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

In the title compound, C₆H₁₂O₄·H₂O, 1,4/2,5-cyclo­hexane­tetrol and water mol­ecules are seen to possess twofold symmetry. All four hydrox­yl groups of the tetrol participate in extensive inter­molecular O-H...O hydrogen bonding to form mol­ecular tapes propagating along the a axis. Translationally related tapes along the c axis are held together by four coordinated water mol­ecules.

S1. Comment

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, (I), (Ramanathan et al., 1966; Craigie et al., 1968) and toxocarol (Zeying & Mingzhe, 1987). Betitol was reported to be present in very small amounts in sugarbeet molasses. However, the occurrence of betitol has never been confirmed 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 through single-crystal X-ray crystallography, has been reported (Zeying & Mingzhe, 1987).

Tetrol (I) was first isolated from the marine alga Monochrysis 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 configuration assigned by comparison of the calculated and experimental circular dichroism 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 SeO₂/H₂O₂ (Maras et al., 1998) or with silver benzoate/iodine (Prevost reaction; McCasland et al., 1954, 1963) gave only (I) or predominantly so. The expected 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. With this background, we report here the crystal structure of (I).

Although the synthetic route adopted in this study yields (I) in the racemic form, spontaneous resolution during crystallization 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 modification 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 conglomerate of two enantiomeric forms is interesting and probably the consequence of a kinetically favoured pathway.

The D₂-symmetric tetrol crystallizes as a monohydrate (Fig. 1). The tetrol and water molecules exhibit twofold symmetry, coincident with the crystal symmetry. The puckering parameters (Cremer & Pople, 1975) for the cyclohexane ring [q₂ = 0.031 (2) Å, q₃ = 0.556 (2) Å, ϕ₂ = 150 (4)°, Q_T = 0.557 (2) Å and θ₂ = 3.4 (2)°] describe a slightly distorted chair conformation. The total puckering amplitude Q_T is smaller than that for an ideal chair (0.63 Å). The ϕ₂ value of 150° corresponds to a twisted-boat conformation. Therefore, the cyclohexane ring is distorted from an ideal chair conformation and is flattened at atom C2, allowing the C1—C2—C3 bond angle to increase to 113.04 (14)° while the other internal ring angles remain close to the tetrahedral values. The flattening 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 [at (2 − x, y, 1 − z)] and C3.

Each water molecule is linked to four tetrol molecules via O—H···O hydrogen bonds in a pseudotetrahedral coordination (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 (O2—H2O···O1) by connecting the tetrol molecules further along the direction of the 2₁ axis. Therefore, a closer analysis of the O—H···O hydrogen-bond connectivity among the tetrol molecules reveals a helical O—H···O hydrogen-bond motif, with the helix axis coinciding with the 2₁ axis at (1/4, y, 1/2) and (3/4, y, 1/2) (Figs. 2 and 3).

To summarize, the supramolecular assembly of the title compound can be described as molecular tapes along the longest crystallographic axis, i.e. a = 10.675 Å (Fig. 3). The tapes are translated along the c axis and are held in space by water molecules which are sandwiched between them.

S2. Experimental

Although a number of synthetic routes towards (I) have been reported in the literature, we found the following procedure particularly 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 20% Na₂SO₃ solution, followed by extraction of the mixture of epoxides with dichloromethane. The combined extracts were washed with saturated NaHCO₃ solution and then dried over anhydrous Na₂SO₄. Evaporation of the solvent afforded the crude mixture (0.800 g) of syn- and anti-diepoxides, which was used directly for the 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.

S3. Refinement

Due to the absence of any significant anomalous scatterers (Z > Si), attempts to confirm the absolute structure by refinement of the Flack (1983) parameter led to an inconclusive value of −0.5 (1) (Flack & Bernardinelli, 2000). Therefore, the intensities of the Friedel pairs (289) were averaged prior to merging of data in C2 and the absolute configuration was assigned arbitrarily. The reported value of R_int corresponds to subsequent merging of equivalent reflections in this space group. All CH₂, CH and OH H atoms of the tetrol were placed in geometrically idealized positions and constrained to ride on their parent atoms, with C—H distances in the range 0.97–0.98 Å and U_iso(H) = 1.2U_eq(C), and O—H distances fixed at 0.82 Å and U_iso(H) = 1.5U_eq(O). The H atom of the water molecule was located in a difference Fourier map and its position was refined freely, along with an isotropic displacement parameter.

Computing details

Data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1998); data reduction: SAINT; program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and CAMERON (Watkin et al., 1993); software used to prepare material for publication: PLATON (Spek, 2003).

Figures

	Fig. 1. A view of tetrol (I), with 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 operator (2 − x, y, 1 − z).
	Fig. 2. The molecular packing of (I), veiwed along the b axis. H atoms bonded to C atoms have been omitted for clarity. Dotted lines indicate hydrogen bonds. Symbols of the 21 axis are shown for one unit cell, around which the helical O—H···O hydrogen-bonding motif is formed.
	Fig. 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 symbol of the 21 axis parallel to the b axis at (1/4, y, 1/2) is shown.

