research communications
(1R,3S)-3-(1H-Benzo[d]imidazol-2-yl)-1,2,2-trimethylcyclopentane-1-carboxylic acid as a new anti-diabetic active pharmaceutical ingredient
aV.N. Karazin Kharkiv National University, 4 Svobody Sq., Kharkiv, 61077, Ukraine, bState Scientific Institution Institute for Single Crystals of the National Academy of Sciences of Ukraine, 61001, Kharkov, Ukraine, cNational University of Pharmacy, 53 Pushkinska St., Kharkiv, 61002, Ukraine, dFederal State Autonomous Educational Institution of Higher Education Belgorod State University, 85, Pobedy St., Belgorod, 308015, Russian Federation, eExperimental Plant for Dental Materials Vladmiva, 81d, Michurin St., Belgorod, 308015, Russian Federation, and fChemical Diversity Research Institute, 2A Rabochaya St., Khimki, Moscow Region, 141400, Russian Federation
*Correspondence e-mail: ikonovalova0210@gmail.com
The chiral title compound, C16H20N2O2, which can be used for producing active pharmaceutical ingredients for treatment of type 2 pancreatic diabetes and other pathologies dependent on insulin resistance, was prepared from (1R,3S)-camphoric acid and o-phenylenediamine. It crystallized from an ethanol solution in the chiral monoclinic P21 The five-membered ring adopts a twisted conformation with the methyl-substituted C atoms displaced by −0.273 (5) and 0.407 (5) Å from the mean plane through the other three atoms. In the crystal, molecules are linked by O—H⋯N hydrogen bonds, forming chains along the a-axis direction. Hirshfeld surface analysis and two-dimensional fingerprint plots were used to analyze the intermolecular contacts present in the crystal.
Keywords: crystal structure; Hirshfeld surface; 1H-benzo[d]imidazol-2-yl-1,2,2-trimethylcyclopentane-carboxylic acid; active pharmaceutical ingredient; anti-diabetic agents; type 2 diabetes.
CCDC reference: 2019647
1. Chemical context
The incidence of diabetes has taken on the character of an epidemic in the world. According to the forecasts of the World Health Organization, the number of patients with diabetes will double and reach 300 million people by 2025 (Zimmet et al., 2001). In this regard, developing and introducing new antidiabetic drugs is of great importance.
A great number of camphoric acid as well as benzimidazole derivatives exhibit different types of biological activities (Merzlikin et al., 2008; Ivachtchenko et al., 2002, 2019; Kovalenko et al., 1998).
Our research on the molecular design, construction and synthesis of new benzimidazole derivatives of 1,2,2,3-tetramethylcyclopentane-1-carboxylic acid has shown that (1R,3S)-3-(1H-benzo[d]imidazol-2-yl)-1,2,2-trimethylcyclopentane-1-carboxylic acid, 4, exhibits pronounced antidiabetic activity and, in particular, antihyperglycemic effect, which reduces insulin resistance and restores the physiological function of pancreatic β-cells (Jain et al., 2009; Chuev et al., 2017).
Racemic and enantiomeric crystals are known to possess different activities, which is very important in the pharmaceutical industry. We have found that the disadvantage of the (±) and (-) forms of compound 4 described in the patent of Merzlikin et al. (2009) is their poor bioavailability as compared to the (+) form. To obtain (1R,3S)-3-(1H-benzo[d] imidazol-2-yl)-1,2,2-trimethylcyclopentane-1-carboxylic acid 4, the enantiomerically pure (1R,3S)-camphoric acid 1 was used.
In the first stage, (1R,5S)-1,8,8-trimethyl-3-oxabicyclo[3.2.1]octane-2,4-dione [D-(+)-camphoric anhydride] 2 was obtained by refluxing a mixture of (1R,3S)-camphoric acid and acetic anhydride for 2 h (Dong et al., 2016) (Fig. 1).
In the second stage, the synthesis of (1R,3S)-3-(1H-benzo[d]imidazol-2-yl)-1,2,2- trimethylcyclopentane-1-carboxylic acid 4 was carried out according to Fig. 2 via cyclocondensation of D-(+)-camphoric anhydride 2 with o-phenylenediamine 3 in a mixture of toluene and DMF (383 K) by refluxing for several hours (Fig. 2).
It should be noted that during the synthesis, the configuration of the chiral centers did not change and the structure of the title molecule was unambiguously confirmed by X-ray analysis.
