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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

Synthesis and structure of clozapine N-oxide hemi(hydro­chloride): an infinite hydrogen-bonded poly[n]catenane

crossmark logo

aSchool of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, 3010, Australia, bAdvanced Molecular Technologies, Unit 1, 7-11 Rocco Drive, Scoresby, Victoria, 3179, Australia, and cBruker AXS GmbH, Oestliche Rheinbrueckenstr. 49, 76187 Karlsruhe, Germany
*Correspondence e-mail: whitejm@unimelb.edu.au

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 19 September 2022; accepted 21 September 2022; online 27 September 2022)

The structure of the title compound, 2C18H19ClN4O·HCl or (CNO)2·HCl (C36H39Cl3N8O2), at 100 K has tetra­gonal (I4/m) symmetry. The dihedral angle between the benzene rings of the fused ring system of the CNO mol­ecule is 40.08 (6)° and the equivalent angle between the seven-membered ring and its pendant N-oxide ring is 31.14 (7)°. The structure contains a very strong, symmetrical O—H⋯O hydrogen bond [O⋯O = 2.434 (2) Å] between two equivalent R3N+—O moieties, which share a proton lying on a crystallographic twofold rotation axis. These units then form a (CNO)4·(HCl)2 ring by way of two equivalent N—H⋯Cl hydrogen bonds (Cl site symmetry m). These rings are catenated into infinite chains propagating along the c-axis direction by way of shape complementarity and directional C—H⋯N and C—H⋯π inter­actions.

1. Chemical context

Coordination-driven self-assembly of supra­molecular structures is a major focus area of materials science. However, hydrogen-bond-driven self-assembly has been less well studied, most likely as a consequence of the weakness of hydrogen bonding relative to coordinate bonding. Nevertheless, the directionality of hydrogen bonding can lend it to the controllable formation of supra­molecular networks (González-Rodríguez & Schenning, 2011[González-Rodríguez, D. & Schenning, A. P. H. J. (2011). Chem. Mater. 23, 310-325.]; Steiner, 2002[Steiner, T. (2002). Angew. Chem. Int. Ed. 41, 48-76.]; Prins et al., 2001[Prins, L. J., Reinhoudt, D. N. & Timmerman, P. (2001). Angew. Chem. Int. Ed. 40, 2382-2426.]). The simplest infinite inter­locking systems are the one-dimensional polycatenanes (poly[n]catenanes). Such systems have been described involving inter­penetrating metallocycles of silver/bis­(2-methyl­imidazol­yl) (Jin et al., 2006[Jin, C. M., Lu, H., Wu, L. Y. & Huang, J. (2006). Chem. Commun. pp. 5039-5041.], 2008[Jin, C.-M., Wu, L.-Y., Lu, H. & Xu, Y. (2008). Cryst. Growth Des. 8, 215-218.], 2018[Jin, T., Zhou, J., Pan, Y., Huang, Y. & Jin, C. (2018). J. Mol. Struct. 1160, 222-226.]) and mercury/1,2-bis­[(pyridin-4-yl­thio)­meth­yl]benzene (Xue et al., 2015[Xue, H., Jiang, F., Chen, Q., Yuan, D., Pang, J., Lv, G., Wan, X., Liang, L. & Hong, M. (2015). Chem. Commun. 51, 13706-13709.]). However, the lack of many examples beyond these suggests that the self-assembly of this inter­esting topological architecture is not easily achieved. Here, we report the serendipitous discovery of an infinite one-dimensional polycatenane architecture templated by a chloride anion that forms upon the attempted recrystallization of clozapine N-oxide (C18H19ClN4O; hereafter CNO) mono-hydro­chloride, an inactive metabolite of clozapine that is utilized as an actuator of engineered muscarinic acetyl­choline receptors (Armbruster et al., 2007[Armbruster, B. N., Li, X., Pausch, M. H., Herlitze, S. & Roth, B. L. (2007). Proc. Natl Acad. Sci. USA, 104, 5163-5168.]; Urban & Roth, 2015[Urban, D. J. & Roth, B. L. (2015). Annu. Rev. Pharmacol. Toxicol. 55, 399-417.]; Dong et al., 2010[Dong, S., Allen, J. A., Farrell, M. & Roth, B. L. (2010). Mol. BioSyst. 6, 1376-1380.]; Gomez et al., 2017[Gomez, J. L., Bonaventura, J., Lesniak, W., Mathews, W. B., Sysa-Shah, P., Rodriguez, L. A., Ellis, R. J., Richie, C. T., Harvey, B. K., Dannals, R. F., Pomper, M. G., Bonci, A. & Michaelides, M. (2017). Science, 357, 503-507.]).

As part of efforts to develop a water-soluble salt form of CNO (van der Peet et al., 2018[Peet, P. L. van der, Gunawan, C., Abdul-Ridha, A., Ma, S., Scott, D. J., Gundlach, A. L., Bathgate, R. A. D., White, J. M. & Williams, S. J. (2018). MethodsX, 5, 257-267.]) we synthesized CNO·HBr and CNO·HCl by formation of the salt in methanol (Scheme 1).

