(1S*,2S*,4S*,5S*)-Cyclohexane-1,2,4,5-tetrol monohydrate

Full text of DOI:10.1107/S0108270105011066

organic compounds
Acta Crystallographica Section C
Crystal Structure
silver benzoate/iodine (Prevost reaction; McCasland et al.,
954, 1963) gave only (I) or predominantly (I). The expected
1
Communications
formation of the isomeric meso tetrol, i.e. (1S*,2S*,4R*,5R*)-
cyclohexane-1,2,4,5-tetrol, either failed to occur or formed an
extremely minor alternative during the course of the reaction.
Although a number of synthetic routes towards (I) have
appeared in the literature, the single-crystal X-ray diffraction
analysis of (I), unlike toxocarol, has not been reported so
far. Against this background, we report here the crystal
structure of (I).
ISSN 0108-2701
(
1
1S*,2S*,4S*,5S*)-Cyclohexane-
,2,4,5-tetrol monohydrate
Goverdhan Mehta,* Saikat Sen and Siddharth Dey
Although the synthetic route adopted in this study yields (I)
in the racemic form, spontaneous resolution during crystal-
lization causes tetrol (I) to pack in the chiral space group C2
(Z = 2). Hence, the crystal structure reported in this
communication corresponds to any one of the enantiomers of
the title compound. Such a spontaneous resolution for a
different cyclohexanetetrol, (II) (also obtained as a racemic
modi®cation through synthesis), has been recently reported by
us (Mehta et al., 2005). It is well known that 90% of the
compounds that are capable of crystallizing in racemic or
chiral space groups prefer the former (Gavezzotti, 2002; Brock
et al., 1991). Therefore, the preference of the two racemic
cyclohexanetetrols, (I) and (II), to crystallize as a conglom-
erate of two enantiomeric forms is interesting and probably
the consequence of a kinetically favoured pathway.
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012,
Karnataka, India
Correspondence e-mail: gm@orgchem.iisc.ernet.in
Received 18 March 2005
Accepted 8 April 2005
Online 13 May 2005
In the title compound, C H O ÁH O, 1,4/2,5-cyclohexane-
6
12
4
2
tetrol and water molecules are seen to possess twofold
symmetry. All four hydroxyl groups of the tetrol participate in
extensive intermolecular OÐHÁ Á ÁO hydrogen bonding to
form molecular tapes propagating along the a axis. Transla-
tionally related tapes along the c axis are held together by four
coordinated water molecules.
The D -symmetric tetrol crystallizes as a monohydrate
2
Comment
(Fig. 1). The tetrol and water molecules exhibit twofold
symmetry, coincident with the crystal symmetry. The puck-
ering parameters (Cremer & Pople, 1975) for the cyclohexane
The title compound, (I), belongs to the class of only three
cyclohexanetetrol isomers which have been isolated from
nature to date (Maras et al., 1998). These are betitol (von
Lippmann et al., 1901), D-(+)-1,4/2,5-cyclohexanetetrol
Ê
Ê
ꢀ
ring [q = 0.031 (2) A, q = 0.556 (2) A, ' = 150 (4) , Q =
0
2
3
2
T
Ê
ꢀ
.557 (2) A and ꢀ = 3.4 (2) ] describe a slightly distorted chair
2
conformation. The total puckering amplitude Q is smaller
T
(
(
Ramanathan et al., 1966; Craigie et al., 1968) and toxocarol
Zeying & Mingzhe, 1987). Betitol was reported to be present
Ê
ꢀ
than that for an ideal chair (0.63 A). The ' value of 150
2
corresponds to a twisted-boat conformation. Therefore, the
cyclohexane ring is distorted from an ideal chair conformation
and is ¯attened at atom C2, allowing the C1ÐC2ÐC3 bond
in very small amounts in sugarbeet molasses. However, the
occurrence of betitol has never been con®rmed and the
structure remains uncertain (Anderson, 1972). Toxocarol,
isolated from a plant source (Toxocarpus himalensis Falc. Ex.
