Crystal structure of 5,5-bis-(4-methyl-benz-yl)pyrimidine-2,4,6(1H,3H,5H)-trione monohydrate.

The asymmetric unit of the title compound, C20H20N2O3·H2O, contains two independent mol-ecules (A and B), with similar conformations and two independent water mol-ecules. In the crystal, N-H⋯O and Owater-H⋯O hydrogen bonds link all moieties into two crystallographically independent kinds of sheets parallel to the ac plane. These independent sheets, each containing either A or B mol-ecules, are further alternately stacked along the b axis and inter-connected via C-H⋯πar-yl inter-actions.

Chemical Context

Barbituric acid and its derivatives have historically been classified as compounds which act on the central nervous system (Barbachyn et al., 2007 ▸). These compounds have been widely used as therapeutic drugs such as anxiolytics, sedatives, hypnotics and anti-convulsants (Coupey, 1997 ▸). Recent investigations on barbituric acid derivatives revealed the applications of these compounds as anti­bacterial (Yilmaz et al., 2006 ▸; Sweidan et al., 2011 ▸), anti-viral (Clercq, 1986a ▸,b ▸; Baba et al., 1987 ▸), analgesic (Vida et al., 1975 ▸), anti-hypertensive (Bassin & Bleck, 2008 ▸) and as anti-cancer (Humar et al., 2004 ▸; Singh et al., 2009 ▸) agents. 5-Fluoro­uracil is a barbituric acid analogue, which has been widely employed as a clinically useful anti-cancer drug (Heidelberger & Arafield, 1963 ▸).

Inspired by the above facts, the title compound was synthesized by Knoevenagel condensation reaction (Prajapati and Gohain, 2006 ▸). A double-benzyl­ated product of barbituric acid was obtained by using two equivalents of 4-methyl benzyl chloride in the presence of catalytic amounts of 1,8-di­aza­bicyclo­undec-7-ene (DBU) and solvent aceto­nitrile. The obtained compound was characterized by 1H-NMR and mass spectroscopy. We report herein on its crystal structure.

Structural commentary

The title compound (I) (Fig. 1 ▸) crystallizes with two mol­ecules, A and B, in the asymmetric unit along with two water mol­ecules of crystallization. In both mol­ecules, the pyrimidine rings are nearly planar [r.m.s. deviations of 0.039 and 0.040 Å] and can be considered as a pseudo-mirror plane for each mol­ecule. In A, the benzene rings form dihedral angles of 49.70 (17) and 51.66 (17)° with the pyrimidine ring and are inclined each to other by 62.9 (2)°. In B, the corresponding angles are 50.44 (18), 69.90 (19) and 59.8 (2)°, respectively. In the related compound 5,5-di­benzyl­barbituric acid monohydrate (II) (Bhatt et al., 2007 ▸), which crystallizes with one independent mol­ecule and one water molecule in the asymmetric unit, the dihedral angles between the pyrimidine and two benzene rings are 54.09 (11) and 62.71 (11)°.

Figure 1

A view of (I), showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Supra­molecular features

In the first level of packing, the independent mol­ecules are linked directly to their symmetry equivalents via strong N2—HN2⋯O4 (A) and N3—HN3⋯O7 (B) hydrogen bonds (Table 1 ▸), forming chains running along a-axis direction. Thus, the graph set motif is C(6)C(6). Six chains pass through the unit cell. These chains are linked via water mol­ecules through N1—H1⋯O1 and O1—H1B⋯O5 (for A) and N4—HN4⋯O2 and O2—H2A⋯O8 (for B) hydrogen bonds (Table 1 ▸), each forming graph set motif D(2). In addition, the symmetry-dependent parallel chains are inter­connected via bridging water mol­ecules through O—H⋯O3 and O1—HIB⋯O5 (for A) and O2—H2B⋯O6 and O2—H2A⋯O8 (for B) hydrogen bonds (Table 1 ▸), forming sheets parallel to the ac plane (Fig. 2 ▸). The alternate sheets formed by A or B mol­ecules and water mol­ecules are inter­connected via C—H⋯π inter­actions (Fig. 3 ▸, Table 1 ▸), thus forming a three-dimensional structure.

Table 1

Hydrogen-bond geometry (, )

Cg is the centroid of the C13C18 benzene ring.

