The 1,3-diaxial dibromo interaction

Article abstract of DOI:10.1071/CH05043

The non-bonding interaction between two bromine atoms sited 1,3-diaxially on a simple cyclohexane ring is explored by X-ray crystallography. The ring is distorted to allow the bromine atoms an interatomic distance of 3.54 A. CSIRO 2005.

Full text of DOI:10.1071/CH05043

Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2005, 58, 535–538
The 1,3-Diaxial Dibromo Interaction
Paul V. Bernhardt,A Raymond M. Carman,A,B and Tri T. LeA
A Department of Chemistry, University of Queensland, Brisbane QLD 4072, Australia.
B Corresponding author. Email: carman@chemistry.uq.edu.au
The non-bonding interaction between two bromine atoms sited 1,3-diaxially on a simple cyclohexane ring is explored
by X-ray crystallography. The ring is distorted to allow the bromine atoms an interatomic distance of 3.54 Å.
Manuscript received: 9 February 2005.
Final version: 13 April 2005.
Me
Introduction
Br
1
O
Me
1
Br
2
The interatomic distance between two non-bonded atoms
situated 1,3-diaxially on an undistorted cyclohexane ring is
1.78 Å.The distance between the two bonded atoms in molec-
ular bromine is 2.29 Å. Therefore, considerable repulsion
must occur between two non-bonded bromine atoms placed
1,3-diaxially on a cyclohexane system. A search of the X-ray
literature did not provide any simple 1,3-diaxial dibromide
cyclohexane structures, but a 1,3-diaxial interaction has been
reported[1] for compound 1. However, the interaction in com-
pound 1 is complicated by both a geminal dibromide and the
anomericeffectsofthespiro-1,3-dioxaneappendage.Wenow
report an examination of the terpinolene tetrabromide 2.
Me
4
2
H
O
Ph
Me
Me
8
3
Br
4
Br
Br
8
Br
Br
1
2
3
Me
Br
Br
Br
Br
Me
Me
Me
Me
Br
H
Br
4
5
Br
Br
BrϪ
Br
Me
Me
Me
Me
H
H
Me
Me
Brϩ
Results and Discussion
Br
Br
Br
2
The bromination of terpinolene 3 was first reported by Otto
Wallach[2] in 1885 when he prepared a crystalline tetrabro-
mide and noticed its instability even at room temperature.
Later workers[3–6] observed two forms of terpinolene tetra-
bromide. The second, more stable form was obtained either
by recrystallizing or melting the unstable form. Interest-
ingly, both these forms have had cell dimensions previously
examined by crystallographers.[3,7]
Me
Br
Br
Br
Br
Br
Me
Me
Me
Ring
flip
H
Me
Me
H
Br
Br
Br
ent-5
Scheme 1.
Through NMR spectroscopic examination Venzke[8]
showedthattheunstableisomerhadexpectedstructure2.This
is formed by initial addition of bromine to the more electron-
rich 4,8-double bond of terpinolene 3 to provide dibromide
4 followed by trans-diaxial addition of bromine to the 1,2-
double bond. The stable isomer has structure 5, in which Br1
and Br2 are equatorial.
In principal, the rearrangement of 2 to give 5 could pro-
ceed by a Barton–Winstein rearrangement either about the
C1 C2 bond and involve Br1 and Br2 or about the C4 C8
bond and involve Br4 and Br8. Venzke[8] showed by radio-
active bromide labelling that the rearrangement actually
occurs about Br4 and Br8 with concomitant ring-flip to avoid
the large bromoisopropyl group becoming axial (Scheme 1).
At that time it was not possible to determine whether it
was Br4 that attacked C8 while Br8 departed (as shown
in Scheme 1) or whether the alternative pathway occurred,
namely that Br8 attacked C4 while Br4 departed.
