Crystal structure of 4-nitro-phenyl 6-O-ethyl-β-d-galacto-pyran-oside monohydrate.

The synthesis and crystal structure of the title compound, C14H19NO8·H2O, prepared in three steps from 6-O-ethyl-1,2;3,4-di-O-iso-propyl-idene-α-d-galacto-pyran-ose using protecting-group strategies employed in carbohydrate chemistry, is reported. The asymmetric unit consists of a single galactoside mol-ecule, in which the pyran-oid ring has a 4C1 conformation and the 4-nitro-phenyl moiety is essentially planar. In the crystal, each carbohydrate is surrounded by other d-galactose residues and water mol-ecules, linked by O-H⋯O hydrogen bonds involving all hy-droxy groups, giving a two-dimensional substructure lying parallel to (100) and extended into three dimensions by C-H⋯O inter-actions.

Chemical context

Small mol­ecules containing d-galactose moieties substituted at non-anomeric positions have been assayed against galacto­sidases (Viana et al., 2011 ▸; McCarter et al., 1992 ▸; Huber & Gaunt, 1983 ▸) and lectins (Butera et al., 2009 ▸; Salameh et al., 2005 ▸). Trypanosoma cruzi trans-sialidase (TcTS) (Mendonça-Previato et al., 2010 ▸), an enzyme involved in Chagas’s disease infection, is inhibited by β-d-galacto­pyran­osides substituted at the C6 ring site, which are in general more potent than the corresponding analogues modified at other ring positions of the carbohydrate (Harrison et al., 2011 ▸). In this context, the title compound C14H19NO8 was designed and synthesized to be evaluated against TcTS and T. cruzi invasion of host cells. The synthesis and crystal structure of this compound as the monohydrate (I) is reported herein.

Structural commentary

In the structure of the title monohydrated compound (I) (Fig. 1 ▸), the pyran­oid ring adopts a 4 C 1 conformation, with puckering parameters Q = 0.569 (2) Å, θ = 4.6 (2)° and φ = 51 (3)°. The anomeric beta form and d-galacto configuration of the carbohydrate with C1(S), C2(R), C3(S), C4(R) and C5(R) are consistent with that expected from the synthesis. The length of the glycosidic bond is 1.408 (2) Å and the bond angles around the anomeric carbon atom (C1) range from 106.40 (16) to 111.35 (17)°. The 4-nitro­phenyl substituent at C1 located in an equatorial position is essentially planar, with a r.m.s. deviation of 0.02 Å for non-hydrogen atoms [torsion angle C9—C10—N1—O11 = 179.0 (4)°]. The angle between the mean plane of the 4-nitro­phenyl substituent (defined by atoms C7–C12/N1/O11/O12) and the mean sugar plane (defined by C1–C5/O5 atoms) is 57.45 (11)° [torsion angle O5—C1—O1—O7 = −79.8 (2)°]. An intra­molecular C13—H13B⋯O5 inter­action is also present (Table 1 ▸).

Figure 1

The mol­ecular structure of the title compound with the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2B⋯O6i	0.82	1.85	2.670 (2)	179
O3—H3B⋯O1W ii	0.82	1.91	2.711 (2)	167
O4—H4B⋯O3iii	0.82	1.97	2.785 (2)	170
O1W—H1WA⋯O2iv	0.89	1.90	2.776 (3)	166
O1W—H1WB⋯O3v	0.89	2.39	3.208 (2)	154
C3—H3A⋯O4vi	0.98	2.35	3.283 (3)	158
C13—H13A⋯O12vii	0.97	2.55	3.167 (3)	121
C13—H13B⋯O5	0.97	2.53	3.173 (3)	123

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) ; (vi) ; (vii) .

