Methyl 2-(4-bromo­phenyl)-1-(5-tert-butyl-1H-pyrazol-3-yl)-1H-benz­imidazole-5-carboxyl­ate: a hydrogen-bonded chain of edge-fused centrosymmetric rings

In the title compound, C₂₂H₂₁BrN₄O₂, the imidazole and pyrazole rings are almost orthogonal to each other, but the ester unit is effectively coplanar with the adjacent aryl rings. The mol­ecules are linked into a chain of edge-fused centrosymmetric rings by a combination of N-H...O and C-H...[pi](arene) hydrogen bonds.

S1. Comment

The imidazole core is a common moiety in a large number of natural products and pharmacologically active compounds (Adams et al., 1998). In particular, the benzimidazole unit may be considered structurally isosteric with the purine unit of nucleotides, so that this unit can readily interact with biopolymers, thus conferring potential activity for chemotherapeutic applications upon compounds containing the benzimidazole unit (Ören et al., 1998). The pyrazole core is also frequently found in compounds with significant biological activity (Park et al., 2005; Insuasty et al., 2008). As part of a synthetic programme aimed at the development of antitumour compounds containing a combination of benzimidazole and pyrazole units, we have now prepared methyl 2-(4-bromophenyl)-1-(5-tert-butyl-1H-pyrazol-3-yl)-1H-benzimidazole-5-carboxylate, (I), using an oxidative cyclocondensation of an ortho-diaminobenzene derivative having a pyrazole residue linked to one amino group with an arylaldehyde, in this case the condensation between methyl 3-amino-4-(5-tert-butyl-1H-pyrazol-3-ylamino)benzoate and 4-bromobenzaldehyde. Although similar oxidative cyclocondensation routes to benzimidazoles have recently been reported, these all involve reactions in solution, as opposed to the solvent-free procedure employed here, and, in general, involve the addition of specific oxidizing agents to the reaction medium (Bressi et al., 2010; Murai et al., 2010; Tonelli et al., 2010), whereas no such oxidant was required for the high-yield synthesis of (I). Here, we report the molecular and supramolecular structure of (I), which we compare with the related compound methyl 1-(5-methyl-1H-pyrazol-3-yl)-1H-benzo[d]imidazole-5- carboxylate, (II), which was prepared using a rather similar synthetic approach, namely a simple cyclocondensation of methyl 3-amino-4-[(5-methyl-1H-pyrazole-3-yl)amino]benzoate with trimethyl orthoformate (Portilla et al., 2007).

The molecular conformation of (I) is dominated by the dihedral angles between the plane of the imidazole ring and those of the pyrazole and brominated aryl rings. These dihedral angles are 83.30 (15) and 26.90 (14)°, respectively, and the near orthogonality of the imidazole and pyrazole rings presents a marked contrast with the conformation adopted by (II) (Portilla et al., 2007). Compound (II) crystallizes with Z' = 2 in space group P1, as opposed to Z' = 1 in space group P2₁/c for (I), and the dihedral angles between the planes of the imidazole and pyrazole rings in the two independent molecules are 5.5 (2) and 5.9 (2)°, so that the ring systems in the molecules of (II) are very nearly planar. By contrast, the ester groups in (II) are both rotated out of the planes of the adjacent aryl rings by ca 15°, whereas the ester group in (I) is effectively coplanar with the adjacent aryl ring: the maximum deviations of the non-H atoms in the ester group of (I) from the mean plane of the adjacent aryl ring occur for the two O atoms, each displaced by only 0.068 (2) Å, as the relevant torsion angles confirm (Table 1). Finally, the tert-butyl group adopts a conformation in which the projection of the C16—C19 bond is almost orthogonal to the pyrazole plane. The molecule of (I) has no internal symmetry and hence it is conformationally chiral. However, the centrosymmetric space group accommodates equal numbers of the two conformational enantiomers.

The conformational differences between the molecules of (I) and (II) cannot plausibly be interpreted in terms of intramolecular factors only. More probably, they are determined primarily by the different direction-specific intermolecular forces which are manifest in the two crystal structures, in particular the different patterns of the hydrogen bonds, which involve both the pyrazole ring and the ester unit in each compound, and which are discussed below.