[Scheme 1]

The latter compound has been reported previously (Allen et al., 2019[Allen, D. C., Carlson, T. L., Xiong, Y., Jin, J., Grant, K. A. & Cuzon Carlson, V. C. (2019). J. Pharmacol. Exp. Ther. 368, 199-207.]), but its preparation was not described. Elemental analysis of the precipitated CNO·HCl was consistent with the proposed structure in Scheme 1. Although crystals suitable for single crystal X-ray analysis were not obtained from the crude precipitate, powder X-ray diffraction of the precipitate suggested the material was substanti­ally crystalline. To obtain structural verification and to locate the site of protonation, we attempted to grow single crystals of CNO·HCl for single crystal X-ray analysis. Slow evaporation of a solution of CNO·HCl from a variety of solvents, or by diffusion of diethyl ether into a variety of solvents consistently yielded small orange block-shaped crystals of the title hemi­hydro­chloride, which were found to be no longer soluble in water or other solvents (Scheme 2).

[Scheme 2]

2. Structural commentary

Single-crystal X-ray diffraction analysis of the orange crystals revealed that the CNO·HCl salt implied by the analysis for the initially formed salt (above) had lost half an equivalent of HCl upon crystallization and crystallized as a hemi­hydro­chloride, (CNO)2·HCl, in the tetra­gonal space group I4/m (Scheme 2 and Fig. 1[link]). In this structure, two mol­ecules of CNO, which are related by a crystallographic twofold axis, share a proton, which is located on the rotation axis and forms a strong, essentially linear and apparently symmetric O—H⋯O/O⋯H—O hydrogen bond between the two mol­ecules via the N-oxide moieties [O1⋯O1i = 2.434 (2) Å; symmetry code (i) −x, 1 − y, z]. Within the structure, the chloride counter-ion (Cl2) is located on a crystallographic mirror plane and accepts equivalent N—H⋯Cl hydrogen bonds [N1⋯Cl2 = 3.3259 (14) Å] to two mirror-related (CNO)2H+ moieties resulting in the formation of a cyclic structure templated by the Cl counter-ions (Fig. 2[link]). The diazepine ring core in (CNO)2·HCl adopts a boat conformation (Table 1[link]) in which the N1(H) group is at the bow and the C7=N2 imine group is the stern. A consequence of the boat conformation is the mean planes of the two fused benzene rings lie at an angle 40.08 (6)° to one another; this represents a less puckered ring to that observed in the (CNO)·MeOH solvate in which the aromatic rings are at an angle of 56.2° (van der Peet et al., 2018[Peet, P. L. van der, Gunawan, C., Abdul-Ridha, A., Ma, S., Scott, D. J., Gundlach, A. L., Bathgate, R. A. D., White, J. M. & Williams, S. J. (2018). MethodsX, 5, 257-267.]) demonstrating the flexibility of this ring system. The equivalent angle between the seven-membered diazepine ring and its pendant N-oxide ring is 31.14 (7)°

Table 1
Selected torsion angles (°)

C8—N1—C1—C2 55.7 (2) C7—N2—C9—C8 33.5 (2)
C9—N2—C7—C2 3.2 (2) C1—N1—C8—C9 −54.0 (2)
N1—C1—C2—C7 0.9 (2) N2—C9—C8—N1 −4.9 (2)
N2—C7—C2—C1 −35.2 (2)    
[Figure 1]
Figure 1
The mol­ecular structure of (CNO)2·HCl showing 50% displacement ellipsoids with C-bound H atoms omitted for clarity. The unlabelled atoms are generated by the symmetry operationx, 1 − y, z.
[Figure 2]
Figure 2
The cyclic tetra­mer (CNO)4·(HCl)2 templated by N—H⋯Cl hydrogen-bonding inter­actions.

3. Supra­molecular features

The tetra­meric cyclic structures are catenated and form infinite chains extending along the z-direction (Figs. 3[link] and 4[link]) in which adjacent links in the chain are related by a 42 screw axis. The catenated rings form both as a result of general complementarity in the shapes of the inter­nal cavities of the inter­acting (CNO)2 dimers related by the symmetry operation ([{1\over 2}] − y, [{1\over 2}] + x, [{1\over 2}] − z), and further stabilized by four equivalent non-classical hydrogen-bonding inter­actions involving the polarized C—H bond adjacent to the N-oxide moiety; (C15—H15A⋯N1, Table 2[link]) in addition to four equivalent C—H⋯π inter­actions [H15A⋯C8 = 2.706 (2) Å] (Fig. 5[link]). Solvent voids, which account for approximately 17% of the unit-cell volume, lie between the catenated chains: the disordered solvent was accounted for using the Squeeze procedure in PLATON (Spek, 2015[Spek, A. L. (2015). Acta Cryst. C71, 9-18.]). To establish the relationship between the original material and that obtained after crystallization, powder X-ray diffraction data were obtained for the orange crystals and compared to that for the original material (Fig. 6[link]). The two powder diffraction patterns are substanti­ally different, which is consistent with the combustion analysis of the original material that analysed as (CNO)·HCl, whereas the crystallized material is (CNO)2·HCl. Application of the same approach to CNO·HBr did not lead to an equivalent polymeric material.

