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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 74| Part 10| October 2018| Pages 1388-1391
https://doi.org/10.1107/S2056989018012094

Crystal structure and Hirshfeld surface analysis of di­ethyl 2-[4-(4-fluoro­phen­yl)-2-methyl-4-oxobutan-2-yl]malonate

CROSSMARK_Color_square_no_text.svg
Sandeep Chandrashekharappa,a Keshab M. Bairagi,b Mahendra K. Mohan,a Katharigatta N. Venugopalac* and Susanta K. Nayakb*

aInstitute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK Campus, Bellary Road, Bangalore 560 065, Karnataka, India, bDepartment of Chemistry, Visvesvaraya National Institute of Technology, Nagpur 440 010, Maharashtra, India, and cDepartment of Biotechnology and Food Technology, Durban University of Technology, Durban 4001, South Africa
*Correspondence e-mail: katharigattav@dut.ac.za, sknayak@chm.vnit.ac.in

Edited by A. V. Yatsenko, Moscow State University, Russia (Received 31 July 2018; accepted 25 August 2018; online 7 September 2018)

The title compound, C18H23FO5, was synthesized by reacting diethyl malonate with 1-(4-fluoro­phen­yl)-3-methyl­but-2-en-1-one. The mol­ecule adopts a loose conformation stabilized by weak C—H⋯O and C—H⋯π inter­actions. In the crystal, the mol­ecules are joined by C—H⋯O contacts into infinite chains along the b-axis direction with a C(6) graph-set motif. Hirshfeld surface analysis and fingerprint plots demonstrate the predominance of H⋯H, O⋯H and F⋯H inter­molecular inter­actions in the crystal structure.

CCDC reference: 1863914

Similar articles

1. Chemical context

Polyfunctionalized reactions are used to synthesize the bioactive compounds that are inter­esting core structures for the development of new drug mol­ecules. The direct functionalization of chemical inter­mediates has attracted extensive attention of synthetic chemists (Fournier et al., 1994[Fournier, C., Hamon, M., Hamon, M., Wannebroucq, J., Petiprez, S., Pruvo, J. & Hecquet, B. (1994). Int. J. Pharm. 106, 41-49.]; Liu & Couldwell, 2005[Liu, J. K. & Couldwell, W. T. (2005). Neurocrit. Care, 2, 124-132.]; Markham & Faulds, 1998[Markham, A. & Faulds, D. (1998). Drugs, 56, 251-256.]) for the construction of heterocyclic compounds that are known to exhibit various pharmacological properties such as anti­cancer (Kasumbwe et al., 2017[Kasumbwe, K., Venugopala, K. N., Mohanlall, V. & Odhav, B. (2017). Anticancer Agents Med. Chem. 17, 276-285.]), anti­mosquito (Venugopala et al., 2013a[Venugopala, K. N., Krishnappa, M., Nayak, S. K., Subrahmanya, B. K., Vaderapura, J. P., Chalannavar, R. K., Gleiser, R. M. & Odhav, B. (2013a). Eur. J. Med. Chem. 65, 295-303.]), anti-tubercular (Narayanaswamy et al., 2013b[Narayanaswamy, V. K., Nayak, S. K., Pillay, M., Prasanna, R., Coovadia, Y. M. & Odhav, B. (2013b). Chem. Biol. Drug Des. 81, 219-227.]), anti-HIV (Poty et al., 2015[Poty, S., Désogère, P., Goze, C., Boschetti, F., D'huys, T., Schols, D., Cawthorne, C., Archibald, S. J., Maëcke, H. R. & Denat, F. (2015). Dalton Trans. 44, 5004-5016.]), anti-diabetic (Shahidpour et al., 2015[Shahidpour, S., Panahi, F., Yousefi, R., Nourisefat, M., Nabipoor, M. & Khalafi-Nezhad, A. (2015). Med. Chem. Res. 24, 3086-3096.]) and anti-microbial (Ji et al., 2015[Ji, C., Miller, P. A. & Miller, M. J. (2015). ACS Med. Chem. Lett. 6, 707-710.]) activities. The title compound, achieved by Michael addition (Simamura et al., 1954[Simamura, O., Inamoto, N. & Suehiro, T. (1954). Bull. Chem. Soc. Jpn, 27, 221-225.]), is an important precursor in the construction of the heterocyclic compound N2-(3-(di­fluoro­meth­oxy)-4-(3-methyl-1H-1,2,4-triazol-1-yl)phen­yl)-7-(4-fluoro­phen­yl)-N4,5,5-tri­methyl-6,7-di­hydro-5H-cyclo­penta­[d]pyrimidine-2,4-di­amine, which is a modulator of β-amyloid peptide production in treating Alzheimer's disease (Boy et al., 2015[Boy, K. M., Mercer, S. E., Olson, R. E. & Zhuo, X. (2015). Difluoromethoxy compound with low bioactivation potential for the reduction of β-amyloid production. Application WO2015153709A1.]).