2. Structural commentary
The 4 (Fig. 3). The bicyclic fragment is planar with a maximum deviation of 0.016 (6) Å (for atom C16). The saturated five-membered ring adopts a twisted conformation in which the deviations of atoms C11 and C12 from the mean-square plane through the remaining ring atoms are −0.273 (5) and 0.407 (5) Å, respectively. The cyclopentane ring is turned in relation to the N1—C1 endocyclic bond, the N1—C1—C8—C9 torsion angle being −30.0 (7)°. It can be assumed that the weak intramolecular C9—H9B⋯N1 (H⋯N = 2.53 Å, C—H⋯N = 108°) hydrogen bond additionally stabilizes such a location of the saturated ring. The methyl group on the C11 atom is located in the axial position [C9—C10—C11—C15 = 87.5 (6)°]. The carboxyl group has an equatorial orientation and is almost coplanar to the endocyclic C10–C11 bond [the C9—C10—C11—C16 and C10—C11—C16—O1 torsion angles are −150.8 (5) and 13.9 (8)°, respectively]. This position is stabilized by the formation of weak intramolecular C10—H10A⋯O1 and C15—H15B⋯O2 hydrogen bonds between the vicinal and geminal substituents (H⋯O = 2.43 and 2.42 Å, C—H⋯O = 103 and 100°, respectively). The presence of geminal substituents on neighboring atoms of the pentane ring leads to significant steric repulsion (the shortened intramolecular contacts are given in Table 1), which causes elongation of the C8—C12 bond to 1.571 (7) Å, compared with its mean value of 1.556 Å (Burgi et al., 1994).
contains one molecule of the title compound
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3. Supramolecular features
In the crystal, molecules of 4 form layers parallel to the (100) plane as a result of the strong N2—H⋯O1 and O2—H⋯N1 and weak C14—H14C⋯C2(π) intermolecular hydrogen bonds (Table 2, Fig. 4a,b). The neighboring layers are not bound any specific interactions (Fig. 4a). It is interesting to note that the molecules are linked by hydrogen bonds that use the O—H⋯N heterosynthon instead of the carboxylic acid dimer homosynthon. Despite the presence of an aromatic ring in the molecule, no stacking interactions are observed in the crystal of 4. Instead of π– π interactions, C—H⋯π interactions are formed (Table 2, Fig. 4b).
4. Hirshfeld surface analysis
Crystal Explorer 17.5 (Turner et al., 2017) was used to analyze the interactions in the crystal and fingerprint plots mapped over dnorm (Figs. 5 and 6) were generated. The molecular Hirshfeld surfaces were obtained using a standard (high) surface resolution with the three-dimensional dnorm surfaces mapped over a fixed color scale of −0.716 (red) to 1.406 (blue) a.u. The red spots indicate regions of donor–acceptor interactions or short contacts. There are three red spots in the dnorm surface for 4 (Fig. 5), which correspond to the interactions listed in Table 2.
All of the intermolecular interactions of the title compound are shown in the two-dimensional fingerprint plot presented in Fig. 6a. The fingerprint plots indicate that the principal contributions are from H⋯H (61.7%; Fig. 6b), C⋯H/H⋯C (18.1%; Fig. 6c), O⋯H/H⋯O (13.5%; Fig. 6d) and N⋯H/H⋯N (6.6%; Fig. 6e) contacts. The H⋯H interactions appear in the middle of the plot scattered over a large area, while the C⋯H/H⋯C contacts are represented by the `wings' of the plot. O⋯H/H⋯O interactions appear as inner spikes and the N⋯H/H⋯N contacts, corresponding to the O—H⋯N interaction, are represented by a pair of sharp outer spikes, which indicate they are the strongest interactions in the crystal of 4.
5. Database survey
A search of the Cambridge Structural Database (CSD, Version 5.41, November 2019; Groom et al., 2016) for the 1,2,2-trimethylcyclopentane-1-carboxylic acid skeleton yielded 27 hits. Only one structure involves a benzothiazol-2′-yl ring in position 3, viz. (1R,3S)-(+)-cis-1,3-bis(benzothiazol-2′-yl)-1,2,2-trimethylcyclopentane (CSD refcode XUMXIM; Gilbert et al., 2002). The cyclopentane ring has the twist conformation with the atoms C1 and C4 displaced by 0.48 (1) and −0.26 (2) Å from the mean plane through the other three atoms [cf. 0.407 (5) Å and −0.273 (5) Å in the title compound].