Table 2
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O1—H1A⋯O1i 1.22 (1) 1.22 (1) 2.434 (2) 179 (4)
N1—H1⋯Cl2 0.86 (2) 2.46 (2) 3.3259 (14) 176 (2)
C15—H15A⋯O1i 0.97 2.64 3.2598 (19) 122
C15—H15A⋯N1ii 0.97 2.51 3.416 (2) 156
C15—H15B⋯Cl1iii 0.97 2.91 3.8431 (17) 162
Symmetry codes: (i) [-x, -y+1, z]; (ii) [-y+{\script{1\over 2}}, x+{\script{1\over 2}}, -z+{\script{1\over 2}}]; (iii) [-x+{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+{\script{1\over 2}}].
[Figure 3]
Figure 3
Partial structure of (CNO)2·HCl catenated chain showing two members of the poly[n]catenane; adjacent links in the chain are related by a 42 screw axis.
[Figure 4]
Figure 4
Partial structure of (CNO)2·HCl catenated chain showing three members of the poly[n]catenane; adjacent links in the chain are related by a 42 screw axis.
[Figure 5]
Figure 5
C—H⋯N and C—H⋯π inter­actions at the inter­face of neighbouring tetra­meric (CNO)4·(HCl) rings in the poly[n]catenane.
[Figure 6]
Figure 6
Overlay of powder patterns of the initial precipitate of (CNO)·HCl and the recrystallized material (CNO)2·HCl.

4. Database survey

The formation of strong hydrogen bonds is predicted to occur when the pKa value for the donor acid matches that for the acceptor's conjugate acid form (Gilli et al., 2009[Gilli, P., Pretto, V., Bertolasi, V. & Gilli, G. (2009). Acc. Chem. Res. 42, 33-44.]). In this structure, a strong hydrogen bond between a protonated tertiary amine N-oxide and its conjugate base is predicted. A search of the Cambridge Structural Database (2022.2.0, September 2022; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) for structures containing the R3N—OH⋯O—NR3 moiety with constraints on the R factor to 5% or less and only organic structures surveyed gave eight good-quality structures (CSD refcodes: RAJDAL (Bettencourt et al., 2021[Bettencourt, C. J., Chow, S., Moore, P. W., Read, C. D. G., Jiao, Y., Bakker, J. P., Zhao, S., Bernhardt, P. V. & Williams, C. M. (2021). Aust. J. Chem. 74, 652-659.]), AJESEQ (Wlaźlak et al., 2018[Wlaźlak, E., Kalinowska-Tłuścik, J., Nitek, W., Klejna, S., Mech, K., Macyk, W. & Szaciłowski, K. (2018). ChemElectroChem, 5, 3486-3497.]), AREREW (Moore et al., 2016[Moore, P. W., Jiao, Y., Mirzayans, P. M., Sheng, L. N. Q., Hooker, J. P. & Williams, C. M. (2016). Eur. J. Org. Chem. pp. 3401-3407.]), BAYDEK (Jaskólski et al., 1982[Jaskólski, M., Olovsson, I., Tellgren, R. & Mickiewicz-Wichłacz, D. (1982). Acta Cryst. B38, 291-294.]), EPSPOX (Małuszyńska & Okaya, 1977[Małuszyńska, H. & Okaya, Y. (1977). Acta Cryst. B33, 3049-3054.]), FUBMAS (Moore et al., 2015[Moore, P. W., Mirzayans, P. M. & Williams, C. M. (2015). Chem. Eur. J. 21, 3567-3571.]), NUCDUK (Krzywda et al., 1996[Krzywda, S., Jaskólski, M., Gdaniec, M., Dega-Szafran, Z., Grundwald-Wyspiańska, M., Szafran, M., Dauter, Z. & Davies, G. (1996). J. Mol. Struct. 375, 197-206.]) and OBECUV (Bohmer et al., 2011[Bohmer, V., Brusko, V. & Bolte, M. (2011). Private Communication (refcode OBECUV). CCDC, Cambridge, England. https://doi.org/10.5517/ccx8ltk]): these structures are characterized by O⋯O distances ranging from 2.426–2.445 Å, which is comparable to the O⋯O distance of 2.434 (2) Å in this structure, thus all can be classified as strong O—H⋯O hydrogen bonds as predicted.

