Inter- and intramolecular C—H...π interactions in morphine bis­(1-naph­tho­ate)

The crystal structure of morphine bis­(1-naph­tho­ate) [or 7,8-di­de­hydro-4,5-epoxy-17-methyl­morphinan-2,6-diyl bis­(naph­thal­ene-1-carboxyl­ate)], C₃₉H₃₁NO₅, determined at 123 K, shows extensive C—H...π interactions in the crystal lattice. Of particular interest is an intramolecular C—H...π interaction within the unit cell between the two naphthoyl groups. Comparison of the opiate scaffolds of morphine bis­(1-naph­tho­ate) and morphine shows only a small increase in strain due to the steric bulk of the naphthoyl groups. The crystal packing shows distinct areas of packing for the naphthalene/aromatic groups and the opiate backbone. Extensive inter- and intramolecular C—H...π interactions lead to a densely packed aromatic region in the crystal lattice.

S1. Comment

Opiate-derived compounds have been widely investigated for their medicinal properties (Schmidhammer, 1998; Rawal, 1999). During our research on the development of modified and improved synthetic pathways to pharmaceutical opiates, we have encountered problems with opiate products binding to various transition metals. In particular, Fe^II and Fe^III in the Polonoski reaction and MnO₂ in oxidation protocols have been especially problematic. The improved work-up procedures we have used to tackle this problem include competitive binding (Scammells et al., 2002) and ionic liquid extraction (Singer & Scammells, 2001). When using morphine as a starting material in opiate synthesis it is usual to protect either one or both of the hydroxyl groups. Our latest approach to inhibit binding of the opiate to the transition metal is by applying suitable protecting group methodology.

We reasoned that the O atoms of the phenol, ether and hydroxy groups (3-, 4/5- and 6-positions, respectively) of morphine and related opiates may be responsible for these interactions with transition metal ions. As a result, we were interested in employing a protecting group that addressed this issue, and we chose to investigate protection of the 3- and 6-OH group by the 1-naphthoyl group. This group not only reduces the electron density of the O atom in the 3- and 6-positions (via its electron-withdrawing resonance effect) but also supplies considerable steric bulk to further inhibit binding of transition metals to the opiate pocket. However, because of the close spatial proximity of the two alcohol groups of morphine-derived opiates, we were interested in determining the orientations of the ester groups and which of the ester groups would be more distorted from its normal position. Other properties we were hoping to affect were polarity and solubility, in particular the ease of purification of the opiate intermediates by improved column chromatography characteristics and the ease of crystallization of the product from related opiate by-products.

In the title compound, (I) (Fig. 1), the phenol naphthalenecarboxylate group (Nap1) is in an orientation favouring intramolecular C—H···π interactions (Table 1) with the naphthalenecarboxylate group attached to the secondary alcohol (Nap2). The distance between the Nap1 and Nap2 planes and the interplanar angle [65.22 (6) °] can be interpreted as a C—H···π non-bonding interaction.

Intermolecular C—H···π interactions between this molecule and its closest neighbours are also present in the crystal lattice. (Fig. 2 and Table 1). There are extensive intra- and intermolecular C—H···π interactions within the crystal lattice. The interactions involving atoms C3 and C37 generate a ladder along [100] while that involving atom C22 generates a spiral chain along [100].

Several crystal structures of benzoyl-protected phenols have been solved, the simplest being phenol benzoylate (Shibakami & Sekiya, 1995). The angle between the phenol C—O bond and the benzene ring in phenol benzoylate is 3.3°, which is similar to the angle for the analogous bond in (I) [5.1 (s.u. value?) °]. The dihedral angle between the phenol aromatic ring and the carboxy group is 63.3° in phenol benzoylate [cf.76.7 (4)° for the dihedral angle C1—C2—O2—C18 in (I)]. The dihedral angle between the benzoyl aromatic ring and the carboxy group in phenol benzoylate is 8.8° [cf. values in (I) of O3—C18—C19—C20 = 41.6 (4) and O5—C29—C30—C31 = 25.7 (4)°].

