research communications
1-Ethyl 2-methyl 3,4-bis(acetyloxy)pyrrolidine-1,2-dicarboxylate:
Hirshfeld surface analysis and computational chemistryaLaboratório de Cristalografia, Esterodinâmica e Modelagem Molecular, Departamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos, SP, Brazil, bDepartmento de Física, Universidade Federal de São Carlos, 13565-905 São Carlos, SP, Brazil, cInstituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil, dInstituto de Química, Universidade Estadual de Campinas, UNICAMP, CP 6154, CEP 13084-917 Campinas, Brazil, and eResearch Centre for Crystalline Materials, School of Science and Technology, Sunway University, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia
*Correspondence e-mail: ignez@df.ufscar.br
The title compound, C13H19NO8, is based on a tetra-substituted pyrrolidine ring, which has a twisted conformation about the central C—C bond; the Cm—Ca—Ca—Cme torsion angle is 38.26 (15)° [m = methylcarboxylate, a = acetyloxy and me = methylene]. While the N-bound ethylcarboxylate group occupies an equatorial position, the remaining substituents occupy axial positions. In the crystal, supramolecular double-layers are formed by weak methyl- and methylene-C—H⋯O(carbonyl) interactions involving all four carbonyl-O atoms. The two-dimensional arrays stack along the c axis without directional interactions between them. The Hirshfeld surface is dominated by H⋯H (55.7%) and H⋯C/C⋯H (37.0%) contacts; H⋯H contacts are noted in the inter-double-layer region. The interaction energy calculations point to the importance of the dispersion energy term in the stabilization of the crystal.
Keywords: crystal structure; pyrrolidine; Hirshfeld surface analysis; NCI plots; computational chemistry.
CCDC reference: 2005478
1. Chemical context
A number of diseases, especially diabetes but also including viral diseases, cystic fibrosis and cancer, can be treated with α-glucosidase inhibitors (Dhameja & Gupta, 2019; Kiappes et al., 2018); for a review of the relevant patent literature, see Brás et al. (2014). Imino- and aza-sugars are strong inhibitors of the enzyme and are attracting current interest for chaperone therapy of Gaucher disease (Matassini et al., 2020). The tri-hydroxyl-substituted compound, aminociclitol, (I), is a known α-glucosidase inhibitor and is a natural product, being found in several plants (Assefa et al., 2020). The synthesis of (I) can proceed from several key intermediates (Garcia, 2008; Liu & Ma, 2017) and it is this consideration that prompted the structural investigation of the title compound, C13H19NO8, (II). Specifically, the HCl salt of (I) can be prepared from (II) after being subjected to a sequence of reactions comprising a reduction step, reflux acid hydrolysis, chromatographic purification on ion-exchange resin Dowex-H+ and, finally, hydrochloride formation. In this way, (I)·HCl was obtained in 67% yield (Garcia, 2008). In connection with supporting structural studies (Zukerman-Schpector et al., 2017) of crucial intermediates related to the synthesis of pharmacologically active (I), herein, the crystal and molecular structures of (II) are described. This is complemented by a detailed analysis of the supramolecular architecture by Hirshfeld surface analysis, non-covalent interactions plots and computational chemistry.
2. Structural commentary
The molecular structure of (II), Fig. 1, features a tetra-substituted pyrrolidine ring. The conformation of the five-membered ring is best described as being twisted about the C2—C3 bond; the C1—C2—C3—C4 torsion angle is 38.26 (15)° indicating a (+)syn-clinal configuration. With respect to the five-membered ring, the N-bound methylcarboxylate substituent occupies an equatorial position; the sum of angles about the N1 atom amounts to 360°, indicating this is an sp2 centre. At the C1–C3 centres, the methylcarboxylate and 2 × acetyloxy substituents, respectively, occupy axial positions. For the molecule illustrated in Fig. 1, the of each of the C1–C3 atoms is R, S and S, respectively; the centrosymmetric contains equal numbers of each enantiomer. When viewed towards the approximate plane through the pyrrolidine ring, the N-bound substituent is approximately co-planar, the C2-acetyloxy lies to one side of the plane, and the C1- and C3-substituents lie to the other side.
