β-Nitrostyrene derivatives - A conformational study by combined Raman spectroscopy and ab initio MO calculations

Article abstract of DOI:10.1016/j.molstruc.2004.01.012

A complete conformational analysis of β-nitrostyrene and β-methyl-β-nitrostyrene derivatives was carried out by Raman spectroscopy coupled to ab initio MO calculations. Apart from the optimised geometrical parameters of the most stable conformers of the molecules under study, the corresponding harmonic vibrational frequencies were calculated, as well as potential-energy profiles for several internal rotations within the molecules. At the light of these results, a complete assignment of the Raman spectra of the solid samples was performed. The conformational behaviour of this kind of systems was found to be mainly determined by the stabilising effect of π-electron delocalisation.

Full text of DOI:10.1016/j.molstruc.2004.01.012

Journal of Molecular Structure 692 (2004) 91–106
www.elsevier.com/locate/molstruc
b-Nitrostyrene derivatives—a conformational study by combined
Raman spectroscopy and ab initio MO calculations
R. Calheirosa,b, N. Milhazesc,d, F. Borgesc, M.P.M. Marquesa,b,
*
aResearch Unit ‘Molecular Physical-Chemistry’, University of Coimbra, 3001-401 Coimbra, Portugal
bDepartment of Biochemistry, Faculty of Sciences and Technology, University Coimbra, Ap. 3126, 3001-401 Coimbra, Portugal
cDepartment of CEQUP/Chemistry, Faculty of Sciences and Technology, University of Porto, 4169-007 Porto, Portugal
dSuperior Institute of Health Sciences-North, 4580 Paredes, Portugal
Received 11 November 2003; revised 9 January 2004; accepted 12 January 2004
Abstract
A complete conformational analysis of b-nitrostyrene and b-methyl-b-nitrostyrene derivatives was carried out by Raman spectroscopy
coupled to ab initio MO calculations. Apart from the optimised geometrical parameters of the most stable conformers of the molecules under
study, the corresponding harmonic vibrational frequencies were calculated, as well as potential-energy profiles for several internal rotations
within the molecules. At the light of these results, a complete assignment of the Raman spectra of the solid samples was performed. The
conformational behaviour of this kind of systems was found to be mainly determined by the stabilising effect of p-electron delocalisation.
q 2004 Elsevier B.V. All rights reserved.
Keywords: b-nitrostyrene; b-methyl-b-nitrostyrene; Raman spectroscopy; Ab initio calculations; Conformational analysis
1. Introduction
promising anticancer drugs [7,8]. In fact, some reported
studies [8] propose a nitrovinyl side chain attached to an
aromatic ring as the pharmacophore structure of a new
group of pro-apoptotic agents.
b-Nitrostyrenes and their derivatives are important
starting materials for the synthesis of a variety of useful
building blocks, such as nitroalkanes, amines, ketoximes,
hydroxylamines and aldoximes [1,2]. Moreover, conjugated
nitroalkenes are exceptionally good Michael acceptors,
namely towards organometallic reagents [3] and vitamin C
[4]. Nitrostyrenes are activated alkenes displaying an
electron-withdrawing NO2 group, which have been shown
to predominate in the ground state E (trans) configuration of
the nitro and phenyl groups relative to the carbon chain
double bond [5].
Once the biological activity of this type of compounds is
thought to be strongly dependent on their structural
characteristics—similarly to what has been found for
phenolic acids and phenolic ester analogues [9]—a series
of ring-substituted nitrostyrenes was synthesised in our lab,
and screened for their in vitro and in vivo antiproliferative
and cytotoxic properties (both in human cancer cells and in
live mice).
The present work reports the conformational analysis of
b-nitrostyrene derivatives, as well as of some of their
analogues and synthetic precursors, by Raman spectroscopy
coupled to ab initio MO methods (at the DFT level).
The compounds studied were: 1,2-dihydroxybenzene
(catechol, CAT), 3,4-dihydroxybenzaldehyde (3,4-OH-
BA), styrene (S), b-methyl-styrene (MeS), b-nitrostyrene
(NS), b-methyl-b-nitrostyrene (MeNS), 3,4-dihydroxy-b-
nitrostyrene (3,4-OH-NS) and 3,4-dihydroxy-b-methyl-b-
nitrostyrene (3,4-OH-MeNS) (Fig. 1).
Apart from their well recognised antimicrobial and
antifungal activities [6], nitrostyrene derivatives have lately
been shown to constitute a novel class of chemical
compounds with good potential for further development as
*
Corresponding author. Address: Department of Biochemistry, Faculty
of Sciences and Technology, University Coimbra, Ap. 3126, 3001-401
Coimbra, Portugal. Tel.: þ351-239854462; fax: þ351-239826541.
E-mail address: pmc@ci.uc.pt (M.P.M. Marques).
0022-2860/$ - see front matter q 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2004.01.012

92
R. Calheiros et al. / Journal of Molecular Structure 692 (2004) 91–106
Fig. 1. Schematic representation of the b-nitrostyrene derivatives, and their analogues, studied in the present work. For NS, MeNS, 3,4-OH-NS and 3,4-OH-
MeNS, the calculated (B3LYP/6-31G**) lowest energy conformers are displayed (the atom numbering is included, and is applicable to all the compounds
studied, irrespective of the type of atom).
2. Experimental
The remaining residues were recrystallised from diethy-
lether/petroleum ether. The synthesised compounds were
identified by both NMR and electron impact mass spectra
(EI-MS).
2.1. Synthesis
b-Methyl-b-nitrostyrene (MeNS). Yield 6.38 g, 83%; 1H
NMR d: 2.38 (3H, s, CH3), 7.47–7.51 (3H, m, ArH), 7.56–
7.59 (2H, m, ArH), 8.08 (1H, s, H(a)); 13C NMR d: 13.9
CH3, 129.0 (2 £ C HAr), 129.2 C(b), 130.3 (2 £ CHAr),
133.2 C HAr, 147.7 C(1); EI-MS m/z (%): 163 (Mþz, 16),
146 (15), 115 (100), 105 (99), 91 (56), 77 (51), 65 (15); m.p.
58–61 8C.
The synthetic procedure was adapted from Parker et al.
[10] with slight modifications. A mixture of the benzal-
dehyde (5.0 g), with the corresponding substitution pattern,
and ammonium acetate (0.5 g) was dissolved in nitroethane
(50 ml)—for the b-methyl-b-nitrostyrene derivatives—or
in nitromethane (50 ml)—for the b-nitrostyrene deriva-
tives—and refluxed for 5 h. After cooling to room
temperature the reaction mixtures were partially evaporated
in a rotary evaporator, diluted with diethyl ether and washed
twice with water. The organic layer was dried over
anhydrous magnesium sulphate, filtered and concentrated.
3,4-Dihydroxy-b-nitrostyrene (3,4-OH-NS). Yield
1
2.26 g, 34%; H NMR d: 6.81 (1H, d; J ¼ 8:7; H(5)), 7.19
(1H, d; J ¼ 2:2; H(2)), 7.20 (1H, dd; J ¼ 8:0; 2.2, H(6)),
7.93 (1H, d; J ¼ 13:5; H(a)), 7.98 (1H, d; J ¼ 13:5; H(b)),