Several properties of (I) were affected by the presence of the large naphthoyl-protecting groups [cf. codeine methyl ether (CME) or morphine]. (I) was considerably less polar than CME or morphine, and purification of (I) by column chromatography was successful using 10% methanol in dichloromethane. In this solvent system, morphine and CME had an R_f value of 0.0. Compound (I) also has a much lower solubility than morphine or CME in methanol and thus has the potential for facile purification of the desired opiate product from by-products during further synthesis.

This work has demonstrated that the bulky naphthoyl group can be attached to the morphine scaffold to give morphine di-(naphthalene-1-carboxylate), which has significantly different physical properties to related opiates. Intramolecular C—H···π non-bonding interactions are present in the unit cell, as well as extensive intermolecular C—H···π interactions within the crystal lattice.

S2. Experimental

Compound (I) was prepared by stirring (-)-morphine and 1-naphthoyl chloride together at room temperature in pyridine for 16 h, and then heating the mixture at 333 K for 4 h. The crude product was purified by column chromatography in order to remove a small amount of morphine mono-(naphthalene-1-carboxylate). Prism-like crystals of (I) were grown by slow evaporation of a methanol solution (m.p. 462.5–464 K).

S3. Refinement

The Flack (1983) test results were ambiguous so the Friedel pairs were merged and the absolute structure was assigned by reference to (-)-morphine.

Computing details

Data collection: Collect (Nonius, 1997–2000); cell refinement: HKL SCALEPACK (Otwinowski & Minor, 1997); data reduction: HKL DENZO (Otwinowski & Minor, 1997) and SCALEPACK; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures

	Fig. 1. ORTEP-3 (Farrugia, 1997) view of (I). Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. The C—H···π interactions in (I). Molecules are labelled by symmetry operator.

(I)

Crystal data

C39H31NO5	Dx = 1.306 Mg m^−3
Mr = 593.67	Melting point = 189.5–191 K
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 20348 reflections
a = 7.8435 (1) Å	θ = 3.5–27.9°
b = 9.7218 (2) Å	µ = 0.09 mm^−1
c = 39.5921 (9) Å	T = 123 K
V = 3019.0 (1) Å^3	Prismatic, colourless
Z = 4	0.22 × 0.18 × 0.15 mm
F(000) = 1248

Data collection

Nonius KappaCCD diffractometer	2498 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.068
Horizonally mounted graphite crystal monochromator	θmax = 27.9°, θmin = 3.7°
Detector resolution: 9 pixels mm^-1	h = −10→10
CCD rotation images, thick slices scans	k = −12→7
20279 measured reflections	l = −52→32
4065 independent reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.051	H-atom parameters constrained
wR(F^2) = 0.112	w = 1/[σ^2(Fo^2) + (0.0421P)^2 + 0.662P] where P = (Fo^2 + 2Fc^2)/3
S = 1.03	(Δ/σ)max < 0.001
4065 reflections	Δρmax = 0.23 e Å^−3
407 parameters	Δρmin = −0.25 e Å^−3
0 restraints	Absolute structure: Flack (1983)
Primary atom site location: structure-invariant direct methods

