(S,S)-4''-Cyano-7,7''-dimeth­oxy-3',6'-dioxodispiro­[indane-2,2'-piperazine-5',2''-indane]-4-carboxamide methanol solvate: inter­rupting the amide-to-amide hydrogen-bonded tape

The title methanol solvate, C₂₄H₂₂N₄O₅·CH₃OH, forms an extended three-dimensional hydrogen-bonded structure, assisted by the presence of several good donor and acceptor sites. It shows none of the crystal packing features typically expected of piperazinediones, such as amide-to-amide R₂²(8) hydrogen bonding. In this structure the methanol solvent appears to play only a space-filling role; it is not involved in any hydrogen bonding and instead is disordered over several sites. This study reports, to the best of our knowledge, the first crystal structure of an indane-containing piperazinedione compound which exhibits a three-dimensional hydrogen-bonded structure formed by classical (N-H...O and N-H...N) hydrogen-bonding inter­actions.

S1. Comment

We are pursuing a program of organic crystal engineering using a piperazinedione-based molecular scaffold to explore the effects of substituents on the crystal packing and bulk properties of such molecules (Ntirampebura et al., 2008; Weatherhead-Kloster et al., 2005; Kloster et al., 2003; Jagadish et al., 2003; Williams, Jagadish, Lansdown et al., 1999; Williams, Jagadish, Lyon et al., 1999). We consider the pentacyclic molecular framework depicted in Fig. 1 suitable for use in the exploration of structural effects on weak intermolecular associative forces and an appropriate scaffold for the design of compounds that could possess useful bulk properties. The conformational freedom of such molecules is restricted, limiting the number of possible packing options. At the same time, the attachment of groups to the scaffold can provide structural and functional variability. For example, incorporation of electron donor (D) and acceptor (A) groups, as shown in Fig. 1, renders the molecule chiral and dipolar. The central 1,4-piperazine-2,5-dione ring is known to favour the formation of supramolecular `one-dimensional' tapes through reciprocal amide-to-amide R₂²(8) hydrogen bonding (Bernstein et al., 1995) and in observance of the hydrogen-bonding priority rules as determined by Etter (1990). The control of order in the second and third dimensions (Fig. 1, x and y axes) depends on harnessing van der Waals interactions, arene interactions, Coulombic interactions and/or additional hydrogen-bonding interactions, all of which are affected by variation of ring substituents.

While the majority of piperazinedione-containing compounds do reliably form extended R²₂(8) hydrogen-bonded tapes, our studies and those of others (Howes et al., 1983; Caira et al., 2002) have shown that the crystal structure can be solvent-dependant and that not all compounds follow the R²₂(8) hydrogen-bonding pattern. We report here the methanol solvate, (I), of (S,S)-cyclo-[(2-amino-4-carbamoyl-7-methoxy-2,3-dihydro-1H-indene-2-carboxylic acid)(2-amino-4-cyano-7-methoxy-2,3-dihydro-1H-indene-2-carboxylic acid)], which is an example of a piperazinedione-containing compound that does not follow the general trend.

The structure of (I) is shown in the scheme and the conformer present in the crystal is shown in Fig. 2. The compound crystallizes in the space group P2₁2₁2₁, consistent with its chiral nature. The molecular dimensions are unexceptional. The indane rings, which are perpendicular to the piperazinedione ring, exhibit minimal flexibility, with the cyclopentene rings both adopting envelope conformations. A mean plane fitted through atoms C2 and C5–C12 has an r.m.s. deviation of 0.1172 Å, while a mean plane fitted through atoms C4 and C15–C22 has an r.m.s. deviation of 0.1084 Å. The methoxy groups are essentially coplanar with the arene unit of the indane group, while the benzamide group is not; the angle between a mean plane fitted through atoms O4, N3, C14 and C10 and a plane fitted through the six-membered ring is 41.40 (9)°.

