Polymorphic form IV of olanzapine

2-Methyl-4-(4-methyl­piperazin-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepine, C₁₇H₂₀N₄S, commonly known as olanzapine, is a psychotropic agent that belongs to the thienobenzodi­azepine class of drugs. A new polymorph form IV was obtained upon attempted cocrystallization with nicotinamide in a 1:1 ratio from an ethyl acetate solution. Two butterfly-like mol­ecules form centrosymmetric dimers stabilized by weak C—H...π inter­actions between the 4-methyl­piperazin-1-yl fragment and the benzene/thio­phene aromatic system. Form IV consists of a herringbone arrangement of dimers, whereas the previously reported form II has parallel dimers. Both crystal structures are sustained by an N—H...N hydrogen bond.

S1. Comment

Olanzapine [systematic name: 2-methyl-4-(4-methylpiperazin-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepine], (I), is a frontline psychotropic drug marketed by Eli Lilly under the brand name Zyprexa. It is one of the top 20 prescription drugs based on a recent survey (Craig & Stitzel, 1997; Lindsley, 2010). It is a yellow crystalline solid that is practically insoluble in water (43 mg l^-1), sparingly soluble in acetonitrile and ethyl acetate, and freely soluble in chloroform. According to the Biopharmaceutics Classification System (BCS), olanzapine belongs to the Class II category, namely a drug with low solubility and high permeability. Six solid-state forms of olanzapine have been characterized (Bunnell et al., 1996, 1998; Hamied et al., 2002; Sundaram et al., 2006; Reguri & Chakka, 2005; Wawrzycka-Gorczyca et al., 2004), together with a few solvates and hydrates (Reutzel-Edens et al., 2003; Almarsson et al., 2007; Hickey & Remenar, 2006; Wawrzycka-Gorczyca et al., 2004, 2007; Capuano et al., 2003; Larsen, 1997; Bunnell et al., 1997; Kotar-Zordan et al., 2005; Dalmases Barjoan et al., 2006, 2007) and salts with carboxylic acids (Keltjens, 2005; Simonic et al., 2006; Kozluk, 2007; Bush, 2008; Mesar et al., 2008; Ravikumar et al., 2005; Sridhar & Ravikumar, 2007; Thakuria & Nangia, 2011). Only one X-ray crystal structure of olanzapine has been reported to date (Reutzel-Edens et al., 2003; Wawrzycka-Gorczyca et al., 2004), the powder X-ray diffraction pattern (PXRD) of which matched that of a polymorph designated form II in US patents (Bunnell et al., 1996, 1998). We now report the X-ray crystal structure of a polymorph of olanzapine, designated form IV (Hamied et al., 2002) by PXRD overlay.

The molecule of (I) has a central seven-membered diazepine ring which is fused with a benzene, a thiophene and an N-methylpiperazine ring (Fig. 1). The boat conformation of the central 1,5-diazepine ring defines the overall butterfly shape of the molecule, but the N-methylpiperazine ring can have conformational variation (Reutzel-Edens et al., 2003).

Cocrystallization of olanzapine with nicotinamide in 1:1 ratio from ethyl acetate afforded block-shaped pale-yellow crystals of olanzapine form IV in the space group P2₁/c. The expected cocrystal with nicotinamide was not obtained. Such observations are not unusual (Day et al., 2006; Li et al., 2011; Sanphui et al., 2011; Vishweshwar et al., 2005). The asymmetric unit of olanzapine form IV contains one molecule of olanzapine, having a single hydrogen-bond donor, N2—H2, and two exposed acceptors, imine atom N1 and piperazine atom N4, which are hydrogen-bonded in the crystal structure.

Two butterfly-like molecules form centrosymmetric dimers (Reutzel-Edens et al., 2003; Wawrzycka-Gorczyca et al., 2004) in the crystal structures of both forms IV and II, which are stabilized by weak C—H···π interactions between the 4-methylpiperazin-1-yl fragment (C15—H15 in form IV) and the benzene/thiophene aromatic system. Theoretical calculations estimated that this C—H···π binding energy is about 8 kcal mol^-1 (1 kcal mol^-1 = 4.184 kJ mol^-1) (Wawrzycka-Gorczyca et al., 2007). The packing of such dimer motifs in the two structures is completely different: form IV consists of a herringbone arrangement of dimers, whereas they are parallel in form II (Fig. 2).

