The crystal structure, Hirshfeld surface analysis and energy frameworks of 2-[2-(meth­oxy­carbon­yl)-3,6-bis­(meth­oxy­meth­oxy)phen­yl]acetic acid

Tiouabi, M.; Tabacchi, R.; Stoeckli-Evans, H.

doi:10.1107/S2056989020007987

research communications

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ISSN: 2056-9890

Volume 76| Part 7| July 2020| Pages 1101-1106

https://doi.org/10.1107/S2056989020007987

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The crystal structure, Hirshfeld surface analysis and energy frameworks of 2-[2-(methoxycarbonyl)-3,6-bis(methoxymethoxy)phenyl]acetic acid

Mustapha Tiouabi,^a Raphaël Tabacchi ^a and Helen Stoeckli-Evans ^b ^*

^aInstitute of Chemistry, University of Neuchâtel, Av. de Bellevax 51, CH-2000 Neuchâtel, Switzerland, and ^bInstitute of Physics, University of Neuchâtel, rue Emile-Argand 11, CH-2000 Neuchâtel, Switzerland
^*Correspondence e-mail: helen.stoeckli-evans@unine.ch

Edited by J. Ellena, Universidade de Sâo Paulo, Brazil (Received 11 May 2020; accepted 15 June 2020; online 19 June 2020)

In the title compound, C₁₄H₁₈O₈, (I), the methoxycarbonyl [–C(=O)OCH₃] and the acetic acid [–CH₂C(=O)OH] groups are inclined to the benzene ring by 79.24 (11) and 76.71 (13)°, respectively, and are normal to each other with a dihedral angle of 90.00 (13)°. In the crystal, molecules are linked by a pair of O—H⋯O hydrogen bonds forming the familiar acetic acid inversion dimer. The dimers are linked by two C—H⋯O hydrogen bonds and an offset π–π interaction [intercentroid distance = 3.6405 (14) Å], forming layers lying parallel to the (10 $[\overline{1}]$ ) plane. The layers are linked by a third C—H⋯O hydrogen bond and a C—H⋯π interaction to form a supramolecular framework.

Keywords: crystal structure; isocoumarin; hydrogen bonding; C—H⋯π interactions; offset π–π interactions; supramolecular framework; Hirshfeld surface analysis; energy frameworks.

CCDC reference: 2009890

1. Chemical context

Isocoumarins are among the phytotoxins produced by the Ceratocystis fimbriata species. The latter are pathogenic agents responsible for the infections of coffee and plane trees (Gremaud & Tabacchi, 1994 ; Bürki et al., 2003 ). The analysis of the culture medium of Ophiostoma ulmi, a pathogenic agent responsible for elm disease and classified in the family of Ceratocystis, enabled Michel (2001 ) to isolate sixteen metabolites including four isocoumarins without apparent toxicity and a new natural product, 3-methyl-3,5,8-trihydroxy-3,4-dihydroisocoumarin, found in the extract of diseased wood. Qualitatively, the latter is present in trace amounts; however, the toxicity of this metabolite is possible, since the activity is not necessarily proportional to the concentration.

The title compound (I), is a key intermediate for the proposed total synthesis of 3-methyl-3,5,8-trihydroxy-3,4-dihydroisocoumarin, and its synthesis is illustrated in Fig. 1 (Tiouabi, 2005 ). It was synthesized from hydroquinone (1), which was first brominated to give compound 2. The latter was then reacted with NaH and ClCH₂OCH₃ to give compound 3, so protecting the hydroxyl groups. Reacting 3 with tetramethylpiperidene with n-butyllithium and CH₂(CO₂CH₃)₂ resulted in the formation of compound 4. Finally 4 was reacted with various quantities of KOH in methanol/water (2:1) to give the title compound, I. The highest yield (81%) was obtained by reacting 20 equivalents of KOH in methanol/water (2:1) at 298 K under stirring for 16 h. Interestingly, the same reaction with reflux for 30 minutes yielded the diacid, 2-(carboxymethyl)-3,6-dihydroxybenzoic acid (5), with a yield of 82% (Fig. 1).

Figure 1
The reaction scheme resulting in the formation of the title compound, I.