[Scheme 1]

2. Structural commentary

The title compound crystallizes in the monoclinic crystal system in the space group P21/n, with one mol­ecule in the asymmetric unit (Z′ = 1). The mol­ecular conformation is stabilized by an intra­molecular C—H⋯O hydrogen bonds and C—H⋯π inter­action (Fig. 1[link], Table 1[link]) and short O3⋯O7 contact [3.007 (2) Å]. All bonds between sp3-hybridized atoms adopt staggered conformations, thus indicating that steric tensions are absent from this mol­ecule. The dihedral angle between the two ester groups of the malonate residue is 61.79 (5)°; the dihedral angles formed by aromatic ring with adjacent and opposite ester groups are 56.66 (4) and 16.08 (4)°, respectively. The dihedral angle between aromatic ring and ketone carbonyl unit is 14.04 (5)°.

Table 1
Hydrogen-bond geometry (Å, °)

Cg is the centroid of the C1–C6 aromatic ring.
D—H⋯A D—H H⋯A D⋯A D—H⋯A
C10—H10C⋯O4 0.98 2.40 3.057 (2) 124
C11—H11B⋯O1 0.98 2.55 3.167 (2) 121
C12—H12⋯O1 1.00 2.36 3.056 (2) 126
C15—H15B⋯O2i 0.98 2.54 3.500 (2) 168
C15—H15C⋯Cg 0.98 2.93 3.836 (2) 154
Symmetry code: (i) [-x+{\script{1\over 2}}, y+{\script{1\over 2}}, -z+{\script{1\over 2}}].
[Figure 1]
Figure 1
The asymmetric unit of the title compound with 50% probability ellipsoids with atom labelling. The intra­molecular C—H⋯π inter­action is shown as a dotted line.

3. Supra­molecular features

In the crystal of the title compound, the shortest inter­molecular contact is C15–H15B⋯O2, which join the mol­ecules into infinite chains with graph-set motif C(6) (Etter et al., 1990[Etter, M. C., MacDonald, J. C. & Bernstein, J. (1990). Acta Cryst. B46, 256-262.]) along the b-axis direction (Table 1[link], Fig. 2[link]). There are also a few other H⋯O contacts at the level of the sum of covalent radii.

[Figure 2]
Figure 2
Crystal packing of the title compound. The C—H⋯O hydrogen bonds form infinite chains along the b-axis direction.