5. Synthesis and crystallization

Preparation of clozapine N-oxide hydro­chloride (CNO·HCl)

A 250 ml round-bottom flask was charged with clozapine N-oxide (5.00 g, 0.015 mol) and methanol (50 ml) and stirred under N2. Initially, the solid dissolved but then precipitated as a presumed CNO·methano­late adduct. A solution of HCl in ethyl acetate (2.8 M, 6 ml, 0.017 mol, 1.1 eq) was added slowly to the suspension. After 10 min the solid dissolved, and then precipitated as a faint yellow solid. The suspension was stirred for 1 h, then the solid was collected by filtration, and washed with ethyl acetate to afford CNO·HCl as a yellow solid (2.2 g, 39%). Degradation point: 473–478 K (corrected); 1H NMR (400 MHz, CD3OD) δ 3.35–3.45 (m, 6 H), 3.65–3.80 (m, 4 H), 3.95 (br s, 2 H), 6.83 (d, J 8.4 Hz, 1 H), 6.87 (d, J 2.4, 8.4 Hz, 1 H), 6.97 (dd, J = 2.4 Hz, 1H), 7.01 (dd, J 1.0, 8.0 Hz, 1H), 7.06 (dt, J 1.1, 7.6 Hz, 1H), 7.33 (dd, J 1.4, 7.8 Hz, 1H), 7.37 (dt, J 1.5, 6.4 Hz, 1H); 13C NMR (100 MHz, CD3OD) δ 43.1, 58.9, 65.3, 121.5, 121.6, 123.6, 124.3, 125.1, 127.4, 129.6, 131.2, 133.9, 142.5, 143.1, 155.5, 164.0. Elemental analysis: calculated for C18H20Cl2N4O: C 57.0, H 5.3, N 14.8. Found: C 56.8, H 5.6, N 14.8.

Preparation of clozapine N-oxide hemi­hydro­chloride (CNO)2·HCl

The above material (CNO·HCl) was recrystallized by diffusion of diethyl ether into a methanol solution giving (CNO)2·HCl as small orange blocks.

Preparation of clozapine N-oxide hydro­bromide

A 25 ml round-bottom flask was charged with clozapine N-oxide (1.00 g, 2.92 mmol, 1 eq.) and methanol (5 ml) and stirred under N2. Initially, the solid dissolved but then precipitated as a presumed CNO·methano­late adduct. The solution was cooled in an ice–water bath and 48% HBr in water (0.35 ml, 3.07 mmol, 1.05 eq) was added slowly to the suspension. The mixture stirred for 1 h at rt, without formation of a precipitate. The solvent was evaporated and the residue suspended in EtOAc (10 ml). The resulting solid was collected by filtration and washed with EtOAc to afford CNO·HBr as a yellow solid (1.1 g, 89%). Degradation point: 483–493 K (corrected); 1H NMR (400 MHz, CD3OD) δ 3.68 (s, 3 H), 3.87 (br d, J 11.6 Hz, 2 H), 3.9–4.2 (m, 6 H), 7.01 (d, J 8.6 Hz, 1 H), 7.13–7.23 (m, 3 H), 7.27 (br s, 1 H), 7.53–7.60 (m, 2 H); 13C NMR (100 MHz, CD3OD) δ 44.7, 57.8, 57.9, 64.6, 64.7, 122.6, 124.9, 125.0, 126.7, 126.8, 128.4, 130.0, 133.1, 136.5, 145.9, 156.4.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3[link]. Regions of the unit cell occupied by disordered solvent (1409 Å3; ≃ 18.1% of the unit-cell volume) were processed with the Squeeze algorithm in PLATON (Spek, 2015[Spek, A. L. (2015). Acta Cryst. C71, 9-18.]); the stated composition, density, etc. do not take account of the solvent.

Table 3
Experimental details

Crystal data
Chemical formula 2C18H19ClN4O·HCl
Mr 722.10
Crystal system, space group Tetragonal, I4/m
Temperature (K) 100
a, c (Å) 17.305 (2), 26.040 (5)
V3) 7798 (3)
Z 8
Radiation type Synchrotron, λ = 0.710757 Å
μ (mm−1) 0.28
Crystal size (mm) 0.06 × 0.05 × 0.04
 
Data collection
Diffractometer ADSC Quantum 210r
No. of measured, independent and observed [I > 2σ(I)] reflections 66433, 5901, 5096
Rint 0.049
(sin θ/λ)max−1) 0.741
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.049, 0.138, 1.03
No. of reflections 5901
No. of parameters 231
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.81, −0.49
Computer programs: AS QEGUI, XDS (Kabsch, 1993[Kabsch, W. (1993). J. Appl. Cryst. 26, 795-800.]), SHELXT (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2016/6 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), 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.]) and WinGX (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]).

Supporting information


Computing details top

Data collection: AS QEGUI; cell refinement: XDS (Kabsch, 1993); data reduction: XDS (Kabsch, 1993); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2016/6 (Sheldrick, 2015b); molecular graphics: Mercury (Macrae et al., 2020); software used to prepare material for publication: WinGX (Farrugia, 2012).