2. Structural commentary

The molecular structure of compound I is illustrated in Fig. 2. The methoxymethyl group (mean plane 1: C2/C7/O1/O2/C8; r.m.s. deviation = 0.009 Å) is inclined to the benzene ring by 79.24 (11)°. The plane of the acetic acid unit (mean plane 2: C13/C14/O7/O8; r.m.s. deviation = 0.014 Å) is inclined to the benzene ring by 76.71 (13) °. Planes 1 and 2 are normal to each other with a dihedral angle of 90.00 (13)°. The methoxymethoxy side chains (O3–C9–O4–C10 and O5–C11–O6–C12) are displaced to opposite sides of the benzene ring. They have twisted conformations as seen from the torsion angles given in Table 3.

Table 3
Selected torsion angles (°) in compound I compared to those in compounds GEZPUZ, GEZQAG and IVIQIP

I
C3—O3—C9—O4	−77.8 (2)
C10—O4—C9—O3	−67.6 (2)
C6—O5—C11—O6	−61.3 (2)
C12—O6—C11—O5	−65.5 (2)

GEZPUZ^a
C7—O4—C13—O1	67.1 (3)
C16—O1—C13—O4	56.3 (3)
C8—O5—C12—O6	−80.1 (2)
C17—O6—C12—O5	−65.8 (3)

GEZQAG^a
C7—O2—C12—O7	−71.2 (8)
C16—O7—C12—O2	−67.6 (9)
C9—O3—C10—O6	86.1 (7)
C17—O6—C10—O3	76.6 (8)

IVIQIP^b,^c
C1—O1—C8—O2	−68.9 (2)
C9—O2—C8—O1	−66.1 (2)
(a) Nakayama et al. (2018); (b) Zhang et al. (2017); (c) compound IVIQIP possesses inversion symmetry.

Figure 2
The molecular structure of compound I, with atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

3. Supramolecular features

In the crystal of I, molecules are linked by a pair of O—H⋯O hydrogen bonds (O8—H8⋯O7ⁱ) forming an inversion dimer with an R₂²(8) ring motif (Fig. 3 and Table 1). The dimers are linked by two C—H⋯O hydrogen bonds (C9—H9B⋯O6ⁱⁱ and C11—H11A⋯O1ⁱⁱⁱ) and offset π–π interactions between inversion-related benzene rings, so forming layers lying parallel to (10 $[\overline{1}]$ ). The layers are linked by a third C—H⋯O hydrogen bond (C13—H13B⋯O4^iv) and a C—H⋯π interaction to form a supramolecular framework (Table 1 and Fig. 4). Details of the offset π–π interaction are as follows: Cg⋯Cgⁱⁱⁱ = 3.6405 (14) Å, where Cg is the centroid of the C1–C6 benzene ring; interplanar distance = 3.5911 (9) Å; offset = 0.597 Å; symmetry code: (iii) −x, −y + 1, −z.

Table 1
Hydrogen-bond geometry (Å, °)

Cg is the centroid of the C1–C6 benzene ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O8—H8⋯O7ⁱ	0.84	1.85	2.676 (2)	168
C9—H9B⋯O6ⁱⁱ	0.99	2.43	3.256 (3)	140
C11—H11A⋯O1ⁱⁱⁱ	0.99	2.38	3.366 (3)	175
C13—H13B⋯O4^iv	0.99	2.50	3.421 (3)	155
C12—H12B⋯Cg^v	0.98	2.66	3.451 (3)	138
Symmetry codes: (i) -x+1, -y+1, -z+1; (ii) x, y+1, z; (iii) -x, -y+1, -z; (iv) x+1, y, z; (v) -x, -y+1, -z+1.

Figure 3
A view normal to plane (10 $[\overline{1}]$ ) of the layer structure in the crystal of compound I. Hydrogen bonds (Table 1

) are shown as dashed lines and offset π–π interactions as orange double arrows. For clarity, only the H atoms involved in the intermolecular interactions have been included.

Figure 4
A view along the b axis of the crystal packing of compound I. The hydrogen bonds (Table 1

) are shown as dashed lines. The offset π–π interactions are indicated by orange double arrows, and the C—H⋯π interactions by blue dashed arrows. For clarity, only the H atoms involved in the intermolecular interactions have been included.