Supra­molecular features

In the crystal, a carbohydrate moiety is connected to eight neighboring d-galactose residues by several direct and water-mediated classical hydrogen bonds (Table 1 ▸), establishing a network of inter­actions (Fig. 2 ▸). Regarding only the O—H⋯O inter­action type, there are O2—H2B⋯O6i, O3—H3B⋯O1W ii and O4—H4B⋯O3iii hydrogen bonds. In addition, there is a single-water bridge connecting O3 to O2 of a nearby galactoside mol­ecule (O1W—H1WA⋯O2iv and O1W—H1WB⋯O3v; for symmetry codes, see Table 1 ▸). A two-dimensional substructure in the form of a sheet lying parallel to (100) is formed. The overall three-dimensional supra­molecular aggregation is completed by inter­molecular C—H⋯O inter­actions: C3—H3A⋯O4vi connects carbohydrate rings stacked along the a axis and C13—H13A⋯O12vii connects ethyl and nitro groups along the c axis. The 4-nitro­phenyl substituent groups are arranged in parallel planes (Fig. 3 ▸), with an inter­planar distance of 3.4355 (14) Å, but the slip angle (48.3°) prevents overlapping and therefore no π–π inter­actions are present [ring-centroid separation = 5.163 (2) Å].

Figure 2

Selected inter­actions in the crystal lattice with O—H⋯O hydrogen bonds shown as turquoise dashed lines and C—H⋯O inter­actions shown as blue dashed lines.

Figure 3

Crystal packing of the title compound, showing the stacked galactoside mol­ecules along the a axis. For clarity, H atoms are not shown.

Database survey

To the best of our knowledge, this is the first report of the crystal structure of an aryl 6-O-substituted-β-d-galacto­pyran­oside in the literature. In the Cambridge Structural Database (Version 5.38; Groom et al., 2016 ▸), the structural data for the closely related analogue 4-nitro­phenyl β-d-galacto­pyran­oside have been deposited (CSD Refcode VUCYO1; Gubica et al., 2009 ▸). Both galactosides are monohydrates and their mol­ecular geometry and inter­molecular inter­action profiles in the crystal lattice are quite similar. The aromatic ring of the 6-unsubstituted galactoside is less planar due to the increased rotation of the N1—C10 bond, since the angle between the mean planes of the phenyl and nitro groups is ca 5.1°, compared to 2.6 (5)° in the title compound. According to the authors (Gubica et al., 2009 ▸), the deviation from coplanarity of these fragments in the 4-nitro­phenyl β-d-galacto­pyran­oside structure is due to inter­molecular inter­actions involving the nitro group. In our crystallographic study on compound (I) we did not observe classical hydrogen bonds to 4-nitro­phenyl O-atom acceptors, but only the weak C13—H13A⋯O12 inter­action noted above.

Synthesis and crystallization

The chemical synthesis of 4-nitro­phenyl 6-O-ethyl-β-d-galacto­pyran­oside monohydrate (I) was achieved in three steps, as shown in Fig. 4 ▸.

Figure 4

Synthesis of the title compound (I): (i) AcCl, MeOH, HCl(aq), room temperature, closed system; (ii) 4-nitro­phenol, LiOH·H2O, acetone/H2O, room temperature; (iii) MeONa/MeOH, CH2Cl2, 273 K. The water mol­ecule of crystallization of (I) is not represented.

Initially the O-alkyl­ation of 1,2;3,4-di-O-iso­propyl­idene-α-d-galacto­pyran­ose was carried out as reported in the literature furnishing the 6-O-alkyl­ated derivative (2) (Cironi & Varela, 2001 ▸; McKeown & Hayward, 1960 ▸). Next, the peracetyl­ated α-d-galacto­pyranosyl chloride (3) was prepared in a three-step one-pot reaction as follows. To a solution of (2) (0.59 g, 2.06 mmol) in acetyl chloride (2.92 mL, 41.13 mmol) was added methanol (0.42 mL) under ice-bath conditions. The mixture was stirred at room temperature for 2h in a closed system and concentrated hydro­chloric acid (0.34 mL) was then added and the resulting mixture was stirred at room temperature for 24 h, also in a closed system. The reaction was quenched with crushed ice (about 30 mL) and the mixture was extracted with di­chloro­methane (3 × 25 mL). The organic layers were washed with a saturated aqueous sodium bicarbonate solution (2 × 60 mL) and water (60 mL), then dried over anhydrous sodium sulfate and concentrated. The brown oil obtained (0.68 g, 94% yield) was used in the next step without further purification.

