 3.
Conf.
O(1)
C(1)
S(1)
S(2)
N(1)
C(2)
C(7)
C(13)
H(8)a
H(18)a
H(6)
c1
c2
c3
−0.516
−0.486
−0.459
0.570
0.603
0.450
−0.309
−0.257
−0.340
−0.283
−0.271
−0.330
−0.254
−0.277
−0.209
0.024
0.006
0.174
0.283
0.227
0.276
0.268
0.301
0.259
0.125
–
–
0.079
0.088
0.060
0.103
0.090b
0.085b
Notes: aThe ortho-phenyl hydrogen H(8) and H(18) atoms which are nearest to the carbonyl oxygen atom (see Scheme 1).
bThe H(8)/H(12) and H(18)/H(14) mean charge values.
quasi-equatorial geometry) along with practically the same π(π∗) → σ(σ∗) hyperconjugative
interactions (for the axial geometry) for the c1, c2 and c3 conformers (see below). Neverthe-
less, the suitable geometries of the two more stable c1 and c2 conformers (Figure 1) originate
short contacts between the oppositely charged [O(1) (ca. -0.51e)· · · H(8) (ca. 0.13e)] and [O(1)
(ca. −0.49e)· · · H(18) (ca. 0.10e)] atoms, respectively, whose interatomic distances (2.43 and
2.57Å) are shorter than the sum of the van der Waals radii (ꢀ vdW) (2.72Å) by 0.29 and 0.15Å,
respectively. Therefore, these short contacts should electrostatically stabilize the c1 conformer to
a larger extent than the c2 conformer, and should be absent for the c3 conformer. The Charges
from Electrostatic Potentials using a Grid based method (CHELPEG) atomic charges at selected
atoms at the B3LYP/6-31G(d,p) level for compound 3 are presented in Table 3.
Table 2 shows that the dipole moment of the c2 conformer (ca. 5.8D) is significantly larger
than the dipole moments for the c1 and c3 conformers, whose values are close to ca. 3.5D. This
behavior may be rationalized as follows: Figure 1(b) highlights that the c2 conformer presents the
δ−
[Cδ+
O
δ−], [Cδ+(2) S (1) Cδ+(7)] and [Cδ+(2) S (2) Cδ−(13)] dipoles pointing toward
δ−
=
−
−
−
−
the same direction, which in turn results in the highest resultant dipole moment. On the other
hand, Figure 1(a) shows that, for the c1 conformer, while the Cδ+ = Oδ− dipole and the
[Cδ+(2) S (1) Cδ−(7)] dipole point in the same direction, the [Cδ+(2) S (2) Cδ−(13)]
δ+
δ+
−
−
−
−
dipole points in the opposite direction, originating a smaller resultant dipole moment. In the same
way, Figure 1(c) shows that while the Cδ+ = Oδ−δ+dipole and the [Cδ+(2) S (2) Cδ−(13)]
δ+
−
−
dipole point in the same direction, the [Cδ+(2) S (1) Cδ−(7)] dipole points in the opposite
direction, creating a smaller resultant dipole moment.
−
−
Inthegasphaseof 3, thecarbonylfrequenciesforthe c1, c2 andc3 conformersareveryclose, that
is, of ca. 1654, 1655 and 1656 cm−1, respectively.Thistrendisin linewith Oδ−(CO) · · · Sδ− contacts
−
of the S Ph group, which bears the quasi-equatorial geometry whose interatomic distances for
the c1, c2 and c3 conformers are 3.06, 3.10 and 2.83Å, respectively. These short contacts lead to
δ−
δ−
dipoles for the c3
the strongest repulsive field effect (10) between the Cδ+
O
and Cδ+
S
=
−
conformer, whose Oδ−(CO) · · · Sδ− interatomic distance is smaller than ꢀ vdW radii (3.32Å) by
0.49Å with respect to the c1 and c2 conformers, and whose Oδ−(CO) · · · Sδ− interatomic distance
mean value (ca. 3.08Å) is smaller than the ꢀvdW radii by ca. 0.24Å. Therefore, the highest
carbonyl frequency was found for the c3 conformer relative to those of the c1 and c2 conformers
(Table 2), which is in agreement with the computed carbonyl frequencies. However, it seems
reasonable to advance that in a solution of solvents with increasing polarity, the close values of
the carbonyl stretching frequencies for the c1, c2 and c3 conformers of 3 should lead to a single
carbonyl band (Table 1).