8-Chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine N-oxide hemi(hydrochloride) top
Crystal data top
2C18H19ClN4O·HClDx = 1.230 Mg m3
Mr = 722.10Synchrotron radiation, λ = 0.710757 Å
Tetragonal, I4/mCell parameters from 5908 reflections
a = 17.305 (2) Åθ = 1.4–31.8°
c = 26.040 (5) ŵ = 0.28 mm1
V = 7798 (3) Å3T = 100 K
Z = 8Block, yellow
F(000) = 30240.06 × 0.05 × 0.04 mm
Data collection top
ADSC Quantum 210r
diffractometer
5096 reflections with I > 2σ(I)
Radiation source: MX1 Beamline Australian SynchrotronRint = 0.049
Silicon Double Crystal monochromatorθmax = 31.8°, θmin = 1.4°
ω Scan scansh = 2525
66433 measured reflectionsk = 2525
5901 independent reflectionsl = 3636
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.049 w = 1/[σ2(Fo2) + (0.0661P)2 + 11.4576P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.138(Δ/σ)max = 0.001
S = 1.03Δρmax = 0.81 e Å3
5901 reflectionsΔρmin = 0.49 e Å3
231 parametersExtinction correction: SHELXL2016/6 (Sheldrick 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraintsExtinction coefficient: 0.0069 (5)
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
Cl10.13932 (3)0.04426 (2)0.37292 (2)0.03680 (13)
Cl20.16534 (4)0.44691 (3)0.5000000.03563 (15)
O10.02559 (6)0.43450 (7)0.13599 (5)0.0285 (2)
N30.17304 (7)0.39022 (7)0.21729 (5)0.0225 (2)
N20.15846 (7)0.30145 (7)0.28157 (5)0.0228 (2)
N10.18161 (8)0.38441 (8)0.37970 (5)0.0261 (3)
N40.10378 (8)0.43810 (8)0.12165 (5)0.0248 (3)
C10.23713 (9)0.42470 (8)0.35074 (6)0.0242 (3)
C70.18814 (8)0.36630 (8)0.26780 (5)0.0216 (3)
C20.24220 (8)0.41696 (8)0.29712 (6)0.0228 (3)
C100.15645 (9)0.18517 (9)0.32919 (6)0.0252 (3)
H100.1508090.1591890.2981480.030*
C140.14157 (9)0.46872 (8)0.21112 (6)0.0239 (3)
H14A0.1705720.5044430.2323870.029*
H14B0.0881440.4696100.2223690.029*
C90.16811 (8)0.26540 (8)0.32932 (6)0.0228 (3)
C160.13708 (9)0.35868 (9)0.12884 (6)0.0254 (3)
H16A0.1905850.3584440.1177410.030*
H16B0.1088300.3221180.1077410.030*
C150.14617 (9)0.49399 (8)0.15559 (6)0.0245 (3)
H15A0.1237250.5450670.1520030.029*
H15B0.1998750.4968100.1450890.029*
C30.29823 (9)0.46033 (9)0.27067 (6)0.0256 (3)
H30.3028040.4547290.2352820.031*
C110.15328 (9)0.14442 (9)0.37477 (6)0.0291 (3)
C50.33991 (10)0.52005 (10)0.34901 (7)0.0317 (3)
H50.3714970.5549180.3662720.038*
C80.17647 (9)0.30343 (9)0.37683 (6)0.0253 (3)
C170.13260 (9)0.33393 (8)0.18470 (5)0.0237 (3)
H17A0.0789310.3303140.1951750.028*
H17B0.1560370.2833740.1887210.028*
C60.28604 (9)0.47695 (10)0.37606 (6)0.0291 (3)
H60.2822590.4827560.4114750.035*
C40.34685 (9)0.51128 (9)0.29616 (7)0.0294 (3)
H40.3837310.5392930.2780390.035*
C130.17144 (12)0.26047 (10)0.42216 (6)0.0352 (4)
H130.1760530.2857370.4535310.042*
C120.15973 (11)0.18114 (10)0.42162 (7)0.0361 (4)
H120.1563230.1533760.4521170.043*
C180.10927 (11)0.46237 (11)0.06669 (6)0.0345 (4)