The intermolecular interaction N2—H2···N1ⁱ [symmetry code: (i) x, -y+1/2, z+1/2] (Table 1) links the molecules in form IV into extended chains which can be described by the graph-set notation C(5) (Bernstein et al., 1995), and thereby connects the inversion-related dimers to form columns along the c axis. A similar, slightly shorter, interaction [H···N = 2.27 (2) Å] leading to similar chains occurs in the form II structure. The chains in form IV are further enhanced by a very weak intermolecular C—H···N interaction between piperazine atom N4 and a methyl H atom, H8B, on the thiophene ring of the molecule two links further on in the chain. This C—H···N interaction can be described with a graph-set notation of C(10).

Related literature

For related literature, see: Almarsson et al. (2007); Bernstein et al. (1995); Bunnell et al. (1996, 1997, 1998); Bush (2008); Capuano et al. (2003); Craig & Stitzel (1997); Dalmases & Bessa Bellmunt (2006); Dalmases & Herbera Espinal (2007); Day et al. (2006); Hamied et al. (2002); Hickey & Remenar (2006); Keltjens (2005); Kotar-Zordan, Lenarsic, Grcman, Smrkolj, Meden, Simonic, Zupet, Gnidovec & Benkic (2005); Kozluk (2007); Larsen (1997); Li et al. (2011); Lindsley (2010); Mesar et al. (2008); Ravikumar et al. (2005); Reguri & Chakka (2005); Reutzel-Edens, Bush, Magee, Stephenson & Byrn (2003); Sanphui et al. (2011); Simonic et al. (2006); Sridhar & Ravikumar (2007); Sundaram et al. (2006); Thakuria & Nangia (2011); Vishweshwar et al. (2005); Wawrzycka-Gorczyca, Borowski, Osypiuk-Tomasik, Mazur & Koziol (2007); Wawrzycka-Gorczyca, Koziol, Glice & Cybulski (2004).

S2. Experimental

A solution of olanzapine (60 mg, 0.2 mmol) and nicotinamide (24 mg, 0.2 mmol) in 1:1 ratio in ethyl acetate (approximately 10 ml) was allowed to evaporate slowly at room temperature for 5–10 d. Complete evaporation of the solvent resulted in a mixture of crytalline nicotinamide and olanzapine. Colourless transparent crystals of nicotinamide were manually separated. Olanzapine form IV, as yellow block-shaped crystals, was selected for X-ray diffraction. Because the polymorph was obtained from a cocrystallization experiment, the phase purity of the bulk sample could not be confirmed by powder diffraction.

S3. Refinement

The N-bonded atom H2 was located from a difference-electron density map, and its positional and isotropic displacement parameters were refined freely. H atoms attached to C atoms were positioned geometrically and treated as riding on their C atoms, with C—H = 0.96 Å and U_iso(H) = 1.5U_eq(C) for methyl, C—H = 0.97 Å and U_iso(H) = 1.2U_eq(C) for methylene, and C—H = 0.93 Å and U_iso(H) = 1.2U_eq(C) for aromatic H atoms.

Computing details

Data collection: SMART (Bruker, 2002); cell refinement: SMART (Bruker, 2002); data reduction: SAINT (Bruker, 2002); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: PLATON (Spek, 2009).

Figures

	Fig. 1. The molecular structure of olanzapine form IV, showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. (a) The parallel stacking of olanzapine dimers in olanzapine form II. (b) The herringbone arrangement of dimers in form IV.

2-Methyl-4-(4-methylpiperazin-1-yl)-10H- thieno[2,3-b][1,5]benzodiazepin

Crystal data

C17H20N4S	F(000) = 664
Mr = 312.44	Dx = 1.279 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 5126 reflections
a = 9.9130 (8) Å	θ = 2.4–26.0°
b = 16.5329 (13) Å	µ = 0.20 mm^−1
c = 9.9992 (8) Å	T = 298 K
β = 98.023 (1)°	Block, yellow
V = 1622.7 (2) Å^3	0.30 × 0.30 × 0.20 mm
Z = 4

