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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 75| Part 8| August 2019| Pages 1162-1168
https://doi.org/10.1107/S2056989019009654

Bis(mefloquinium) butane­dioate ethanol monosolvate: crystal structure and Hirshfeld surface analysis

CROSSMARK_Color_square_no_text.svg
James L. Wardell,a‡ Mukesh M. Jotanib and Edward R. T. Tiekinkc*

aFundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil, bDepartment of Physics, Bhavan's Sheth R. A. College of Science, Ahmedabad, Gujarat 380001, India, and cResearch Centre for Crystalline Materials, School of Science and Technology, Sunway University, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia
*Correspondence e-mail: edwardt@sunway.edu.my

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 3 July 2019; accepted 6 July 2019; online 12 July 2019)

The asymmetric unit of the centrosymmetric title salt solvate, 2C17H17F6N2O+· C4H4O42−·CH3CH2OH, (systematic name: 2-{[2,8-bis­(tri­fluoro­meth­yl)quinolin-4-yl](hy­droxy)meth­yl}piperidin-1-ium butane­dioate ethanol monosolvate) comprises two independent cations, with almost superimposable conformations and each approximating the shape of the letter L, a butane­dioate dianion with an all-trans conformation and an ethanol solvent mol­ecule. In the crystal, supra­molecular chains along the a-axis direction are sustained by charge-assisted hy­droxy-O—H⋯O(carboxyl­ate) and ammonium-N—H⋯O(carboxyl­ate) hydrogen bonds. These are connected into a layer via C—F⋯π(pyrid­yl) contacts and π–π stacking inter­actions between quinolinyl-C6 and –NC5 rings of the independent cations of the asymmetric unit [inter-centroid separations = 3.6784 (17) and 3.6866 (17) Å]. Layers stack along the c-axis direction with no directional inter­actions between them. The analysis of the calculated Hirshfeld surface reveals the significance of the fluorine atoms in surface contacts. Thus, by far the greatest contribution to the surface contacts, i.e. 41.2%, are of the type F⋯H/H⋯F and many of these occur in the inter-layer region. However, these contacts occur at separations beyond the sum of the van der Waals radii for these atoms. It is noted that H⋯H contacts contribute 29.8% to the overall surface, with smaller contributions from O⋯H/H⋯O (14.0%) and F⋯F (5.7%) contacts.

CCDC reference: 1938793

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1. Chemical context

Malaria continues to be a major worldwide health issue and vast populations in tropical countries, including visitors to those regions, are susceptible to the disease, which is spread by parasites such as Plasmodium falciparum (Maguire et al., 2006[Maguire, J. D., Krisin Marwoto, H., Richie, T. L., Fryauff, D. J. & Baird, J. K. (2006). Clin. Infect. Dis. 42, 1067-1072.]). The problem is compounded by the parasites' abilities to develop resistance to drugs, such as to the once popular chloro­quine (Grabias & Kumar, 2016[Grabias, B. & Kumar, S. (2016). Expert Opin. Drug Saf. 15, 903-910.]). Mefloquine, [2,8-bis(tri­fluoro­meth­yl)quinolin-4-yl]-piperidin-2-yl­methanol, is a drug used against malaria (Tickell-Pa­inter et al., 2017[Tickell-Painter, M., Maayan, N., Saunders, R., Pace, C. & Sinclair, D. (2017). Cochrane Database Syst. Rev. 10 art. no. CD006491.]). The mol­ecule contains two adjacent chiral centres, i.e. one at the carbon atom carrying the hy­droxy group and one at the link connecting the piperidinyl ring to the rest of the mol­ecule. The drug is commonly marketed as Lariam, which is the hydro­chloride salt, comprising (R*,S*)-(2-{[2,8-bis­(tri­fluoro­meth­yl)quinolin-4-yl](hy­droxy­meth­yl)piperidin-1-ium chloride and its (S*,R*) enanti­omer. While the former is effective against malaria, the latter has an affinity for the adenosine acceptors in the brain, inducing serious psychiatric and neurologic side-effects (Nevin, 2017[Nevin, R. L. (2017). Pharmacol. Res. pp. 5, article No. e00328.]). Hence, experiments at resolving the enanti­omers are of practical importance (Engwerda et al., 2019[Engwerda, A. H. J., Maassen, R., Tinnemans, P., Meekes, H., Rutjes, F. P. J. T. & Vlieg, E. (2019). Angew. Chem. Int. Ed. 58, 1670-1673.]). Herein, as continuation of our anion-exchange experiments of the racemic salt and attendant structural studies (Wardell et al., 2016[Wardell, J. L., Jotani, M. M. & Tiekink, E. R. T. (2016). Acta Cryst. E72, 1618-1627.]; Wardell, Wardell et al., 2018[Wardell, J. L., Wardell, S. M. S. V., Jotani, M. M. & Tiekink, E. R. T. (2018). Acta Cryst. E74, 895-900.]; Wardell, Jotani et al., 2018[Wardell, J. L., Jotani, M. M. & Tiekink, E. R. T. (2018). Acta Cryst. E74, 1851-1856.]; Wardell & Tiekink, 2019[Wardell, J. L. & Tiekink, E. R. T. (2019). Z. Kristallogr. New Cryst. Struct. 234, 687-689.]), the crystal and mol­ecular structures of the butane­dioate salt, isolated as an ethanol monosolvate, are described along with an analysis of the calculated Hirshfeld surfaces.

[Scheme 1]

2. Structural commentary

The asymmetric unit of the salt solvate, (I)[link], comprises two mefloquinium cations, a butane­dioate dianion and a solvent ethanol mol­ecule; the mol­ecular structures of the ions are shown in Fig. 1[link]. Evidence of proton transfer during crystallization is seen in the relatively small difference in the C O bond lengths of the dianion, i.e. C35—O3, O4 = 1.236 (4) and 1.285 (3) Å, and C38—O5, O6 = 1.255 (4) and 1.271 (4) Å. While normally these bond lengths might be expected to be closer to equivalent, as noted below, each of the O4 and O6 atoms participate in two strong charge-assisted hydrogen bonds, see Supra­molecular features, which explains the slightly longer C O bond lengths formed by these atoms. Further support for proton transfer leading to the formation of piperidin-1-ium cations is supported by the pattern of hydrogen bonding involving the ammonium-N—H hydrogen atoms, as discussed below in Supra­molecular features.

[Figure 1]
Figure 1
The mol­ecular structures of the ionic components of the asymmetric unit of (I)[link] showing the atom-labelling scheme and displacement ellipsoids at the 50% probability level: (a) the N1-containing cation, (b) the N3-cation and (c) the butane­dioate dianion.

The cations exhibit very similar mol­ecular geometries, as highlighted in the overlay diagram of Fig. 2[link]. There are two chiral centres in each cation and the illustrated cations are R at C12 and S at C13 for the N1-cation, and R at C29 and S at C30 for the N3-cation, i.e. each conforms to the [(+)-erythro-mefloquinium] isomer; space-group symmetry indicates that the unit cell contains equal numbers of both enanti­omers. The r.m.s. deviation for the ten atoms comprising the N1-quinolinyl residue is 0.0254 Å [0.0256 Å for the N3-quinolinyl residue], with the hy­droxy-O1 and ammonium-N2 atoms lying to either side of the plane, i.e. −0.323 (4) and 1.302 (6) Å, respectively [0.255 (4) Å for O2 and −1.348 (6) Å for N4]. The dihedral angle of 72.55 (9)° [71.48 (9)°] formed between the fused ring system and the least-squares plane through the piperinium ring indicates that, to a first approximation, the mol­ecule has the shape of the letter L. Referring to Table 1[link], an intra­molecular charge-assisted ammonium-N+—H⋯O(hy­droxy) hydrogen-bond is formed as the hydroxyl-O1 and ammonium-N2 atoms lie to the same side of the cation with the O1—C12—C13—N2 torsion angle of −63.4 (3)° indicating a + syn-clinal relationship [O2—C29—C30—N4 = −68.4 (3)°].