The rearrangement about Br4 and Br8 (Scheme 1), as
opposed to one that might occur about Br1 and Br2, provides
the enantiomer of 5 (ent-5). Since terpinolene 3 is achiral,
most of the work on these compounds has been carried out
on racemic 2, and thereby it has not been possible to exam-
ine the chirality of 5. However, Venzke[9] later synthesized
chiral isomer 2 and showed that ent-5 is indeed formed after
rearrangement.
The instability of isomer 2 is undoubtedly the result of
1,3-diaxial repulsion of the two bromine atoms sited at C2
© CSIRO 2005
10.1071/CH05043
0004-9425/05/070535

536
P. V. Bernhardt, R. M. Carman and T. T. Le
Br8
C8
Br8
Br1
C7
C9
C9
C5
C8
C5
C6
C6
C1
C1
C7
C4
C4
C10
Br1
C10
C3
C2
C3
C2
Br4
Br2
Br4
Fig. 3. ORTEP drawing of the diequatorial tetrabromide 5 (30%
ellipsoids).
Br2
Fig. 1. ORTEP drawing of the diaxial tetrabromide 2 (30% ellipsoids).
Br8
C9
C5
C6
C8
C4
C1
C7
C10
C3
C2
Br4
Fig. 4. ORTEP drawing of dibromide 4 (30% ellipsoids).
representation illustrated in Fig. 2. The separation between
Br1 and Br8 (4.06 Å) is clearly in excess of the sum of their
van der Waals radii.
Fig. 2. Space-filling portrayal of compound 2, viewed with C3 in the
centre. The isopropyl methyl groups on the left are eclipsed. The van der
Waals radii used in generating the picture were C 1.70, H 1.20, and Br
1.85 Å. The image was created with ORTEP3 and rendered with PovRay
version 3.5.
A consequence of this diaxial Br· · ·Br repulsion is that Br4
is pushed towards C8 (Br4· · ·C8 2.84 Å) and Br8 is some-
what further from C4 (2.88 Å). Therefore, we speculate that
it is probably attack by Br4 of C8 which initiates the rear-
rangement to give structure 5 (Scheme 1) rather than attack
of Br8 on C4. These distances are reproduced by molecu-
lar mechanics calculations using PC Model 8.5 (Br2· · ·Br4
3.49 Å, Br4· · ·C8 2.91 Å, and Br8· · ·C4 2.97 Å).
and C4. This interaction cannot be relieved by a simple ring-
flip as this would then place the larger bromoisopropyl group
in an extremely unfavourable axial environment. In order to
examinetheseeffectstheX-raycrystalstructureofcompound
2 has been determined at low temperature (Fig. 1).
In relation to previous literature, when transformed to
the variant space group P21/a (a 15.423, b 9.915, c 9.477 Å,
β 113.93◦), the cell dimensions of compound 2 are consistent
with the optical measurements taken on a crystalline sample
of ‘compound A’ reported by Henry and Paget,[3] and earlier
still (before the discovery of X-rays!) by Hintze.[7]
The cis-diaxial atoms Br2 and Br4 are separated by a dis-
tance of 3.54 Å and the cyclohexane chair is distorted to
compensate for the closeness of this non-bonded repulsion
(the van der Waals radius of Br is 1.85 Å). For compari-
son, the C2· · ·C4 separation is 2.63 Å. The distortion of the
cyclohexane ring is most evident upon inspection of the dihe-
dral angles (C1 C2 C3 C4 39.6◦, C2 C3 C4 C5 36.4◦,
and C3 C4 C5 C6 41.5◦). Furthermore, the distortion is
localized around the two diaxial Br atoms as shown by the
fact that the dihedral angles for C4 C5 C6 C1 (52.2◦) and
C5 C6 C1 C2 (53.6◦) more closely approach the ideal
60◦ of an undistorted ring. The C2 Br2 and C4 Br4 vec-
tors are tilted by approximately 26◦ relative to each other,
which is consistent with the reported[1] angle (approx. 28◦)
in spiro compound 1, but unlike the parallel nature of the
two axial bonds in an undistorted chair. The abuttal of Br2
and Br4 in structure 2 is clearly depicted in the space-filling
The X-ray crystal structure of the isomeric diequato-
rial tetrabromide 5 (Fig. 3) reveals a relatively undisturbed
cyclohexyl ring.The greatest distortions are C2 C3 C4 C5
(44.9◦) and C3 C4 C5 C6 (44.3◦), with all the other dihe-
dral angles being within 7◦ of their ideal value. Nevertheless,
the Br1· · ·Br2 separation is relatively short (3.48 Å), even
more so than the Br2· · ·Br4 distance seen in the structure of
compound 2. However, in compound 5 the cyclohexyl ring
is less able to distort in order to relieve this 1,2-interaction.
