4,1',6'-Trichloro-4,1',6'-trideoxysucrose monohydrate

At 160 K, the gluco­pyran­osyl ring in 1,6-di­chloro-1,6-di­deoxy-[beta]-D-fructo­furan­osyl 4-chloro-4-deoxy-[alpha]-D-gluco­pyran­oside monohydrate, C₁₂H₁₉Cl₃O₈·H₂O, has a near ideal ⁴C₁ chair conformation, while the fructo­furan­osyl ring has a ⁴T₃ conformation. The conformation of the sugar mol­ecule is quite different to that of sucralose, particularly in the conformation about the glycosidic linkage, which affects the observed pattern of intramolecular hydrogen bonds. A complex series of intermolecular hydrogen bonds links the sugar and water mol­ecules into an infinite three-dimensional framework.

S1. Comment

Halogenated analogues of sucrose generally have intense sweetness, with many being several times sweeter than sucrose. This is rather puzzling, since halogenated analogues of all other sugars are either much less sweet than their parent sugar and/or very bitter. It is still not very clear why this is so, nor is it well understood which structural features of a molecule are responsible for producing a sweet taste. The most accepted explanation for sweetness is that a sweet molecule requires the formation of a pair of hydrogen bonds, AH···B, with the receptor site (Shallenberger & Acree, 1967), as well as the presence of a hydrophobic centre, γ (Kier, 1972). The location of the AH,B,γ tripartite glucophore in sucrose and its sweet analogues is still far from certain. As a continuation of our research programme on the structure-sweetness relationship of sugars, we now report the crystal structure of 1,6-dichloro-1,6-dideoxy-β-D-fructofuranosyl 4-chloro-4-deoxy-α-D-glucopyranoside monohydrate or 4,1',6'-trichloro-4,1',6'-trideoxysucrose monohydrate, (I). \sch

The absolute configuration of (I) has been determined confidently by refinement of the absolute structure parameter (Flack, 1983) and is shown in Fig. 1. Compound (I) is isostructural with 1',6'-dibromo-4-fluoro-4,1',6'-trideoxysucrose monohydrate (Linden et al., 2001), including the pattern of hydrogen bonds. The bond lengths and angles of (I) also generally agree with those of sucralose, which is the C4 epimer of (I) (Kanters et al., 1988). However, the conformation about the glycosidic C—O bond of (I) is quite different from that found for sucralose. This is mainly a result of rotation about the C7—O1 bond, as shown by a comparison of the torsion angles for these two compounds (Table 1). The epimerization at C4 apparently alters the most stable packing arrangement, which leads to the molecule twisting into the most economic conformation that allows this packing. As a result, there is a difference in the intramolecular hydrogen bonds formed by each compound. In sucralose, the two sugar rings are linked by an intramolecular O2—H···O8 hydrogen bond [labelled as O2—H···O13 by Kanters et al. (1988)], whereas in (I), O2—H is involved in an intermolecular hydrogen bond and, instead, O8—H forms a very weak intramolecular hydrogen bond with the glycosidic O1 atom (Table 2).

The glucopyranoside ring in (I) adopts a slightly distorted ⁴C₁ chair conformation, with puckering parameters (Cremer and Pople, 1975) Q = 0.5914 (15) Å, q₂ = 0.0365 (14) Å, q₃ = 0.5903 (15) Å, θ = 3.48 (14)° and ϕ₂ = 152 (2)°. This distortion is slightly larger than that in sucralose (θ = 1.9°; Kanters et al., 1988). The fructofuranosyl residue has a twisted ⁹T₈ conformation [i.e. ⁴T₃ with conventional furanosyl ring numbering; q₂ = 0.4081 (15) Å and ϕ₂ = 272.5 (2)°], with atoms C8 and C9 being -0.287 (4) and 0.384 (4) Å, respectively, from the plane defined by atoms O10, C7 and C10. As in sucrose (Brown & Levy, 1963, 1973), the hydroxymethyl group of the glucopyranosyl ring has the familiar gauche-gauche conformation. In sucralose, the gauche-trans conformation is preferred over gauche-gauche, as this avoids an unfavourable 1,3-peri interaction. The C7 and C10 chloromethyl substituents of (I) are both gauche-trans. In sucralose, the former substituent has the gauche-gauche conformation, while the latter, as in (I), is gauche-trans.

