Theoretical and infrared studies on the conformational isomerism of trans-2-bromo-alkoxycyclohexanes

Article abstract of DOI:10.1016/j.saa.2011.06.023

The infrared spectra of trans-2-bromo-alkoxycyclohexanes (alcoxy = OMe, OEt, OⁱPr and O^tBu) were obtained for the neat liquid, and the C-Br stretching mode was quantitatively analyzed to give insight about the conformational isomeris

Full text of DOI:10.1016/j.saa.2011.06.023

Spectrochimica Acta Part A 81 (2011) 359–362
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Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Theoretical and infrared studies on the conformational isomerism of
trans-2-bromo-alkoxycyclohexanes
Josué M. Sillaa, Claudimar J. Duarteb, Matheus P. Freitasa,∗, Teodorico C. Ramalhoa,
Rodrigo A. Cormanichc, Francisco P. Santosc, Cláudio F. Tormenac, Roberto Rittnerc
a Department of Chemistry, Federal University of Lavras, CP 3037, 37200-000, Lavras, MG, Brazil
b Department of Chemistry, Federal University of São Carlos, CP 676, 13565-905, São Carlos, SP, Brazil
c Chemistry Institute, State University of Campinas, CP 6154, 13083-970, Campinas, SP, Brazil
a r t i c l e i n f o
a b s t r a c t
The infrared spectra of trans-2-bromo-alkoxycyclohexanes (alcoxy = OMe, OEt, OiPr and OtBu) were
obtained for the neat liquid, and the C–Br stretching mode was quantitatively analyzed to give insight
about the conformational isomerism of these compounds. Frequency calculations supported the band
assignments, and the relative band intensities suggest that the diaxial conformer is prevalent for the
methoxy and tert-butoxy derivatives (51 and 56%, respectively), while the diequatorial form is preponder-
ant for the ethoxy and isopropoxy derivatives (76 and 77%, respectively). Therefore, the size of the alkoxy
group plays a determinant role in determining the conformational preferences of the title compounds.
© 2011 Elsevier B.V. All rights reserved.
Article history:
Received 26 April 2011
Received in revised form 1 June 2011
Accepted 13 June 2011
Keywords:
trans-2-Bromo-alkoxycyclohexanes
Conformational analysis
Infrared spectroscopy
Steric effects
Alkoxy groups
1. Introduction
Theoretical calculations have been widely applied to support
and explain experimental observations, such as to help in assign-
Intramolecular hydrogen bond has shown to play a deter-
minant role in the conformational isomerism of trans-2-
bromocyclohexanol, both in the vapor phase as in solution of a
nonpolar solvent [1,2]. The replacement of the hydroxyl group
in trans-2-bromocyclohexanol by a methoxy group increases the
population of the diaxial conformer, since internal hydrogen
bond as a stabilizing force of the diequatorial form disappears
[2]. Abraham et al. [3] have studied the conformational iso-
merism of trans-2-fluorocyclohexanol and its methyl ether, and
they found that OH. . .F hydrogen bonding in the fluorohy-
drin governs its conformational isomerism, while the OMe. . .F
interaction does not occur. Therefore, the conformational iso-
merism of trans-2-bromo-alkoxycyclohexanes may be ruled by
classical steric and electrostatic effects, in addition to hyper-
conjugative interactions. However, conformer populations and
links with the size of the alkoxy groups have not been sys-
tematically analyzed by infrared and theoretical approaches yet.
Therefore, the study of the series methoxy, ethoxy, isopropoxy and
tert-butoxy groups in trans-2-bromo-alkoxycyclohexanes (Fig. 1) is
of interest.
ing infrared absorptions [4]. Infrared spectroscopy is useful for the
determination of conformational isomerism, e.g. by using the rela-
tive band intensities to obtain conformer populations. Despite the
problem of molar absorptivities (ε) [5–7], which may differ signifi-
cantly from one conformer to another and, in this case, conformer
populations cannot be estimated directly from the measurement of
band intensities without previous knowledge of ε, accurate quan-
tifications have been obtained, e.g. for 2-methoxycyclohexanone,
in which four conformers could be identified by analyzing the C
O
stretching mode, giving results in agreement with theoretical cal-
culations [8].
Thus, trans-2-bromo-alkoxycyclohexanes (alkoxy = methoxy,
ethoxy, isopropoxy and tert-butoxy) were synthesized, and their
infrared spectra were obtained for the neat liquid. The C–Br stretch-
ing vibration for each conformer was assigned with the aid of high
level theoretical calculations and conformer populations deter-
mined by direct measurement of band intensities.
2. Experimental
2.1. Syntheses
The
trans-2-bromo-alkoxycyclohexanes
were
prepared
∗
by the reaction of cyclohexene using the N,N-dibromo-
toluenesulfonamide (TsNBr2) as the bromine source, and the
Corresponding author. Tel.: +55 35 3829 1891; fax: +55 35 3829 1271.
E-mail address: matheus@dqi.ufla.br (M.P. Freitas).
1386-1425/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.saa.2011.06.023