DHA	DH	HA	D A	DHA
N1HN1O1	0.86	1.94	2.787(4)	167
O1H1AO3i	0.84(3)	2.13(3)	2.949(3)	162
O1H1BO5ii	0.90(3)	1.90(3)	2.794(4)	175
N2HN2O4iii	0.86	1.94	2.767(2)	162
O2H2AO8iv	0.86(6)	1.88(6)	2.739(4)	177
O2H2BO6v	0.82(3)	2.16(3)	2.961(3)	169
N3HN3O7vi	0.86	1.90	2.739(2)	164
N4HN4O2	0.86	1.92	2.761(4)	166
C22H22Cg vii	0.93	2.97	3.5693	124

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

Figure 2

A portion of the crystal packing viewed along [100] and showing two kinds of hydrogen-bonded (thin blue lines) sheets, each containing either A or B mol­ecules. H atoms not involved in hydrogen bonding have been omitted for clarity.

Figure 3

A portion of the crystal packing viewed along [100] and showing C—H⋯π inter­actions as dotted lines. Magenta dots show the centroids of aryl rings. Thin blue lines denote hydrogen bonds. H atoms not involved in inter­molecular inter­actions were omitted for clarity.

There are several inter­esting differences between the two chemically closely related structures (I) and (II) (differing only by a methyl group on the two benzene rings). Firstly, (I) crystallizes in the ortho­rhom­bic space group Pca21, whereas (II) crystallizes in the monoclinic space group P21/n. Secondly, (I) crystallizes with two mol­ecules in its asymmetric unit, while (II) crystallizes with one independent mol­ecule. Lastly, in the crystal of compound (II), hydrogen bonding leads to a two-dimensional network in contrast to the three-dimensional architecture formed in (I).

Synthesis and crystallization

To an ice-cooled stirring solution of acetonitrile (5 ml), 4-methyl benzyl chloride (0.5 g, 0.0035 mol), 1,8-diazabicycloundec-7-ene (DBU) (0.5 g, 0.0035 mol) and barbituric acid (0.22 g, 0.0017 mol) were added. The reaction mixture was stirred to the room temperature and then refluxed for 8 h. Thin-layer chromatography showed the absence of any starting material. The reaction mixture was cooled and poured into ice-cold water. The solid obtained was extracted with ethyl acetate and the organic layer was washed with saturated ammonium chloride solution and dried over anhydrous sodium sulphate. The solvent was removed under reduced pressure to give the title compound as a white solid (Yield 0.54 g, 91.83%).

Colourless prisms of the title compound suitable for diffraction studies were grown from an ethyl acetate–petroleum ether solvent system in the ratio 2.5:7.5, by the solvent evaporation technique.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. The water H atoms were located in a difference Fourier map and freely refined. The amino and C-bound H atoms were fixed geometrically (N—H = 0.86, C—H = 0.93–0.97 Å) and allowed to ride on their parent atoms with 1.5U eq(C) for methyl H atoms and = 1.2U eq(N,C) for other H atoms.

Table 2

Experimental details

Crystal data
Chemical formula	C20H20N2O3H2O
M r	354.40
Crystal system, space group	Orthorhombic, P c a21
Temperature (K)	296
a, b, c ()	13.0920(17), 19.198(3), 15.827(2)
V (3)	3978.1(9)
Z	8
Radiation type	Mo K
(mm1)	0.08
Crystal size (mm)	0.39 0.27 0.19
Data collection
Diffractometer	Bruker APEXII
Absorption correction	Multi-scan (SADABS; Bruker, 2009 ▸)
T min, T max	0.973, 0.984
No. of measured, independent and observed [I > 2(I)] reflections	61392, 8543, 4909
R int	0.057
(sin /)max (1)	0.649
Refinement
R[F 2 > 2(F 2)], wR(F 2), S	0.049, 0.135, 0.98
No. of reflections	8543
No. of parameters	489
No. of restraints	29
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
max, min (e 3)	0.20, 0.14
Absolute structure	Flack (1983 ▸), 4587 Friedel pairs
Absolute structure parameter	0.1(1)

Computer programs: APEX2, SAINT-Plus and XPREP (Bruker, 2009 ▸), SHELXS97 and SHELXL97 (Sheldrick, 2008 ▸) and Mercury (Macrae et al., 2008 ▸).

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S205698901402619X/cv5478sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S205698901402619X/cv5478Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S205698901402619X/cv5478Isup3.cml

CCDC reference: 1036677

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

C20H20N2O3·H2O	Prism
Mr = 354.40	Dx = 1.183 Mg m−3
Orthorhombic, Pca21	Melting point: 443 K
Hall symbol: P 2c -2ac	Mo Kα radiation, λ = 0.71073 Å
a = 13.0920 (17) Å	Cell parameters from 138 reflections
b = 19.198 (3) Å	θ = 1.9–27.5°
c = 15.827 (2) Å	µ = 0.08 mm−1
V = 3978.1 (9) Å3	T = 296 K
Z = 8	Prism, colourless
F(000) = 1504	0.39 × 0.27 × 0.19 mm