6. Synthesis and crystallization
(1R,3S)-3-(1H-Benzo[d]imidazol-2-yl)-1,2,2-trimethylcyclopentane-1-carboxylic acid, 4
In a glass reactor equipped with a Dean–Stark receiver, D-(+)-camphoric anhydride 2 (2.20 kg, 12.1 mol), o-phenylenediamine 3 (1.31 kg, 12.1 mol), toluene (11.46 L) and dimethylformamide (0.91 L) were charged. Under stirring, the reaction mixture was heated to boiling (383 K). The mixture was refluxed and the released water was collected in the Dean–Stark receiver. When the removal of water had finished, the reaction mixture was cooled to room temperature. The precipitate that formed was filtered in vacuo using a Nutsche filter. The precipitate was thoroughly squeezed, washed twice with toluene (1.4 L) and re-squeezed. Then the precipitate was washed on the filter with 70% water–ethanol (3.7 L), heated to a temperature of 348±5 K. Finally, the precipitate of the product 4 was thoroughly squeezed and dried at 343 K for 4 h, yielding 2.41 kg (73.2%) of a white crystal-like powder that is practically insoluble in water, soluble in 96% alcohol, m.p. 527–528 K. UV (ethanol) λmax (∊): 204 nm (48960), 245 nm (6800), 275 nm (9160), 281 nm (9320); IR (KBr): ν (cm−1) 3450 (O—H), 3286 (N—H), 2970, 2935, 2887 (C—H), 1673 (C=O), 1529, 1456, 1436, 1373, 1279, 1358, 1167, 1124, 1057, 740; 1H NMR (400 MHz, DMSO-d6) δ 12.22 (s.br, 1H, OH), 12.10 (s.br, 1H, NH), 7.52 (s.br, 1H, H-4, H-7), 7.44 (s.br, 1H, H-4, H-7), 7.10 (t, J = 4.5 Hz, 2H, H-5, H-6), 3.41–3.31 (m, 1H, CH), 2.64–2.54 (m, 1H,CH), 2.43–2.33 (m, 1H, CH), 2.05–1.95 (m, 1H, CH), 1.55–1.45 (m, 1H, CH), 1.25 (s, 3H, CH3), 1.14 (s, 3H, CH3), 0.61 (s, 3H, CH3); LC/MS m/z (%): 273.2 [MH]+ (100); found, %: C 70.88; H 7.83; N 10.55. C16H20N2O2. Calculated, %: C 70.56; H 7.40; N 10.29.
Further crystallization by slow evaporation of an ethanol solution was carried out to provide single block-like colorless crystals (Fig. 7) suitable for X-ray diffraction analysis.
7. Refinement
Crystal data, data collection and structure . H atoms were included in calculated positions and treated as riding on their parent C atom: C—H = 0.82–0.98 Å with Uiso(H) = 1.5Ueq(C-methyl and O-hydroxyl) and 1.2Ueq(C) for other H atoms. The cannot be determined reliably, because there is no X-ray because of the absence of heavy atoms in the molecule.
details are summarized in Table 3Supporting information
CCDC reference: 2019647
https://doi.org/10.1107/S2056989020010439/dj2007sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989020010439/dj2007Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2056989020010439/dj2007Isup3.cml
Data collection: CrysAlis PRO (Rigaku OD, 2018); cell
CrysAlis PRO (Rigaku OD, 2018); data reduction: CrysAlis PRO (Rigaku OD, 2018); program(s) used to solve structure: ShelXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).C16H20N2O2 | F(000) = 292 |