Unlike sucralose, the structure of which is anhydrous, the asymmetric unit of (I) contains one sugar molecule and one water molecule. The sugar and water molecules are linked into an infinite three-dimensional framework by a complex series of intermolecular hydrogen bonds (Table 2), which involves all available hydrogen-bond donors in these molecules. Atom O8, which is the donor in the weak intramolecular hydrogen bond described above, also acts as a donor for a much stronger intermolecular interaction and as an acceptor of two intermolecular interactions. When considered individually, the intermolecular hydrogen bonds involving the donor atoms O3, O6, O8 and O9 link the molecules into infinite one-dimensional chains which have unitary graph-set motifs (Bernstein et al., 1995) of C(9), C(7), C(5) and C(9), respectively. The chain involving atom O6 as the donor runs parallel to the x axis, while each of the others runs parallel to the y axis. Atom O2 acts as a hydrogen-bond donor to atom O13 of the water molecule, which, in turn donates hydrogen bonds to two other sugar molecules. Considering the path through each of the H atoms of the water molecule separately, each of these patterns forms an infinite one-dimensional sugar···water···sugar···water··· chain which has a binary graph-set motif of C²₂(12). One of these chains runs parallel to the x axis, while the other runs parallel to the y axis. The intramolecular hydrogen bond involving the O8···O1 interaction creates a five-membered loop with a graph-set motif of S(5).

Currently, the most accepted explanation for sweetness is the Shallenberger & Acree-Kier AH,B,γ model mentioned above (Shallenberger & Acree, 1967; Kier, 1972). For sugars, the distance parameters are A···B ≈ 2.8, A···γ ≈ 3.5 and γ···B ≈ 5.5 Å. The location of the AH,B,γ glucophore in sucrose and the intensely sweet halogenated sucrose analogues is still being debated (Shallenberger & Lindley, 1977; Hough & Khan, 1978, 1993; van der Heijden et al., 1985; Mathlouthi & Seuvre, 1988; Hough, 1989; van der Heijden, 1993; Hooft et al., 1993; Lichtenthaler & Immel, 1993; Mathlouthi et al., 1993; Tsuami et al., 1994). However, work by Tsuami et al. (1994) strongly suggests that, in sucrose derivatives, O8—H,O2 (i.e. O3'-H,O2 in the normal numbering convention) acts as the AH,B grouping. Since all galactosucrose C4—Cl derivatives are intensely sweet compared with the corresponding sucrose C4—Cl epimers [sucralose is 650 times sweeter than sucrose (Hough & Khan, 1978; Jenner, 1981; Lee, 1982, 1983, 1987)], it is very likely that the halogen at C4 functions as a γ-site.

Kanters et al. (1988) proposed that a possible AH,B,γ system in sucralose is O8—H,O2,Cl4, where O2···O8 = 2.80, O2···Cl4 = 4.46 and O8···Cl4 = 6.45 Å. These dimensions correspond quite well with the Shallenberger & Acree-Kier AH,B,γ model. In contrast, the corresponding geometric pattern in (I) [O2···O8 = 4.2108 (14), O2···Cl4 = 5.1119 (12) and O8···Cl4 = 6.7555 (11) Å] does not correlate well with this tripartite model. This could possibly explain why (I), which is 100 times sweeter than sucrose (Hough & Khan, 1993), has only a fraction of the sweetness of sucralose. All of the other C4-halodeoxy sucrose analogues that have been tested also have very much lower sweetness than the corresponding galacto epimer (Muhammad Sofian & Lee, 2002). In addition, 4,6,1',6'-tetrachloro-4,6,1',6'-tetradeoxysucrose is only half as sweet as the corresponding galacto epimer (Lee, 1987). This offers strong support to our earlier prediction (Lee et al., 1999) that not only is the halogen substituent at C4 (as well as that at C8) important in determining the sweetness of halodeoxy sucrose analogues, but the stereochemical disposition of these halogen atoms is critical as well.

