research communications
Structural investigation of methyl 3-(4-fluorobenzoyl)-7-methyl-2-phenylindolizine-1-carboxylate, an inhibitory drug towards Mycobacterium tuberculosis
aDepartment of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhauri, Bhopal 462066, India, bDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Kingdom of Saudi Arabia, cDepartment of Biotechnology and Food Technology, Durban University of Technology, Durban 4001, South Africa, and dInstitute for Stem Cell Biology and Regenerative Medicine, NCBS, TIFR, GKVK, Bellary Road, Bangalore 560 065, India
*Correspondence e-mail: dchopra@iiserb.ac.in
The title compound, C24H18FNO3, crystallizes in the monoclinic centrosymmetric P21/n and its molecular conformation is stabilized via C—H⋯O intramolecular interactions. The supramolecular network mainly comprises C—H⋯O, C—H⋯F and C—H⋯π interactions, which contribute towards the formation of the The different intermolecular interactions have been further analysed via Hirshfeld surface analysis and fingerprint plots.
Keywords: crystal structure; anti-TB activity drug; intermolecular interactions; Hirshfeld surface analysis; fingerprint plot.
CCDC reference: 1865697
1. Chemical context
Indolizine represents an interesting heterocyclic scaffold in which the nitrogen atom belongs to both of the fused six- and five-membered rings. It is a well-known pharmacophore endowed with various promising pharmacological properties. For instance, indolizines have been found to exhibit analgesic (Vaught et al., 1990), anticancer (Butler, 2008; Sandeep et al., 2016a,b), antidiabetic (Mederski et al., 2012), antihistaminic (Cingolani et al., 1990), anti-microbial (Hazra et al., 2011) and antiviral (Mishra & Tiwari, 2011) activity. It has also been found to act as cyclo-oxygenase (COX-2) inhibitor (Chandrashekharappa et al., 2018b) and to have larvicidal activity against Anopheles arabiensis (Chandrashekharappa et al., 2018a).
The title compound, comprising a substituted indolizine unit, displays a modest activity against susceptible H37Rv strains of Mycobacterium tuberculosis (Venugopala et al., 2019). Besides the tremendous scope of the pharmacological studies on indolizine-based compounds, the substitution of fluorine on the benzoyl ring, the presence of flexible moieties and of competitive hydrogen-bond acceptors (namely, oxygen O2 in the ester group at C6 and O3 in the carbonyl group at C8) make the structural study of the title compound of extreme relevance. In addition, it is of importance to observe the cooperative interplay of weak interactions that contribute towards the consolidation of the In the present paper, we report the molecular and of the title compound, highlighting its molecular conformation and analysing the different intermolecular interactions via Hirshfeld surface analysis and fingerprint plots.
2. Structural commentary
The title compound crystallizes in the centrosymmetric monoclinic P21/n The molecular structure comprises one methylindolizine heterocyclic moiety (N1/C1–C9) consisting of fused six- and five-membered rings (N1/C1–C5, centroid Cg1 and N1/C5–C8, centroid Cg2). The heterocycle is substituted at the carbon atoms C6, C7 and C8 with a methoxy carbonyl group, a phenyl ring (C12–C17, centroid Cg3), and a fluorobenzoyl ring [C18/O3/C19–C24/F1, centroid Cg4], respectively (Fig. 1). The molecular structure possesses three conformational due to the with respect to the C6—C10, C7—C12, and C8—C18 single bonds. The molecular conformation is stabilized by the presence of intramolecular C1—H1⋯O3 [C1⋯O3 = 2.853 (3) Å] and C4—H4⋯O2 [C4⋯O2 = 2.927 (2) Å] interactions (Table 1) and by π–π stacking [Cg3⋯Cg4 = 3.5084 (13) Å]. The dihedral angle between the mean plane through ring Cg3 (coloured in green in Fig. 2) and the mean plane of the indolizine skeleton (coloured in red) is 59.05 (9)°, while the dihedral angle between the mean plane through the phenyl ring and that through the fluorobenzoyl ring (coloured in blue) is as small as 19.04 (10),° showing the nearly parallel position of the rings. The torsion angles N1—C8—C18—C19 and C8—C18—C19—C24 are −161.74 (19) and 46.2 (3)°, respectively.