Table 1
Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of the (N1,C1–C4,C9) ring.
D—H⋯A D—H H⋯A D⋯A D—H⋯A
N2—H1N⋯O1 0.88 (3) 2.49 (3) 2.806 (4) 102 (2)
N4—H3N⋯O2 0.88 (2) 2.54 (3) 2.863 (4) 103 (2)
O1—H1O⋯O6 0.84 (3) 1.81 (3) 2.653 (3) 175 (2)
O2—H2O⋯O4i 0.84 (2) 1.82 (2) 2.656 (3) 170 (3)
N2—H1N⋯O5ii 0.88 (3) 1.97 (3) 2.830 (4) 165 (3)
N2—H2N⋯O4i 0.88 (3) 1.82 (3) 2.694 (4) 173 (3)
N4—H3N⋯O3ii 0.88 (2) 1.99 (3) 2.832 (4) 161 (3)
N4—H4N⋯O6 0.89 (3) 1.92 (3) 2.789 (4) 168 (3)
O7—H7O⋯O5 0.85 (3) 1.88 (3) 2.729 (4) 176 (7)
C30—H30⋯O7 1.00 2.40 3.296 (4) 149
C10—F3⋯Cg1iii 1.32 (1) 3.28 (1) 4.101 (3) 120 (1)
Symmetry codes: (i) x-1, y, z; (ii) -x, -y+2, -z; (iii) -x, -y+1, -z.
[Figure 2]
Figure 2
An overlay diagram of the N1- (red image) and N3-containing cations. The cations have been superimposed so that the C5N rings of the quinolinyl residues are coincident.

In the butane­dioate dianion, the C35—C36—C38—C39 torsion angle of 175.4 (3)° indicates an all-trans conformation (+ anti-periplanar). The dihedral angle formed between the terminal carboxyl­ate residues is 51.0 (2)°, indicating that the dianion is considerably twisted.

3. Supra­molecular features

The most prominent feature of the mol­ecular packing is the formation of twisted supra­molecular chains propagating parallel to the a-axis direction, Table 1[link] and Fig. 3[link]a. Each of the cation-bound hy­droxy groups forms a charge-assisted hy­droxy-O—H⋯O(carboxyl­ate) hydrogen bond to a carboxyl­ate-O atom, at opposite ends of the butane­dioate dianion. In addition, each of the four ammonium-N—H hydrogen atoms connects to a carboxyl­ate-O atom, each derived from a different carboxyl­ate residue, via a charge-assisted ammonium-N—H⋯O(carboxyl­ate) hydrogen bond. Thus, each of the O4 and O6 atoms accept two charge-assisted hydrogen bonds. The carboxyl­ate-O5 atom accepts a hydrogen bond from the solvent ethanol mol­ecule, while ethanol-O7 participates in a methine-C—H⋯O inter­action, Table 1[link]. The carboxyl­ate-O3 atom forms only one hydrogen bond. The number and strength of hydrogen bonds formed by the carboxyl­ate-O atoms correlates with the magnitude of the C O bond lengths, e.g. the C35—O3 < C38—O5 < C38—O6 C35—O4 (see comment in Structural Commentary).

[Figure 3]
Figure 3
Mol­ecular packing in (I)[link]: (a) The supra­molecular chain along the a axis, being sustained by O—H⋯O (orange dashed lines) and N—H⋯O (blue dashed lines) hydrogen bonding with non-participating H atoms omitted and (b) a view of the unit-cell contents shown in projection down the a axis, the axis of propagation of the chain shown in (a). The C—Cl⋯π, and C—F⋯π inter­actions are shown as pink and purple dashed lines, respectively.

The connections between the chains leading to supra­molecular layers that stack along the c-axis direction are of the type C—F⋯π(pyrid­yl), Table 1[link], occurring between N1-containing cations, and π–π stacking inter­actions between the independent mol­ecules comprising the asymmetric unit. The latter occur between the C6 ring of the N1-quinolinyl residue (C4–C9) and each of the N3-quinolinyl-bound pyridyl (N3,C18–C21,C26) [inter-centroid separation = 3.6784 (17) Å, angle of inclination = 4.27 (14)°] and C6 (C21–C26) [3.6866 (17) Å, angle of inclination = 3.67 (14)°] rings. A view of the unit-cell contents is shown in Fig. 3[link]b.

4. Hirshfeld surface analysis

The analysis of Hirshfeld surface calculations for (I)[link] was performed in order to learn more about the supra­molecular association, in particular, about the inter-layer connections, following established procedures (Tan et al., 2019[Tan, S. L., Jotani, M. M. & Tiekink, E. R. T. (2019). Acta Cryst. E75, 308-318.]) and employing Crystal Explorer 17 (Turner et al., 2017[Turner, M. J., Mckinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). Crystal Explorer 17. The University of Western Australia.]). Such analyses have proven useful for salts with multiple components comprising the asymmetric unit (Jotani et al., 2019[Jotani, M. M., Wardell, J. L. & Tiekink, E. R. T. (2019). Z. Kristallogr. Cryst. Mater. 234, 43-57.]).

It is clearly evident from the numerous characteristic red spots on the Hirshfeld surfaces mapped over dnorm for the constituents of (I)[link], shown in Fig. 4[link], that the butane­dioate dianion plays a crucial role in forming significant inter­actions with each of the two independent mefloquinium cations as well as with the ethanol solvent mol­ecule. The O—H⋯O and N—H⋯O hydrogen bonds summarized in Table 1[link] are characterized as bright-red spots on the Hirshfeld surface mapped over dnorm for the dianion, Fig. 4[link]a and b, and near the respective donors on the Hirshfeld surfaces of the ethanol mol­ecule, Fig. 4[link]c, and mefloquinium cations in Fig. 4[link]d and e. The effects of the short inter-atomic contacts on the packing of (I)[link], summarized in Table 2[link], are also evident as the faint-red spots near the respective atoms, Fig. 4[link]. The blue and red regions corresponding to positive and negative potentials, respectively, around the atoms of the dianion and solvent ethanol mol­ecule, Fig. 5[link], and cations, Fig. 6[link], on the Hirshfeld surfaces mapped over electrostatic potential also represent donors and acceptors of the respective hydrogen bonds. The additional influence of the C—F⋯π contacts involving the F2 and F3 atoms inter­acting with the (C4–C9) and N1-pyridyl rings of the N1-quinolinyl residue are viewed as blue bumps and bright-orange concave regions, respectively, on the Hirshfeld surface mapped with the shape-index property in Fig. 7[link]. The π–π contacts formed between the (C4–C9) ring of the O1-cation and each of the (C21–C26) and N3-pyridyl rings of the O2-cation are illustrated in Fig. 8[link].

