Crystal structure of 3,6-dihy­droxy-4,5-di­methyl­benzene-1,2-dicarbaldehyde

Yamazaki, S.; Nishiyama, K.; Yagi, S.; Haraguchi, T.; Akitsu, T.

doi:10.1107/S2056989018012495

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Volume 74| Part 10| October 2018| Pages 1424-1426

https://doi.org/10.1107/S2056989018012495

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Crystal structure of 3,6-dihydroxy-4,5-dimethylbenzene-1,2-dicarbaldehyde

Shu Yamazaki,^a Kazuki Nishiyama,^a Shiomi Yagi,^a Tomoyuki Haraguchi ^a and Takashiro Akitsu ^a ^*

^aDepartment of Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
^*Correspondence e-mail: akitsu@rs.kagu.tus.ac.jp

Edited by L. Van Meervelt, Katholieke Universiteit Leuven, Belgium (Received 23 July 2018; accepted 4 September 2018; online 14 September 2018)

The title compound, C₁₀H₁₀O₄, was synthesized from tetramethyl-1,4-benzoquinone. In the crystal, the almost planar molecule (r.m.s. deviation = 0.024 Å) forms intramolecular hydrogen bonds between the aldehyde and hydroxy groups and exhibits C_2v symmetry. This achiral molecule crystallizes in the chiral space group P2₁ with intermolecular O—H⋯O and C—H⋯O hydrogen bonding and C—H⋯π and C=O⋯π interactions stabilizing the crystal packing.

Keywords: crystal structure; alkylating agents; chiral crystallization.

CCDC reference: 1865811

1. Chemical context

A number of benzo- and naphthoquinone derivatives with one or two side chains being capable of alkylation after reduction were found to exhibit inhibitory activity against the growth of transplantable tumours in mice. Furthermore, inhibition of nucleic acid biosynthesis and of the activities of coenzyme Q mediated enzyme systems are also known for related compounds composed of 3,6-dihydroxy-4,5-dimethylbenzene-1,2-dicarbaldehyde (Lin & Loo, 1977 ; Lin et al., 1978 ). According to the literature, these compounds are synthesized from tetramethyl-1,4-benzoquinone (Lin & Loo, 1977; Lin et al., 1978). Here we report the molecular and crystal structure of an achiral derviative crystallizing in a chiral space group.

2. Structural commentary

The molecular structure of the title compound consists of a benzene ring substituted by two methyl groups, two hydroxy groups and two aldehyde groups (Fig. 1). The molecular point group symmetry is C_2v (H atoms excluded). The C—C bond lengths of the methyl substituents are 1.511 (2) and 1.508 (2) Å, the C—O bond lengths of the hydroxy substituents are 1.354 (2) and 1.350 (2) Å, and the C—C bond lengths of the aldehyde substituents are 1.464 (2) and 1.462 (2) Å. Two intramolecular O—H⋯H hydrogen bonds between the hydroxy and aldehyde functions are observed (Table 1 and Fig. 1). The molecule is essentially planar (r.m.s. deviation = 0.024 Å), with the largest deviation found for atom O2 [0.047 (1) Å].

Table 1
Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of ring C1–C6.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3⋯O2	0.84	1.87	2.6079 (19)	146
O4—H4⋯O1	0.84	1.82	2.5592 (19)	146
O3—H3⋯O4ⁱ	0.84	2.40	3.036 (2)	133
O4—H4⋯O2ⁱⁱ	0.84	2.34	2.809 (2)	116
C7—H7⋯O2ⁱⁱⁱ	0.95	2.51	3.427 (2)	162
C10—H10B⋯Cg1^iv	0.98	3.13	3.645	114
Symmetry codes: (i) x-1, y-1, z; (ii) x+1, y+1, z; (iii) $[-x, y+{\script{1\over 2}}, -z+1]$ ; (iv) x+1, y, z.