4. Hirshfeld surfaces analysis

The approach based on Hirshfeld surfaces is a tool for visualizing the inter­molecular inter­action (Spackman & Jayatilaka, 2009[Spackman, M. A. & Jayatilaka, D. (2009). CrystEngComm, 11, 19-32.]). The Hirshfeld surfaces and two-dimensional fingerprint plot generated using CrystalExplorer 3.1 (Wolff et al., 2012[Wolff, S., Grimwood, D., McKinnon, J., Turner, M., Jayatilaka, D. & Spackman, M. (2012). CrystalExplorer. The University of Western Australia, Perth, Australia.]) are presented in Figs. 3[link] and 4[link]. The red spots on the Hirshfeld surface correspond to the C15—H15B⋯O2 contact, whereas the blue areas are completely free from close contacts, thus indicating that the only important contact is of the C—H⋯O type. The fingerprint plots (Fig. 4[link]) show that the H⋯H inter­molecular contacts give the largest contribution of 56.8%, and the observed white spots on the dnorm surface are considered to be weak inter­actions. The O⋯H/H⋯O contacts, which are shown as a sharp spike in the fingerprint plots, correspond to 22.8% of the total inter­actions. The percentage contribution of other weak inter­actions are as follows: H⋯F/F⋯H – 10.7%, C⋯H/H⋯C – 6.5%, C⋯O/O⋯C – 1.7%, C⋯C – 1.2% and F⋯O/O⋯F – 0.2%.

[Figure 3]
Figure 3
Hirshfeld surface of the title compound mapped over dnorm.
[Figure 4]
Figure 4
Two-dimensional fingerprint plots and relative contributions of various inter­actions to the Hirshfeld surface of the title compound.

5. Database survey

A search in the Cambridge Structural Database (version 5.39, last updated May 2018; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) for the fragments F—C6H4—C(=O)—CH2 and C6H4—C(=O)—CH2—CH2—CH(COO)2 gave 102 and 62 hits, respectively. Among them, two hits, (S)-ethyl-2-(4-t-butyl­benzyl­sulfan­yl)-4-(4-fluoro­phen­yl)-4-oxo­butano­ate (refcode: YOGMEO; Kowalczyk et al., 2014[Kowalczyk, R., Wierzba, A. J., Boratyński, P. J. & Bąkowicz, J. (2014). Tetrahedron, 70, 5834-5842.]) and dimethyl (S)-2-(1-(4-nitro­phen­yl)-1,4-dioxo­pentan-3-yl) malonate (refcode: YUFSOJ; Lippur et al., 2015[Lippur, K., Kaabel, S., Järving, I., Rissanen, K. & Kanger, T. (2015). J. Org. Chem. 80, 6336-6341.]) are the most closely related to the title crystal structure. The dihedral angles between the adjacent alkyl ester group and the aromatic ring in YOGMEO, YUFSOJ and the title structure are 78.97 (3), 39.37 (2) and 56.66 (4)°, respectively. As in the title structure, in YUFSOJ there are inter­molecular C—H⋯O contacts involving the methyl groups, whereas in YOGMEO the C—H⋯O contacts are formed with a hydrogen atom of the aromatic group.

6. Synthesis and crystallization

To a stirred solution of diethyl malonate (1 g, 6.25 mmol) in tetra­hydro­furan (5 ml), sodium hydride (0.33 g, 13.75 mmol) was added at 273 K. The reaction mixture was allowed to stir for 15 min. A solution of 1-(4-fluoro­phen­yl)-3-methyl­but-2-en-1-one (1.11 g, 6.25 mmol) in THF was added into the reaction mixture. The reaction mixture was then allowed to stir overnight at room temperature. The completion of the reaction was monitored by thin layer chromatography. The reaction mixture was quenched with saturated ammonium chloride and extracted with ethyl acetate (2 × 25 ml). The combined organic layer was washed with water (2 × 25 ml), brine (25 ml), dried over sodium sulfate and evaporated under reduced pressure to obtain the crude product, which was purified by column chromatography using 60–120 mesh silica gel with ethyl acetate and hexane eluent (v/v = 1:2). Single crystals of the title compound were obtained by slow evaporation from acetone solvent at room temperature.

7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. All hydrogen atoms were placed in idealized positions (C—H = 0.95–1.00 Å) and refined using riding model with Uiso = 1.2 or 1.5Ueq(C). The methyl groups were allowed to rotate.