R. Calheiros et al. / Journal of Molecular Structure 692 (2004) 91–106
93
9.70 (2H, brs, OH); 13C NMR d: 116.0 C HAr, 116.4 C HAr,
121.5 C(1), 123.8 C HAr, 134.6 C(a), 140.4 C(b), 145.8
C(3), 150.5 C(4); EI-MS m/z (%): 181 (Mþz, 100), 134 (85),
89 (47), 77 (31), 63 (24); m.p. 148–151 8C.
Quantitative potential-energy profiles for rotation around
different bonds within the molecule were obtained, by
scanning the corresponding dihedrals and using least-
squares fitted Fourier-type functions of a dihedral angle, t
[26,27]:
3,4-Dihydroxy-b-methyl-b-nitrostyrene
(3,4-OH-
1
MeNS). Yield 2.55 g, 35%; H NMR d: 2.40 (3H, s, CH3)
6.85 (1H, d; J ¼ 8:2; H(5)), 6.97 (1H, dd; J ¼ 8:3; 2.0,
H(6)), 7.05 (1H, d; J ¼ 2:0; H(2)), 7.96 (1H, s, H(a)), 9.58
(2H, brs, OH); 13C NMR d: 14.0 C H3, 116.0 C HAr, 117.5
C HAr, 123.1 C(1), 124.0 C HAr, 134.2 C(a), 144.3C(b),
145.6 C(3), 148.4 C(4); EI-MS m/z (%): 195 (Mþz, 99), 148
(69), 138 (24), 119 (16), 110 (17), 103 (100), 91 (40), 83
(23), 77 (53), 65 (23), 55 (17); m.p. 140–141 8C.
3
2
X
X
1
2
1
2
P ¼
Pn½1 2 cosðntފ þ
P0m sinðmtÞ
ð1Þ
n¼1
m¼1
The parameters Pn and P0m correspond to potential-energy
(Vn and Vm terms), bond-distance or bond-angle differences
relative to a reference value. According to the symmetry of
the nitrostyrene molecules presently studied, namely the
methyl substituted ones, both cosine and sine terms were
considered in the fitting of the experimental data.
2.2. Apparatus
1Hand13CNMRdata wereacquired, atroomtemperature,
on a Bru¨ker AMX 300 spectrometer operating at 300.13 and
75.47 MHz, respectively. Dimethylsulfoxide-d6 was used as
a solvent; chemical shifts are expressed in d (ppm) values
relative to tetramethylsilane (TMS) as internal reference;
coupling constants ðJÞ are given in Hertz. Assignments were
also made from distortionless enhancement by polarization
transfer (DEPT) (see italicised values). EI-MS were carried
outonaVGAutoSpec instrument; thedataare reportedas m/z
(% of relative intensity of the most important fragments).
2.4. Spectroscopic methods
The Raman spectra were obtained, at room temperature,
on a triple monochromator Jobin-Yvon T64000 Raman
system (0.640 m, f/7.5) with holographic gratings of
1800 grooves mm21. The detection system was a non-
intensified Charge Coupled Device (CCD). The entrance slit
was set to 100 mm and the slit between the premonochro-
mator and the spectrograph was opened to 14.0 mm. The
514.5 nm line of an Arþ laser (Coherent, model Innova 300)
was used as excitation radiation, providing 5–100 mW at
the sample position. Samples (pure solids) were sealed in
Kimax glass capillary tubes of 0.8 mm inner diameter.
Under the above mentioned conditions, the error in
¨
Melting points were obtained on a Kofler microscope
(Reichert Thermovar) and are uncorrected.
2.3. Ab initio MO calculations
The ab initio calculations—full geometry optimisation
and calculation of the harmonic vibrational frequencies—
were performed using the GAUSSIAN 98W program [11],
within the Density Functional Theory (DFT) approach, in
order to properly account for the electron correlation effects
(particularly important in this kind of systems). The widely
employed hybrid method denoted by B3LYP [12–17],
which includes a mixture of HF and DFT exchange terms
and the gradient-corrected correlation functional of Lee et al.
[18,19], as proposed and parameterised by Becke [20,21],
was used, along with the double-zeta split valence basis sets
6-31G* and 6-31G** [22,23].
wavenumbers was estimated to be within 1 cm21
.
In some cases, the Arþ laser 514.5 nm excitation line led
to quite strong fluorescence backgrounds, which were
avoided by lowering the laser power or, when this was not
enough, by using a 1064 nm line provided by a Nd:YAG
laser (FT-Raman experiments).
Fourier transform Raman spectra were recorded on a
RFS 100/S Bruker spectrometer, with a 1808 geometry,
equipped with an InGaAs detector. Near-infrared excitation
was provided by the 1064 nm line of a Nd:YAG laser
(Coherent, model Compass-1064/500N). A laser power of
200 mW at the sample position was used in all cases, and
Molecular geometries were fully optimised by the Berny
algorithm, using redundant internal coordinates [24]: the
bond lengths to within ca. 0.1 pm and the bond angles to
within ca. 0.18. The final root-mean-square (rms) gradients
were always less than 3 £ 1024 hartree bohr21 or
hartree rad21. No geometrical constraints were imposed
on the molecules under study. The 6-31G** basis set was
used for all geometry optimisations, while for most of the
rotational energy barrier calculations the smaller basis set 6-
31G* was found to yield good results. All frequency
calculations were run at the B3LYP/6-31G** level and
wavenumbers above 400 cm21 were scaled [25] before
comparing them with reported experimental data.
resolution was set to 2 cm21
.
FT-IR data was collected (in KBr pellets) on a MATSON
7000 spectrometer, operating in the 400–4000 cm21 range,
using a 2 cm21 resolution.
2.5. Chemicals
trans-b-Nitrostyrene, 1,2-dihydroxybenzene, 3,4-dihy-
droxybenzaldehyde, styrene, trans-b-methylstyrene,
ammonium acetate, nitroethane and nitromethane were
´
purchased from Sigma-Aldrich Quımica S.A. (Sintra,
Portugal). All other reagents and solvents were pro-analysis
grade, purchased from Merck (Lisbon, Portugal).

94
R. Calheiros et al. / Journal of Molecular Structure 692 (2004) 91–106
3. Results and discussion
(3,4-OH-MeNS). The effect of several structural parameters
on the overall stability of these molecules was investigated:
(i) orientation of the phenolic hydroxyls, relative to the
ring—dihedrals (H17O8C5C4) and (H18O7C6C5) equal to 0
or 1808 (Fig. 1); (ii) relative orientation of the aromatic ring
and the NO2 group relative to the C9yC10 bond—
(C3C9C10N11) dihedral equal to 0 or 1808, defining a Z or
E configuration, respectively; (iii) position of the methyl
3.1. Ab initio MO calculations
A complete geometry optimisation was carried out for some
of the nitrostyrenes under study, namely: b-nitrostyrene (NS),
b-methyl-b-nitrostyrene (MeNS), 3,4-dihydroxy-b-nitrostyrene
(3,4-OH-NS) and 3,4-dihydroxy-b-methyl-b-nitrostyrene
Fig. 2. Schematic representation of the calculated (B3LYP/6-31G**) conformers for b-nitrostyrene (NS), b-methyl-b-nitrostyrene (MeNS) and 3,4-dihydroxy-
b-nitrostyrene (3,4-OH-NS) (displaying intramolecular hydrogen bonds—distances in pm. Relative energies are in kJ mol21).

