On the4 JHH long-range coupling in 2-bromocyclohexanone: Conformational insights

Article abstract of DOI:10.1002/mrc.2385

2-Bromocyclohexanone is a model compound in which a ⁴J _H2,H6 coupling constant is observed, whereas the corresponding ⁴-4_H2,H4 is absent. The observed long-range coupling is not only a result of the known W-type

Full text of DOI:10.1002/mrc.2385

Note
Received: 9 June 2008
Revised: 6 August 2008
Accepted: 5 November 2008
Published online in Wiley Interscience: 17 December 2008
(www.interscience.com) DOI 10.1002/mrc.2385
On the 4JHH long-range coupling in
2-bromocyclohexanone: conformational
insights
a
a∗
b
´
Jakelyne V. Coelho, Matheus P. Freitas, Claudio F. Tormena
and Roberto Rittnerb
4
2-Bromocyclohexanone is a model compound in which a JH2,H6 coupling constant is observed, whereas the corresponding
4JH2,H4 is absent. The observed long-range coupling is not only a result of the known W-type coupling, in the axial conformation,
butalsobecauseofthelessusualdiaxial spin–spincouplingintheequatorialconformer.Thecarbonylgroupplaysadetermining
role in describing the coupling pathway, as concluded by natural bond orbital (NBO) analysis; although the σC2–H2 → σ∗
the W-type coupling, the strong σC2–H2 → π∗C=O and σC6–H6 → π∗C=O hyperconjugations in the equatorial conformer define an
enhancedcouplingpathwayfor4JH2,H6, despitetheinhibition ofthiscouplingbecauseof nO →σ∗C(O)–C interactionandthelarge
carbonyl angle. These findings provide the experimental evidence that orbital interactions contribute for the conformational
C1(O)–C6
and σC6–H6 → σ∗
interactions in the axial conformer contribute for transmitting the spin information associated with
C1(O)–C2
c
isomerism of 2-bromocyclohexanone. Copyright ꢀ 2008 John Wiley & Sons, Ltd.
Keywords: NMR; 4JHH; 2-bromocyclohexanone; carbonyl group; NBO
Introduction
Experimental and Computation
2-Bromocyclohexanone was prepared by brominating cyclohex-
anone with Br2 in ether. 1H NMR spectra were acquired on a Varian
GEMINI 300 spectrometer, operating at 300.07 MHz. Samples were
preparedassolutionsof20 mg ofsolutein0.6 mlofsolvent(CDCl3,
CD2Cl2, pyridine-d6, CD3CN and DMSO-d6), and the spectra were
recorded at 300 K. The variable temperature experiments were
carried out at 293, 273, 253, 233, and 213 K, from CD2Cl2 solutions.
1H NMR (300.07 MHz, CDCl3, 25 ◦C, TMS): δ (ppm) = 1.75 (m, 1H,
H4), 1.84 (m, 1H, H5ꢁ), 1.96 (m, 1H, H5), 2.03 (m, 1H, H4ꢁ), 2.25 (m,
1H, H3), 2.35 (m, 2H, H3ꢁ and H6), 2.98 (dddd, 1H, 4J(H,H) = 0.7 Hz,
2-Bromocyclohexanone undergoes conformational isomerization
between the axial and equatorial forms (Fig. 1).[1–8] The 2-position
hydrogen, free of interference in the 1H NMR spectrum, exhibits
three coupling constants, owing to its spin–spin interaction
4
with H-3, H-3ꢁ, and H-6.[1] The long-range JH2,H6 coupling is
expected to operate in the axial conformer, according to the W-
coupling pathway,[9] whilst the corresponding diaxial coupling
in the equatorial conformer is usually smaller or even not
observed.[10]
4
Long-range JH,H coupling constants were measured in rigid
2
3J(H,H) = 5.6 and 9.7 Hz, J(H,H) = 14.4 Hz; H6ꢁ), 4.45 (ddd, 1H,
tert-butylcyclohexanes,[11] with W-type coupling constants being
significantly larger than diaxial and equatorial–axial couplings.
4J(H,H) = 1.5 Hz, 3J(H,H) = 4.6 and 6.2 Hz).
Geometry optimizations were carried out at the MP2/aug-cc-
pVDZ level. Given the important role played by hyperconjugative
interactions in the Fermi contact (FC) transmission in long-range
couplings, hyperconjugative interactions were evaluated using
the natural bond orbital (NBO)[13] analyses as implemented in
the Gaussian03 program,[14] at the B3LYP/aug-cc-pVTZ level. DFT
4
However, JH2,H4 is not observed in 2-bromocyclohexanone, i.e.
only a through-carbonyl long-range coupling has been observed
in this compound for H2. The carbonyl group has shown to
3
play a driving role in the through-the-bridge JC,H couplings
3,4
(actually
J
couplings) in norbornanone, in which a σC3–C4
C,H
→ σ∗
interaction defines an additional coupling pathway
, but not for
C2=O
C4,H1
4
calculations of all four terms of JH2,H6 [FC; spin dipolar (SD);
3,4
3,4
for
J
J
; consequently, the former
C1,H4
paramagnetic spin orbit (PSO); and diamagnetic spin orbit (DSO)]
coupling constant was found to be significantly larger than
3,4
[12]
J
.
C1,H4
Since the conformational isomerism of 2-bromocyclohexanone
is expected to be governed by orbital interactions, especially
those involving the π∗
orbital, in addition to steric and
∗
Correspondence to: Matheus P. Freitas, Departamento de Química, Universi-
dade Federal de Lavras, Caixa Postal 3037, 37200-000 Lavras, MG, Brazil.
E-mail: matheus@ufla.br
C=O
electrostatic interactions, the investigation of the origins of the
4
a
DepartamentodeQuímica,UniversidadeFederaldeLavras,CP3037,37200-000
Lavras, MG, Brazil
through-carbonyl long-range JH2,H6 coupling must provide an
experimental insight about the hyperconjugation role in this
model system. To corroborate the 1H NMR findings, theoretical
approaches were applied to rationalize the results.
b
Department of Organic Chemistry, Chemistry Institute, State University of
Campinas, CP 6154, 13084-971 Campinas, SP, Brazil
c
Magn. Reson. Chem. 2009, 47, 348–351
www.soci.org
Copyright ꢀ 2008 John Wiley & Sons, Ltd.

