research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2056-9890

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

Edited by C. Massera, Università di Parma, Italy (Received 22 January 2020; accepted 16 March 2020; online 20 March 2020)

The title compound, C24H18FNO3, crystallizes in the monoclinic centrosymmetric space group 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 crystal structure. The different inter­molecular inter­actions have been further analysed via Hirshfeld surface analysis and fingerprint plots.

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[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.]), anti­cancer (Butler, 2008[Butler, M. S. (2008). Nat. Prod. Rep. 25, 475-516.]; Sandeep et al., 2016a[Sandeep, C., Padmashali, B., Venugopala, K. N., Kulkarni, R. S., Venugopala, R. & Odhav, B. (2016a). Asian J. Chem. 28, 1043-1048.],b[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.]), anti­diabetic (Mederski et al., 2012[Mederski, W., Beier, N., Burgdorf, L. T., Gericke, R., Klein, M. & Tsaklakidis, C. (2012). US Patent 8(106,067 B2).]), anti­histaminic (Cingolani et al., 1990[Cingolani, G. M., Claudi, F., Massi, M. & Venturi, F. (1990). Eur. J. Med. Chem. 25, 709-712.]), anti-microbial (Hazra et al., 2011[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.]) and anti­viral (Mishra & Tiwari, 2011[Mishra, B. B. & Tiwari, V. K. (2011). Opportunity Challenge and Scope of Natural Products in Medicinal Chemistry, 1-61.]) activity. It has also been found to act as cyclo-oxygenase (COX-2) inhibitor (Chandrashekharappa et al., 2018b[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.]) and to have larvicidal activity against Anopheles arabiensis (Chandrashekharappa et al., 2018a[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.]).

[Scheme 1]

The title compound, comprising a substituted indolizine unit, displays a modest activity against susceptible H37Rv strains of Mycobacterium tuberculosis (Venugopala et al., 2019[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.]). 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 crystal lattice. In the present paper, we report the mol­ecular and crystal structure 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 space group. 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[link]). The mol­ecular structure possesses three conformational degrees of freedom due to the free rotation 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[link]) and by ππ stacking [Cg3⋯Cg4 = 3.5084 (13) Å]. The dihedral angle between the mean plane through ring Cg3 (coloured in green in Fig. 2[link]) 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.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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+{\script{3\over 2}}, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]; (ii) x, y-1, z; (iii) x, y+1, z; (iv) -x, -y+1, -z; (v) [x-{\script{1\over 2}}, -y+{\script{3\over 2}}, z-{\script{1\over 2}}]; (vi) [-x+{\script{1\over 2}}, y+{\script{1\over 2}}, -z+{\script{1\over 2}}].
[Figure 1]
Figure 1
Ellipsoid plot of the title compound drawn with 50% probability ellipsoids. Dotted lines indicate intra­molecular C—H⋯O inter­actions. Cg1, Cg3 and Cg4 represent the centroids of the six-membered rings N1/C1–C5, C12–C17 and C18/O3/C19–C24/F1, respectively, while Cg2 represents the five-membered ring N1/C5–C8.
[Figure 2]
Figure 2
Dihedral angles between the mean plane passing through the C12–C17 ring (green) and the C18/O3/C19–C24/F1 ring (blue) and through the indolizine skeleton (red).

3. Supra­molecular features

The list of all intra- and inter­molecular inter­actions along with their geometrical parameters have been reported in Table 1[link]. The inter­actions included for investigation are based on the distance criteria of vdW + 0.4 Å (Dance, 2003[Dance, I. (2003). New J. Chem. 27, 22-27.]). 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[link]. Two adjacent ribbons are connected to each other via C11—H11B⋯F1v [C11⋯F1 = 3.0585 (3) Å, 104°; symmetry code: (v) x − [{1\over 2}], −y + [{3\over 2}], z − [{1\over 2}]] (Fig. 3[link]) and C21—H21⋯O3i [C21⋯O3 = 3.399 (3) Å, 149°; symmetry code: (i) −x + [{3\over 2}], y + [{1\over 2}], −z + [{1\over 2}]] (Fig. 4[link]) 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[Hathwar, V. R., Bhowal, R. & Chopra, D. (2020). J. Mol. Struct. 1208, 1278642 https://doi. org/10.1016/j. molstruc. 2020.127864]), 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—H9Cπ(C1) [C9⋯C1vii = 3.7431 (5) Å; symmetry code: (vii) −x + 1, −y, −z], C11—H11Aπ(C5) [C11⋯C5iv = 3.4906 (4) Å; symmetry code: (iv) −x, −y + 1, −z], C11—H11Cπ(C8) [C11⋯C8viii = 3.6590 (5) Å; symmetry code: (viii) −x + 1, −y + 1, −z] (Fig. 4[link]), giving rise to a layered supra­molecular structure. From this analysis, it can be stated that the formation of the crystal structure 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.

