research communications
Stereochemistry of the methylidene-bridged quinazoline-isoquinoline alkaloid 3-{[6,7-dimethoxy-1-(4-nitrophenyl)-1,2,3,4-tetrahydroisoquinolin-2-yl]methylidene}-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-9-one methanol monosolvate
aLaboratory of Thermophysics of Multiphase Systems, Institute of Ion-Plasm and Laser Technologies named after U.A. Arifov, Academy of Sciences of Uzbekistan,100125, Durmon yuli st. 33, Tashkent, Uzbekistan, bS.Yunusov Institute of Chemistry of Plant Substances, Academy of Science of, Uzbekistan, Mirzo Ulugbek Str. 77, 100170 Tashkent, Uzbekistan, and cInstitute of Inorganic Chemistry, RWTH Aachen University, Landoltweg 1, 52056, Aachen, Germany
*Correspondence e-mail: a_tojiboev@yahoo.com
Two potentially bioactive fragments, namely a tricyclic quinazoline derivative with an exocyclic alkene moiety and a substituted isoquinoline, are coupled to give 3-{[6,7-dimethoxy-1-(4-nitrophenyl)-1,2,3,4-tetrahydroisoquinolin-2-yl]methylidene}-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-9-one. The target product crystallizes as a methanol solvate, C29H26N4O5·CH4O, and is E configured. The alternative Z isomer would necessarily imply either considerable twist about the central double bond or very unfavourable intramolecular contacts between sterically more demanding substituents. The main residue and the co-crystallized solvent molecule aggregate to discrete pairs via a classical O—H⋯O hydrogen bond with a distance of 2.8581 (7) Å between the methanol OH donor and the quinazolinone O=C acceptor.
Keywords: quinazoline; isoquinoline; steric congestion; hydrogen bonding; crystal structure.
CCDC reference: 2004621
1. Chemical context
The synthesis of the title compound, 3-[1′-(4′′-nitrophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-yl)]-methylidene-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-9-one methanol solvate, (III) is shown in Fig. 1. It combines two well-known bioactive scaffolds, namely a tricyclic quinazoline derivative (I) and a substituted isoquinoline (II).
Tricyclic quinazoline ; Eguchi, 2006; Shakhidoyatov et al., 2014). The reason for the wide interest in studying these substances lies in their multi-facetted biological activity: they have been associated with antibacterial (Jantova et al., 2004), tumor growth-inhibiting (Aoyagi et al., 1999; Kuneš et al., 2000; Foster et al., 1999; Forsch et al., 2002; Abdel-Jalil et al., 2005), antifungal (Dandia et al., 2005; Nikhil et al., 2011), antihyperglycemic (Ram et al., 2003) and anti-inflammatory (Yeh-Long et al., 2004) activity. They have been used as a bronchodilator (Jindal et al., 2002), cholinesterase inhibitor (Decker, 2005), antifolate (Rosowsky et al., 2000) and as a protein kinase inhibitor (Levitzki et al., 2003). Additional reports suggest these derivatives are used as anti-cancer (Manoj et al., 2013), anti-HIV (Zaigang et al., 2009), anticonvulsant and antihypertensive (Muruganantham et al., 2004) drugs and as antioxidants (Srinubabu et al., 2014). The Cambridge Structural Database (CSD, version 5.40, update February 2019; Groom et al., 2016) contains 118 structurally characterized substituted tricyclic quinazolines. Different methods for their efficient synthesis have been developed (Bowman et al., 2007; Deetz et al., 2001; Kamal et al., 2001, 2004; Lee et al., 2003; Liu et al., 2005). The reactive centres in the tricyclic quinazoline scaffold allow for further derivatization via electrophilic or nucleophiles substitution.
are frequently encountered in nature (Michael, 1997Isoquinoline et al., 2014), anti-AIDS (Uesawa et al., 2011), antifungal activity (Kashiwada et al., 2005) and cardiovascular effects (Candenas et al., 1990). Antagonists for the pathogenesis of neurological diseases, such as Parkinson's disease (Zaima et al., 2012) have also been described. A group of synthetic 1-aryltetrahydroisoquinoline derivatives show antiepileptic (Gitto et al., 2003), analgesic (Tursunkhodzhaeva et al., 2012) and sedative-anxiolytic activity (Mirzaev et al., 2017).
represent a particularly popular and widespread group of Even for fairly simple isoquinoline derivatives, biological activity has been reported. Examples include analgetic, anti-inflammatory and anti-cancer properties (JeetahOver the years the synthetic interest in the quest for new isoquinoline derivatives has not declined (Bentley, 2006; Zhurakulov et al., 2013, 2014, 2015), because even minor changes in the molecular geometry may lead to improved therapeutic effects. Both moieties mentioned above, a quinazoline and an isoquinoline, have been successfully connected by a methylidene bridge (Elmuradov et al., 1998, 2008; Turdibayev et al., 2011; Zhurakulov et al., 2015). This coupling reaction allows two potentially bioactive components to be combined in a single molecule. In view of the high chemical and biological activity of isoquinoline and tricyclic quinazoline we expect that the combination of both scaffolds as in the target compound of the present study could lead to unprecedented properties.