3. Supramolecular features
The list of all intra- and intermolecular interactions along with their geometrical parameters have been reported in Table 1. The interactions included for investigation are based on the distance criteria of vdW + 0.4 Å (Dance, 2003). In the crystal, the molecules are primarily assembled through concomitant C2/15—H2/15⋯O1ii/O3iii interactions [C2⋯O1ii = 3.531 (4) Å, 157°; C15⋯O3iii = 3.519 (4) Å, 137°; symmetry codes: (ii) x, y − 1, z; (iii) x, y + 1, z] and C1—H1⋯π(C15)ii [C1⋯C15 = 3.6064 (3) Å, 152°], forming ribbons along the [010] direction, as shown by the green shading in Fig. 3. Two adjacent ribbons are connected to each other via C11—H11B⋯F1v [C11⋯F1 = 3.0585 (3) Å, 104°; symmetry code: (v) x − , −y + , z − ] (Fig. 3) and C21—H21⋯O3i [C21⋯O3 = 3.399 (3) Å, 149°; symmetry code: (i) −x + , y + , −z + ] (Fig. 4) interactions in a zigzag fashion along [001], resulting in the formation of a molecular sheet parallel to the ac plane. Analogous C—H⋯F interactions have been investigated, showing that where the angularity is in the range 90 to 140°, the σ-hole on fluorine is directed towards the electron density of the C—H bond (Hathwar et al., 2020), underlining the importance of interactions with low angularity. The molecular sheets are closely stacked along the a-axis direction via weak interactions such as C9—H9C⋯π(C1) [C9⋯C1vii = 3.7431 (5) Å; symmetry code: (vii) −x + 1, −y, −z], C11—H11A⋯π(C5) [C11⋯C5iv = 3.4906 (4) Å; symmetry code: (iv) −x, −y + 1, −z], C11—H11C⋯π(C8) [C11⋯C8viii = 3.6590 (5) Å; symmetry code: (viii) −x + 1, −y + 1, −z] (Fig. 4), giving rise to a layered supramolecular structure. From this analysis, it can be stated that the formation of the is mainly governed by several C—H⋯O and C—H⋯π interactions, while the C—H⋯F interactions play a secondary but supporting role in its overall consolidation.
4. Database survey
A search for the 2-phenylindolizine skeleton in the CSD (version 5.40, update of August 2019; Groom et al., 2016) was carried out. Out of the 39 hits for unsubstituted phenyl rings attached to indolizine, the majority of entries gave reports of varied synthetic procedures and methodologies to obtain these compounds, underlining their importance. The near-infrared emissive properties of KIVLIN, KIVLOT, KIVLUZ (Gayton et al., 2019) and KENFAN (McNamara et al., 2017) have also been reported.
Structural details of compounds such as CAJTAI (Aslanov et al., 1983), EMUTOV (Liu, et al., 2003), FEDQAH (Liu, et al., 2005), GIYLOP (Sonnenschein & Schneider, 1997), ODEFIN (Qian et al., 2006), PNOIZA, PNOIZB, PNOIZE, PNOIZF (Tafeenkov & Aslanov, 1980), ROLKIM (Tafeenkov & Au, 1996) and TIGXOX (Liu, et al., 2007) have also been deposited. Almost all of these molecules are substituted at the C8 position with electron-withdrawing substituents such as –COMe, –CH2CN, –CN, –N=O, –CH=C(Ph)(CN), etc.
In particular, the papers reporting TIGXOX (Liu et al., 2007), FEDQAH (Liu et al., 2005) and ODEFIN (Qian et al., 2006) discuss the structural features of molecules comprising the 2-phenyl indolizine skeleton, showing high fluorescent efficiency. In these reports, the respective dihedral angles between the mean plane of the indolizine skeleton and the plane of the phenyl ring are ca 53, 39 and 49 and 45°, comparable to that reported in the title compound.
5. Hirshfeld surface analysis and fingerprint plots
The significance of the cumulative effect of the interactions involved in the et al., 2009). The Hirshfeld surfaces and the two-dimensional fingerprint plots were calculated using CrystalExplorer (Version 17.5; Wolff et al., 2012) and are shown in Figs. 5 and 6, respectively. The red spots on the HS surface illustrate the presence of supramolecular interactions such as C—H⋯O, C—H⋯π and C—H⋯F whereas the blue regions indicate the lack of contact distances shorter than the sum of the van der Waals radii. The fingerprint plots represent the individual contributions of the different interactions. Fig. 6 shows that the major contribution comes from H⋯H (47.1%), O⋯H/H⋯O (13.1%), C⋯H/ H⋯C (21.4%), H⋯F/F⋯H (9.0%), C⋯C (1.9%) and N⋯H/H⋯N (1.7%) contacts. The relatively high percentage of C⋯H/H⋯C contacts indicates how the contribution of all of the C—H⋯π interactions plays an important role in consolidating the crystal packing.
can be visualized qualitatively through Hirshfeld surface analysis (Spackman6. Synthesis and crystallization
All chemicals were obtained from Sigma–Aldrich and used without further purification. A mixture of methyl 3-phenylpropiolate (1) (160 mg, 1 mmol), 4-methylpyridine (2) (93 mg, 1 mmol), 2-bromo-1-(4-fluorophenyl)ethan-1-one (3) (217 mg, 1 mmol), and triethylamine (0.101 mg, 1 mmol) in 4.5 mL of acetonitrile were added to a 10 mL microwave tube under a nitrogen atmosphere (Fig. 7). A microwave initiator was used to irradiate the reaction mixture at 373 K for about 5 min. The reaction was monitored via TLC. The solvent was then removed under reduced pressure, the crude residue was diluted with water and the aqueous layer was extracted twice with ethyl acetate, and the combined organic solvent was washed with a brine solution. The organic layer was removed under reduced pressure and the remaining residue was subjected to using 60–120 mesh silica gel with an ethyl acetate and hexane solvent system to afford 0.3414 g (88% yield) of the title compound (Venugopala et al., 2019). Suitable single crystals of the compound were grown by the slow evaporation of acetone at ambient conditions.