[Figure 3]
Figure 3
Crystal packing of title compound showing the formation of mol­ecular sheets parallel to the bc plane via C—H⋯O, C—H⋯π and C—H⋯F inter­actions.
[Figure 4]
Figure 4
Stacking of mol­ecular sheets along the a-axis direction, primarily via C—H⋯π and C—H⋯F inter­actions, resulting in a layered supra­molecular architecture.

4. Database survey

A search for the 2-phenyl­indolizine skeleton in the CSD (version 5.40, update of August 2019; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) 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[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.]) and KENFAN (McNamara et al., 2017[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.]) have also been reported.

Structural details of compounds such as CAJTAI (Aslanov et al., 1983[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.]), EMUTOV (Liu, et al., 2003[Liu, W., Ou, S., He, X., Hu, H., Wu, Q. & Huang, Z. (2003). J. Chem. Crystallogr. 33, 795-798.]), FEDQAH (Liu, et al., 2005[Liu, W.-W., Li, Y.-Z., Sun, R.-K., Hu, H.-W., Wu, Q.-J. & Huang, Z.-X. (2005). Acta Cryst. E61, o445-o447.]), GIYLOP (Sonnenschein & Schneider, 1997[Sonnenschein, H. & Schneider, M. (1997). Z. Kristallogr. New Cryst. Struct. 212, 161-162.]), ODEFIN (Qian et al., 2006[Qian, B.-H., Liu, W.-W., Lu, L.-D. & Hu, H.-W. (2006). Acta Cryst. E62, o2363-o2364.]), PNOIZA, PNOIZB, PNOIZE, PNOIZF (Tafeenkov & Aslanov, 1980[Tafeenkov, V. A. & Aslanov, L. A. (1980). Zh. Strukt. Khim. 21, 69-78.]), ROLKIM (Tafeenkov & Au, 1996[Tafeenkov, V. A. & Au, O. (1996). Zh. Strukt. Khim. 37, 1181-1185.]) and TIGXOX (Liu, et al., 2007[Liu, W.-W., Wang, L., Tang, L.-J., Cao, W. & Hu, H.-W. (2007). Acta Cryst. E63, o3518.]) 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[Liu, W.-W., Wang, L., Tang, L.-J., Cao, W. & Hu, H.-W. (2007). Acta Cryst. E63, o3518.]), FEDQAH (Liu et al., 2005[Liu, W.-W., Li, Y.-Z., Sun, R.-K., Hu, H.-W., Wu, Q.-J. & Huang, Z.-X. (2005). Acta Cryst. E61, o445-o447.]) and ODEFIN (Qian et al., 2006[Qian, B.-H., Liu, W.-W., Lu, L.-D. & Hu, H.-W. (2006). Acta Cryst. E62, o2363-o2364.]) 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 crystal structure can be visualized qualitatively through Hirshfeld surface analysis (Spackman et al., 2009[Spackman, M. A. & Jayatilaka, D. (2009). CrystEngComm, 11, 19-32.]). The Hirshfeld surfaces and the two-dimensional fingerprint plots were calculated using CrystalExplorer (Version 17.5; Wolff et al., 2012[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.]) and are shown in Figs. 5[link] and 6[link], 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[link] 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.

[Figure 5]
Figure 5
The Hirshfeld surface of title compound mapped over dnorm. Dashed lines indicate hydrogen bonds.
[Figure 6]
Figure 6
The fingerprint plots of the title compound showing the different contributions deriving from the O⋯H/H⋯O, N⋯H/H⋯N, C⋯H/H⋯C, H⋯F/F⋯H, C⋯C and H⋯H contacts.

6. 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[link]). 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 column chromatography 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[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.]). Suitable single crystals of the compound were grown by the slow evaporation of acetone at ambient conditions.

[Figure 7]
Figure 7
The reaction scheme for the synthesis of the title compound.