There is strong bond fixation within the imidazole ring, as exemplified by the C2—N3 and N3—C3a distances (Table 1). In the adjacent aryl ring, the longest of the peripheral C—C bonds is C5—C6, while the exocyclic C5—C51 bond is short for its type [mean value (Allen et al., 1987) 1.487 Å, lower-quartile value 1.480 Å]. However, the remaining bond distances provide no evidence for any significant polarization or charge separation in the molecular fragment between atoms N1 and O51.

The molecules of (I) are linked by a combination of N—H···O and C—H···π(arene) hydrogen bonds (Table 2). However, despite the presence within the molecule of two essentially unencumbered aryl rings, aromatic π–π stacking interactions are absent from the crystal structure of (I), nor are there any short intermolecular contacts involving pairs of Br atoms (Ramasubbu et al., 1986). It is convenient to consider first the actions of the two independent hydrogen bonds, and then their action in combination. The pyrazole ring atom N11 at (x, y, z) acts as hydrogen-bond donor to carbonyl atom O51 in the molecule at (1 - x, 1 - y, 2 - z), so forming a cyclic centrosymmetric R²₂(22) (Bernstein et al., 1995) ring, centred at (1/2, 1/2, 1). Pyrazole ring atom C14 at (x, y, z) acts as hydrogen-bond donor to the brominated aryl ring C21–C26 in the molecule at (-x, 1 - y, 1 - z), so forming a second cyclic centrosymmetric motif, this time centred at (0, 1/2, 1/2). The combination of these two ring motifs, and their propagation by inversion, leads to the formation of a chain of edge-fused rings running parallel to the [101] direction, in which the rings formed by pairs of N—H···O hydrogen bonds are centred at (n + 1/2, 1/2, n + 1), where n represents an integer, while the rings formed by pairs of C—H···π(arene) hydrogen bonds are centred at (n, 1/2, n + 1/2), where n again represents an integer (Fig. 2).

The hydrogen bonds present in (I) and the resulting supramolecular structure provide an interesting contrast with those in (II) (Portilla et al., 2007). As noted above, (II) crystallizes with Z' = 2 and each of the independent molecules forms an independent hydrogen-bonded substructure. Each of the two types of molecule in (II) participates in one N—H···N and one C—H···O hydrogen bond, in which the donors are both components of the pyrazole ring, as in (I), while the acceptors are, respectively, the two-coordinated N atom of the imidazole ring and the carbonyl O atom. Each type of molecule in (II) then forms a hydrogen-bonded sheet containing a single type of R⁴₄(28) ring and in which the component molecules are all related to one another by translation. There are no direction-specific interactions between the two types of sheets, which are stacked alternately along [001], and, in particular, there are no direction-specific interactions between the two independent molecules.

Compounds (I) and (II) thus differ, despite their similar molecular constitutions, in their crystallization characteristics (space groups and Z' values); in their molecular conformations; in their hydrogen bonds, where the same two donors are present but involved with different sets of acceptors; and in their overall hydrogen-bonded structures, a chain of fused rings in (I) and two independent sheets in (II).

Related literature

For related literature, see: Adams et al. (1998); Allen et al. (1987); Bernstein et al. (1995); Bressi et al. (2010); Insuasty et al. (2008); Murai et al. (2010); Park et al. (2005); Portilla et al. (2007); Ramasubbu et al. (1986); Tonelli et al. (2010); Ören et al. (1998).