Bruker APEXII diffractometer	4909 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.057
Graphite monochromator	θmax = 27.5°, θmin = 1.9°
phi and φ scans	h = −16→16
Absorption correction: multi-scan (SADABS; Bruker, 2009)	k = −24→24
Tmin = 0.973, Tmax = 0.984	l = −19→20
61392 measured reflections	1 standard reflections every 1 reflections
8543 independent reflections	intensity decay: 1%

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.049	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.135	w = 1/[σ2(Fo2) + (0.0724P)2] where P = (Fo2 + 2Fc2)/3
S = 0.98	(Δ/σ)max < 0.001
8543 reflections	Δρmax = 0.20 e Å−3
489 parameters	Δρmin = −0.14 e Å−3
29 restraints	Absolute structure: Flack (1983), 4587 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.1 (1)

Experimental. All the solvents employed were of analytical grade. Starting materials and reagents were purchased from Sigma Chemical co. (Saint Louis, USA). The reaction progress was monitored by thin layer chromatography using TLC Silica gel 60 F254 (Merck), and spots were visualized by using ultraviolet light of 254 nm. Melting point was determined by using open capillary and uncorrected value is given. 1H-NMR spectrum was recorded on Jeol-400 MHz NMR instrument using CDCl3/DMSO-d6 as solvent. Chemical shift values were expressed in δ (p.p.m.) relative to tetramethylsilane (TMS) as an internal reference standard. Mass spectrum of the compound was recorded on Shimadzu LC-2010EV with ESI probe.1H-NMR spectral data of I clearly indicated the formation of I. In the spectrum, a singlet at δ (p.p.m.) value 2.23 corresponds to the two para-methyl groups, while, a singlet signal at δ (p.p.m.) value 3.22 is for four alkyl protons (two CH2 groups) and two doublets at 6.93 and 7.07 corresponds to the eight aromatic protons. Two NH protons of the barbituric acid moiety appeared at δ value 7.85 as a singlet. Mass spectrum of I gave a peak with (m/z) value = 335.0 which exactly matches with its calculated mass.