7. Refinement
Crystal data, data collection and structure . The hydrogen atoms were placed in idealized positions and refined using a riding model with Uiso(H) =1.2Ueq(C) or 1.5Ueq(C-methyl).
details are summarized in Table 2
|
Supporting information
CCDC reference: 1865697
https://doi.org/10.1107/S2056989020003837/xi2021sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989020003837/xi2021Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2056989020003837/xi2021Isup3.cml
Data collection: APEX2 (Bruker, 2012); cell
SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: X-SEED (Barbour, 2001) and Mercury (Macrae et al., 2020); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015) and PLATON (Spek, 2020).C24H18FNO3 | F(000) = 808 |
Mr = 387.39 | Dx = 1.383 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
a = 7.3246 (11) Å | Cell parameters from 27523 reflections |
b = 9.8460 (13) Å | θ = 2.2–27.6° |
c = 25.837 (4) Å | µ = 0.10 mm−1 |
β = 93.318 (3)° | T = 173 K |
V = 1860.2 (5) Å3 | Block, yellow |
Z = 4 | 0.32 × 0.18 × 0.04 mm |
Bruker Kappa Duo APEXII diffractometer | 2641 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.090 |
0.5° φ scans and ω scans | θmax = 27.6°, θmin = 2.2° |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | h = −9→9 |
Tmin = 0.855, Tmax = 1.000 | k = −12→12 |
27523 measured reflections | l = −33→33 |
4296 independent reflections |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.050 | H-atom parameters constrained |
wR(F2) = 0.131 | w = 1/[σ2(Fo2) + (0.0555P)2 + 0.455P] where P = (Fo2 + 2Fc2)/3 |
S = 1.00 | (Δ/σ)max < 0.001 |
4296 reflections | Δρmax = 0.29 e Å−3 |
265 parameters | Δρmin = −0.30 e Å−3 |
0 restraints | Extinction correction: SHELXL-2014/7 (Sheldrick 2015, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0044 (8) |
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 | ||
F1 | 0.4480 (2) | 0.70181 (14) | 0.32107 (5) | 0.0563 (4) | |
O1 | 0.2787 (2) | 0.69998 (15) | 0.00174 (6) | 0.0381 (4) | |
O2 | 0.1668 (2) | 0.53237 (14) | −0.04937 (5) | 0.0302 (4) | |
O3 | 0.5350 (2) | 0.21447 (15) | 0.16777 (5) | 0.0336 (4) | |
N1 | 0.3494 (2) | 0.26669 (16) | 0.06884 (6) | 0.0230 (4) | |
C1 | 0.3588 (3) | 0.1276 (2) | 0.07210 (8) | 0.0293 (5) | |
H1 | 0.4025 | 0.0857 | 0.1035 | 0.035* | |
C2 | 0.3057 (3) | 0.0502 (2) | 0.03060 (8) | 0.0294 (5) | |
H2 | 0.3148 | −0.0459 | 0.0330 | 0.035* | |
C3 | 0.2368 (3) | 0.1106 (2) | −0.01642 (8) | 0.0269 (5) | |
C4 | 0.2282 (3) | 0.2488 (2) | −0.01917 (7) | 0.0252 (5) | |
H4 | 0.1830 | 0.2906 | −0.0505 | 0.030* | |
C5 | 0.2850 (3) | 0.3307 (2) | 0.02346 (7) | 0.0232 (4) | |