Classical procedures in carbohydrate chemistry were employed in the next two steps (Conchie et al., 1957 ▸). The glycosyl­ation of 4-nitro­phenol with (3) in alkaline medium gave (4) in 46% yield. Treatment with sodium methoxide to remove the acetyl groups furnished (I) (as the monohydrate), in 84% yield. Colorless crystals of (I) (m.p. 424.1–424.9 K) suitable for X-ray diffraction analysis were obtained by slow evaporation of an acetone solution (about 0.7 mg/mL) at room temperature.

Spectrometric data. [α]D 28 −46 (c 1.0, DMSO). IR max (cm−1): 3354 (O—H), 1608, 1592, 1493 (C=C), 1511, 1349 (NO2), 1249, 1074 (C—O), 846 (C—H aromatic out-of-plane bending). 1H NMR (400 MHz, DMSO-d): δ H 8.20 (d, 2H, J ortho 9.2 Hz, CHCNO2), 7.22 (d, 2H, J ortho 9.2 Hz, OCCH), 5.28 (d, 1H, J OH-2,2 5.2 Hz, OH-2), 5.05 (d, 1H, J 1,2 7.6 Hz, H-1), 4.91 (d, 1H, J OH-3,3 5.7 Hz, OH-3), 4.64 (d, 1H, J OH-4,4 4.6 Hz, OH-4), 3.85 (t, 1H, J 5,6a 5.4 Hz, J 5,6b 5.4 Hz, H-5), 3.71–3.66 (m, 1H, H-4), 3.63 (ddd, 1H, J 2,1 7.6 Hz, J 2,OH-2 5.2 Hz, J 2,3 9.2 Hz, H-2), 3.55 (dd, 1H, J 6a,5 5.4 Hz, J 6a,6b 10.2 Hz, H-6a), 3.50–3.39 (m, 4H, H-3, H-6b and OCHCH3), 1.09 (t, 3H, J ortho 6.9 Hz, OCH2 CH). 13C NMR (100 MHz, DMSO-d): δ C 162.4 (OCCH), 141.6 (CHCNO2), 125.6 (CHCNO2), 116.5 (OCCH), 100.3 (C-1), 73.8 (C-5), 73.0 (C-3), 70.0 (C-2), 69.1 (C-6), 68.3 (C-4), 65.7 (OCHCH3), 15.1 (OCH2 CH).

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. Oxygen-bound H atoms were located in a difference-Fourier map and refined with distance restraints of 0.82 Å (hy­droxy group H) and 0.89 Å (water H) with U iso(H) = 1.5 U eq(O). Carbon-bound H atoms were constrained to an ideal geometry with C—H distances in the range 0.93–0.98 Å, U iso(H) = 1.5 U eq(C) for methyl H atoms and U iso(H) = 1.2 U eq(C) for other H atoms. In the absence of significant anomalous scattering effects, the Flack structure parameter (Flack, 1983 ▸) is essentially meaningless in this analysis and the absolute configuration is inferred from the known d-galacto configuration of the starting material, and remained unchanged during the synthesis. The beta configuration of C1 is confirmed by the coupling constant J 1,2 = 7.6 Hz, obtained from NMR spectroscopy.

Table 2

Experimental details

Crystal data
Chemical formula	C14H19NO8·H2O
M r	347.32
Crystal system, space group	Orthorhombic, P212121
Temperature (K)	293
a, b, c (Å)	5.1628 (3), 8.1593 (3), 38.5755 (16)
V (Å3)	1624.99 (13)
Z	4
Radiation type	Mo Kα
μ (mm−1)	0.12
Crystal size (mm)	0.20 × 0.15 × 0.10
Data collection
Diffractometer	Rigaku OD Xcalibur, Atlas, Gemini Ultra
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2015 ▸)
T min, T max	0.835, 1.000
No. of measured, independent and observed [I > 2/s(I)] reflections	26976, 4265, 3597
R int	0.038
(sin θ/λ)max (Å−1)	0.704
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.046, 0.108, 1.08
No. of reflections	4265
No. of parameters	218
H-atom treatment	H-atom parameters constrained
Δρmax, Δρmin (e Å−3)	0.20, −0.23

Computer programs: CrysAlis PRO (Rigaku OD, 2015 ▸), SHELXS97 and SHELXTL (Sheldrick, 2008 ▸), SHELXL2016 (Sheldrick, 2015 ▸), Mercury (Macrae et al., 2008 ▸), PLATON (Spek, 2009 ▸) and publCIF (Westrip, 2010 ▸).

Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989017004595/zs2376sup1.cif

CCDC reference: 1539718

Additional supporting information: crystallographic information; 3D view; checkCIF report

C14H19NO8·H2O	Dx = 1.420 Mg m−3
Mr = 347.32	Melting point: 424.5 K
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 8847 reflections
a = 5.1628 (3) Å	θ = 2.5–28.5°
b = 8.1593 (3) Å	µ = 0.12 mm−1
c = 38.5755 (16) Å	T = 293 K
V = 1624.99 (13) Å3	Rod, colourless
Z = 4	0.20 × 0.15 × 0.10 mm
F(000) = 736

Rigaku OD Xcalibur, Atlas, Gemini Ultra diffractometer	4265 independent reflections
Radiation source: fine-focus sealed X-ray tube, Enhance (Mo) X-ray Source	3597 reflections with I > 2/s(I)
Graphite monochromator	Rint = 0.038
Detector resolution: 10.4186 pixels mm-1	θmax = 30.0°, θmin = 2.5°
ω scans	h = −7→7
Absorption correction: multi-scan (CrysAlis PRO; Rigaku OD, 2015)	k = −11→11
Tmin = 0.835, Tmax = 1.000	l = −54→52
26976 measured reflections

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.046	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.108	H-atom parameters constrained
S = 1.08	w = 1/[σ2(Fo2) + (0.0448P)2 + 0.4091P] where P = (Fo2 + 2Fc2)/3
4265 reflections	(Δ/σ)max < 0.001
218 parameters	Δρmax = 0.20 e Å−3
0 restraints	Δρmin = −0.23 e Å−3

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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.

	x	y	z	Uiso*/Ueq
O1	0.2973 (3)	0.04259 (19)	0.13258 (4)	0.0359 (4)
O2	0.3964 (4)	−0.11807 (19)	0.06875 (4)	0.0413 (4)
H2B	0.3333	−0.1933	0.0800	0.062*
O3	0.1726 (3)	0.0335 (2)	0.00904 (4)	0.0331 (4)
H3B	0.0444	−0.0206	0.0142	0.050*
O4	−0.1450 (3)	0.2630 (2)	0.04353 (4)	0.0340 (4)
H4B	−0.2160	0.3194	0.0287	0.051*
O5	0.1951 (3)	0.27596 (18)	0.10442 (3)	0.0300 (3)
O6	0.1929 (4)	0.63541 (19)	0.10524 (4)	0.0388 (4)
O11	1.0131 (8)	0.2628 (5)	0.25526 (8)	0.1100 (12)
O12	0.7670 (9)	0.0893 (4)	0.28005 (6)	0.1237 (14)
N1	0.8375 (8)	0.1651 (4)	0.25473 (7)	0.0748 (10)
C1	0.3383 (4)	0.1298 (3)	0.10156 (5)	0.0285 (4)
H1	0.5228	0.1538	0.0984	0.034*
C2	0.2387 (5)	0.0236 (3)	0.07205 (5)	0.0283 (4)
H2A	0.0581	−0.0078	0.0762	0.034*
C3	0.2607 (4)	0.1215 (2)	0.03863 (5)	0.0257 (4)
H3A	0.4454	0.1433	0.0350	0.031*
C4	0.1277 (4)	0.2877 (3)	0.04194 (5)	0.0254 (4)
H4A	0.1685	0.3539	0.0215	0.030*
C5	0.2224 (4)	0.3771 (2)	0.07412 (5)	0.0266 (4)
H5	0.4057	0.4049	0.0711	0.032*
C6	0.0717 (5)	0.5319 (3)	0.08045 (6)	0.0340 (5)
H6A	0.0534	0.5910	0.0588	0.041*
H6B	−0.1005	0.5037	0.0886	0.041*
C7	0.4348 (5)	0.0860 (3)	0.16169 (6)	0.0350 (5)
C8	0.3682 (7)	−0.0008 (3)	0.19102 (6)	0.0521 (7)
H8	0.2354	−0.0778	0.1902	0.062*
C9	0.5004 (8)	0.0274 (4)	0.22159 (7)	0.0629 (9)
H9	0.4563	−0.0297	0.2416	0.076*
C10	0.6952 (6)	0.1392 (4)	0.22221 (6)	0.0515 (7)
C11	0.7581 (8)	0.2284 (5)	0.19380 (7)	0.0651 (9)
H11	0.8884	0.3069	0.1950	0.078*
C12	0.6266 (7)	0.2019 (4)	0.16305 (7)	0.0596 (9)
H12	0.6684	0.2623	0.1434	0.072*
C13	0.0993 (6)	0.6211 (3)	0.14011 (6)	0.0431 (6)
H13A	0.2266	0.6673	0.1558	0.052*
H13B	0.0799	0.5059	0.1458	0.052*
C14	−0.1538 (7)	0.7057 (5)	0.14554 (9)	0.0696 (10)
H14A	−0.1984	0.7024	0.1697	0.104*
H14B	−0.2858	0.6514	0.1323	0.104*
H14C	−0.1400	0.8177	0.1381	0.104*
O1W	0.7487 (4)	0.8396 (2)	0.01513 (5)	0.0579 (6)
H1WA	0.6231	0.8390	0.0309	0.087*
H1WB	0.7808	0.7339	0.0114	0.087*