7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. 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).

Table 2
Experimental details

Crystal data
Chemical formula C24H18FNO3
Mr 387.39
Crystal system, space group Monoclinic, P21/n
Temperature (K) 173
a, b, c (Å) 7.3246 (11), 9.8460 (13), 25.837 (4)
β (°) 93.318 (3)
V3) 1860.2 (5)
Z 4
Radiation type Mo Kα
μ (mm−1) 0.10
Crystal size (mm) 0.32 × 0.18 × 0.04
 
Data collection
Diffractometer Bruker Kappa Duo APEXII
Absorption correction Multi-scan (SADABS; Bruker, 2008[Bruker (2008). SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.855, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections 27523, 4296, 2641
Rint 0.090
(sin θ/λ)max−1) 0.652
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.050, 0.131, 1.00
No. of reflections 4296
No. of parameters 265
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.29, −0.30
Computer programs: APEX2 (Bruker, 2012[Bruker (2012). APEX2. Bruker AXS Inc., Madison, Wisconsin, USA.]), SAINT (Bruker, 2008[Bruker (2008). SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), X-SEED (Barbour, 2001[Barbour, L. J. (2001). J. Supramol. Chem. 1, 189-191.]), Mercury (Macrae et al., 2020[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.]), SHELXL2014 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]) and PLATON (Spek, 2020[Spek, A. L. (2020). Acta Cryst. E76, 1-11.]).

Supporting information


Computing details top

Data collection: APEX2 (Bruker, 2012); cell refinement: 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).