Moreover, the single-point PCM calculations (Table 4) show a strong solvent effect on the
relative populations of c1, c2 and c3 conformers of 3. In fact, even in the non-polar solvent CCl4,
the relative population of the most polar c2 conformer becomes the predominant one (64%) relative
to those of the less polar c1 and c3 conformers. In the more polar solvents (CHCl3, CH2Cl2 and
CH3CN), the c2 conformer is practically the only one present whose population varies from 76%
to 88%. Therefore, it seems reasonable to suggest that the single carbonyl band found in solution

622 P.R. Olivato et al.
Table 4. Single-point PCM solvent effect on the minimum energy gas phase for the conformations of 3 at the
B3LYP/6-31G(d,p) level; relative energies (E, kJ mol−1) and dipole moments (μ, D)
Gas phase
Pc
CCl4
CHCl3
CH2Cl2
CH3CN
Conf.a Eb
μ
νCO
E
P
μ
E
P
μ
E
P
μ
E
P
μ
d
c1
c2
c3
0
44.0 3.74 1654.4 0.78 16.8 4.28 1.26 8.9 4.73 1.61 5.5 4.99 1.98 3.1 5.28
0.21 30.6 5.80 1654.7 63.5 6.75 75.5 7.57 82.6 8.00 88.3 8.52
0.33 25.4 3.43 1656.1 0.69 19.7 3.92 0.93 15.6 4.34 1.15 12.0 4.59 1.37 8.7 4.87
0
0
0
0
Notes: aConformer attribution.
bRelative energy.
cMolar fraction in percentage.
dScaling factor of 0.950.
Table 5. Selected dihedral angles (◦) for the X-ray diffraction structures of compounds 1–4.
Comp.
Y
αa
β
γ
δ
αꢀ
βꢀ
γ ꢀ
δꢀ
1b
2c
3d
4e
OMe 60.84 (14) 154.33 (8) −106.48 (11) 13.72 (19) −49.98(17) −66.04 (10) 77.44 (11) −40.74(15)
Me 65.30 (16) 153.97 (10) −115.80 (13) 12.2 (2) −45.45(17) −62.08 (12) 78.55 (14) −43.61(17)
H
64.23 (17) 157.38 (11) −115.91 (15) 13.1 (3) −46.74(18) −64.87 (12) 71.68 (16)) −42.33(18)
Cl
60.9 (2)
153.07 (14) −113.91 (19) 11.0 (3)
−49.4 (2) −60.15 (16) 80.2 (2)
−40.9 (2)
Notes: aFor dihedral angle designations, see Scheme 1.
b-eFrom (4–7).
(CCl4, CHCl3, CH2Cl2 and CH3CN) for compounds 1–5 (Table 1) may be ascribed to the most
polar c2 conformer.
The most polar c2 conformer, which is the predominant conformer in solution, has the same
geometry as the single conformer in the solid state. In fact, Table 5 shows that the X-ray single-
crystal dihedral angles (α – δ and αꢀ − δꢀ) of the conformer for compounds 1–4 are almost the same
to the corresponding dihedral angles for the most polar c2 conformer for 3 in the gas phase (Table 2)
(4–7). Therefore, similar to the gas phase of 3, in the solid state of 1–4, short contacts between
the oppositely charged [Oδ−(1)· · · Hδ+(18)] atoms, whose mean interatomic distance of 2.58Å
is shorter than the ꢀvdW radii (2.72Å) by 0.14Å, were detected. Therefore, this electrostatic
ꢀ
interaction should contribute to the intra-molecular stabilization of the c2 conformer.