S2. Experimental

Carbon tetrachloride (1.5 ml, 9.74 mmol) was added dropwise to a stirred solution of 3,4-di-O-acetyl-β-D-fructofuranosyl 2,3,6-tri-O-acetyl-α-D-galactopyranoside (0.67 g, 1.21 mmol) in pyridine (10 ml) and triphenylphosphine (1.90 g, 7.25 mmol) at 273 K under an argon atmosphere. The reaction mixture was stirred at 273 K for 30 min, at room temperature for another 30 min, and then heated at ~358 K until all starting material had reacted (thin-layer chromatography, ethyl acetate-hexane, 1:2). Work-up in the usual manner and flash column chromatography (ethyl acetate-hexane, 1:2) gave 3,4-di-O-acetyl-1,6-dichloro-1,6-dideoxy-β-D-fructofuranosyl 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-D-glucopyranoside (0.66 g, 89%) as a colourless syrup. Spectroscopic analysis: [α]_D +23.2° (c 2.26, CHCl₃); ¹H NMR (300.13 MHz, CDCl₃, δ, p.p.m.): 2.01, 2.03, 2.04, 2.06, 2.12 (5 × s, 15H, 5 × CH₃), 3.49–3.72 (m, 4H, H1'A,B, H6'A,B), 3.82 (t, 1H, J_3,4 = J_4,5 = 10.1 Hz, H4), 4.15–4.46 (m, 4H, H5, H5', H6A,B), 4.77 (dd, 1H, J_1,2 = 3.5, J_2,3 = 10.1 Hz, H2), 5.31 (t, 1H, J_3',4' = J_4',5' = 5.9 Hz, H4'), 5.41 (t, 1H, J_2,3 = J_3,4 = 10.1 Hz, H3), 5.57 (d, 1H, J_1,2 = 3.5 Hz, H1), 5.60 (d, 1H, J_3',4' = 5.9 Hz, H3'); ¹³C NMR (75.47 MHz, CDCl₃, δ, p.p.m.): 170.2, 169.9, 169.6, 169.4, 169.4 (COCH₃), 104.3 (C2'), 90.1 (C1), 81.2 (C5'), 76.0, 75.9 (C3', C4'), 70.9 (C3), 70.7 (C5), 70.5 (C2), 62.5 (C6), 54.9 (C4), 44.7, 43.7 (C1', C6'), and 20.5, 20.5, 20.4, 20.4, 20.3 (COCH₃); HRMS-ESI (positive mode), calculated for [M + Na]⁺: 629.0331:631.0302:633.0512; found: 629.0583:631.0560:633.0527.

A solution of this 4,1',6'-trichloro derivative (0.12 g, 0.197 mmol) in methanol was treated with methanolic NaOMe at pH ~9 for 1 h at room temperature, after which thin-layer chromatography (methanol-CHCl₃, 3:17) showed only one slower moving product. The mixture was neutralized using Amberlite IR120 (H⁺) ion-exchange resin, filtered and concentrated to give the title compound, (I) (0.071 g, 90%), m.p. 382–383 K (methanol). Spectroscopic analysis: [α]_D +44.8° (c 1.36, methanol); ¹H NMR 300.13 MHz, D₂O, δ, p.p.m., the assignments employ the crystallographic atom numbering used in Fig. 1): 4.14 (dd, 1H, J_1,2 = 3.8, J_2,3 = 9.7 Hz, H2), 4.30–4.68 (m, 11H, H3, H4, H5, H6A,B, H9, H10, H11A,B, H12A,B), 4.93 (d, 1H, J_8,9 = 8.0 Hz, H8), 6.01 (d, 1H, J_1,2 = 3.8 Hz, H1); ¹³C NMR (75.47 MHz, D₂O, δ, p.p.m.): 104.1 (C7), 93.4 (C1), 81.7 (C10), 76.9, 75.9 (C8, C9), 73.5 (C3), 73.1, (C5), 72.0 (C2), 61.0 (C6), 58.5 (C4), and 45.4, 44.0 (C11, C12); HRMS-ESI (positive mode), calculated for [M + Na]⁺: 396.0145:398.0116:400.0086; found: 396.0139:398.0110:400.0083. Suitable crystals were obtained by slow evaporation of a solution of (I) in methanol.