3. Supramolecular features
There are two classes of identifiable non-covalent C—H⋯O interactions occurring in the crystal of (II). As identified in PLATON (Spek, 2020), methyl-C9—H⋯O5(carbonyl) contacts (Table 1) occur between centrosymmetrically related molecules to form a dimeric aggregate and an 18-membered {⋯OCOC3OCH}2 synthon, Fig. 2(a). The second level, i.e. weaker, of C—H⋯O interactions assemble molecules into a supramolecular layer in the ab plane, Fig. 2(b), at separations beyond normally accepted values in PLATON (Spek, 2020). Here, a methylene-C3—H atom is bifurcated, forming contacts with the carbonyl-O1 and O3 atoms of a translationally related molecule along the a-axis direction. This is complemented by a methyl-C11—H⋯O7(carbonyl) interaction occurring along the b-axis direction, Fig. 2(c). The layer thus formed by these contacts is connected into a double-layer via the methyl-C9—H⋯O5(carbonyl) interactions mentioned above. The double-layers stack along the c axis without directional interactions between them.
4. Non-covalent interaction plots
Before embarking on a more detailed analysis of the overall molecular packing of (II), in particular of the inter-layer region along the c axis, non-covalent interaction plots (Johnson et al., 2010; Contreras-García et al., 2011) were calculated to analyse in more detail the nature of the specified C—H⋯O contacts described in Supramolecular features. This method analyses the electron density (and derivatives) around the specified intermolecular contacts and generates colour-based isosurfaces as detailed in the cited literature. The results, through a three-colour scheme, enable the visualization of contacts as being attractive (blue isosurface), repulsive (red) or otherwise. For the weak interactions in focus, a green isosurface indicates a weakly attractive interaction.
The isosurfaces for three identified C—H⋯O contacts are given in the upper view of Fig. 3, and each displays a green isosurface indicating weakly attractive interactions. The lower views of Fig. 3 show the plots of RDG versus sign(λ2)ρ(r) for the three sets of C—H⋯O interactions. The green peaks apparent at density values less than 0.0 a.u. indicate these are weakly attractive interactions.
5. Hirshfeld surface analysis
In order to understand further the interactions operating in the crystal of (II), the calculated Hirshfeld surfaces were mapped over the normalized contact distance, dnorm (McKinnon et al., 2004) and electrostatic potential (Spackman et al., 2008) with associated two-dimensional (2-D) (full and delineated) fingerprint (FP) plots (Spackman & McKinnon, 2002). These were generated using Crystal Explorer 17 (Turner et al., 2017) following literature procedures (Tan et al., 2019). The potentials were calculated using the STO-3G basis set at the Hartree–Fock level of theory. The bright-red spots on the Hirshfeld surface mapped over dnorm, Fig. 4(a), near the carbonyl-O (O1, O3, O5 and O7) and methyl-C—H (H3 and H9B) atoms correspond to the C—H⋯O interactions listed in Table 1. These observations were confirmed through the Hirshfeld surface mapped over the calculated electrostatic potential in Fig. 4(b), where the surface around carbonyl-O and methyl-C—H atoms are shown in red (negative electrostatic potential) and blue (positive electrostatic potential), respectively. Besides the C—H⋯O interactions listed in Table 1, a long C13—H13A⋯O5 interaction is reflected in the dnorm surface as a faint red spot in Fig. 5(a). In addition, short, intra-layer C⋯O contacts with separations 0.01–0.04 Å shorter than the sum of their van der Waals radii, Table 2, are observed as faint red spots on the dnorm surface in Fig. 5(b), reflecting the specific influence of the C8, C10 and O1 atoms participating in these contacts.
The corresponding two-dimensional fingerprint plot for the Hirshfeld surface of (II) is shown with characteristic pseudo-symmetric wings in the upper left and lower right sides of the de and di diagonal axes, respectively, in Fig. 6(a). The individual H⋯H, H⋯O/O⋯H, H⋯C/C⋯H, O⋯O, O⋯C/C⋯O and H⋯N/N⋯H contacts are illustrated in the delineated two-dimensional fingerprint plots (FP) in Fig. 6(b)–(g), respectively; the percentage contributions from different interatomic contacts are summarized in Table 3. The H⋯H contacts contribute 55.7% to the overall Hirshfeld surface with a beak-shape distribution in the FP with shortest de = di ∼2.4 Å. This short interatomic H⋯H contact involving the methyl-H11C and methylene-H4B atoms, Table 2, is around the sum of their van der Waals separation and occurs in the intra-layer region along the b axis. Consistent with the C—H⋯O interactions making the major contribution to the directional interactions in the crystal, H⋯O/O⋯H contacts contribute 37.0% to the overall Hirshfeld surface. A distinctive feature in the FP of Fig. 6(c), is the two symmetric spikes at de + di ∼2.4 Å. Although H⋯C/C⋯H, O⋯O, O⋯C/C⋯O and H⋯N/N⋯H appear as splash-like distributions of points at de + di ∼3.0 Å, Fig. 6(d)–(g), their contributions to the overall Hirshfeld surface are each below than 3.0%. These contacts and the remaining interatomic contacts have only a small effect on the packing, as the sum of their contributions to the overall Hirshfeld surface is less than 8%.