Figure 1 highlights the close similarity between the Oak Ridge Thermal Ellipsoid Plot (ORTEP)
view of the c2ꢀ conformer (d) and the gas phase structure of the c2 conformer (b) of 3. Therefore,
−
−
besides the C H· · · O and the C H· · · πPh intermolecular interactions (4–7), the dipole moment
coupling seems to be the major factor responsible for the large energy gain for the crystal packing
of derivatives 1–4.
In order to rationalize the orbital interactions which stabilize the c1, c2 and c3 conformers for
the title compounds, NBO analysis (12) was performed. Table 6 presents selected NBO energy
interactions between donor and acceptor orbitals for the referred conformers of 3.
The majority of the orbital interactions present energy values which are very close to each
other for the c1, c2 and c3 conformers, except for the weak LPO1 → σ∗
interaction
−
−
C8 H8(o Ph)
(hydrogen bond), whose energy value is 0.6 kcal mol−1, which is only present for the c1 conformer.
The most important orbital interaction is the LPN1 → π∗
O1, which corresponds to the
[O C N ↔ O C N ] conjugation whose mean energy value is 68 kcal mol for all of the
=
C1
+
−
−1
= −
− =
conformers. In the carboxamide group, there are also two higher energy interactions (through
bond coupling) (13), LPO1 → σ∗
and LPO1 → σ∗C1−C2, whose mean values are of ca. 25
C1−N1
and ca. 22 kcal mol−1, respectively, for the three c1, c2 and c3 conformers. There are also the
LPO1 → σ∗
(hydrogen bond) interactions, whose mean value is ca. 1.3 kcal mol−1, along
C6−H6

Journal of Sulfur Chemistry 623
Table 6. Comparison of significant NBO energies (kcal mol−1) of the
corresponding interacting orbitals for the c1, c2 and c3 conformers of 3
at the B3LYP/6-31G(d,p) level.
Orbitals
c1
c2
c3
LPN1 → π∗
66.5
24.8
22.0
0.6
69.5
24.5
22.5
–
66.7
25.0
21.0
–
=
LPO1 → σC∗1C-1N1 O1
LPO1 → σC∗1-C2
LPO1 → σC∗8-H8
LPO1 → σC∗18-H18
LPO1 → σC∗6-H6
a
–
–
–
1.3
–
1.4
0.9
–
1.2
–
LPS1 → π∗
=
LPS2 → π∗C1 O1
1.3
1.2
1.4
–
1.6
1.7
1.3
–
=
LPS1 → π∗C1 O1
1.1
1.2
1.0
0.6
4.9
1.6
4.7
2.8
136.7
=
LPS2 → π∗C7 C12
=
πC1
→ Cσ1∗7 C18
=
=
O1
C2-S1
πC1
→ σ∗
1.8
1.1
4.4
2.2
6.0
135.6
1.9
1.5
4.4
1.8
6.8
134.9
O1
σC2-S1 → π∗ C2-S2
=
σC2-S2 → π∗C1 O1
=
π∗
→ Cσ1∗ O1
=
π∗C1 O1 → σ∗
C2-S1
=
C1 O1
Eb
C2-S2
ꢀ
Notes: aInteraction energy smaller than 0.5 kcal mol−1
.
bSumming up of the energies of the interacting orbitals.
withtheLPS1 → π∗
O1 andLPS2 → π∗
O1 superjacentinteractions(14), whosemeanvalue
=
C1
=
C1
is ca. 1.3 kcal mol−1
.