Dibromide 4 (Fig. 4) has no Br· · ·Br contacts and the only
distortion of the ring arises from the C1 C2 double bond as
expected for a cyclohexene ring system.

The 1,3-Diaxial Dibromo Interaction
537
Molecular mechanics (MM3) predicts a free energy differ-
ence of 10.0 kJ mol−1 between isomers 2 and 5, and suggests
that an equilibrium mixture of the two at 27◦C might con-
tain approximately 1.7% of unstable isomer 2. On the other
hand, MMX software predicts an energy difference of only
7.0 kJ mol−1, in which case 5.7% of isomer 2 would exist
in an equilibrated mixture. NMR spectroscopic examination
of pure compound 2 in CDCl3 showed the rapid formation
of isomer 5 (H2eq (dt) of compound 2 at δ 4.81 equili-
brating with H2ax (dd) of isomer 5 at δ 4.91). After one
hour, as well as three, six, and fourteen days (about 25◦C
in CDCl3), the amounts of isomer 5 present were approxi-
mately 5, 58, 83, and 98%, respectively. After 30 days, the
mixture had totally rearranged to give isomer 5 with unde-
tectable (<0.5%) amounts of isomer 2 present. Although, as
previously observed[8] this is not a true equilibrium because
olefinic decomposition products are also slowly formed, it
does suggest an energy difference of >13 kJ mol−1 between
the two isomers.
The steric interaction of the two bromines at C2 and C4
in compound 2 might be expected to provide a γ-effect upon
the chemical shifts of the two relevant carbon atoms, thereby
causing them to be more electronically shielded and moved
to a higher field in the NMR spectrum. A similar γ-effect
might be expected for C6. This is indeed true as the shifts
of C2, C4, and C6 (δ 55.0, 73.4, and 36.6, respectively, in
compound 2) move to a lower field (δ 60.8, 79.2, and 40.7,
respectively) upon relief of this interaction in compound 5.
73.4 (C4), 69.0 (C1), 55.0 (C2), 40.2 (C3), 36.6 (C5 and C6), 33.7 (C7),
31.2 and 30.4 (C9 and C10).
Dibromide 4
Terpinolene 3 (0.85 g) in ethanol (1.0 mL) and diethyl ether (5.0 mL)
at 0◦C was treated dropwise with bromine (1.0 g) in cold diethyl
ether (3.0 mL). The diethyl ether was then removed at below room
temperature and the resultant solid was collected by filtration and
washed with ice-cold ethanol. The product was recrystallized from ace-
tone (−18◦C) to provide plates of ( )-4,8-dibromo-p-menth-1-ene 4,
mp 69◦C (lit.[10,11] 69◦C), with a 1H NMR spectrum as previously
reported[11] and characterized by a resonance at δ 5.30 (br m, H2).