4. Hirshfeld surface analysis and two-dimensional fingerprint plots

The Hirshfeld surface analysis (Spackman & Jayatilaka, 2009 ), the associated two-dimensional fingerprint plots and the calculation of the energy frameworks (McKinnon et al., 2007 ) were performed with CrystalExplorer17.5 (Turner et al., 2017 ), following the protocol outlined in the recent article by Tiekink and collaborators (Tan et al., 2019 ). The Hirshfeld surface is colour-mapped with the normalized contact distance, d_norm, from red (distances shorter than the sum of the van der Waals radii) through white to blue (distances longer than the sum of the van der Waals radii). The energy frameworks (Turner et al., 2015 ; Tan et al., 2019) are represented by cylinders joining the centroids of molecular pairs using red, green and blue colour codes for the electrostatic (E_ele), dispersion (E_dis) and total energy (E_tot) components, respectively. The radius of the cylinder is proportional to the magnitude of the interaction energy.

A view of the Hirshfeld surface of I mapped over d_norm is shown in Fig. 5. The short interatomic O⋯H/H⋯O contacts are indicated by the large red spots. Other C—H⋯O contacts are indicated by faint red spots. A full list of short interatomic contacts in the crystal of I are given in Table 2. The majority of the significant contacts are O⋯H and C⋯H contacts, as confirmed by the two-dimensional fingerprint plots (Fig. 6). The principal intermolecular contacts for I are delineated into H⋯H (48.0%) (Fig. 6b), O⋯H/H⋯O (41.1%) (Fig. 6c), C⋯H/H⋯C (7.2%) (Fig. 6d) and C⋯C (2.7%) (Fig. 6e) contacts. The intermolecular contacts are therefore almost equally distributed between electrostatic and dispersion forces, as shown in Fig. 7a and 7b. The energy frameworks (Fig. 7) were adjusted to the same scale factor of 80 with a cut-off value of 5 kJ mol⁻¹ within a radius of 5 Å about a central molecule, and were obtained using the wave function calculated at the HF/3-21G level of theory.

Table 2
Short interatomic contacts (Å)^a in the crystal of compound I

Atom1	Atom2	Length	Length − VdW
O7	H8ⁱ	1.850	−0.870
O7	O8ⁱ	2.676	−0.364
O1	H11Aⁱⁱⁱ	2.379	−0.341
O6	H9B^vi	2.432	−0.288
O4	H13B^v	2.501	−0.219
H8	C14ⁱ	2.703	−0.197
O5	H10Cⁱⁱⁱ	2.637	−0.083
C12	H9B^vi	2.882	−0.018
O4	H8A^v	2.723	0.003
O7	C8^viii	3.223	0.003
O7	H8B^viii	2.726	0.006
O2	H8B^viii	2.731	0.011
H8	H8ⁱ	2.416	0.016
C2	H12B^vii	2.932	0.032
O6	C9^vi	3.256	0.036
H8B	C14^viii	2.954	0.054
C9	H8A^v	2.957	0.057
C1	H12B^vii	2.968	0.068
C3	H12B^vii	2.968	0.068
H10C	C11ⁱⁱⁱ	2.969	0.069
H9B	H8A^v	2.482	0.082
(a) Calculated using Mercury (Macrae et al., 2020 ). Symmetry codes: (i) −x + 1, −y + 1, −z + 1; (iii) −x, −y + 1, −z; (v) x − 1, y, z; (vi) x, y − 1, z; (vii) −x, −y + 1, −z + 1; (viii) −x + 1, −y + 2, −z + 1.

Figure 5
The Hirshfeld surface of compound I mapped over d_norm, in the colour range −0.6996 to 1.3669 a.u..

Figure 6
(a) The full two-dimensional fingerprint plot for compound I, and fingerprint plots delineated into (b) H⋯H (48.0%), (c) O⋯H/H⋯O (41.1%), (d) C⋯H/H⋯C (7.2%) and (e) C⋯C (2.7%) contacts.

Figure 7
The energy frameworks for I viewed down the c-axis direction comprising, (a) electrostatic potential forces (E_ele), (b) dispersion forces (E_dis) and (c) total (E_tot) energy for a cluster about a reference molecule of I. The energy frameworks were adjusted to the same scale factor of 80 with a cut-off value of 5 kJ mol⁻¹ within a 5 Å radius of a selected central molecule.

The calculation of the energy framework results in a colour-coded molecular cluster related to the specific interaction energy, see Fig. 8a. The individual energy components, electrostatic (E_ele), polarization (E_pol), dispersion (E_dis) and repulsion (E_rep) energies and the sum of these components (E_tot) for the interactions relative to a reference molecule (*) are shown in Fig. 8b.

Figure 8
The colour-coding interaction mapping within 5 Å of the centering (*) molecular cluster.