R. Calheiros et al. / Journal of Molecular Structure 692 (2004) 91–106
95
Table 1
Table 1 (continued)
Optimised geometries for the most stable conformers of NS, MeNS and
3,4-OH-NS (B3LYP/6-31G** level of calculation)
m (D)a
NS 1
5.8
MeNS 1
5.2
3,4-OH-NS 1
6.2
m (D)a
NS 1
5.8
MeNS 1
5.2
3,4-OH-NS 1
6.2
C2–C3–C9–H19
C3–C9–C10–H20
C9–C10–C20–H21
C9–C10–C20–H22
2180.0
0.0
151.8
2180.0
0.0
2137.4
216.9
Bond lengths (pm)
b
C1–C2
139.0
139.3
140.8
140.9
139.1
139.6
139.6
146.4
134.6
149.6
138.9
140.8
141.2
138.4
140.8
139.6
145.3
134.3
C2–C3
C3–C4
C4–C5
C5–C6
C6–C1
C3–C9
C9–C10
C10–C20
C5–O8
C6–O7
C10–N11
N11–O12
140.9
140.7
139.3
139.5
139.9
146.0
134.0
a
1D ¼ 1/3 £ 1022 cm.
b
Atoms are numbered according to Fig. 1; the same atom numbering is
applicable to all the compounds studied, irrespective of the type of atom.
group relative to the ring OH’s—dihedral (C10C9C3C4)
either 0 or 1808. The conformational behaviour of this kind
of compounds is mainly determined by electronic effects, as
well as by the possibility of occurrence of (C)H· · ·O
intramolecular hydrogen bonds, which are medium strength,
directional interactions (with a preference for linearity),
long known to be relevant for the overall stability of
numerous systems [28].
137.4
135.4
144.7
123.5
123.5
0.96
145.1
123.5
123.3
148.4
123.3
123.2
N
11–O13
O8–H17
O7–H18
C1–H14
C2–H15
C4–H16
C5–H8
0.97
108.6
108.5
108.6
108.5
108.6
108.7
108.0
108.6
108.4
108.6
108.6
108.6
108.6
108.4
108.4
108.8
Two stable conformations were calculated for both NS
and MeNS, while six were obtained for the dihydroxylated
analogue 3,4-OH-NS, only one of these, in each case, being
significantly populated at room temperature (Fig. 2). All the
conformers were found to display a planar or quasi-planar
geometry, differing in the configuration of the phenyl and
NO2 groups relative to the linear chain double bond—either
E or Z—and in the orientation of the ring hydroxyls. The E
conformers with identical orientations of the ring OH’s were
determined to be the lowest energy ones (Table 1).
C6–H7
C9–H19
C10–H20
108.7
108.0
C20–H21
109.1
109.1
109.6
C20–H22
C20–H23
Bond angles (8)
C2–C3–C4
118.5
123.2
127.1
118.2
124.1
129.1
130.1
118.3
123.5
127.4
C2–C3–C9
For 3,4-OH-MeNS, in turn, ten different conformers
were calculated (Figs. 3 and 4), the most stable ones also
having an E orientation of the aromatic ring and the terminal
nitro group relative to the C9yC10 bond
((C3C9C10N11) ¼ 1808/(C20C10C9C3) ¼ 08), along with an
identical orientation of both OH ring substituents—
conformers 1 ðDE ¼ 0Þ; 2 (DE ¼ 0:6 kJ mol21) and 3
(DE ¼ 1:5 kJ mol21)—with populations at room tempera-
ture of 43, 34 and 23%, respectively (Table 2). Actually, the
large energy difference between conformations 2 and 4
(DE ¼ 13:6 kJ mol21) is due solely to the change in the
(C3C9C10N11) dihedral angle from 180 to 08 (Fig. 3). In fact,
despite the small O13· · ·H16(C) interatomic distance
(201 pm, Fig. 3) in 3,4-OH-MeNS 4, leading to the
formation of a 7-membered intramolecular ring, the
H15· · ·H19 and H23· · ·H19 steric hindrance (H· · ·H distances
of 216 and 214 pm, respectively) overrules that stabilising
factor. As expected, no stable geometry was obtained when
both ring hydroxyl groups are directed towards each other.
However, three conformers were found for opposite
orientations of the phenolic OH’s—3,4-OH-MeNS 5
(DE ¼ 18:1 kJ mol21), 9 (DE ¼ 33:9 kJ mol21) and 10
(DE ¼ 38:7 kJ mol21)—these being the less stable ones
(e.g. 3,4-OH-MeNS 5 vs. 3,4-OH-MeNS 1 and 2, Fig. 3).
For such an arrangement of the OH groups, a (C3C9C10C20)
C3–C9–C10
C9–C10–C20
C6–C5–O8
114.6
120.3
115.8
124.6
110.3
115.5
127.7
C9–C10–N11
C10–N11–O12
120.5
115.7
124.8
115.7
116.4
124.0
O
12–N11–O13
C5–O8–H17
C10–C9–H19
C9–C10–H20
C10–C20–H21
115.9
127.8
115.0
110.1
110.1
109.2
106.7
C10–C20–H22
H
H
21–C20–H22
21–C20–H23
Dihedral angles (8)
C3–C4–C5–C6
C5–C4–C3–C9
C4–C3–C9–C10
C3–C9–C10–C20
C3–C9–C10–N11
C9–C10–N11–O12
C9–C10–N11–O13
C4–C5–O8–H17
C5–C6–O7–H18
C3–C4–C5–H8
C4–C5–C6–H7
C5–C6–C1–H14
C6–C1–C2–H15
C2–C3–C4–H16
0.0
0.0
21.3
2179.7
152.3
0.0
180.0
180.0
2180.0
23.9
177.8
180.0
180.0
0.0
180.0
2180.0
0.0
2177.5
2.0
0.0
0.0
2180.0
180.0
180.0
180.0
180.0
179.2
2179.4
2178.4
2177.6
2178.5
180.0
180.0
180.0

96
R. Calheiros et al. / Journal of Molecular Structure 692 (2004) 91–106
Fig. 3. Schematic representation of the calculated (B3LYP/6-31G**) lowest energy conformers for 3,4-OH-MeNS (displaying intramolecular hydrogen
bonds—distances in pm).
dihedral equal to 08 yielded more stable geometries than
(C3C9C10C20) ¼ 1808—3,4-OH-MeNS 5 vs. 9 (Figs. 3
and 4)—on account of the steric repulsion between H15
and H19 (H15· · ·H19 of 215 pm), and H19 and H22 (H15· · ·H19
of 217 pm), which is present in conformer 9. In contrast,
whenever the two ring hydroxyls display the same
orientation an energetically favoured geometry results,
probably due to the formation of intramolecular hydrogen
interactions between O8 and H18, or O7 and H17 (O· · ·H
distances between 211 and 214 pm, Fig. 3).
Moreover, for a (C3C9C10N11) dihedral equal to 1808, a
syn orientation of the NO2 group relative to the OH ring

R. Calheiros et al. / Journal of Molecular Structure 692 (2004) 91–106
97
Fig. 4. Schematic representation of the relative conformational energies (and populations, at 25 8C) of the calculated (B3LYP/6-31G**) conformers for
3,4-OH-MeNS.
substituents is energetically favoured, as it allows a more
effective electron delocalisation—3,4-OH-MeNS
the double bond in the carbon side chain of the 3,4-OH-
MeNS molecule. The analysis of the Fourier components of
the corresponding potential-energy variation (Fig. 5)
manifests the preference for a planar geometry of the
nitro group, once the cosine term in 908 is clearly
destabilising—V2908 ¼ 30:2 kJ mol21—as compared to the
60 and 1808 contributions—V11808 and V3608 equal to
21.2 kJ mol21—e.g. geometries 3,4-OH-MeNS 1, ðO12N11
C10C9Þ ¼ 2177:18=DE ¼ 0 and 3,4-OH-MeNS 8,
ðO12N11C10C9Þ ¼ 17:58=DE ¼ 24:1 kJ mol21. The negative
value of V3608 is also explained by the stabilising intramo-
lecular H-bond type interactions, which may occur between
NO2 and one of the methyl hydrogen atoms (e.g. conformers
1, 2 or 3, O12· · ·H(C20) ca. 236 pm, Fig. 3). The energy
barrier for this internal rotation process—from ðO12C11C10
1
ðDE ¼ 0Þ vs. 2 (DE ¼ 0:6 kJ mol21). Also, the zero
(C4C3C9C10) dihedral in conformation 2 leads to a serious
steric hindrance between atoms H22 and H16, and H19 and
H15 (H22· · ·H16 and H19· · ·H15 distances equal to 215 and
236 pm, respectively, Fig. 3). As to the position of the
methyl group, it was verified that the geometries displaying
a (C4C3C9C10) dihedral angle of 08, a syn orientation
relative to the ring hydroxyls is favoured (3,4-OH-MeNS 2
(DE ¼ 0:6 kJ mol21) vs. 3 (DE ¼ 1:5 kJ mol21), Fig. 3).
Conformer 3,4-OH-MeNS 10 ((C4C3C9C10) ¼ 1808) was
found to be highly unfavoured relative to 3,4-OH-MeNS 5
((C4C3C9C10) ¼ 08), due to the formation of a medium
strength intramolecular H-bond between O12 and H23 in the
latter (O· · ·H distance of 236 pm, Fig. 3), which can not
occur in the former (O· · ·H distance of 257 pm).
C9Þ ¼ 90 to 1808—was calculated to be 31.8 kJ mol21
.
The internal rotation of the 3,4-OH-MeNS methyl group,
in turn, is associated to a variation of dihedral
(H22C20C10C9), which was studied for the most stable
geometry of the molecule (E configuration, with ðH17O8C5
C4Þ=ðH18O7C6C5Þ ¼ 08Þ: The best fitting of the
experimental data was obtaining by using a combination of
Although both hydroxyl groups were found to be
coplanar with the aromatic ring in all conformers calculated
for 3,4-OH-MeNS, the remaining part of the molecule
deviates from planarity—(C2C3C9C10) ca. 238,
(C20C10C9C3) ca. 48 and (O12N11C10C9) ca. 28—the most
stable geometries displaying one of the methyl hydrogens
approaching an oxygen from the NO2 group, which allows a
medium strength H-bond to be formed (O· · ·H distances
between 235 and 237 pm, Fig. 3), as well as a minimisation
of the H–H steric repulsions.
both cosine and sine terms—V3608 ¼ 20:7 kJ mol21
,
V06308 ¼ 0:8 kJ mol21 and V06308 ¼ 1:1 kJ mol21 (Fig. 6)—a
maximum being obtained for ðH22C20C10C9Þ ¼ 158; and
three minima occurring for ðH22C20C10C9Þ ¼ 105 (the most
favoured geometry), 30 and 908. This conformational
behaviour is a consequence of the balance between the
stabilising (C20)H· · ·O(N11) intramolecular hydrogen-type
interactions and the energetically unfavoured (C20)H· · ·H15
steric hindrances (Table 3).
Rotational isomerism was also investigated for the
methyl-nitrostyrene 3,4-OH- -MeNS, by scanning particular
dihedral angles—(O12N11C10C9), (H22C20C10N11) and
(C10C9C3C4)—which define, respectively, the internal
rotation of the nitro and methyl groups, and the orientation
of the pendant carbon chain relative to the aromatic ring.
The value of the (O12N11C10C9) dihedral determines the
rotation around the C10–N11 bond, i.e. the orientation of the
NO2 terminal relative to both the aromatic ring and
The orientation of the carbon side chain relative to the
aromatic ring is defined by the dihedral angle (C10C9C3C4).
Once more, the values of the Fourier components of the
corresponding potential-energy variation reflect a clear
preference for planarity—a minimum occurs for ðC10C9C3