Table 2
Experimental details

Crystal data
Chemical formula C18H23FO5
Mr 338.36
Crystal system, space group Monoclinic, P21/n
Temperature (K) 153
a, b, c (Å) 7.3066 (6), 11.5182 (9), 20.2701 (17)
β (°) 93.673 (2)
V (Å3) 1702.4 (2)
Z 4
Radiation type Mo Kα
μ (mm−1) 0.10
Crystal size (mm) 0.22 × 0.13 × 0.10
 
Data collection
Diffractometer Bruker Kappa DUO APEXII
Absorption correction Multi-scan (SADABS; Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.])
Tmin, Tmax 0.929, 0.941
No. of measured, independent and observed [I > 2σ(I)] reflections 15690, 4045, 2835
Rint 0.053
(sin θ/λ)max (Å−1) 0.657
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.042, 0.104, 1.03
No. of reflections 4045
No. of parameters 222
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.26, −0.21
Computer programs: APEX2 and SAINT (Bruker, 2014[Bruker (2014). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2014 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]), PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]), Mercury (Macrae et al., 2008[Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.]), WinGX (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]) and PARST (Nardelli, 1995[Nardelli, M. (1995). J. Appl. Cryst. 28, 659.]).

Supporting information

CCDC reference: 1863914

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989018012094/yk2116sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989018012094/yk2116Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989018012094/yk2116Isup3.cml

checkCIF report


Computing details top

Data collection: APEX2 (Bruker, 2014); cell refinement: SAINT (Bruker, 2014); data reduction: SAINT (Bruker, 2014); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: PLATON (Spek, 2009) and Mercury (Macrae et al., 2008); software used to prepare material for publication: WinGX (Farrugia, 2012), PLATON (Spek, 2009) and PARST (Nardelli, 1995).