The crystal packing of (I) is very different from most other piperazinedione compounds. The presence of benzamide and nitrile groups permits the formation of an alternative extended three-dimensional hydrogen-bonded network. The methanol solvate molecule, removed using SQUEEZE routine of PLATON (Spek, 2003), has no role in the hydrogen bonding; this explains the desolvation observed when the crystals were removed from the mother liquor. Fig. 3 shows (I) in a space-filling representation, with the methanol molecule shown in one of its several orientations. It would seem that the methanol molecule occupies space between the two methoxy groups but, suprisingly, with no appreciable interactions between compound and solvent to anchor the methanol in one orientation. Instead, it is disordered over several positions in this `pocket'. An a axis projection (Fig. 4) shows how the R²₂(8) motif is avoided. Two motifs are found, each sharing a single N—H···O interaction between the piperazinedione rings. One motif can be described as R²₂(13), in which the acetamide group acts as a donor, and the second can be described as R²₂(12), in which the acetamide acts as an acceptor. These two motifs allow the structure to extend in the a and b directions. The second N—H acetamide H atom forms an N—H···N interaction with an adjacent nitrile group, and this interaction allows the crystal structure to propagate along the c axis (Fig. 5). From this analysis, it can be seen that no good hydrogen-bond donor or acceptor is left without a partner, and so the solvent methanol molecule, while perhaps playing a space-filling role for the three-dimensional structure, does not form a part of the three-dimensional hydrogen-bonded framework itself. Unlike other indane-containing piperazinedione crystal structures, arene interactions are not a significant force in this crystal structure, there being essentially just one interaction (Fig. 6), which most probably results from the orientation of the molecules to maximize hydrogen bonding.

In summary, while the majority of indane-containing piperazinedione compounds produce predicatable R₂²(8) crystal packing motifs, the properties of which can be tuned by appropriate ring subsitution, there are compounds which do not follow this trend. In the case of (I), the benzamide group provides the piperazinedione ring with competition for hydrogen-bonding donor and acceptor sites, and also involves the nitrile group as an acceptor. Maximization of hydrogen bonding in this compound requires that the amide-to-amide R₂²(8) motif be displaced in favour of a more complex and extensive hydrogen-bonded network.

S2. Experimental

The synthesis of (I) has been described elsewhere (Jagadish et al., 2003). Crystallization was effected by heating a suspension of the compound in methanol until dissolution was complete. The hot methanolic solution was allowed to cool slowly in an oil bath overnight.

S3. Refinement

H atoms were initially located in a difference Fourier map. N-bound H atoms were refined freely. C-bound H atoms were refined using a riding model, with U_iso(H) = 1.5U_eq for methyl H atoms and U_iso(H) = 1.2U_eq(H) for all others. C—H distances were constrained to 0.95 Å for aryl H atoms, 0.98 Å for methyl H atoms and 0.99 Å for methylene H atoms. The unit cell contains two solvent-accessible voids of 279 ų each. A difference map revealed a series of electron-density peaks corresponding to partially desolvated methanol disordered over many positions. No multi-part disorder model could be refined satsfactorily and so the residual electron density was removed using the SQUEEZE routine of PLATON (Spek, 2003). Friedel pairs were merged during refinement.

Computing details

Data collection: SMART (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and Mercury (Version 2.0; Macrae et al., 2006); software used to prepare material for publication: SHELXTL (Sheldrick, 2008), publCIF (Westrip, 2008) and local programs.

Figures

	Fig. 1. Intermolecular R^22(8) hydrogen-bonding interactions (dashed lines) in piperazinediones.
	Fig. 2. The molecular structure of (I), with the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 3. A space-filling representation of the asymmetric unit of (I), with the solvent methanol molecule shown in one of several orientations.
	Fig. 4. Hydrogen-bonding interactions parallel to the b axis in (I). The long c axis of the unit cell has been truncated for clarity.
	Fig. 5. Illustration of how N—H···N hydrogen bonds allow the structure of (I) to propagate parallel with the c axis.
	Fig. 6. The only aromatic stacking interaction in (I); the distance is approximate and in Å.

4''-cyano-7,7''-dimethoxy-3',6'-dioxodispiro[indane-2,2'-piperazine- 5',2''-indane]-4-carboxamide methanol solvate

Crystal data

C24H22N4O5·CH4O	Dx = 1.233 Mg m^−3
Mr = 478.50	Melting point: 230 K
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 4713 reflections
a = 9.6409 (7) Å	θ = 2.3–25.1°
b = 10.4629 (8) Å	µ = 0.09 mm^−1
c = 25.5588 (19) Å	T = 170 K
V = 2578.2 (3) Å^3	Block, colourless
Z = 4	0.44 × 0.19 × 0.10 mm
F(000) = 1008