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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
C6	0.8772 (3)	0.7536 (2)	0.0448 (3)	0.1148 (12)
H6	0.8098	0.7382	0.0448	0.138*
C19	0.9200 (4)	0.6505 (2)	0.1358 (3)	0.174 (2)
H19A	0.9340	0.6568	0.1949	0.262*
H19B	0.9595	0.6122	0.1147	0.262*
H19C	0.8487	0.6409	0.1281	0.262*
C39	0.8413 (4)	0.8470 (2)	0.2588 (3)	0.205 (3)
H39A	0.8257	0.8861	0.2944	0.308*
H39B	0.8045	0.8512	0.2066	0.308*
H39C	0.9133	0.8461	0.2474	0.308*
C40	0.7798 (5)	0.1883 (2)	0.2643 (4)	0.192 (2)
H40A	0.8105	0.1576	0.3049	0.288*
H40B	0.8263	0.1956	0.2182	0.288*
H40C	0.7179	0.1678	0.2434	0.288*
H2B	0.520 (2)	0.5106 (14)	0.109 (2)	0.088 (10)*
H2A	0.583 (3)	0.513 (2)	0.036 (4)	0.156 (19)*
H1A	1.225 (2)	0.9802 (12)	0.272 (2)	0.092 (10)*
H1B	1.1706 (19)	1.0021 (12)	0.342 (2)	0.070 (8)*
C1	0.9482 (4)	0.7161 (2)	0.0883 (3)	0.1193 (12)
C2	1.0471 (4)	0.7405 (2)	0.0846 (2)	0.1205 (13)
H2	1.0982	0.7152	0.1115	0.145*
C3	1.0739 (3)	0.8016 (2)	0.0421 (2)	0.1027 (11)
H3	1.1413	0.8168	0.0427	0.123*
C4	1.0001 (2)	0.83994 (14)	−0.00130 (15)	0.0727 (7)
C5	0.9012 (2)	0.81420 (17)	0.0001 (2)	0.0877 (9)
H5	0.8500	0.8376	−0.0291	0.105*
C7	1.02806 (17)	0.90622 (13)	−0.04658 (16)	0.0715 (7)
H7A	0.9901	0.9082	−0.0992	0.086*
H7B	1.1001	0.9044	−0.0608	0.086*
C8	1.00757 (17)	0.97436 (13)	0.00349 (16)	0.0563 (6)
C9	0.89331 (16)	0.98272 (13)	0.01741 (17)	0.0522 (6)
C10	0.91876 (18)	1.00450 (11)	0.1679 (2)	0.0510 (6)
C11	1.06796 (15)	0.97321 (12)	0.08499 (16)	0.0561 (6)
C12	1.04400 (17)	1.03834 (13)	−0.04920 (18)	0.0678 (7)
H12A	1.1174	1.0350	−0.0565	0.081*
H12B	1.0132	1.0356	−0.1048	0.081*
C13	1.01968 (17)	1.10829 (15)	−0.01215 (17)	0.0685 (7)
C14	0.9285 (2)	1.14188 (16)	−0.0302 (2)	0.0845 (8)
H14	0.8828	1.1210	−0.0673	0.101*
C15	0.9035 (3)	1.2049 (2)	0.0051 (3)	0.1032 (11)
H15	0.8415	1.2257	−0.0085	0.124*
C16	0.9688 (4)	1.23778 (19)	0.0602 (3)	0.1149 (12)
C17	1.0608 (4)	1.2054 (2)	0.0784 (3)	0.1245 (14)
H17	1.1066	1.2268	0.1152	0.149*
C18	1.0859 (2)	1.14120 (18)	0.0425 (2)	0.0941 (9)
H18	1.1481	1.1204	0.0556	0.113*
C20	0.9419 (4)	1.3093 (2)	0.0984 (4)	0.180 (2)
H20A	0.9712	1.3131	0.1538	0.270*