Diethyl 2-[4-(4-fluorophenyl)-2-methyl-4-oxobutan-2-yl]propanedioate top
Crystal data top
C18H23FO5F(000) = 720
Mr = 338.36Dx = 1.320 Mg m−3
Dm = 1.32 Mg m−3
Dm measured by
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
a = 7.3066 (6) ÅCell parameters from 2274 reflections
b = 11.5182 (9) Åθ = 5.4–52.6°
c = 20.2701 (17) ŵ = 0.10 mm−1
β = 93.673 (2)°T = 153 K
V = 1702.4 (2) Å3Block, colorless
Z = 40.22 × 0.13 × 0.10 mm
Data collection top
Bruker Kappa DUO APEXII
diffractometer		2835 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.053
0.5° φ scans and ω scansθmax = 27.8°, θmin = 2.0°
Absorption correction: multi-scan
(SADABS; Sheldrick, 2015)		h = −9→9
Tmin = 0.929, Tmax = 0.941k = −15→15
15690 measured reflectionsl = −26→23
4045 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)] = 0.042H-atom parameters constrained
wR(F2) = 0.104 w = 1/[σ2(Fo2) + (0.0423P)2 + 0.1543P]
where P = (Fo2 + 2Fc2)/3
S = 1.02(Δ/σ)max < 0.001
4045 reflectionsΔρmax = 0.26 e Å−3
222 parametersΔρmin = −0.21 e Å−3
0 restraintsExtinction correction: SHELXL2014 (Sheldrick, 2015), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0022 (6)
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
F10.81620 (15)0.89772 (7)0.46296 (5)0.0405 (3)
O10.74992 (16)0.35297 (9)0.46976 (5)0.0307 (3)
O20.42377 (17)0.28973 (10)0.24940 (5)0.0383 (3)
O30.45134 (15)0.40181 (8)0.34014 (5)0.0262 (3)
O40.56685 (18)0.04282 (10)0.28153 (5)0.0411 (3)
O50.45277 (15)0.05130 (8)0.38152 (5)0.0258 (3)
C10.8140 (2)0.78062 (13)0.45372 (7)0.0268 (4)
C20.8913 (2)0.73723 (13)0.39876 (7)0.0260 (3)
H20.94560.78730.36830.031*
C30.8875 (2)0.61769 (12)0.38918 (7)0.0221 (3)
H30.93810.58560.35120.026*
C40.8102 (2)0.54422 (12)0.43457 (7)0.0205 (3)
C50.7325 (2)0.59304 (13)0.48947 (7)0.0247 (3)
H50.67820.54400.52040.030*
C60.7340 (2)0.71182 (13)0.49918 (7)0.0285 (4)
H60.68090.74510.53640.034*
C70.8023 (2)0.41483 (13)0.42581 (7)0.0217 (3)
C80.8624 (2)0.36640 (12)0.36098 (7)0.0224 (3)
H8A0.99770.37240.36200.027*
H8B0.81290.41830.32520.027*
C90.8105 (2)0.24080 (12)0.34080 (7)0.0223 (3)
C100.8648 (2)0.22647 (14)0.26926 (7)0.0294 (4)
H10A0.99700.23950.26750.044*
H10B0.79780.28300.24080.044*
H10C0.83440.14770.25380.044*
C110.9171 (2)0.15246 (13)0.38520 (8)0.0331 (4)
H11A0.88710.07360.36990.050*
H11B0.88320.16160.43090.050*
H11C1.04910.16590.38310.050*
C120.5999 (2)0.22011 (12)0.34749 (7)0.0218 (3)
H120.57540.23450.39480.026*
C130.4813 (2)0.30483 (13)0.30589 (7)0.0232 (3)
C140.3506 (2)0.49428 (13)0.30408 (7)0.0261 (4)
H14A0.22250.46980.29300.031*
H14B0.40890.51170.26240.031*
C150.3541 (2)0.60000 (13)0.34758 (8)0.0288 (4)
H15A0.29840.58140.38900.043*
H15B0.28480.66270.32490.043*
H15C0.48120.62480.35720.043*