360
J.M. Silla et al. / Spectrochimica Acta Part A 81 (2011) 359–362
β
R
O
α
α
β
O
R
Scheme 1. Synthesis of the trans-2-bromo-alkoxycyclohexanes studied. R = Me, Et,
Br
iPr, tBu.
Br
R = Me, Et, iPr, and tBu
2.3. Theoretical calculations
Fig. 1. Conformational equilibrium of trans-2-bromo-alkoxycyclohexanes.
Stable conformers were identified by locating the energy min-
ima in the 2D (for methoxy and t-butoxy derivatives) or 3D (for
ethoxy and isopropoxy derivatives) potential energy surfaces, built
by means of semi-empirical AM1 calculations. Each minimum was
subsequently optimized at the B3LYP/aug-cc-pVDZ level and the
frequency calculations carried out at this same level. All calcula-
tions were performed using the Gaussian 03W program [10].
corresponding alcohol (methanol, ethanol, isopropanol and tert-
butanol), according to the procedure described in the literature
(Scheme 1) [9].
The TsNBr2 (1.2 mmol) was added to a solution of ciclohexene
(1.1 mmol) in 5 mL of the corresponding alcohol at room tempera-
ture. The TsNBr2 color disappears immediately. After the complete
reaction (ca. 10 min), about 200 mg of sodium thiosulfate was added
and the reaction mixture was stirred by 20 min. Thus, the reac-
tion mixture was taken up in ether, washed with brine, dried with
sodium sulfate and concentrated. The pure products were obtained
by carrying out purification with flash chromatography on silica gel
(230–400 mesh) using petroleum ether-EtOAc (5%) as eluent.
3. Results and discussion
The infrared spectra for the neat liquid of trans-2-bromo-
alkoxycyclohexanes (Fig. 2) were analyzed in the C–Br stretching
range (ca. 620–710 cm−1), which is free from strong superposition
of interfering bands. Three bands are observed in this region, being
the one centered by 670 cm−1 as due to CH2 rocking and some
contribution of C-O-C bending in the diaxial conformation, accord-
ing to DFT frequency calculations. Therefore, only the two other
bands of this region are referred to the ꢀC–Br mode and will be used
in this study to analyze the conformational isomerism of the title
compounds.
According to the calculations, several conformers are origi-
nated by the rotation of the H–C–O–C (˛) and C–O–C–C/H (ˇ)
(for ethoxy and isopropoxy derivatives) torsional angles, while the
tert-butoxy derivative shows only two stable conformers (Table 1).
The diaxial conformers exhibit C–Br stretching frequencies values
smaller than the diequatorial conformers, as a general rule. Also, the
2.2. Infrared measurements
Infrared spectra were obtained from a FTIR Digilab Excalibur
FTS 3000, using an ATR apparatus, and 32 scans with resolution
of 2 cm−1. Bands deconvolution was performed using Lorentzian
functions. The conformational isomerism between diaxial and
diequatorial forms was determined by measuring the relative band
intensities of each conformation (assignment of conformer fre-
quencies was based on frequency calculations).
0.24
0.60
OEt derivative
OMe derivative
0.55
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.20
0.16
0.12
0.08
0.04
0.00
620 630 640 650 660 670 680 690 700 710
640
650
660
670
680
690
700
Wavenumber (cm-1
)
Wavenumber (cm-1
)
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.44
0.40
0.36
0.32
0.28
0.24
i Pr derivative
O
t Bu derivative
O
630 640 650 660 670 680 690 700 710
Wavenumber (cm -1
620 630 640 650 660 670 680 690 700
-1
)
Wavenumber (cm
)
Fig. 2. Deconvoluted infrared spectra of trans-2-bromo-alkoxycyclohexanes (neat liquid) in the C–Br stretching region.