H18A0.0799730.4273720.0457390.052*
H18B0.1623860.4616300.0560600.052*
H18C0.0889900.5137020.0629730.052*
H10.1789 (13)0.3988 (13)0.4114 (9)0.037 (6)*
H1A0.0000000.5000000.1357 (17)0.077 (14)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0421 (2)0.02417 (19)0.0442 (2)0.00136 (15)0.01026 (17)0.00663 (15)
Cl20.0513 (4)0.0331 (3)0.0224 (2)0.0004 (2)0.0000.000
O10.0225 (5)0.0313 (6)0.0318 (6)0.0003 (4)0.0012 (4)0.0007 (4)
N30.0265 (6)0.0200 (5)0.0210 (5)0.0002 (4)0.0015 (4)0.0017 (4)
N20.0234 (6)0.0225 (5)0.0224 (5)0.0017 (4)0.0001 (4)0.0013 (4)
N10.0321 (7)0.0252 (6)0.0211 (6)0.0006 (5)0.0007 (5)0.0034 (4)
N40.0263 (6)0.0271 (6)0.0210 (6)0.0012 (5)0.0007 (4)0.0003 (4)
C10.0234 (6)0.0237 (6)0.0256 (7)0.0024 (5)0.0024 (5)0.0013 (5)
C70.0216 (6)0.0219 (6)0.0214 (6)0.0025 (5)0.0000 (5)0.0024 (5)
C20.0219 (6)0.0214 (6)0.0249 (6)0.0018 (5)0.0018 (5)0.0015 (5)
C100.0234 (6)0.0241 (7)0.0282 (7)0.0020 (5)0.0025 (5)0.0007 (5)
C140.0272 (7)0.0211 (6)0.0233 (6)0.0015 (5)0.0014 (5)0.0014 (5)
C90.0203 (6)0.0236 (6)0.0246 (6)0.0021 (5)0.0006 (5)0.0006 (5)
C160.0286 (7)0.0256 (7)0.0220 (6)0.0001 (6)0.0009 (5)0.0028 (5)
C150.0264 (7)0.0228 (6)0.0241 (6)0.0020 (5)0.0011 (5)0.0003 (5)
C30.0239 (6)0.0236 (6)0.0293 (7)0.0010 (5)0.0000 (5)0.0010 (5)
C110.0286 (7)0.0238 (7)0.0349 (8)0.0030 (6)0.0051 (6)0.0046 (6)
C50.0275 (7)0.0284 (7)0.0392 (9)0.0019 (6)0.0071 (6)0.0053 (6)
C80.0258 (7)0.0257 (7)0.0245 (7)0.0022 (5)0.0009 (5)0.0001 (5)
C170.0275 (7)0.0230 (6)0.0205 (6)0.0010 (5)0.0005 (5)0.0027 (5)
C60.0294 (7)0.0304 (7)0.0274 (7)0.0016 (6)0.0056 (6)0.0055 (6)
C40.0233 (7)0.0262 (7)0.0387 (8)0.0019 (5)0.0006 (6)0.0014 (6)
C130.0494 (10)0.0340 (8)0.0224 (7)0.0029 (7)0.0001 (7)0.0013 (6)
C120.0477 (10)0.0327 (8)0.0279 (8)0.0034 (7)0.0032 (7)0.0070 (6)
C180.0464 (9)0.0368 (8)0.0203 (7)0.0016 (7)0.0000 (6)0.0033 (6)
Geometric parameters (Å, º) top
Cl1—C111.7506 (17)C9—C81.409 (2)
O1—N41.4051 (17)C16—C171.518 (2)
O1—H1A1.2169 (12)C16—H16A0.9700
N3—C71.4035 (18)C16—H16B0.9700
N3—C171.4692 (18)C15—H15A0.9700
N3—C141.4723 (18)C15—H15B0.9700
N2—C71.2852 (19)C3—C41.388 (2)
N2—C91.4012 (19)C3—H30.9300
N1—C11.406 (2)C11—C121.380 (2)
N1—C81.406 (2)C5—C61.386 (2)
N1—H10.86 (2)C5—C41.390 (2)
N4—C181.494 (2)C5—H50.9300
N4—C151.5016 (19)C8—C131.398 (2)
N4—C161.502 (2)C17—H17A0.9700
C1—C61.403 (2)C17—H17B0.9700
C1—C21.405 (2)C6—H60.9300
C7—C21.492 (2)C4—H40.9300
C2—C31.406 (2)C13—C121.388 (3)
C10—C111.382 (2)C13—H130.9300
C10—C91.403 (2)C12—H120.9300
C10—H100.9300C18—H18A0.9600
C14—C151.513 (2)C18—H18B0.9600
C14—H14A0.9700C18—H18C0.9600
C14—H14B0.9700
N4—O1—H1A107.9 (6)N4—C15—H15A109.5
C7—N3—C17115.75 (12)C14—C15—H15A109.5
C7—N3—C14116.31 (11)N4—C15—H15B109.5
C17—N3—C14111.87 (11)C14—C15—H15B109.5
C7—N2—C9126.07 (13)H15A—C15—H15B108.1
C1—N1—C8120.58 (13)C4—C3—C2121.53 (15)