4JrmHH long-range couplings in 2-bromocyclohexanone
reproduce the electronic density in the nuclear regions, since this
point is particularly important when calculating the FC term. For
O and Br, an aug-cc-pVDZ basis set was applied.
H5
H3
H4'
H5
H6'
Br
O
H6'
H4
H3
H5'
H6
Br
H4'
H3'
H4
H6
H2
H5'
H3'
H2
O
Results and Discussion
Figure 1. Conformers of 2-bromocyclohexanone.
2-Bromocyclohexanone experiences axial–equatorial isomeriza-
tion, andthiscanbedemonstratedbychangesinsuitablecoupling
constants, e.g.3JH2,H3, when varying solvents and temperature.
The calculated MP2/aug-cc-pVDZ energy difference (Eeq – Eax) be-
were carried out using the EPR-III basis set for C and H,[15] which
is of a triple-zeta quality and includes diffuse and polarization
functions. The s part of this basis set is enhanced to better
tween the two conformers in the isolated state is 2.1 kcal mol−1
which is in agreement with the experimental value; this energy
,
Table 1. Dependencies of coupling constants (Hz) with solvents and temperature (◦C) for 2-bromocyclohexanonea
Solvent
3JH2,H3
3JH2,H3
4JH2,H6
Temp.b
3JH2,H3
3JH2,H3
4JH2,H6
ꢁ
ꢁ
CDCl3
6.2
7.0
7.6
8.5
9.2
4.6
4.8
4.8
5.1
5.2
1.5
1.5
1.4
1.4
1.3
20
0
7.0
7.3
7.6
8.0
8.5
4.6
4.7
4.8
4.8
5.0
1.4
1.4
1.4
1.5
1.5
CD2Cl2
Pyridine-d6
CD3CN
–20
–40
–60
DMSO-d6
a Solvent dielectric constants: 4.8 (CDCl3), 9.0 (CD2Cl2), 12.4 (pyridine-d6), 37.5 (CD3CN), and 46.7 (DMSO-d6).
b Experiments with variable temperature were performed in CD2Cl2 solution.
F2
(ppm)
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
F1(ppm)
Figure 2. COSY spectrum of 2-bromocyclohexanone. There is no correlation between H-2 and H-4.
c
Magn. Reson. Chem. 2009, 47, 348–351
Copyright ꢀ 2008 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/mrc