In order to relieve any steric strain between the two phenyl rings of the 3, they are kept away
from each other (Figure 1 (a–c)). In fact, both the Ph-S(1) and Ph-S(2) groups present γ and
γ ꢀ dihedral angles of ca.101◦ and ca.84◦, respectively, which indicates that both phenyl rings
−
−
are almost perpendicular to the C(2) S(1) and C(2) S(2) bonds, which practically hinder the
2p(S) → π∗ conjugation. In fact, the LPS1 → π∗
and LPS2 → π∗
conjugation
=
C7 C12
=
C17 C18
Ph
mean value is only ca.1.3 kcal mol−1 for both interactions.
= − −
Additionally, in the O C C S fragment, there are also three pairs of hyperconjugative
interactions for the c1, c2 and c3 conformers: (a) πC1
→ σ∗
; πC1
→ σ∗ S2; (b)
=
=
O1
→Cσ2−∗ S1 S1; π∗O1
→ σ∗
,
S2
−
C2
σC2
→ π∗
O1; σ
→ π∗
and (c) π∗
=
C1
=
C1
=
=
O
C1 O1
C1 O1
−
S1
−
C2 S2
−
−
with the summing up mean energy value for each pair being ca.C12.8, ca. 6.0 and ca. 8C.12 kcal
mol−1, respectively.
Finally, the summing up of the selected delocalization energies for the c1, c2 and c3 conformers
are practically the same (ca. 136 kcal mol−1). Therefore, the observed order of stability in the
gas phase for which the c1 conformer (44%) is slightly more stable than the c2 one (31%), and
the c3 conformer is the least stable (25%) one, may be explained on the grounds of electrostatic
δ−
δ+
interactions, as pointed out above. In fact, the [O
· · · H ] short contact analysis showed that
o-Ph
(CO)
the c1 conformer is stabilized by electrostatic (hydrogen bond) interaction to a larger extent than
the c2 conformer, and this interaction is absent for the c3 conformer. The shortest [Oδ− · · · H
]
δ+
o-Ph
(CO)
contact for the c1 conformer is in line with the weak LPO1 → σC∗8-H18 (o-Ph) interaction (hydrogen
bond) whose delocalization energy value is ca. 0.6 kcal mol−1, which is only present for the c1
conformer. Moreover, the strongest repulsive field effect between the Cδ+
O
and Cδ+–Sδ−
δ−
=
dipoles (for the S–Ph group which bears the quasi-equatorial geometry) for the c3 conformer

624 P.R. Olivato et al.
with respect to the c1 and c2 conformers is also responsible for the larger stabilization of the c1
and c2 conformers with respect to the c3 conformer.
3. Conclusion
Theoretical calculations (for 3) indicate that the title compounds (for 1–5) exist in the gas phase
as three conformers. The c1 conformer is less polar and slightly more stable than the most polarc2
conformer. The c3 conformer is the least polar and least stable conformer. The summing up of the
selected delocalization orbital energies is practically the same (ca. 136 kcal mol−1) for the c1, c2
δ+
and c3 conformers of 3. Therefore, the trend of the [Oδ− · · · H ] (hydrogen bond) attractive
o-Ph
(CO)
δ−
electrostatic interactions along with the trend of the [O
· · · Sδ−] repulsive electrostatic inter-
(CO)
actions are the main factors which determine the observed computed relative populations for the
c1 (44%), c2 (31%) and c3 (25%) conformers. Moreover, the IR single carbonyl stretching bond
found (for 1–5) in solvents of increasing relative permissivity (CCl4, CHCl3, CH2Cl2, CH3CN),
in agreement with PCM calculations (for 3) shows that the most polar conformer, c2, is practically
ꢀ
unique in solution (for 1–5) and that the geometry is very close to that of the conformer c2 in the
solid state (for 1–4).
4. Experimental section
4.1. Materials
All solvents for IR measurements were spectrograde and were used without further purification.