Table 2
Summary of short inter­atomic contacts (Å) in (I)a

Contact Distance Symmetry operation
F1⋯H6 2.50 1 + x, y, z
F6⋯C32 3.096 (4) x, −1 + y, z
O1⋯H37B 2.45 x, y, z
O1⋯C38 3.038 (4) -x, −y, −1 − z
O2⋯H36B 2.50 −1 + x, y, z
O2⋯C36 3.090 (4) −1 + x, y, z
O4⋯H12 2.53 1 + x, y, z
O6⋯H22 2.50 x, y, z
O7⋯H31B 2.55 x, y, z
H1O⋯H37B 2.14 x, y, z
H12⋯H29 2.06 x, y, z
H34A⋯H39A 2.22 -x, 2 − y, −z
Notes: (a) The inter­atomic distances are calculated in Crystal Explorer (Turner et al., 2017[Turner, M. J., Mckinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). Crystal Explorer 17. The University of Western Australia.]) whereby the X—H bond lengths are adjusted to their neutron values.
[Figure 4]
Figure 4
Views of the Hirshfeld surface of (I)[link] mapped over dnorm for the: (a) and (b) dianion in the range −0.229 to + 1.450 arbitrary units (a.u.), (c) ethanol mol­ecule (−0.169 to +1.471 a.u.), (d) and (e) O1-containing cation (−0.229 to + 2.242 a.u.) and (f) and (g) O2-containing cation (−0.219 to +2.159 a.u.).
[Figure 5]
Figure 5
Views of Hirshfeld surface mapped over electrostatic potential for the: (a) and (b) dianion in the range −0.072 to +0.066 atomic units (au) and (c) ethanol mol­ecule (−0.077 to +0.159 au). The red and blue regions represent negative and positive electrostatic potentials, respectively.
[Figure 6]
Figure 6
Views of Hirshfeld surface mapped over electrostatic potential for the: (a) O1-containing cation in the range −0.262 to +0.215 atomic units (au) and (b) O2-containing cation (−0.255 to +0.198 au). The red and blue regions represent negative and positive electrostatic potentials, respectively.
[Figure 7]
Figure 7
A view of Hirshfeld surface mapped over the shape-index property highlighting the inter­molecular C—F⋯π/π⋯F—C contacts by blue bumps and bright-orange concave regions.
[Figure 8]
Figure 8
A view of Hirshfeld surface mapped over dnorm for the O1-containing cation in the range −0.229 to + 2.242 arbitrary units highlighting the intra­molecular π–π contacts between the (C4–C9) ring of the O1-containing cation and the (C21–C26) and N3-pyridyl rings of the O2-containing cation by red and black dotted lines, respectively.

The overall two-dimensional fingerprint plot for (I)[link], Fig. 9[link]a, and those delineated into specific H⋯H, O⋯H/H⋯O, F⋯H/H⋯F, C⋯F/⋯C and C⋯O/O⋯C contacts (McKinnon et al., 2007[McKinnon, J. J., Jayatilaka, D. & Spackman, M. A. (2007). Chem. Commun. pp. 3814-3816.]) are illustrated in Fig. 9[link]b-e; the percentage contributions from the different inter-atomic contacts to the Hirshfeld surface are summarized in Table 3[link]. The relatively small percentage contribution from H⋯H contacts to the Hirshfeld surface in the overall packing of (I)[link] is due to the formation of a wide range of different inter­molecular inter­actions between the constituent cations, dianions and solvent ethanol mol­ecule. This is well-evidenced in the long list of contacts in Table 3[link]. The presence of two tri­fluoro­methyl groups in each of the independent cations results in a major contribution from fluorine atoms to the Hirshfeld surface of (I)[link], as highlighted in Table 3[link]. Indeed, the major contributor of contacts to the surface is of the type F⋯H/H⋯F, at 41.2%. Many of these occur in the inter-layer region at separations greater than the sum of the van der Waals radii.

Table 3
Percentage contributions of inter­atomic contacts to the Hirshfeld surface for (I)

Contact Percentage contribution
H⋯H 29.8
O⋯H/H⋯O 14.0
F⋯H/H⋯F 41.2
F⋯F 5.7
C⋯H/H⋯C 4.1
C⋯F/F⋯C 2.8
N⋯H/H⋯N 1.0
C⋯N/N⋯C 0.5
C⋯O/O⋯C 0.3
O⋯O 0.2
F⋯N/N⋯F 0.2
C⋯C 0.2
F⋯O/O⋯F 0.1
[Figure 9]
Figure 9
(a) The full two-dimensional fingerprint plot for (I)[link] and (b)–(f) those delineated into H⋯H, O⋯H/H⋯O, F⋯H/H⋯F, C⋯F/F⋯C and C⋯O/O⋯C contacts, respectively.

The presence of a cone-shaped tip at de + di 2.2 Å in the fingerprint plot delineated into H⋯H contacts in Fig. 9[link]b, is an indication of the short inter­atomic H⋯H contact between symmetry-related piperidinium-H34A and ethanol-H39A atoms, Table 2[link]. The other short H⋯H contacts summarized in Table 2[link] occur between the hydrogen atoms of the cations and dianion within the asymmetric unit. In the fingerprint plot delineated into O⋯H/H⋯O contacts, Fig. 9[link]c, the pair of long spikes with their tips at de + di ∼1.8 Å are due to the O—H⋯O and N—H⋯O hydrogen bonds involving the carboxyl­ate-O4 atom of the dianion whereas the points corresponding to N—H⋯O hydrogen bonds involving the O3 and O5 atoms of the dianion and those involved in short inter­atomic O⋯H contacts, Table 2[link], are merged within the plot. The pair of conical tips at de + di ∼2.5 Å in the fingerprint plot delineated into F⋯H/H⋯F contacts, Fig. 9[link]d, represent the presence of these short contacts. The effect of inter­molecular C—F⋯π/π⋯F—C and short inter­atomic C⋯F/F⋯C contacts on the mol­ecular packing, Table 3[link], results in a small but measurable contribution of 2.8% to the Hirshfeld surface of (I)[link] and are viewed as the pair of forceps-like tips at de + di ∼3.1 Å in Fig. 9[link]e. The presence of short inter­atomic C⋯O/O⋯C contacts involving the hydroxyl-O1 and -O2 atoms are characterized as a pair of leaf-like tips at de + di ∼3.0 Å in Fig. 9[link]f. Finally, the presence of π–π stacking inter­actions between the (C4–C9) ring of the O1-cation and the (C21–C26) and N3-pyridyl rings of the O2-cation are reflected in the 3.4 and 3.3% contributions from C⋯C contacts to the Hirshfeld surfaces of the individual cations; although the contribution from these contacts to the surfaces in the overall structure of (I)[link] is negligible as these are embedded within the asymmetric unit.

5. Database survey

As indicated in the Chemical context, the specific enanti­omer of Lariam is important in terms of pharmacological activity. Hence, considerable investment has been made in attempting to resolve the enanti­omers by salt formation. During such studies, a seemingly high propensity towards kryptoracemic behaviour has been revealed. Kryptoracemic behaviour is related to the rare phenomenon where enanti­omeric mol­ecules crystallize in one of the 65 Sohncke space groups, i.e. space groups which lack an inversion centre, a rotatory inversion axis, a glide plane or a mirror plane. In these circumstances, the enanti­omeric mol­ecules are related by non-crystallographic symmetry, e.g. a non-crystallographic centre of inversion. A review of this phenomenon has appeared for organic compounds (Fábián & Brock, 2010[Fábián, L. & Brock, C. P. (2010). Acta Cryst. B66, 94-103.]) where such behaviour is found in only 0.1% of structures. There are about 30 mefloquine/derivatives in the Cambridge Structural Database (Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) and of these, there are two examples of kryptoracemates (Jotani et al., 2016[Jotani, M. M., Wardell, J. L. & Tiekink, E. R. T. (2016). Z. Kristallogr. 231, 247-255.]; Wardell, Wardell et al., 2016[Wardell, J. L., Jotani, M. M. & Tiekink, E. R. T. (2016). Acta Cryst. E72, 1618-1627.]). Further, in a very recent study, 34 new mefloquine salts were reported of which two were kryptoracemates (Engwerda et al., 2019[Engwerda, A. H. J., Maassen, R., Tinnemans, P., Meekes, H., Rutjes, F. P. J. T. & Vlieg, E. (2019). Angew. Chem. Int. Ed. 58, 1670-1673.]). Such a high adoption of kryptoracemic behaviour by these species suggest that further, systematic structural studies are warranted.

6. Synthesis and crystallization

A solution of mefloquinium chloride (1 mmol) and sodium succinate (2 mmol) in ethanol (15 ml) was refluxed for 30 min. The reaction mixture was left at room temperature and after three days, colourless platy crystals of (I)[link] were collected; m.p. 505–505 K. Yield of recrystallized product 65%.