J. V. Coelho et al.
difference decreases with increasing the medium polarity.[2] The
H2-C-C-H3 dihedral angle in the equatorial conformer is close to
180◦ and, according to the early work by Karplus,[16–18] the cor-
axial
H6
axial-H+
H6
axial-H+'
H
+
O
O
H2
O+
H6
H
3
responding JH2,H3 coupling constant is expected to be larger
3
H2
H2
than in the axial conformer (the calculated JH2,H3 coupling
constant corresponds to 3.6 and 14.4 Hz for the axial and equa-
torial conformers, respectively); thus, the average of this value
is dependent on conformational changes. The JH2,H3 coupling
Br
Br
Br
3
1.6 Hz
2.5 Hz
2.3 Hz
constants of Table 1 indicate that the conformational equilib-
rium is shifted toward the equatorial conformer on going from
less to more polar solvents, and from higher to lower tempera-
tures in CD2Cl2 solution. However, the long-range 4JH2,H6 coupling
constant varies negligibly when changing medium and temper-
ature conditions, indicating that the diaxial coupling and the
well-known W-type coupling are of similar magnitude. More-
equatorial
equatorial-H+
equatorial-H+'
H6
H2
H6
H2
H6
H2
4
H
Br
Br
Br
over, no JH2,H4 coupling is observed in 2-bromocyclohexanone,
+
O
O
O
+
as confirmed by COSY experiments (Fig. 2), suggesting that the
carbonyl group plays an important role in transmitting the spin
H
2.0 Hz
4.1 Hz
3.9 Hz
4
information along the coupling pathway. The JH2,H6 couplings
in cis−4 − t-butyl-2-bromocyclohexanone (4JH2,H6 = 1.2 Hz) and
4
Figure 3. Calculated long-range JH2,H6 coupling constants for 2-
bromocyclohexanone and for the protonated derivatives.
in trans-4-t-butyl-2-bromocyclohexanone (4JH2 ,H6
ꢁ
ꢁ = 1.7 Hz) cor-
roborate with results for 2-bromocyclohexanone. The advantage
of 4-t-butyl derivatives is related to their rigid structure; in this
case, the coupled hydrogen is fixed, which is favorable for the
transmission of the spin–spin coupling.
4
[19,20]
4
comparison with JH2,H4
.
Thus, why is the JH2,H6 coupling
observed for the equatorial conformer (actually, the calculated
value is slightly superior to the corresponding W coupling), while
4
The calculated JH2,H6 coupling constants for the axial and
4
the JH2,H4 W-coupling does not appear in the spectrum? Both
equatorial conformers (Fig. 3) are in excellent agreement with the
experimental values. Also, the calculated coupling constants were
found to be very similar in the two conformers, as previously
supposed. These calculated long-range coupling constants were
σC2–H2 and σC6–H6 bonding orbitals (which contain the H2 and H6
nuclei) strongly interact with the π∗
orbital in the equatorial
C=O
conformer, and this hyperconjugation defines the 4JH2,H6 coupling
pathway (Table 2). The weaker σC2–H2 → σ∗
and σC6–H6
4
found to be quite superior than JH2,H4, which are in fact not
C1(O)–C6
→ σ∗
hyperconjugative interactions contribute for the W
couplingintheaxialconformer(theseinteractionsareofsecondary
4
observed in the experimental spectrum (calculated JH2eq,H4eq
=
C1(O)–C2
4
1.1 Hz and JH2eq,H4ax = −0.8 Hz for the axial conformer, and
importance in the equatorial conformer). The σC2–H2 → σ∗
4JH2ax,H4ax = 0.4 Hz and JH2ax,H4eq = −0.1 Hz for the equatorial
4
C3–C4
and σC6–H6 → σ∗C4–C5 interactions, and corresponding reciprocal
4
conformer). JH2,H6 couplings can be described using the two
hyperconjugations, are substantially smaller in both conformers.