Data collection

Bruker SMART 1000 CCD diffractometer	2821 independent reflections
Radiation source: sealed tube	2290 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.053
thin–slice ω scans	θmax = 26.3°, θmin = 1.6°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −11→11
Tmin = 0.962, Tmax = 0.992	k = −12→13
20487 measured reflections	l = −29→30

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.029	Hydrogen site location: difference Fourier map
wR(F^2) = 0.068	H atoms treated by a mixture of independent and constrained refinement
S = 0.98	w = 1/[σ^2(Fo^2) + (0.0341P)^2] where P = (Fo^2 + 2Fc^2)/3
2821 reflections	(Δ/σ)max < 0.001
317 parameters	Δρmax = 0.12 e Å^−3
0 restraints	Δρmin = −0.16 e Å^−3

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
O1	0.89973 (14)	−0.11162 (12)	0.22062 (5)	0.0309 (3)
O2	0.97357 (15)	0.34853 (12)	0.13658 (5)	0.0359 (4)
O3	0.53507 (14)	0.26430 (15)	0.31939 (6)	0.0482 (4)
O4	1.13837 (14)	0.30198 (13)	0.41850 (5)	0.0367 (4)
O5	0.46687 (14)	0.12011 (15)	0.05317 (6)	0.0465 (4)
N1	0.88631 (16)	0.01722 (15)	0.15032 (6)	0.0252 (4)
N2	0.94574 (17)	0.22640 (15)	0.20877 (6)	0.0274 (4)
N3	1.1482 (2)	0.09850 (17)	0.38956 (7)	0.0325 (4)
N4	1.0860 (2)	0.0011 (2)	−0.05770 (8)	0.0631 (6)
C1	0.89550 (18)	−0.00246 (18)	0.20159 (7)	0.0242 (4)
C2	0.89295 (19)	0.11447 (17)	0.23639 (7)	0.0245 (4)
C3	0.9373 (2)	0.24793 (18)	0.15746 (7)	0.0262 (4)
C4	0.87583 (19)	0.14115 (17)	0.12414 (7)	0.0244 (4)
C5	0.7415 (2)	0.1374 (2)	0.25591 (7)	0.0312 (5)
H5A	0.6921	0.1985	0.2329	0.037*
H5B	0.6887	0.0564	0.2573	0.037*
C6	0.76166 (19)	0.19199 (18)	0.30973 (7)	0.0272 (5)
C7	0.6648 (2)	0.2544 (2)	0.34026 (8)	0.0362 (5)
C8	0.7045 (2)	0.3022 (2)	0.38899 (9)	0.0403 (6)
H8	0.6390	0.3446	0.4107	0.048*
C9	0.8407 (2)	0.28719 (19)	0.40548 (8)	0.0352 (5)
H9	0.8681	0.3230	0.4380	0.042*
C10	0.9382 (2)	0.22141 (18)	0.37589 (7)	0.0270 (4)
C11	0.89601 (19)	0.17274 (17)	0.32731 (7)	0.0246 (4)
C12	0.97792 (19)	0.09878 (18)	0.28693 (7)	0.0260 (4)
H12A	0.9857	0.0076	0.2968	0.031*
H12B	1.0722	0.1348	0.2828	0.031*
C13	0.4300 (2)	0.3253 (3)	0.34984 (11)	0.0683 (8)
H13A	0.4188	0.2797	0.3831	0.102*
H13B	0.3421	0.3240	0.3306	0.102*
H13C	0.4570	0.4140	0.3568	0.102*
C14	1.0822 (2)	0.21062 (18)	0.39654 (7)	0.0286 (5)
C15	0.7229 (2)	0.17237 (19)	0.10969 (8)	0.0296 (5)
H15A	0.6576	0.1311	0.1343	0.036*
H15B	0.7063	0.2657	0.1097	0.036*
C16	0.70837 (19)	0.11786 (19)	0.05570 (7)	0.0271 (4)
C17	0.5870 (2)	0.09455 (19)	0.02774 (8)	0.0325 (5)
C18	0.5966 (2)	0.0473 (2)	−0.02330 (8)	0.0405 (6)
H18	0.5147	0.0306	−0.0428	0.049*
C19	0.7250 (2)	0.0252 (2)	−0.04525 (9)	0.0419 (6)
H19	0.7304	−0.0062	−0.0801	0.050*
C20	0.8455 (2)	0.0474 (2)	−0.01787 (8)	0.0330 (5)
C21	0.8355 (2)	0.09439 (18)	0.03381 (7)	0.0269 (4)
C22	0.95004 (19)	0.12899 (18)	0.07056 (7)	0.0261 (4)
H22A	0.9939	0.2108	0.0603	0.031*
H22B	1.0218	0.0614	0.0715	0.031*