S3. Refinement

The asymmetric unit of (I) contains one molecule of the title sugar and one molecule of water. The hydroxy and water H atoms were located in a difference Fourier map and their positions were refined freely along with individual isotropic displacement parameters. All other H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms, with C—H distances in the range 0.99–1.00 Å and U_iso(H) = 1.2U_eq(C). The determined absolute configuration agreed with that expected for a natural sucrose derivative. Three low-angle reflections were omitted from the final cycles of refinement because their observed intensities were much lower than the calculated values, as a result of being partially obscured by the beam stop.

Computing details

Data collection: COLLECT (Nonius, 2000); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997); data reduction: DENZO-SMN and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2002).

Figures

Fig. 1. A view of the asymmetric unit of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are represented by spheres of arbitrary size.

1,6-dichloro-1,6-dideoxy-β-D-fructofuranosyl 4-chloro-4-deoxy-α-D-glucopyranoside monohydrate

Crystal data

C12H19Cl3O8·H2O	Dx = 1.641 Mg m^−3
Mr = 415.65	Melting point: 382 K
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 41833 reflections
a = 7.5571 (1) Å	θ = 2.0–30.0°
b = 9.4931 (1) Å	µ = 0.59 mm^−1
c = 23.4455 (2) Å	T = 160 K
V = 1681.99 (3) Å^3	Prism, colourless
Z = 4	0.25 × 0.15 × 0.10 mm
F(000) = 864

Data collection

Nonius KappaCCD area-detector diffractometer	4903 independent reflections
Radiation source: Nonius FR591 sealed-tube generator	4460 reflections with I > 2σ(I)
Horizontally mounted graphite crystal monochromator	Rint = 0.056
Detector resolution: 9 pixels mm^-1	θmax = 30.0°, θmin = 3.2°
ϕ and ω scans with κ offsets	h = −10→10
Absorption correction: multi-scan (Blessing, 1995)	k = −13→13
Tmin = 0.819, Tmax = 0.947	l = −32→32
51545 measured reflections

Refinement

Refinement on F^2	Hydrogen site location: geom & difmap
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.028	w = 1/[σ^2(Fo^2) + (0.0355P)^2 + 0.3153P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.068	(Δ/σ)max = 0.001
S = 1.05	Δρmax = 0.25 e Å^−3
4900 reflections	Δρmin = −0.29 e Å^−3
247 parameters	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0078 (11)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), with 2099 Friedel pairs
Secondary atom site location: difference Fourier map	Absolute structure parameter: 0.02 (4)

Special details

Experimental. Solvent used: MeOH Cooling Device: Oxford Cryosystems Cryostream 700 Crystal mount: glued on a glass fibre Mosaicity (°.): 0.400 (1) Frames collected: 780 Seconds exposure per frame: 26 Degrees rotation per frame: 1.3 Crystal-Detector distance (mm): 36.0

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.

Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane)

5.5245 (0.0053) x + 6.2481 (0.0062) y + 4.2209 (0.0424) z = 10.8733 (0.0126)

* 0.0000 (0.0000) O10 * 0.0000 (0.0000) C7 * 0.0000 (0.0000) C10 - 0.2867 (0.0038) C8 0.3840 (0.0037) C9

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
Cl1	1.01472 (6)	0.61104 (5)	0.458502 (16)	0.03053 (10)
Cl2	0.38866 (5)	0.98095 (4)	0.305645 (16)	0.02644 (9)
Cl4	1.29372 (5)	1.10677 (4)	0.455920 (15)	0.02280 (9)
O1	0.79089 (13)	1.01469 (10)	0.34395 (4)	0.0158 (2)
O2	0.81450 (16)	1.30123 (11)	0.32371 (4)	0.0204 (2)
H2	0.719 (3)	1.358 (2)	0.3228 (9)	0.038 (6)*
O3	1.14077 (15)	1.33948 (12)	0.38046 (5)	0.0217 (2)
H3	1.162 (3)	1.353 (2)	0.3470 (10)	0.034 (6)*
O5	0.76957 (13)	1.05622 (11)	0.44364 (4)	0.0170 (2)
O6	0.93821 (17)	1.05814 (13)	0.55833 (5)	0.0256 (2)
H6	0.838 (3)	1.084 (2)	0.5603 (10)	0.037 (6)*
O8	0.77306 (14)	0.91754 (11)	0.23459 (4)	0.0179 (2)
H8	0.839 (3)	0.983 (2)	0.2414 (8)	0.028 (5)*
O9	1.01630 (17)	0.65735 (12)	0.25578 (5)	0.0220 (2)
H9	1.073 (3)	0.698 (3)	0.2323 (11)	0.045 (7)*
O10	0.79028 (14)	0.78503 (11)	0.37967 (4)	0.0180 (2)
C1	0.73718 (19)	1.10882 (15)	0.38832 (5)	0.0161 (3)
H1	0.6080	1.1291	0.3842	0.019*
C2	0.84151 (19)	1.24501 (15)	0.37920 (6)	0.0162 (3)
H21	0.8036	1.3161	0.4082	0.019*
C3	1.0390 (2)	1.21467 (15)	0.38670 (6)	0.0164 (3)
H31	1.0778	1.1436	0.3578	0.020*
C4	1.06511 (19)	1.15537 (15)	0.44634 (6)	0.0168 (3)
H4	1.0313	1.2279	0.4753	0.020*
C5	0.95270 (18)	1.02375 (15)	0.45459 (6)	0.0169 (3)
H5	0.9919	0.9516	0.4262	0.020*
C6	0.9635 (2)	0.95865 (16)	0.51352 (6)	0.0208 (3)
H61	0.8726	0.8840	0.5168	0.025*
H62	1.0809	0.9137	0.5182	0.025*
C7	0.71439 (19)	0.87935 (15)	0.33938 (6)	0.0158 (3)
C8	0.7732 (2)	0.82107 (15)	0.28072 (5)	0.0158 (3)
H81	0.6926	0.7414	0.2706	0.019*
C9	0.95376 (19)	0.75910 (15)	0.29506 (6)	0.0171 (3)
H91	1.0428	0.8363	0.2994	0.020*
C10	0.9162 (2)	0.69190 (15)	0.35276 (6)	0.0168 (3)
H10	0.8608	0.5973	0.3470	0.020*
C11	1.0773 (2)	0.67710 (17)	0.38999 (6)	0.0211 (3)
H111	1.1356	0.7699	0.3943	0.025*
H112	1.1625	0.6117	0.3719	0.025*