3-(4-Fluorobenzoyl)-7-methyl-2-phenylindolizine-1-carboxylate top
Crystal data top
C24H18FNO3F(000) = 808
Mr = 387.39Dx = 1.383 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
a = 7.3246 (11) ÅCell parameters from 27523 reflections
b = 9.8460 (13) Åθ = 2.2–27.6°
c = 25.837 (4) ŵ = 0.10 mm1
β = 93.318 (3)°T = 173 K
V = 1860.2 (5) Å3Block, yellow
Z = 40.32 × 0.18 × 0.04 mm
Data collection top
Bruker Kappa Duo APEXII
diffractometer
2641 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.090
0.5° φ scans and ω scansθmax = 27.6°, θmin = 2.2°
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
h = 99
Tmin = 0.855, Tmax = 1.000k = 1212
27523 measured reflectionsl = 3333
4296 independent reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.050H-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 reflectionsΔρmax = 0.29 e Å3
265 parametersΔρmin = 0.30 e Å3
0 restraintsExtinction correction: SHELXL-2014/7 (Sheldrick 2015, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0044 (8)
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
F10.4480 (2)0.70181 (14)0.32107 (5)0.0563 (4)
O10.2787 (2)0.69998 (15)0.00174 (6)0.0381 (4)
O20.1668 (2)0.53237 (14)0.04937 (5)0.0302 (4)
O30.5350 (2)0.21447 (15)0.16777 (5)0.0336 (4)
N10.3494 (2)0.26669 (16)0.06884 (6)0.0230 (4)
C10.3588 (3)0.1276 (2)0.07210 (8)0.0293 (5)
H10.40250.08570.10350.035*
C20.3057 (3)0.0502 (2)0.03060 (8)0.0294 (5)
H20.31480.04590.03300.035*
C30.2368 (3)0.1106 (2)0.01642 (8)0.0269 (5)
C40.2282 (3)0.2488 (2)0.01917 (7)0.0252 (5)
H40.18300.29060.05050.030*
C50.2850 (3)0.3307 (2)0.02346 (7)0.0232 (4)
C60.2913 (3)0.4722 (2)0.03281 (7)0.0232 (4)
C70.3565 (3)0.4924 (2)0.08437 (7)0.0225 (4)
C80.3910 (3)0.3647 (2)0.10738 (7)0.0229 (4)
C90.1754 (3)0.0225 (2)0.06142 (8)0.0356 (5)
H9A0.10010.07600.08650.053*
H9B0.10350.05370.04910.053*
H9C0.28260.01250.07810.053*
C100.2478 (3)0.5806 (2)0.00470 (7)0.0248 (5)
C110.1182 (3)0.6340 (2)0.08794 (8)0.0315 (5)
H11A0.03230.69880.07390.047*
H11B0.06060.59020.11880.047*
H11C0.22850.68220.09740.047*
C120.3881 (3)0.6250 (2)0.11063 (7)0.0250 (5)
C130.5610 (3)0.6581 (2)0.13180 (7)0.0287 (5)
H130.66100.59890.12690.034*
C140.5889 (3)0.7767 (2)0.15993 (8)0.0363 (6)
H140.70760.79840.17430.044*
C150.4445 (4)0.8634 (2)0.16707 (8)0.0387 (6)
H150.46310.94430.18670.046*
C160.2724 (4)0.8320 (2)0.14543 (8)0.0390 (6)
H160.17290.89180.15020.047*
C170.2443 (3)0.7144 (2)0.11693 (8)0.0326 (5)
H170.12630.69450.10160.039*
C180.4633 (3)0.3265 (2)0.15900 (7)0.0253 (5)
C190.4534 (3)0.4247 (2)0.20269 (7)0.0257 (5)
C200.6087 (3)0.4441 (2)0.23563 (8)0.0324 (5)
H200.71570.39240.23070.039*
C210.6082 (3)0.5381 (2)0.27542 (8)0.0385 (6)
H210.71440.55340.29750.046*
C220.4491 (4)0.6086 (2)0.28191 (8)0.0374 (6)
C230.2923 (3)0.5899 (2)0.25163 (8)0.0328 (5)
H230.18430.63930.25790.039*
C240.2955 (3)0.4967 (2)0.21143 (8)0.0283 (5)
H240.18830.48200.18970.034*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0812 (12)0.0445 (9)0.0415 (8)0.0051 (8)0.0116 (7)0.0201 (7)
O10.0596 (11)0.0203 (8)0.0333 (8)0.0034 (7)0.0062 (7)0.0057 (7)