Figure 1
The molecular structure of the title compound, showing the atom-numbering scheme and displacement ellipsoids drawn at the 50% probability level.

3. Supramolecular features

In the crystal, molecules are connected along the b axis by O—H⋯O hydrogen bonds and along the c axis by C—H⋯O hydrogen bonds (Table 1 and Fig. 2). As a result, chiral crystals composed of achiral molecules are formed. Many examples of such chiral crystals forming from achiral molecules have been reported for decades, but the prediction of chiral crystallization is still impossible (Koshima & Matsuura, 1998 ; Matsuura & Koshima, 2005 ).

Figure 2
A view of the O—H⋯O hydrogen bonds (dashed lines) present in the crystal lattice of the title compound.

The C8=O2 carbonyl group is stacked on top of the aromatic ring, with the O2⋯Cg1 distance being 3.4846 (19) Å (Cg1 is the centroid of ring C1–C6).

In addition, a weak C—H⋯π interaction C10—H10B⋯Cg1 (3.131 Å) is also found (Table 1 and Fig. 3).

Figure 3
Part of the crystal packing showing the C—H⋯π stacking interactions.

4. Database survey

A search in the Cambridge Structural Database (CSD, Version 5.39, update May 2018; Groom et al., 2016 ) for similar 1,2-dicarbaldehyde structures returned five relevant entries: benzene-1,2-dicarbaldehyde [IHEMAJ (Britton, 2002 ) and IHEMAJ01 (Mendenhall et al., 2003 )], naphthalene-1,2-dicarbaldehyde (FIYQOT; Britton, 1999 ), a chromene-5,6-dicarbaldehyde derivative (IDUCUH; am Ende et al., 2013 ) and a cobalt benzene-1,2-dicarbaldehyde complex (JUKZAQ; Lenges et al., 1999 ). In the first four structures, the aldehyde functions show C—H⋯O interactions (H⋯O distances from 2.226 to 2.360 Å). This is not the case for the cobalt complex JUKZAQ, where the two aldehyde O atoms are facing each other and complexed with cobalt, nor with the title compound where the two aldehyde O atoms are involved in intramolecular hydrogen bonds and the two aldehyde H atoms are facing each other.

The intramolecular O—H⋯O interaction between the 1-carbaldehyde and 2-hydroxy groups is also observed in compounds such as 1,8-dihydroxy-2-naphthaldehyde (BABXUA; Peng et al., 2015 ) and 2,4,6-trihydroxybenzene-1,3,5-tricarbaldehyde (WEPPUE; von Richthofen et al., 2013 ).

5. Synthesis and crystallization

A mixture of tetramethyl-1,4-benzoquinone (2.0406 g, 12.4 mmol) and concentrated piperidine (98.0%, 35 ml) was stirred at room temperature for 35 h. The mixture was evaporated and a white intermediate product was obtained. To a solution of the obtained intermediate product dissolved in acetic acid (18 ml), a mixture of CrO₃ (1.77 g) and 50% acetic acid (35 ml) was added dropwise at 353 K. After 10 min, the reaction mixture was poured onto crushed ice (100 g). The solution was filtered by vacuum filtration and a crude compound was obtained. The crude compound was dissolved in toluene and purified by silica column chromatography to afford 0.567 g (yield 23.5%) of the title compound as a yellow solid (single crystals served for X-ray analysis). IR (KBr, cm⁻¹): 1633 (s), 3436 (m).

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. All H atoms were located in difference Fourier maps. C-bound H atoms were constrained using a riding model [C—H = 0.98 Å and U_iso(H) = 1.5U_eq(C) for methyl H atoms, and C—H = 0.95 Å and U_iso(H) = 1.2U_eq(C) for the aldehyde H atoms]. O-bound H atoms were constrained using a riding model [O—H = 0.84 Å and U_iso(H) = 1.5U_eq(O) for hydroxy H atoms].