C160.5405 (2)0.09577 (13)0.33143 (7)0.0247 (3)
C170.3988 (2)−0.07089 (12)0.37518 (7)0.0285 (4)
H17A0.5063−0.11960.36660.034*
H17B0.3050−0.08090.33820.034*
C180.3222 (2)−0.10521 (13)0.43942 (8)0.0325 (4)
H18A0.4151−0.09250.47570.049*
H18B0.2879−0.18750.43780.049*
H18C0.2137−0.05800.44660.049*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0591 (7)0.0204 (5)0.0428 (6)0.0001 (4)0.0096 (5)−0.0073 (4)
O10.0479 (8)0.0261 (6)0.0187 (5)−0.0084 (5)0.0049 (5)0.0033 (5)
O20.0477 (8)0.0406 (7)0.0252 (6)0.0070 (6)−0.0085 (5)−0.0085 (5)
O30.0358 (7)0.0219 (6)0.0208 (5)0.0039 (5)0.0003 (4)0.0000 (4)
O40.0665 (9)0.0319 (7)0.0269 (6)−0.0175 (6)0.0188 (6)−0.0121 (5)
O50.0378 (7)0.0175 (5)0.0227 (5)−0.0069 (5)0.0075 (5)−0.0008 (4)
C10.0324 (9)0.0199 (8)0.0279 (8)−0.0001 (6)−0.0004 (7)−0.0038 (6)
C20.0322 (9)0.0245 (8)0.0216 (8)−0.0043 (6)0.0038 (6)0.0014 (6)
C30.0236 (8)0.0250 (8)0.0178 (7)−0.0026 (6)0.0038 (6)−0.0028 (6)
C40.0222 (8)0.0220 (7)0.0172 (7)−0.0023 (6)−0.0010 (6)−0.0002 (6)
C50.0281 (9)0.0281 (8)0.0182 (7)−0.0042 (6)0.0031 (6)−0.0004 (6)
C60.0333 (9)0.0322 (9)0.0208 (8)0.0015 (7)0.0069 (6)−0.0070 (7)
C70.0224 (8)0.0238 (8)0.0187 (7)−0.0034 (6)−0.0009 (6)0.0005 (6)
C80.0262 (8)0.0219 (8)0.0194 (7)−0.0025 (6)0.0041 (6)0.0001 (6)
C90.0270 (8)0.0197 (8)0.0206 (7)−0.0008 (6)0.0048 (6)−0.0012 (6)
C100.0324 (9)0.0297 (9)0.0273 (8)−0.0027 (7)0.0105 (7)−0.0068 (7)
C110.0372 (10)0.0239 (8)0.0376 (9)0.0034 (7)−0.0032 (7)0.0006 (7)
C120.0299 (9)0.0196 (7)0.0162 (7)−0.0042 (6)0.0049 (6)−0.0007 (6)
C130.0244 (8)0.0244 (8)0.0213 (8)−0.0054 (6)0.0056 (6)−0.0011 (6)
C140.0276 (9)0.0279 (8)0.0227 (8)0.0013 (6)0.0004 (6)0.0070 (6)
C150.0320 (9)0.0273 (9)0.0275 (8)0.0058 (7)0.0048 (7)0.0055 (7)
C160.0295 (9)0.0234 (8)0.0214 (8)−0.0037 (6)0.0036 (6)−0.0009 (6)
C170.0412 (10)0.0177 (8)0.0266 (8)−0.0071 (7)0.0031 (7)−0.0024 (6)
C180.0450 (11)0.0229 (8)0.0302 (9)−0.0092 (7)0.0073 (7)−0.0006 (7)
Geometric parameters (Å, º) top
F1—C11.3617 (17)C9—C111.537 (2)
O1—C71.2212 (17)C9—C121.572 (2)
O2—C131.2070 (17)C10—H10A0.9800
O3—C131.3407 (17)C10—H10B0.9800
O3—C141.4633 (17)C10—H10C0.9800
O4—C161.2070 (17)C11—H11A0.9800
O5—C161.3372 (17)C11—H11B0.9800
O5—C171.4650 (17)C11—H11C0.9800
C1—C61.374 (2)C12—C131.523 (2)
C1—C21.375 (2)C12—C161.5254 (19)
C2—C31.391 (2)C12—H121.0000
C2—H20.9500C14—C151.503 (2)
C3—C41.396 (2)C14—H14A0.9900
C3—H30.9500C14—H14B0.9900
C4—C51.399 (2)C15—H15A0.9800
C4—C71.502 (2)C15—H15B0.9800
C5—C61.382 (2)C15—H15C0.9800
C5—H50.9500C17—C181.503 (2)
C6—H60.9500C17—H17A0.9900
C7—C81.518 (2)C17—H17B0.9900
C8—C91.5442 (19)C18—H18A0.9800
C8—H8A0.9900C18—H18B0.9800
C8—H8B0.9900C18—H18C0.9800
C9—C101.537 (2)
C13—O3—C14116.19 (11)C9—C11—H11B109.5