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6. Energy frameworks
The pairwise interaction energies between the molecules in the crystal of (II) were calculated using the wave function at the B3LYP/6-31G(d,p) level of theory. The total energy comprise four terms: electrostatic (Eele), polarization (Epol), dispersion (Edis) and exchange-repulsion (Erep) and were scaled as 1.057, 0.740, 0.871 and 0.618, respectively (Edwards et al., 2017). The characteristics of the intermolecular interactions in term of their energies are collated in Table 4. In the absence of conventional hydrogen bonding in the crystal, the dispersive component makes the major contribution to the interaction energies (Table 4). According to the total interaction energy, molecules within the supramolecular double layer are stabilized by C—H⋯O interaction, C⋯O short contacts and long-range H⋯H contacts. Whereas molecules between the supramolecular double layers are stabilized by long-range H⋯H contacts. Views of the energy framework diagrams down the b axis are shown in Fig. 7 and serve to emphasize the contribution of dispersion forces in the stabilization of the crystal.
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7. Database survey
There are no close precedents for the substitution pattern observed in the tetra-substituted pyrrolidine ring of (II) with, arguably, the most closely related structure being that of (III) (KULQEP; Szcześniak et al., 2015), at least in terms of the substitution pattern around the ring; the chemical diagram for (III) is shown in Fig. 8.
8. Synthesis and crystallization
A solution of (2R,3S,4S)-3,4-bis(acetyloxy)-1-(ethoxycarbonyl)pyrrolidine-2-carboxylic acid (40 mg, 0.132 mmol) in methanol (1 ml) was cooled to 273–278 K after which an excess of a cold, freshly prepared solution of CH2N2 in ether was added. The mixture was stirred at room temperature for 10 min. Excess CH2N2 was eliminated by purging the balloon with a dry air flow. The purge was collected on a solution of HOAc in MeOH. The reaction solution was concentrated to dryness and the residue was purified by flash on silica gel, using a mixture of EtOAc/n-hexane (1:3). Yield: 41.7 mg (quantitative) of (II). Colourless irregular crystals for the X-ray analysis were obtained by the slow evaporation of its n-hexane solution. M.p. 347.6–348.7 K.
The 1H and 13C NMR reflect the presence of two conformational rotamers in solution. 1H NMR (500 MHz, CDCl3): δ = 5.38 (s, 1H, H3); 5.11 (s, 1H, H4); 4.51 and 4.42 (2s, 1H, H2); 4.23–4.05 (2m, 2H, CH2CH3); 3.91 and 3.87 (2dd, J = 12.8 Hz and 5.5 Hz, 1H, H4a); 3.772 and 3.766 (2s, 3H, CO2CH3); 3.63 and 3.59 (2d, J = 12.8 Hz, 1H, H4b); 2.10 and 2.09 (2s, 3H, Ac); 2.01 and 2.00 (2s, 3H, Ac); 1.28 and 1.21 (2t, J = 7.0 Hz, 3H, CH2CH3). 1H NMR (500 MHz, C6D6, r.t.): δ = 5.62 (s, 1H, H3); 5.07 and 5.02 (2ap t, J = 2.7 Hz, 1H, H3); 4.78 (s, 0.6H, H1); 4.55 (s, 0.4H, H1); 4.12 and 4.10 (2q, J = 7.0 Hz, 0.4H, CH2CH3); 4.01–3.88 (q + m, J = 7.0 Hz, 2H, CH2CH3 and H4a); 3.84–3.76 (m, 1H, H4b); 3.65 (dd, J = 12.2 Hz and 2.4 Hz, 0.6H, H4a); 3.31 and 3.30 (2s, 3H, CO2CH3); 1.48 and 1.45 (2s, 3H, Ac); 1.43 and 1.42 (2s, 3H, Ac); 0.94 and 0.92 (2t, J = 7.0 Hz, 3H, CH2CH3). 13C NMR (125 MHz, CDCl3, r.t.): δ = 169.4; 169.3; 169.2; 168.8; 168.7; 154.8; 154.4; 77.9; 76.9; 74.5; 73.5; 63.6; 63.5; 61.9; 61.7; 52.7; 52.6; 50.6; 50.4; 20.74; 20.70; 20.65; 14.5. Microanalysis calculated for C13H19NO8: C 49.21, H 6.04, N 4.41%. Found: C 48.89, H 6.52, N 4.50%.