Table 2
Experimental details

Crystal data
Chemical formula	C₁₀H₁₀O₄
M_r	194.18
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	100
a, b, c (Å)	5.251 (2), 6.317 (2), 12.999 (5)
β (°)	91.643 (4)
V (Å³)	431.0 (3)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	0.12
Crystal size (mm)	0.38 × 0.30 × 0.13

Data collection
Diffractometer	Bruker APEXII CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2001 )
T_min, T_max	0.785, 0.785
No. of measured, independent and observed [I > 2σ(I)] reflections	2328, 1228, 1207
R_int	0.014
(sin θ/λ)_max (Å⁻¹)	0.650

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.029, 0.082, 1.06
No. of reflections	1228
No. of parameters	131
No. of restraints	1
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.25, −0.22
Absolute structure	Flack x determined using 179 quotients [(I⁺)−(I⁻)]/[(I⁺)+(I⁻)] (Parsons et al., 2013 )
Absolute structure parameter	0.5 (6)
Computer programs: APEX2 and SAINT (Bruker, 2014 ), SHELXT2014 (Sheldrick, 2015a ), SHELXL2014 (Sheldrick, 2015b ), SHELXTL (Sheldrick, 2008 ), WinGX (Farrugia, 2012 ), Mercury (Macrae et al., 2006 ) and publCIF (Westrip, 2010 ).

Supporting information

CCDC reference: 1865811

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2056989018012495/vm2211sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989018012495/vm2211Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989018012495/vm2211Isup3.cml

checkCIF report

Computing details top

Data collection: APEX2 (Bruker, 2014); cell refinement: SAINT (Bruker, 2014); data reduction: SAINT (Bruker, 2014); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008), WinGX (Farrugia, 2012), Mercury (Macrae et al., 2006) and publCIF (Westrip, 2010).

3,6-Dihydroxy-4,5-dimethylbenzene-1,2-dicarbaldehyde top

Crystal data top

C₁₀H₁₀O₄	F(000) = 204
M_r = 194.18	D_x = 1.496 Mg m⁻³
Monoclinic, P2₁	Mo Kα radiation, λ = 0.71073 Å
a = 5.251 (2) Å	Cell parameters from 2083 reflections
b = 6.317 (2) Å	θ = 3.1–27.5°
c = 12.999 (5) Å	µ = 0.12 mm⁻¹
β = 91.643 (4)°	T = 100 K
V = 431.0 (3) Å³	Prism, yellow
Z = 2	0.38 × 0.30 × 0.13 mm

Data collection top

Bruker APEXII CCD diffractometer	1228 independent reflections
Radiation source: fine-focus sealed tube	1207 reflections with I > 2σ(I)
Detector resolution: 8.3333 pixels mm^-1	R_int = 0.014
φ and ω scans	θ_max = 27.5°, θ_min = 1.6°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −6→6
T_min = 0.785, T_max = 0.785	k = −3→8
2328 measured reflections	l = −16→16

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.029	w = 1/[σ²(F_o²) + (0.0523P)² + 0.0966P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.082	(Δ/σ)_max < 0.001
S = 1.06	Δρ_max = 0.25 e Å⁻³
1228 reflections	Δρ_min = −0.22 e Å⁻³
131 parameters	Absolute structure: Flack x determined using 179 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
1 restraint	Absolute structure parameter: 0.5 (6)