1H NMR (DMSO-d6): δ: 1.15–1.27 (2H, m), 1.32–1.47 (6H, m), 1.48–1.57 (2H, br. d), 1.65–1.74 (2H, br. d), 2.33 (4H, s; succinate), 2.58–2.67 (2H, br. t), 3.00–3.11 (4H, m), 5.58 (2H, d, J = 8 Hz), 7.95 (2H, t, J = 8 Hz), 8.10 (2H, s), 8.37 (2H, t, J = 7.2 Hz), 8.75 (2H, d, J = 8 Hz), resonances due to OH and NH were not observed. Resonances due to ethanol solvate were also present: 3.45 (q, J = 7.0 Hz) and 1.07 (t, J = 7.0 Hz). 13C NMR (DMSO-d6): δ: 22.92, 24.28, 24.71, 31.76, 45.55, 60.57, 70.33, 115.58, 119.89 (JC,F = 273.8 Hz), 122.34, 122.64 (JC,F = 271.7 Hz), 127.77 (JC,F = 29.0 Hz), 127.76, 129.40, 129.9 (JC,F = 5.2Hz), 142.74, 146.56 (JC,F = 34.5 Hz), 153.13, 175.32). 19F NMR (DMSO-d6); δ: −58.83, −66.63. IR (cm−1) 3500–2100 (br), 1589 (br), 1514, 1454, 1430, 1371, 1312, 1267, 1217, 1182, 1111, 1053, 1018, 986, 941,910, 837, 777, 546, 445.

7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 4[link]. The carbon-bound H atoms were placed in calculated positions (C—H = 0.95–1.00 Å) and were included in the refinement in the riding-model approximation, with Uiso(H) set to 1.2–1.5Ueq(C). The O- and N-bound H atoms were refined with distance restraints 0.84±0.01 and 0.88±0.01 Å, respectively, and refined with Uiso(H) = 1.5Ueq(O) and 1.2Ueq(N), respectively. Owing to poor agreement, the (0[\overline{1}]2) reflection was omitted from the final cycles of refinement.

Table 4
Experimental details

Crystal data
Chemical formula 2C17H17F6N2O+·C4H4O42−·C2H6O
Mr 920.79
Crystal system, space group Triclinic, P[\overline{1}]
Temperature (K) 120
a, b, c (Å) 10.0405 (2), 14.6482 (4), 14.6547 (4)
α, β, γ (°) 100.745 (1), 93.830 (2), 98.497 (2)
V (Å3) 2084.41 (9)
Z 2
Radiation type Mo Kα
μ (mm−1) 0.14
Crystal size (mm) 0.42 × 0.05 × 0.03
 
Data collection
Diffractometer Bruker–Nonius Roper CCD camera on κ-goniostat
Absorption correction Multi-scan (SADABS;Sheldrick, 2007[Sheldrick, G. M. (2007). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.849, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections 42885, 9543, 6505
Rint 0.085
(sin θ/λ)max (Å−1) 0.651
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.074, 0.180, 1.04
No. of reflections 9543
No. of parameters 590
No. of restraints 7
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.60, −0.58
Computer programs: DENZO (Otwinowski & Minor, 1997[Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York: Academic Press.]) and COLLECT (Hooft, 1998[Hooft, R. W. W. (1998). COLLECT. Nonius BV, Delft, The Netherlands.]), SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2014 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]), ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]), DIAMOND (Brandenburg, 2006[Brandenburg, K. (2006). DIAMOND. Crystal Impact GbR, Bonn, Germany.]) and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Supporting information

CCDC reference: 1938793

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2056989019009654/hb7838sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989019009654/hb7838Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989019009654/hb7838Isup3.cml

checkCIF report


Computing details top

Data collection: COLLECT (Hooft, 1998); cell refinement: DENZO (Otwinowski & Minor, 1997) and COLLECT (Hooft, 1998); data reduction: DENZO (Otwinowski & Minor, 1997) and COLLECT (Hooft, 1998); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and DIAMOND (Brandenburg, 2006); software used to prepare material for publication: publCIF (Westrip, 2010).

2-{[2,8-Bis(trifluoromethyl)quinolin-4-yl](hydroxy)methyl}piperidin-1-ium butanedioate ethanol monosolvate top
Crystal data top
2C17H17F6N2O+·C4H4O42−·C2H6OZ = 2
Mr = 920.79F(000) = 952
Triclinic, P1Dx = 1.467 Mg m−3
a = 10.0405 (2) ÅMo Kα radiation, λ = 0.71073 Å
b = 14.6482 (4) ÅCell parameters from 32862 reflections
c = 14.6547 (4) Åθ = 2.9–27.5°
α = 100.745 (1)°µ = 0.14 mm−1
β = 93.830 (2)°T = 120 K
γ = 98.497 (2)°Plate, colourless
V = 2084.41 (9) Å30.42 × 0.05 × 0.03 mm
Data collection top
Bruker–Nonius Roper CCD camera on κ-goniostat
diffractometer		9543 independent reflections
Radiation source: Bruker–Nonius FR591 rotating anode6505 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.085
Detector resolution: 9.091 pixels mm-1θmax = 27.6°, θmin = 2.9°
φ & ω scansh = −12→13
Absorption correction: multi-scan
(SADABS;Sheldrick, 2007)		k = −18→19
Tmin = 0.849, Tmax = 1.000l = −19→19
42885 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.074Hydrogen site location: mixed
wR(F2) = 0.180H atoms treated by a mixture of independent and constrained refinement
S = 1.04 w = 1/[σ2(Fo2) + (0.0525P)2 + 4.9226P]
where P = (Fo2 + 2Fc2)/3
9543 reflections(Δ/σ)max < 0.001
590 parametersΔρmax = 0.60 e Å−3
7 restraintsΔρmin = −0.58 e Å−3
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.