	U11	U22	U33	U12	U13	U23
O1	0.0504 (10)	0.0340 (8)	0.0232 (7)	−0.0048 (8)	−0.0058 (7)	0.0061 (6)
O2	0.0589 (11)	0.0259 (8)	0.0391 (9)	0.0043 (8)	0.0131 (8)	0.0045 (7)
O3	0.0378 (8)	0.0389 (8)	0.0226 (7)	−0.0109 (7)	0.0029 (6)	−0.0054 (6)
O4	0.0266 (8)	0.0428 (9)	0.0326 (8)	−0.0055 (7)	−0.0060 (7)	0.0056 (7)
O5	0.0428 (9)	0.0267 (7)	0.0205 (6)	0.0025 (7)	−0.0005 (7)	0.0016 (6)
O6	0.0548 (11)	0.0289 (8)	0.0326 (8)	−0.0085 (8)	0.0020 (8)	−0.0043 (7)
O11	0.101 (2)	0.158 (3)	0.0708 (18)	−0.019 (3)	−0.0407 (17)	−0.029 (2)
O12	0.211 (4)	0.120 (2)	0.0396 (12)	−0.013 (3)	−0.0491 (19)	0.0032 (15)
N1	0.104 (3)	0.082 (2)	0.0393 (14)	0.021 (2)	−0.0273 (16)	−0.0178 (14)
C1	0.0346 (11)	0.0263 (10)	0.0247 (9)	−0.0019 (9)	−0.0023 (9)	0.0051 (8)
C2	0.0335 (11)	0.0256 (9)	0.0258 (9)	−0.0022 (9)	0.0035 (9)	0.0010 (8)
C3	0.0283 (10)	0.0289 (10)	0.0199 (8)	−0.0053 (9)	0.0013 (8)	−0.0012 (8)
C4	0.0275 (10)	0.0287 (10)	0.0200 (9)	−0.0053 (8)	−0.0007 (8)	0.0044 (8)
C5	0.0305 (11)	0.0259 (9)	0.0234 (9)	−0.0055 (9)	−0.0031 (8)	0.0034 (8)
C6	0.0435 (13)	0.0289 (10)	0.0296 (10)	0.0001 (10)	−0.0060 (9)	0.0001 (9)
C7	0.0494 (14)	0.0309 (11)	0.0248 (10)	0.0063 (10)	−0.0055 (10)	−0.0004 (9)
C8	0.085 (2)	0.0448 (15)	0.0267 (11)	−0.0106 (15)	−0.0050 (13)	0.0029 (10)
C9	0.109 (3)	0.0573 (17)	0.0229 (11)	−0.002 (2)	−0.0065 (15)	0.0044 (12)
C10	0.071 (2)	0.0533 (16)	0.0296 (12)	0.0133 (16)	−0.0161 (13)	−0.0103 (12)
C11	0.074 (2)	0.079 (2)	0.0422 (15)	−0.024 (2)	−0.0151 (15)	−0.0040 (15)
C12	0.076 (2)	0.069 (2)	0.0341 (13)	−0.0261 (18)	−0.0139 (14)	0.0098 (13)
C13	0.0567 (16)	0.0445 (14)	0.0282 (11)	−0.0012 (13)	0.0004 (11)	−0.0034 (11)
C14	0.0544 (19)	0.097 (3)	0.0570 (18)	0.0062 (19)	0.0048 (15)	−0.0203 (18)
O1W	0.0500 (11)	0.0482 (11)	0.0753 (13)	−0.0145 (10)	0.0207 (11)	−0.0187 (10)