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	−0.0284 (4)	−0.0096 (3)	0.36308 (8)	0.0258 (7)
C2	0.0132 (4)	0.0184 (3)	0.39621 (8)	0.0298 (8)
C3	0.1789 (5)	−0.0061 (3)	0.40675 (9)	0.0338 (8)
H3	0.2087	0.0100	0.4297	0.041*
C4	0.3019 (4)	−0.0534 (3)	0.38452 (8)	0.0320 (8)
H4	0.4157	−0.0659	0.3921	0.038*
C5	0.2594 (4)	−0.0832 (3)	0.35084 (8)	0.0281 (8)
C6	0.0918 (4)	−0.0648 (3)	0.34178 (8)	0.0250 (7)
C7	0.0140 (4)	−0.0841 (3)	0.30730 (8)	0.0257 (7)
C8	−0.1393 (4)	0.0154 (3)	0.31061 (8)	0.0271 (8)
H8	−0.2386	−0.0226	0.2978	0.032*
C9	−0.0998 (4)	0.1631 (3)	0.29781 (8)	0.0277 (8)
H9	−0.1631	0.1775	0.2762	0.033*
C10	0.0841 (4)	0.1943 (4)	0.29157 (8)	0.0297 (8)
H10	0.1213	0.2868	0.2938	0.036*
C11	0.1980 (4)	0.0998 (4)	0.28306 (8)	0.0297 (8)
H11	0.3115	0.1274	0.2781	0.036*
C12	0.1521 (4)	−0.0495 (3)	0.28112 (8)	0.0270 (8)
H12	0.1067	−0.0696	0.2580	0.032*
C13	0.3036 (4)	−0.1471 (3)	0.28833 (8)	0.0307 (8)
H13	0.3926	−0.1265	0.2710	0.037*
C14	0.3870 (4)	−0.1197 (4)	0.32353 (8)	0.0328 (8)
H14A	0.4506	−0.2028	0.3306	0.039*
H14B	0.4699	−0.0435	0.3213	0.039*
C15	−0.0426 (4)	−0.2335 (3)	0.30211 (9)	0.0306 (8)
H15A	−0.1280	−0.2579	0.3195	0.037*
H15B	−0.0974	−0.2426	0.2797	0.037*
C16	0.1065 (4)	−0.3320 (3)	0.30431 (9)	0.0346 (9)
H16A	0.1481	−0.3358	0.3279	0.042*
H16B	0.0684	−0.4254	0.2978	0.042*
C17	0.3848 (5)	−0.3896 (4)	0.28184 (9)	0.0448 (10)
H17A	0.4312	−0.3991	0.3047	0.067*
H17B	0.4750	−0.3584	0.2665	0.067*
H17C	0.3412	−0.4787	0.2742	0.067*
C18	−0.2301 (4)	−0.0021 (4)	0.42977 (8)	0.0311 (8)
C19	−0.3634 (4)	0.0738 (3)	0.44873 (8)	0.0294 (8)
C20	−0.4162 (4)	0.1987 (4)	0.43702 (9)	0.0361 (9)
H20	−0.3602	0.2393	0.4182	0.043*
C21	−0.5529 (5)	0.2678 (4)	0.45255 (10)	0.0426 (10)
H21	−0.5899	0.3539	0.4439	0.051*
C22	−0.6327 (5)	0.2124 (4)	0.47998 (10)	0.0455 (10)
H22	−0.7245	0.2602	0.4903	0.055*
C23	−0.5793 (4)	0.0836 (4)	0.49308 (9)	0.0355 (8)
C24	−0.6603 (5)	0.0242 (4)	0.52175 (10)	0.0473 (11)
H24	−0.7524	0.0711	0.5322	0.057*
C25	−0.6083 (5)	−0.0979 (5)	0.53431 (10)	0.0491 (11)
H25	−0.6654	−0.1367	0.5532	0.059*
C26	−0.4712 (5)	−0.1672 (4)	0.51968 (10)	0.0441 (10)
H26	−0.4336	−0.2517	0.5291	0.053*
C27	−0.3898 (4)	−0.1147 (4)	0.49171 (9)	0.0367 (9)
H27	−0.2976	−0.1638	0.4818	0.044*
C28	−0.4426 (4)	0.0120 (3)	0.47759 (8)	0.0291 (8)