Refinement. Owing to poor agreement, possibly to interference from the beam-stop, one reflection, i.e. (0 -1 2), was omitted from the final cycles of refinement.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
F10.2808 (2)0.67260 (18)0.16134 (18)0.0504 (7)
F20.2712 (2)0.65790 (19)0.01402 (19)0.0506 (7)
F30.2412 (2)0.53596 (15)0.07419 (19)0.0430 (6)
F4−0.1087 (2)0.38548 (14)0.16771 (16)0.0344 (5)
F5−0.03229 (19)0.48942 (14)0.29119 (15)0.0319 (5)
F6−0.2296 (2)0.40671 (14)0.28320 (16)0.0364 (5)
O1−0.0896 (2)0.82971 (15)−0.04003 (16)0.0212 (5)
H1O−0.061 (4)0.869 (2)0.0096 (16)0.032*
N1−0.0028 (2)0.57189 (18)0.12924 (19)0.0207 (6)
N2−0.3489 (3)0.78367 (18)−0.13680 (19)0.0190 (5)
H1N−0.289 (3)0.8273 (18)−0.152 (2)0.023*
H2N−0.390 (3)0.811 (2)−0.0906 (17)0.023*
C10.0642 (3)0.6271 (2)0.0803 (2)0.0198 (6)
C20.0089 (3)0.6897 (2)0.0331 (2)0.0190 (6)
H20.06310.7264−0.00190.023*
C3−0.1251 (3)0.6968 (2)0.0384 (2)0.0188 (6)
C4−0.2021 (3)0.6417 (2)0.0930 (2)0.0181 (6)
C5−0.3393 (3)0.6472 (2)0.1083 (2)0.0223 (7)
H5−0.38520.68850.07990.027*
C6−0.4056 (3)0.5940 (2)0.1630 (2)0.0237 (7)
H6−0.49710.59890.17280.028*
C7−0.3403 (3)0.5318 (2)0.2053 (3)0.0260 (7)
H7−0.38810.49520.24350.031*
C8−0.2090 (3)0.5233 (2)0.1922 (2)0.0217 (7)
C9−0.1351 (3)0.5793 (2)0.1366 (2)0.0195 (6)
C100.2142 (3)0.6225 (2)0.0822 (2)0.0244 (7)
C11−0.1435 (3)0.4521 (2)0.2331 (3)0.0259 (7)
C12−0.1883 (3)0.7644 (2)−0.0125 (2)0.0184 (6)
H12−0.24410.80000.03090.022*
C13−0.2802 (3)0.7122 (2)−0.1001 (2)0.0176 (6)
H13−0.35060.6652−0.08150.021*
C14−0.4440 (3)0.7429 (2)−0.2226 (2)0.0263 (7)
H14A−0.48160.7940−0.24570.032*
H14B−0.52020.6991−0.20710.032*
C15−0.3715 (4)0.6904 (3)−0.2983 (2)0.0295 (8)
H15A−0.30330.7359−0.31960.035*
H15B−0.43760.6596−0.35240.035*
C16−0.3015 (3)0.6160 (2)−0.2630 (2)0.0262 (7)
H16A−0.37040.5665−0.24840.031*
H16B−0.25010.5861−0.31230.031*
C17−0.2054 (3)0.6606 (2)−0.1756 (2)0.0201 (6)
H17A−0.16490.6110−0.15170.024*
H17B−0.13120.7056−0.19180.024*
F7−0.6032 (3)0.6297 (2)0.3672 (3)0.0874 (12)
F8−0.6420 (2)0.7695 (2)0.3979 (2)0.0572 (8)
F9−0.5432 (2)0.7145 (2)0.50201 (19)0.0670 (9)
F10−0.1334 (2)0.67918 (15)0.55849 (15)0.0343 (5)
F11−0.1959 (2)0.55632 (14)0.44945 (16)0.0371 (5)
F120.0147 (2)0.60063 (14)0.49868 (15)0.0332 (5)
O2−0.4008 (2)0.92583 (16)0.18909 (16)0.0236 (5)
H2O−0.424 (4)0.897 (2)0.1338 (12)0.035*
N3−0.3160 (3)0.71100 (19)0.4089 (2)0.0229 (6)
N4−0.1656 (3)1.06682 (18)0.20532 (19)0.0186 (5)
H3N−0.240 (2)1.071 (2)0.172 (2)0.022*
H4N−0.114 (3)1.036 (2)0.168 (2)0.022*
C18−0.4157 (3)0.7498 (2)0.3795 (2)0.0239 (7)
C19−0.4077 (3)0.8153 (2)0.3206 (2)0.0221 (7)
H19−0.48480.84130.30360.027*
C20−0.2853 (3)0.8408 (2)0.2883 (2)0.0188 (6)
C21−0.1731 (3)0.7995 (2)0.3149 (2)0.0188 (6)
C22−0.0438 (3)0.8172 (2)0.2819 (2)0.0191 (6)
H22−0.02870.85940.24020.023*
C230.0591 (3)0.7740 (2)0.3097 (2)0.0229 (7)
H230.14480.78580.28640.027*
C240.0399 (3)0.7124 (2)0.3722 (2)0.0224 (7)
H240.11260.68310.39070.027*
C25−0.0821 (3)0.6942 (2)0.4067 (2)0.0223 (7)
C26−0.1939 (3)0.7360 (2)0.3771 (2)0.0191 (6)
C27−0.5505 (3)0.7155 (3)0.4130 (3)0.0339 (8)
C28−0.1002 (3)0.6326 (2)0.4778 (2)0.0259 (7)
C29−0.2730 (3)0.9119 (2)0.2244 (2)0.0182 (6)
H29−0.22210.88820.17100.022*
C30−0.1964 (3)1.0076 (2)0.2770 (2)0.0187 (6)
H30−0.10910.99780.30760.022*
C31−0.0944 (3)1.1651 (2)0.2457 (2)0.0243 (7)
H31A−0.08411.20150.19530.029*
H31B−0.00291.16280.27390.029*
C32−0.1729 (3)1.2135 (2)0.3186 (3)0.0291 (8)
H32A−0.26111.22130.28910.035*
H32B−0.12231.27680.34670.035*
C33−0.1966 (4)1.1559 (2)0.3949 (3)0.0309 (8)
H33A−0.10871.15050.42650.037*
H33B−0.24941.18800.44200.037*
C34−0.2739 (3)1.0578 (2)0.3511 (2)0.0253 (7)
H34A−0.28801.02020.40020.030*
H34B−0.36381.06340.32260.030*
O30.3721 (2)0.87780 (16)−0.09688 (16)0.0245 (5)
O40.5232 (2)0.85378 (16)0.00986 (16)0.0246 (5)
O50.1931 (2)1.05633 (15)0.18195 (15)0.0217 (5)
O60.0086 (2)0.96016 (15)0.10987 (16)0.0215 (5)
C350.4142 (3)0.8829 (2)−0.0146 (2)0.0194 (6)
C360.3374 (3)0.9243 (2)0.0649 (2)0.0212 (6)
H36A0.30960.87520.10110.025*
H36B0.39930.97620.10720.025*
C370.2127 (3)0.9620 (2)0.0338 (2)0.0188 (6)
H37A0.24071.01500.00240.023*
H37B0.15350.9118−0.01230.023*
C380.1328 (3)0.9955 (2)0.1142 (2)0.0176 (6)
O70.1253 (3)1.0539 (3)0.3588 (2)0.0587 (9)
H7O0.147 (6)1.052 (4)0.3036 (17)0.088*
C390.2349 (6)1.0663 (5)0.4209 (4)0.083 (2)
H39A0.20251.04730.47800.100*
H39B0.26821.13490.43750.100*
C400.3465 (6)1.0231 (7)0.4013 (4)0.105 (3)
H40A0.32640.95690.40700.158*
H40B0.42421.05520.44560.158*
H40C0.36791.02650.33770.158*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0210 (11)0.0686 (16)0.0492 (15)0.0145 (10)−0.0092 (10)−0.0207 (13)
F20.0212 (11)0.0813 (18)0.0645 (17)0.0170 (11)0.0168 (10)0.0419 (15)
F30.0250 (11)0.0294 (11)0.0778 (18)0.0147 (9)0.0100 (11)0.0087 (11)