2. Structural commentary
The title compound crystallizes in the monoclinic P21/n with one molecule of the target heterocycle and one molecule of methanol in the A displacement ellipsoid plot and the numbering scheme for both molecules are provided in Fig. 2.
The methoxy substituents associated with O1 and O2 are displaced slightly out of the mean plane defined by the aromatic ring in the dihydroisoquinoline moiety (C4A–C8A), with out-of-plane distances of 0.082 (3) Å for C9 and 0.221 (3) Å for C10. The twist conformation of the heterocyclic ring of the dihydroisoquinoline moiety and the equatorial position of the nitrophenyl substituent observed here are similar to those in related structures (Olszak et al., 1996; Turgunov et al., 2016). C1, C4, C4A and C8A are coplanar within error, whereas C3 and N2 are on opposite sides of this plane. The nitrophenyl substituent C11–C16 and the aromatic part of the dihydroisoquinoline (C4A–C8A) form an angle of 75.70 (14)°. The main motivation for our crystallographic study was to establish the configuration about the C17=C18 double bond. Intuition suggests that the E configuration should clearly be favoured, and our experiment confirms this expectation. In order to further explore the steric congestion of an alternative Z configuration, we generated such a hypothetical molecule by 180° rotation of the complete tricyclic quinazoline moiety about C17=C18. The resulting geometry is depicted in Fig. 3.
The prohibitively short intramolecular contact between N19 and C3, shown as a dashed red line, amounts to only 2.05 Å without taking the hydrogen atoms attached to C3 into account. If the two parts of the target molecule are perceived as at least moderately rigid groups, such an alternative Z configuration can safely be excluded. It is important to note, however, that this construction of a hypothetical Z-configured molecule relies on the experimentally established geometry of the semi-rigid isoquinoline and quinazoline moieties. The tricyclic quinazoline system, formed by three fused rings, shows deviations from planarity for the sp3 carbon atoms, with maximum displacements of 0.126 (3) Å for C26 and 0.110 (3) Å for C25 on opposite sides of the mean plane.
3. Supramolecular features
An O⋯H—O hydrogen bond links the co-crystallized methanol molecule to the keto group of the quinazoline moiety and gives rise to a D(2) graph-set motif (Table 1). Additional short contacts involve non-classical C—H⋯O interactions, with H⋯O distances ranging between 2.29 and 2.59 Å, forming a complex three-dimensional network (Table 1, Fig. 4).
Stacking (Fig. 5) occurs between the pyrrole rings of neighbouring molecules about a centre of inversion [symmetry code: (i) 1 − x, 1 − y, 1 − z], with a distance between the centroids Cg1⋯Cg1i of 3.832 (2) Å and a ring slippage of 1.246 Å. Both short intermolecular contacts together lead to a supramolecular layer structure parallel to the (010) plane.
4. Hirshfeld surface analysis
The Hirshfeld surface analysis (Spackman & Jayatilaka, 2009) and the associated two-dimensional (2D) fingerprint plot (McKinnon et al., 2007) were performed with CrystalExplorer17 (Turner et al., 2017). The Hirshfeld surface for the main molecule in III, mapped with dnorm and its interaction with the co-crystallized solvent molecule is represented in Fig. 6. Colours on the Hirshfeld surface encode contact distances (red - close, white - medium, blue - long) between atoms on either side of the surface. The most obvious intermolecular interaction, the classical O⋯H—O hydrogen bond, shows up as a prominent deep-red spot on the surface, oriented towards the co-crystallized methanol molecule. The less-pronounced red features on the surface are associated with C—H⋯O contacts. Fig. 7 shows a 2D fingerprint plot for the contacts between O and H atoms. These contacts are responsible for the short lateral `spikes' on either side of the main diagonal of the plot.