C6 | 0.2913 (3) | 0.4722 (2) | 0.03281 (7) | 0.0232 (4) | |
C7 | 0.3565 (3) | 0.4924 (2) | 0.08437 (7) | 0.0225 (4) | |
C8 | 0.3910 (3) | 0.3647 (2) | 0.10738 (7) | 0.0229 (4) | |
C9 | 0.1754 (3) | 0.0225 (2) | −0.06142 (8) | 0.0356 (5) | |
H9A | 0.1001 | 0.0760 | −0.0865 | 0.053* | |
H9B | 0.1035 | −0.0537 | −0.0491 | 0.053* | |
H9C | 0.2826 | −0.0125 | −0.0781 | 0.053* | |
C10 | 0.2478 (3) | 0.5806 (2) | −0.00470 (7) | 0.0248 (5) | |
C11 | 0.1182 (3) | 0.6340 (2) | −0.08794 (8) | 0.0315 (5) | |
H11A | 0.0323 | 0.6988 | −0.0739 | 0.047* | |
H11B | 0.0606 | 0.5902 | −0.1188 | 0.047* | |
H11C | 0.2285 | 0.6822 | −0.0974 | 0.047* | |
C12 | 0.3881 (3) | 0.6250 (2) | 0.11063 (7) | 0.0250 (5) | |
C13 | 0.5610 (3) | 0.6581 (2) | 0.13180 (7) | 0.0287 (5) | |
H13 | 0.6610 | 0.5989 | 0.1269 | 0.034* | |
C14 | 0.5889 (3) | 0.7767 (2) | 0.15993 (8) | 0.0363 (6) | |
H14 | 0.7076 | 0.7984 | 0.1743 | 0.044* | |
C15 | 0.4445 (4) | 0.8634 (2) | 0.16707 (8) | 0.0387 (6) | |
H15 | 0.4631 | 0.9443 | 0.1867 | 0.046* | |
C16 | 0.2724 (4) | 0.8320 (2) | 0.14543 (8) | 0.0390 (6) | |
H16 | 0.1729 | 0.8918 | 0.1502 | 0.047* | |
C17 | 0.2443 (3) | 0.7144 (2) | 0.11693 (8) | 0.0326 (5) | |
H17 | 0.1263 | 0.6945 | 0.1016 | 0.039* | |
C18 | 0.4633 (3) | 0.3265 (2) | 0.15900 (7) | 0.0253 (5) | |
C19 | 0.4534 (3) | 0.4247 (2) | 0.20269 (7) | 0.0257 (5) | |
C20 | 0.6087 (3) | 0.4441 (2) | 0.23563 (8) | 0.0324 (5) | |
H20 | 0.7157 | 0.3924 | 0.2307 | 0.039* | |
C21 | 0.6082 (3) | 0.5381 (2) | 0.27542 (8) | 0.0385 (6) | |
H21 | 0.7144 | 0.5534 | 0.2975 | 0.046* | |
C22 | 0.4491 (4) | 0.6086 (2) | 0.28191 (8) | 0.0374 (6) | |
C23 | 0.2923 (3) | 0.5899 (2) | 0.25163 (8) | 0.0328 (5) | |
H23 | 0.1843 | 0.6393 | 0.2579 | 0.039* | |
C24 | 0.2955 (3) | 0.4967 (2) | 0.21143 (8) | 0.0283 (5) | |
H24 | 0.1883 | 0.4820 | 0.1897 | 0.034* |
U11 | U22 | U33 | U12 | U13 | U23 | |
F1 | 0.0812 (12) | 0.0445 (9) | 0.0415 (8) | 0.0051 (8) | −0.0116 (7) | −0.0201 (7) |
O1 | 0.0596 (11) | 0.0203 (8) | 0.0333 (8) | −0.0034 (7) | −0.0062 (7) | 0.0057 (7) |
O2 | 0.0413 (9) | 0.0238 (8) | 0.0248 (7) | 0.0018 (7) | −0.0048 (6) | 0.0033 (6) |
O3 | 0.0420 (9) | 0.0259 (8) | 0.0323 (8) | 0.0073 (7) | −0.0035 (7) | 0.0032 (7) |
N1 | 0.0271 (10) | 0.0201 (9) | 0.0219 (8) | 0.0005 (7) | 0.0025 (7) | 0.0018 (7) |
C1 | 0.0363 (13) | 0.0213 (11) | 0.0304 (11) | 0.0029 (9) | 0.0019 (9) | 0.0052 (9) |
C2 | 0.0369 (13) | 0.0192 (11) | 0.0324 (11) | 0.0007 (9) | 0.0036 (9) | −0.0004 (9) |
C3 | 0.0282 (11) | 0.0251 (12) | 0.0280 (11) | −0.0045 (9) | 0.0057 (9) | −0.0019 (9) |