S2. Experimental

A mixture of methyl 3-amino-4-(5-tert-butyl-1H-pyrazol-3-ylamino)benzoate (1 mmol) and 4-bromobenzaldehyde (1.2 mmol) was heated at 413 K in the absence of solvent for 2 h. After the complete disappearance of the starting material (as monitored by thin-layer chromatography), the mixture was cooled to ambient temperature and the crude product was purified by column chromatography on silica gel using a chloroform–methanol (40:1 v/v) mixture as eluent, to afford the title compound, (I). Slow evaporation of the solution in chloroform-methanol at ambient temperature and in air gave colourless crystals of (I) suitable for single-crystal X-ray diffraction (yield 92%, m.p. 534 K). MS (70 eV, EI) m/z (%): 454/452 (100/98, M⁺), 439/437 [24/24, (M—CH₃)⁺], 423/421 [25/25, (M—OCH₃)⁺], 397 (11), 395 (14). Analysis, found: C 58.2, H 4.8, N 12.3%; C₂₂H₂₁BrN₄O₂ requires: C 58.3, H 4.7, N 12.4%.

S3. Refinement

All H atoms were located in a difference map and then treated as riding atoms in geometrically idealized positions, with C—H = 0.95 (ring C—H) or 0.98 Å (methyl) and N—H = 0.88 Å, and with U_iso(H) = kU_eq(carrier), where k = 1.5 for the methyl groups, which were permitted to rotate but not to tilt, or 1.2 for all other H atoms.

Computing details

Data collection: COLLECT (Nonius, 1999); cell refinement: DIRAX/LSQ (Duisenberg et al., 2000); data reduction: EVALCCD (Duisenberg et al., 2003); program(s) used to solve structure: SIR2004 (Burla et al., 2005); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures

	Fig. 1. The molecular structure of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. A stereoview of part of the crystal structure of (I), showing the formation of a hydrogen-bonded chain of edge-fused centrosymmetric rings running parallel to the [101] direction. For the sake of clarity, H atoms not involved in the motifs shown have been omitted.

Methyl 2-(4-bromophenyl)-1-(5-tert-butyl-1H-pyrazol-3-yl)- 1H-benzimidazole-5-carboxylate

Crystal data

C22H21BrN4O2	F(000) = 928
Mr = 453.33	Dx = 1.532 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 4516 reflections
a = 8.1296 (15) Å	θ = 3.0–27.5°
b = 22.187 (3) Å	µ = 2.12 mm^−1
c = 11.152 (3) Å	T = 120 K
β = 102.222 (18)°	Block, colourless
V = 1965.9 (7) Å^3	0.28 × 0.20 × 0.18 mm
Z = 4

Data collection

Bruker Nonius KappaCCD area-detector diffractometer	4516 independent reflections
Radiation source: Bruker Nonius FR591 rotating anode	3190 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.063
Detector resolution: 9.091 pixels mm^-1	θmax = 27.5°, θmin = 3.0°
ϕ and ω scans	h = −10→10
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	k = −28→28
Tmin = 0.589, Tmax = 0.683	l = −14→13
30453 measured reflections

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)] = 0.041	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.083	H-atom parameters constrained
S = 1.05	w = 1/[σ^2(Fo^2) + (0.0249P)^2 + 2.0888P] where P = (Fo^2 + 2Fc^2)/3
4516 reflections	(Δ/σ)max = 0.001
266 parameters	Δρmax = 0.53 e Å^−3
0 restraints	Δρmin = −0.59 e Å^−3