Data collection

CCD area detector diffractometer	3202 independent reflections
Radiation source: fine-focus sealed tube	2963 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.026
ϕ and ω scans	θmax = 26.0°, θmin = 2.1°
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	h = −12→12
Tmin = 0.942, Tmax = 0.961	k = −20→20
16674 measured reflections	l = −12→12

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)] = 0.047	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.119	H atoms treated by a mixture of independent and constrained refinement
S = 1.12	w = 1/[σ^2(Fo^2) + (0.0543P)^2 + 0.6929P] where P = (Fo^2 + 2Fc^2)/3
3202 reflections	(Δ/σ)max = 0.005
205 parameters	Δρmax = 0.29 e Å^−3
0 restraints	Δρmin = −0.23 e Å^−3

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F² for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating -R-factor-obs 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
S1	0.40573 (5)	0.19412 (3)	0.25828 (5)	0.0407 (2)
N1	0.60588 (15)	0.13996 (9)	−0.13305 (14)	0.0354 (5)
N2	0.58482 (16)	0.25183 (10)	0.09664 (17)	0.0393 (5)
N3	0.39428 (15)	0.08739 (10)	−0.20153 (15)	0.0373 (5)
N4	0.21058 (16)	−0.00388 (10)	−0.38737 (15)	0.0402 (5)
C1	0.71583 (18)	0.16340 (11)	−0.03516 (18)	0.0351 (5)
C2	0.71107 (18)	0.21911 (11)	0.06962 (18)	0.0360 (5)
C3	0.48458 (18)	0.19517 (10)	0.11415 (17)	0.0340 (5)
C4	0.44100 (17)	0.13255 (11)	0.03005 (17)	0.0328 (5)
C5	0.48642 (17)	0.12223 (10)	−0.10305 (17)	0.0318 (5)
C6	0.34527 (18)	0.08211 (11)	0.08539 (18)	0.0363 (5)
C7	0.31347 (18)	0.10787 (12)	0.20525 (18)	0.0381 (5)
C8	0.2159 (2)	0.07292 (15)	0.2909 (2)	0.0527 (7)
C9	0.8306 (2)	0.24460 (13)	0.1468 (2)	0.0477 (7)
C10	0.9558 (2)	0.21593 (16)	0.1236 (2)	0.0571 (8)
C11	0.9623 (2)	0.15930 (16)	0.0242 (2)	0.0561 (8)
C12	0.8438 (2)	0.13368 (13)	−0.0541 (2)	0.0450 (6)
C13	0.24802 (18)	0.10372 (12)	−0.22012 (19)	0.0391 (6)
C14	0.1691 (2)	0.02767 (13)	−0.26309 (19)	0.0446 (6)
C15	0.3566 (2)	−0.01971 (12)	−0.3664 (2)	0.0445 (6)
C16	0.43736 (19)	0.05594 (13)	−0.32484 (18)	0.0414 (6)
C17	0.1354 (3)	−0.07709 (14)	−0.4323 (2)	0.0608 (8)
H2	0.596 (2)	0.2877 (13)	0.159 (2)	0.043 (6)*
H6	0.30820	0.03560	0.04250	0.0440*
H8A	0.13970	0.10880	0.29090	0.0790*
H8B	0.26090	0.06620	0.38170	0.0790*