5. Database survey
A search in the Cambridge Structural Database (CSD, version 5.40, update February 2019; Groom et al., 2016) gave seven occurrences of molecules containing the 3-methylidene-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-9-one moiety with a similar planar conformation as in the title structure. A search for the 1′-(4′′-nitrophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-yl moiety gave only three hits with similar conformations for the isoquinoline fragment: 1-(4-nitrophenyl)-N-(2,3,4,6-tetra-O-pivaloyl-β-D-galactopyranosyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (ABUTIA01; Allef et al., 2007) and two additional structures with a chloro-substituted phenyl ring, namely 2-acetyl-1(R)-(4′-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (ADOCUS; Gitto et al., 2007) and N-acetyl-1-(4-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (LEFFIM; Gao et al., 2006).
6. Synthesis and crystallization
3-Hydroxymethylidene-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-9-one (I) was synthesized according to the method of Oripov et al. (1979). Compound III was obtained from reaction of 1-(4′-nitrophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (0.164 g, 0.522 mmol) with 3-hydroxymethylidene-1,2,3,4-tetrahydropyrrolo[2,1-b]-quinazolin-9-one (0.122 g, 0.522 mmol). Yield 0.22 g, 86%; m.p. 462–465 K (after crystallization from methanol), Rf 0.81 (CHCl3/MeOH 14:1). A detailed report on the synthesis of III and its characterization by NMR, IR and is available (Zhurakulov et al., 2015). Crystals suitable for X-ray diffraction were obtained from a solution in methanol by slow evaporation of the solvent at room temperature.
7. details
Crystal data, data collection parameters and . H atoms on C atoms were positioned geometrically and treated as riding on their parent atoms, with C—H = 0.95 (aromatic), 0.98 (methyl), 0.99 (methylene) or 1.00 Å (tertiary C atom) and were refined with Uiso(H) = 1.5Ueq(C) for methyl H atoms and 1.2Ueq(C) otherwise. The H atom in the hydroxy group of the co-crystallized methanol was refined with a distance restraint [target distance O—H = 0.84 (2) Å] and with Uiso(H) = 1.2Ueq(O). The anisotropic displacement parameters of N1 and O3 atom were subjected to an enhanced rigid-bond restraint (Thorn et al., 2012).
results are summarized in Table 2
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Supporting information
CCDC reference: 2004621
https://doi.org/10.1107/S2056989020006696/fy2144sup1.cif
contains datablocks I, test. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989020006696/fy2144Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2056989020006696/fy2144Isup3.cml
Data collection: APEX2 (Bruker, 2001); cell