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
N1	0.2676 (3)	0.49301 (9)	0.69172 (18)	0.0170 (4)
C2	0.2777 (3)	0.46952 (11)	0.5786 (2)	0.0177 (5)
N3	0.3166 (3)	0.41260 (9)	0.58411 (18)	0.0189 (4)
C3a	0.3372 (3)	0.39700 (11)	0.7060 (2)	0.0186 (6)
C4	0.3852 (3)	0.34280 (11)	0.7629 (2)	0.0189 (6)
H4	0.4070	0.3085	0.7176	0.023*
C5	0.4005 (3)	0.34027 (11)	0.8890 (2)	0.0188 (5)
C6	0.3678 (3)	0.39082 (12)	0.9550 (2)	0.0206 (6)
H6	0.3791	0.3876	1.0413	0.025*
C7	0.3199 (3)	0.44479 (11)	0.8992 (2)	0.0206 (6)
H7	0.2972	0.4790	0.9443	0.025*
C7a	0.3065 (3)	0.44683 (11)	0.7742 (2)	0.0178 (5)
N11	0.2919 (3)	0.63971 (9)	0.78950 (19)	0.0195 (5)
H11	0.3487	0.6721	0.8189	0.023*
N12	0.3658 (2)	0.58776 (9)	0.76770 (18)	0.0190 (5)
C13	0.2369 (3)	0.55258 (11)	0.7247 (2)	0.0166 (5)
C14	0.0846 (3)	0.58028 (11)	0.7209 (2)	0.0210 (6)
H14	−0.0242	0.5632	0.6950	0.025*
C15	0.1227 (3)	0.63733 (11)	0.7620 (2)	0.0176 (5)
C16	0.0115 (3)	0.69082 (12)	0.7662 (2)	0.0210 (6)
C17	0.1038 (4)	0.73939 (13)	0.8488 (3)	0.0352 (7)
H17A	0.1472	0.7227	0.9307	0.053*
H17B	0.0264	0.7726	0.8544	0.053*
H17C	0.1977	0.7544	0.8147	0.053*
C18	−0.1432 (3)	0.67128 (13)	0.8121 (3)	0.0310 (7)
H18A	−0.2023	0.6396	0.7585	0.046*
H18B	−0.2183	0.7059	0.8115	0.046*
H18C	−0.1089	0.6557	0.8959	0.046*
C19	−0.0409 (4)	0.71540 (14)	0.6367 (3)	0.0347 (7)
H19A	0.0596	0.7268	0.6065	0.052*
H19B	−0.1125	0.7509	0.6369	0.052*
H19C	−0.1034	0.6844	0.5830	0.052*
C21	0.2523 (3)	0.50332 (11)	0.4636 (2)	0.0187 (5)
C22	0.3327 (3)	0.48167 (11)	0.3741 (2)	0.0190 (5)
H22	0.4069	0.4483	0.3924	0.023*
C23	0.3075 (3)	0.50732 (12)	0.2605 (2)	0.0206 (6)
H23	0.3622	0.4917	0.1998	0.025*
C24	0.2014 (3)	0.55615 (12)	0.2353 (2)	0.0216 (6)
Br24	0.16288 (4)	0.590511 (14)	0.07803 (3)	0.03342 (10)
C25	0.1218 (3)	0.57930 (11)	0.3223 (2)	0.0223 (6)
H25	0.0495	0.6132	0.3038	0.027*
C26	0.1479 (3)	0.55293 (11)	0.4361 (2)	0.0213 (6)
H26	0.0936	0.5689	0.4966	0.026*
C51	0.4566 (3)	0.28500 (12)	0.9577 (2)	0.0201 (6)
O51	0.4738 (2)	0.28010 (8)	1.06720 (16)	0.0219 (4)
O52	0.4863 (2)	0.24012 (8)	0.88699 (16)	0.0248 (4)
C52	0.5320 (4)	0.18372 (12)	0.9483 (3)	0.0299 (7)
H52A	0.6382	0.1885	1.0084	0.045*
H52B	0.5455	0.1530	0.8879	0.045*