J.M. Silla et al. / Spectrochimica Acta Part A 81 (2011) 359–362
361
Table 1
Relative energies (Erel in kcal mol−1, and conformer percentages in parenthesis) for conformers 1–9 at the isolated state (B3LYP/aug-cc-pVDZ), dipole moments (ꢁ, in
debye), geometrical parameters (dihedral angles, in degrees), and experimental and calculated frequencies (cm−1) for the C–Br stretching vibration (calculated intensities,
in km mol−1, and experimental relative intensities, in %, given in parenthesis).
OR
Parameter
Diaxial
Diequatorial
1
2
3
4
5
6
7
8
9
OMe
Erel
ꢁ
0.5 (24)
1.7
6.6 (0)
2.9
0.7 (18)
2.2
2.5 (1)
3.2
0 (57)
3.3
˛
32.8
208.3
651 (32)
315.8
646 (26)
171.8
324.7
684 (34)
H–C–O–C
ꢀC–Br calc.
ꢀC–Br exp.b
Erel
638 (35)
642 (51)
2.0 (2)
2.0
685 (32)
693 (49)
2.6 (1)
3.3
OEt
1.7 (3)
1.9
0.5 (21)
1.9
9.2 (0)
3.0
0.7 (15)
2.3
1.6 (3)
3.1
0 (50)
3.1
1.3 (6)
2.7
ꢁ
˛
1.2
76.1
633 (35)
647 (24)
3.1 (0)
2.3
25.5
276.5
634 (38)
31.7
181.8
641 (33)
195.0
260.0
652 (32)
318.1
173.3
646 (24)
173.6
182.6
686 (30)
692 (76)
0 (48)
2.6
327.4
86.0
685 (33)
329.6
178.0
687 (33)
359.4
282.5
685 (34)
H–C–O–C
ˇC–O–C–C
ꢀC–Br calc.
ꢀC–Br exp.b
Erel
OiPr
0.5 (21)
2.0
0.9 (10)
2.3
0.5 (21)
3.1
3.7 (0)
2.9
ꢁ
˛
4.2
27.9
37.7
639 (31)
331.1
322.7
638 (25)
0.8
42.7
683 (33)
693 (77)
0.8 (21)
2.8
326.4
323.4
685 (32)
338.3
181.7
687 (33)
H–C–O–C
ˇC–O–C–H
ꢀC–Br calc.
ꢀC–Br exp.b
Erel
179.2
626 (33)
644 (23)
0 (79)
2.3
OtBua
ꢁ
˛
4.4
339.8
H–C–O–C
ꢀC–Br calc.
ꢀC–Br exp.b
623 (27)
627 (56)
688 (32)
693 (44)
a
Although two minima for each of the diaxial and diequatorial conformers of trans-2-bromo-tert-butoxycyclohexane have been identified in PES, only the exceedingly
more stable forms converged to stable structures at the B3LYP/aug-cc-pVDZ level using the available means.
b
The experimental frequencies are an average of the conformer frequencies pertaining to the diaxial or diequatorial forms.
calculated frequencies for diaxial conformers are close to each
other, as well as for the diequatorial conformers, giving rise to
slightly broad bands for diaxial and diequatorial forms in the exper-
imental spectra. Moreover, the calculated band intensities do not
differ substantially from one conformer to another, suggesting that
the problem of molar absorptivity in quantifying the conformer
populations by the direct measurement of relative band intensities
must not be significant.
of Table 1 for the isolated state, especially because of the lack of
important intermolecular interactions, such as hydrogen bonding,
and also due to the modest difference in polarity between diaxial
and diequatorial conformers (significant difference between dipole
moments of diaxial and diequatorial forms would mean strong
dependence of conformer populations with medium). Therefore,
the conformers with low calculated energies in Table 1 are sup-
posed to be the determinant ones for the appearance of infrared
absorptions.
Conformers with higher energies should be present in negli-
gible amounts in the neat liquid, and such energies are expected
to exhibit some parallelism with the calculated relative energies
Two bands centered at 642 and 693 cm−1 for trans-2-bromo-
methoxycyclohexane are of similar intensities (Fig. 2), indicating no
Fig. 3. Preferred conformations for the trans-2-bromo-alkoxycyclohexanes.