Hook. f.) was found to be 1,4/2,3-cyclohexanetetrol and its
structure, as determined by single-crystal X-ray crystal-
lography, has been reported (Zeying & Mingzhe, 1987).
ꢀ
angle to increase to 113.04 (14) , while the other internal ring
angles remain close to the tetrahedral values. The ¯attening of
the cyclohexane ring at C2 can be attributed to the non-
bonded 1,3-diaxial interaction between atom O1 and the H
atoms bonded to atoms C2(2 � x, y, 1 � z) and C3.
Tetrol (I) was ®rst isolated from the marine alga Mono-
chrysis lutheri and later from an alga of the genus Porphydium
(
Ramanathan et al., 1966; Craigie et al., 1968). The molecular
structure of (I) was deduced on the basis of its physical and
spectroscopic data, and its absolute con®guration was assigned
by comparison of the calculated and experimental circular
dichroism (CD) spectrum.
From a purely synthetic perspective, tetrol (I) is intriguing,
as it is obtained as the sole product in the acid-catalysed
hydrolysis of syn- or anti-cyclohexane diepoxide (Zelinsky &
Titowa, 1931; Craig et al., 1967). Direct hydroxylation of 1,4-
cyclohexadiene with SeO /H O (Maras et al., 1998) or with
Figure 1
A view of tetrol (I), showing the atom-numbering scheme. Displacement
ellipsoids are drawn at the 50% probability level and H atoms are shown
as small spheres of arbitrary radii. Unlabelled atoms are related to
labelled atoms by the symmetry code (2 � x, y, 1 � z).
2
2
2
o358 # 2005 International Union of Crystallography
DOI: 10.1107/S0108270105011066
Acta Cryst. (2005). C61, o358±o360

organic compounds
Ê
longest crystallographic axis, i.e. a = 10.675 A (Fig. 3). The
tapes are translated along the c axis and are held in space by
water molecules which are sandwiched between them.
Each water molecule is linked to four tetrol molecules via
OÐHÁ Á ÁO hydrogen bonds in a pseudo-tetrahedral coordi-
nation (Fig. 2). This supramolecular assembly involves the
equatorial hydroxyl groups (O2) acting as acceptors and the
axial hydroxyl groups (O1) acting as donors. The ±OH groups
in (I) maximize their hydrogen-bonding potential (O2Ð
H2OÁ Á ÁO1; Table 2) by connecting the tetrol molecules
Experimental
Although a number of synthetic routes towards (I) have been
reported in the literature, we found the following procedure parti-
cularly convenient as it avoids the use of any hazardous or expensive
chemicals. To a solution of m-chloroperbenzoic acid (70% purity,
3.173 g, 12.87 mmol) in dichloromethane (10 ml), cooled to 273 K,
was added 1,4-cyclohexadiene (0.500 g, 0.6 ml, 6.24 mmol). The
reaction was stirred at the above temperature for 8 h and then at
room temperature for 14 h. The excess peracid was decomposed with
further along the direction of the 2 axis. Therefore, a closer
1
analysis of the OÐHÁ Á ÁO hydrogen-bond connectivity among
the tetrol molecules reveals a helical OÐHÁ Á ÁO hydrogen-
bond motif, with the helix axis coinciding with the 2 axis at
1
1
4
1
3
1
(
, y, ) and ( , y, ) (Figs. 2 and 3).
2 4 2
To summarize, the supramolecular assembly of the title
compound can be described as molecular tapes along the
2
0% Na
epoxides with dichloromethane. The combined extracts were washed
with saturated NaHCO solution and then dried over anhydrous
Na SO . Evaporation of the solvent afforded a crude mixture
0.800 g) of syn- and anti-diepoxides, which was used directly for the
2 3
SO solution, followed by extraction of the mixture of
3
2
4
(
next step. The mixture of diepoxides was stirred with 10% aqueous
acetic acid (1 ml) at 325 K for 24 h. Complete evaporation of the
volatiles under reduced pressure and repeated washing of the residue
with dichloromethane gave (I) as a colourless solid (yield 0.740 g,
80%, over two steps). Suitable crystals of (I) were obtained by slow
evaporation of an ethanol solution.