F40.0393 (12)0.0239 (10)0.0413 (13)0.0132 (8)0.0039 (9)0.0037 (9)
F50.0298 (11)0.0327 (11)0.0343 (12)0.0066 (8)−0.0040 (9)0.0112 (9)
F60.0360 (11)0.0318 (11)0.0482 (14)0.0061 (9)0.0097 (10)0.0225 (10)
O10.0189 (11)0.0214 (11)0.0216 (13)0.0002 (8)−0.0014 (9)0.0033 (9)
N10.0161 (12)0.0221 (13)0.0230 (15)0.0049 (10)−0.0009 (10)0.0016 (11)
N20.0162 (13)0.0197 (13)0.0201 (15)0.0033 (10)−0.0002 (10)0.0017 (11)
C10.0158 (14)0.0208 (15)0.0208 (17)0.0049 (11)−0.0011 (12)−0.0011 (13)
C20.0147 (14)0.0213 (15)0.0200 (17)0.0024 (11)0.0014 (11)0.0027 (13)
C30.0202 (15)0.0163 (14)0.0193 (17)0.0047 (11)−0.0001 (12)0.0017 (12)
C40.0139 (14)0.0192 (15)0.0195 (17)0.0027 (11)−0.0001 (11)0.0002 (12)
C50.0183 (15)0.0226 (16)0.0259 (18)0.0063 (12)0.0009 (12)0.0025 (14)
C60.0125 (14)0.0267 (16)0.0312 (19)0.0030 (12)0.0026 (12)0.0043 (14)
C70.0192 (16)0.0276 (17)0.032 (2)0.0017 (13)0.0030 (13)0.0078 (15)
C80.0211 (15)0.0187 (15)0.0241 (18)0.0036 (12)−0.0007 (12)0.0021 (13)
C90.0189 (15)0.0173 (14)0.0216 (17)0.0049 (11)0.0002 (12)0.0010 (12)
C100.0178 (15)0.0251 (16)0.0297 (19)0.0058 (12)−0.0008 (13)0.0036 (14)
C110.0230 (16)0.0239 (16)0.031 (2)0.0034 (13)0.0022 (14)0.0075 (15)
C120.0127 (14)0.0198 (15)0.0229 (17)0.0040 (11)0.0000 (11)0.0047 (13)
C130.0156 (14)0.0219 (15)0.0165 (16)0.0045 (11)0.0022 (11)0.0052 (12)
C140.0243 (16)0.0326 (18)0.0203 (18)0.0088 (13)−0.0045 (13)0.0002 (14)
C150.0336 (19)0.0365 (19)0.0172 (18)0.0116 (15)−0.0039 (14)0.0003 (15)
C160.0264 (17)0.0268 (17)0.0230 (19)0.0041 (13)0.0033 (13)−0.0013 (14)
C170.0205 (15)0.0176 (15)0.0228 (18)0.0039 (11)0.0038 (12)0.0045 (13)
F70.0547 (18)0.0618 (19)0.127 (3)−0.0282 (14)0.0462 (19)−0.0129 (19)
F80.0204 (11)0.098 (2)0.0746 (19)0.0233 (12)0.0199 (11)0.0562 (17)
F90.0271 (12)0.144 (3)0.0493 (17)0.0202 (14)0.0152 (11)0.0595 (19)
F100.0382 (12)0.0429 (12)0.0272 (12)0.0135 (9)0.0061 (9)0.0139 (10)
F110.0348 (12)0.0283 (11)0.0494 (14)−0.0020 (9)0.0005 (10)0.0177 (10)
F120.0325 (11)0.0342 (11)0.0385 (13)0.0146 (9)−0.0008 (9)0.0159 (10)
O20.0196 (11)0.0317 (13)0.0199 (13)0.0086 (9)−0.0029 (9)0.0047 (10)
N30.0180 (13)0.0271 (14)0.0257 (16)0.0047 (10)0.0039 (11)0.0090 (12)
N40.0184 (13)0.0221 (13)0.0167 (14)0.0072 (10)0.0028 (10)0.0046 (11)
C180.0174 (15)0.0301 (17)0.0241 (18)0.0027 (12)0.0015 (12)0.0058 (14)
C190.0144 (14)0.0258 (16)0.0272 (19)0.0059 (12)0.0034 (12)0.0053 (14)
C200.0171 (14)0.0190 (15)0.0186 (17)0.0019 (11)−0.0005 (11)0.0006 (12)
C210.0143 (14)0.0207 (15)0.0198 (17)0.0015 (11)−0.0004 (11)0.0021 (13)
C220.0184 (15)0.0215 (15)0.0172 (16)0.0033 (11)0.0008 (11)0.0034 (12)
C230.0138 (14)0.0256 (16)0.0281 (19)0.0037 (12)0.0014 (12)0.0024 (14)
C240.0211 (15)0.0201 (15)0.0252 (18)0.0057 (12)−0.0020 (12)0.0023 (13)
C250.0219 (15)0.0207 (15)0.0232 (18)0.0026 (12)−0.0024 (12)0.0041 (13)
C260.0187 (15)0.0184 (14)0.0185 (17)0.0024 (11)−0.0009 (12)0.0007 (12)
C270.0206 (17)0.044 (2)0.039 (2)0.0029 (15)0.0051 (15)0.0150 (18)
C280.0248 (17)0.0272 (17)0.0271 (19)0.0069 (13)0.0003 (13)0.0079 (15)
C290.0141 (14)0.0211 (15)0.0196 (17)0.0051 (11)0.0009 (11)0.0030 (13)
C300.0179 (14)0.0226 (15)0.0160 (16)0.0057 (11)0.0026 (11)0.0026 (12)
C310.0212 (16)0.0232 (16)0.0284 (19)0.0010 (12)−0.0007 (13)0.0080 (14)
C320.0265 (17)0.0225 (16)0.036 (2)0.0081 (13)−0.0040 (14)−0.0009 (15)
C330.040 (2)0.0285 (18)0.0228 (19)0.0104 (15)0.0041 (15)−0.0023 (15)
C340.0284 (17)0.0270 (17)0.0219 (18)0.0071 (13)0.0099 (13)0.0041 (14)
O30.0218 (11)0.0347 (13)0.0185 (13)0.0113 (9)0.0004 (9)0.0046 (10)
O40.0181 (11)0.0343 (13)0.0224 (13)0.0115 (9)−0.0002 (9)0.0033 (10)
O50.0206 (11)0.0249 (11)0.0186 (12)0.0031 (9)0.0006 (9)0.0023 (9)
O60.0150 (10)0.0225 (11)0.0261 (13)0.0024 (8)0.0035 (9)0.0027 (9)
C350.0149 (14)0.0185 (15)0.0261 (18)0.0035 (11)0.0024 (12)0.0071 (13)
C360.0194 (15)0.0266 (16)0.0194 (17)0.0082 (12)0.0030 (12)0.0056 (13)
C370.0146 (14)0.0222 (15)0.0193 (17)0.0042 (11)0.0012 (11)0.0028 (13)
C380.0170 (14)0.0190 (15)0.0189 (17)0.0068 (11)0.0015 (11)0.0061 (12)
O70.0374 (16)0.111 (3)0.0352 (18)0.0244 (17)0.0060 (13)0.0237 (19)
C390.074 (4)0.136 (6)0.040 (3)0.053 (4)−0.015 (3)−0.004 (3)
C400.052 (3)0.220 (9)0.058 (4)0.060 (4)0.004 (3)0.036 (5)
Geometric parameters (Å, º) top
F1—C101.328 (4)N4—C311.502 (4)
F2—C101.333 (4)N4—C301.502 (4)
F3—C101.321 (4)N4—H3N0.882 (10)
F4—C111.338 (4)N4—H4N0.882 (10)
F5—C111.338 (4)C18—C191.403 (5)
F6—C111.352 (4)C18—C271.518 (5)
O1—C121.406 (4)C19—C201.373 (4)
O1—H1O0.840 (10)C19—H190.9500
N1—C11.319 (4)C20—C211.419 (4)
N1—C91.358 (4)C20—C291.522 (4)
N2—C131.495 (4)C21—C221.421 (4)
N2—C141.497 (4)C21—C261.423 (4)
N2—H1N0.880 (10)C22—C231.366 (4)
N2—H2N0.883 (10)C22—H220.9500
C1—C21.401 (4)C23—C241.404 (5)
C1—C101.517 (4)C23—H230.9500
C2—C31.370 (4)C24—C251.365 (5)