H8C	0.18430	0.02130	0.25520	0.0790*
H9	0.82630	0.28190	0.21580	0.0570*
H10	1.03510	0.23470	0.17470	0.0690*
H11	1.04600	0.13830	0.00950	0.0670*
H12	0.84960	0.09550	−0.12140	0.0540*
H13A	0.22670	0.14520	−0.28840	0.0470*
H13B	0.22160	0.12350	−0.13620	0.0470*
H14A	0.18570	−0.01270	−0.19230	0.0530*
H14B	0.07230	0.03950	−0.27750	0.0530*
H15A	0.38380	−0.04060	−0.44930	0.0530*
H15B	0.37680	−0.06060	−0.29700	0.0530*
H16A	0.53390	0.04350	−0.30940	0.0500*
H16B	0.42180	0.09610	−0.39600	0.0500*
H17A	0.16170	−0.09480	−0.51630	0.0910*
H17B	0.03950	−0.06590	−0.44440	0.0910*
H17C	0.15560	−0.11870	−0.36560	0.0910*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0454 (3)	0.0453 (3)	0.0327 (3)	0.0028 (2)	0.0106 (2)	−0.0057 (2)
N1	0.0334 (8)	0.0422 (8)	0.0306 (8)	0.0020 (6)	0.0050 (6)	0.0007 (6)
N2	0.0415 (9)	0.0349 (8)	0.0420 (9)	−0.0020 (7)	0.0080 (7)	−0.0047 (7)
N3	0.0315 (8)	0.0505 (9)	0.0306 (8)	0.0027 (6)	0.0068 (6)	−0.0070 (7)
N4	0.0432 (9)	0.0439 (9)	0.0329 (8)	−0.0062 (7)	0.0035 (7)	−0.0012 (7)
C1	0.0334 (9)	0.0404 (10)	0.0318 (9)	−0.0008 (7)	0.0061 (7)	0.0078 (7)
C2	0.0376 (10)	0.0369 (9)	0.0336 (9)	−0.0022 (7)	0.0056 (7)	0.0060 (7)
C3	0.0359 (9)	0.0364 (9)	0.0302 (9)	0.0056 (7)	0.0060 (7)	0.0007 (7)
C4	0.0327 (9)	0.0370 (9)	0.0288 (8)	0.0022 (7)	0.0047 (7)	0.0004 (7)
C5	0.0343 (9)	0.0329 (9)	0.0283 (8)	0.0044 (7)	0.0049 (7)	0.0017 (7)
C6	0.0374 (9)	0.0400 (10)	0.0314 (9)	−0.0018 (7)	0.0050 (7)	0.0012 (7)
C7	0.0363 (9)	0.0455 (10)	0.0327 (9)	0.0023 (8)	0.0055 (7)	0.0042 (8)
C8	0.0540 (13)	0.0667 (14)	0.0403 (11)	−0.0028 (10)	0.0165 (9)	0.0061 (10)
C9	0.0491 (12)	0.0516 (12)	0.0412 (11)	−0.0093 (9)	0.0020 (9)	−0.0002 (9)
C10	0.0388 (11)	0.0764 (16)	0.0533 (13)	−0.0110 (10)	−0.0037 (9)	0.0045 (12)
C11	0.0327 (10)	0.0801 (16)	0.0557 (13)	0.0048 (10)	0.0065 (9)	0.0114 (12)
C12	0.0394 (10)	0.0561 (12)	0.0409 (10)	0.0044 (9)	0.0104 (8)	0.0048 (9)
C13	0.0322 (9)	0.0505 (11)	0.0348 (9)	0.0044 (8)	0.0059 (7)	−0.0028 (8)
C14	0.0393 (10)	0.0592 (13)	0.0359 (10)	−0.0056 (9)	0.0077 (8)	−0.0001 (9)
C15	0.0509 (12)	0.0480 (11)	0.0349 (10)	0.0054 (9)	0.0071 (8)	−0.0045 (8)
C16	0.0355 (10)	0.0571 (12)	0.0324 (9)	0.0013 (8)	0.0075 (7)	−0.0064 (8)
C17	0.0703 (16)	0.0553 (14)	0.0555 (14)	−0.0195 (12)	0.0041 (11)	−0.0049 (11)