H52C	0.4434	0.1712	0.9905	0.045*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0173 (11)	0.0148 (11)	0.0194 (11)	−0.0022 (9)	0.0052 (9)	−0.0040 (9)
C2	0.0151 (12)	0.0179 (13)	0.0202 (13)	−0.0026 (10)	0.0039 (10)	−0.0053 (11)
N3	0.0223 (11)	0.0158 (11)	0.0184 (11)	0.0000 (10)	0.0043 (9)	−0.0027 (9)
C3a	0.0171 (13)	0.0188 (14)	0.0203 (13)	−0.0033 (10)	0.0048 (11)	−0.0033 (10)
C4	0.0202 (13)	0.0145 (13)	0.0228 (14)	−0.0035 (11)	0.0063 (11)	−0.0042 (10)
C5	0.0177 (13)	0.0166 (13)	0.0231 (14)	−0.0044 (11)	0.0069 (11)	−0.0025 (11)
C6	0.0207 (13)	0.0219 (14)	0.0206 (14)	−0.0041 (11)	0.0075 (11)	−0.0034 (10)
C7	0.0209 (13)	0.0184 (13)	0.0237 (15)	−0.0004 (11)	0.0078 (11)	−0.0059 (11)
C7a	0.0163 (13)	0.0147 (13)	0.0221 (13)	−0.0012 (10)	0.0036 (10)	−0.0019 (10)
N11	0.0198 (11)	0.0131 (11)	0.0266 (12)	−0.0010 (9)	0.0066 (9)	−0.0057 (9)
N12	0.0182 (11)	0.0167 (11)	0.0221 (11)	0.0019 (9)	0.0043 (9)	−0.0044 (9)
C13	0.0176 (13)	0.0154 (13)	0.0176 (13)	0.0005 (10)	0.0054 (10)	−0.0032 (10)
C14	0.0161 (12)	0.0226 (15)	0.0244 (14)	−0.0029 (11)	0.0046 (11)	−0.0085 (11)
C15	0.0185 (13)	0.0190 (13)	0.0164 (13)	−0.0003 (11)	0.0060 (10)	−0.0008 (10)
C16	0.0219 (13)	0.0191 (14)	0.0222 (14)	0.0041 (11)	0.0054 (11)	−0.0024 (11)
C17	0.0368 (17)	0.0256 (16)	0.0434 (18)	0.0089 (14)	0.0087 (15)	−0.0092 (14)
C18	0.0252 (15)	0.0331 (17)	0.0382 (17)	0.0101 (13)	0.0148 (13)	0.0043 (14)
C19	0.0381 (17)	0.0358 (18)	0.0317 (17)	0.0165 (14)	0.0107 (14)	0.0088 (14)
C21	0.0175 (13)	0.0179 (13)	0.0199 (13)	−0.0031 (11)	0.0025 (11)	−0.0045 (11)
C22	0.0162 (13)	0.0154 (13)	0.0247 (13)	−0.0005 (10)	0.0030 (11)	−0.0026 (11)
C23	0.0178 (13)	0.0231 (14)	0.0217 (14)	−0.0012 (11)	0.0060 (11)	−0.0025 (11)
C24	0.0189 (13)	0.0226 (14)	0.0219 (14)	−0.0036 (11)	0.0014 (11)	0.0045 (11)
Br24	0.03519 (17)	0.03752 (18)	0.02821 (16)	0.00734 (15)	0.00819 (12)	0.01153 (14)
C25	0.0200 (13)	0.0174 (14)	0.0292 (15)	0.0027 (11)	0.0044 (11)	0.0005 (11)
C26	0.0204 (14)	0.0187 (14)	0.0252 (14)	−0.0004 (11)	0.0058 (11)	−0.0052 (11)
C51	0.0173 (13)	0.0193 (14)	0.0245 (15)	−0.0059 (11)	0.0065 (11)	−0.0014 (11)
O51	0.0272 (10)	0.0182 (9)	0.0204 (10)	−0.0039 (8)	0.0054 (8)	−0.0011 (8)
O52	0.0405 (11)	0.0130 (9)	0.0236 (10)	−0.0004 (8)	0.0128 (9)	−0.0014 (8)
C52	0.0471 (19)	0.0138 (14)	0.0305 (16)	−0.0011 (13)	0.0123 (14)	0.0008 (12)