9. details
Crystal data, data collection and structure . The carbon-bound H atoms were placed in calculated positions (C—H = 0.96–0.98 Å) and were included in the in the riding-model approximation, with Uiso(H) set to 1.2–1.5Ueq(C).
details are summarized in Table 5
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Supporting information
CCDC reference: 2005478
https://doi.org/10.1107/S205698902000701X/hb7916sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S205698902000701X/hb7916Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S205698902000701X/hb7916Isup3.cml
Data collection: CAD-4 EXPRESS (Enraf Nonius, 1989); cell
CAD-4 EXPRESS (Enraf Nonius, 1989); data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to solve structure: SIR2014 (Burla et al., 2015); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012), MarvinSketch (ChemAxon, 2010) and DIAMOND (Brandenburg, 2006); software used to prepare material for publication: publCIF (Westrip, 2010).C13H19NO8 | Z = 2 |
Mr = 317.29 | F(000) = 336 |
Triclinic, P1 | Dx = 1.338 Mg m−3 |
a = 6.8291 (5) Å | Mo Kα radiation, λ = 0.71073 Å |
b = 7.8670 (11) Å | Cell parameters from 25 reflections |
c = 15.814 (3) Å | θ = 10.8–18.2° |
α = 100.607 (11)° | µ = 0.11 mm−1 |
β = 99.011 (10)° | T = 290 K |
γ = 105.054 (7)° | Irregular, colourless |
V = 787.5 (2) Å3 | 0.40 × 0.35 × 0.10 mm |
Enraf Nonius TurboCAD-4 diffractometer | θmax = 30.0°, θmin = 2.7° |
Radiation source: Enraf Nonius FR590 | h = −9→9 |
non–profiled ω/2θ scans | k = 0→11 |
4880 measured reflections | l = −22→21 |
4573 independent reflections | 3 standard reflections every 120 min |
2571 reflections with I > 2σ(I) | intensity decay: 2% |
Rint = 0.020 |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.042 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.128 | H-atom parameters constrained |
S = 0.99 | w = 1/[σ2(Fo2) + (0.0579P)2 + 0.0763P] where P = (Fo2 + 2Fc2)/3 |
4573 reflections | (Δ/σ)max = 0.001 |
203 parameters | Δρmax = 0.18 e Å−3 |
0 restraints | Δρmin = −0.17 e Å−3 |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.28490 (19) | 0.08131 (19) | 0.64555 (9) | 0.0568 (3) | |
O2 | 0.12213 (18) | 0.24723 (18) | 0.57354 (8) | 0.0513 (3) | |
O3 | 0.35221 (19) | 0.33818 (18) | 0.83767 (9) | 0.0586 (3) | |
O4 | 0.20434 (18) | 0.14935 (17) | 0.91551 (8) | 0.0504 (3) | |
O5 | −0.5275 (2) | −0.0729 (2) | 0.83254 (9) | 0.0662 (4) | |
O6 | −0.32790 (16) | −0.06328 (15) | 0.73314 (7) | 0.0424 (3) | |
O7 | −0.2014 (3) | 0.6135 (2) | 0.78612 (11) | 0.0753 (4) | |