H20B	0.8690	1.3139	0.1022	0.270*
H20C	0.9687	1.3456	0.0629	0.270*
C21	0.8100 (4)	0.7794 (2)	0.3035 (3)	0.1294 (14)
C22	0.8734 (3)	0.7433 (2)	0.3546 (3)	0.1207 (12)
H22	0.9391	0.7598	0.3642	0.145*
C23	0.8418 (2)	0.68184 (19)	0.3932 (2)	0.0984 (11)
H23	0.8869	0.6585	0.4287	0.118*
C24	0.7465 (2)	0.65484 (16)	0.38039 (18)	0.0820 (8)
C25	0.6804 (3)	0.6924 (2)	0.3298 (2)	0.1110 (12)
H25	0.6142	0.6764	0.3210	0.133*
C26	0.7127 (4)	0.7546 (2)	0.2916 (3)	0.1376 (16)
H26	0.6674	0.7794	0.2577	0.165*
C27	0.71252 (17)	0.58865 (16)	0.42374 (18)	0.0824 (9)
H27A	0.6397	0.5916	0.4342	0.099*
H27B	0.7464	0.5857	0.4781	0.099*
C28	0.73450 (17)	0.52040 (14)	0.37356 (17)	0.0655 (7)
C29	0.67384 (16)	0.52234 (14)	0.29184 (18)	0.0635 (6)
C30	0.82374 (18)	0.49247 (12)	0.20860 (19)	0.0514 (6)
C31	0.84770 (17)	0.51243 (15)	0.35966 (18)	0.0630 (7)
C32	0.69710 (19)	0.45597 (16)	0.42547 (17)	0.0812 (8)
H32A	0.7295	0.4571	0.4806	0.097*
H32B	0.6240	0.4601	0.4342	0.097*
C33	0.7185 (2)	0.38700 (16)	0.38549 (18)	0.0784 (8)
C34	0.8099 (2)	0.3523 (2)	0.3962 (2)	0.1020 (10)
H34	0.8596	0.3716	0.4311	0.122*
C35	0.8296 (4)	0.2887 (3)	0.3557 (4)	0.1307 (16)
H35	0.8928	0.2673	0.3622	0.157*
C36	0.7556 (5)	0.2579 (2)	0.3061 (3)	0.1243 (12)
C37	0.6641 (4)	0.2918 (2)	0.2993 (3)	0.1226 (13)
H37	0.6127	0.2711	0.2676	0.147*
C38	0.6443 (2)	0.3541 (2)	0.3365 (2)	0.0993 (10)
H38	0.5808	0.3750	0.3293	0.119*
N1	1.01988 (13)	0.98950 (10)	0.15858 (17)	0.0572 (6)
HN1	1.0568	0.9904	0.2035	0.069*
N2	0.85962 (14)	0.99882 (10)	0.09608 (16)	0.0534 (5)
HN2	0.7952	1.0062	0.1017	0.064*
N3	0.88084 (14)	0.49787 (10)	0.28006 (15)	0.0558 (6)
HN3	0.9455	0.4913	0.2743	0.067*
N4	0.72171 (13)	0.50664 (10)	0.21786 (16)	0.0584 (6)
HN4	0.6847	0.5055	0.1730	0.070*
O1	1.16630 (18)	0.99390 (14)	0.2863 (2)	0.0976 (8)
O2	0.57806 (19)	0.51299 (15)	0.0904 (2)	0.1084 (10)
O3	0.88202 (13)	1.02084 (10)	0.23583 (12)	0.0709 (5)
O4	1.15820 (10)	0.95863 (10)	0.08464 (13)	0.0775 (5)
O5	0.83276 (12)	0.97775 (9)	−0.04055 (11)	0.0726 (5)
O6	0.86065 (13)	0.47823 (10)	0.14088 (12)	0.0709 (5)
O7	0.58342 (12)	0.53645 (12)	0.29178 (14)	0.0953 (6)
O8	0.90867 (13)	0.51705 (12)	0.41774 (13)	0.0874 (6)