362
J.M. Silla et al. / Spectrochimica Acta Part A 81 (2011) 359–362
significant prevalence of a given conformation. In fact, conformers
1, 3 and 7 (Fig. 3) are the main contributors for the conformational
isomerism between diaxial (1 and 3) and diequatorial (7) forms for
this compound (see calculated relative energies in Table 1). Pop-
ulation of the diequatorial conformer increases by increasing the
alkoxy chain, giving ethoxy and isopropoxy derivatives (76 and
77% of diequatorial conformer, respectively). These results indi-
cate that syn-1,3-diaxial repulsions are more destabilizing than the
steric hindrance between bromine and the alkoxy groups. How-
ever, the figure changes for the tert-butoxy derivative, in which the
diaxial conformer is more stable than the diequatorial one and is
populated by 56% in the equilibrium. Opposite to ethoxy and iso-
propoxy derivatives, which may direct the alkoxy group far from
the bromine atom in the diequatorial conformer (e.g. conformers 8
and 6 (Fig. 3) of the ethoxy and isopropoxy derivatives, respec-
tively), the tert-butoxy compound cannot avoid the interaction
between bromine and methyl groups in the diequatorial conformer,
even with the ˛ dihedral angle making the O–C(CH3)3 bond being
directed in the opposite side in relation to the bromine atom,
since in the diaxial conformation, the t-butoxy group is completely
pointed back toward the cyclohexane ring.
and RR), and FAPEMIG and FAPESP for the studentships (to JMS,
RAC and FPS).
References
[1] C.J. Duarte, M.P. Freitas, J. Mol. Struct. 930 (2009) 135.
[2] M.P. Freitas, C.F. Tormena, R. Rittner, R.J. Abraham, J. Phys. Org. Chem. 16 (2003)
27.
[3] R.J. Abraham, T.A.D. Smith, W.A. Thomas, J. Chem. Soc., Perkin Trans. 2 (1996)
1949.
[4] A. Kovács, V. Izvekov, G. Keresztury, C.J. Nielsen, P. Klæboe, Chem. Phys. 335
(2007) 205.
[5] H. Bodot, D.D. Dicko, Y. Gounelle, Bull. Soc. Chim. Fr. (1967) 870.
[6] M.P. Freitas, C.F. Tormena, R. Rittner, R.J. Abraham, Spectrochim. Acta A 59
(2003) 1783.
[7] J.V. Coelho, M.P. Freitas, T.C. Ramalho, C.R. Martins, M. Bitencourt, R.A. Cor-
manich, C.F. Tormena, R. Rittner, Chem. Phys. Lett. 494 (2010) 26.
[8] M.P. Freitas, C.F. Tormena, R. Rittner, Spectrochim. Acta A 59 (2003) 1177.
[9] P. Pukhan, P. Chakraborty, D. Kataki, J. Org. Chem. 71 (2006) 7533.
[10] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheese-
man, 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. Strat-
mann, 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. Ste-
fanov, 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. John-
son, W. Chen, M.W. Wong, C. Gonzalez, J.A. Pople, Gaussian 03, Revision D.02,
Gaussian, Pittsburgh, 2004.
Acknowledgements
Authors thank FAPEMIG and FAPESP for the financial support of
this research, as well as CNPq for the fellowships (to MPF, TCR, CFT