O20.0413 (9)0.0238 (8)0.0248 (7)0.0018 (7)0.0048 (6)0.0033 (6)
O30.0420 (9)0.0259 (8)0.0323 (8)0.0073 (7)0.0035 (7)0.0032 (7)
N10.0271 (10)0.0201 (9)0.0219 (8)0.0005 (7)0.0025 (7)0.0018 (7)
C10.0363 (13)0.0213 (11)0.0304 (11)0.0029 (9)0.0019 (9)0.0052 (9)
C20.0369 (13)0.0192 (11)0.0324 (11)0.0007 (9)0.0036 (9)0.0004 (9)
C30.0282 (11)0.0251 (12)0.0280 (11)0.0045 (9)0.0057 (9)0.0019 (9)
C40.0282 (11)0.0248 (11)0.0228 (10)0.0010 (9)0.0020 (8)0.0008 (8)
C50.0235 (10)0.0234 (11)0.0228 (10)0.0005 (8)0.0032 (8)0.0033 (8)
C60.0255 (11)0.0214 (10)0.0228 (10)0.0001 (8)0.0020 (8)0.0010 (8)
C70.0239 (11)0.0206 (10)0.0233 (10)0.0014 (8)0.0028 (8)0.0005 (8)
C80.0260 (11)0.0207 (10)0.0219 (9)0.0001 (8)0.0021 (8)0.0014 (8)
C90.0460 (14)0.0281 (12)0.0326 (12)0.0038 (10)0.0005 (10)0.0039 (10)
C100.0268 (11)0.0243 (11)0.0237 (10)0.0000 (9)0.0033 (8)0.0015 (9)
C110.0382 (13)0.0302 (12)0.0256 (10)0.0028 (10)0.0036 (9)0.0077 (9)
C120.0373 (12)0.0183 (10)0.0197 (9)0.0001 (9)0.0028 (9)0.0029 (8)
C130.0375 (12)0.0237 (11)0.0253 (10)0.0035 (9)0.0056 (9)0.0008 (9)
C140.0494 (15)0.0283 (12)0.0311 (12)0.0106 (11)0.0033 (11)0.0014 (10)
C150.0653 (17)0.0199 (12)0.0311 (12)0.0025 (11)0.0026 (11)0.0030 (10)
C160.0589 (16)0.0251 (12)0.0333 (12)0.0136 (11)0.0062 (11)0.0012 (10)
C170.0407 (13)0.0267 (12)0.0301 (11)0.0059 (10)0.0009 (10)0.0018 (9)
C180.0254 (11)0.0259 (11)0.0247 (10)0.0020 (9)0.0026 (8)0.0024 (9)
C190.0344 (12)0.0223 (11)0.0202 (9)0.0025 (9)0.0000 (9)0.0045 (8)
C200.0371 (13)0.0289 (12)0.0305 (11)0.0013 (10)0.0046 (10)0.0022 (10)
C210.0498 (16)0.0324 (13)0.0316 (12)0.0036 (11)0.0130 (11)0.0016 (10)
C220.0614 (17)0.0235 (12)0.0268 (11)0.0004 (11)0.0024 (11)0.0027 (9)
C230.0420 (14)0.0298 (12)0.0269 (11)0.0020 (10)0.0058 (10)0.0018 (9)
C240.0346 (12)0.0274 (12)0.0228 (10)0.0028 (9)0.0010 (9)0.0018 (9)
Geometric parameters (Å, º) top
F1—C221.367 (2)C11—H11A0.9800
O1—C101.206 (2)C11—H11B0.9800
O2—C101.353 (2)C11—H11C0.9800
O2—C111.442 (2)C12—C131.389 (3)
O3—C181.236 (2)C12—C171.389 (3)
N1—C11.373 (3)C13—C141.384 (3)
N1—C51.389 (2)C13—H130.9500
N1—C81.408 (2)C14—C151.380 (3)
C1—C21.354 (3)C14—H140.9500
C1—H10.9500C15—C161.384 (3)
C2—C31.419 (3)C15—H150.9500
C2—H20.9500C16—C171.382 (3)
C3—C41.364 (3)C16—H160.9500
C3—C91.499 (3)C17—H170.9500
C4—C51.409 (3)C18—C191.491 (3)
C4—H40.9500C19—C241.387 (3)
C5—C61.414 (3)C19—C201.393 (3)
C6—C71.403 (3)C20—C211.383 (3)
C6—C101.465 (3)C20—H200.9500
C7—C81.407 (3)C21—C221.375 (3)
C7—C121.483 (3)C21—H210.9500
C8—C181.456 (3)C22—C231.364 (3)
C9—H9A0.9800C23—C241.388 (3)
C9—H9B0.9800C23—H230.9500
C9—H9C0.9800C24—H240.9500
C10—O2—C11115.09 (16)H11A—C11—H11C109.5
C1—N1—C5121.17 (17)H11B—C11—H11C109.5
C1—N1—C8129.22 (17)C13—C12—C17119.06 (19)
C5—N1—C8109.56 (16)C13—C12—C7120.09 (18)
C2—C1—N1120.09 (19)C17—C12—C7120.76 (19)
C2—C1—H1120.0C14—C13—C12120.5 (2)
N1—C1—H1120.0C14—C13—H13119.7
C1—C2—C3120.92 (19)C12—C13—H13119.7
C1—C2—H2119.5C15—C14—C13120.1 (2)
C3—C2—H2119.5C15—C14—H14120.0
C4—C3—C2118.41 (18)C13—C14—H14120.0
C4—C3—C9121.74 (19)C14—C15—C16119.7 (2)
C2—C3—C9119.85 (18)C14—C15—H15120.2
C3—C4—C5121.33 (19)C16—C15—H15120.2