C4 | 0.0282 (11) | 0.0248 (11) | 0.0228 (10) | −0.0010 (9) | 0.0020 (8) | 0.0008 (8) |
C5 | 0.0235 (10) | 0.0234 (11) | 0.0228 (10) | 0.0005 (8) | 0.0032 (8) | 0.0033 (8) |
C6 | 0.0255 (11) | 0.0214 (10) | 0.0228 (10) | 0.0001 (8) | 0.0020 (8) | 0.0010 (8) |
C7 | 0.0239 (11) | 0.0206 (10) | 0.0233 (10) | 0.0014 (8) | 0.0028 (8) | 0.0005 (8) |
C8 | 0.0260 (11) | 0.0207 (10) | 0.0219 (9) | 0.0001 (8) | 0.0021 (8) | −0.0014 (8) |
C9 | 0.0460 (14) | 0.0281 (12) | 0.0326 (12) | −0.0038 (10) | 0.0005 (10) | −0.0039 (10) |
C10 | 0.0268 (11) | 0.0243 (11) | 0.0237 (10) | 0.0000 (9) | 0.0033 (8) | 0.0015 (9) |
C11 | 0.0382 (13) | 0.0302 (12) | 0.0256 (10) | 0.0028 (10) | −0.0036 (9) | 0.0077 (9) |
C12 | 0.0373 (12) | 0.0183 (10) | 0.0197 (9) | −0.0001 (9) | 0.0028 (9) | 0.0029 (8) |
C13 | 0.0375 (12) | 0.0237 (11) | 0.0253 (10) | −0.0035 (9) | 0.0056 (9) | 0.0008 (9) |
C14 | 0.0494 (15) | 0.0283 (12) | 0.0311 (12) | −0.0106 (11) | 0.0033 (11) | −0.0014 (10) |
C15 | 0.0653 (17) | 0.0199 (12) | 0.0311 (12) | −0.0025 (11) | 0.0026 (11) | −0.0030 (10) |
C16 | 0.0589 (16) | 0.0251 (12) | 0.0333 (12) | 0.0136 (11) | 0.0062 (11) | 0.0012 (10) |
C17 | 0.0407 (13) | 0.0267 (12) | 0.0301 (11) | 0.0059 (10) | −0.0009 (10) | 0.0018 (9) |
C18 | 0.0254 (11) | 0.0259 (11) | 0.0247 (10) | −0.0020 (9) | 0.0026 (8) | 0.0024 (9) |
C19 | 0.0344 (12) | 0.0223 (11) | 0.0202 (9) | −0.0025 (9) | 0.0000 (9) | 0.0045 (8) |
C20 | 0.0371 (13) | 0.0289 (12) | 0.0305 (11) | 0.0013 (10) | −0.0046 (10) | 0.0022 (10) |
C21 | 0.0498 (16) | 0.0324 (13) | 0.0316 (12) | −0.0036 (11) | −0.0130 (11) | 0.0016 (10) |
C22 | 0.0614 (17) | 0.0235 (12) | 0.0268 (11) | −0.0004 (11) | −0.0024 (11) | −0.0027 (9) |
C23 | 0.0420 (14) | 0.0298 (12) | 0.0269 (11) | 0.0020 (10) | 0.0058 (10) | 0.0018 (9) |
C24 | 0.0346 (12) | 0.0274 (12) | 0.0228 (10) | −0.0028 (9) | 0.0010 (9) | 0.0018 (9) |
F1—C22 | 1.367 (2) | C11—H11A | 0.9800 |
O1—C10 | 1.206 (2) | C11—H11B | 0.9800 |
O2—C10 | 1.353 (2) | C11—H11C | 0.9800 |
O2—C11 | 1.442 (2) | C12—C13 | 1.389 (3) |
O3—C18 | 1.236 (2) | C12—C17 | 1.389 (3) |
N1—C1 | 1.373 (3) | C13—C14 | 1.384 (3) |
N1—C5 | 1.389 (2) | C13—H13 | 0.9500 |
N1—C8 | 1.408 (2) | C14—C15 | 1.380 (3) |
C1—C2 | 1.354 (3) | C14—H14 | 0.9500 |
C1—H1 | 0.9500 | C15—C16 | 1.384 (3) |
C2—C3 | 1.419 (3) | C15—H15 | 0.9500 |
C2—H2 | 0.9500 | C16—C17 | 1.382 (3) |
C3—C4 | 1.364 (3) | C16—H16 | 0.9500 |
C3—C9 | 1.499 (3) | C17—H17 | 0.9500 |
C4—C5 | 1.409 (3) | C18—C19 | 1.491 (3) |
C4—H4 | 0.9500 | C19—C24 | 1.387 (3) |
C5—C6 | 1.414 (3) | C19—C20 | 1.393 (3) |
C6—C7 | 1.403 (3) | C20—C21 | 1.383 (3) |
C6—C10 | 1.465 (3) | C20—H20 | 0.9500 |