Tetrabromide 5
Isomer 2 was boiled in ethanol (10 min), the solvent was removed,
and the resultant solid was recrystallized from acetone (−18◦C) to
provide plates of ( )-(1RS,2RS,4SR)-1,2,4,8-tetrabromo-p-menthane 5,
mp 122◦C (lit.[3,8] 121–122◦C).∗ δH 4.91 (dd, H2ax), 2.89 (ddd, H6ax),
2.84 (dd, H3ax), 2.67 (ddd, H3eq), 2.54 (ddd, H6eq), 2.44 (br ddd, H5ax),
2.02 (partly obscured m, H5eq), 1.99 and 1.97 (two Me s, H9 and H10),
1.87 (Me s, H7), consistent with that reported;[8] with J2ax,3ax 12.0,
J2ax,3eq 4.6, J3ax,3eq −15.1, J3eq,5eq 2.9, J5ax,5eq ≈ −15, J5ax,6ax ≈ 13.4,
J5ax,6eq 4.0, J5eq,6ax 4.1, J5eq,6eq 2.9, J6ax,6eq −13.9 Hz. The spectrum
did not show any sign of isomer 2 (δ 4.81) at time zero or after two
months at 25◦C. δC 79.2 (C4), 73.2 (C8), 65.8 (C1), 60.8 (C2), 45.0
(C3), 40.7 (C6), 34.2 (C5), 31.1 and 30.9 (C9 and C10), 25.4 (C7).
Crystallography
Compound 2
C10H16Br4, M 455.87, T 150(2) K, monoclinic, space group P21/n,
a 9.477(1), b 9.915(3), c 14.461(3) Å, β 102.87(1)◦, V 1324.7(5) Å3,
Z 4, F(000) 864, Dc 2.286 g cm−3, µ 121.16 cm−1, 2336 unique data
(2θmax 50◦), R 0.0376 [for 1532 reflections with I > 2σ(I)], wR2 0.1015
(all data).
Experimental
1H and 13C NMR spectra were conducted in CDCl3 solutions at ambient
temperature and were recorded using both Bruker 400 and 500 MHz
spectrometers. Assignments were made using DEPT, HSQC, HMBC,
COSY, and double quantum filtered COSY pulse sequences. Correlation
experiments for compound 2 were further run at 10◦C for improved
stability of the compound.
Compound 4
C10H16Br2, M 296.05, T 150(2) K, monoclinic, space group P21/c,
a 5.929(2), b 10.608(3), c 17.65(1) Å, β 95.51(3)◦, V 1105.0(8) Å3, Z 4,
F(000) 584, Dc 1.780 g cm−3, µ 72.85 cm−1, 1926 unique data (2θmax
50◦, Rint 0.0632), R 0.0403 [for 1224 reflections with I > 2σ(I)], wR2
0.1055 (all data).
Tetrabromide 2
In a modification of the method of Briggs and Sutherland[10] and
Venzke,[8] terpinolene 3 (0.85 g) in ethanol (1.0 mL) and diethyl ether
(5.0 mL)at0◦Cwastreateddropwisewithbromine(2.0 g)incolddiethyl
ether (3.0 mL). The diethyl ether was then removed at below room tem-
perature and the resultant solid was collected by filtration and washed
with ice-cold ethanol. The crystals were stirred with a small volume of
acetone at room temperature to achieve a saturated solution. The liquid
was decanted off and cooled slowly to −18◦C to provide plates of ( )-
(1RS,2RS,4RS)-1,2,4,8-tetrabromo-p-menthane 2, mp 115◦C (lit.[3,8]
115–116◦C, 119◦C). δH (on a solution made up immediately before
running the spectrum) 4.81 (ddd, H2eq), 3.57 (very poorly resolved br
d, H3ax), 2.93 (very poorly resolved br t, H6ax), 2.67 (br d, H3eq), 2.43
(ddd, H5ax), 2.34 (br d, H6eq), 2.08, 2.03, 2.01 (three Me), 1.98 (partly
obscured dddd, H5eq), consistent with that reported;[8] with J2eq,3ax
2.0, J2eq,3eq 5.2, J2eq,6eq 2.0, J3ax,3eq ≈ −15, J5ax,5eq −15.0, J5ax,6ax
12.4, J5ax,6eq 3.5, J5eq,6ax ≈ 4, J6ax,6eq ≈ −15 Hz. The 1H NMR spec-
trum showed only trace amounts of isomer 5 (δ 4.91) at time zero, but
increasing amounts of isomer 5 were observed as the solution was stored
at room temperature.After 30 days, the spectrum showed approximately
98% of compound 5 and isomer 2 could not be detected. δC 74.4 (C8),
Compound 5
C10H16Br2, M 455.87, T 293(2) K, monoclinic, space group C2/c,
a 19.690(7), b 6.213(1), c 23.685(9) Å, β 109.63(3)◦, V 2729.1(15) Å3,
Z 8, F(000) 416, Dc 2.219 g cm−3, µ 117.62 cm−1, 2404 unique data
(2θmax 50◦, Rint 0.0524), R 0.0507 [for 1181 reflections with I > 2σ(I)],
wR2 0.1502 (all data).