5. Database survey

A search of the Cambridge Structural Database (CSD, Version 5.41, last update March 2020; Groom et al., 2016 ) for the 3,6-bis(methoxymethoxy)phenyl substructure gave only six hits. Three compounds are of particular interest, namely 1-[2-bromo-3,6-bis(methoxymethoxy)phenyl]-1-methoxyheptan-2-ol (CSD refcode GEZPUZ; Nakayama et al., 2018 ), 7-bromo-4-methoxy-5,8-bis(methoxymethoxy)-3-pentyl-3,4-dihydro-1H-2-benzopyran-1-one (GEZQAG; Nakayama et al., 2018) and 2,2′-{[2,5-bis(methoxymethoxy)-1,4-phenylene]dimethylylidene}dimalononitrile (IVIQIP; Zhang et al., 2017 ). The first two, GEZPUZ and GEZQAG [compounds 17 and 20 in the publication by Nakayama et al. (2018)], are key intermediates in the synthesis of the dihydroisocoumarin-type natural products, eurotiumide A and eurotiumide B. Compound IVIQIP [compound 1c in the publication by Zhang et al. (2017)] was synthesized in a study of organic solid fluorophores. The conformation of the –O–CH₂–O–CH₃ side chains are compared to that in compound I in Fig. 9 and Table 3. In GEZPUZ and GEZQAG these side chains are twisted and directed to the same side of the benzene ring. In IVIQIP they are also twisted but directed to opposite sides of the benzene ring as in compound I.

Figure 9
A view of the molecular structures of I, GEZPUZ, GEZQAGr and IVIQIP. The original atom-labelling schemes have been used for the latter three compounds. For clarity, H atoms have been omitted

A search of the CSD for the substructure 2-(2-(methoxycarbonyl)phenyl)acetic acid gave zero hits.

6. Synthesis and crystallization

The synthesis of compound I is illustrated in Fig. 1. Full details of the syntheses and spectroscopic and analytical data for compounds 2–5 and I are available in the PhD thesis of Tiouabi (2005). It can be downloaded from the website https://doc.rero.ch/record, a digital library where many theses of Swiss universities are deposited. Colourless block-like crystals of I were obtained by slow evaporation of a solution in acetone-d₆.

7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 4. The OH and C-bound H atoms were included in calculated positions and treated as riding atoms: O—H = 0.84 Å, C—H = 0.95–0.99 Å with U_iso(H) = 1.5U_eq(OH and C-methyl) and 1.2U_eq(C) for other H-atoms.

Table 4
Experimental details

Crystal data
Chemical formula	C₁₄H₁₈O₈
M_r	314.28
Crystal system, space group	Triclinic, P $[\overline{1}]$
Temperature (K)	173
a, b, c (Å)	8.5628 (12), 9.6623 (13), 9.9767 (12)
α, β, γ (°)	112.534 (14), 94.744 (15), 97.999 (16)
V (Å³)	746.60 (19)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	0.12
Crystal size (mm)	0.30 × 0.30 × 0.20

Data collection
Diffractometer	Stoe IPDS 1
Absorption correction	Multi-scan (MULABS; Spek, 2020 )
T_min, T_max	0.827, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	6011, 2752, 1557
R_int	0.065
(sin θ/λ)_max (Å⁻¹)	0.617

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.045, 0.108, 0.83
No. of reflections	2752
No. of parameters	204
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.25, −0.23
Computer programs: EXPOSE, CELL and INTEGRATE in IPDS-I (Stoe & Cie, 2004 ), SHELXS97 (Sheldrick, 2008 ), Mercury (Macrae et al., 2020), SHELXL2018/3 (Sheldrick, 2015 ), PLATON (Spek, 2020) and publCIF (Westrip, 2010 ).

Intensity data were measured using a Stoe IPDS I, a one-circle diffractometer. For the triclinic system often only 93% of the Ewald sphere is accessible, which explains why the alert diffrn_reflns_laue_measured_fraction_full value (0.942) below minimum (0.95) is given. This involves 155 random reflections out of the expected 2692 for the IUCr cutoff limit of sin θ/λ = 0.60.

Supporting information

CCDC reference: 2009890

Crystal structure: contains datablocks I, Global. DOI: https://doi.org/10.1107/S2056989020007987/ex2033sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989020007987/ex2033Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989020007987/ex2033Isup3.cml

checkCIF report

Computing details top

Data collection: EXPOSE in IPDS-I (Stoe & Cie, 2004); cell refinement: CELL in IPDS-I (Stoe & Cie, 2004); data reduction: INTEGRATE in IPDS-I (Stoe & Cie, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015); molecular graphics: Mercury (Macrae et al., 2020); software used to prepare material for publication: SHELXL2018/3 (Sheldrick, 2015), PLATON (Spek, 2020) and publCIF (Westrip, 2010).