98
R. Calheiros et al. / Journal of Molecular Structure 692 (2004) 91–106
Table 2
Relative energies and optimised geometries for the most stable
conformers of 3,4-dihydroxy-b-methyl-b-nitrostyrene (3,4-OH-MeNS)
(B3LYP/6-31G** level of calculation)
DE
(kJ mol21)/m(D)a
3,4-OH-MeNS
1
0.0/5.1
3,4-OH-MeNS
2
0.6/5.7
3,4-OH-MeNS
3
1.5/7.3
Bond lengths (pm)
b
C1–C2
C2–C3
139.2
140.8
141.4
138.3
140.9
139.3
145.8
134.9
149.6
137.4
135.5
148.0
123.4
123.4
96.5
139.3
140.7
141.1
138.8
140.8
139.3
146.0
134.8
149.6
136.0
137.1
148.1
123.4
123.4
96.9
139.1
140.8
141.3
138.5
140.9
139.3
145.7
134.9
149.6
137.4
135.5
147.8
123.4
123.5
96.5
C3–C4
C4–C5
C5–C6
C6–C1
C3–C9
C9–C10
C10–C20
C5–O8
Fig. 5. Optimised conformational energy profile, and its
Fourier deconvolution, for the internal rotation around the N11–C10
bond of 3,4-OH-MeNS. V1 ¼ 21:2 kJ mol21
,
V2 ¼ 30:2 kJ mol21
,
V3 ¼ 21:2 kJ mol21 (B3LYP/6-31G* level of calculation).
C6–O7
C10–N11
N11–O12
N11–O13
O8–H17
O7–H18
C1–H14
C2–H15
C4–H16
C9–H19
C20–H21
C20–H22
C20–H23
C4Þ ¼ 1508 and the cosine term in 908 is by far the primary
positive contribution to this profile, V2908 ¼ 12:5 kJ mol21
,
as compared to the one in 1808, V11808 ¼ 23:1 kJ mol21
(Fig. 7). This may be attributed to the significant
stabilisation due to p-electron delocalisation, which is
considerably more effective for a linear zig-zag like
unsaturated chain, coplanar with the aromatic ring. The
fact that the lowest energy conformation was not found to
occur for a (C10C9C3C4) dihedral equal to 1808 is explained
by the presence of the methyl group, responsible for
(C20)H· · ·H15 destabilising interactions, which are mini-
mised in the slightly tilted geometry ððC10C9C3C4Þ ¼ 1508;
(C20)H· · ·H15 distances of 222 and 275 pm) as compared to
the completely planar one (ðC10C9C3C4Þ ¼ 1808;
97.0
96.6
97.0
108.5
108.2
108.8
108.6
109.1
109.6
109.1
108.7
108.5
108.2
108.6
109.6
109.1
109.1
108.4
108.5
108.5
108.6
109.1
109.8
109.1
Bond angles (8)
C2–C3–C4
C2–C3–C9
C3–C9–C10
C9–C10–C20
C6–C5–O8
C9–C10–N11
C10–N11–O12
O12–N11–O13
C5–O8–H17
C10–C9–H19
C10–C20–H21
C10–C20–H22
H21–C20–H22
H21–C20–H23
117.9
124.8
129.8
129.9
114.6
115.6
119.6
123.8
110.2
114.5
110.0
112.1
109.2
108.5
117.9
117.7
130.0
129.9
114.4
115.7
119.6
123.8
110.3
114.6
110.1
112.2
109.0
108.7
118.4
117.4
129.7
130.1
120.4
115.6
119.6
123.8
107.9
114.7
112.0
110.1
106.8
108.6
(C20)H· · ·H15 distances of 222 pm).
A value of
16.5 kJ mol21 was determined for the energy barrier
corresponding to this internal rotational process—from
(C10C9C3C4) equal to 150–908.
The results presently obtained are in perfect accordance
with previously reported data on catechol [29], styrene [30]
and b-methylstyrene [31], which were, however, deter-
mined by either semi-empirical methods (e.g. AM1), or by
Dihedral angles (8)
C3–C4–C5–C6
C5–C4–C3–C9
21.3
2179.9
157.5
24.1
177.4
2177.2
2.3
0.4
21.3
2179.7
223.4
24.6
177.1
2177.4
2.0
0.0
179.9
23.6
C4–C3–C9–C10
C3–C9–C10–C20
C3–C9–C10–N11
C9–C10–N11–O12
C9–C10–N11–O13
C4–C5–O8–H17
C5–C6–O7–H18
C5–C6–C1–H14
C6–C1–C2–H15
C2–C3–C4–H16
C2–C3–C9–H19
C9–C10–C20–H21
C9–C10–C20–H22
4.0
2177.5
177.3
22.2
179.6
178.5
2179.2
2179.7
2175.9
21.5
20.1
0.0
20.1
2178.4
2177.5
2178.8
156.7
221.5
99.3
179.1
179.6
175.9
220.4
221.9
99.3
2100.3
20.6
a
Total value of energy for the most stable conformer of 3,4-OH-
MeNS is 2703,925705439 Hartree (1 Hartree ¼ 2625.5001 kJ mol21);
1D ¼ 1/3 £ 1022 cm.
Fig. 6. Optimised conformational energy profile, and its Fourier
deconvolution, for the internal rotation around the C20–C10 bond of 3,4-
OH-MeNS. V6 ¼ 20:7 kJ mol21, V30 ¼ 0:8 kJ mol21, V06 ¼ 1:1 kJ mol21
(B3LYP/6-31G* level of calculation).
b
Atoms are numbered according to Fig. 1; the same atom numbering
is applicable to all the compounds studied, irrespective of the type of
atom.