C7—C8 | 1.407 (3) | C21—C22 | 1.375 (3) |
C7—C12 | 1.483 (3) | C21—H21 | 0.9500 |
C8—C18 | 1.456 (3) | C22—C23 | 1.364 (3) |
C9—H9A | 0.9800 | C23—C24 | 1.388 (3) |
C9—H9B | 0.9800 | C23—H23 | 0.9500 |
C9—H9C | 0.9800 | C24—H24 | 0.9500 |
C10—O2—C11 | 115.09 (16) | H11A—C11—H11C | 109.5 |
C1—N1—C5 | 121.17 (17) | H11B—C11—H11C | 109.5 |
C1—N1—C8 | 129.22 (17) | C13—C12—C17 | 119.06 (19) |
C5—N1—C8 | 109.56 (16) | C13—C12—C7 | 120.09 (18) |
C2—C1—N1 | 120.09 (19) | C17—C12—C7 | 120.76 (19) |
C2—C1—H1 | 120.0 | C14—C13—C12 | 120.5 (2) |
N1—C1—H1 | 120.0 | C14—C13—H13 | 119.7 |
C1—C2—C3 | 120.92 (19) | C12—C13—H13 | 119.7 |
C1—C2—H2 | 119.5 | C15—C14—C13 | 120.1 (2) |
C3—C2—H2 | 119.5 | C15—C14—H14 | 120.0 |
C4—C3—C2 | 118.41 (18) | C13—C14—H14 | 120.0 |
C4—C3—C9 | 121.74 (19) | C14—C15—C16 | 119.7 (2) |
C2—C3—C9 | 119.85 (18) | C14—C15—H15 | 120.2 |
C3—C4—C5 | 121.33 (19) | C16—C15—H15 | 120.2 |
C3—C4—H4 | 119.3 | C17—C16—C15 | 120.4 (2) |
C5—C4—H4 | 119.3 | C17—C16—H16 | 119.8 |
N1—C5—C4 | 118.07 (18) | C15—C16—H16 | 119.8 |
N1—C5—C6 | 107.26 (16) | C16—C17—C12 | 120.2 (2) |
C4—C5—C6 | 134.66 (18) | C16—C17—H17 | 119.9 |
C7—C6—C5 | 107.94 (17) | C12—C17—H17 | 119.9 |
C7—C6—C10 | 125.01 (18) | O3—C18—C8 | 121.78 (18) |
C5—C6—C10 | 126.97 (17) | O3—C18—C19 | 118.57 (17) |
C6—C7—C8 | 108.49 (17) | C8—C18—C19 | 119.64 (17) |
C6—C7—C12 | 126.51 (17) | C24—C19—C20 | 119.31 (19) |
C8—C7—C12 | 124.99 (17) | C24—C19—C18 | 122.16 (18) |
C7—C8—N1 | 106.72 (16) | C20—C19—C18 | 118.54 (19) |
C7—C8—C18 | 131.69 (18) | C21—C20—C19 | 120.6 (2) |
N1—C8—C18 | 121.52 (17) | C21—C20—H20 | 119.7 |
C3—C9—H9A | 109.5 | C19—C20—H20 | 119.7 |
C3—C9—H9B | 109.5 | C22—C21—C20 | 117.8 (2) |
H9A—C9—H9B | 109.5 | C22—C21—H21 | 121.1 |
C3—C9—H9C | 109.5 | C20—C21—H21 | 121.1 |
H9A—C9—H9C | 109.5 | C23—C22—F1 | 118.3 (2) |
H9B—C9—H9C | 109.5 | C23—C22—C21 | 123.6 (2) |
O1—C10—O2 | 121.96 (18) | F1—C22—C21 | 118.1 (2) |
O1—C10—C6 | 125.95 (18) | C22—C23—C24 | 117.9 (2) |
O2—C10—C6 | 112.09 (17) | C22—C23—H23 | 121.0 |
O2—C11—H11A | 109.5 | C24—C23—H23 | 121.0 |
O2—C11—H11B | 109.5 | C19—C24—C23 | 120.7 (2) |
H11A—C11—H11B | 109.5 | C19—C24—H24 | 119.6 |
O2—C11—H11C | 109.5 | C23—C24—H24 | 119.6 |
C5—N1—C1—C2 | 0.4 (3) | C7—C6—C10—O2 | −172.44 (18) |
C8—N1—C1—C2 | 177.53 (19) | C5—C6—C10—O2 | 11.1 (3) |
N1—C1—C2—C3 | −1.2 (3) | C6—C7—C12—C13 | −121.3 (2) |
C1—C2—C3—C4 | 1.2 (3) | C8—C7—C12—C13 | 57.4 (3) |
C1—C2—C3—C9 | −178.8 (2) | C6—C7—C12—C17 | 62.2 (3) |
C2—C3—C4—C5 | −0.4 (3) | C8—C7—C12—C17 | −119.0 (2) |
C9—C3—C4—C5 | 179.56 (19) | C17—C12—C13—C14 | 1.7 (3) |