Geometric parameters (Å, º)

S1—C3	1.7328 (18)	C11—C12	1.384 (3)
S1—C7	1.737 (2)	C13—C14	1.511 (3)
N1—C1	1.414 (2)	C15—C16	1.512 (3)
N1—C5	1.295 (2)	C6—H6	0.93
N2—C2	1.424 (2)	C8—H8A	0.96
N2—C3	1.394 (2)	C8—H8B	0.96
N3—C5	1.373 (2)	C8—H8C	0.96
N3—C13	1.461 (2)	C9—H9	0.93
N3—C16	1.456 (2)	C10—H10	0.93
N4—C14	1.459 (2)	C11—H11	0.93
N4—C15	1.457 (3)	C12—H12	0.93
N4—C17	1.459 (3)	C13—H13A	0.97
N2—H2	0.86 (2)	C13—H13B	0.97
C1—C12	1.398 (3)	C14—H14A	0.97
C1—C2	1.401 (3)	C14—H14B	0.97
C2—C9	1.386 (3)	C15—H15A	0.97
C3—C4	1.365 (2)	C15—H15B	0.97
C4—C5	1.473 (2)	C16—H16A	0.97
C4—C6	1.431 (3)	C16—H16B	0.97
C6—C7	1.350 (3)	C17—H17A	0.96
C7—C8	1.495 (3)	C17—H17B	0.96
C9—C10	1.378 (3)	C17—H17C	0.96
C10—C11	1.374 (3)
S1···N1^i	3.4699 (16)	H8A···C10^ix	2.90
S1···C5^i	3.3870 (18)	H8A···C11^ix	3.10
S1···H15B^ii	3.07	H8A···H10^ix	2.53
S1···H13A^i	3.19	H8B···N4^x	2.69
N1···S1^iii	3.4699 (16)	H8B···C15^x	2.93
N1···N2^iii	3.224 (2)	H8B···H16B^x	2.60
N2···N1^i	3.224 (2)	H8C···H12^ii	2.35
N1···H2^iii	2.39 (2)	H9···C1^i	3.00
N4···H8B^iv	2.69	H9···C12^i	2.68
C5···S1^iii	3.3870 (18)	H9···H12^i	2.59
C9···C12^i	3.592 (3)	H10···H8A^vi	2.53
C12···C9^iii	3.592 (3)	H11···H13B^vi	2.43
C1···H9^iii	3.00	H12···H8C^ii	2.35
C3···H15B^ii	3.08	H12···H9^iii	2.59
C7···H16A^ii	3.03	H13A···S1^iii	3.19
C9···H17C^ii	3.01	H13B···H11^ix	2.43
C9···H17A^v	2.96	H15A···C16^vii	3.07
C10···H8A^vi	2.90	H15B···S1^ii	3.07
C11···H8A^vi	3.10	H15B···C3^ii	3.08
C12···H9^iii	2.68	H16A···C7^ii	3.03
C15···H8B^iv	2.93	H16B···H8B^iv	2.60
C16···H15A^vii	3.07	H16B···H2^iii	2.59
C16···H2^iii	3.04 (2)	H17A···C9^xi	2.96
C17···H17B^viii	3.09	H17B···C17^viii	3.09
H2···N1^i	2.39 (2)	H17B···H17B^viii	2.52
H2···C16^i	3.04 (2)	H17C···C9^ii	3.01
C3—S1—C7	91.93 (8)	C7—C8—H8A	109
C1—N1—C5	122.90 (15)	C7—C8—H8B	110
C2—N2—C3	115.43 (15)	C7—C8—H8C	110
C5—N3—C13	124.25 (15)	H8A—C8—H8B	109
C5—N3—C16	120.85 (15)	H8A—C8—H8C	109
C13—N3—C16	111.19 (14)	H8B—C8—H8C	109
C14—N4—C15	109.52 (15)	C2—C9—H9	119
C14—N4—C17	111.49 (16)	C10—C9—H9	119
C15—N4—C17	110.48 (17)	C9—C10—H10	120
C3—N2—H2	113.3 (14)	C11—C10—H10	120
C2—N2—H2	111.9 (13)	C10—C11—H11	120
N1—C1—C12	115.88 (16)	C12—C11—H11	120
N1—C1—C2	126.51 (16)	C1—C12—H12	119
C2—C1—C12	117.29 (17)	C11—C12—H12	119
N2—C2—C9	118.99 (17)	N3—C13—H13A	110
N2—C2—C1	120.94 (16)	N3—C13—H13B	110
C1—C2—C9	120.06 (17)	C14—C13—H13A	110
S1—C3—C4	111.34 (13)	C14—C13—H13B	110
N2—C3—C4	127.00 (16)	H13A—C13—H13B	108