C16—O5—C17116.16 (11)H11A—C11—H11B109.5
F1—C1—C6118.74 (14)C9—C11—H11C109.5
F1—C1—C2118.01 (14)H11A—C11—H11C109.5
C6—C1—C2123.25 (14)H11B—C11—H11C109.5
C1—C2—C3117.86 (14)C13—C12—C16109.85 (12)
C1—C2—H2121.1C13—C12—C9112.35 (12)
C3—C2—H2121.1C16—C12—C9112.98 (12)
C2—C3—C4120.92 (13)C13—C12—H12107.1
C2—C3—H3119.5C16—C12—H12107.1
C4—C3—H3119.5C9—C12—H12107.1
C3—C4—C5118.84 (13)O2—C13—O3123.55 (14)
C3—C4—C7122.56 (13)O2—C13—C12125.75 (14)
C5—C4—C7118.58 (13)O3—C13—C12110.68 (11)
C6—C5—C4120.75 (14)O3—C14—C15107.93 (11)
C6—C5—H5119.6O3—C14—H14A110.1
C4—C5—H5119.6C15—C14—H14A110.1
C1—C6—C5118.37 (14)O3—C14—H14B110.1
C1—C6—H6120.8C15—C14—H14B110.1
C5—C6—H6120.8H14A—C14—H14B108.4
O1—C7—C4120.29 (13)C14—C15—H15A109.5
O1—C7—C8122.59 (13)C14—C15—H15B109.5
C4—C7—C8117.12 (12)H15A—C15—H15B109.5
C7—C8—C9119.59 (12)C14—C15—H15C109.5
C7—C8—H8A107.4H15A—C15—H15C109.5
C9—C8—H8A107.4H15B—C15—H15C109.5
C7—C8—H8B107.4O4—C16—O5123.54 (13)
C9—C8—H8B107.4O4—C16—C12126.51 (14)
H8A—C8—H8B107.0O5—C16—C12109.95 (12)
C10—C9—C11109.24 (13)O5—C17—C18106.84 (12)
C10—C9—C8106.06 (12)O5—C17—H17A110.4
C11—C9—C8110.99 (12)C18—C17—H17A110.4
C10—C9—C12112.26 (12)O5—C17—H17B110.4
C11—C9—C12108.15 (12)C18—C17—H17B110.4
C8—C9—C12110.15 (12)H17A—C17—H17B108.6
C9—C10—H10A109.5C17—C18—H18A109.5
C9—C10—H10B109.5C17—C18—H18B109.5
H10A—C10—H10B109.5H18A—C18—H18B109.5
C9—C10—H10C109.5C17—C18—H18C109.5
H10A—C10—H10C109.5H18A—C18—H18C109.5
H10B—C10—H10C109.5H18B—C18—H18C109.5
C9—C11—H11A109.5
F1—C1—C2—C3−179.48 (13)C11—C9—C12—C13179.22 (12)
C6—C1—C2—C30.1 (2)C8—C9—C12—C1357.76 (15)
C1—C2—C3—C4−1.1 (2)C10—C9—C12—C1664.78 (15)
C2—C3—C4—C51.4 (2)C11—C9—C12—C16−55.81 (15)
C2—C3—C4—C7179.59 (13)C8—C9—C12—C16−177.27 (11)
C3—C4—C5—C6−0.8 (2)C14—O3—C13—O2−3.2 (2)
C7—C4—C5—C6−179.03 (13)C14—O3—C13—C12175.51 (12)
F1—C1—C6—C5−179.90 (13)C16—C12—C13—O2−36.6 (2)
C2—C1—C6—C50.6 (2)C9—C12—C13—O290.11 (18)
C4—C5—C6—C1−0.2 (2)C16—C12—C13—O3144.81 (13)
C3—C4—C7—O1172.84 (14)C9—C12—C13—O3−88.52 (15)
C5—C4—C7—O1−9.0 (2)C13—O3—C14—C15−172.32 (13)
C3—C4—C7—C8−6.9 (2)C17—O5—C16—O44.1 (2)
C5—C4—C7—C8171.30 (13)C17—O5—C16—C12−175.80 (12)
O1—C7—C8—C916.5 (2)C13—C12—C16—O472.5 (2)
C4—C7—C8—C9−163.76 (13)C9—C12—C16—O4−53.8 (2)
C7—C8—C9—C10171.38 (13)C13—C12—C16—O5−107.55 (14)
C7—C8—C9—C11−70.08 (17)C9—C12—C16—O5126.14 (13)
C7—C8—C9—C1249.67 (17)C16—O5—C17—C18173.97 (13)
C10—C9—C12—C13−60.19 (16)
Hydrogen-bond geometry (Å, º) top
Cg is the centroid of the C1–C6 aromatic ring.
D—H···AD—HH···AD···AD—H···A
C10—H10C···O40.982.403.057 (2)124
C11—H11B···O10.982.553.167 (2)121
C12—H12···O11.002.363.056 (2)126
C15—H15B···O2i0.982.543.500 (2)168
C15—H15C···Cg0.982.933.836 (2)154
Symmetry code: (i) −x+1/2, y+1/2, −z+1/2.
 