SAINT-Plus (Bruker, 2009); data reduction: SAINT-Plus (Bruker, 2009); program(s) used to solve structure: SHELXT (Sheldrick, 2015); program(s) used to refine structure: SHELXL2014/7 (Sheldrick, 2015); molecular graphics: PLATON (Spek, 2020); software used to prepare material for publication: publCIF (Westrip, 2010).C29H26N4O5·CH4O | F(000) = 1144 |
Mr = 542.58 | Dx = 1.376 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
a = 16.326 (4) Å | Cell parameters from 1353 reflections |
b = 8.0566 (19) Å | θ = 3.0–19.8° |
c = 20.565 (5) Å | µ = 0.10 mm−1 |
β = 104.497 (6)° | T = 100 K |
V = 2618.9 (11) Å3 | Rod, yellow |
Z = 4 | 0.55 × 0.09 × 0.08 mm |
Bruker APEX CCD diffractometer | 4821 independent reflections |
Radiation source: microsource | 2918 reflections with I > 2σ(I) |
Multilayer optics monochromator | Rint = 0.114 |
ω scans | θmax = 25.4°, θmin = 1.4° |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | h = −19→19 |
Tmin = 0.665, Tmax = 0.745 | k = −9→9 |
25889 measured reflections | l = −24→24 |
Refinement on F2 | 4 restraints |
Least-squares matrix: full | Hydrogen site location: mixed |
R[F2 > 2σ(F2)] = 0.061 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.164 | w = 1/[σ2(Fo2) + (0.0677P)2 + 0.4688P] where P = (Fo2 + 2Fc2)/3 |
S = 1.04 | (Δ/σ)max < 0.001 |
4821 reflections | Δρmax = 0.39 e Å−3 |
367 parameters | Δρmin = −0.35 e Å−3 |
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 | 0.08305 (12) | 1.1111 (2) | 0.65060 (10) | 0.0267 (5) | |
O2 | 0.14565 (12) | 1.0007 (2) | 0.77066 (9) | 0.0256 (5) | |
O4 | 0.71000 (15) | 1.2323 (3) | 0.94869 (12) | 0.0522 (7) | |
O3 | 0.60907 (14) | 1.4105 (3) | 0.94156 (11) | 0.0385 (6) | |
O5 | 0.70612 (13) | 0.3657 (3) | 0.50686 (10) | 0.0303 (5) | |
N1 | 0.63699 (17) | 1.2806 (4) | 0.92532 (13) | 0.0338 (7) | |
N2 | 0.46055 (15) | 0.8631 (3) | 0.66495 (12) | 0.0238 (6) | |
N19 | 0.59083 (15) | 0.4135 (3) | 0.66290 (12) | 0.0260 (6) | |
N24A | 0.62119 (15) | 0.5026 (3) | 0.56116 (12) | 0.0241 (6) | |
C1 | 0.42173 (18) | 0.8773 (4) | 0.72189 (14) | 0.0221 (7) | |
H1 | 0.4208 | 0.7639 | 0.7415 | 0.026* | |
C3 | 0.44128 (19) | 1.0014 (4) | 0.61757 (15) | 0.0266 (7) | |
H3B | 0.4754 | 0.9925 | 0.5841 | 0.032* | |
H3A | 0.4551 | 1.1081 | 0.6418 | 0.032* | |
C4 | 0.34774 (18) | 0.9951 (4) | 0.58261 (14) | 0.0269 (7) | |
H4B | 0.3321 | 1.0936 | 0.5534 | 0.032* | |
H4A | 0.3356 | 0.8947 | 0.5540 | 0.032* | |
C4A | 0.29609 (19) | 0.9915 (4) | 0.63407 (14) | 0.0236 (7) | |
C5 | 0.21208 (19) | 1.0482 (4) | 0.61679 (15) | 0.0248 (7) | |
H5 | 0.1879 | 1.0853 | 0.5723 | 0.030* | |
C6 | 0.16455 (18) | 1.0508 (4) | 0.66287 (15) | 0.0237 (7) | |
C7 | 0.19881 (18) | 0.9950 (3) | 0.72862 (14) | 0.0226 (7) | |
C8 | 0.28131 (19) | 0.9378 (3) | 0.74592 (14) | 0.0226 (7) | |
H8 | 0.3048 | 0.8982 | 0.7902 | 0.027* | |
C8A | 0.33064 (18) | 0.9374 (3) | 0.69924 (14) | 0.0213 (7) | |
C9 | 0.0470 (2) | 1.1711 (4) | 0.58366 (15) | 0.0331 (8) | |