C23	0.3392 (2)	0.0933 (3)	0.02583 (10)	0.0592 (7)
H23A	0.3349	0.1447	−0.0062	0.089*
H23B	0.2603	0.1146	0.0484	0.089*
H23C	0.3356	0.0024	0.0167	0.089*
C24	0.9809 (3)	0.0211 (2)	−0.04037 (9)	0.0426 (6)
H2N	0.991 (2)	0.290 (2)	0.2276 (8)	0.043 (6)*
H1N	0.886 (2)	−0.054 (2)	0.1278 (7)	0.037 (6)*
H3A	1.101 (2)	0.029 (2)	0.3778 (8)	0.042 (7)*
H3B	1.238 (3)	0.093 (2)	0.4035 (9)	0.059 (7)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0419 (8)	0.0209 (8)	0.0298 (8)	0.0012 (6)	−0.0042 (6)	0.0034 (6)
O2	0.0574 (9)	0.0211 (8)	0.0291 (8)	−0.0059 (7)	−0.0012 (7)	0.0012 (6)
O3	0.0301 (8)	0.0599 (11)	0.0545 (10)	0.0128 (7)	0.0018 (7)	−0.0150 (8)
O4	0.0486 (9)	0.0272 (8)	0.0342 (8)	−0.0058 (7)	−0.0111 (7)	−0.0022 (7)
O5	0.0265 (8)	0.0573 (11)	0.0556 (10)	−0.0009 (8)	−0.0053 (7)	0.0041 (9)
N1	0.0343 (10)	0.0191 (9)	0.0223 (10)	−0.0004 (7)	−0.0023 (8)	−0.0017 (7)
N2	0.0393 (10)	0.0208 (9)	0.0223 (9)	−0.0038 (8)	−0.0058 (8)	0.0007 (7)
N3	0.0361 (11)	0.0258 (10)	0.0356 (10)	0.0013 (9)	−0.0085 (9)	−0.0011 (8)
N4	0.0549 (14)	0.0825 (16)	0.0521 (14)	0.0085 (13)	0.0102 (12)	−0.0192 (12)
C1	0.0235 (10)	0.0238 (11)	0.0254 (11)	−0.0016 (9)	−0.0010 (9)	0.0016 (9)
C2	0.0298 (10)	0.0199 (10)	0.0237 (10)	0.0022 (9)	−0.0004 (8)	−0.0002 (8)
C3	0.0313 (11)	0.0224 (11)	0.0250 (11)	0.0041 (9)	−0.0024 (9)	−0.0023 (9)
C4	0.0299 (11)	0.0196 (10)	0.0237 (10)	0.0002 (8)	−0.0032 (8)	0.0004 (8)
C5	0.0305 (11)	0.0311 (11)	0.0319 (12)	0.0016 (9)	−0.0036 (9)	−0.0008 (9)
C6	0.0288 (11)	0.0267 (11)	0.0262 (11)	0.0032 (9)	0.0008 (8)	0.0001 (9)
C7	0.0328 (12)	0.0335 (13)	0.0424 (14)	0.0043 (10)	0.0033 (10)	−0.0034 (10)
C8	0.0366 (12)	0.0424 (13)	0.0420 (14)	0.0043 (10)	0.0100 (11)	−0.0128 (11)
C9	0.0467 (13)	0.0305 (12)	0.0283 (12)	−0.0022 (10)	0.0026 (10)	−0.0064 (9)
C10	0.0363 (11)	0.0212 (10)	0.0236 (11)	−0.0028 (9)	0.0021 (9)	0.0018 (8)
C11	0.0316 (10)	0.0183 (10)	0.0237 (10)	−0.0022 (8)	0.0029 (9)	0.0029 (8)
C12	0.0293 (10)	0.0229 (11)	0.0259 (11)	0.0016 (8)	−0.0022 (8)	0.0006 (9)
C13	0.0341 (14)	0.078 (2)	0.093 (2)	0.0202 (13)	0.0087 (14)	−0.0248 (17)
C14	0.0431 (12)	0.0236 (11)	0.0191 (10)	−0.0044 (10)	0.0012 (9)	0.0033 (9)
C15	0.0292 (11)	0.0287 (11)	0.0310 (12)	0.0021 (9)	−0.0007 (9)	0.0038 (9)
C16	0.0318 (11)	0.0235 (11)	0.0259 (11)	0.0005 (9)	−0.0038 (9)	0.0045 (9)
C17	0.0282 (11)	0.0297 (12)	0.0395 (12)	−0.0008 (9)	−0.0041 (10)	0.0071 (10)
C18	0.0436 (14)	0.0402 (13)	0.0376 (14)	−0.0046 (11)	−0.0165 (11)	−0.0010 (10)
C19	0.0568 (15)	0.0417 (14)	0.0272 (13)	−0.0057 (11)	−0.0107 (11)	−0.0055 (10)
C20	0.0407 (12)	0.0308 (12)	0.0274 (12)	−0.0015 (10)	−0.0017 (10)	−0.0037 (9)
C21	0.0322 (11)	0.0223 (11)	0.0261 (11)	−0.0008 (9)	−0.0020 (9)	0.0034 (9)
C22	0.0290 (10)	0.0264 (11)	0.0228 (10)	0.0003 (9)	−0.0008 (8)	−0.0003 (9)
C23	0.0272 (12)	0.0672 (18)	0.0833 (19)	−0.0084 (12)	−0.0196 (13)	0.0235 (15)
C24	0.0534 (15)	0.0461 (15)	0.0281 (13)	0.0006 (12)	−0.0027 (11)	−0.0103 (11)