O8 | −0.08692 (17) | 0.40628 (15) | 0.84074 (7) | 0.0426 (3) | |
N1 | 0.0250 (2) | 0.1764 (2) | 0.69258 (9) | 0.0433 (3) | |
C1 | 0.0322 (2) | 0.0990 (2) | 0.76913 (10) | 0.0372 (3) | |
H1 | 0.041065 | −0.024702 | 0.752792 | 0.045* | |
C2 | −0.1782 (2) | 0.0948 (2) | 0.79177 (10) | 0.0357 (3) | |
H2 | −0.177363 | 0.096071 | 0.853908 | 0.043* | |
C3 | −0.2178 (2) | 0.2626 (2) | 0.76694 (10) | 0.0388 (3) | |
H3 | −0.364464 | 0.257939 | 0.758613 | 0.047* | |
C4 | −0.1353 (2) | 0.2683 (2) | 0.68313 (11) | 0.0430 (4) | |
H4A | −0.244190 | 0.204920 | 0.631224 | 0.052* | |
H4B | −0.076679 | 0.392201 | 0.679209 | 0.052* | |
C5 | 0.1565 (2) | 0.1615 (2) | 0.63798 (10) | 0.0424 (4) | |
C6 | 0.2518 (3) | 0.2410 (3) | 0.50973 (13) | 0.0631 (5) | |
H6A | 0.234590 | 0.116529 | 0.480776 | 0.076* | |
H6B | 0.396809 | 0.298206 | 0.538377 | 0.076* | |
C7 | 0.1853 (4) | 0.3399 (4) | 0.44469 (15) | 0.0818 (7) | |
H7A | 0.041201 | 0.282919 | 0.417435 | 0.123* | |
H7B | 0.266749 | 0.337723 | 0.400460 | 0.123* | |
H7C | 0.204764 | 0.463198 | 0.474089 | 0.123* | |
C8 | 0.2155 (2) | 0.2132 (2) | 0.84352 (11) | 0.0404 (3) | |
C9 | 0.3834 (3) | 0.2283 (4) | 0.98760 (14) | 0.0766 (7) | |
H9A | 0.506912 | 0.224946 | 0.966399 | 0.115* | |
H9B | 0.370682 | 0.160845 | 1.032257 | 0.115* | |
H9C | 0.391528 | 0.351722 | 1.012025 | 0.115* | |
C10 | −0.4972 (2) | −0.1374 (2) | 0.76304 (12) | 0.0461 (4) | |
C11 | −0.6347 (3) | −0.3050 (3) | 0.69971 (16) | 0.0697 (6) | |
H11A | −0.581462 | −0.404559 | 0.706145 | 0.104* | |
H11B | −0.639848 | −0.289168 | 0.640732 | 0.104* | |
H11C | −0.771979 | −0.329842 | 0.711270 | 0.104* | |
C12 | −0.0926 (3) | 0.5768 (2) | 0.84243 (13) | 0.0500 (4) | |
C13 | 0.0585 (4) | 0.7066 (3) | 0.92107 (15) | 0.0696 (6) | |
H13A | 0.194942 | 0.735689 | 0.908739 | 0.104* | |
H13B | 0.058933 | 0.652183 | 0.970653 | 0.104* | |
H13C | 0.018502 | 0.815216 | 0.934292 | 0.104* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0482 (7) | 0.0740 (9) | 0.0610 (8) | 0.0303 (7) | 0.0206 (6) | 0.0223 (7) |
O2 | 0.0509 (7) | 0.0668 (8) | 0.0457 (6) | 0.0205 (6) | 0.0212 (5) | 0.0231 (6) |
O3 | 0.0431 (6) | 0.0550 (8) | 0.0714 (8) | 0.0012 (6) | 0.0106 (6) | 0.0205 (7) |
O4 | 0.0476 (6) | 0.0545 (7) | 0.0462 (6) | 0.0117 (6) | 0.0003 (5) | 0.0186 (6) |
O5 | 0.0573 (8) | 0.0702 (10) | 0.0703 (9) | 0.0073 (7) | 0.0301 (7) | 0.0171 (8) |
O6 | 0.0357 (5) | 0.0405 (6) | 0.0475 (6) | 0.0065 (5) | 0.0088 (5) | 0.0092 (5) |
O7 | 0.0854 (11) | 0.0571 (9) | 0.0929 (11) | 0.0370 (8) | 0.0070 (9) | 0.0284 (8) |