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

Crystal data

C6H12O4·H2O	F(000) = 180
Mr = 166.17	Dx = 1.394 Mg m^−3
Monoclinic, C2	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C 2y	Cell parameters from 500 reflections
a = 10.675 (2) Å	θ = 3.4–27.2°
b = 7.3502 (15) Å	µ = 0.12 mm^−1
c = 5.1968 (11) Å	T = 296 K
β = 103.877 (3)°	Block, colourless
V = 395.86 (14) Å^3	0.50 × 0.45 × 0.43 mm
Z = 2

Data collection

Bruker SMART CCD area-detector diffractometer	465 independent reflections
Radiation source: fine focus sealed tube	461 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.022
ϕ and ω scans	θmax = 27.0°, θmin = 3.4°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −13→13
Tmin = 0.922, Tmax = 0.950	k = −8→9
1567 measured reflections	l = −6→6

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.033	w = 1/[σ^2(Fo^2) + (0.0529P)^2 + 0.07P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.082	(Δ/σ)max < 0.001
S = 1.17	Δρmax = 0.21 e Å^−3
465 reflections	Δρmin = −0.30 e Å^−3
58 parameters	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
1 restraint	Extinction coefficient: 0.52 (4)
Primary atom site location: structure-invariant direct methods	Absolute structure: see text
Secondary atom site location: difference Fourier map

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	0.92576 (14)	0.0206 (3)	0.4646 (3)	0.0261 (4)
C2	0.87236 (16)	0.1937 (3)	0.3212 (3)	0.0281 (5)
C3	0.92668 (14)	0.3657 (3)	0.4719 (3)	0.0267 (4)
O1	0.88087 (11)	0.00866 (19)	0.7032 (3)	0.0323 (4)
O2	0.87963 (12)	0.52462 (19)	0.3210 (3)	0.0400 (5)
O1W	1.0000	0.7151 (3)	0.0000	0.0365 (5)
H1	0.8940	−0.0844	0.3514	0.031*
H2A	0.7792	0.1939	0.2936	0.034*
H2B	0.8921	0.1953	0.1485	0.034*
H3	0.9006	0.3696	0.6402	0.032*
H1O	0.9126	−0.0811	0.7880	0.048*
H2O	0.8013	0.5318	0.3018	0.060*
H1W	0.962 (2)	0.651 (4)	0.083 (5)	0.035 (6)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0229 (8)	0.0225 (8)	0.0347 (8)	−0.0012 (7)	0.0103 (6)	−0.0021 (7)
C2	0.0236 (8)	0.0280 (10)	0.0319 (8)	0.0001 (7)	0.0052 (6)	−0.0003 (7)
C3	0.0252 (9)	0.0223 (8)	0.0351 (9)	0.0020 (7)	0.0124 (6)	0.0038 (7)
O1	0.0292 (6)	0.0310 (7)	0.0407 (7)	0.0013 (6)	0.0163 (5)	0.0066 (6)
O2	0.0289 (7)	0.0300 (8)	0.0654 (10)	0.0061 (6)	0.0196 (6)	0.0170 (7)
O1W	0.0489 (11)	0.0262 (9)	0.0406 (10)	0.000	0.0229 (9)	0.000

Geometric parameters (Å, º)

C1—C1^i	1.539 (3)	C3—H3	0.9800
C1—H1	0.9800	O1—C1	1.435 (2)
C2—C1	1.515 (3)	O1—H1O	0.8200
C2—C3	1.526 (2)	O2—C3	1.429 (2)
C2—H2A	0.9700	O2—H2O	0.8200
C2—H2B	0.9700	O1W—H1W	0.81 (3)
C3—C3^i	1.522 (3)
C1—C2—C3	113.04 (14)	C3—C2—H2B	109.0
C1^i—C1—H1	109.3	C3^i—C3—H3	109.2
C1—C2—H2A	109.0	O1—C1—C2	108.19 (14)
C1—C2—H2B	109.0	O1—C1—C1^i	109.35 (16)
C1—O1—H1O	109.5	O1—C1—H1	109.3
C2—C1—C1^i	111.24 (11)	O2—C3—C3^i	108.37 (10)
C2—C1—H1	109.3	O2—C3—C2	110.79 (13)
C2—C3—H3	109.2	O2—C3—H3	109.2
C3^i—C3—C2	110.20 (10)	H2A—C2—H2B	107.8
C3—O2—H2O	109.5	H1W—O1W—H1W^ii	110 (3)
C3—C2—H2A	109.0
C1—C2—C3—O2	176.33 (14)	C3—C2—C1—O1	66.39 (16)
C1—C2—C3—C3^i	56.40 (19)	C3—C2—C1—C1^i	−53.7 (2)

Symmetry codes: (i) −x+2, y, −z+1; (ii) −x+2, y, −z.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1O···O1W^iii	0.82	1.96	2.777 (2)	176
O1—H1O···O1W^iv	0.82	1.96	2.777 (2)	176
O2—H2O···O1^v	0.82	1.95	2.756 (2)	169
O1W—H1W···O2	0.81 (3)	1.92 (3)	2.724 (2)	172 (3)

Symmetry codes: (iii) x, y−1, z+1; (iv) −x+2, y−1, −z+1; (v) −x+3/2, y+1/2, −z+1.