C1—N1—C5—C4 | 0.4 (3) | C7—C12—C13—C14 | −174.86 (18) |
C8—N1—C5—C4 | −177.26 (17) | C12—C13—C14—C15 | −0.2 (3) |
C1—N1—C5—C6 | 179.55 (18) | C13—C14—C15—C16 | −0.8 (3) |
C8—N1—C5—C6 | 1.9 (2) | C14—C15—C16—C17 | 0.2 (3) |
C3—C4—C5—N1 | −0.4 (3) | C15—C16—C17—C12 | 1.3 (3) |
C3—C4—C5—C6 | −179.2 (2) | C13—C12—C17—C16 | −2.2 (3) |
N1—C5—C6—C7 | −1.1 (2) | C7—C12—C17—C16 | 174.28 (19) |
C4—C5—C6—C7 | 177.8 (2) | C7—C8—C18—O3 | −157.8 (2) |
N1—C5—C6—C10 | 175.82 (18) | N1—C8—C18—O3 | 19.0 (3) |
C4—C5—C6—C10 | −5.3 (4) | C7—C8—C18—C19 | 21.5 (3) |
C5—C6—C7—C8 | 0.0 (2) | N1—C8—C18—C19 | −161.76 (18) |
C10—C6—C7—C8 | −177.05 (19) | O3—C18—C19—C24 | −134.5 (2) |
C5—C6—C7—C12 | 178.88 (19) | C8—C18—C19—C24 | 46.2 (3) |
C10—C6—C7—C12 | 1.9 (3) | O3—C18—C19—C20 | 45.5 (3) |
C6—C7—C8—N1 | 1.2 (2) | C8—C18—C19—C20 | −133.8 (2) |
C12—C7—C8—N1 | −177.78 (18) | C24—C19—C20—C21 | −2.6 (3) |
C6—C7—C8—C18 | 178.3 (2) | C18—C19—C20—C21 | 177.43 (19) |
C12—C7—C8—C18 | −0.7 (3) | C19—C20—C21—C22 | 1.4 (3) |
C1—N1—C8—C7 | −179.3 (2) | C20—C21—C22—C23 | 0.6 (3) |
C5—N1—C8—C7 | −1.9 (2) | C20—C21—C22—F1 | −179.8 (2) |
C1—N1—C8—C18 | 3.2 (3) | F1—C22—C23—C24 | 178.97 (19) |
C5—N1—C8—C18 | −179.35 (17) | C21—C22—C23—C24 | −1.4 (3) |
C11—O2—C10—O1 | −1.0 (3) | C20—C19—C24—C23 | 1.7 (3) |
C11—O2—C10—C6 | 179.33 (17) | C18—C19—C24—C23 | −178.30 (19) |
C7—C6—C10—O1 | 7.9 (3) | C22—C23—C24—C19 | 0.2 (3) |
C5—C6—C10—O1 | −168.6 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
C1—H1···O3 | 0.95 | 2.26 | 2.853 (3) | 120 |
C4—H4···O2 | 0.95 | 2.38 | 2.927 (2) | 116 |
C21—H21···O3i | 0.95 | 2.54 | 3.399 (3) | 149 |
C2—H2···O1ii | 0.95 | 2.63 | 3.531 (4) | 157 |
C15—H15···O3iii | 0.95 | 2.76 | 3.519 (4) | 137 |
C1—H1···C15ii | 0.95 | 2.74 | 3.6064 (3) | 152 |
C11—H11A···C5iv | 0.98 | 2.74 | 3.4906 (1) | 133 |
C11—H11B···F1v | 0.98 | 2.67 | 3.0585 (3) | 104 |
C23—H23···O3vi | 0.95 | 2.67 | 3.4875 (3) | 143 |
Symmetry codes: (i) −x+3/2, y+1/2, −z+1/2; (ii) x, y−1, z; (iii) x, y+1, z; (iv) −x, −y+1, −z; (v) x−1/2, −y+3/2, z−1/2; (vi) −x+1/2, y+1/2, −z+1/2. |
Acknowledgements
The authors are grateful to the Deanship of Scientific Research, King Faisal University, Kingdom of Saudi Arabia for financial support and encouragement. AH thanks IISER Bhopal for a research fellowship. The authors are thankful to the
of IISER Bhopal for research facilities and infrastructure.Funding information
Funding for this research was provided by: Indian Institute of Science Education and Research Bhopal; the Deanship of Scientific Research, King Faisal University, Kingdom of Saudi Arabia (through Research Group grant No. 17122011).