Intensity data were collected on an Enraf–Nonius CAD4 four-
circle diffractometer using graphite monochromated MoKα radiation
(λ 0.71073 Å) in the ω–2θ scan mode. Data for compounds 2 and 4
were collected at 150 K with the aid of an Oxford Cryostream Cooler,
while compound 5 was measured at room temperature. Lattice dimen-
sions were determined by a least-squares fit of the setting parameters
of 25 independent reflections. Data reduction and empirical absorption
corrections (ψ-scans) were performed with the WINGX package.[12]
Structures were solved by direct methods with SHELXS and refined by
full matrix least-squares analysis with SHELXL97.[13] All non-H atoms
were refined with anisotropic thermal parameters, and H-atoms were
constrained at estimated positions using a riding model. The atomic
nomenclature defined in Figs 1, 3, and 4 is drawn with ORTEP3.[14]
The space-filling diagram (Fig. 2) was produced with ORTEP3 and
∗Despite reports[3,8] that isomers 2 and 5 give a large mixed melting point depression, the two isomers interconvert at their melting point and thus the melting
points are dependent upon the rate of heating. We do not consider that the melting point value provides a reliable means for distinguishing between these two
isomers.

538
P. V. Bernhardt, R. M. Carman and T. T. Le
rendered with PovRay version 3.5. Crystallographic data for the struc-
tural analysis have been deposited with the Cambridge Crystallographic
Data Centre (CCDC deposition numbers: 262356 for 2, 262357 for
4, and 262358 for 5). Copies of this information may be obtained
free of charge from the Director, CCDC, 12 Union Road, Cambridge,
CB2 1EZ, UK (fax +44 1223 336033; email deposit@ccdc.cam.ac.uk,
or http://www.ccdc.cam.ac.uk).
[2] O. Wallach, Liebigs Ann. 1885, 230, 262.
[3] J. A. Henry, H. Paget, J. Chem. Soc. 1931, 23.
[4] J. D. Briasco, J. Murray, J. Appl. Chem. 1952, 2, 187.
[5] W. R. Owen, M.Sc. Thesis 1955 (University of Queensland:
Brisbane).
[6] M. J. Gallagher, M.Sc. Thesis 1960 (University of Queensland:
Brisbane).
[7] C. Hintze, Z. Krystallogr. 1885, 10, 258.
[8] R. M. Carman, B. N. Venzke, Aust. J. Chem. 1971, 24, 1905.
[9] R. M. Carman, B. N. Venzke, Aust. J. Chem. 1974, 27, 383.
[10] L. H. Briggs, M. D. Sutherland, J. Org. Chem. 1942, 7, 397.
doi:10.1021/JO01199A001
[11] R. M. Carman, B. N. Venzke, Aust. J. Chem. 1971, 24, 665.
[12] L. J. Farrugia, J. Appl. Crystallogr. 1999, 32, 837. doi:10.1107/
S0021889899006020
[13] G. M. Sheldrick, SHELX97—Programs for Crystal Structure
Analysis (Release 97–2) 1998 (Universität Göttingen: Göttingen).
[14] L. J. Farrugia, J. Appl. Crystallogr. 1997, 30, 565. doi:10.1107/
S0021889897003117
Acknowledgments
R.M.C. thanks William Kitching and Sharon Chow for pro-
viding laboratory space and equipment, and Douglas Breck-
nell for assistance with molecular mechanics calculations.
References
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