2-[2-(Methoxycarbonyl)-3,6-bis(methoxymethoxy)phenyl]acetic acid top

Crystal data top

C₁₄H₁₈O₈	Z = 2
M_r = 314.28	F(000) = 332
Triclinic, P1	D_x = 1.398 Mg m⁻³
a = 8.5628 (12) Å	Mo Kα radiation, λ = 0.71073 Å
b = 9.6623 (13) Å	Cell parameters from 3063 reflections
c = 9.9767 (12) Å	θ = 2.2–25.8°
α = 112.534 (14)°	µ = 0.12 mm⁻¹
β = 94.744 (15)°	T = 173 K
γ = 97.999 (16)°	Block, colourless
V = 746.60 (19) Å³	0.30 × 0.30 × 0.20 mm

Data collection top

Stoe IPDS 1 diffractometer	2752 independent reflections
Radiation source: fine-focus sealed tube	1557 reflections with I > 2σ(I)
Plane graphite monochromator	R_int = 0.065
φ rotation scans	θ_max = 26.0°, θ_min = 2.3°
Absorption correction: multi-scan (MULABS; Spek, 2020)	h = −10→10
T_min = 0.827, T_max = 1.000	k = −11→11
6011 measured reflections	l = −11→11

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.045	H-atom parameters constrained
wR(F²) = 0.108	w = 1/[σ²(F_o²) + (0.0527P)²] where P = (F_o² + 2F_c²)/3
S = 0.83	(Δ/σ)_max < 0.001
2752 reflections	Δρ_max = 0.25 e Å⁻³
204 parameters	Δρ_min = −0.23 e Å⁻³
0 restraints	Extinction correction: (SHELXL2018/3; Sheldrick, 2015), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.019 (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