Mr = 272.34 | Dx = 1.231 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71073 Å |
a = 7.9805 (7) Å | Cell parameters from 748 reflections |
b = 10.8671 (8) Å | θ = 3.6–20.3° |
c = 8.4912 (7) Å | µ = 0.08 mm−1 |
β = 94.056 (7)° | T = 293 K |
V = 734.55 (10) Å3 | Plate, colourless |
Z = 2 | 0.3 × 0.2 × 0.1 mm |
Rigaku Oxford Diffraction Xcalibur, Sapphire3 diffractometer | 2455 independent reflections |
Radiation source: fine-focus sealed X-ray tube, Enhance (Mo) X-ray Source | 1731 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.058 |
Detector resolution: 16.1827 pixels mm-1 | θmax = 25.0°, θmin = 3.1° |
ω scans | h = −9→8 |
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2018) | k = −12→11 |
Tmin = 0.182, Tmax = 1.000 | l = −9→10 |
4859 measured reflections |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.065 | w = 1/[σ2(Fo2) + (0.0794P)2] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.180 | (Δ/σ)max < 0.001 |
S = 1.04 | Δρmax = 0.15 e Å−3 |
2455 reflections | Δρmin = −0.19 e Å−3 |
185 parameters | Absolute structure: Flack x determined using 459 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) |
1 restraint | Absolute structure parameter: −1.8 (10) |
Primary atom site location: dual |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.3639 (6) | 0.5406 (4) | 0.7106 (5) | 0.0801 (12) | |
O2 | 0.2632 (6) | 0.7051 (3) | 0.5806 (5) | 0.0755 (12) | |
H2 | 0.289977 | 0.738749 | 0.665107 | 0.113* | |
N1 | 0.6692 (5) | 0.3376 (4) | 0.1635 (5) | 0.0593 (11) | |
N2 | 0.5767 (6) | 0.4717 (4) | −0.0168 (5) | 0.0673 (13) | |
H2A | 0.510294 | 0.522765 | −0.067258 | 0.081* | |
C1 | 0.5454 (7) | 0.4112 (5) | 0.1190 (6) | 0.0584 (13) | |
C2 | 0.7894 (7) | 0.3527 (5) | 0.0550 (7) | 0.0604 (14) | |
C3 | 0.7336 (8) | 0.4365 (5) | −0.0588 (7) | 0.0654 (14) | |
C4 | 0.8269 (10) | 0.4678 (6) | −0.1848 (8) | 0.0831 (19) | |
H4 | 0.786965 | 0.523797 | −0.261269 | 0.100* | |
C5 | 0.9807 (11) | 0.4124 (8) | −0.1914 (9) | 0.096 (2) | |
H5 | 1.047951 | 0.432369 | −0.272757 | 0.115* | |
C6 | 1.0379 (9) | 0.3261 (7) | −0.0773 (9) | 0.090 (2) | |
H6 | 1.142413 | 0.289532 | −0.084821 | 0.108* | |
C7 | 0.9429 (8) | 0.2942 (7) | 0.0460 (8) | 0.0759 (17) | |
H7 | 0.980342 | 0.235604 | 0.120267 | 0.091* | |
C8 | 0.3928 (7) | 0.4359 (5) | 0.2036 (6) | 0.0580 (13) | |
H8 | 0.300846 | 0.455808 | 0.125078 | 0.070* | |
C9 | 0.3372 (7) | 0.3271 (5) | 0.3025 (7) | 0.0679 (15) | |
H9A | 0.245558 | 0.283181 | 0.246369 | 0.082* | |
H9B | 0.429868 | 0.270412 | 0.324145 | 0.082* | |
C10 | 0.2806 (9) | 0.3803 (5) | 0.4556 (8) | 0.0716 (16) | |
H10A | 0.360495 | 0.359711 | 0.543071 | 0.086* | |
H10B | 0.171604 | 0.347548 | 0.477382 | 0.086* | |
C11 | 0.2707 (6) | 0.5205 (5) | 0.4334 (7) | 0.0597 (14) | |