H9B | 0.0804 | 1.2652 | 0.5743 | 0.050* | |
H9C | −0.0114 | 1.2071 | 0.5798 | 0.050* | |
H9A | 0.0474 | 1.0821 | 0.5513 | 0.050* | |
C10 | 0.1823 (2) | 0.9721 (4) | 0.84092 (15) | 0.0346 (9) | |
H10B | 0.2047 | 0.8588 | 0.8474 | 0.052* | |
H10C | 0.1389 | 0.9865 | 0.8659 | 0.052* | |
H10A | 0.2283 | 1.0515 | 0.8574 | 0.052* | |
C11 | 0.47684 (18) | 0.9873 (4) | 0.77600 (14) | 0.0213 (7) | |
C12 | 0.55019 (19) | 0.9188 (4) | 0.81757 (15) | 0.0279 (8) | |
H12 | 0.5636 | 0.8057 | 0.8123 | 0.033* | |
C13 | 0.6034 (2) | 1.0145 (4) | 0.86629 (15) | 0.0297 (8) | |
H13 | 0.6534 | 0.9687 | 0.8945 | 0.036* | |
C14 | 0.58186 (19) | 1.1787 (4) | 0.87291 (15) | 0.0258 (7) | |
C15 | 0.51115 (19) | 1.2512 (4) | 0.83252 (14) | 0.0262 (7) | |
H15 | 0.4986 | 1.3649 | 0.8375 | 0.031* | |
C16 | 0.45834 (19) | 1.1526 (4) | 0.78389 (14) | 0.0256 (7) | |
H16 | 0.4087 | 1.1997 | 0.7556 | 0.031* | |
C17 | 0.50221 (18) | 0.7246 (4) | 0.65647 (15) | 0.0223 (7) | |
H17 | 0.5061 | 0.6442 | 0.6909 | 0.027* | |
C18 | 0.53988 (18) | 0.6787 (4) | 0.60744 (15) | 0.0238 (7) | |
C18A | 0.58472 (18) | 0.5214 (4) | 0.61466 (14) | 0.0223 (7) | |
C19A | 0.64138 (18) | 0.2763 (4) | 0.66009 (15) | 0.0239 (7) | |
C20 | 0.6513 (2) | 0.1578 (4) | 0.71145 (16) | 0.0303 (8) | |
H20 | 0.6216 | 0.1704 | 0.7454 | 0.036* | |
C21 | 0.7038 (2) | 0.0237 (4) | 0.71301 (17) | 0.0381 (9) | |
H21 | 0.7100 | −0.0558 | 0.7480 | 0.046* | |
C22 | 0.7478 (2) | 0.0034 (5) | 0.66366 (18) | 0.0440 (10) | |
H22 | 0.7848 | −0.0886 | 0.6657 | 0.053* | |
C23 | 0.7382 (2) | 0.1152 (4) | 0.61231 (17) | 0.0343 (8) | |
H23 | 0.7675 | 0.0995 | 0.5783 | 0.041* | |
C23A | 0.68515 (18) | 0.2530 (4) | 0.60979 (15) | 0.0258 (7) | |
C24 | 0.67353 (18) | 0.3723 (4) | 0.55492 (15) | 0.0250 (7) | |
C25 | 0.59868 (19) | 0.6360 (4) | 0.51134 (15) | 0.0279 (8) | |
H25B | 0.5610 | 0.5943 | 0.4690 | 0.033* | |
H25A | 0.6499 | 0.6847 | 0.5014 | 0.033* | |
C26 | 0.55278 (19) | 0.7643 (4) | 0.54499 (14) | 0.0262 (7) | |
H26A | 0.5876 | 0.8656 | 0.5571 | 0.031* | |
H26B | 0.4978 | 0.7955 | 0.5146 | 0.031* | |
C27 | 0.8885 (3) | 0.3496 (6) | 0.4479 (2) | 0.0611 (12) | |
H27A | 0.9489 | 0.3688 | 0.4521 | 0.092* | |
H27B | 0.8599 | 0.3294 | 0.4007 | 0.092* | |
H27C | 0.8814 | 0.2527 | 0.4748 | 0.092* | |
O6 | 0.85271 (16) | 0.4911 (3) | 0.47115 (13) | 0.0523 (7) | |
H6 | 0.8044 (18) | 0.458 (5) | 0.4864 (18) | 0.063* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0260 (12) | 0.0294 (13) | 0.0210 (11) | 0.0026 (10) | −0.0010 (9) | 0.0009 (10) |
O2 | 0.0272 (12) | 0.0292 (13) | 0.0193 (11) | 0.0022 (10) | 0.0034 (9) | 0.0007 (10) |
O4 | 0.0356 (15) | 0.0495 (17) | 0.0555 (17) | −0.0046 (13) | −0.0185 (13) | 0.0101 (14) |
O3 | 0.0387 (14) | 0.0441 (16) | 0.0304 (13) | −0.0057 (12) | 0.0045 (11) | −0.0113 (12) |
O5 | 0.0311 (12) | 0.0356 (14) | 0.0269 (12) | −0.0003 (10) | 0.0123 (10) | −0.0025 (11) |