C12	0.5173 (2)	0.87220 (16)	0.35207 (6)	0.0195 (3)
H121	0.4968	0.9019	0.3920	0.023*
H122	0.4771	0.7734	0.3483	0.023*
O13	0.54492 (16)	0.48629 (13)	0.33160 (5)	0.0249 (2)
H131	0.508 (3)	0.474 (3)	0.3642 (10)	0.042 (6)*
H132	0.461 (3)	0.471 (3)	0.3077 (11)	0.052 (7)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0362 (2)	0.0363 (2)	0.01909 (17)	0.01106 (18)	0.00113 (15)	0.00731 (16)
Cl2	0.01736 (17)	0.0379 (2)	0.02404 (18)	0.00413 (15)	−0.00283 (14)	0.00083 (16)
Cl4	0.01674 (16)	0.02794 (17)	0.02372 (17)	0.00041 (14)	−0.00249 (13)	0.00025 (15)
O1	0.0162 (5)	0.0165 (5)	0.0148 (4)	−0.0017 (4)	0.0026 (4)	−0.0018 (4)
O2	0.0248 (6)	0.0221 (5)	0.0143 (5)	0.0057 (4)	0.0011 (4)	0.0027 (4)
O3	0.0257 (6)	0.0228 (5)	0.0168 (5)	−0.0084 (4)	0.0004 (4)	0.0000 (4)
O5	0.0150 (5)	0.0226 (5)	0.0135 (4)	−0.0004 (4)	0.0011 (4)	0.0019 (4)
O6	0.0261 (6)	0.0357 (6)	0.0151 (5)	0.0086 (5)	0.0016 (4)	−0.0008 (4)
O8	0.0202 (5)	0.0189 (5)	0.0146 (4)	−0.0010 (4)	−0.0007 (4)	0.0005 (4)
O9	0.0263 (6)	0.0205 (5)	0.0191 (5)	0.0039 (4)	0.0073 (4)	−0.0007 (4)
O10	0.0184 (5)	0.0213 (5)	0.0143 (4)	0.0034 (4)	0.0021 (4)	0.0017 (4)
C1	0.0168 (6)	0.0189 (6)	0.0127 (6)	0.0022 (5)	0.0008 (5)	−0.0002 (5)
C2	0.0201 (7)	0.0159 (6)	0.0127 (6)	0.0024 (5)	0.0011 (5)	−0.0006 (5)
C3	0.0185 (7)	0.0160 (6)	0.0147 (6)	−0.0025 (5)	0.0025 (5)	−0.0005 (5)
C4	0.0153 (7)	0.0190 (6)	0.0161 (6)	0.0007 (5)	−0.0008 (5)	−0.0010 (5)
C5	0.0160 (6)	0.0198 (6)	0.0150 (6)	0.0006 (5)	−0.0005 (5)	−0.0005 (5)
C6	0.0238 (8)	0.0223 (7)	0.0164 (6)	0.0029 (6)	0.0008 (6)	0.0027 (6)
C7	0.0145 (6)	0.0177 (6)	0.0152 (6)	−0.0013 (5)	0.0004 (5)	0.0002 (5)
C8	0.0177 (7)	0.0167 (6)	0.0128 (6)	−0.0014 (5)	0.0002 (5)	−0.0014 (5)
C9	0.0180 (7)	0.0177 (7)	0.0155 (6)	0.0008 (5)	0.0015 (5)	−0.0016 (5)
C10	0.0181 (7)	0.0164 (6)	0.0159 (6)	−0.0003 (5)	0.0020 (5)	0.0006 (5)
C11	0.0206 (8)	0.0236 (7)	0.0193 (7)	0.0033 (6)	0.0018 (5)	0.0023 (6)
C12	0.0140 (7)	0.0243 (8)	0.0201 (7)	−0.0006 (6)	0.0015 (5)	0.0021 (5)
O13	0.0202 (6)	0.0367 (7)	0.0179 (5)	0.0007 (5)	−0.0006 (4)	0.0005 (5)