	U11	U22	U33	U12	U13	U23
C6	0.137 (3)	0.088 (3)	0.119 (3)	−0.038 (2)	−0.003 (2)	−0.026 (2)
C19	0.312 (6)	0.093 (3)	0.119 (3)	−0.044 (3)	0.006 (4)	−0.005 (2)
C39	0.362 (8)	0.094 (3)	0.159 (4)	−0.046 (4)	0.014 (5)	−0.006 (3)
C40	0.294 (7)	0.109 (3)	0.172 (5)	0.019 (4)	0.044 (5)	0.025 (3)
C1	0.190 (4)	0.088 (3)	0.080 (2)	−0.001 (3)	−0.010 (3)	−0.019 (2)
C2	0.179 (4)	0.103 (3)	0.079 (2)	0.028 (3)	−0.022 (3)	0.003 (2)
C3	0.113 (2)	0.108 (3)	0.087 (2)	0.022 (2)	−0.009 (2)	−0.009 (2)
C4	0.0893 (18)	0.0841 (18)	0.0448 (15)	0.0125 (16)	0.0001 (14)	−0.0115 (14)
C5	0.094 (2)	0.087 (2)	0.082 (2)	−0.0126 (17)	−0.0143 (17)	−0.0221 (18)
C7	0.0651 (14)	0.105 (2)	0.0445 (16)	0.0115 (13)	0.0061 (12)	−0.0133 (15)
C8	0.0431 (11)	0.0879 (17)	0.0379 (13)	−0.0012 (12)	0.0014 (10)	0.0050 (13)
C9	0.0401 (12)	0.0792 (15)	0.0375 (16)	−0.0035 (10)	−0.0045 (11)	0.0052 (11)
C10	0.0432 (12)	0.0672 (15)	0.0426 (18)	−0.0026 (9)	0.0024 (13)	0.0077 (11)
C11	0.0365 (11)	0.0798 (16)	0.0520 (15)	−0.0043 (11)	0.0038 (11)	0.0030 (13)
C12	0.0529 (12)	0.097 (2)	0.0537 (16)	−0.0022 (12)	0.0092 (12)	0.0155 (15)
C13	0.0573 (13)	0.094 (2)	0.0543 (18)	−0.0113 (13)	−0.0003 (12)	0.0191 (15)
C14	0.0796 (18)	0.086 (2)	0.088 (2)	−0.0055 (15)	−0.0074 (15)	0.0160 (17)
C15	0.101 (2)	0.099 (3)	0.110 (3)	−0.002 (2)	0.006 (2)	0.029 (2)
C16	0.172 (4)	0.086 (3)	0.086 (3)	0.002 (3)	0.017 (3)	0.014 (2)
C17	0.178 (4)	0.114 (3)	0.082 (3)	−0.035 (3)	−0.038 (3)	0.011 (2)
C18	0.095 (2)	0.098 (2)	0.089 (2)	−0.0124 (18)	−0.0202 (17)	0.0148 (18)
C20	0.275 (6)	0.117 (3)	0.148 (4)	0.007 (3)	0.036 (4)	−0.011 (3)
C21	0.192 (4)	0.114 (3)	0.083 (3)	−0.010 (3)	−0.015 (3)	−0.039 (2)
C22	0.140 (3)	0.099 (3)	0.123 (3)	−0.013 (2)	−0.010 (3)	−0.030 (3)
C23	0.095 (2)	0.108 (3)	0.091 (3)	0.004 (2)	−0.0182 (18)	−0.036 (2)
C24	0.0795 (17)	0.115 (2)	0.0511 (16)	0.0048 (17)	−0.0033 (15)	−0.0236 (17)
C25	0.114 (2)	0.130 (3)	0.089 (3)	0.009 (2)	−0.034 (2)	−0.026 (2)
C26	0.203 (5)	0.109 (3)	0.100 (3)	0.015 (3)	−0.054 (3)	−0.018 (3)
C27	0.0600 (15)	0.135 (3)	0.0525 (18)	0.0095 (15)	0.0060 (12)	−0.0218 (18)
C28	0.0446 (12)	0.114 (2)	0.0377 (15)	−0.0038 (13)	0.0058 (11)	−0.0082 (15)
C29	0.0391 (12)	0.1030 (19)	0.0486 (15)	−0.0098 (12)	−0.0013 (11)	0.0014 (14)
C30	0.0467 (13)	0.0750 (16)	0.0327 (16)	−0.0054 (10)	−0.0042 (12)	0.0004 (10)
C31	0.0447 (13)	0.108 (2)	0.0363 (16)	−0.0031 (12)	−0.0027 (12)	−0.0025 (13)
C32	0.0672 (14)	0.133 (3)	0.0432 (15)	−0.0126 (16)	0.0118 (13)	0.0041 (17)
C33	0.0753 (17)	0.112 (2)	0.0479 (17)	−0.0106 (16)	0.0049 (14)	0.0165 (17)
C34	0.084 (2)	0.125 (3)	0.096 (2)	−0.0012 (19)	−0.0010 (18)	0.034 (2)
C35	0.127 (3)	0.118 (4)	0.147 (4)	0.027 (3)	0.024 (3)	0.053 (3)
C36	0.171 (4)	0.105 (3)	0.097 (3)	−0.002 (3)	0.026 (3)	0.011 (2)
C37	0.146 (4)	0.123 (3)	0.099 (3)	−0.004 (3)	−0.008 (3)	0.008 (3)
C38	0.101 (2)	0.113 (3)	0.084 (2)	−0.0056 (19)	−0.0081 (18)	0.004 (2)
N1	0.0406 (10)	0.0901 (14)	0.0408 (15)	−0.0008 (8)	−0.0098 (10)	0.0026 (10)
N2	0.0325 (9)	0.0872 (14)	0.0405 (14)	0.0011 (7)	−0.0005 (10)	0.0027 (8)
N3	0.0336 (10)	0.0979 (15)	0.0360 (15)	−0.0022 (8)	0.0001 (10)	−0.0017 (9)
N4	0.0423 (11)	0.0982 (15)	0.0347 (14)	−0.0044 (8)	−0.0038 (10)	−0.0027 (9)
O1	0.0577 (12)	0.192 (2)	0.0431 (15)	0.0075 (11)	−0.0041 (12)	−0.0181 (12)
O2	0.0582 (13)	0.223 (3)	0.0443 (16)	0.0125 (12)	−0.0046 (12)	0.0058 (14)
O3	0.0593 (10)	0.1132 (14)	0.0402 (11)	0.0041 (9)	0.0053 (8)	−0.0093 (9)
O4	0.0389 (8)	0.1202 (15)	0.0733 (12)	0.0012 (8)	−0.0007 (8)	−0.0006 (11)
O5	0.0535 (9)	0.1195 (15)	0.0448 (11)	−0.0020 (9)	−0.0080 (9)	−0.0004 (10)
O6	0.0649 (10)	0.1105 (14)	0.0373 (11)	0.0007 (9)	0.0047 (8)	−0.0088 (10)
O7	0.0366 (9)	0.174 (2)	0.0751 (13)	−0.0020 (10)	−0.0013 (9)	−0.0119 (13)
O8	0.0517 (9)	0.1655 (18)	0.0449 (11)	0.0017 (10)	−0.0126 (9)	−0.0159 (11)