Funding information

The authors are thankful to the National Research Foundation (96807 and 98884), South Africa and Durban University of Technology, South Africa, for support and encouragement. KMB thanks VNIT Nagpur for support of a research fellowship.

References

First citationBoy, K. M., Mercer, S. E., Olson, R. E. & Zhuo, X. (2015). Difluoromethoxy compound with low bioactivation potential for the reduction of β-amyloid production. Application WO2015153709A1.  Google Scholar
 First citationBruker (2014). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
 First citationEtter, M. C., MacDonald, J. C. & Bernstein, J. (1990). Acta Cryst. B46, 256–262.  CSD CrossRef CAS Web of Science IUCr Journals Google Scholar
 First citationFarrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationFournier, C., Hamon, M., Hamon, M., Wannebroucq, J., Petiprez, S., Pruvo, J. & Hecquet, B. (1994). Int. J. Pharm. 106, 41–49.  CrossRef Web of Science Google Scholar
 First citationGroom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179.  Web of Science CSD CrossRef IUCr Journals Google Scholar
 First citationJi, C., Miller, P. A. & Miller, M. J. (2015). ACS Med. Chem. Lett. 6, 707–710.  Web of Science CrossRef Google Scholar
 First citationKasumbwe, K., Venugopala, K. N., Mohanlall, V. & Odhav, B. (2017). Anticancer Agents Med. Chem. 17, 276–285.  Web of Science CrossRef Google Scholar
 First citationKowalczyk, R., Wierzba, A. J., Boratyński, P. J. & Bąkowicz, J. (2014). Tetrahedron, 70, 5834–5842.  Web of Science CrossRef Google Scholar
 First citationLippur, K., Kaabel, S., Järving, I., Rissanen, K. & Kanger, T. (2015). J. Org. Chem. 80, 6336–6341.  Web of Science CrossRef Google Scholar
 First citationLiu, J. K. & Couldwell, W. T. (2005). Neurocrit. Care, 2, 124–132.  Web of Science CrossRef Google Scholar
 First citationMacrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466–470.  Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
 First citationMarkham, A. & Faulds, D. (1998). Drugs, 56, 251–256.  Web of Science CrossRef Google Scholar
 First citationNarayanaswamy, V. K., Nayak, S. K., Pillay, M., Prasanna, R., Coovadia, Y. M. & Odhav, B. (2013b). Chem. Biol. Drug Des. 81, 219–227.  Web of Science CrossRef Google Scholar
 First citationNardelli, M. (1995). J. Appl. Cryst. 28, 659.  CrossRef IUCr Journals Google Scholar
 First citationPoty, S., Désogère, P., Goze, C., Boschetti, F., D'huys, T., Schols, D., Cawthorne, C., Archibald, S. J., Maëcke, H. R. & Denat, F. (2015). Dalton Trans. 44, 5004–5016.  Web of Science CrossRef Google Scholar
 First citationShahidpour, S., Panahi, F., Yousefi, R., Nourisefat, M., Nabipoor, M. & Khalafi-Nezhad, A. (2015). Med. Chem. Res. 24, 3086–3096.  Web of Science CrossRef Google Scholar
 First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationSheldrick, G. M. (2015). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
 First citationSimamura, O., Inamoto, N. & Suehiro, T. (1954). Bull. Chem. Soc. Jpn, 27, 221–225.  CrossRef Google Scholar
 First citationSpackman, M. A. & Jayatilaka, D. (2009). CrystEngComm, 11, 19–32.  Web of Science CrossRef CAS Google Scholar
 First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationVenugopala, K. N., Krishnappa, M., Nayak, S. K., Subrahmanya, B. K., Vaderapura, J. P., Chalannavar, R. K., Gleiser, R. M. & Odhav, B. (2013a). Eur. J. Med. Chem. 65, 295–303.  Web of Science CrossRef Google Scholar
 First citationWolff, S., Grimwood, D., McKinnon, J., Turner, M., Jayatilaka, D. & Spackman, M. (2012). CrystalExplorer. The University of Western Australia, Perth, Australia.  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.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 74| Part 10| October 2018| Pages 1388-1391
https://doi.org/10.1107/S2056989018012094
Follow Acta Cryst. E
Sign up for e-alerts
E-alerts
Follow Acta Cryst. on Twitter
Twitter
Follow us on facebook
Facebook
Sign up for RSS feeds
RSS