Geometric parameters (Å, º)

Cl1—C11	1.7880 (15)	C3—C4	1.5204 (19)
Cl2—C12	1.7877 (15)	C3—H31	1.0000
Cl4—C4	1.8022 (14)	C4—C5	1.523 (2)
O1—C7	1.4130 (17)	C4—H4	1.0000
O1—C1	1.4302 (16)	C5—C6	1.5159 (19)
O2—C2	1.4210 (17)	C5—H5	1.0000
O2—H2	0.90 (2)	C6—H61	0.9900
O3—C3	1.4199 (18)	C6—H62	0.9900
O3—H3	0.81 (2)	C7—C12	1.520 (2)
O5—C1	1.4113 (16)	C7—C8	1.5475 (19)
O5—C5	1.4409 (17)	C8—C9	1.523 (2)
O6—C6	1.4256 (18)	C8—H81	1.0000
O6—H6	0.80 (2)	C9—C10	1.5224 (19)
O8—C8	1.4172 (16)	C9—H91	1.0000
O8—H8	0.81 (2)	C10—C11	1.504 (2)
O9—C9	1.4158 (17)	C10—H10	1.0000
O9—H9	0.80 (3)	C11—H111	0.9900
O10—C7	1.4223 (17)	C11—H112	0.9900
O10—C10	1.4438 (17)	C12—H121	0.9900
C1—C2	1.529 (2)	C12—H122	0.9900
C1—H1	1.0000	O13—H131	0.82 (2)
C2—C3	1.530 (2)	O13—H132	0.86 (3)
C2—H21	1.0000
C7—O1—C1	120.48 (11)	O6—C6—H62	108.9
C2—O2—H2	111.1 (14)	C5—C6—H62	108.9
C3—O3—H3	109.6 (16)	H61—C6—H62	107.7
C1—O5—C5	113.96 (10)	O1—C7—O10	110.92 (11)
C6—O6—H6	112.0 (16)	O1—C7—C12	115.25 (12)
C8—O8—H8	110.0 (14)	O10—C7—C12	103.70 (11)
C9—O9—H9	107.0 (18)	O1—C7—C8	105.96 (11)
C7—O10—C10	111.16 (10)	O10—C7—C8	104.43 (11)
O5—C1—O1	113.47 (11)	C12—C7—C8	116.07 (12)
O5—C1—C2	109.76 (11)	O8—C8—C9	114.76 (12)
O1—C1—C2	106.28 (11)	O8—C8—C7	116.54 (11)
O5—C1—H1	109.1	C9—C8—C7	101.49 (11)
O1—C1—H1	109.1	O8—C8—H81	107.9
C2—C1—H1	109.1	C9—C8—H81	107.9
O2—C2—C1	111.80 (11)	C7—C8—H81	107.9
O2—C2—C3	108.41 (11)	O9—C9—C10	110.76 (12)
C1—C2—C3	109.13 (11)	O9—C9—C8	114.76 (12)
O2—C2—H21	109.2	C10—C9—C8	101.00 (11)
C1—C2—H21	109.2	O9—C9—H91	110.0
C3—C2—H21	109.2	C10—C9—H91	110.0
O3—C3—C4	109.48 (12)	C8—C9—H91	110.0
O3—C3—C2	111.05 (12)	O10—C10—C11	109.69 (11)
C4—C3—C2	107.56 (11)	O10—C10—C9	104.75 (11)
O3—C3—H31	109.6	C11—C10—C9	113.80 (12)
C4—C3—H31	109.6	O10—C10—H10	109.5
C2—C3—H31	109.6	C11—C10—H10	109.5
C3—C4—C5	110.38 (11)	C9—C10—H10	109.5
C3—C4—Cl4	109.49 (10)	C10—C11—Cl1	109.88 (10)
C5—C4—Cl4	107.99 (10)	C10—C11—H111	109.7
C3—C4—H4	109.7	Cl1—C11—H111	109.7
C5—C4—H4	109.7	C10—C11—H112	109.7
Cl4—C4—H4	109.7	Cl1—C11—H112	109.7
O5—C5—C6	107.55 (11)	H111—C11—H112	108.2
O5—C5—C4	109.73 (11)	C7—C12—Cl2	112.82 (10)