C12 | 0.4144 (6) | 0.5465 (5) | 0.3225 (6) | 0.0575 (12) | |
C13 | 0.5865 (7) | 0.5408 (6) | 0.4150 (7) | 0.0707 (15) | |
H13A | 0.597970 | 0.463626 | 0.469595 | 0.106* | |
H13B | 0.595652 | 0.606974 | 0.490044 | 0.106* | |
H13C | 0.673547 | 0.548409 | 0.343119 | 0.106* | |
C14 | 0.3983 (9) | 0.6692 (5) | 0.2366 (8) | 0.0764 (17) | |
H14A | 0.491174 | 0.679383 | 0.171902 | 0.115* | |
H14B | 0.398423 | 0.734744 | 0.312382 | 0.115* | |
H14C | 0.295039 | 0.670837 | 0.171336 | 0.115* | |
C15 | 0.0964 (7) | 0.5560 (7) | 0.3588 (8) | 0.0811 (18) | |
H15A | 0.079109 | 0.518462 | 0.256632 | 0.122* | |
H15B | 0.089416 | 0.643848 | 0.348102 | 0.122* | |
H15C | 0.011624 | 0.527941 | 0.425166 | 0.122* | |
C16 | 0.3042 (6) | 0.5877 (5) | 0.5895 (7) | 0.0612 (15) |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.100 (3) | 0.086 (3) | 0.053 (2) | 0.005 (2) | −0.011 (2) | 0.006 (2) |
O2 | 0.103 (3) | 0.063 (2) | 0.058 (3) | 0.012 (2) | −0.014 (2) | −0.0111 (18) |
N1 | 0.067 (3) | 0.060 (3) | 0.051 (3) | 0.004 (2) | 0.001 (2) | 0.001 (2) |
N2 | 0.083 (3) | 0.067 (3) | 0.050 (3) | 0.003 (2) | −0.004 (2) | 0.006 (2) |
C1 | 0.070 (3) | 0.060 (3) | 0.043 (3) | −0.001 (3) | −0.006 (2) | −0.001 (2) |
C2 | 0.063 (3) | 0.066 (3) | 0.051 (3) | −0.002 (3) | 0.000 (2) | −0.006 (3) |
C3 | 0.078 (4) | 0.063 (3) | 0.055 (3) | −0.010 (3) | 0.004 (3) | −0.005 (3) |
C4 | 0.104 (5) | 0.088 (4) | 0.059 (4) | −0.026 (4) | 0.016 (3) | −0.001 (3) |
C5 | 0.098 (5) | 0.119 (6) | 0.073 (5) | −0.039 (5) | 0.027 (4) | −0.019 (4) |
C6 | 0.075 (4) | 0.113 (6) | 0.083 (5) | −0.011 (4) | 0.012 (4) | −0.026 (5) |
C7 | 0.071 (4) | 0.090 (4) | 0.066 (4) | 0.000 (3) | 0.001 (3) | −0.011 (3) |
C8 | 0.068 (3) | 0.056 (3) | 0.049 (3) | 0.002 (2) | −0.007 (2) | −0.002 (2) |
C9 | 0.074 (4) | 0.055 (3) | 0.074 (4) | −0.001 (3) | 0.003 (3) | −0.001 (3) |
C10 | 0.088 (4) | 0.061 (3) | 0.066 (4) | −0.005 (3) | 0.008 (3) | 0.005 (3) |
C11 | 0.056 (3) | 0.055 (3) | 0.067 (4) | 0.003 (2) | −0.004 (2) | 0.000 (3) |
C12 | 0.061 (3) | 0.052 (3) | 0.058 (3) | 0.001 (2) | −0.002 (2) | 0.003 (2) |
C13 | 0.064 (3) | 0.071 (3) | 0.075 (4) | 0.000 (3) | −0.005 (3) | −0.010 (3) |
C14 | 0.102 (5) | 0.058 (3) | 0.069 (4) | 0.007 (3) | 0.003 (3) | 0.007 (3) |
C15 | 0.063 (3) | 0.097 (4) | 0.081 (4) | 0.005 (4) | −0.012 (3) | −0.019 (4) |
C16 | 0.057 (3) | 0.068 (4) | 0.058 (4) | 0.001 (3) | 0.001 (3) | −0.005 (3) |
O1—C16 | 1.216 (6) | C5—C6 | 1.401 (11) |
O2—C16 | 1.319 (6) | C6—C7 | 1.380 (9) |
N1—C1 | 1.307 (7) | C8—C9 | 1.533 (8) |
N1—C2 | 1.386 (7) | C8—C12 | 1.571 (7) |
N2—C1 | 1.366 (7) | C9—C10 | 1.520 (9) |
N2—C3 | 1.381 (8) | C10—C11 | 1.536 (8) |
C1—C8 | 1.481 (8) | C11—C12 | 1.560 (8) |
C2—C3 | 1.378 (8) | C11—C15 | 1.537 (7) |
C2—C7 | 1.387 (8) | C11—C16 | 1.520 (8) |