C3—C4—H4119.3C17—C16—C15120.4 (2)
C5—C4—H4119.3C17—C16—H16119.8
N1—C5—C4118.07 (18)C15—C16—H16119.8
N1—C5—C6107.26 (16)C16—C17—C12120.2 (2)
C4—C5—C6134.66 (18)C16—C17—H17119.9
C7—C6—C5107.94 (17)C12—C17—H17119.9
C7—C6—C10125.01 (18)O3—C18—C8121.78 (18)
C5—C6—C10126.97 (17)O3—C18—C19118.57 (17)
C6—C7—C8108.49 (17)C8—C18—C19119.64 (17)
C6—C7—C12126.51 (17)C24—C19—C20119.31 (19)
C8—C7—C12124.99 (17)C24—C19—C18122.16 (18)
C7—C8—N1106.72 (16)C20—C19—C18118.54 (19)
C7—C8—C18131.69 (18)C21—C20—C19120.6 (2)
N1—C8—C18121.52 (17)C21—C20—H20119.7
C3—C9—H9A109.5C19—C20—H20119.7
C3—C9—H9B109.5C22—C21—C20117.8 (2)
H9A—C9—H9B109.5C22—C21—H21121.1
C3—C9—H9C109.5C20—C21—H21121.1
H9A—C9—H9C109.5C23—C22—F1118.3 (2)
H9B—C9—H9C109.5C23—C22—C21123.6 (2)
O1—C10—O2121.96 (18)F1—C22—C21118.1 (2)
O1—C10—C6125.95 (18)C22—C23—C24117.9 (2)
O2—C10—C6112.09 (17)C22—C23—H23121.0
O2—C11—H11A109.5C24—C23—H23121.0
O2—C11—H11B109.5C19—C24—C23120.7 (2)
H11A—C11—H11B109.5C19—C24—H24119.6
O2—C11—H11C109.5C23—C24—H24119.6
C5—N1—C1—C20.4 (3)C7—C6—C10—O2172.44 (18)
C8—N1—C1—C2177.53 (19)C5—C6—C10—O211.1 (3)
N1—C1—C2—C31.2 (3)C6—C7—C12—C13121.3 (2)
C1—C2—C3—C41.2 (3)C8—C7—C12—C1357.4 (3)
C1—C2—C3—C9178.8 (2)C6—C7—C12—C1762.2 (3)
C2—C3—C4—C50.4 (3)C8—C7—C12—C17119.0 (2)
C9—C3—C4—C5179.56 (19)C17—C12—C13—C141.7 (3)
C1—N1—C5—C40.4 (3)C7—C12—C13—C14174.86 (18)
C8—N1—C5—C4177.26 (17)C12—C13—C14—C150.2 (3)
C1—N1—C5—C6179.55 (18)C13—C14—C15—C160.8 (3)
C8—N1—C5—C61.9 (2)C14—C15—C16—C170.2 (3)
C3—C4—C5—N10.4 (3)C15—C16—C17—C121.3 (3)
C3—C4—C5—C6179.2 (2)C13—C12—C17—C162.2 (3)
N1—C5—C6—C71.1 (2)C7—C12—C17—C16174.28 (19)
C4—C5—C6—C7177.8 (2)C7—C8—C18—O3157.8 (2)
N1—C5—C6—C10175.82 (18)N1—C8—C18—O319.0 (3)
C4—C5—C6—C105.3 (4)C7—C8—C18—C1921.5 (3)
C5—C6—C7—C80.0 (2)N1—C8—C18—C19161.76 (18)
C10—C6—C7—C8177.05 (19)O3—C18—C19—C24134.5 (2)
C5—C6—C7—C12178.88 (19)C8—C18—C19—C2446.2 (3)
C10—C6—C7—C121.9 (3)O3—C18—C19—C2045.5 (3)
C6—C7—C8—N11.2 (2)C8—C18—C19—C20133.8 (2)
C12—C7—C8—N1177.78 (18)C24—C19—C20—C212.6 (3)
C6—C7—C8—C18178.3 (2)C18—C19—C20—C21177.43 (19)
C12—C7—C8—C180.7 (3)C19—C20—C21—C221.4 (3)
C1—N1—C8—C7179.3 (2)C20—C21—C22—C230.6 (3)
C5—N1—C8—C71.9 (2)C20—C21—C22—F1179.8 (2)
C1—N1—C8—C183.2 (3)F1—C22—C23—C24178.97 (19)
C5—N1—C8—C18179.35 (17)C21—C22—C23—C241.4 (3)
C11—O2—C10—O11.0 (3)C20—C19—C24—C231.7 (3)
C11—O2—C10—C6179.33 (17)C18—C19—C24—C23178.30 (19)
C7—C6—C10—O17.9 (3)C22—C23—C24—C190.2 (3)
C5—C6—C10—O1168.6 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C1—H1···O30.952.262.853 (3)120
C4—H4···O20.952.382.927 (2)116
C21—H21···O3i0.952.543.399 (3)149
C2—H2···O1ii0.952.633.531 (4)157
C15—H15···O3iii0.952.763.519 (4)137
C1—H1···C15ii0.952.743.6064 (3)152
C11—H11A···C5iv0.982.743.4906 (1)133
C11—H11B···F1v0.982.673.0585 (3)104
C23—H23···O3vi0.952.673.4875 (3)143
Symmetry codes: (i) x+3/2, y+1/2, z+1/2; (ii) x, y1, z; (iii) x, y+1, z; (iv) x, y+1, z; (v) x1/2, y+3/2, z1/2; (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 CIF 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).

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