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O4	0.7944 (2)	0.8239 (2)	0.27690 (9)	0.0183 (3)
H4	0.7357	0.8998	0.3237	0.027*
O2	−0.0040 (2)	0.1772 (2)	0.38214 (9)	0.0193 (3)
O1	0.5175 (2)	0.9141 (2)	0.42970 (9)	0.0190 (3)
O3	0.2530 (2)	0.0865 (2)	0.21917 (9)	0.0174 (3)
H3	0.1418	0.0689	0.2635	0.026*
C3	0.5775 (3)	0.3220 (3)	0.17026 (11)	0.0136 (3)
C8	0.1144 (3)	0.3446 (3)	0.38843 (12)	0.0150 (4)
H8	0.0717	0.4408	0.4414	0.018*
C4	0.7113 (3)	0.5092 (3)	0.18410 (12)	0.0133 (3)
C1	0.3173 (3)	0.4049 (3)	0.31924 (12)	0.0128 (3)
C2	0.3797 (3)	0.2696 (3)	0.23855 (12)	0.0129 (3)
C7	0.3981 (3)	0.7489 (3)	0.41517 (12)	0.0153 (4)
H7	0.2619	0.7174	0.4592	0.018*
C5	0.6521 (3)	0.6468 (3)	0.26629 (12)	0.0134 (4)
C6	0.4550 (3)	0.5985 (3)	0.33345 (12)	0.0125 (3)
C9	0.6387 (3)	0.1702 (3)	0.08493 (12)	0.0177 (4)
H9A	0.6259	0.2441	0.0187	0.027*
H9B	0.5177	0.0521	0.0848	0.027*
H9C	0.8122	0.1159	0.0958	0.027*
C10	0.9192 (3)	0.5739 (3)	0.11251 (13)	0.0179 (4)
H10A	1.0138	0.4482	0.0915	0.027*
H10B	1.0356	0.6726	0.1481	0.027*
H10C	0.8431	0.6429	0.0515	0.027*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O4	0.0187 (6)	0.0167 (7)	0.0198 (6)	−0.0064 (6)	0.0074 (5)	−0.0031 (5)
O2	0.0174 (5)	0.0194 (6)	0.0214 (6)	−0.0060 (6)	0.0049 (4)	−0.0018 (5)
O1	0.0228 (6)	0.0164 (6)	0.0180 (5)	−0.0036 (6)	0.0033 (5)	−0.0035 (5)
O3	0.0179 (5)	0.0158 (6)	0.0186 (6)	−0.0052 (6)	0.0051 (4)	−0.0035 (5)
C3	0.0127 (7)	0.0166 (8)	0.0117 (7)	0.0021 (7)	0.0015 (6)	−0.0001 (7)
C8	0.0130 (7)	0.0172 (9)	0.0148 (7)	−0.0010 (7)	0.0022 (6)	0.0000 (7)
C4	0.0108 (6)	0.0163 (8)	0.0130 (7)	0.0007 (6)	0.0024 (5)	0.0020 (7)
C1	0.0109 (6)	0.0151 (8)	0.0123 (6)	0.0000 (7)	0.0009 (5)	0.0007 (7)
C2	0.0115 (6)	0.0128 (9)	0.0144 (7)	−0.0017 (6)	0.0000 (6)	0.0010 (6)
C7	0.0162 (7)	0.0154 (8)	0.0142 (7)	0.0003 (7)	0.0018 (6)	0.0012 (7)
C5	0.0114 (6)	0.0151 (9)	0.0137 (7)	−0.0014 (7)	0.0001 (5)	0.0011 (7)
C6	0.0115 (6)	0.0139 (8)	0.0120 (7)	0.0001 (6)	0.0011 (5)	0.0011 (7)
C9	0.0185 (7)	0.0192 (9)	0.0157 (7)	0.0000 (7)	0.0034 (6)	−0.0048 (7)
C10	0.0146 (7)	0.0227 (9)	0.0166 (7)	−0.0003 (7)	0.0062 (6)	0.0012 (7)

Geometric parameters (Å, º) top

O4—C5	1.350 (2)	C4—C10	1.511 (2)
O4—H4	0.84	C1—C2	1.399 (2)
O2—C8	1.228 (2)	C1—C6	1.431 (2)
O1—C7	1.229 (2)	C7—C6	1.462 (2)
O3—C2	1.354 (2)	C7—H7	0.95
O3—H3	0.84	C5—C6	1.406 (2)
C3—C4	1.385 (3)	C9—H9A	0.98
C3—C2	1.424 (2)	C9—H9B	0.98
C3—C9	1.508 (2)	C9—H9C	0.98
C8—C1	1.464 (2)	C10—H10A	0.98
C8—H8	0.95	C10—H10B	0.98
C4—C5	1.419 (2)	C10—H10C	0.98