Geometric parameters (Å, º)

O1—C1	1.242 (2)	C8—C9	1.388 (3)
O2—C3	1.231 (2)	C9—H9	0.9500
O3—C7	1.364 (2)	C9—C10	1.389 (3)
O3—C13	1.428 (2)	C10—C11	1.402 (2)
O4—C14	1.233 (2)	C10—C14	1.490 (3)
O5—C17	1.355 (2)	C11—C12	1.513 (2)
O5—C23	1.443 (3)	C12—H12A	0.9900
N1—C1	1.330 (2)	C12—H12B	0.9900
N1—C4	1.463 (2)	C13—H13A	0.9800
N1—H1N	0.94 (2)	C13—H13B	0.9800
N2—C2	1.459 (2)	C13—H13C	0.9800
N2—C3	1.333 (2)	C15—H15A	0.9900
N2—H2N	0.93 (2)	C15—H15B	0.9900
N3—C14	1.346 (3)	C15—C16	1.500 (3)
N3—H3A	0.91 (2)	C16—C17	1.393 (3)
N3—H3B	0.94 (2)	C16—C21	1.370 (3)
N4—C24	1.125 (3)	C17—C18	1.398 (3)
C1—C2	1.513 (2)	C18—H18	0.9500
C2—C5	1.562 (3)	C18—C19	1.379 (3)
C2—C12	1.538 (2)	C19—H19	0.9500
C3—C4	1.525 (2)	C19—C20	1.376 (3)
C4—C15	1.555 (3)	C20—C21	1.413 (3)
C4—C22	1.550 (2)	C20—C24	1.452 (3)
C5—H5A	0.9900	C21—C22	1.494 (2)
C5—H5B	0.9900	C22—H22A	0.9900
C5—C6	1.502 (3)	C22—H22B	0.9900
C6—C7	1.381 (3)	C23—H23A	0.9800
C6—C11	1.386 (3)	C23—H23B	0.9800
C7—C8	1.396 (3)	C23—H23C	0.9800
C8—H8	0.9500
C7—O3—C13	118.11 (17)	C2—C12—C11	103.91 (14)
C17—O5—C23	117.31 (17)	C2—C12—H12A	111.0
C1—N1—C4	126.36 (16)	C2—C12—H12B	111.0
C1—N1—H1N	118.8 (12)	C11—C12—H12A	111.0
C4—N1—H1N	114.9 (12)	C11—C12—H12B	111.0
C2—N2—C3	126.18 (17)	H12A—C12—H12B	109.0
C2—N2—H2N	119.1 (13)	O3—C13—H13A	109.5
C3—N2—H2N	114.7 (13)	O3—C13—H13B	109.5
C14—N3—H3A	120.6 (13)	O3—C13—H13C	109.5
C14—N3—H3B	116.3 (14)	H13A—C13—H13B	109.5
H3A—N3—H3B	122 (2)	H13A—C13—H13C	109.5
O1—C1—N1	122.04 (18)	H13B—C13—H13C	109.5
O1—C1—C2	120.93 (16)	O4—C14—N3	121.91 (19)
N1—C1—C2	116.94 (17)	O4—C14—C10	120.76 (18)
N2—C2—C1	111.04 (15)	N3—C14—C10	117.33 (18)
N2—C2—C5	110.92 (15)	C4—C15—H15A	111.1
N2—C2—C12	107.83 (15)	C4—C15—H15B	111.1
C1—C2—C5	109.13 (15)	C4—C15—C16	103.13 (15)
C1—C2—C12	113.50 (15)	H15A—C15—H15B	109.1
C5—C2—C12	104.24 (14)	H15A—C15—C16	111.1
O2—C3—N2	123.62 (18)	H15B—C15—C16	111.1
O2—C3—C4	119.66 (16)	C15—C16—C17	128.11 (17)