N1 | 0.0309 (17) | 0.0416 (19) | 0.0256 (16) | −0.0090 (14) | 0.0007 (13) | 0.0040 (14) |
N2 | 0.0272 (14) | 0.0218 (15) | 0.0218 (14) | 0.0028 (12) | 0.0054 (11) | 0.0016 (12) |
N19 | 0.0301 (15) | 0.0237 (15) | 0.0247 (15) | 0.0019 (12) | 0.0076 (12) | 0.0005 (12) |
N24A | 0.0232 (14) | 0.0241 (15) | 0.0235 (14) | 0.0000 (12) | 0.0032 (11) | 0.0004 (12) |
C1 | 0.0255 (16) | 0.0211 (17) | 0.0191 (16) | 0.0013 (13) | 0.0047 (13) | 0.0037 (14) |
C3 | 0.0306 (18) | 0.0245 (19) | 0.0249 (17) | 0.0010 (15) | 0.0070 (14) | 0.0035 (15) |
C4 | 0.0306 (18) | 0.0263 (19) | 0.0219 (17) | −0.0025 (15) | 0.0029 (14) | −0.0001 (15) |
C4A | 0.0318 (18) | 0.0168 (17) | 0.0211 (17) | −0.0018 (14) | 0.0047 (14) | −0.0020 (14) |
C5 | 0.0304 (18) | 0.0218 (18) | 0.0185 (16) | −0.0018 (14) | −0.0012 (14) | −0.0003 (14) |
C6 | 0.0239 (17) | 0.0189 (17) | 0.0235 (17) | −0.0003 (14) | −0.0029 (14) | 0.0006 (14) |
C7 | 0.0268 (18) | 0.0162 (16) | 0.0233 (17) | −0.0028 (14) | 0.0036 (14) | −0.0006 (14) |
C8 | 0.0331 (18) | 0.0146 (16) | 0.0168 (16) | −0.0017 (14) | 0.0002 (14) | −0.0009 (13) |
C8A | 0.0230 (16) | 0.0158 (16) | 0.0213 (17) | −0.0038 (13) | −0.0016 (13) | −0.0025 (13) |
C9 | 0.0310 (18) | 0.039 (2) | 0.0235 (18) | 0.0068 (16) | −0.0032 (15) | −0.0002 (16) |
C10 | 0.039 (2) | 0.043 (2) | 0.0218 (18) | 0.0109 (17) | 0.0081 (15) | 0.0058 (16) |
C11 | 0.0216 (16) | 0.0244 (18) | 0.0172 (16) | −0.0012 (13) | 0.0037 (13) | 0.0020 (14) |
C12 | 0.0292 (18) | 0.0254 (19) | 0.0283 (18) | 0.0042 (15) | 0.0061 (15) | 0.0049 (15) |
C13 | 0.0260 (18) | 0.032 (2) | 0.0265 (18) | −0.0008 (15) | −0.0017 (14) | 0.0081 (16) |
C14 | 0.0252 (17) | 0.030 (2) | 0.0207 (17) | −0.0049 (14) | 0.0021 (14) | −0.0015 (15) |
C15 | 0.0281 (18) | 0.0268 (19) | 0.0236 (17) | 0.0010 (15) | 0.0063 (15) | −0.0001 (15) |
C16 | 0.0257 (17) | 0.0284 (19) | 0.0214 (17) | −0.0017 (15) | 0.0034 (14) | 0.0014 (15) |
C17 | 0.0230 (16) | 0.0179 (17) | 0.0235 (17) | −0.0009 (13) | 0.0011 (14) | 0.0011 (14) |
C18 | 0.0225 (16) | 0.0240 (18) | 0.0242 (17) | −0.0027 (13) | 0.0044 (14) | −0.0005 (14) |
C18A | 0.0199 (16) | 0.0237 (18) | 0.0226 (17) | −0.0038 (13) | 0.0038 (13) | −0.0040 (14) |
C19A | 0.0203 (16) | 0.0202 (18) | 0.0290 (18) | −0.0054 (13) | 0.0023 (14) | −0.0048 (15) |
C20 | 0.0304 (18) | 0.033 (2) | 0.0269 (18) | 0.0010 (16) | 0.0062 (15) | −0.0002 (16) |
C21 | 0.043 (2) | 0.037 (2) | 0.035 (2) | 0.0123 (17) | 0.0106 (17) | 0.0080 (17) |
C22 | 0.048 (2) | 0.042 (2) | 0.043 (2) | 0.0239 (19) | 0.0138 (19) | 0.0072 (19) |
C23 | 0.037 (2) | 0.034 (2) | 0.034 (2) | 0.0098 (16) | 0.0120 (16) | 0.0017 (17) |
C23A | 0.0213 (16) | 0.0265 (18) | 0.0282 (18) | 0.0010 (14) | 0.0036 (14) | −0.0012 (15) |
C24 | 0.0207 (16) | 0.0246 (18) | 0.0279 (18) | −0.0036 (14) | 0.0025 (14) | −0.0063 (15) |