	x	y	z	U_iso*/U_eq
O1	0.25754 (19)	0.8960 (2)	0.1239 (2)	0.0457 (5)
O2	0.30589 (19)	0.94409 (18)	0.3608 (2)	0.0427 (5)
O3	−0.08148 (17)	0.86702 (16)	0.21564 (19)	0.0354 (4)
O4	−0.36196 (18)	0.82093 (18)	0.1605 (2)	0.0411 (5)
O5	0.12039 (17)	0.34010 (16)	0.18992 (18)	0.0313 (4)
O6	−0.07328 (18)	0.23819 (17)	0.29737 (19)	0.0357 (4)
O7	0.35707 (18)	0.58696 (18)	0.45712 (19)	0.0373 (4)
O8	0.52484 (19)	0.4650 (2)	0.3133 (2)	0.0449 (5)
H8	0.548084	0.441888	0.384533	0.067*
C1	0.1715 (2)	0.5912 (2)	0.2067 (2)	0.0255 (5)
C2	0.1204 (2)	0.7231 (2)	0.2130 (2)	0.0255 (5)
C3	−0.0431 (2)	0.7295 (2)	0.2044 (3)	0.0266 (5)
C4	−0.1531 (2)	0.6025 (2)	0.1876 (3)	0.0290 (5)
H4	−0.263625	0.606043	0.179939	0.035*
C5	−0.1034 (2)	0.4714 (2)	0.1817 (3)	0.0292 (5)
H5	−0.179938	0.384882	0.170246	0.035*
C6	0.0580 (2)	0.4643 (2)	0.1925 (2)	0.0262 (5)
C7	0.2333 (2)	0.8614 (2)	0.2243 (3)	0.0284 (5)
C8	0.4160 (3)	1.0825 (3)	0.3806 (3)	0.0494 (7)
H8A	0.495875	1.056174	0.314572	0.074*
H8B	0.469429	1.131775	0.482449	0.074*
H8C	0.356664	1.152557	0.357997	0.074*
C9	−0.2285 (3)	0.8986 (3)	0.2679 (3)	0.0376 (6)
H9A	−0.238127	0.869474	0.352219	0.045*
H9B	−0.226769	1.009573	0.303253	0.045*
C10	−0.3713 (3)	0.8721 (3)	0.0443 (3)	0.0509 (7)
H10A	−0.362356	0.983164	0.085357	0.076*
H10B	−0.473812	0.824240	−0.019781	0.076*
H10C	−0.284222	0.844062	−0.012623	0.076*
C11	0.0113 (3)	0.2090 (2)	0.1794 (3)	0.0314 (5)
H11A	−0.065027	0.172092	0.087538	0.038*
H11B	0.071162	0.126917	0.174037	0.038*
C12	0.0227 (3)	0.2754 (3)	0.4335 (3)	0.0487 (7)
H12A	0.078802	0.191711	0.426820	0.073*
H12B	−0.044987	0.291178	0.510676	0.073*
H12C	0.100661	0.368863	0.457137	0.073*
C13	0.3446 (2)	0.5742 (3)	0.2107 (3)	0.0313 (6)
H13A	0.356492	0.490502	0.118404	0.038*
H13B	0.409856	0.669321	0.215295	0.038*
C14	0.4080 (2)	0.5412 (2)	0.3378 (3)	0.0305 (5)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0385 (9)	0.0556 (11)	0.0457 (13)	−0.0099 (8)	−0.0036 (8)	0.0315 (9)
O2	0.0435 (10)	0.0378 (9)	0.0348 (12)	−0.0124 (7)	−0.0001 (8)	0.0095 (8)
O3	0.0246 (8)	0.0319 (8)	0.0551 (13)	0.0073 (7)	0.0093 (7)	0.0217 (8)
O4	0.0259 (8)	0.0473 (10)	0.0627 (14)	0.0081 (7)	0.0063 (8)	0.0351 (9)
O5	0.0300 (8)	0.0276 (8)	0.0384 (11)	0.0054 (6)	0.0041 (7)	0.0156 (7)
O6	0.0350 (9)	0.0405 (9)	0.0339 (12)	0.0031 (7)	0.0048 (7)	0.0189 (8)
O7	0.0339 (9)	0.0460 (9)	0.0320 (12)	0.0076 (7)	0.0029 (8)	0.0159 (8)
O8	0.0354 (9)	0.0633 (11)	0.0482 (14)	0.0216 (8)	0.0067 (8)	0.0311 (10)
C1	0.0224 (10)	0.0305 (11)	0.0229 (14)	0.0026 (9)	0.0015 (9)	0.0112 (9)
C2	0.0245 (11)	0.0282 (11)	0.0243 (15)	0.0007 (9)	0.0016 (9)	0.0127 (9)
C3	0.0269 (11)	0.0283 (11)	0.0281 (15)	0.0075 (9)	0.0032 (9)	0.0144 (10)
C4	0.0219 (11)	0.0340 (12)	0.0320 (16)	0.0036 (9)	0.0019 (9)	0.0151 (10)
C5	0.0239 (11)	0.0299 (12)	0.0312 (15)	−0.0015 (9)	0.0006 (9)	0.0123 (10)
C6	0.0266 (11)	0.0283 (11)	0.0248 (15)	0.0060 (9)	0.0022 (9)	0.0118 (10)
C7	0.0233 (11)	0.0333 (12)	0.0313 (16)	0.0057 (9)	0.0019 (10)	0.0161 (11)
C8	0.0392 (14)	0.0377 (14)	0.055 (2)	−0.0118 (11)	0.0019 (13)	0.0082 (12)
C9	0.0320 (12)	0.0371 (13)	0.0486 (19)	0.0120 (10)	0.0119 (11)	0.0191 (12)
C10	0.0426 (15)	0.0641 (17)	0.060 (2)	0.0190 (13)	0.0137 (13)	0.0355 (15)
C11	0.0370 (13)	0.0257 (11)	0.0293 (16)	0.0006 (9)	0.0014 (10)	0.0111 (10)
C12	0.0506 (16)	0.0578 (17)	0.0354 (19)	0.0046 (13)	0.0034 (12)	0.0187 (13)
C13	0.0237 (11)	0.0346 (12)	0.0395 (17)	0.0064 (9)	0.0054 (10)	0.0186 (11)
C14	0.0206 (11)	0.0317 (12)	0.0389 (18)	0.0009 (9)	0.0013 (10)	0.0158 (11)