C29	−0.3269 (4)	0.2904 (3)	0.32364 (8)	0.0282 (8)
C30	−0.3655 (4)	0.4028 (3)	0.34800 (8)	0.0274 (8)
C31	−0.2400 (4)	0.4973 (3)	0.35490 (8)	0.0304 (8)
H31	−0.1305	0.4859	0.3451	0.036*
C32	−0.2699 (4)	0.6103 (4)	0.37609 (9)	0.0310 (8)
H32	−0.1813	0.6747	0.3803	0.037*
C33	−0.4246 (4)	0.6281 (3)	0.39064 (9)	0.0329 (8)
H33	−0.4431	0.7045	0.4052	0.039*
C34	−0.5590 (4)	0.5342 (3)	0.38447 (8)	0.0280 (8)
C35	−0.7207 (4)	0.5515 (4)	0.40014 (9)	0.0334 (9)
H35	−0.7398	0.6290	0.4143	0.040*
C36	−0.8487 (4)	0.4590 (4)	0.39526 (9)	0.0353 (9)
H36	−0.9561	0.4716	0.4059	0.042*
C37	−0.8205 (4)	0.3448 (4)	0.37436 (9)	0.0352 (9)
H37	−0.9102	0.2806	0.3709	0.042*
C38	−0.6671 (4)	0.3235 (4)	0.35878 (9)	0.0314 (8)
H38	−0.6516	0.2445	0.3450	0.038*
C39	−0.5307 (4)	0.4181 (4)	0.36301 (8)	0.0262 (7)
N1	0.2455 (3)	−0.2886 (3)	0.28206 (7)	0.0329 (7)
O1	−0.1801 (3)	0.0174 (2)	0.34684 (5)	0.0300 (5)
O2	−0.1054 (3)	0.0819 (2)	0.41801 (5)	0.0341 (6)
O3	−0.2301 (3)	−0.1242 (3)	0.42426 (6)	0.0460 (7)
O4	−0.1569 (3)	0.2668 (2)	0.32179 (6)	0.0298 (6)
O5	−0.4283 (3)	0.2277 (3)	0.30652 (6)	0.0401 (6)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0264 (16)	0.0238 (18)	0.0271 (18)	−0.0034 (15)	0.0010 (14)	0.0003 (16)
C2	0.0347 (19)	0.0275 (19)	0.0270 (18)	−0.0030 (16)	0.0069 (15)	−0.0042 (16)
C3	0.045 (2)	0.032 (2)	0.0240 (18)	−0.0026 (18)	−0.0028 (16)	−0.0039 (16)
C4	0.0306 (18)	0.033 (2)	0.033 (2)	−0.0008 (16)	−0.0040 (15)	0.0024 (16)
C5	0.0289 (17)	0.0274 (18)	0.0280 (19)	−0.0003 (16)	0.0006 (15)	−0.0011 (16)
C6	0.0242 (16)	0.0243 (18)	0.0265 (18)	−0.0030 (15)	0.0000 (14)	−0.0011 (15)
C7	0.0212 (15)	0.0302 (19)	0.0256 (18)	−0.0012 (15)	0.0019 (14)	−0.0030 (16)
C8	0.0230 (16)	0.0324 (19)	0.0257 (17)	−0.0032 (15)	0.0026 (14)	−0.0027 (16)
C9	0.0267 (17)	0.032 (2)	0.0245 (18)	0.0033 (16)	−0.0009 (15)	−0.0048 (15)
C10	0.0285 (17)	0.033 (2)	0.0271 (19)	−0.0056 (16)	0.0022 (16)	0.0028 (16)
C11	0.0249 (17)	0.038 (2)	0.0264 (19)	−0.0017 (16)	0.0018 (14)	0.0049 (17)
C12	0.0242 (16)	0.035 (2)	0.0222 (17)	0.0013 (15)	0.0024 (13)	−0.0002 (15)
C13	0.0274 (17)	0.038 (2)	0.0269 (19)	0.0016 (16)	0.0040 (15)	0.0007 (16)
C14	0.0252 (17)	0.040 (2)	0.033 (2)	0.0041 (16)	0.0020 (15)	0.0006 (17)
C15	0.0312 (18)	0.033 (2)	0.028 (2)	−0.0044 (16)	0.0010 (15)	−0.0033 (16)