O8 | 0.0440 (6) | 0.0367 (6) | 0.0497 (6) | 0.0151 (5) | 0.0096 (5) | 0.0122 (5) |
N1 | 0.0395 (7) | 0.0576 (9) | 0.0448 (7) | 0.0230 (6) | 0.0144 (6) | 0.0243 (6) |
C1 | 0.0345 (7) | 0.0403 (8) | 0.0423 (8) | 0.0148 (6) | 0.0098 (6) | 0.0168 (7) |
C2 | 0.0327 (7) | 0.0348 (8) | 0.0397 (8) | 0.0087 (6) | 0.0082 (6) | 0.0105 (6) |
C3 | 0.0322 (7) | 0.0404 (8) | 0.0458 (8) | 0.0125 (6) | 0.0082 (6) | 0.0127 (7) |
C4 | 0.0411 (8) | 0.0497 (10) | 0.0446 (8) | 0.0186 (7) | 0.0094 (7) | 0.0196 (7) |
C5 | 0.0359 (7) | 0.0520 (10) | 0.0389 (8) | 0.0111 (7) | 0.0086 (6) | 0.0118 (7) |
C6 | 0.0635 (12) | 0.0808 (15) | 0.0527 (11) | 0.0219 (11) | 0.0292 (9) | 0.0195 (10) |
C7 | 0.0946 (17) | 0.112 (2) | 0.0566 (12) | 0.0356 (15) | 0.0357 (12) | 0.0387 (13) |
C8 | 0.0357 (7) | 0.0424 (9) | 0.0477 (9) | 0.0155 (7) | 0.0101 (6) | 0.0154 (7) |
C9 | 0.0645 (13) | 0.0948 (18) | 0.0570 (12) | 0.0172 (12) | −0.0142 (10) | 0.0169 (12) |
C10 | 0.0358 (8) | 0.0443 (9) | 0.0596 (10) | 0.0088 (7) | 0.0106 (7) | 0.0200 (8) |
C11 | 0.0448 (10) | 0.0558 (12) | 0.0917 (16) | −0.0003 (9) | 0.0043 (10) | 0.0075 (11) |
C12 | 0.0516 (9) | 0.0402 (9) | 0.0677 (12) | 0.0181 (8) | 0.0229 (9) | 0.0213 (9) |
C13 | 0.0803 (14) | 0.0425 (11) | 0.0764 (14) | 0.0050 (10) | 0.0192 (12) | 0.0075 (10) |
O1—C5 | 1.2098 (19) | C3—H3 | 0.9800 |
O2—C5 | 1.345 (2) | C4—H4A | 0.9700 |
O2—C6 | 1.446 (2) | C4—H4B | 0.9700 |
O3—C8 | 1.1961 (19) | C6—C7 | 1.484 (3) |
O4—C8 | 1.3312 (19) | C6—H6A | 0.9700 |
O4—C9 | 1.445 (2) | C6—H6B | 0.9700 |
O5—C10 | 1.195 (2) | C7—H7A | 0.9600 |
O6—C10 | 1.3499 (19) | C7—H7B | 0.9600 |
O6—C2 | 1.4385 (18) | C7—H7C | 0.9600 |
O7—C12 | 1.195 (2) | C9—H9A | 0.9600 |
O8—C12 | 1.348 (2) | C9—H9B | 0.9600 |
O8—C3 | 1.4496 (19) | C9—H9C | 0.9600 |
N1—C5 | 1.351 (2) | C10—C11 | 1.483 (3) |
N1—C1 | 1.4518 (19) | C11—H11A | 0.9600 |
N1—C4 | 1.464 (2) | C11—H11B | 0.9600 |
C1—C8 | 1.524 (2) | C11—H11C | 0.9600 |
C1—C2 | 1.528 (2) | C12—C13 | 1.496 (3) |
C1—H1 | 0.9800 | C13—H13A | 0.9600 |
C2—C3 | 1.521 (2) | C13—H13B | 0.9600 |
C2—H2 | 0.9800 | C13—H13C | 0.9600 |
C3—C4 | 1.523 (2) | ||
C5—O2—C6 | 115.92 (14) | O2—C6—H6B | 110.4 |
C8—O4—C9 | 115.73 (15) | C7—C6—H6B | 110.4 |
C10—O6—C2 | 116.20 (12) | H6A—C6—H6B | 108.6 |
C12—O8—C3 | 118.19 (13) | C6—C7—H7A | 109.5 |
C5—N1—C1 | 121.34 (13) | C6—C7—H7B | 109.5 |
C5—N1—C4 | 125.77 (13) | H7A—C7—H7B | 109.5 |
C1—N1—C4 | 112.89 (12) | C6—C7—H7C | 109.5 |
N1—C1—C8 | 111.47 (13) | H7A—C7—H7C | 109.5 |
N1—C1—C2 | 102.32 (12) | H7B—C7—H7C | 109.5 |