C6—C5—C4	114.83 (12)	C7—C12—H121	109.0
O5—C5—H5	108.2	Cl2—C12—H121	109.0
C6—C5—H5	108.2	C7—C12—H122	109.0
C4—C5—H5	108.2	Cl2—C12—H122	109.0
O6—C6—C5	113.23 (12)	H121—C12—H122	107.8
O6—C6—H61	108.9	H131—O13—H132	109 (2)
C5—C6—H61	108.9
C5—O5—C1—O1	58.47 (15)	C1—O1—C7—C8	168.45 (11)
C5—O5—C1—C2	−60.26 (14)	C10—O10—C7—O1	−102.70 (13)
C7—O1—C1—O5	61.02 (16)	C10—O10—C7—C12	133.02 (12)
C7—O1—C1—C2	−178.27 (11)	C10—O10—C7—C8	11.03 (15)
O5—C1—C2—O2	179.37 (11)	O1—C7—C8—O8	−40.69 (16)
O1—C1—C2—O2	56.29 (14)	O10—C7—C8—O8	−157.89 (12)
O5—C1—C2—C3	59.44 (14)	C12—C7—C8—O8	88.64 (16)
O1—C1—C2—C3	−63.63 (13)	O1—C7—C8—C9	84.71 (12)
O2—C2—C3—O3	59.95 (15)	O10—C7—C8—C9	−32.49 (14)
C1—C2—C3—O3	−178.06 (11)	C12—C7—C8—C9	−145.96 (12)
O2—C2—C3—C4	179.73 (11)	O8—C8—C9—O9	−73.76 (15)
C1—C2—C3—C4	−58.28 (14)	C7—C8—C9—O9	159.66 (12)
O3—C3—C4—C5	178.28 (12)	O8—C8—C9—C10	167.08 (11)
C2—C3—C4—C5	57.51 (15)	C7—C8—C9—C10	40.50 (13)
O3—C3—C4—Cl4	−62.97 (13)	C7—O10—C10—C11	137.63 (12)
C2—C3—C4—Cl4	176.25 (9)	C7—O10—C10—C9	15.12 (15)
C1—O5—C5—C6	−175.78 (11)	O9—C9—C10—O10	−156.89 (12)
C1—O5—C5—C4	58.68 (14)	C8—C9—C10—O10	−34.88 (13)
C3—C4—C5—O5	−56.65 (14)	O9—C9—C10—C11	83.32 (15)
Cl4—C4—C5—O5	−176.31 (9)	C8—C9—C10—C11	−154.68 (12)
C3—C4—C5—C6	−177.91 (12)	O10—C10—C11—Cl1	58.21 (14)
Cl4—C4—C5—C6	62.44 (14)	C9—C10—C11—Cl1	175.17 (10)
O5—C5—C6—O6	−72.85 (16)	O1—C7—C12—Cl2	59.60 (14)
C4—C5—C6—O6	49.59 (18)	O10—C7—C12—Cl2	−178.97 (9)
C1—O1—C7—O10	−78.79 (14)	C8—C7—C12—Cl2	−65.09 (15)
C1—O1—C7—C12	38.64 (17)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O13^i	0.90 (2)	1.80 (2)	2.6964 (17)	170 (2)
O3—H3···O8^ii	0.81 (2)	2.07 (2)	2.8722 (15)	171 (2)
O6—H6···O3^iii	0.80 (2)	2.16 (2)	2.8384 (17)	143 (2)
O8—H8···O1	0.81 (2)	2.450 (19)	2.7280 (13)	101.4 (15)
O8—H8···O9^ii	0.81 (2)	1.99 (2)	2.7870 (16)	169 (2)
O9—H9···O2^iv	0.80 (3)	1.85 (3)	2.6410 (16)	175 (3)
O13—H131···O6^v	0.82 (2)	1.91 (2)	2.7364 (16)	176 (2)
O13—H132···O8^vi	0.86 (3)	2.09 (3)	2.9340 (16)	167 (2)

Symmetry codes: (i) x, y+1, z; (ii) −x+2, y+1/2, −z+1/2; (iii) x−1/2, −y+5/2, −z+1; (iv) −x+2, y−1/2, −z+1/2; (v) x−1/2, −y+3/2, −z+1; (vi) −x+1, y−1/2, −z+1/2.