Geometric parameters (Å, º)

N1—C2	1.383 (3)	C17—H17A	0.9800
C2—N3	1.300 (3)	C17—H17B	0.9800
N3—C3a	1.379 (3)	C17—H17C	0.9800
C3a—C4	1.377 (3)	C18—H18A	0.9800
C4—C5	1.386 (4)	C18—H18B	0.9800
C5—C6	1.398 (3)	C18—H18C	0.9800
C6—C7	1.367 (4)	C19—H19A	0.9800
C7—C7a	1.376 (4)	C19—H19B	0.9800
C7a—N1	1.368 (3)	C19—H19C	0.9800
C3a—C7a	1.394 (3)	C21—C26	1.384 (4)
C5—C51	1.466 (4)	C21—C22	1.390 (4)
N1—C13	1.409 (3)	C22—C23	1.365 (4)
C2—C21	1.462 (4)	C22—H22	0.9500
C4—H4	0.9500	C23—C24	1.376 (4)
C6—H6	0.9500	C23—H23	0.9500
C7—H7	0.9500	C24—C25	1.375 (4)
N11—C15	1.345 (3)	C24—Br24	1.877 (3)
N11—N12	1.346 (3)	C25—C26	1.373 (4)
N11—H11	0.8800	C25—H25	0.9500
N12—C13	1.313 (3)	C26—H26	0.9500
C13—C14	1.375 (3)	C51—O51	1.205 (3)
C14—C15	1.360 (3)	C51—O52	1.323 (3)
C14—H14	0.9500	O52—C52	1.437 (3)
C15—C16	1.499 (3)	C52—H52A	0.9800
C16—C17	1.510 (4)	C52—H52B	0.9800
C16—C18	1.517 (4)	C52—H52C	0.9800
C16—C19	1.518 (4)
C7a—N1—C2	106.3 (2)	C16—C17—H17B	109.5
C7a—N1—C13	123.7 (2)	H17A—C17—H17B	109.5
C2—N1—C13	129.8 (2)	C16—C17—H17C	109.5
N3—C2—N1	112.5 (2)	H17A—C17—H17C	109.5
N3—C2—C21	121.8 (2)	H17B—C17—H17C	109.5
N1—C2—C21	125.6 (2)	C16—C18—H18A	109.5
C2—N3—C3a	105.6 (2)	C16—C18—H18B	109.5
C4—C3a—N3	129.6 (2)	H18A—C18—H18B	109.5
C4—C3a—C7a	120.5 (2)	C16—C18—H18C	109.5
N3—C3a—C7a	109.9 (2)	H18A—C18—H18C	109.5
C3a—C4—C5	117.3 (2)	H18B—C18—H18C	109.5
C3a—C4—H4	121.4	C16—C19—H19A	109.5
C5—C4—H4	121.4	C16—C19—H19B	109.5
C4—C5—C6	121.0 (2)	H19A—C19—H19B	109.5
C4—C5—C51	121.0 (2)	C16—C19—H19C	109.5
C6—C5—C51	118.0 (2)	H19A—C19—H19C	109.5
C7—C6—C5	122.1 (2)	H19B—C19—H19C	109.5
C7—C6—H6	119.0	C26—C21—C22	118.4 (2)
C5—C6—H6	119.0	C26—C21—C2	124.7 (2)
C6—C7—C7a	116.3 (2)	C22—C21—C2	116.9 (2)
C6—C7—H7	121.8	C23—C22—C21	121.5 (2)
C7a—C7—H7	121.8	C23—C22—H22	119.3
N1—C7a—C7	131.5 (2)	C21—C22—H22	119.3
N1—C7a—C3a	105.7 (2)	C22—C23—C24	118.8 (2)
C7—C7a—C3a	122.8 (2)	C22—C23—H23	120.6
C15—N11—N12	113.6 (2)	C24—C23—H23	120.6
C15—N11—H11	123.2	C25—C24—C23	121.2 (2)
N12—N11—H11	123.2	C25—C24—Br24	119.8 (2)
C13—N12—N11	102.85 (19)	C23—C24—Br24	118.9 (2)
N12—C13—C14	112.9 (2)	C26—C25—C24	119.3 (2)
N12—C13—N1	118.8 (2)	C26—C25—H25	120.3
C14—C13—N1	128.3 (2)	C24—C25—H25	120.3
C15—C14—C13	105.4 (2)	C25—C26—C21	120.8 (2)