C5—O4—H4	109.5	C6—C7—H7	118.4
C2—O3—H3	109.5	O4—C5—C6	122.08 (14)
C4—C3—C2	119.60 (14)	O4—C5—C4	116.85 (13)
C4—C3—C9	121.36 (14)	C6—C5—C4	121.06 (16)
C2—C3—C9	119.04 (16)	C5—C6—C1	118.92 (14)
O2—C8—C1	123.97 (16)	C5—C6—C7	118.66 (16)
O2—C8—H8	118.0	C1—C6—C7	122.42 (13)
C1—C8—H8	118.0	C3—C9—H9A	109.5
C3—C4—C5	119.97 (14)	C3—C9—H9B	109.5
C3—C4—C10	121.60 (15)	H9A—C9—H9B	109.5
C5—C4—C10	118.43 (17)	C3—C9—H9C	109.5
C2—C1—C6	119.38 (13)	H9A—C9—H9C	109.5
C2—C1—C8	119.46 (16)	H9B—C9—H9C	109.5
C6—C1—C8	121.15 (15)	C4—C10—H10A	109.5
O3—C2—C1	122.45 (14)	C4—C10—H10B	109.5
O3—C2—C3	116.47 (14)	H10A—C10—H10B	109.5
C1—C2—C3	121.05 (16)	C4—C10—H10C	109.5
O1—C7—C6	123.30 (15)	H10A—C10—H10C	109.5
O1—C7—H7	118.4	H10B—C10—H10C	109.5

C2—C3—C4—C5	0.4 (2)	C3—C4—C5—O4	178.32 (14)
C9—C3—C4—C5	−178.85 (15)	C10—C4—C5—O4	−2.5 (2)
C2—C3—C4—C10	−178.81 (15)	C3—C4—C5—C6	−1.3 (2)
C9—C3—C4—C10	2.0 (2)	C10—C4—C5—C6	177.94 (14)
O2—C8—C1—C2	1.9 (2)	O4—C5—C6—C1	−178.18 (14)
O2—C8—C1—C6	−177.34 (15)	C4—C5—C6—C1	1.4 (2)
C6—C1—C2—O3	−178.32 (13)	O4—C5—C6—C7	2.0 (2)
C8—C1—C2—O3	2.5 (2)	C4—C5—C6—C7	−178.41 (15)
C6—C1—C2—C3	−0.2 (2)	C2—C1—C6—C5	−0.6 (2)
C8—C1—C2—C3	−179.44 (14)	C8—C1—C6—C5	178.56 (15)
C4—C3—C2—O3	178.56 (14)	C2—C1—C6—C7	179.16 (16)
C9—C3—C2—O3	−2.2 (2)	C8—C1—C6—C7	−1.6 (2)
C4—C3—C2—C1	0.4 (2)	O1—C7—C6—C5	−1.6 (2)
C9—C3—C2—C1	179.61 (14)	O1—C7—C6—C1	178.61 (14)

Hydrogen-bond geometry (Å, º) top

Cg1 is the centroid of ring C1-C6.

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···O2	0.84	1.87	2.6079 (19)	146
O4—H4···O1	0.84	1.82	2.5592 (19)	146
O3—H3···O4ⁱ	0.84	2.40	3.036 (2)	133
O4—H4···O2ⁱⁱ	0.84	2.34	2.809 (2)	116
C7—H7···O2ⁱⁱⁱ	0.95	2.51	3.427 (2)	162
C10—H10···Cg1^iv	0.98	3.13	3.645	114

Symmetry codes: (i) x−1, y−1, z; (ii) x+1, y+1, z; (iii) −x, y+1/2, −z+1; (iv) x+1, y, z.

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