O1—C1	1.408 (2)	C5—H5	0.9800
O1—C7	1.375 (3)	C5—C6	1.504 (3)
O2—H2B	0.8200	C6—H6A	0.9700
O2—C2	1.420 (3)	C6—H6B	0.9700
O3—H3B	0.8201	C7—C8	1.379 (3)
O3—C3	1.423 (2)	C7—C12	1.370 (4)
O4—H4B	0.8199	C8—H8	0.9300
O4—C4	1.424 (3)	C8—C9	1.382 (4)
O5—C1	1.408 (3)	C9—H9	0.9300
O5—C5	1.438 (2)	C9—C10	1.358 (5)
O6—C6	1.421 (3)	C10—C11	1.355 (4)
O6—C13	1.434 (3)	C11—H11	0.9300
O11—N1	1.207 (5)	C11—C12	1.384 (4)
O12—N1	1.212 (4)	C12—H12	0.9300
N1—C10	1.469 (4)	C13—H13A	0.9700
C1—H1	0.9800	C13—H13B	0.9700
C1—C2	1.520 (3)	C13—C14	1.493 (4)
C2—H2A	0.9800	C14—H14A	0.9600
C2—C3	1.521 (3)	C14—H14B	0.9600
C3—H3A	0.9800	C14—H14C	0.9600
C3—C4	1.526 (3)	O1W—H1WA	0.8898
C4—H4A	0.9800	O1W—H1WB	0.8902
C4—C5	1.520 (3)
C7—O1—C1	119.10 (18)	C6—C5—H5	108.9
C2—O2—H2B	109.5	O6—C6—C5	112.37 (18)
C3—O3—H3B	109.5	O6—C6—H6A	109.1
C4—O4—H4B	109.4	O6—C6—H6B	109.1
C1—O5—C5	111.77 (15)	C5—C6—H6A	109.1
C6—O6—C13	115.74 (19)	C5—C6—H6B	109.1
O11—N1—O12	123.3 (3)	H6A—C6—H6B	107.9
O11—N1—C10	119.0 (3)	O1—C7—C8	114.2 (2)
O12—N1—C10	117.7 (4)	C12—C7—O1	125.6 (2)
O1—C1—H1	110.5	C12—C7—C8	120.2 (2)
O1—C1—C2	107.33 (16)	C7—C8—H8	120.3
O5—C1—O1	106.40 (16)	C7—C8—C9	119.5 (3)
O5—C1—H1	110.5	C9—C8—H8	120.3
O5—C1—C2	111.35 (17)	C8—C9—H9	120.2
C2—C1—H1	110.5	C10—C9—C8	119.5 (3)
O2—C2—C1	109.70 (18)	C10—C9—H9	120.2
O2—C2—H2A	110.3	C9—C10—N1	118.8 (3)
O2—C2—C3	107.99 (16)	C11—C10—N1	119.6 (3)
C1—C2—H2A	110.3	C11—C10—C9	121.6 (3)
C1—C2—C3	108.08 (16)	C10—C11—H11	120.3
C3—C2—H2A	110.3	C10—C11—C12	119.4 (3)
O3—C3—C2	113.03 (16)	C12—C11—H11	120.3
O3—C3—H3A	106.8	C7—C12—C11	119.7 (3)
O3—C3—C4	111.82 (17)	C7—C12—H12	120.1
C2—C3—H3A	106.8	C11—C12—H12	120.1
C2—C3—C4	111.25 (16)	O6—C13—H13A	109.0
C4—C3—H3A	106.8	O6—C13—H13B	109.0
O4—C4—C3	108.80 (17)	O6—C13—C14	112.9 (2)