C3—C4 | 1.388 (8) | C12—C13 | 1.534 (7) |
C4—C5 | 1.372 (10) | C12—C14 | 1.521 (8) |
C1—N1—C2 | 106.3 (5) | C10—C9—C8 | 106.8 (5) |
C1—N2—C3 | 107.9 (5) | C9—C10—C11 | 106.7 (5) |
N1—C1—N2 | 111.0 (5) | C10—C11—C12 | 102.7 (4) |
N1—C1—C8 | 127.0 (5) | C10—C11—C15 | 109.7 (5) |
N2—C1—C8 | 121.9 (5) | C15—C11—C12 | 112.9 (5) |
N1—C2—C7 | 129.6 (6) | C16—C11—C10 | 111.4 (5) |
C3—C2—N1 | 109.9 (5) | C16—C11—C12 | 110.4 (4) |
C3—C2—C7 | 120.5 (6) | C16—C11—C15 | 109.7 (4) |
N2—C3—C4 | 132.6 (6) | C11—C12—C8 | 101.4 (4) |
C2—C3—N2 | 104.9 (5) | C13—C12—C8 | 110.6 (4) |
C2—C3—C4 | 122.5 (6) | C13—C12—C11 | 110.7 (4) |
C5—C4—C3 | 117.0 (7) | C14—C12—C8 | 111.1 (4) |
C4—C5—C6 | 120.9 (6) | C14—C12—C11 | 114.0 (5) |
C7—C6—C5 | 121.6 (7) | C14—C12—C13 | 108.8 (5) |
C6—C7—C2 | 117.5 (7) | O1—C16—O2 | 122.4 (5) |
C1—C8—C9 | 113.9 (5) | O1—C16—C11 | 124.8 (5) |
C1—C8—C12 | 113.2 (4) | O2—C16—C11 | 112.8 (5) |
C9—C8—C12 | 105.1 (4) | ||
N1—C1—C8—C9 | −30.0 (7) | C7—C2—C3—N2 | 177.5 (5) |
N1—C1—C8—C12 | 90.0 (6) | C7—C2—C3—C4 | −1.0 (8) |
N1—C2—C3—N2 | −0.1 (6) | C8—C9—C10—C11 | 10.7 (7) |
N1—C2—C3—C4 | −178.6 (5) | C9—C8—C12—C11 | −35.1 (5) |
N1—C2—C7—C6 | 179.1 (5) | C9—C8—C12—C13 | 82.4 (6) |
N2—C1—C8—C9 | 153.8 (5) | C9—C8—C12—C14 | −156.6 (5) |
N2—C1—C8—C12 | −86.2 (6) | C9—C10—C11—C12 | −32.7 (6) |
N2—C3—C4—C5 | −178.8 (6) | C9—C10—C11—C15 | 87.5 (6) |
C1—N1—C2—C3 | −1.0 (6) | C9—C10—C11—C16 | −150.8 (5) |
C1—N1—C2—C7 | −178.3 (6) | C10—C11—C12—C8 | 41.1 (5) |
C1—N2—C3—C2 | 1.1 (6) | C10—C11—C12—C13 | −76.3 (5) |
C1—N2—C3—C4 | 179.4 (6) | C10—C11—C12—C14 | 160.6 (5) |
C1—C8—C9—C10 | 140.0 (5) | C10—C11—C16—O1 | 13.9 (8) |
C1—C8—C12—C11 | −160.0 (4) | C10—C11—C16—O2 | −166.9 (5) |
C1—C8—C12—C13 | −42.5 (6) | C12—C8—C9—C10 | 15.6 (6) |
C1—C8—C12—C14 | 78.5 (6) | C12—C11—C16—O1 | −99.5 (6) |
C2—N1—C1—N2 | 1.7 (6) | C12—C11—C16—O2 | 79.7 (5) |
C2—N1—C1—C8 | −174.8 (5) | C15—C11—C12—C8 | −76.9 (5) |
C2—C3—C4—C5 | −0.8 (9) | C15—C11—C12—C13 | 165.7 (5) |
C3—N2—C1—N1 | −1.8 (6) | C15—C11—C12—C14 | 42.6 (6) |
C3—N2—C1—C8 | 174.9 (5) | C15—C11—C16—O1 | 135.5 (6) |
C3—C2—C7—C6 | 2.0 (8) | C15—C11—C16—O2 | −45.3 (7) |
C3—C4—C5—C6 | 1.4 (10) | C16—C11—C12—C8 | 160.0 (4) |
C4—C5—C6—C7 | −0.4 (10) | C16—C11—C12—C13 | 42.6 (6) |
C5—C6—C7—C2 | −1.3 (9) | C16—C11—C12—C14 | −80.5 (5) |
D—H···A | D—H | H···A | D···A | D—H···A |
O2—H2···N1i | 0.82 | 1.82 | 2.631 (6) | 170 |
N2—H2A···O1ii | 0.86 | 2.16 | 2.871 (6) | 140 |
C14—H14C···C2iii | 0.96 | 2.81 | 3.439 (8) | 124 |
Symmetry codes: (i) −x+1, y+1/2, −z+1; (ii) x, y, z−1; (iii) −x+1, y+1/2, −z. |
The van der Waals radii sum values (Zefirov et al., 1997) are given in parentheses. |
H8···H15A | 2.26 (2.34) | H15B···H14C | 2.32 (2.34) |
H13C···C1 | 2.57 (2.87) | H13B···C16 | 2.54 (2.87) |
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