C1—N1—H1114.0 (15)C4—C3—H3119.2
C8—N1—H1109.5 (15)C2—C3—H3119.2
O1—N4—C18109.17 (12)C12—C11—C10121.41 (15)
O1—N4—C15110.03 (11)C12—C11—Cl1119.43 (13)
C18—N4—C15110.59 (12)C10—C11—Cl1119.16 (13)
O1—N4—C16107.20 (11)C6—C5—C4120.17 (15)
C18—N4—C16110.61 (12)C6—C5—H5119.9
C15—N4—C16109.18 (12)C4—C5—H5119.9
C6—C1—C2119.37 (14)C13—C8—N1119.28 (14)
C6—C1—N1118.67 (14)C13—C8—C9119.13 (15)
C2—C1—N1121.88 (13)N1—C8—C9121.24 (13)
N2—C7—N3116.40 (13)N3—C17—C16110.00 (12)
N2—C7—C2128.37 (13)N3—C17—H17A109.7
N3—C7—C2115.03 (12)C16—C17—H17A109.7
C1—C2—C3118.60 (14)N3—C17—H17B109.7
C1—C2—C7121.68 (13)C16—C17—H17B109.7
C3—C2—C7119.68 (13)H17A—C17—H17B108.2
C11—C10—C9120.58 (14)C5—C6—C1120.92 (15)
C11—C10—H10119.7C5—C6—H6119.5
C9—C10—H10119.7C1—C6—H6119.5
N3—C14—C15110.58 (12)C3—C4—C5119.38 (15)
N3—C14—H14A109.5C3—C4—H4120.3
C15—C14—H14A109.5C5—C4—H4120.3
N3—C14—H14B109.5C12—C13—C8121.79 (16)
C15—C14—H14B109.5C12—C13—H13119.1
H14A—C14—H14B108.1C8—C13—H13119.1
N2—C9—C10114.92 (13)C11—C12—C13118.44 (15)
N2—C9—C8125.70 (13)C11—C12—H12120.8
C10—C9—C8118.63 (13)C13—C12—H12120.8
N4—C16—C17110.97 (12)N4—C18—H18A109.5
N4—C16—H16A109.4N4—C18—H18B109.5
C17—C16—H16A109.4H18A—C18—H18B109.5
N4—C16—H16B109.4N4—C18—H18C109.5
C17—C16—H16B109.4H18A—C18—H18C109.5
H16A—C16—H16B108.0H18B—C18—H18C109.5
N4—C15—C14110.53 (12)
C8—N1—C1—C6127.64 (15)C18—N4—C15—C14179.16 (13)
C8—N1—C1—C255.7 (2)C16—N4—C15—C1457.23 (15)
C9—N2—C7—N3177.72 (13)N3—C14—C15—N457.38 (16)
C9—N2—C7—C23.2 (2)C1—C2—C3—C41.4 (2)
C17—N3—C7—N26.69 (19)C7—C2—C3—C4176.48 (14)
C14—N3—C7—N2127.72 (14)C9—C10—C11—C121.4 (2)
C17—N3—C7—C2168.54 (12)C9—C10—C11—Cl1179.55 (11)
C14—N3—C7—C257.05 (17)C1—N1—C8—C13132.81 (16)
C6—C1—C2—C32.0 (2)C1—N1—C8—C954.0 (2)
N1—C1—C2—C3178.72 (13)N2—C9—C8—C13168.37 (15)
C6—C1—C2—C7175.82 (13)C10—C9—C8—C131.2 (2)
N1—C1—C2—C70.9 (2)N2—C9—C8—N14.9 (2)
N2—C7—C2—C135.2 (2)C10—C9—C8—N1174.45 (14)
N3—C7—C2—C1150.21 (14)C7—N3—C17—C16166.50 (12)
N2—C7—C2—C3146.92 (15)C14—N3—C17—C1657.13 (16)
N3—C7—C2—C327.63 (19)N4—C16—C17—N357.28 (16)
C7—N3—C14—C15166.35 (12)C4—C5—C6—C10.8 (2)
C17—N3—C14—C1557.55 (16)C2—C1—C6—C51.0 (2)
C7—N2—C9—C10156.61 (14)N1—C1—C6—C5177.76 (15)
C7—N2—C9—C833.5 (2)C2—C3—C4—C50.3 (2)
C11—C10—C9—N2170.69 (14)C6—C5—C4—C31.4 (2)
C11—C10—C9—C80.0 (2)N1—C8—C13—C12174.49 (17)
O1—N4—C16—C1761.75 (15)C9—C8—C13—C121.1 (3)
C18—N4—C16—C17179.32 (13)C10—C11—C12—C131.5 (3)
C15—N4—C16—C1757.41 (16)Cl1—C11—C12—C13179.46 (14)
O1—N4—C15—C1460.16 (15)C8—C13—C12—C110.2 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1A···O1i1.22 (1)1.22 (1)2.434 (2)179 (4)
N1—H1···Cl20.86 (2)2.46 (2)3.3259 (14)176 (2)
C15—H15A···O1i0.972.643.2598 (19)122
C15—H15A···N1ii0.972.513.416 (2)156
C15—H15B···Cl1iii0.972.913.8431 (17)162
Symmetry codes: (i) x, y+1, z; (ii) y+1/2, x+1/2, z+1/2; (iii) x+1/2, y+1/2, z+1/2.
 