O4—C4—H4A	109.0	H13A—C13—H13B	107.8
O4—C4—C5	110.55 (17)	C14—C13—H13A	109.0
C3—C4—H4A	109.0	C14—C13—H13B	109.0
C5—C4—C3	110.47 (17)	C13—C14—H14A	109.5
C5—C4—H4A	109.0	C13—C14—H14B	109.5
O5—C5—C4	110.93 (16)	C13—C14—H14C	109.5
O5—C5—H5	108.9	H14A—C14—H14B	109.5
O5—C5—C6	107.41 (17)	H14A—C14—H14C	109.5
C4—C5—H5	108.9	H14B—C14—H14C	109.5
C6—C5—C4	111.64 (17)	H1WA—O1W—H1WB	104.0
O1—C1—C2—O2	−67.1 (2)	C1—O5—C5—C6	−177.75 (17)
O1—C1—C2—C3	175.37 (17)	C1—C2—C3—O3	179.94 (18)
O1—C7—C8—C9	177.4 (3)	C1—C2—C3—C4	−53.3 (2)
O1—C7—C12—C11	−177.0 (3)	C2—C3—C4—O4	−70.0 (2)
O2—C2—C3—O3	61.3 (2)	C2—C3—C4—C5	51.5 (2)
O2—C2—C3—C4	−171.91 (17)	C3—C4—C5—O5	−53.3 (2)
O3—C3—C4—O4	57.4 (2)	C3—C4—C5—C6	−173.06 (17)
O3—C3—C4—C5	178.97 (16)	C4—C5—C6—O6	−166.46 (18)
O4—C4—C5—O5	67.2 (2)	C5—O5—C1—O1	179.69 (16)
O4—C4—C5—C6	−52.6 (2)	C5—O5—C1—C2	−63.7 (2)
O5—C1—C2—O2	176.81 (16)	C6—O6—C13—C14	−77.1 (3)
O5—C1—C2—C3	59.3 (2)	C7—O1—C1—O5	−79.8 (2)
O5—C5—C6—O6	71.7 (2)	C7—O1—C1—C2	160.93 (19)
O11—N1—C10—C9	179.0 (4)	C7—C8—C9—C10	−0.5 (5)
O11—N1—C10—C11	−2.0 (5)	C8—C7—C12—C11	1.6 (5)
O12—N1—C10—C9	−2.8 (5)	C8—C9—C10—N1	−178.7 (3)
O12—N1—C10—C11	176.2 (4)	C8—C9—C10—C11	2.3 (5)
N1—C10—C11—C12	178.9 (3)	C9—C10—C11—C12	−2.1 (5)
C1—O1—C7—C8	176.3 (2)	C10—C11—C12—C7	0.1 (6)
C1—O1—C7—C12	−4.9 (4)	C12—C7—C8—C9	−1.4 (5)
C1—O5—C5—C4	60.0 (2)	C13—O6—C6—C5	−96.4 (2)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2B···O6i	0.82	1.85	2.670 (2)	179
O3—H3B···O1Wii	0.82	1.91	2.711 (2)	167
O4—H4B···O3iii	0.82	1.97	2.785 (2)	170
O1W—H1WA···O2iv	0.89	1.90	2.776 (3)	166
O1W—H1WB···O3v	0.89	2.39	3.208 (2)	154
C3—H3A···O4vi	0.98	2.35	3.283 (3)	158
C13—H13A···O12vii	0.97	2.55	3.167 (3)	121
C13—H13B···O5	0.97	2.53	3.173 (3)	123