Crystal data
�
3
C
M
6
H
12
O
4
ÁH
= 166.17
Monoclinic, C2
2
O
D
x
= 1.394 Mg m
r
Mo Kꢂ radiation
Cell parameters from 500
re¯ections
Ê
a = 10.675 (2) A
b = 7.3502 (15) A
Ê
c = 5.1968 (11) A
Ê
ꢀ
ꢀ = 3.4±27.2
ꢃ = 0.12 mm
T = 296 (2) K
� 1
ꢀ
ꢁ
= 103.877 (3)
Ê
3
V = 395.86 (14) A
Z = 2
Block, colourless
0.50 Â 0.45 Â 0.43 mm
Figure 2
The molecular packing of (I), viewed along the b axis. H atoms bonded to
C atoms have been omitted for clarity. Dotted lines indicate hydrogen
Data collection
1
bonds. Symbols of the 2 axis are shown for one unit cell, around which
Bruker SMART CCD area-detector
diffractometer
465 independent re¯ections
461 re¯ections with I > 2ꢄ(I)
the helical OÐHÁ Á ÁO hydrogen-bonding motif is formed.
'
and ! scans
Absorption correction: multi-scan
SADABS; Sheldrick, 1996)
min = 0.922, Tmax = 0.950
567 measured re¯ections
Rint = 0.022
ꢀ
ꢀ
max = 27.0
(
T
h = � 13 ! 13
k = � 8 ! 9
l = � 6 ! 6
1
Re®nement
2
2
2
2
Re®nement on F
2
o
w = 1/[ꢄ (F ) + (0.0529P)
2
R[F > 2ꢄ(F )] = 0.033
wR(F ) = 0.082
S = 1.17
+ 0.07P]
where P = (F
(Á/ꢄ)max < 0.001
2
2
o
2
c
+ 2F
)/3
Ê
� 3
4
5
65 re¯ections
8 parameters
Áꢅmax = 0.21 e A
Ê
� 3
Áꢅmin = � 0.30 e A
H atoms treated by a mixture of
independent and constrained
re®nement
Extinction correction: SHELXL97
(Sheldrick, 1997)
Extinction coef®cient: 0.52 (4)
Table 1
Selected geometric parameters ( ).
ꢀ
i
C3 ÐC3ÐC2
C1ÐC2ÐC3
C2ÐC1ÐC1
113.04 (14)
111.24 (11)
110.20 (10)
i
Figure 3
The molecular tapes, formed by the tetrol molecules of (I), propagating
along the a axis. H atoms bonded to C atoms, and the water molecules,
have been omitted for clarity. Dotted lines indicate hydrogen bonds. The
C1ÐC2ÐC3ÐO2
C1ÐC2ÐC3ÐC3
176.33 (14)
56.40 (19)
C3ÐC2ÐC1ÐO1
C3ÐC2ÐC1ÐC1
66.39 (16)
� 53.7 (2)
i
i
1
1
symbol of the 2
1
axis parallel to the b axis at ( , y, ) is shown.
Symmetry code: (i) 2 � x; y; 1 � z.
4
2
ꢁ
Acta Cryst. (2005). C61, o358±o360
Mehta et al.
C H O
6 12 4
ÁH O
2
o359

organic compounds
Table 2
Hydrogen-bond geometry (A, ).
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: OB1226). Services for accessing these data are
described at the back of the journal.
Ê
ꢀ
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
ii
O1ÐH1OÁ Á ÁO1W
0.82
0.82
0.81 (3)
1.96
1.95
1.92 (3)
2.777 (2)
2.756 (2)
2.724 (2)
176
169
172 (3)
iii
O2ÐH2OÁ Á ÁO1
References
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Ê
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The authors thank the DST, Government of India, for the
CCD facility at Bangalore. One of us (SD) thanks JNCASR
for the award of a Summer Research Fellowship.
ꢁ
o360 Mehta et al.
C H
6
12
O
4
ÁH
2
O
Acta Cryst. (2005). C61, o358±o360