C6—C1	1.363 (5)	C16—C20	1.541 (6)
C6—C5	1.397 (5)	C17—C18	1.396 (5)
C19—C1	1.513 (6)	C21—C22	1.351 (6)
C39—C21	1.534 (6)	C21—C26	1.373 (5)
C40—C36	1.524 (6)	C22—C23	1.392 (5)
C1—C2	1.378 (6)	C23—C24	1.367 (4)
C2—C3	1.396 (5)	C24—C25	1.383 (5)
C3—C4	1.396 (4)	C24—C27	1.511 (4)
C4—C5	1.386 (4)	C25—C26	1.403 (6)
C4—C7	1.506 (4)	C27—C28	1.559 (4)
C7—C8	1.553 (3)	C28—C31	1.506 (3)
C8—C11	1.513 (3)	C28—C29	1.518 (4)
C8—C9	1.521 (3)	C28—C32	1.564 (4)
C8—C12	1.559 (4)	C29—O7	1.214 (3)
C9—O5	1.216 (3)	C29—N4	1.362 (4)
C9—N2	1.357 (3)	C30—O6	1.207 (3)
C10—O3	1.218 (3)	C30—N3	1.360 (3)
C10—N1	1.363 (3)	C30—N4	1.371 (3)
C10—N2	1.380 (4)	C31—O8	1.221 (3)
C11—O4	1.214 (2)	C31—N3	1.361 (4)
C11—N1	1.360 (3)	C32—C33	1.494 (4)
C12—C13	1.500 (4)	C33—C34	1.380 (4)
C13—C18	1.378 (4)	C33—C38	1.393 (4)
C13—C14	1.386 (4)	C34—C35	1.403 (6)
C14—C15	1.372 (5)	C35—C36	1.380 (6)
C15—C16	1.374 (5)	C36—C37	1.368 (6)
C16—C17	1.387 (6)	C37—C38	1.358 (6)
C1—C6—C5	122.8 (4)	C26—C21—C39	118.6 (5)
C6—C1—C2	116.1 (4)	C21—C22—C23	121.0 (4)
C6—C1—C19	121.7 (5)	C24—C23—C22	121.9 (3)
C2—C1—C19	122.2 (5)	C23—C24—C25	117.3 (3)
C1—C2—C3	122.8 (4)	C23—C24—C27	121.4 (3)
C4—C3—C2	120.4 (4)	C25—C24—C27	121.2 (3)
C5—C4—C3	116.8 (3)	C24—C25—C26	120.4 (4)
C5—C4—C7	122.4 (3)	C21—C26—C25	121.0 (4)
C3—C4—C7	120.8 (3)	C24—C27—C28	114.9 (2)
C4—C5—C6	121.0 (3)	C31—C28—C29	113.1 (2)
C4—C7—C8	115.3 (2)	C31—C28—C27	110.0 (2)
C11—C8—C9	113.1 (2)	C29—C28—C27	108.5 (2)
C11—C8—C7	109.4 (2)	C31—C28—C32	107.7 (2)
C9—C8—C7	109.44 (19)	C29—C28—C32	107.7 (2)
C11—C8—C12	107.91 (19)	C27—C28—C32	109.8 (2)
C9—C8—C12	107.17 (18)	O7—C29—N4	119.8 (2)
C7—C8—C12	109.7 (2)	O7—C29—C28	121.1 (2)
O5—C9—N2	119.9 (2)	N4—C29—C28	119.10 (19)
O5—C9—C8	121.6 (2)	O6—C30—N3	122.4 (2)
N2—C9—C8	118.5 (2)	O6—C30—N4	122.0 (2)
O3—C10—N1	122.3 (3)	N3—C30—N4	115.6 (2)
O3—C10—N2	121.7 (2)	O8—C31—N3	120.2 (2)
N1—C10—N2	116.0 (2)	O8—C31—C28	121.7 (2)
O4—C11—N1	120.5 (2)	N3—C31—C28	118.0 (2)
O4—C11—C8	120.5 (2)	C33—C32—C28	114.8 (2)
N1—C11—C8	119.00 (18)	C34—C33—C38	117.0 (3)
C13—C12—C8	115.6 (2)	C34—C33—C32	122.5 (3)
C18—C13—C14	117.2 (3)	C38—C33—C32	120.5 (3)
C18—C13—C12	121.5 (2)	C33—C34—C35	121.6 (4)
C14—C13—C12	121.3 (3)	C36—C35—C34	120.3 (4)
C15—C14—C13	122.2 (3)	C37—C36—C35	117.0 (4)
C14—C15—C16	121.0 (4)	C37—C36—C40	124.4 (6)
C15—C16—C17	117.8 (4)	C35—C36—C40	118.5 (6)
C15—C16—C20	121.1 (4)	C38—C37—C36	123.6 (4)
C17—C16—C20	121.1 (5)	C37—C38—C33	120.5 (3)
C16—C17—C18	121.0 (4)	C11—N1—C10	126.2 (2)
C13—C18—C17	120.8 (3)	C9—N2—C10	126.29 (19)
C22—C21—C26	118.3 (5)	C30—N3—C31	127.6 (2)
C22—C21—C39	123.1 (5)	C29—N4—C30	125.7 (2)
C5—C6—C1—C2	−1.3 (5)	C39—C21—C26—C25	179.0 (4)
C5—C6—C1—C19	−179.7 (3)	C24—C25—C26—C21	0.0 (6)