Geometric parameters (Å, º) top

O1—C7	1.196 (3)	C4—C5	1.374 (3)
O2—C7	1.329 (3)	C4—H4	0.9500
O2—C8	1.461 (3)	C5—C6	1.391 (3)
O3—C3	1.379 (2)	C5—H5	0.9500
O3—C9	1.429 (3)	C8—H8A	0.9800
O4—C9	1.400 (3)	C8—H8B	0.9800
O4—C10	1.425 (3)	C8—H8C	0.9800
O5—C6	1.372 (2)	C9—H9A	0.9900
O5—C11	1.429 (2)	C9—H9B	0.9900
O6—C11	1.390 (3)	C10—H10A	0.9800
O6—C12	1.417 (3)	C10—H10B	0.9800
O7—C14	1.240 (3)	C10—H10C	0.9800
O8—C14	1.308 (3)	C11—H11A	0.9900
O8—H8	0.8400	C11—H11B	0.9900
C1—C2	1.386 (3)	C12—H12A	0.9800
C1—C6	1.408 (3)	C12—H12B	0.9800
C1—C13	1.513 (3)	C12—H12C	0.9800
C2—C3	1.406 (3)	C13—C14	1.499 (3)
C2—C7	1.496 (3)	C13—H13A	0.9900
C3—C4	1.383 (3)	C13—H13B	0.9900

C7—O2—C8	115.27 (19)	O4—C9—O3	113.0 (2)
C3—O3—C9	116.23 (16)	O4—C9—H9A	109.0
C9—O4—C10	113.21 (19)	O3—C9—H9A	109.0
C6—O5—C11	117.44 (16)	O4—C9—H9B	109.0
C11—O6—C12	113.99 (18)	O3—C9—H9B	109.0
C14—O8—H8	109.5	H9A—C9—H9B	107.8
C2—C1—C6	119.14 (18)	O4—C10—H10A	109.5
C2—C1—C13	123.33 (18)	O4—C10—H10B	109.5
C6—C1—C13	117.51 (18)	H10A—C10—H10B	109.5
C1—C2—C3	120.27 (18)	O4—C10—H10C	109.5
C1—C2—C7	122.31 (18)	H10A—C10—H10C	109.5
C3—C2—C7	117.40 (18)	H10B—C10—H10C	109.5
O3—C3—C4	124.46 (18)	O6—C11—O5	112.89 (17)
O3—C3—C2	115.83 (17)	O6—C11—H11A	109.0
C4—C3—C2	119.71 (18)	O5—C11—H11A	109.0
C5—C4—C3	120.44 (19)	O6—C11—H11B	109.0
C5—C4—H4	119.8	O5—C11—H11B	109.0
C3—C4—H4	119.8	H11A—C11—H11B	107.8
C4—C5—C6	120.48 (18)	O6—C12—H12A	109.5
C4—C5—H5	119.8	O6—C12—H12B	109.5
C6—C5—H5	119.8	H12A—C12—H12B	109.5
O5—C6—C5	125.22 (17)	O6—C12—H12C	109.5
O5—C6—C1	114.84 (17)	H12A—C12—H12C	109.5
C5—C6—C1	119.94 (19)	H12B—C12—H12C	109.5
O1—C7—O2	122.7 (2)	C14—C13—C1	113.74 (19)
O1—C7—C2	125.0 (2)	C14—C13—H13A	108.8
O2—C7—C2	112.25 (19)	C1—C13—H13A	108.8
O2—C8—H8A	109.5	C14—C13—H13B	108.8
O2—C8—H8B	109.5	C1—C13—H13B	108.8
H8A—C8—H8B	109.5	H13A—C13—H13B	107.7
O2—C8—H8C	109.5	O7—C14—O8	123.2 (2)
H8A—C8—H8C	109.5	O7—C14—C13	122.6 (2)
H8B—C8—H8C	109.5	O8—C14—C13	114.1 (2)

C6—C1—C2—C3	−0.3 (3)	C13—C1—C6—O5	2.6 (3)
C13—C1—C2—C3	178.2 (2)	C2—C1—C6—C5	1.4 (3)
C6—C1—C2—C7	−178.5 (2)	C13—C1—C6—C5	−177.2 (2)
C13—C1—C2—C7	0.0 (3)	C8—O2—C7—O1	1.1 (3)
C9—O3—C3—C4	24.5 (3)	C8—O2—C7—C2	−178.97 (19)
C9—O3—C3—C2	−154.8 (2)	C1—C2—C7—O1	99.6 (3)
C1—C2—C3—O3	178.31 (19)	C3—C2—C7—O1	−78.6 (3)
C7—C2—C3—O3	−3.4 (3)	C1—C2—C7—O2	−80.3 (3)
C1—C2—C3—C4	−1.0 (3)	C3—C2—C7—O2	101.5 (2)
C7—C2—C3—C4	177.3 (2)	C10—O4—C9—O3	−67.6 (2)
O3—C3—C4—C5	−178.0 (2)	C3—O3—C9—O4	−77.8 (2)
C2—C3—C4—C5	1.2 (3)	C12—O6—C11—O5	−65.5 (2)
C3—C4—C5—C6	−0.1 (3)	C6—O5—C11—O6	−61.3 (2)
C11—O5—C6—C5	−1.9 (3)	C2—C1—C13—C14	119.8 (2)
C11—O5—C6—C1	178.44 (19)	C6—C1—C13—C14	−61.7 (3)
C4—C5—C6—O5	179.1 (2)	C1—C13—C14—O7	−29.8 (3)
C4—C5—C6—C1	−1.2 (3)	C1—C13—C14—O8	152.52 (19)
C2—C1—C6—O5	−178.9 (2)