C25 | 0.0280 (17) | 0.032 (2) | 0.0231 (17) | −0.0015 (15) | 0.0052 (14) | 0.0017 (15) |
C26 | 0.0265 (17) | 0.0252 (18) | 0.0260 (18) | −0.0002 (14) | 0.0049 (14) | 0.0027 (15) |
C27 | 0.060 (3) | 0.072 (3) | 0.048 (3) | 0.019 (2) | 0.007 (2) | −0.011 (2) |
O6 | 0.0492 (17) | 0.0592 (19) | 0.0511 (17) | −0.0084 (14) | 0.0174 (14) | −0.0151 (14) |
O1—C6 | 1.379 (3) | C10—H10C | 0.9800 |
O1—C9 | 1.439 (4) | C10—H10A | 0.9800 |
O2—C7 | 1.371 (3) | C11—C16 | 1.384 (4) |
O2—C10 | 1.438 (3) | C11—C12 | 1.399 (4) |
O4—N1 | 1.232 (3) | C12—C13 | 1.384 (4) |
O3—N1 | 1.221 (3) | C12—H12 | 0.9500 |
O5—C24 | 1.236 (3) | C13—C14 | 1.384 (4) |
N1—C14 | 1.470 (4) | C13—H13 | 0.9500 |
N2—C17 | 1.341 (4) | C14—C15 | 1.373 (4) |
N2—C3 | 1.462 (4) | C15—C16 | 1.394 (4) |
N2—C1 | 1.469 (3) | C15—H15 | 0.9500 |
N19—C18A | 1.304 (4) | C16—H16 | 0.9500 |
N19—C19A | 1.389 (4) | C17—C18 | 1.357 (4) |
N24A—C24 | 1.379 (4) | C17—H17 | 0.9500 |
N24A—C18A | 1.384 (3) | C18—C18A | 1.452 (4) |
N24A—C25 | 1.467 (4) | C18—C26 | 1.518 (4) |
C1—C8A | 1.522 (4) | C19A—C20 | 1.403 (4) |
C1—C11 | 1.527 (4) | C19A—C23A | 1.409 (4) |
C1—H1 | 1.0000 | C20—C21 | 1.374 (4) |
C3—C4 | 1.517 (4) | C20—H20 | 0.9500 |
C3—H3B | 0.9900 | C21—C22 | 1.393 (4) |
C3—H3A | 0.9900 | C21—H21 | 0.9500 |
C4—C4A | 1.510 (4) | C22—C23 | 1.367 (5) |
C4—H4B | 0.9900 | C22—H22 | 0.9500 |
C4—H4A | 0.9900 | C23—C23A | 1.401 (4) |
C4A—C8A | 1.388 (4) | C23—H23 | 0.9500 |
C4A—C5 | 1.404 (4) | C23A—C24 | 1.458 (4) |
C5—C6 | 1.367 (4) | C25—C26 | 1.539 (4) |
C5—H5 | 0.9500 | C25—H25B | 0.9900 |
C6—C7 | 1.402 (4) | C25—H25A | 0.9900 |
C7—C8 | 1.383 (4) | C26—H26A | 0.9900 |
C8—C8A | 1.399 (4) | C26—H26B | 0.9900 |
C8—H8 | 0.9500 | C27—O6 | 1.418 (4) |
C9—H9B | 0.9800 | C27—H27A | 0.9800 |
C9—H9C | 0.9800 | C27—H27B | 0.9800 |
C9—H9A | 0.9800 | C27—H27C | 0.9800 |
C10—H10B | 0.9800 | O6—H6 | 0.957 (18) |
C6—O1—C9 | 116.0 (2) | C13—C12—H12 | 119.7 |
C7—O2—C10 | 117.3 (2) | C11—C12—H12 | 119.7 |
O3—N1—O4 | 123.7 (3) | C14—C13—C12 | 118.4 (3) |
O3—N1—C14 | 118.5 (3) | C14—C13—H13 | 120.8 |
O4—N1—C14 | 117.7 (3) | C12—C13—H13 | 120.8 |
C17—N2—C3 | 125.4 (2) | C15—C14—C13 | 122.9 (3) |
C17—N2—C1 | 120.2 (2) | C15—C14—N1 | 118.3 (3) |
C3—N2—C1 | 114.1 (2) | C13—C14—N1 | 118.8 (3) |
C18A—N19—C19A | 115.6 (2) | C14—C15—C16 | 117.8 (3) |
C24—N24A—C18A | 123.9 (3) | C14—C15—H15 | 121.1 |
C24—N24A—C25 | 123.0 (2) | C16—C15—H15 | 121.1 |
C18A—N24A—C25 | 113.1 (2) | C11—C16—C15 | 121.2 (3) |
N2—C1—C8A | 111.4 (2) | C11—C16—H16 | 119.4 |
N2—C1—C11 | 109.5 (2) | C15—C16—H16 | 119.4 |
C8A—C1—C11 | 113.0 (2) | N2—C17—C18 | 131.5 (3) |
N2—C1—H1 | 107.6 | N2—C17—H17 | 114.3 |
C8A—C1—H1 | 107.6 | C18—C17—H17 | 114.3 |
C11—C1—H1 | 107.6 | C17—C18—C18A | 118.2 (3) |
N2—C3—C4 | 108.2 (2) | C17—C18—C26 | 133.6 (3) |
N2—C3—H3B | 110.0 | C18A—C18—C26 | 108.0 (2) |