N2—C3—C4	116.70 (17)	C15—C16—C21	111.13 (16)
N1—C4—C3	111.55 (14)	C17—C16—C21	120.73 (18)
N1—C4—C15	111.12 (15)	O5—C17—C16	115.95 (17)
N1—C4—C22	107.42 (15)	O5—C17—C18	125.02 (19)
C3—C4—C15	110.33 (15)	C16—C17—C18	119.03 (19)
C3—C4—C22	111.97 (15)	C17—C18—H18	120.1
C15—C4—C22	104.19 (14)	C17—C18—C19	119.9 (2)
C2—C5—H5A	111.1	H18—C18—C19	120.1
C2—C5—H5B	111.1	C18—C19—H19	119.2
C2—C5—C6	103.32 (14)	C18—C19—C20	121.5 (2)
H5A—C5—H5B	109.1	H19—C19—C20	119.2
H5A—C5—C6	111.1	C19—C20—C21	118.5 (2)
H5B—C5—C6	111.1	C19—C20—C24	121.69 (19)
C5—C6—C7	127.57 (17)	C21—C20—C24	119.84 (18)
C5—C6—C11	111.26 (16)	C16—C21—C20	120.38 (17)
C7—C6—C11	121.17 (18)	C16—C21—C22	111.17 (16)
O3—C7—C6	115.78 (18)	C20—C21—C22	128.42 (18)
O3—C7—C8	125.01 (18)	C4—C22—C21	103.54 (15)
C6—C7—C8	119.21 (19)	C4—C22—H22A	111.1
C7—C8—H8	120.3	C4—C22—H22B	111.1
C7—C8—C9	119.35 (19)	C21—C22—H22A	111.1
H8—C8—C9	120.3	C21—C22—H22B	111.1
C8—C9—H9	119.0	H22A—C22—H22B	109.0
C8—C9—C10	122.06 (19)	O5—C23—H23A	109.5
H9—C9—C10	119.0	O5—C23—H23B	109.5
C9—C10—C11	117.77 (18)	O5—C23—H23C	109.5
C9—C10—C14	118.38 (17)	H23A—C23—H23B	109.5
C11—C10—C14	123.81 (17)	H23A—C23—H23C	109.5
C6—C11—C10	120.36 (17)	H23B—C23—H23C	109.5
C6—C11—C12	109.94 (16)	N4—C24—C20	179.8 (3)
C10—C11—C12	129.69 (17)
C4—N1—C1—O1	177.72 (17)	C9—C10—C11—C12	179.64 (18)
C4—N1—C1—C2	0.9 (3)	C14—C10—C11—C6	−176.88 (18)
C3—N2—C2—C1	30.0 (3)	C14—C10—C11—C12	1.9 (3)
C3—N2—C2—C5	−91.6 (2)	C6—C11—C12—C2	18.1 (2)
C3—N2—C2—C12	154.89 (18)	C10—C11—C12—C2	−160.86 (18)
O1—C1—C2—N2	156.03 (16)	N2—C2—C12—C11	91.74 (16)
O1—C1—C2—C5	−81.4 (2)	C1—C2—C12—C11	−144.82 (15)
O1—C1—C2—C12	34.4 (2)	C5—C2—C12—C11	−26.21 (18)
N1—C1—C2—N2	−27.1 (2)	C9—C10—C14—O4	−40.1 (3)
N1—C1—C2—C5	95.47 (19)	C9—C10—C14—N3	140.75 (19)
N1—C1—C2—C12	−148.77 (16)	C11—C10—C14—O4	137.56 (19)
C2—N2—C3—O2	173.95 (17)	C11—C10—C14—N3	−41.5 (3)
C2—N2—C3—C4	−4.6 (3)	N1—C4—C15—C16	−90.53 (17)