Hydrogen-bond geometry (Å, º) top

Cg is the centroid of the C1–C6 benzene ring.

D—H···A	D—H	H···A	D···A	D—H···A
C4—H4···O4	0.95	2.41	3.022 (3)	122
O8—H8···O7ⁱ	0.84	1.85	2.676 (2)	168
C9—H9B···O6ⁱⁱ	0.99	2.43	3.256 (3)	140
C11—H11A···O1ⁱⁱⁱ	0.99	2.38	3.366 (3)	175
C13—H13B···O4^iv	0.99	2.50	3.421 (3)	155
C12—H12B···Cg^v	0.98	2.66	3.451 (3)	138

Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) x, y+1, z; (iii) −x, −y+1, −z; (iv) x+1, y, z; (v) −x, −y+1, −z+1.

Short interatomic contacts (Å)^a in the crystal of compound I top

Atom1	Atom2	Length	Length-VdW
O7	H8ⁱ	1.850	-0.870
O7	O8ⁱ	2.676	-0.364
O1	H11Aⁱⁱⁱ	2.379	-0.341
O6	H9B^vi	2.432	-0.288
O4	H13B^v	2.501	-0.219
H8	C14ⁱ	2.703	-0.197
O5	H10Cⁱⁱⁱ	2.637	-0.083
C12	H9B^vi	2.882	-0.018
O4	H8A^v	2.723	0.003
O7	C8^viii	3.223	0.003
O7	H8B^viii	2.726	0.006
O2	H8B^viii	2.731	0.011
H8	H8ⁱ	2.416	0.016
C2	H12B^vii	2.932	0.032
O6	C9^vi	3.256	0.036
H8B	C14^viii	2.954	0.054
C9	H8A^v	2.957	0.057
C1	H12B^vii	2.968	0.068
C3	H12B^vii	2.968	0.068
H10C	C11ⁱⁱⁱ	2.969	0.069
H9B	H8A^v	2.482	0.082

(a) Calculated using Mercury (Macrae et al., 2020). Symmetry codes: (i) -x + 1, -y + 1, -z + 1; (iii) -x, -y + 1, -z; (v) x - 1, y, z; (vi) x, y - 1, z; (vii) -x, -y + 1, -z + 1; (viii) -x + 1, -y + 2, -z + 1.

Selected torsion angles (°) in compound I compared to those in compounds GEZPUZ, GEZQAG and IVIQIP top

I
C3—O3—C9—O4	-77.8 (2)
C10—O4—C9—O3	-67.6 (2)
C6—O5—C11—O6	-61.3 (2)
C12—O6—C11—O5	-65.5 (2)

GEZPUZ^a
C7—O4—C13—O1	67.1 (3)
C16—O1—C13—O4	56.3 (3)
C8—O5—C12—O6	-80.1 (2)
C17—O6—C12—O5	-65.8 (3)

GEZQAG^a
C7—O2—C12—O7	-71.2 (8)
C16—O7—C12—O2	-67.6 (9)
C9—O3—C10—O6	86.1 (7)
C17—O6—C10—O3	76.6 (8)

IVIQIP^b^,^c
C1—O1—C8—O2	-68.9 (2)
C9—O2—C8—O1	-66.1 (2)

(a) Nakayama et al. (2018); (b) Zhang et al. (2017); (c) compound IVIQIP possesses inversion symmetry.

Acknowledgements

RT and HSE are grateful to the University of Neuchâtel for their support over the years.

Funding information

Funding for this research was provided by: Swiss National Science Foundation and the University of Neuchâtel.

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