C4—C3—H3B | 110.0 | N19—C18A—N24A | 124.4 (3) |
N2—C3—H3A | 110.0 | N19—C18A—C18 | 126.9 (3) |
C4—C3—H3A | 110.0 | N24A—C18A—C18 | 108.7 (3) |
H3B—C3—H3A | 108.4 | N19—C19A—C20 | 117.9 (3) |
C4A—C4—C3 | 109.9 (2) | N19—C19A—C23A | 123.5 (3) |
C4A—C4—H4B | 109.7 | C20—C19A—C23A | 118.5 (3) |
C3—C4—H4B | 109.7 | C21—C20—C19A | 120.4 (3) |
C4A—C4—H4A | 109.7 | C21—C20—H20 | 119.8 |
C3—C4—H4A | 109.7 | C19A—C20—H20 | 119.8 |
H4B—C4—H4A | 108.2 | C20—C21—C22 | 120.5 (3) |
C8A—C4A—C5 | 118.8 (3) | C20—C21—H21 | 119.7 |
C8A—C4A—C4 | 121.3 (3) | C22—C21—H21 | 119.7 |
C5—C4A—C4 | 119.9 (3) | C23—C22—C21 | 120.3 (3) |
C6—C5—C4A | 121.2 (3) | C23—C22—H22 | 119.8 |
C6—C5—H5 | 119.4 | C21—C22—H22 | 119.8 |
C4A—C5—H5 | 119.4 | C22—C23—C23A | 120.1 (3) |
C5—C6—O1 | 124.6 (3) | C22—C23—H23 | 120.0 |
C5—C6—C7 | 120.3 (3) | C23A—C23—H23 | 120.0 |
O1—C6—C7 | 115.0 (3) | C23—C23A—C19A | 120.1 (3) |
O2—C7—C8 | 125.3 (3) | C23—C23A—C24 | 120.7 (3) |
O2—C7—C6 | 115.8 (3) | C19A—C23A—C24 | 119.2 (3) |
C8—C7—C6 | 118.9 (3) | O5—C24—N24A | 120.5 (3) |
C7—C8—C8A | 121.0 (3) | O5—C24—C23A | 126.3 (3) |
C7—C8—H8 | 119.5 | N24A—C24—C23A | 113.2 (3) |
C8A—C8—H8 | 119.5 | N24A—C25—C26 | 104.1 (2) |
C4A—C8A—C8 | 119.8 (3) | N24A—C25—H25B | 110.9 |
C4A—C8A—C1 | 121.7 (3) | C26—C25—H25B | 110.9 |
C8—C8A—C1 | 118.5 (3) | N24A—C25—H25A | 110.9 |
O1—C9—H9B | 109.5 | C26—C25—H25A | 110.9 |
O1—C9—H9C | 109.5 | H25B—C25—H25A | 109.0 |
H9B—C9—H9C | 109.5 | C18—C26—C25 | 105.2 (2) |
O1—C9—H9A | 109.5 | C18—C26—H26A | 110.7 |
H9B—C9—H9A | 109.5 | C25—C26—H26A | 110.7 |
H9C—C9—H9A | 109.5 | C18—C26—H26B | 110.7 |
O2—C10—H10B | 109.5 | C25—C26—H26B | 110.7 |
O2—C10—H10C | 109.5 | H26A—C26—H26B | 108.8 |
H10B—C10—H10C | 109.5 | O6—C27—H27A | 109.5 |
O2—C10—H10A | 109.5 | O6—C27—H27B | 109.5 |
H10B—C10—H10A | 109.5 | H27A—C27—H27B | 109.5 |
H10C—C10—H10A | 109.5 | O6—C27—H27C | 109.5 |
C16—C11—C12 | 119.1 (3) | H27A—C27—H27C | 109.5 |
C16—C11—C1 | 122.5 (3) | H27B—C27—H27C | 109.5 |
C12—C11—C1 | 118.3 (3) | C27—O6—H6 | 109 (2) |
C13—C12—C11 | 120.5 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
O6—H6···O5 | 0.96 | 1.91 | 2.8581 (7) | 171 |
C1—H1···O1i | 1.00 | 2.55 | 3.4040 (8) | 143 |
C1—H1···O2i | 1.00 | 2.37 | 3.2444 (8) | 146 |
C4—H4A···O5ii | 0.99 | 2.45 | 3.4346 (8) | 172 |
C9—H9B···O6iii | 0.98 | 2.54 | 3.5042 (9) | 169 |
C15—H15···O1iv | 0.95 | 2.44 | 3.3402 (8) | 159 |
C16—H16···O2iv | 0.95 | 2.59 | 3.3246 (8) | 134 |
C17—H17···N19 | 0.95 | 2.47 | 2.8805 (7) | 106 |
C25—H25A···O4v | 0.99 | 2.29 | 3.1224 (8) | 141 |
Symmetry codes: (i) −x+1/2, y−1/2, −z+3/2; (ii) −x+1, −y+1, −z+1; (iii) −x+1, −y, −z+1; (iv) −x+1/2, y+1/2, −z+3/2; (v) −x+3/2, y−1/2, −z+3/2. |
Funding information
Funding for this research was provided by: the Istedod Foundation of the Republic of Uzbekistan.
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