C1—N1—C4—C3	24.7 (3)	C3—C4—C15—C16	145.21 (15)
C1—N1—C4—C15	−98.9 (2)	C22—C4—C15—C16	24.86 (19)
C1—N1—C4—C22	147.73 (18)	C4—C15—C16—C17	165.47 (19)
O2—C3—C4—N1	159.11 (17)	C4—C15—C16—C21	−16.4 (2)
O2—C3—C4—C15	−76.9 (2)	C23—O5—C17—C16	−178.17 (19)
O2—C3—C4—C22	38.7 (2)	C23—O5—C17—C18	1.7 (3)
N2—C3—C4—N1	−22.2 (2)	C15—C16—C17—O5	−2.5 (3)
N2—C3—C4—C15	101.77 (19)	C15—C16—C17—C18	177.59 (19)
N2—C3—C4—C22	−142.68 (17)	C21—C16—C17—O5	179.52 (18)
N2—C2—C5—C6	−90.68 (18)	C21—C16—C17—C18	−0.4 (3)
C1—C2—C5—C6	146.67 (16)	O5—C17—C18—C19	179.8 (2)
C12—C2—C5—C6	25.12 (19)	C16—C17—C18—C19	−0.3 (3)
C2—C5—C6—C7	165.03 (19)	C17—C18—C19—C20	0.6 (3)
C2—C5—C6—C11	−14.9 (2)	C18—C19—C20—C21	−0.2 (3)
C13—O3—C7—C6	178.5 (2)	C18—C19—C20—C24	178.4 (2)
C13—O3—C7—C8	−1.6 (3)	C15—C16—C21—C20	−177.53 (18)
C5—C6—C7—O3	1.9 (3)	C15—C16—C21—C22	0.6 (2)
C5—C6—C7—C8	−178.0 (2)	C17—C16—C21—C20	0.7 (3)
C11—C6—C7—O3	−178.16 (18)	C17—C16—C21—C22	178.84 (18)
C11—C6—C7—C8	2.0 (3)	C19—C20—C21—C16	−0.5 (3)
O3—C7—C8—C9	−179.2 (2)	C19—C20—C21—C22	−178.20 (19)
C6—C7—C8—C9	0.7 (3)	C24—C20—C21—C16	−179.08 (19)
C7—C8—C9—C10	−2.6 (3)	C24—C20—C21—C22	3.2 (3)
C8—C9—C10—C11	1.8 (3)	C16—C21—C22—C4	15.6 (2)
C8—C9—C10—C14	179.67 (19)	C20—C21—C22—C4	−166.5 (2)
C5—C6—C11—C10	177.23 (17)	N1—C4—C22—C21	93.32 (16)
C5—C6—C11—C12	−1.8 (2)	C3—C4—C22—C21	−143.88 (15)
C7—C6—C11—C10	−2.7 (3)	C15—C4—C22—C21	−24.64 (18)
C7—C6—C11—C12	178.23 (17)	C19—C20—C24—N4	145 (100)
C9—C10—C11—C6	0.8 (3)	C21—C20—C24—N4	−37 (89)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2N···O1^i	0.93 (2)	1.98 (2)	2.889 (2)	165.7 (19)
N1—H1N···O4^ii	0.94 (2)	1.93 (2)	2.867 (2)	173.6 (18)
N3—H3A···O2^ii	0.91 (2)	2.05 (2)	2.944 (2)	166.3 (19)
N3—H3B···N4^iii	0.94 (2)	2.19 (2)	3.078 (3)	156 (2)
C12—H12B···O1^i	0.99	2.67	3.257 (2)	118
C12—H12A···O2^ii	0.99	2.41	3.301 (2)	149

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