C16	0.041 (2)	0.031 (2)	0.032 (2)	0.0012 (17)	0.0044 (17)	−0.0046 (16)
C17	0.048 (2)	0.048 (2)	0.038 (2)	0.017 (2)	0.0068 (19)	0.0009 (19)
C18	0.0362 (19)	0.032 (2)	0.0255 (18)	−0.0056 (18)	−0.0011 (15)	−0.0015 (17)
C19	0.0306 (17)	0.0278 (19)	0.0297 (19)	−0.0040 (16)	−0.0049 (15)	−0.0056 (16)
C20	0.042 (2)	0.035 (2)	0.031 (2)	−0.0018 (18)	−0.0067 (17)	−0.0045 (17)
C21	0.044 (2)	0.040 (2)	0.044 (2)	0.0066 (19)	−0.0122 (19)	−0.002 (2)
C22	0.038 (2)	0.047 (3)	0.052 (3)	0.0063 (19)	−0.004 (2)	−0.015 (2)
C23	0.0310 (18)	0.040 (2)	0.036 (2)	−0.0044 (18)	0.0014 (16)	−0.0098 (18)
C24	0.045 (2)	0.052 (3)	0.044 (2)	−0.010 (2)	0.016 (2)	−0.019 (2)
C25	0.056 (3)	0.049 (3)	0.042 (2)	−0.021 (2)	0.014 (2)	−0.011 (2)
C26	0.056 (2)	0.036 (2)	0.041 (2)	−0.007 (2)	0.002 (2)	0.0030 (19)
C27	0.039 (2)	0.034 (2)	0.037 (2)	−0.0044 (18)	0.0042 (18)	−0.0043 (17)
C28	0.0285 (16)	0.0283 (19)	0.0306 (19)	−0.0028 (16)	−0.0011 (15)	−0.0088 (16)
C29	0.0238 (16)	0.031 (2)	0.030 (2)	0.0015 (16)	−0.0025 (15)	0.0001 (16)
C30	0.0271 (17)	0.0257 (18)	0.0293 (19)	0.0052 (15)	−0.0032 (14)	0.0041 (16)
C31	0.0257 (16)	0.033 (2)	0.0322 (19)	0.0007 (16)	0.0003 (15)	0.0043 (17)
C32	0.0303 (18)	0.028 (2)	0.035 (2)	−0.0016 (16)	−0.0041 (16)	−0.0003 (16)
C33	0.038 (2)	0.0234 (19)	0.037 (2)	0.0020 (17)	−0.0041 (17)	−0.0033 (16)
C34	0.0275 (17)	0.029 (2)	0.0271 (18)	0.0062 (16)	−0.0031 (14)	0.0030 (16)
C35	0.0325 (19)	0.033 (2)	0.034 (2)	0.0078 (16)	−0.0005 (16)	−0.0048 (17)
C36	0.0283 (18)	0.039 (2)	0.038 (2)	0.0067 (17)	0.0015 (16)	−0.0009 (18)
C37	0.0249 (17)	0.037 (2)	0.043 (2)	−0.0024 (16)	−0.0012 (17)	0.0039 (19)
C38	0.0283 (17)	0.029 (2)	0.037 (2)	0.0051 (16)	−0.0037 (16)	0.0007 (16)
C39	0.0232 (16)	0.0289 (19)	0.0264 (18)	0.0050 (15)	−0.0043 (14)	0.0031 (16)
N1	0.0337 (15)	0.0358 (18)	0.0290 (16)	0.0081 (14)	0.0057 (14)	−0.0021 (14)
O1	0.0253 (11)	0.0385 (14)	0.0261 (13)	0.0021 (11)	0.0030 (10)	−0.0017 (11)
O2	0.0414 (14)	0.0319 (13)	0.0290 (13)	−0.0061 (12)	0.0095 (11)	−0.0042 (11)
O3	0.0536 (17)	0.0326 (15)	0.0519 (17)	−0.0070 (13)	0.0204 (14)	−0.0111 (13)
O4	0.0237 (11)	0.0326 (13)	0.0331 (14)	0.0035 (10)	−0.0019 (10)	−0.0051 (11)
O5	0.0272 (12)	0.0499 (16)	0.0433 (15)	−0.0001 (12)	−0.0035 (12)	−0.0151 (13)

Geometric parameters (Å, º)

C1—C6	1.374 (4)	C18—O3	1.206 (4)
C1—O1	1.378 (4)	C18—O2	1.357 (4)
C1—C2	1.379 (4)	C18—C19	1.484 (5)
C2—C3	1.385 (5)	C19—C20	1.363 (5)
C2—O2	1.411 (4)	C19—C28	1.433 (5)
C3—C4	1.385 (5)	C20—C21	1.407 (5)
C3—H3	0.9500	C20—H20	0.9500
C4—C5	1.404 (4)	C21—C22	1.365 (5)
C4—H4	0.9500	C21—H21	0.9500
C5—C6	1.374 (4)	C22—C23	1.418 (5)
C5—C14	1.515 (4)	C22—H22	0.9500
C6—C7	1.507 (4)	C23—C28	1.418 (5)
C7—C15	1.532 (4)	C23—C24	1.423 (5)
C7—C12	1.536 (4)	C24—C25	1.349 (5)
C7—C8	1.549 (4)	C24—H24	0.9500
C8—O1	1.470 (4)	C25—C26	1.395 (5)
C8—C9	1.555 (5)	C25—H25	0.9500
C8—H8	1.0000	C26—C27	1.376 (5)
C9—O4	1.456 (4)	C26—H26	0.9500
C9—C10	1.494 (4)	C27—C28	1.414 (5)
C9—H9	1.0000	C27—H27	0.9500
C10—C11	1.326 (4)	C29—O5	1.210 (4)
C10—H10	0.9500	C29—O4	1.355 (4)
C11—C12	1.497 (5)	C29—C30	1.488 (4)
C11—H11	0.9500	C30—C31	1.374 (4)
C12—C13	1.547 (4)	C30—C39	1.433 (4)
C12—H12	1.0000	C31—C32	1.402 (5)
C13—N1	1.471 (4)	C31—H31	0.9500
C13—C14	1.562 (4)	C32—C33	1.354 (5)
C13—H13	1.0000	C32—H32	0.9500
C14—H14A	0.9900	C33—C34	1.416 (5)
C14—H14B	0.9900	C33—H33	0.9500
C15—C16	1.514 (5)	C34—C35	1.422 (5)
C15—H15A	0.9900	C34—C39	1.430 (4)
C15—H15B	0.9900	C35—C36	1.362 (5)
C16—N1	1.464 (4)	C35—H35	0.9500
C16—H16A	0.9900	C36—C37	1.402 (5)
C16—H16B	0.9900	C36—H36	0.9500
C17—N1	1.469 (4)	C37—C38	1.368 (5)
C17—H17A	0.9800	C37—H37	0.9500
C17—H17B	0.9800	C38—C39	1.421 (5)
C17—H17C	0.9800	C38—H38	0.9500
C6—C1—O1	112.4 (3)	N1—C17—H17C	109.5
C6—C1—C2	119.9 (3)	H17A—C17—H17C	109.5
O1—C1—C2	127.7 (3)	H17B—C17—H17C	109.5
C1—C2—C3	118.3 (3)	O3—C18—O2	122.0 (3)
C1—C2—O2	120.8 (3)	O3—C18—C19	125.5 (3)
C3—C2—O2	120.6 (3)	O2—C18—C19	112.4 (3)
C4—C3—C2	121.3 (3)	C20—C19—C28	120.9 (3)
C4—C3—H3	119.4	C20—C19—C18	119.0 (3)
C2—C3—H3	119.4	C28—C19—C18	120.0 (3)
C3—C4—C5	120.5 (3)	C19—C20—C21	120.6 (4)
C3—C4—H4	119.8	C19—C20—H20	119.7
C5—C4—H4	119.8	C21—C20—H20	119.7
C6—C5—C4	116.6 (3)	C22—C21—C20	120.6 (4)
C6—C5—C14	118.4 (3)	C22—C21—H21	119.7
C4—C5—C14	124.7 (3)	C20—C21—H21	119.7
C5—C6—C1	123.2 (3)	C21—C22—C23	120.3 (4)
C5—C6—C7	127.4 (3)	C21—C22—H22	119.9
C1—C6—C7	109.1 (3)	C23—C22—H22	119.9
C6—C7—C15	110.9 (3)	C28—C23—C22	119.9 (3)
C6—C7—C12	107.3 (3)	C28—C23—C24	118.9 (4)
C15—C7—C12	108.8 (3)	C22—C23—C24	121.2 (4)
C6—C7—C8	99.2 (2)	C25—C24—C23	121.1 (4)
C15—C7—C8	112.2 (2)	C25—C24—H24	119.5