R. Calheiros et al. / Journal of Molecular Structure 692 (2004) 91–106
99
Table 3
absorptions, the latter being often overlapped with the ring
CyC stretching; rocking, wagging and scissoring modes, at
ca. 500, 700 and 750–800 cm21, respectively; (ii) the linear
chain CyC double bond—stretching vibrations at ca.
1635 cm21; (iii) the aromatic ring—CyC stretching
vibrations, at ca. 1470–1600 cm21; out-of-plane ring
wagging modes—between ca. 870 and 1000 cm21, for this
type of tri-substituted benzenes; (iv) the CH deformations—
both wagging, at ca. 1300 cm21, and rocking modes, at
700–900 cm21; (v) and the CH typical stretching
vibrations, both symmetric and assymmetric, respectively,
around 3000–3250 cm21. While the bands due to the nitro
group—around 1300 and 1600 cm21—are the most intense
ones in the spectra of the nitrostyrenes, for the NO2-free
compounds the strongest features are the ones due to the
Intramolecular (C20)H· · ·H15 and (C20)H· · ·O(N) distances for the distinct
geometries yielded by variation of the (H22C20C10C9) dihedral angle within
the 3,4-OH-MeNS molecule (internal rotation of the CH3 group)
(B3LYP/6-31G** level of calculation)
b
(H22C20C10C9)
DEa
dðC
(pm)
dðC
20ÞH· · ·OðNÞ
(pm)
20ÞH· · ·H15
(8)
(kJ mol21
)
15
4.38
0.14
1.08
1.66
1.11
0.18
–
205
253
30
218/251
220/231
221/221
219/229
218/249
216/266
215/275
212
231
45
222
60
219
75
223
90
231
99c
105
120
236
0
240/286
250/269
1.17
ring wagging modes, at ca. 1000 cm21
.
a
Conformational energies relative to the geometry with
Either in the pure liquid or the solid states, phenols
usually occur as hydrogen-bonded dimers (and oligomers).
Thus, the Raman spectra (in the solid phase) of the
hydroxyl-substituted nitrostyrenes—3,4-OH-NS and
3,4-OH-MeNS—comprise the high frequency pattern
characteristic of the ring hydroxyl stretching modes: a
sharp, moderately intense band at 3520–3400 cm21—free
OH stretch—and a very broad strong absorption near
3300 cm21—O–H· · ·O stretch (Tables 5 and 6). Also
detected are the features at 1315–1400 cm21, correspond-
ing to the in-plane and out-of-plane C–OH deformations
(respectively), and at ca. 1280 cm21, due to the stretching of
the phenol C–O bonds (Tables 5 and 6). In turn, the
b-methyl-b-nitrostyrenes—MeNS and 3,4-OH-MeNS—
yield the typical CH3 vibrational bands (Tables 5 and 6):
symmetric and antisymmetric stretching modes, between
2800 and 3090 cm21; symmetric and antisymmetric defor-
mations, at ca. 1320 and 1510 cm21; rocking modes, around
(H22C20C10C9) ¼ 1058.
b
Atoms are numbered according to Fig. 1.
c
Lowest energy conformer obtained for 3,4-OH-MeNS.
ab initio MO calculations with smaller basis sets than the
ones used along this work.
3.2. Raman spectroscopy
Fig. 8 comprises the Raman spectra of the phenolic
derivatives studied (in the solid state), in the 75–1750 and
2200–3600 cm21 regions. Harmonic vibrational
frequencies were calculated for all conformers of NS,
MeNS, 3,4-OH-NS and 3,4-OH-MeNS. A complete
assignment of the experimental vibrational features was
carried out (Tables 4–6), based on these theoretical
calculations, as well as on results previously reported for
similar systems [34,35].
1000 cm21; and torsions, at 180–250 cm21
.
It was verified that the presence of the methyl group,
responsible for significant inductive effects, as a substituent
of the unsaturated carbon chain, led to clear changes in the
Raman pattern (Fig. 8, Tables 4–6), namely a clear shift (ca.
20–30 cm21) of the n (CyC)chain to higher wavenumbers—
S (1634 cm21) vs. MeS (1663 cm21), NS (1633 cm21) vs.
MeNS (1654 cm21), and 3,4-OH-NS (1612 cm21) vs.
3,4-OH-MeNS (1637 cm21). Furthermore, in the absence
of CH3 substitution, a large deviation (100–120 cm21) of
the NO2 scissoring mode to low frequency values is
detected—NS (737 cm21) vs. MeNS (850 cm21), and
Common to all the compounds investigated are the
features due to: (i) the NO2 group—symmetric
and asymmetric stretching, at 1250–1336 cm21 and
ca. 1550 cm21, respectively, strong and somewhat weaker
3,4-OH-NS (725 cm21
867 cm21). Also, OH substitution of the aromatic ring
was found to give rise to low frequency shifts (62–65 cm21
)
vs. 3,4-OH-MeNS (857/
)
of the ns (NO2) band, which may be explained by electron
delocalisation effects, favoured in the hydroxylated nitros-
tyrenes—NS (1336 cm21) vs. 3,4-OH-NS (1279 cm21),
MeNS (1316 cm21) vs. 3,4-OH-MeNS (1251 cm21).
The only phenolic aldehyde studied—3,4-OH-BA—
exhibits the characteristic nCyO band at 1653 cm21
(Table 4). The aldehyde CH is responsible for the feature
Fig. 7. Optimised conformational energy profile, and its Fourier
deconvolution, for the internal rotation around the C9–C3 bond of 3,4-
OH-MeNS. V1 ¼ 23.1 kJ mol21, V2 ¼ 12.5 kJ mol21 (B3LYP/6-31G*
level of calculation).

100
R. Calheiros et al. / Journal of Molecular Structure 692 (2004) 91–106
Fig. 8. Experimental Raman spectra (75–1750, 2200–3600 cm21) of some of the b-nitrostyrene derivatives and their analogues studied in the present work
(solid state, at 25 8C): (a) CAT; (b) S; (c) MeS; (d) NS; (e) MeNS; (f) 3,4-OH-MeNS. (g) FTIR spectra (400–1750 cm21, in KBr pellet) of 3,4-OH-MeNS.
at 1388 cm21—rocking vibration—as for the characteristic
doublet at ca. 2740 and 2890 cm21, due to a Fermi
resonance process between the overtone of that bending
mode and the CH stretching fundamental.
in Fig. 8. The bands due to the stretching modes of the NO2
group (asymmetric), and the ring and chain double bonds are
easily detected, at 1594, 1612 and 1635 cm21, respectively.
Moreover, the bands at ca. 1500 cm21—CH3 antisymmetric
deformation modes—hardly observed in Raman, appear as
well defined, moderately strong features in the FT-IR
The FT-IR spectrum of the b-methyl-b-nitrostyrene of
3,4-OH-MeNS, in the 400–1750 cm21 range, is represented

R. Calheiros et al. / Journal of Molecular Structure 692 (2004) 91–106
101
Table 4
Raman experimental wavenumbers (cm21) for CAT, 3,4-OH-BA, S and MeS, in the solid state
Experimental Raman
Approximate descriptiona
CAT
3,4-OH-BA
S
MeS
3459
3324
n (O8H17
n (O7H18
)
)
3326
3181
3114
3258
n (CH)ring
n (CH)ring
n (CH)chain
n (CH)ring
n (CH)ring
n (CH)ring
n (CH)ring
n (CH)chain
n (CH)ring
FR (d (CH) þ n (CH))
n (CH2)
3211
3203
3195
3155
3101
3154
3094 (3080b)
3102
3071
3069
3058 (3032c)
3081
3053
3065 (3068b)
3059
3050 (3050b)
3012 (3030b)
3062
3057
3046
3004
3019
2980
2964
2984
2964
2935
2916
n (CH)ring
n (CH)
n (CH)chain
n (CH2)
2909
2890
1653
2874 (2881d)
2852
nas (CH3)
ns (CH3)
n (C ¼ O)
n (C ¼ C)chain
n (CC)ring
n (CC)ring
n (CC)ring
n (CC)ring
d (CH)ring
1634 (1639b)
1663 (1668d)
1647
1621
1609 (1625c)
1645
1592
1582
1532
1474
1450
1604
1599
1578
1498 (1499b)
1579
1516
1476
1495
1452 (1432b)
1415
d (CH)ring þ d (CH2) (sciss.)
d (CH)ring þ das (CH3)
d (CH)ring
1444
1442
1381
1348
1440
1420
1388
d (CH)ring
d (CH) þ n (CC)
ds (CH3)
d (CH)ring
1377 (1390d)
1337
1320
1306
v (CH2)
das (CH3)
1305
d (CH)chain n (CC)ring
d (OH)
n CO)
1292
1271
1275 (1251c)
1254
1277
1210
n (CC)ring
d (CH)chain
1206
1184
1204
1177
n (CC)ring
n (CC)ring
1188
1163
1116
1177
1156
1031
d (CH) þ d (OH)
1164
n (CC)ring
n (CC)
1151
1158
1104
1041 (1014c)
d (CH)ring þ d (OH)
d (CH)ring þ n (CC)ring
g (CH)ring þ t (CH2)
g (CH)ring
1035 (1022b)
1001 (1003b)
973
1002
944
g (CH)ring
v (CH2)
907
846
912 (932b)
777 (771b)
824
809
g (CH)ring
g (CH)ring
812
755
774 (756c)
751
g (CH)ring
d (CC)ring
719
d (CC)ring
d (CC)ring
628
589
502
622
618
581
d (CC)ring
d (CC)ring
557 (548b)
(continued on next page)