References
Aslanov, L. A., Tafeenko, V. A., Paseshnichenko, K. A., Bundel', Y. G., Gromov, S. P. & Gerasimov, B. G. (1983). Zh. Strukt. Khim. (Russ. J. Struct. Chem.), 24, 427–434. CrossRef Google Scholar
Barbour, L. J. (2001). J. Supramol. Chem. 1, 189–191. CrossRef CAS Google Scholar
Bruker (2008). SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruker (2012). APEX2. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Butler, M. S. (2008). Nat. Prod. Rep. 25, 475–516. CrossRef PubMed CAS Google Scholar
Chandrashekharappa, S., Venugopala, K. N., Nayak, S. K., Gleiser, R. M., García, D. A., Kumalo, H. M., Kulkarni, R. S., Mahomoodally, F. M., Venugopala, R., Mohan, M. K. & Odhav, B. (2018a). J. Mol. Struct. 1156, 377–384. CSD CrossRef CAS Google Scholar
Chandrashekharappa, S., Venugopala, K. N., Tratrat, C., Mahomoodally, F. M., Aldhubiab, B. E., Haroun, M., Venugopala, R., Mohan, M. K., Kulkarni, R. S., Attimarad, M. V., Harsha, S. & Odhav, B. (2018b). New J. Chem. 42, 4893–4901. CrossRef CAS Google Scholar
Cingolani, G. M., Claudi, F., Massi, M. & Venturi, F. (1990). Eur. J. Med. Chem. 25, 709–712. CrossRef CAS Google Scholar
Dance, I. (2003). New J. Chem. 27, 22–27. Web of Science CrossRef CAS Google Scholar
Gayton, J., Autry, S. A., Meador, W., Parkin, S. R., Hill, G. A. Jr, Hammer, N. I. & Delcamp, J. H. (2019). J. Org. Chem. 84, 687–697. CSD CrossRef CAS PubMed Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CrossRef IUCr Journals Google Scholar
Hathwar, V. R., Bhowal, R. & Chopra, D. (2020). J. Mol. Struct. 1208, 1278642 https://doi. org/10.1016/j. molstruc. 2020.127864 Google Scholar
Hazra, A., Mondal, S., Maity, A., Naskar, S., Saha, P., Paira, R., Sahu, K. B., Paira, P., Ghosh, S., Sinha, C., Samanta, A., Banerjee, S. & Mondal, N. B. (2011). Eur. J. Med. Chem. 46, 2132–2140. CSD CrossRef CAS PubMed Google Scholar
Liu, W., Ou, S., He, X., Hu, H., Wu, Q. & Huang, Z. (2003). J. Chem. Crystallogr. 33, 795–798. CSD CrossRef CAS Google Scholar
Liu, W.-W., Li, Y.-Z., Sun, R.-K., Hu, H.-W., Wu, Q.-J. & Huang, Z.-X. (2005). Acta Cryst. E61, o445–o447. CSD CrossRef IUCr Journals Google Scholar
Liu, W.-W., Wang, L., Tang, L.-J., Cao, W. & Hu, H.-W. (2007). Acta Cryst. E63, o3518. CSD CrossRef IUCr Journals Google Scholar
Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226–235. Web of Science CrossRef CAS IUCr Journals Google Scholar
McNamara, L. E., Rill, T. A., Huckaba, A. J., Ganeshraj, V., Gayton, J., Nelson, R. A., Sharpe, E. A., Dass, A., Hammer, N. I. & Delcamp, J. H. (2017). Chem. Eur. J. 23, 12494–12501. CSD CrossRef CAS PubMed Google Scholar
Mederski, W., Beier, N., Burgdorf, L. T., Gericke, R., Klein, M. & Tsaklakidis, C. (2012). US Patent 8(106,067 B2). Google Scholar
Mishra, B. B. & Tiwari, V. K. (2011). Opportunity Challenge and Scope of Natural Products in Medicinal Chemistry, 1–61. Google Scholar
Qian, B.-H., Liu, W.-W., Lu, L.-D. & Hu, H.-W. (2006). Acta Cryst. E62, o2363–o2364. CSD CrossRef IUCr Journals Google Scholar
Sandeep, C., Padmashali, B., Venugopala, K. N., Kulkarni, R. S., Venugopala, R. & Odhav, B. (2016a). Asian J. Chem. 28, 1043–1048. CrossRef CAS Google Scholar
Sandeep, C., Venugopala, K. N., Gleiser, R. M., Chetram, A., Padmashali, B., Kulkarni, R. S., Venugopala, R. & Odhav, B. (2016b). Chem. Biol. Drug Des. 88, 899–904. CrossRef CAS PubMed Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2015). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sonnenschein, H. & Schneider, M. (1997). Z. Kristallogr. New Cryst. Struct. 212, 161–162. CSD CrossRef CAS Google Scholar
Spackman, M. A. & Jayatilaka, D. (2009). CrystEngComm, 11, 19–32. Web of Science CrossRef CAS Google Scholar
Spek, A. L. (2020). Acta Cryst. E76, 1–11. Web of Science CrossRef IUCr Journals Google Scholar
Tafeenkov, V. A. & Aslanov, L. A. (1980). Zh. Strukt. Khim. 21, 69–78. Google Scholar
Tafeenkov, V. A. & Au, O. (1996). Zh. Strukt. Khim. 37, 1181–1185. CAS Google Scholar
Vaught, J. L., Carson, J. R., Carmosin, R. J., Blum, P. S., Persico, F. J., Hageman, W. E., Shank, R. P. & Raffa, R. B. (1990). J. Pharmacol. Exp. Ther. 255, 1–10. CAS PubMed Google Scholar
Venugopala, K. N., Tratrat, C., Pillay, M., Mahomoodally, F. M., Bhandary, S., Chopra, D., Morsy, M. A., Haroun, M., Aldhubiab, B. E., Attimarad, M., Nair, A. B., Sreeharsha, N., Venugopala, R., Chandrashekharappa, S., Alwassil, O. I. & Odhav, B. (2019). Antibiotics, 8, 247–263. CrossRef Google Scholar
Wolff, S. K., Grimwood, D. J., McKinnon, J. J., Turner, M. J., Jayatilaka, D. & Spackman, M. A. (2012). CrystalExplorer12.5. University of Western Australia, Perth. Google Scholar
This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.