C8—C1—C2 | 113.23 (13) | O3—C8—O4 | 124.90 (16) |
N1—C1—H1 | 109.9 | O3—C8—C1 | 125.34 (15) |
C8—C1—H1 | 109.9 | O4—C8—C1 | 109.73 (13) |
C2—C1—H1 | 109.9 | O4—C9—H9A | 109.5 |
O6—C2—C3 | 108.78 (12) | O4—C9—H9B | 109.5 |
O6—C2—C1 | 106.68 (12) | H9A—C9—H9B | 109.5 |
C3—C2—C1 | 103.23 (12) | O4—C9—H9C | 109.5 |
O6—C2—H2 | 112.5 | H9A—C9—H9C | 109.5 |
C3—C2—H2 | 112.5 | H9B—C9—H9C | 109.5 |
C1—C2—H2 | 112.5 | O5—C10—O6 | 122.72 (16) |
O8—C3—C2 | 102.26 (11) | O5—C10—C11 | 125.62 (16) |
O8—C3—C4 | 111.80 (12) | O6—C10—C11 | 111.66 (16) |
C2—C3—C4 | 103.54 (13) | C10—C11—H11A | 109.5 |
O8—C3—H3 | 112.8 | C10—C11—H11B | 109.5 |
C2—C3—H3 | 112.8 | H11A—C11—H11B | 109.5 |
C4—C3—H3 | 112.8 | C10—C11—H11C | 109.5 |
N1—C4—C3 | 103.35 (12) | H11A—C11—H11C | 109.5 |
N1—C4—H4A | 111.1 | H11B—C11—H11C | 109.5 |
C3—C4—H4A | 111.1 | O7—C12—O8 | 122.72 (18) |
N1—C4—H4B | 111.1 | O7—C12—C13 | 126.78 (18) |
C3—C4—H4B | 111.1 | O8—C12—C13 | 110.46 (16) |
H4A—C4—H4B | 109.1 | C12—C13—H13A | 109.5 |
O1—C5—O2 | 125.04 (15) | C12—C13—H13B | 109.5 |
O1—C5—N1 | 124.93 (15) | H13A—C13—H13B | 109.5 |
O2—C5—N1 | 110.02 (14) | C12—C13—H13C | 109.5 |
O2—C6—C7 | 106.76 (17) | H13A—C13—H13C | 109.5 |
O2—C6—H6A | 110.4 | H13B—C13—H13C | 109.5 |
C7—C6—H6A | 110.4 | ||
C5—N1—C1—C8 | 76.02 (19) | C2—C3—C4—N1 | −27.36 (15) |
C4—N1—C1—C8 | −103.88 (15) | C6—O2—C5—O1 | −0.3 (3) |
C5—N1—C1—C2 | −162.67 (14) | C6—O2—C5—N1 | −179.62 (15) |
C4—N1—C1—C2 | 17.43 (18) | C1—N1—C5—O1 | 2.0 (3) |
C10—O6—C2—C3 | −96.72 (15) | C4—N1—C5—O1 | −178.13 (17) |
C10—O6—C2—C1 | 152.54 (13) | C1—N1—C5—O2 | −178.67 (14) |
N1—C1—C2—O6 | 80.73 (14) | C4—N1—C5—O2 | 1.2 (2) |
C8—C1—C2—O6 | −159.17 (12) | C5—O2—C6—C7 | 178.98 (17) |
N1—C1—C2—C3 | −33.83 (15) | C9—O4—C8—O3 | −6.4 (3) |
C8—C1—C2—C3 | 86.27 (14) | C9—O4—C8—C1 | 171.57 (15) |
C12—O8—C3—C2 | −176.59 (13) | N1—C1—C8—O3 | −8.7 (2) |
C12—O8—C3—C4 | 73.23 (17) | C2—C1—C8—O3 | −123.40 (18) |
O6—C2—C3—O8 | 168.91 (11) | N1—C1—C8—O4 | 173.33 (13) |
C1—C2—C3—O8 | −78.04 (13) | C2—C1—C8—O4 | 58.60 (17) |
O6—C2—C3—C4 | −74.78 (14) | C2—O6—C10—O5 | 3.0 (2) |
C1—C2—C3—C4 | 38.26 (15) | C2—O6—C10—C11 | −176.72 (15) |
C5—N1—C4—C3 | −173.74 (15) | C3—O8—C12—O7 | 0.4 (2) |
C1—N1—C4—C3 | 6.15 (18) | C3—O8—C12—C13 | −177.58 (14) |
O8—C3—C4—N1 | 82.01 (15) |
D—H···A | D—H | H···A | D···A | D—H···A |
C9—H9B···O5i | 0.96 | 2.53 | 3.403 (3) | 151 |
C3—H3···O1ii | 0.98 | 2.62 | 3.419 (2) | 139 |
C3—H3···O3ii | 0.98 | 2.61 | 3.453 (2) | 144 |
C11—H11A···O7iii | 0.96 | 2.66 | 3.329 (3) | 127 |