102
R. Calheiros et al. / Journal of Molecular Structure 692 (2004) 91–106
Table 4 (continued)
Experimental Raman
Approximate descriptiona
CAT
457
3,4-OH-BA
S
MeS
448
426
445 (426b)
d (CC)ring
g (OH)
g (CCC)
408 (407d)
406
388
362
g (OH)
g (OH)
344
296
351
284
g (CCC)
g (CCC)
t (CH3)
d (CCC)
d (CCC)
239
222
214
212
122
104
80
239
214
211
206
112
Skeletal modes
g (OH)
t (CH3)
132
Skeletal modes
Skeletal modes
Skeletal modes
Skeletal modes
77
72
54
a
Atoms are numbered according to Fig. 1; the same atom numbering is applicable to all the compounds studied, irrespective of the type of atom. d and g
stand for in-plane and out-of-plane deformations, respectively.
b
Calculated values [30].
c
Refs. [29,32,33].
d
Ref. [31].
Table 5
Raman experimental and calculated wavenumbers (cm21) for the most stable conformers of NS, MeNS and 3,4-OH-NS, in the solid state
NS
MeNS
Exp
3,4-OH-NS
Expc
Approximate descriptiona
Exp
Calcb
Calc
Calc
3410
3306
3117
3063
3040
3694 (74;123)
3626 (151;234)
3144 (8;38)
n (O8H17)
n (O7H18) þ n (OH· · ·O)
n (CH)chain
ns (CH)ring
nas (CH)ring
n (CH)
3231
3195
3153
3111
3070
3046
3004
2968
3144 (7;34)
3091 (14;293)
3083 (23;39)
3076 (7;106)
3070 (0;65)
3067 (0;58)
3063 (3;10)
3099 (6;96)
3086 (24;230)
3076 (15;86)
3072 (2;60)
3067 (0;98)
3061 (2;18)
3098 (4;125)
3082 (4;34)
3070
3057
3035
2968
2906
3067 (0;38)
3050 (9;45)
n (CH)chain
n (CH)
nas (CH)ring
2971
2936
2912
2805
2619
3041 (4;49)
3005 (7;82)
2938 (8;160)
nas (CH3)
nas (CH3)
ns (CH3)
2666
2602
2524
2453
2305
1633
1600
1580
1514
1500
2 £ ns (NO2)
2 £ d (CH)
2510
(1000 þ 1336) cm21 comb. mode
1639 (130;666)
1593 (15;569)
1568 (25;5)
1654
1596
1652 (53;646)
1593 (4;486)
1566 (1;22)
1612
1636 (108;493)
1600 (104;768)
1581 (181;314)
1549 (175;263)
1515 (161;3)
n CyC
n (CC)ring
1597
1486
1476
n (CC)ring
nas (NO2)
1555 (150;151)
1480 (5;12)
1505
1484
1561 (171;49)
1479 (5;26)
d (CH)ring
das (CH3)
1440 (10;31)
1429 (43;5)
n (CC)ring þ d (OH)
das (CH3) þ d (CH)
das (CH3) þ d (CH)ring
d (CH)ring þ n (CC)ring
1433 (14;5)
1427 (7;22)
1443
1450
1433 (15;20)

R. Calheiros et al. / Journal of Molecular Structure 692 (2004) 91–106
103
Table 5 (continued)
NS
MeNS
Exp
3,4-OH-NS
Expc
Approximate descriptiona
Exp
Calcb
Calc
Calc
1385
1383 (29;16)
ds (CH3) þ d (CH)chain
1328
1313
1274
1373 (27;37)
d (O7H18)
1395
1336
1349
1316
1335 (18;67)
1319 (395;474)
1313 (4;11)
d (CH)chain þ ds (CH3)
ns (NO2) þ ds (CH3)
d (CH)ring
1338 (517;641)
1318 (6;18)
1337 (416;979)
1314 (2;31)
d (CH) þ d (OH)
d (CH)ring þ n (CC)ring
d (CH) þ n (CC)ring
d (CH)chain
1296
1216
1290 (24;109)
1200 (18;145)
1295
1290 (692;530)
1275 (87;3)
1307 (8;9)
1274 (0;15)
1238 (27;224)
1182 (14;42)
1163 (21;91)
1243
1212
1199
1176
1159
1265 (10;83)
1213 (28;79)
1176 (209;177)
1155 (1;4)
1266
1203
1184
d (CH)chain
d (CH) þ d (O7H18
d (CH)ring
d (O8H17)
)
1185
1166 (5;39)
1133 (165;59)
1145 (0;13)
1070 (5;1)
1015 (1;19)
1164
1102
1080
1034
1145 (0;11)
1085 (11;19)
1066 (6;10)
1027 (0;18)
d (CH)ring
d (CH)
1162
1031
1121
1089 (85;2)
d (CH)ring
r (CH3)
982 (23;5)
976 (0;42)
1000
970
999
1017 (0;20)
993
972
1133 (165;59)
975 (26;4)
d (CH)ring
g (CH)chain
g (CH)
965 (3;0)
957 (70;37)
963 (104;46)
937 (3;5)
n (CN)
976 (4;52)
967 (1;2)
931
d (CC)ring
g (CH)ring
r (CH3)
939 (0;0)
975
942
962 (64;8)
942 (3;12)
922
863
899 (0;2)
838 (1;5)
910 (1;1)
g (CH)ring (as wag)
d (CC)
918
870
855
821
932 (15;58)
897 (2;10)
850 (48;4)
826 (0;9)
826 (4;4)
g (CH)chain þ g (CH)ring (as wag)
g (CH)chain þ g (CH)ring (as wag)
d (NO2) (scis.)
827 (7;8)
817 (6;8)
840
828
820
812
806 (50;8)
798 (8;5)
g (CH)ring (as wag)
d (CC)ring
d (CCC)chain
792 (15;17)
763
804 (8;9)
779
725
772 (5;14)
d (CC)ring
753 (39;2)
720
707
750 (33;8)
704 (6;10)
g (CH)ring (s wag) þ g (CC)ring
v (NO2) þ g (CH)
d (NO2) (sciss.)
707 (0;0)
737
720 (12;23)
704 (13;35)
690
689 (12;4)
g (CH)ring (s wag)
g (CH)ring (s wag) þ v (NO2)
g (CC)ring
710
618
594
574
534
515
693 (10;1)
667 (14;0)
609 (0;7)
585 (20;1)
481 (7;0)
523 (2;2)
617
593
678 (16;4)
608 (0;7)
583 (8;1)
498 (9;18)
521 (7;6)
667 (0;0)
580 (23;3)
566 (8;2)
575 (6;0)
527 (1;5)
459 (71;3)
437 (14;0)
d (CC)ring
d (CC)ring
576
524
531
503
g (CC)
r (NO2) þ d (CC)chain
g (O7H18
)
g (O7H18) þ g (CC)ring
g (CC)chain
g (CC)ring
413
413 (4;16)
396 (0;0)
346 (0;2)
352
285
253
431 (22;2)
384 (3;2)
d (CCC)
g (CC)ring
g (CCC)
d (COH)
d (CCC)
g (CCC)
d (CCN)
404 (2;6)
381 (1;1)
318 (4;1)
291 (1;6)
277 (2;0)
242 (0;1)
226 (154;2)
182 (6;4)
185
132
290 (1;3)
257 (0;2)
281
245
331 (1;1)
284 (1;3)
229
158
g (O8H17
Skeletal modes
)
246 (2;1)
190 (0;3)
149
t (CH3)
(continued on next page)