S1—C3—N2	121.55 (13)	N4—C14—H14A	110
C5—C4—C6	125.77 (16)	N4—C14—H14B	110
C3—C4—C5	122.27 (16)	C13—C14—H14A	110
C3—C4—C6	111.93 (15)	C13—C14—H14B	110
N3—C5—C4	116.10 (15)	H14A—C14—H14B	108
N1—C5—C4	125.99 (15)	N4—C15—H15A	109
N1—C5—N3	117.85 (15)	N4—C15—H15B	109
C4—C6—C7	114.14 (16)	C16—C15—H15A	109
S1—C7—C6	110.60 (14)	C16—C15—H15B	109
S1—C7—C8	119.86 (14)	H15A—C15—H15B	108
C6—C7—C8	129.54 (18)	N3—C16—H16A	110
C2—C9—C10	121.44 (19)	N3—C16—H16B	110
C9—C10—C11	119.38 (19)	C15—C16—H16A	110
C10—C11—C12	119.75 (19)	C15—C16—H16B	110
C1—C12—C11	122.04 (19)	H16A—C16—H16B	108
N3—C13—C14	110.34 (16)	N4—C17—H17A	109
N4—C14—C13	110.09 (16)	N4—C17—H17B	109
N4—C15—C16	111.61 (16)	N4—C17—H17C	109
N3—C16—C15	108.76 (16)	H17A—C17—H17B	110
C4—C6—H6	123	H17A—C17—H17C	110
C7—C6—H6	123	H17B—C17—H17C	109
C3—S1—C7—C6	1.07 (15)	C12—C1—C2—C9	2.1 (3)
C3—S1—C7—C8	−179.21 (16)	N1—C1—C12—C11	172.14 (19)
C7—S1—C3—N2	−176.25 (15)	C12—C1—C2—N2	−179.43 (17)
C7—S1—C3—C4	0.33 (14)	N1—C1—C2—C9	−171.08 (18)
C5—N1—C1—C12	141.50 (18)	N1—C1—C2—N2	7.4 (3)
C1—N1—C5—N3	−169.28 (16)	C1—C2—C9—C10	−0.4 (3)
C5—N1—C1—C2	−45.3 (3)	N2—C2—C9—C10	−178.93 (19)
C1—N1—C5—C4	7.8 (3)	N2—C3—C4—C5	−7.2 (3)
C3—N2—C2—C9	−128.80 (19)	S1—C3—C4—C6	−1.6 (2)
C2—N2—C3—C4	−51.1 (3)	N2—C3—C4—C6	174.77 (17)
C2—N2—C3—S1	124.87 (15)	S1—C3—C4—C5	176.48 (13)
C3—N2—C2—C1	52.7 (2)	C6—C4—C5—N1	−147.70 (18)
C13—N3—C16—C15	−57.3 (2)	C6—C4—C5—N3	29.4 (3)
C16—N3—C13—C14	58.1 (2)	C3—C4—C5—N3	−148.39 (17)
C13—N3—C5—N1	−143.71 (17)	C3—C4—C6—C7	2.5 (2)
C16—N3—C5—C4	−164.67 (16)	C5—C4—C6—C7	−175.49 (17)
C5—N3—C16—C15	143.48 (17)	C3—C4—C5—N1	34.5 (3)
C5—N3—C13—C14	−143.57 (17)	C4—C6—C7—C8	178.13 (19)
C16—N3—C5—N1	12.7 (3)	C4—C6—C7—S1	−2.2 (2)
C13—N3—C5—C4	39.0 (2)	C2—C9—C10—C11	−1.7 (3)
C15—N4—C14—C13	57.9 (2)	C9—C10—C11—C12	2.0 (3)
C14—N4—C15—C16	−59.0 (2)	C10—C11—C12—C1	−0.3 (3)
C17—N4—C15—C16	177.85 (15)	N3—C13—C14—N4	−57.8 (2)
C17—N4—C14—C13	−179.55 (17)	N4—C15—C16—N3	58.2 (2)
C2—C1—C12—C11	−1.7 (3)

Symmetry codes: (i) x, −y+1/2, z+1/2; (ii) −x+1, −y, −z; (iii) x, −y+1/2, z−1/2; (iv) x, y, z−1; (v) −x+1, y+1/2, −z−1/2; (vi) x+1, y, z; (vii) −x+1, −y, −z−1; (viii) −x, −y, −z−1; (ix) x−1, y, z; (x) x, y, z+1; (xi) −x+1, y−1/2, −z−1/2.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···N1^i	0.86 (2)	2.39 (2)	3.224 (2)	165 (2)
C8—H8B···N4^x	0.96	2.69 (1)	3.466 (2)	138

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