C2—H20.9500C24—H240.9500
C3—C41.425 (4)C25—C261.435 (4)
C3—C121.530 (4)C25—C281.504 (5)
C4—C51.422 (4)C29—C301.533 (4)
C4—C91.428 (4)C29—H291.0000
C5—C61.357 (5)C30—C341.519 (4)
C5—H50.9500C30—H301.0000
C6—C71.406 (5)C31—C321.504 (5)
C6—H60.9500C31—H31A0.9900
C7—C81.365 (4)C31—H31B0.9900
C7—H70.9500C32—C331.532 (5)
C8—C91.427 (4)C32—H32A0.9900
C8—C111.503 (4)C32—H32B0.9900
C12—C131.533 (4)C33—C341.529 (5)
C12—H121.0000C33—H33A0.9900
C13—C171.525 (4)C33—H33B0.9900
C13—H131.0000C34—H34A0.9900
C14—C151.519 (5)C34—H34B0.9900
C14—H14A0.9900O3—C351.236 (4)
C14—H14B0.9900O4—C351.285 (4)
C15—C161.529 (5)O5—C381.255 (4)
C15—H15A0.9900O6—C381.271 (4)
C15—H15B0.9900C35—C361.522 (4)
C16—C171.527 (5)C36—C371.517 (4)
C16—H16A0.9900C36—H36A0.9900
C16—H16B0.9900C36—H36B0.9900
C17—H17A0.9900C37—C381.517 (4)
C17—H17B0.9900C37—H37A0.9900
F7—C271.323 (5)C37—H37B0.9900
F8—C271.331 (4)O7—C391.347 (6)
F9—C271.304 (5)O7—H7O0.847 (10)
F10—C281.340 (4)C39—C401.388 (8)
F11—C281.341 (4)C39—H39A0.9900
F12—C281.346 (4)C39—H39B0.9900
O2—C291.409 (3)C40—H40A0.9800
O2—H2O0.841 (10)C40—H40B0.9800
N3—C181.309 (4)C40—H40C0.9800
N3—C261.363 (4)
C12—O1—H1O104 (3)C21—C20—C29121.6 (3)
C1—N1—C9116.7 (3)C22—C21—C20123.7 (3)
C13—N2—C14113.4 (2)C22—C21—C26119.0 (3)
C13—N2—H1N111 (2)C20—C21—C26117.3 (3)
C14—N2—H1N106 (2)C23—C22—C21120.4 (3)
C13—N2—H2N106 (2)C23—C22—H22119.8
C14—N2—H2N112 (2)C21—C22—H22119.8
H1N—N2—H2N108 (3)C22—C23—C24120.8 (3)
N1—C1—C2125.4 (3)C22—C23—H23119.6
N1—C1—C10114.3 (3)C24—C23—H23119.6
C2—C1—C10120.2 (3)C25—C24—C23120.8 (3)
C3—C2—C1118.6 (3)C25—C24—H24119.6
C3—C2—H2120.7C23—C24—H24119.6
C1—C2—H2120.7C24—C25—C26120.1 (3)
C2—C3—C4118.9 (3)C24—C25—C28120.7 (3)
C2—C3—C12119.8 (3)C26—C25—C28119.2 (3)
C4—C3—C12121.3 (3)N3—C26—C21123.3 (3)
C5—C4—C3124.0 (3)N3—C26—C25117.9 (3)
C5—C4—C9118.7 (3)C21—C26—C25118.8 (3)
C3—C4—C9117.3 (3)F9—C27—F7107.9 (3)
C6—C5—C4120.8 (3)F9—C27—F8106.4 (3)
C6—C5—H5119.6F7—C27—F8105.4 (3)
C4—C5—H5119.6F9—C27—C18113.5 (3)
C5—C6—C7120.7 (3)F7—C27—C18111.5 (3)
C5—C6—H6119.7F8—C27—C18111.6 (3)
C7—C6—H6119.7F10—C28—F11107.0 (3)
C8—C7—C6120.8 (3)F10—C28—F12106.1 (3)
C8—C7—H7119.6F11—C28—F12106.4 (3)
C6—C7—H7119.6F10—C28—C25112.0 (3)
C7—C8—C9120.1 (3)F11—C28—C25113.4 (3)
C7—C8—C11120.1 (3)F12—C28—C25111.4 (3)
C9—C8—C11119.7 (3)O2—C29—C20111.7 (2)
N1—C9—C8118.1 (3)O2—C29—C30107.7 (2)
N1—C9—C4123.0 (3)C20—C29—C30110.8 (3)
C8—C9—C4118.8 (3)O2—C29—H29108.9
F3—C10—F1107.1 (3)C20—C29—H29108.9
F3—C10—F2106.5 (3)C30—C29—H29108.9
F1—C10—F2105.9 (3)N4—C30—C34110.2 (2)
F3—C10—C1113.2 (3)N4—C30—C29106.9 (2)
F1—C10—C1111.1 (3)C34—C30—C29113.9 (3)
F2—C10—C1112.5 (3)N4—C30—H30108.6
F5—C11—F4107.0 (3)C34—C30—H30108.6
F5—C11—F6106.0 (3)C29—C30—H30108.6
F4—C11—F6106.2 (3)N4—C31—C32110.6 (3)
F5—C11—C8114.0 (3)N4—C31—H31A109.5
F4—C11—C8112.6 (3)C32—C31—H31A109.5
F6—C11—C8110.6 (3)N4—C31—H31B109.5
O1—C12—C3112.0 (2)C32—C31—H31B109.5
O1—C12—C13107.7 (2)H31A—C31—H31B108.1
C3—C12—C13112.0 (2)C31—C32—C33110.5 (3)
O1—C12—H12108.4C31—C32—H32A109.5
C3—C12—H12108.4C33—C32—H32A109.5
C13—C12—H12108.4C31—C32—H32B109.5
N2—C13—C17110.2 (2)C33—C32—H32B109.5
N2—C13—C12107.1 (2)H32A—C32—H32B108.1
C17—C13—C12113.9 (2)C34—C33—C32109.4 (3)
N2—C13—H13108.5C34—C33—H33A109.8
C17—C13—H13108.5C32—C33—H33A109.8
C12—C13—H13108.5C34—C33—H33B109.8
N2—C14—C15110.6 (3)C32—C33—H33B109.8
N2—C14—H14A109.5H33A—C33—H33B108.2
C15—C14—H14A109.5C30—C34—C33110.9 (3)
N2—C14—H14B109.5C30—C34—H34A109.5
C15—C14—H14B109.5C33—C34—H34A109.5
H14A—C14—H14B108.1C30—C34—H34B109.5
C14—C15—C16111.4 (3)C33—C34—H34B109.5
C14—C15—H15A109.4H34A—C34—H34B108.0
C16—C15—H15A109.4O3—C35—O4123.2 (3)
C14—C15—H15B109.4O3—C35—C36121.1 (3)
C16—C15—H15B109.4O4—C35—C36115.7 (3)
H15A—C15—H15B108.0C37—C36—C35114.3 (3)
C17—C16—C15110.5 (3)C37—C36—H36A108.7
C17—C16—H16A109.5C35—C36—H36A108.7
C15—C16—H16A109.5C37—C36—H36B108.7
C17—C16—H16B109.5C35—C36—H36B108.7
C15—C16—H16B109.5H36A—C36—H36B107.6
H16A—C16—H16B108.1C38—C37—C36112.7 (3)
C13—C17—C16110.9 (2)C38—C37—H37A109.1
C13—C17—H17A109.5C36—C37—H37A109.1
C16—C17—H17A109.5C38—C37—H37B109.1
C13—C17—H17B109.5C36—C37—H37B109.1
C16—C17—H17B109.5H37A—C37—H37B107.8
H17A—C17—H17B108.1O5—C38—O6123.4 (3)
C29—O2—H2O113 (3)O5—C38—C37118.3 (3)
C18—N3—C26116.1 (3)O6—C38—C37118.3 (3)
C31—N4—C30114.0 (2)C39—O7—H7O112 (4)
C31—N4—H3N108 (2)O7—C39—C40122.4 (5)
C30—N4—H3N111 (2)O7—C39—H39A106.7
C31—N4—H4N111 (2)C40—C39—H39A106.7
C30—N4—H4N105 (2)O7—C39—H39B106.7
H3N—N4—H4N108 (3)C40—C39—H39B106.7
N3—C18—C19126.2 (3)H39A—C39—H39B106.6
N3—C18—C27113.7 (3)C39—C40—H40A109.5
C19—C18—C27120.0 (3)C39—C40—H40B109.5
C20—C19—C18118.0 (3)H40A—C40—H40B109.5
C20—C19—H19121.0C39—C40—H40C109.5
C18—C19—H19121.0H40A—C40—H40C109.5
C19—C20—C21119.0 (3)H40B—C40—H40C109.5
C19—C20—C29119.4 (3)