104
R. Calheiros et al. / Journal of Molecular Structure 692 (2004) 91–106
Table 5 (continued)
NS
MeNS
Exp
3,4-OH-NS
Expc
Approximate descriptiona
Exp
Calcb
Calc
Calc
105
95
118 (1;1)
t (CH3)
110
90
130 (2;1)
109 (2;0)
90 (1;3)
37 (0;0)
136 (3;1)
93 (3;0)
70 (2; 1)
37 (0;0)
Skeletal modes
Skeletal modes
Skeletal modes
Skeletal modes
89 (0;5)
65 (1;3)
40 (0;5)
71
a
Atoms are numbered according to Fig. 1; the same atom numbering is applicable to all the compounds studied, irrespective of the type of atom. d and g
stand for in-plane and out-of-plane deformations, respectively.
B3LYP/6-31G** level; wavenumbers above 400 cm21 are scaled by 0.9614 [25] (IR intensities in km mol21; Raman scattering activities in A amu21).
˚
b
c
FT-Raman.
Table 6
Raman and IR experimental and calculated wavenumbers (cm21) for the most stable conformers of 3,4-OH-MeNS, in the solid state
Experimental
Raman
Calculateda
Approximate descriptionb
IR
3,4-OHMeNS 1
3,4-OHMeNS 2
3521
3518
3693 (72;123)
3628 (145;222)
3690 (117;277)
3639 (101;95)
n (O8H17
n (O7H18
)
)
3297
3219
n (OH· · ·O)
n (OH· · ·O)
n (CH)ring
3115 (3;54)
3090 (4;106)
2934 (10;175)
3070 (0;39)
3049 (9;46)
3041 (3;56)
3004 (8;75)
3117 (1;33)
3081 (4;107)
2935 (9;169)
3073 (2;15)
3053 (17;118)
3042 (3;54)
3006 (7;76)
3092
2939
2878
2861
2729
2636
2498
2429
2377
1635
n (CH)ring
nas (CH3)
ns (CH)
nas (CH)
nas (CH3)1 /ns (CH3)2
ns (CH3)1/nas (CH3)2
2 £ ns (NO2)
2 £ d (CH)
1635
1612
1594
1514
1646 (61;620)
1602 (120;303)
1580 (165;105)
1554 (140;8)
1514 (1;40)
1647 (65;747)
1604 (84;865)
1581 (46;2)
n (CyC)chain
n (CC)ring
1606
1512
n (CC)ring
nas (NO2) þ n (CC)ring
1556 (153;89)
1499 (188;0)
1455 (3;88)
n (CC)ring
das (CH3)
1473
1497
1444
1443 (37;19)
1436 (52;5)
1441 (5;41)
das (CH3)
das (CH3) þ n (CC)ring
ds (CH3) þ d (CH)chain þ d (O7H18
1425 (41;15)
1382 (15;76)
1374 (4;81)
1432 (15;25)
1385 (25;15)
1349 (20;66)
1398
1370
1343
1328
1315
1311
1295
1266
1250
1400
1371
)
d (O8H17) þ ds (CH3)2 þ n (CC)ring
1329
1303
1340 (263;739)
1328 (8;67)
d (CH)chain þ ds (CH3) þ d (O7H18
)
2
1273
1258
1314 (342;482)
1294 (394;118)
1280 (52;26)
1261 (198;210)
1183 (4;3)
1317 (209;514)
1303 (323;308)
1283 (534;371)
1240 (26;26)
1180 (55;4)
ns (NO2) þ ds (CH3) þ d (CH)1 þ d (O7H18
d (OH) þ d (CH)1ring þ ns (NO2)2
d (CH)ring þ n (CO)1 þ n (CC)r1ing
d (CH)
)
1172
d (O7H18) þ d (CH)
1120
1102
1037
1001
999
1121
1102
1156 (130;32)
1135 (100;3)
1093 (22;66)
1082 (1;20)
1161 (26;137)
1135 (41;4)
d (CH) þ d (OH)
d (O8H17) þ d (CH)ring
1097 (214;77)
1078 (2;23)
d (CH)ring þ d (O8H17
d (CH3) þ d (CH)chain
r (CH3) þ g (CH)c1hain
d (CH) þ r (CH3)
g (CH)chain
)
998
950
940
920
1026 (38;12)
977 (58;131)
934 (23;0)
1026 (0;22)
950
978 (40;10)
940
932 (17;82)
920
919 (29;10)
932 (65;32)
d (CH) þ r (CH3) þ g (CH)1chain þ d (CH)r1ing (as wag)

R. Calheiros et al. / Journal of Molecular Structure 692 (2004) 91–106
105
Table 6 (continued)
Experimental
Calculateda
3,4-OHMeNS 1
Approximate descriptionb
Raman
866
IR
867
3,4-OHMeNS 2
914 (51;6)
838 (34;2)
821 (10;10)
803 (5;15)
776 (11;13)
767 (8;1)
883 (2;1)
d (CH)ring (as. wag)
858
813
853 (25;7)
841 (49;4)
784 (22;11)
774 (28;9)
740 (4;20)
712 (6;1)
d (CCN) þ d (NO2) (sciss) þ r (CH3) þ d (CH)1ring (s wag)
d (CH)ring (s wag)
d (CH)ring (as wag)
d (CH)ring (s wag) þ n (CO) þ n (CC)
g (CC) þ d (CH)ring (s wag) þ n (CO)
d (NO2)wag
755
758
736
723
706
621
591
578
575
542
535
512
478
459
723
706
712 (1;31)
686 (2;1)
690 (3;25)
668 (1;3)
d (CH3) þ das (CCN) þ g (CC)
g (ring) þ d (CH3)
g (ring)
668 (12;1)
594 (19; 4)
575 (5;8)
590
576
573
596 (10;6)
572 (1;9)
ds (ring)
d (CC)
561 (3;20)
555 (23;6)
532
523 (59;2)
512 (11;12)
r (NO2) þ n (CN)
458 (3;20)
448 (59;2)
435 (34;14)
427 (19;3)
376 (1;15)
348 (1;0)
304 (4;0)
279 (0;2)
244 (10; 4)
239 (1;4)
225 (139;2)
189 (11;2)
163 (2;3)
99 (3;1)
464 (9;10)
449 (4;14)
425 (18;23)
414 (55;2)
376 (1;0)
346 (2;1)
301 (5;0)
291 (3;1)
269 (71;2)
245 (97;4)
222 (7;2)
175 (0;6)
167 (0;0)
97 (1;0)
g (O7H18) þ d (CCC)
g (O7H18) þ g (CCC)chain
g (O7H18) þ g (CCC)
g (CCC)
353
338
d (CH3)
g (CCC)ring þ d (CCN)
d (OH) þ d (COH)
252
d (CCC) þ d (CH3) þ d (O8H17
)
g (OH) þ t (CH3)1
2
t (CH3)1 þ g (O8H17
)
1
d (CH3) þ g (O8H17
)
t (CH3)
t (CH3)
t (CH3)
117
111
77
69 (0;3)
68 (0;3)
Skeletal modes
Skeletal modes
Skeletal modes
73
59 (3;1)
59 (1;1)
58
34 (1;3)
35 (1;3)
a
B3LYP/6-31G** level; wavenumbers above 400 cm21 are scaled by 0.9614 [25] (IR intensities in km mol21; Raman scattering activities in A amu21).
Atoms are numbered according to Fig. 1; the same atom numbering is applicable to all the compounds studied, irrespective of the type of atom. The indices
˚
b
1 and 2 refer to conformers 3,4-OHMeNS 1 and 3,4-OHMeNS 2; d and g stand for in-plane and out-of-plane deformations, respectively.
spectrum. Also, the signal at 1273 cm21, assigned to the NO2
symmetric stretching, is far more intense than in Raman (at
1266 cm21), as well as the features due to the NO2 scissoring
modes, between 850 and 900 cm21, which is in complete
accordance with the theoretical results (Table 6).
scaling according to Scott and Radom [25]), as well as
between these and data previously obtained by the
authors for the carboxylic compounds caffeic acid [34]
and THPPE [35]. Moreover, the present results are in
conformity with those reported for similar molecules,
namely some of the synthetic precursors of the
nitrostyrenes under study [29–33,39] and carboxylated
phenols [36–38].
The spectra did not reveal any changes upon aging of
the compounds, which were stored in the dark in order to
avoid decomposition due to oxidation and/or dimerisation
processes. This is contrary to previous observations in
analogous phenols containing a carboxylic function
instead of a nitro group, which were found to yield
different Raman and FTIR patterns upon aging (even in
the solid state) [36–38]. In turn, it was evident that
similar molecules give rise to rather distinct Raman
patterns—according to their small structural differences—
which allows them to be easily distinguished by this
spectroscopic technique.
4. Conclusions
A complete conformational analysis was carried out
for differently substituted b-nitrostyrenes, through Raman
spectroscopy coupled to ab initio methods. Several
conformers were calculated for b-nitrostyrene (NS), b-
methyl-b-nitrostyrene (MeNS), 3,4-dihydroxy-b-nitrostyr-
ene (3,4-OH-NS) and 3,4-dihydroxy-b-methyl-b-nitros-
tyrene (3,4-OH-MeNS), varying in the orientation of both
A good overall agreement was obtained between the
experimental and calculated frequency values (after