Scheme 2 summarizes the synthetic route to obtain the compounds 1–5.The 3,3-bis[(4ꢀ-substituted
phenylsulfanyl)]-1-methyl-2-piperidinones 1–4 were prepared as previously described (4–7),
while compound 5 is new and was obtained as follows: 4-bromothiophenol (6.1 g, 0.16 mmol)
reacted with bromine (1.64 ml, 0.32 mmol) in dichloromethane (80.0 ml) on hydrated silica
gel support (15.0 g of SiO2 and 7.5 ml of water) to give 4-bromophenyl disulfide (5.11 g,
yield = 84.0%).A yellow solid was obtained after filtration and evaporation without further purifi-
cation (15). 1-Methyl-2-piperidinone (0.89 g, 7.9 mmol) was added dropwise to a cooled (−78◦C)
solution of HMPA (1.75 ml, 7.9 mmol), diisopropylamine (1.1 ml, 7.9 mmol) and butyllithium
(7.0 ml, 7.9 mmol) in THF (15 ml). After 20 min, 4-bromophenyl disulfide (2.97 g, 7.9 mmol)
dissolved in THF (15 ml) was added dropwise to the enolate solution (16). After stirring for
3 h at −78◦C, 80 ml of water was added at room temperature, and extraction with ethyl ether
was performed. After a usual workup, a crude solid was obtained. Purification through flash
chromatography with a solution of hexane and ethyl acetate in a 7:3 ratio gave the pure
1
product (0.40 g, yield = 10.0%; m.p. 110–112◦C). H NMR (500 MHz, CDCl3): δ 7.46–7.50
(m, 8H8,9,11,12,14,15,17,18); 3.21–3.23 (t, 2H5, 3JHH = 6.0 Hz); 2.91 (s, 3H6); 1.96–2.00 (m, 2H3);
1.92–1.95 (m, 2H4). Analysis found: C 44.36; H 3.52; N 2.83%; C18H17OBr2NS2 requires C
44.37%; H 3.52%; N 2.87%.
4.2. IR measurements
The IR spectra were obtained on a FTIR Michelson-Bomem-MB100 spectrophotometer
with 1.0 cm−1 resolution. The carbonyl region (1800–1600 cm−1) was recorded for carbon
tetrachloride, chloroform, dichloromethane and acetonitrile solutions, at a concentration of
2.0 × 10−2 mol dm−3, using a 0.519 mm sodium chloride cell. The carbonyl first overtone
region (3500–3100 cm−1) was recorded for carbon tetrachloride and chloroform solutions

Journal of Sulfur Chemistry 625
(2.0 × 10−2 mol dm−3) using a 1.00 cm quartz cell. The carbonyl bands (fundamental and first
overtone) were deconvoluted by means of the Grams/32 curve fitting program, version 4.04 Level
II (17).
4.3. Theoretical calculations
All calculations were carried out at 298 K using methods and basis sets implemented in the
GAUSSIAN package of programs (G03.E01) (18). Full geometry optimizations and analytical
vibrational frequency calculations were performed on all of the orientations with respect to the
carbonyl group resultant from a systematic conformational search using the ab initio Hartree–Fock
method with the 3-21G basis set (19, 20), allowing complete relaxation of all internal parameters.
The obtained conformations were refined using B3LYP/6-31G(d,p) level (19, 20). Frequency
analyses were carried out to verify the nature of the minimum state of all the stationary points
obtained. To obtain an estimation of the solvation effects on the relative stability of the most
relevant minima, single-point calculations were done for the gas phase optimized structures using
the PCM (21) as implemented in the GAUSSIAN 03. The NBO 3.1 program (12) was used as
implemented in the GAUSSIAN 03 package, and the reported NBO delocalization energies (E2)
are those given by second-order perturbation theory.
Acknowledgements
The authors thank the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for financial support of this
research and the Conselho Nacional de Desenvolvimento Científico and Tecnológico (CNPq) for scholarships to C.R.C.Jr.,
B.C. and J.M.M.S. and fellowships to P.R.O and J.Z.-S.
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