C9—N1—C1—C2−2.4 (5)C27—C18—C19—C20−176.8 (3)
C9—N1—C1—C10174.4 (3)C18—C19—C20—C210.5 (5)
N1—C1—C2—C31.3 (5)C18—C19—C20—C29−179.9 (3)
C10—C1—C2—C3−175.4 (3)C19—C20—C21—C22176.8 (3)
C1—C2—C3—C41.1 (4)C29—C20—C21—C22−2.9 (5)
C1—C2—C3—C12−179.9 (3)C19—C20—C21—C26−2.2 (4)
C2—C3—C4—C5176.1 (3)C29—C20—C21—C26178.1 (3)
C12—C3—C4—C5−2.8 (5)C20—C21—C22—C23−179.1 (3)
C2—C3—C4—C9−2.1 (4)C26—C21—C22—C23−0.2 (5)
C12—C3—C4—C9178.9 (3)C21—C22—C23—C24−0.9 (5)
C3—C4—C5—C6−178.4 (3)C22—C23—C24—C250.1 (5)
C9—C4—C5—C6−0.2 (5)C23—C24—C25—C261.8 (5)
C4—C5—C6—C7−0.4 (5)C23—C24—C25—C28−176.5 (3)
C5—C6—C7—C8−0.1 (5)C18—N3—C26—C21−0.7 (5)
C6—C7—C8—C91.3 (5)C18—N3—C26—C25−179.2 (3)
C6—C7—C8—C11−176.2 (3)C22—C21—C26—N3−176.6 (3)
C1—N1—C9—C8−177.5 (3)C20—C21—C26—N32.4 (5)
C1—N1—C9—C41.2 (5)C22—C21—C26—C251.9 (4)
C7—C8—C9—N1176.8 (3)C20—C21—C26—C25−179.0 (3)
C11—C8—C9—N1−5.6 (5)C24—C25—C26—N3175.9 (3)
C7—C8—C9—C4−2.0 (5)C28—C25—C26—N3−5.8 (4)
C11—C8—C9—C4175.6 (3)C24—C25—C26—C21−2.7 (5)
C5—C4—C9—N1−177.3 (3)C28—C25—C26—C21175.5 (3)
C3—C4—C9—N11.0 (5)N3—C18—C27—F947.0 (5)
C5—C4—C9—C81.4 (4)C19—C18—C27—F9−134.4 (4)
C3—C4—C9—C8179.7 (3)N3—C18—C27—F7−75.0 (4)
N1—C1—C10—F342.1 (4)C19—C18—C27—F7103.5 (4)
C2—C1—C10—F3−140.9 (3)N3—C18—C27—F8167.3 (3)
N1—C1—C10—F1−78.4 (4)C19—C18—C27—F8−14.2 (5)
C2—C1—C10—F198.6 (4)C24—C25—C28—F10118.1 (3)
N1—C1—C10—F2163.0 (3)C26—C25—C28—F10−60.2 (4)
C2—C1—C10—F2−20.0 (4)C24—C25—C28—F11−120.7 (3)
C7—C8—C11—F5−121.8 (3)C26—C25—C28—F1161.1 (4)
C9—C8—C11—F560.6 (4)C24—C25—C28—F12−0.6 (4)
C7—C8—C11—F4116.1 (3)C26—C25—C28—F12−178.9 (3)
C9—C8—C11—F4−61.5 (4)C19—C20—C29—O2−14.1 (4)
C7—C8—C11—F6−2.5 (5)C21—C20—C29—O2165.5 (3)
C9—C8—C11—F6179.9 (3)C19—C20—C29—C30105.9 (3)
C2—C3—C12—O1−15.4 (4)C21—C20—C29—C30−74.4 (4)
C4—C3—C12—O1163.5 (3)C31—N4—C30—C3453.7 (3)
C2—C3—C12—C13105.7 (3)C31—N4—C30—C29177.9 (2)
C4—C3—C12—C13−75.4 (4)O2—C29—C30—N4−68.4 (3)
C14—N2—C13—C1756.2 (3)C20—C29—C30—N4169.2 (2)
C14—N2—C13—C12−179.4 (2)O2—C29—C30—C3453.6 (3)
O1—C12—C13—N2−63.4 (3)C20—C29—C30—C34−68.9 (3)
C3—C12—C13—N2173.1 (2)C30—N4—C31—C32−54.6 (3)
O1—C12—C13—C1758.7 (3)N4—C31—C32—C3356.3 (4)
C3—C12—C13—C17−64.8 (3)C31—C32—C33—C34−58.7 (4)
C13—N2—C14—C15−55.5 (4)N4—C30—C34—C33−55.2 (4)
N2—C14—C15—C1654.4 (4)C29—C30—C34—C33−175.3 (3)
C14—C15—C16—C17−55.4 (4)C32—C33—C34—C3058.3 (4)
N2—C13—C17—C16−55.8 (3)O3—C35—C36—C37−3.0 (4)
C12—C13—C17—C16−176.1 (3)O4—C35—C36—C37177.4 (3)
C15—C16—C17—C1356.0 (3)C35—C36—C37—C38175.4 (3)
C26—N3—C18—C19−1.4 (5)C36—C37—C38—O555.5 (4)
C26—N3—C18—C27177.0 (3)C36—C37—C38—O6−124.1 (3)
N3—C18—C19—C201.5 (5)
Hydrogen-bond geometry (Å, º) top
Cg1 is the centroid of the (N1,C1–C4,C9) ring.
D—H···AD—HH···AD···AD—H···A
N2—H1N···O10.88 (3)2.49 (3)2.806 (4)102 (2)
N4—H3N···O20.88 (2)2.54 (3)2.863 (4)103 (2)
O1—H1O···O60.84 (3)1.81 (3)2.653 (3)175 (2)
O2—H2O···O4i0.84 (2)1.82 (2)2.656 (3)170 (3)
N2—H1N···O5ii0.88 (3)1.97 (3)2.830 (4)165 (3)
N2—H2N···O4i0.88 (3)1.82 (3)2.694 (4)173 (3)
N4—H3N···O3ii0.88 (2)1.99 (3)2.832 (4)161 (3)
N4—H4N···O60.89 (3)1.92 (3)2.789 (4)168 (3)
O7—H7O···O50.85 (3)1.88 (3)2.729 (4)176 (7)
C30—H30···O71.002.403.296 (4)149
C10—F3···Cg1iii1.32 (1)3.28 (1)4.101 (3)120 (1)
Symmetry codes: (i) x−1, y, z; (ii) −x, −y+2, −z; (iii) −x, −y+1, −z.
Summary of short interatomic contacts (Å) in (I)a top
ContactDistanceSymmetry operation
F1···H62.501 + x, y, z
F6···C323.096 (4)x, -1 + y, z
O1···H37B2.45x, y, z
O1···C383.038 (4)-x, -y, -1 - z
O2···H36B2.50-1 + x, y, z
O2···C363.090 (4)-1 + x, y, z
O4···H122.531 + x, y, z
O6···H222.50x, y, z
O7···H31B2.55x, y, z
H1O···H37B2.14x, y, z
H12···H292.06x, y, z
H34A···H39A2.22-x, 2 - y, -z
Notes: (a) The interatomic distances are calculated in Crystal Explorer (Turner et al., 2017) whereby the X—H bond lengths are adjusted to their neutron values.
Percentage contributions of interatomic contacts to the Hirshfeld surface for (I) top
ContactPercentage contribution
H···H29.8
O···H/H···O14.0
F···H/H···F41.2
F···F5.7
C···H/H···C4.1
C···F/F···C2.8
N···H/H···N1.0
C···N/N···C0.5
C···O/O···C0.3
O···O0.2
F···N/N···F0.2
C···C0.2
F···O/O···F0.1
 

Footnotes

‡Additional correspondence author, e-mail: j.wardell@abdn.ac.uk.

Acknowledgements

The use of the EPSRC X-ray crystallographic service at the University of Southampton, England, and the valuable assistance of the staff there is gratefully acknowledged. JLW acknowledges support from CNPq (Brazil).

Funding information

Sunway University Sdn Bhd (grant. No. STR-RCTR-RCCM-001–2019) is thanked for financial support of this work.

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ISSN: 2056-9890
Volume 75| Part 8| August 2019| Pages 1162-1168
https://doi.org/10.1107/S2056989019009654
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