106
R. Calheiros et al. / Journal of Molecular Structure 692 (2004) 91–106
[2] R.S. Varma, K.P. Naicker, P.J. Liesen, Tetrahedron Lett. 39
(1998) 3977.
the pendant arm ring substituent and the phenolic
hydroxyl groups. The conformational preferences of
these compounds were found to be mainly determined
by electrostatic factors, as well as by the formation of
(C)H· · ·O and (O)H· · ·O intramolecular interactions.
Consequently, the calculated relative energies indicate a
clear preference for a planar geometry, i.e. for the
presence of a completely conjugated system, strongly
stabilised through p-electron delocalisation. The few
deviations from planarity were explained by the occur-
rence of strong steric hindrance effects in the planar
conformations. A quantitative potential-energy analysis of
several internal rotation processes within the molecules
under study was carried out.
[3] C.-F. Yao, W.C. Chen, Y.M. Lin, Tetrahedron Lett. 37 (1996) 6339.
[4] M. Schmidt, K. Eger, Pharmazie 51 (1996) 11.
[5] K. Bailey, D. Legault, Org. Magn. Res. 16 (1981) 47.
[6] L.R. Worthen, H.W. Bond, J. Pharm. Sci. 59 (1970) 1185.
[7] J.H. Kim, J.H. Kim, G.E. Lee, J.E. Lee, I.K. Chung, Mol. Pharmacol.
63 (2003) 1117.
[8] S. Kaap, I. Quentin, D. Tamiru, M. Shaheen, K. Eger, H.J. Steinfelder,
Biochem. Pharmacol. 65 (2003) 603.
[9] P. Groupy, A. Fleuriet, M.J. Amiota, J.J. Macheix, J. Agric. Food
Chem. 92 (1991) 39.
[10] M.A. Parker, D. Marona-Lewicka, D. Kurrasch, A.T. Shulgin, D.E.
Nichols, J. Med. Chem. 41 (1998) 1001.
[11] M.J. Frisch, et al., GAUSSIAN 98, Revision A.9, Gaussian Inc,
Pittsburgh PA, 1998.
[12] T.V. Russo, R.L. Martin, P.J. Hay, J. Phys. Chem. 99 (1995) 17085.
[13] A. Ignaczak, J.A.N.F. Gomes, Chem. Phys. Lett. 257 (1996) 609.
[14] F.A. Cotton, X. Feng, J. Am. Chem. Soc. 119 (1997) 7514.
[15] A. Ignaczak, J.A.N.F. Gomes, J. Electroanal. Chem. 420 (1997) 209.
[16] T. Wagener, G. Frenking, Inorg. Chem. 37 (1998) 1805.
[17] F.A. Cotton, X. Feng, J. Am. Chem. Soc. 120 (1998) 3387.
[18] C. Lee, W. Yang, R.G. Parr, Phys. Rev. B37 (1988) 785.
[19] B. Miehlich, A. Savin, H. Stoll, H. Preuss, Chem. Phys. Lett. 157
(1989) 200.
The results gathered along this work are in very good
accordance with the ones obtained in a previous study on the
analogous compounds 3-(3,4-dihydroxyphenyl)-2- -prope-
noic acid (caffeic acid) [34] and 3-(3,4,5-trihydroxyphenyl)-
2-propenoic acid (THPPE) [35].
This kind of conformational analysis based on both
spectroscopic and theoretical methods, yielding information
at the molecular level, is becoming more and more
important for the elucidation of the structure-activity
relationships ruling the properties of compounds of
biological interest, mainly when coupled to biochemical
activity assessment experiments. Evaluation assays on the
anticancer activity of phenolic derivatives—namely the
b-nitrostyrenes described in this work—are presently in
course in our laboratory [40], the knowledge of the
conformational characteristics of such systems being
essential for the interpretation of the biological results.
In fact, this type of structure-activity studies may help to
decide which structural features of a molecule give rise to its
activity, thus contributing for the design of compounds with
enhanced cytotoxic properties (e.g. new anticancer drugs).
[20] A. Becke, Phys. Rev. A38 (1988) 3098.
[21] A. Becke, J. Chem. Phys. 98 (1993) 5648.
[22] P.C. Hariharan, J.A. Pople, Theor. Chim. Acta 28 (1973) 213.
[23] M.M. Francl, W.J. Pietro, W.J. Hehre, J.S. Binkley, M.S. Gordon, D.J.
DeFrees, J.A. Pople, J. Chem. Phys. 77 (1982) 3654.
[24] C. Peng, P.Y. Ayala, H.B. Schlegel, M.J. Frisch, Comp. Chem. 17
(1996) 49.
[25] A.P. Scott, L. Radom, J. Phys. Chem. 100 (1996) 16502.
[26] L. Radom, W.J. Hehre, J.A. Pople, J. Am. Chem. Soc. 94 (1972) 2371.
[27] L.A.E. Batista de Carvalho, A.M. Amorim da Costa, J.J.C. Teixeira-
Dias, J. Mol. Struct. (THEOCHEM) 205 (1990) 327.
[28] G.R. Desiraju, T. Steiner, The weak hydrogen bond in structural
chemistry and biology, IUCr Monographs on Chystallography-9,
Oxford University Press, UK, 1999, and references therein.
´
´
[29] F.J. Ramırez, J.T. Lopez Navarrete, Vib. Spec. 4 (1993) 321.
[30] R. Hargitai, P.G. Szalay, G. Pongor, G. Fogarasi, J. Mol. Struct.
(THEOCHEM) 306 (1994) 293.
[31] Y. Haas, S. Kendler, E. Zingher, H. Zuckermann, S. Zilberg, J. Chem.
Phys. 103 (1995) 37.
Acknowledgements
[32] S.J. Greaves, W.W. Griffith, Spectrochim. Acta 47A (1991) 133.
[33] M. Gerhards, W. Perl, S. Schumm, U. Henrichs, C. Jacoby, K.
Kleinermanns, J. Chem. Phys. 104 (1996) 9362.
RC and MPM thank the Chemistry Department of the
University of Aveiro (in the person of Dr Helena Nogueira),
where the FT-Raman and FT-IR experiments were carried
out. FB and NM acknowledge FCT—Unit I and D n8
226/94, and Project POCTI/QCA III (co-financed by the
european community fund FEDER)—for financial support.
NM is grateful to FCT for a PhD fellowship (PRAXIS
XXI/BD/18520/98).
[34] E. Besien, M.P.M. Marques, J. Mol. Struct. (THEOCHEM) 625
(2003) 265.
[35] Fiuza, S.M., Gomes, C.A., Milhazes, N., Borges, F., Marques,
M.P.M., J. Molec. Struct., in press.
´ ´ ´
[36] S. Sanchez-Cortes, J.V. Garcıa-Ramos, Spectrochim. Acta A55
(1999) 2935.
´ ´
[37] S. Sanchez-Cortes, J.V. Garcıa-Ramos, Appl. Spectrosc. 54
´
(2000) 230.
´ ´
[38] S. Sanchez-Cortes, J.V. Garcıa-Ramos, J. Colloid Interf. Sci. 231
´
(2000) 98.
´
[39] R.E. Clavijo, R. Araya-Maturana, B.K. Cassels, B. Weiss-Lopez,
References
Spectrochim. Acta 50A (1994) 2105.
[40] C.A. Gomes, M.T. Gira˜o da Cruz, J.L. Andrade, N. Milhazes, F.
Borges, M.P.M. Marques, J. Med. Chem. 46 (2003) 5395.
[1] A.G.M. Barret, G.G. Graboski, Chem. Rev. 86 (1986) 751.