C15—C14—H14	127.3	C25—C26—H26	119.6
C13—C14—H14	127.3	C21—C26—H26	119.6
N11—C15—C14	105.2 (2)	O51—C51—O52	122.6 (2)
N11—C15—C16	123.8 (2)	O51—C51—C5	124.2 (2)
C14—C15—C16	130.7 (2)	O52—C51—C5	113.2 (2)
C15—C16—C17	111.0 (2)	C51—O52—C52	115.7 (2)
C15—C16—C18	109.4 (2)	O52—C52—H52A	109.5
C17—C16—C18	109.8 (2)	O52—C52—H52B	109.5
C15—C16—C19	107.7 (2)	H52A—C52—H52B	109.5
C17—C16—C19	109.1 (2)	O52—C52—H52C	109.5
C18—C16—C19	109.8 (2)	H52A—C52—H52C	109.5
C16—C17—H17A	109.5	H52B—C52—H52C	109.5
C7a—N1—C2—N3	1.1 (3)	N12—C13—C14—C15	1.4 (3)
C13—N1—C2—N3	176.7 (2)	N1—C13—C14—C15	179.9 (2)
C7a—N1—C2—C21	−177.6 (2)	N12—N11—C15—C14	0.5 (3)
C13—N1—C2—C21	−2.0 (4)	N12—N11—C15—C16	−173.7 (2)
N1—C2—N3—C3a	−1.2 (3)	C13—C14—C15—N11	−1.1 (3)
C21—C2—N3—C3a	177.5 (2)	C13—C14—C15—C16	172.5 (3)
C2—N3—C3a—C4	−177.2 (3)	N11—C15—C16—C17	−22.1 (4)
C2—N3—C3a—C7a	0.9 (3)	C14—C15—C16—C17	165.3 (3)
N3—C3a—C4—C5	178.2 (2)	N11—C15—C16—C18	−143.4 (2)
C7a—C3a—C4—C5	0.3 (4)	C14—C15—C16—C18	43.9 (4)
C3a—C4—C5—C6	0.2 (4)	N11—C15—C16—C19	97.3 (3)
C3a—C4—C5—C51	−177.9 (2)	C14—C15—C16—C19	−75.3 (3)
C4—C5—C6—C7	−0.2 (4)	N3—C2—C21—C26	151.6 (3)
C51—C5—C6—C7	178.0 (2)	N1—C2—C21—C26	−29.9 (4)
C5—C6—C7—C7a	−0.4 (4)	N3—C2—C21—C22	−25.0 (4)
C2—N1—C7a—C7	178.3 (3)	N1—C2—C21—C22	153.6 (2)
C13—N1—C7a—C7	2.4 (4)	C26—C21—C22—C23	−1.6 (4)
C2—N1—C7a—C3a	−0.5 (3)	C2—C21—C22—C23	175.2 (2)
C13—N1—C7a—C3a	−176.4 (2)	C21—C22—C23—C24	0.8 (4)
C6—C7—C7a—N1	−177.7 (2)	C22—C23—C24—C25	0.2 (4)
C6—C7—C7a—C3a	0.9 (4)	C22—C23—C24—Br24	−178.72 (19)
C4—C3a—C7a—N1	178.0 (2)	C23—C24—C25—C26	−0.4 (4)
N3—C3a—C7a—N1	−0.2 (3)	Br24—C24—C25—C26	178.49 (19)
C4—C3a—C7a—C7	−0.9 (4)	C24—C25—C26—C21	−0.4 (4)
N3—C3a—C7a—C7	−179.1 (2)	C22—C21—C26—C25	1.3 (4)
C15—N11—N12—C13	0.3 (3)	C2—C21—C26—C25	−175.1 (2)
N11—N12—C13—C14	−1.1 (3)	C4—C5—C51—O51	179.3 (2)
N11—N12—C13—N1	−179.7 (2)	C6—C5—C51—O51	1.2 (4)
C7a—N1—C13—N12	80.5 (3)	C4—C5—C51—O52	−1.0 (3)
C2—N1—C13—N12	−94.4 (3)	C6—C5—C51—O52	−179.1 (2)
C7a—N1—C13—C14	−97.9 (3)	O51—C51—O52—C52	3.2 (4)
C2—N1—C13—C14	87.2 (4)	C5—C51—O52—C52	−176.4 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N11—H11···O51^i	0.88	2.01	2.839 (3)	156
C14—H14···Cg^ii	0.95	2.63	3.492 (3)	153

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