dihedral angles H2-C2-C1-C6 (ꢀ1) and C2-C1-C6-H6 (ꢀ2), but angles
defined by bonds along with the coupling pathway can also
dictate the actual coupling. When both dihedral angles are
antiperiplanar, such as in the W-type coupling pathway, electron
delocalization interactions from C2 –H2 and C6 –H6 increase the
Therefore, the π∗
orbital increases the efficiency of the H2-
C=O
C2-C1-C6-H6 coupling pathway to transmit the spin information
associated with the FC term in the equatorial conformer and,
consequently, the σC2–H2 → π∗
and σC6–H6 → π∗
C=O
C=O
interactions contribute to the observation of the averaged 4JH2,H6
4
[9]
FC term of JH2,H6 (according to the calculations, PSO and
DSO terms for this long-range coupling are comparable to FC,
but they cancel each other). However, this is not the case for
the equatorial conformer, because both calculated ꢀ1 and ꢀ2
dihedral angles correspond to 62◦. In addition, the carbonyl
angle [C2-C(O)-C6] in 2-bromocyclohexanone (calculated 115.8◦
and 112.5◦ for the axial and equatorial conformers, respectively)
coupling constant for 2-bromocyclohexanone. On the other hand,
electron delocalization interactions into the σ∗C2–H2 and σ∗
C6–H6
antibonding orbitals cause a decrease in the FC term of 4JH2,H6
.
[9]
To confirm that the π∗
orbital plays an important role for the
C=O
observation of 3JH2,H6, the electron acceptor ability of the π∗
C=O
orbital was enhanced by protonating the carbonyl oxygen; the
expected consequence is an increase of this coupling constant.
4
is larger than the tetrahedral angle, which reduces JH2,H6 in
Table 2. Important hyperconjugative interactions (kcal mol−1) obtained at the B3LYP/aug-cc-pVTZ level for 2-bromocyclohexanone
ꢁ
ꢁ
Interaction
Axial
Equatorial
Axial-H+
Equatorial-H+
Axial-H+
Equatorial-H+
σC2–H2 → π∗
–
–
4.8
5.2
2.3
2.2
–
0.7
1.0
5.3
5.5
2.4
2.2
8.8
0.8
8.0
9.0
–
0.5
0.9
5.5
5.4
2.5
2.1
0.7
8.8
8.5
8.9
–
σC6–H6 → π∗C1=O
σC2–H2 → σ∗C1=O
σC6–H6 → σ∗C1(O)–C6
σC2–H2 → σ∗C1(O)–C2
4.1
4.3
3.0
2.8
20.2
19.1
–
–
–
–
σC6–H6 → σ∗C3–C4
–
–
–
C4–C5
nO → σ∗
22.0
19.9
8.9
0.7
0.8
8.4
nO → σ∗C1–C2
C1–C6
c
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Copyright ꢀ 2008 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2009, 47, 348–351

4JrmHH long-range couplings in 2-bromocyclohexanone
Moreover, in 2-bromocyclohexanone, the nO → σ∗
and nO
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of these interactions takes place, yielding an increase in the 4JH2,H6
coupling (Fig. 3). For the protonated systems, the 4JH2,H6 coupling
constant is significantly larger in the equatorial conformer than
in the axial conformer, indicating that electron delocalizations
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jugative interaction in the equatorial conformer, and a secondary
σC–H → σ∗
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Acknowledgements
The authors are grateful to FAPEMIG (grant CEX 415/06) and
FAPESP (grants 06/03980-2, 05/59649-0 and 05/59571-0) for the
financialsupportofthiswork,andtoCNPqforfinancialsupportand
for fellowships (to MPF, CFT, and RR). CAPES is also acknowledged
for the studentship (to JVC).
G. A. Voth,
P. Salvador,
J. J. Dannenberg,
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c
Magn. Reson. Chem. 2009, 47, 348–351
Copyright ꢀ 2008 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/mrc