Symmetry codes: (i) −x, −y, −z+2; (ii) x−1, y, z; (iii) x, y−1, z. |
Contact | Distance | Symmetry operation |
H4B···H11C | 2.32 | x + 1, y + 1, z |
H9B···O5b | 2.42 | -x, -y, -z + 2 |
H3···O1b | 2.55 | x - 1, y, z |
H3···O3 b | 2.53 | x - 1, y, z |
H11A···O7b | 2.59 | -x, -y + 1, -z |
H13A···O5 | 2.58 | x + 1, y + 1, z |
C8···O5 | 3.191 (2) | x + 1, y, z |
C10···O1 | 3.204 (2) | x - 1, y, z |
C10···O7 | 3.185 (3) | x, y - 1, z |
Notes: (a) The interatomic distances are calculated in Crystal Explorer 17 (Turner et al., 2017) whereby the X—H bond lengths are adjusted to their neutron values. (b) These interactions correspond to the interaction listed in Table 1. |
Contact | Percentage contribution |
H···H | 55.7 |
H···O/O···H | 37.0 |
H···C/C···H | 2.7 |
O···O | 2.3 |
O···C/C···O | 1.9 |
H···C/C···H | 0.4 |
Contact | R (Å) | Eele | Epol | Edis | Erep | Etot |
Intra-double-layer | ||||||
C3—H3···O1ii + | ||||||
C3—H3···O3ii + | ||||||
O1···C10iv + | ||||||
O5···C8ii | 6.8 | -19.4 | -8.3 | -33.6 | 19.3 | -44.0 |
H9B···H13Cv + | ||||||
H13B···H13Bv | 8.2 | -5.1 | -1.6 | -28.4 | 11.0 | -24.5 |
C13—H13A···O5vi + | ||||||
H4B···H11Cvi + | ||||||
H7C···H11Bvi | 9.0 | -8.8 | -2.1 | -20.8 | 10.7 | -22.4 |
C11—H11A···O7iii + | ||||||
C13—H13C···O4iii + | ||||||
C10···O7vii | 7.9 | -8.1 | -2.9 | -20.2 | 12.5 | -20.6 |
H9A···H13Aviii + | ||||||
H9C···H9Cviii | 9.3 | -6.5 | -2.1 | -19.8 | 14.4 | -16.7 |
C9—H9B···O5i | 9.1 | -10.2 | -2.3 | -12.9 | 13.9 | -15.1 |
C7—H7B···O7ix | 9.9 | -3.6 | -0.9 | -15.1 | 4.8 | -14.7 |
Inter-double-layer region | ||||||
H4A···H6Ax + | ||||||
H7B···H11Bx | 8.1 | -5.0 | -1.8 | -41.4 | 17.3 | -31.9 |
H7A···H11Cxi | 8.9 | -0.9 | -0.4 | -10.8 | 6.2 | -6.8 |
Symmetry codes: (i) -x, -y, -z + 2; (ii) x - 1, y, z; (iii) x, y - 1, z; (iv) x + 1, y, z; (v) -x, -y + 1, -z + 2; (vi) x + 1, y + 1, z; (vii) x, y + 1, z; (viii) -x + 1, -y + 1, -z + 2; (ix) -x, -y + 1, -z; (x) -x, -y, -z + 1; (xi) -x - 1, -y, -z + 1. |
Footnotes
‡Additional correspondence author, e-mail: edwardt@sunway.edu.my.
Funding information
The Brazilian agencies Coordination for the Improvement of Higher Education Personnel, CAPES, Finance Code 001 and the National Council for Scientific and Technological Development (CNPq) are acknowledged for grants (312210/2019–1, 433957/2018–2 and 406273/2015–4) to IC, for a fellowship (303207/2017–5) to JZS and a scholarship to SDP. Sunway University Sdn Bhd is also thanked for funding (grant. No. STR-RCTR-RCCM-001–2019).
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