C12—C7—C8	117.9 (3)	C23—C24—H24	119.5
O1—C8—C7	105.1 (2)	C24—C25—C26	120.3 (4)
O1—C8—C9	110.4 (2)	C24—C25—H25	119.9
C7—C8—C9	113.2 (3)	C26—C25—H25	119.9
O1—C8—H8	109.3	C27—C26—C25	120.9 (4)
C7—C8—H8	109.3	C27—C26—H26	119.6
C9—C8—H8	109.3	C25—C26—H26	119.6
O4—C9—C10	105.3 (3)	C26—C27—C28	120.3 (3)
O4—C9—C8	111.5 (2)	C26—C27—H27	119.9
C10—C9—C8	115.7 (3)	C28—C27—H27	119.9
O4—C9—H9	108.0	C27—C28—C23	118.6 (3)
C10—C9—H9	108.0	C27—C28—C19	123.6 (3)
C8—C9—H9	108.0	C23—C28—C19	117.8 (3)
C11—C10—C9	123.5 (3)	O5—C29—O4	122.1 (3)
C11—C10—H10	118.2	O5—C29—C30	126.8 (3)
C9—C10—H10	118.2	O4—C29—C30	111.0 (3)
C10—C11—C12	121.5 (3)	C31—C30—C39	119.7 (3)
C10—C11—H11	119.2	C31—C30—C29	118.3 (3)
C12—C11—H11	119.2	C39—C30—C29	121.9 (3)
C11—C12—C7	110.3 (3)	C30—C31—C32	121.6 (3)
C11—C12—C13	113.6 (3)	C30—C31—H31	119.2
C7—C12—C13	106.4 (2)	C32—C31—H31	119.2
C11—C12—H12	108.8	C33—C32—C31	120.3 (3)
C7—C12—H12	108.8	C33—C32—H32	119.8
C13—C12—H12	108.8	C31—C32—H32	119.8
N1—C13—C12	107.8 (2)	C32—C33—C34	120.7 (3)
N1—C13—C14	116.1 (3)	C32—C33—H33	119.6
C12—C13—C14	112.4 (3)	C34—C33—H33	119.6
N1—C13—H13	106.7	C33—C34—C35	120.8 (3)
C12—C13—H13	106.7	C33—C34—C39	119.7 (3)
C14—C13—H13	106.7	C35—C34—C39	119.4 (3)
C5—C14—C13	113.6 (3)	C36—C35—C34	121.2 (3)
C5—C14—H14A	108.8	C36—C35—H35	119.4
C13—C14—H14A	108.8	C34—C35—H35	119.4
C5—C14—H14B	108.8	C35—C36—C37	119.4 (3)
C13—C14—H14B	108.9	C35—C36—H36	120.3
H14A—C14—H14B	107.7	C37—C36—H36	120.3
C16—C15—C7	111.6 (3)	C38—C37—C36	121.7 (3)
C16—C15—H15A	109.3	C38—C37—H37	119.2
C7—C15—H15A	109.3	C36—C37—H37	119.2
C16—C15—H15B	109.3	C37—C38—C39	120.7 (3)
C7—C15—H15B	109.3	C37—C38—H38	119.6
H15A—C15—H15B	108.0	C39—C38—H38	119.6
N1—C16—C15	111.0 (3)	C38—C39—C34	117.6 (3)
N1—C16—H16A	109.4	C38—C39—C30	124.4 (3)
C15—C16—H16A	109.4	C34—C39—C30	118.0 (3)
N1—C16—H16B	109.4	C16—N1—C17	111.4 (3)
C15—C16—H16B	109.4	C16—N1—C13	113.5 (3)
H16A—C16—H16B	108.0	C17—N1—C13	113.3 (3)
N1—C17—H17A	109.5	C1—O1—C8	105.4 (2)
N1—C17—H17B	109.5	C18—O2—C2	115.0 (3)
H17A—C17—H17B	109.5	C29—O4—C9	117.1 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	H···A	D···A	D—H···A
C3—H3···Cg2^i	2.98	3.711 (4)	135
C21—H21···Cg1	2.80	3.512 (4)	132
C22—H22···Cg2^ii	2.94	3.873 (4)	166
C37—H37···Cg3^iii	3.07	3.690 (4)	124

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