C6—C1—C2—C3	2.7 (6)	C23—C24—C27—C28	−90.5 (3)
C19—C1—C2—C3	−178.9 (3)	C25—C24—C27—C28	93.0 (3)
C1—C2—C3—C4	−2.0 (5)	C24—C27—C28—C31	60.9 (3)
C2—C3—C4—C5	−0.2 (4)	C24—C27—C28—C29	−63.3 (3)
C2—C3—C4—C7	179.4 (3)	C24—C27—C28—C32	179.3 (2)
C3—C4—C5—C6	1.5 (4)	C31—C28—C29—O7	−171.5 (3)
C7—C4—C5—C6	−178.1 (3)	C27—C28—C29—O7	−49.2 (3)
C1—C6—C5—C4	−0.7 (5)	C32—C28—C29—O7	69.6 (3)
C5—C4—C7—C8	82.6 (3)	C31—C28—C29—N4	9.8 (3)
C3—C4—C7—C8	−97.0 (3)	C27—C28—C29—N4	132.0 (2)
C4—C7—C8—C11	59.5 (3)	C32—C28—C29—N4	−109.2 (3)
C4—C7—C8—C9	−64.9 (3)	C29—C28—C31—O8	172.4 (3)
C4—C7—C8—C12	177.7 (2)	C27—C28—C31—O8	50.9 (3)
C11—C8—C9—O5	−172.6 (2)	C32—C28—C31—O8	−68.7 (3)
C7—C8—C9—O5	−50.3 (3)	C29—C28—C31—N3	−9.4 (3)
C12—C8—C9—O5	68.6 (3)	C27—C28—C31—N3	−130.8 (3)
C11—C8—C9—N2	10.0 (3)	C32—C28—C31—N3	109.5 (3)
C7—C8—C9—N2	132.3 (2)	C31—C28—C32—C33	−57.5 (3)
C12—C8—C9—N2	−108.8 (2)	C29—C28—C32—C33	64.8 (3)
C9—C8—C11—O4	171.2 (2)	C27—C28—C32—C33	−177.3 (2)
C7—C8—C11—O4	48.9 (3)	C28—C32—C33—C34	86.1 (3)
C12—C8—C11—O4	−70.4 (3)	C28—C32—C33—C38	−95.3 (3)
C9—C8—C11—N1	−9.5 (3)	C38—C33—C34—C35	3.6 (5)
C7—C8—C11—N1	−131.8 (2)	C32—C33—C34—C35	−177.7 (3)
C12—C8—C11—N1	108.9 (2)	C33—C34—C35—C36	−2.5 (6)
C11—C8—C12—C13	−66.5 (2)	C34—C35—C36—C37	−0.3 (7)
C9—C8—C12—C13	55.6 (3)	C34—C35—C36—C40	−179.1 (4)
C7—C8—C12—C13	174.32 (19)	C35—C36—C37—C38	1.9 (7)
C8—C12—C13—C18	89.4 (3)	C40—C36—C37—C38	−179.4 (4)
C8—C12—C13—C14	−89.2 (3)	C36—C37—C38—C33	−0.6 (7)
C18—C13—C14—C15	−0.7 (4)	C34—C33—C38—C37	−2.1 (5)
C12—C13—C14—C15	178.0 (3)	C32—C33—C38—C37	179.2 (3)
C13—C14—C15—C16	0.2 (5)	O4—C11—N1—C10	−177.7 (2)
C14—C15—C16—C17	0.5 (6)	C8—C11—N1—C10	3.0 (3)
C14—C15—C16—C20	178.6 (4)	O3—C10—N1—C11	−177.6 (2)
C15—C16—C17—C18	−0.6 (6)	N2—C10—N1—C11	3.6 (3)
C20—C16—C17—C18	−178.7 (4)	O5—C9—N2—C10	178.3 (2)
C14—C13—C18—C17	0.6 (4)	C8—C9—N2—C10	−4.3 (3)
C12—C13—C18—C17	−178.1 (3)	O3—C10—N2—C9	178.3 (2)
C16—C17—C18—C13	0.0 (6)	N1—C10—N2—C9	−2.9 (3)
C26—C21—C22—C23	1.2 (6)	O6—C30—N3—C31	−178.9 (3)
C39—C21—C22—C23	−179.4 (4)	N4—C30—N3—C31	3.3 (3)
C21—C22—C23—C24	0.8 (6)	O8—C31—N3—C30	−178.5 (2)
C22—C23—C24—C25	−2.4 (5)	C28—C31—N3—C30	3.3 (4)
C22—C23—C24—C27	−179.0 (3)	O7—C29—N4—C30	177.3 (2)
C23—C24—C25—C26	1.9 (5)	C28—C29—N4—C30	−3.9 (4)
C27—C24—C25—C26	178.5 (3)	O6—C30—N4—C29	179.2 (2)
C22—C21—C26—C25	−1.6 (6)	N3—C30—N4—C29	−2.9 (3)

D—H···A	D—H	H···A	D···A	D—H···A
N1—HN1···O1	0.86	1.94	2.787 (4)	167
O1—H1A···O3i	0.84 (3)	2.13 (3)	2.949 (3)	162
O1—H1B···O5ii	0.90 (3)	1.90 (3)	2.794 (4)	175
N2—HN2···O4iii	0.86	1.94	2.767 (2)	162
O2—H2A···O8iv	0.86 (6)	1.88 (6)	2.739 (4)	177
O2—H2B···O6v	0.82 (3)	2.16 (3)	2.961 (3)	169
N3—HN3···O7vi	0.86	1.90	2.739 (2)	164
N4—HN4···O2	0.86	1.92	2.761 (4)	166
C22—H22···Cgvii	0.93	2.97	3.5693	124