Acknowledgements

The Australian Synchrotron Collaborative Access Program is thanked for beamtime on MX1.

Funding information

Funding for this research was provided by: Australian Research Council (award No. DP160100597; award No. DP180101957); Australian Synchrotron (grant No. 13618b).

References

First citationAllen, D. C., Carlson, T. L., Xiong, Y., Jin, J., Grant, K. A. & Cuzon Carlson, V. C. (2019). J. Pharmacol. Exp. Ther. 368, 199–207.  CrossRef CAS PubMed Google Scholar
First citationArmbruster, B. N., Li, X., Pausch, M. H., Herlitze, S. & Roth, B. L. (2007). Proc. Natl Acad. Sci. USA, 104, 5163–5168.  CrossRef PubMed Google Scholar
First citationBettencourt, C. J., Chow, S., Moore, P. W., Read, C. D. G., Jiao, Y., Bakker, J. P., Zhao, S., Bernhardt, P. V. & Williams, C. M. (2021). Aust. J. Chem. 74, 652–659.  CSD CrossRef CAS Google Scholar
First citationBohmer, V., Brusko, V. & Bolte, M. (2011). Private Communication (refcode OBECUV). CCDC, Cambridge, England. https://doi.org/10.5517/ccx8ltk  Google Scholar
First citationDong, S., Allen, J. A., Farrell, M. & Roth, B. L. (2010). Mol. BioSyst. 6, 1376–1380.  CrossRef CAS PubMed Google Scholar
First citationFarrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationGilli, P., Pretto, V., Bertolasi, V. & Gilli, G. (2009). Acc. Chem. Res. 42, 33–44.  CrossRef PubMed CAS Google Scholar
First citationGomez, J. L., Bonaventura, J., Lesniak, W., Mathews, W. B., Sysa-Shah, P., Rodriguez, L. A., Ellis, R. J., Richie, C. T., Harvey, B. K., Dannals, R. F., Pomper, M. G., Bonci, A. & Michaelides, M. (2017). Science, 357, 503–507.  CrossRef CAS PubMed Google Scholar
First citationGonzález-Rodríguez, D. & Schenning, A. P. H. J. (2011). Chem. Mater. 23, 310–325.  Google Scholar
First citationGroom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179.  Web of Science CrossRef IUCr Journals Google Scholar
First citationJaskólski, M., Olovsson, I., Tellgren, R. & Mickiewicz-Wichłacz, D. (1982). Acta Cryst. B38, 291–294.  CSD CrossRef IUCr Journals Google Scholar
First citationJin, C. M., Lu, H., Wu, L. Y. & Huang, J. (2006). Chem. Commun. pp. 5039–5041.  Web of Science CSD CrossRef Google Scholar
First citationJin, C.-M., Wu, L.-Y., Lu, H. & Xu, Y. (2008). Cryst. Growth Des. 8, 215–218.  CSD CrossRef CAS Google Scholar
First citationJin, T., Zhou, J., Pan, Y., Huang, Y. & Jin, C. (2018). J. Mol. Struct. 1160, 222–226.  CSD CrossRef CAS Google Scholar
First citationKabsch, W. (1993). J. Appl. Cryst. 26, 795–800.  CrossRef CAS Web of Science IUCr Journals Google Scholar
First citationKrzywda, S., Jaskólski, M., Gdaniec, M., Dega-Szafran, Z., Grundwald-Wyspiańska, M., Szafran, M., Dauter, Z. & Davies, G. (1996). J. Mol. Struct. 375, 197–206.  CAS Google Scholar
First citationMacrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226–235.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationMałuszyńska, H. & Okaya, Y. (1977). Acta Cryst. B33, 3049–3054.  CSD CrossRef IUCr Journals Google Scholar
First citationMoore, P. W., Jiao, Y., Mirzayans, P. M., Sheng, L. N. Q., Hooker, J. P. & Williams, C. M. (2016). Eur. J. Org. Chem. pp. 3401–3407.  CSD CrossRef Google Scholar
First citationMoore, P. W., Mirzayans, P. M. & Williams, C. M. (2015). Chem. Eur. J. 21, 3567–3571.  CSD CrossRef CAS PubMed Google Scholar
First citationPeet, P. L. van der, Gunawan, C., Abdul-Ridha, A., Ma, S., Scott, D. J., Gundlach, A. L., Bathgate, R. A. D., White, J. M. & Williams, S. J. (2018). MethodsX, 5, 257–267.  PubMed Google Scholar
First citationPrins, L. J., Reinhoudt, D. N. & Timmerman, P. (2001). Angew. Chem. Int. Ed. 40, 2382–2426.  Web of Science CrossRef CAS Google Scholar
First citationSheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSpek, A. L. (2015). Acta Cryst. C71, 9–18.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSteiner, T. (2002). Angew. Chem. Int. Ed. 41, 48–76.  Web of Science CrossRef CAS Google Scholar
First citationUrban, D. J. & Roth, B. L. (2015). Annu. Rev. Pharmacol. Toxicol. 55, 399–417.  CrossRef CAS PubMed Google Scholar
First citationWlaźlak, E., Kalinowska-Tłuścik, J., Nitek, W., Klejna, S., Mech, K., Macyk, W. & Szaciłowski, K. (2018). ChemElectroChem, 5, 3486–3497.  Google Scholar
First citationXue, H., Jiang, F., Chen, Q., Yuan, D., Pang, J., Lv, G., Wan, X., Liang, L. & Hong, M. (2015). Chem. Commun. 51, 13706–13709.  CSD CrossRef CAS 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
Follow Acta Cryst. E
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds