Crystal structure of 5-hy­droxy­methyl-2-meth­oxy­phenol

Hassan, M.; Ashraf, Z.; Seo, S.-Y.; Kim, D.; Kang, S.K.

doi:10.1107/S205698901501230X

organic compounds

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Volume 71| Part 8| August 2015| Pages o540-o541

https://doi.org/10.1107/S205698901501230X

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Crystal structure of 5-hydroxymethyl-2-methoxyphenol

Mubashir Hassan,^a Zaman Ashraf,^a,^b Sung-Yum Seo,^a Daeyoung Kim ^c and Sung Kwon Kang ^c ^*

^aDepartment of Biology, College of Natural Sciences, Kongju National University, Gongju 314-701, Republic of Korea, ^bDepartment of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan, and ^cDepartment of Chemistry, Chungnam National University, Daejeon 305-764, Republic of Korea
^*Correspondence e-mail: skkang@cnu.ac.kr

Edited by E. R. T. Tiekink, University of Malaya, Malaysia (Received 25 June 2015; accepted 26 June 2015; online 4 July 2015)

In the title compound, C₈H₁₀O₃, the hydroxymethyl group is twisted by 74.51 (13)° from the plane of the benzene ring to which it is connected. By contrast, the benzene and methoxy groups are almost coplanar, making a dihedral angle of 4.0 (2)°. In the crystal, O—H⋯O hydrogen bonds link the molecules into a three-dimensional network.

Keywords: crystal structure; alcoholic hydroxy compounds; O—H⋯O hydrogen bonding.

CCDC reference: 1409010

1. Related literature

For the background to alcoholic hydroxy compounds and their applications, see: Patrick (2001 ); Yasohara et al. (2001 ); Rodríguez-Barrios & Gago (2004 ); Wu et al. (2008 ); Matteelli et al. (2010 ); Coimbra et al. (2010 ); Hans et al. (2010 ); Cordova et al. (2006 ). For the synthesis of derivatives of the title compound, see: Ashraf et al. (2014 , 2015 ).

2. Experimental

2.1. Crystal data

C₈H₁₀O₃
M_r = 154.16
Orthorhombic, P b c a
a = 15.011 (4) Å
b = 6.1354 (18) Å
c = 16.543 (5) Å
V = 1523.6 (7) Å³
Z = 8
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 296 K
0.28 × 0.25 × 0.23 mm

2.2. Data collection

Bruker SMART CCD area-detector diffractometer
28952 measured reflections
1900 independent reflections
1530 reflections with I > 2σ(I)
R_int = 0.025

2.3. Refinement

R[F² > 2σ(F²)] = 0.051
wR(F²) = 0.149
S = 1.07
1900 reflections
108 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.38 e Å⁻³
Δρ_min = −0.42 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯O9ⁱ	0.74 (4)	2.11 (4)	2.773 (2)	150 (4)
O1—H1⋯O10ⁱ	0.74 (4)	2.54 (4)	3.152 (2)	142 (4)
O9—H9⋯O1ⁱⁱ	0.88 (4)	1.78 (4)	2.641 (2)	163 (3)
Symmetry codes: (i) $[x, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ ; (ii) $[-x+1, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

Data collection: SMART (Bruker, 2002 ); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT; program(s) used to solve structure: SHELXS2013 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2015 ); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ); software used to prepare material for publication: WinGX (Farrugia, 2012).

Supporting information

CCDC reference: 1409010

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S205698901501230X/tk5370sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S205698901501230X/tk5370Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S205698901501230X/tk5370Isup3.cml

checkCIF report

Chemical context top

It has been identified that the presence of alcoholic, phenolic hydroxyl and amino groups are particularly important functionalities in biologically active compounds (Patrick, 2001). These important functionalities displayed biological activities because they can facilitate interactions with appropriate receptor molecules (Yasohara et al., 2001). A new class of compounds having an alcoholic hydroxyl group showed high enzyme inhibitory potential and excellent permeation through a Caco-2 cell membrane (Rodríguez-Barrios & Gag, 2004). Some tertiary alcohol derivatives showed significant HIV-1 protease inhibitory activity (Wu et al., 2008). Heterocyclic compounds such as diarylquinolines having a quinolinic central nucleus and alcoholic –OH group at the side-chains exhibited anti-mycobacterial activity (Matteelli et al., 2010). β-Amino alcohols are a class of compounds with a wide range of bioactivities, such as anti-plasmodial (Hans et al., 2010), anti-leishmanial (Coimbra et al., 2010) and anti-proliferative (Cordova et al., 2006). The hydroxy substituted benzoic acids and cinnamic acid analogues have been reported as mushroom tyrosinase inhibitors (Ashraf et al., 2014; Ashraf et al., 2015). Keeping in view the wide range of biological activities of hydroxylated compounds, here we report the synthesis and crystal structure of the title compound, isolated as an intermediate. The title alcohol is a valuable starting material for the synthesis of hydroxy substituted scaffolds.

Synthesis and crystallization top

The title compound was synthesized by the reduction of isovanillin in the presence of sodium borohydride and methanol. The sodium borohydride reduction of aldehydes and ketones to the corresponding alcohols is a commonly used method in organic synthesis. Isovanillin was dissolved in methanol and then sodium borohydride was added at a slow rate to keep the reaction temperature below 25 °C. The excess of sodium borohydride was used to assure the completion of the reaction. After the completion of the reaction the product was obtained by acidic workup (86%, m.p. 135-137 °C). The title compound was crystallized as cubic crystals from a solution of ethyl acetate by slow evaporation.

Refinement top

H atoms on OH groups were located in a difference Fourier map and refined freely [refined O—H distances = 0.74 (4) – 0.88 (4) Å]. The C-bound H atoms were positioned geometrically and refined using riding model, with d(C—H) = 0.93 – 0.97 Å, and with U_iso(H) = 1.2U_eq(C) for phenyl-H and methylene-H and 1.5U_eq(C) for methyl-H atoms.

Related literature top

For the background to alcoholic hydroxy compounds and their applications, see: Patrick (2001); Yasohara et al. (2001); Rodríguez-Barrios & Gago (2004); Wu et al. (2008); Matteelli et al. (2010); Coimbra et al. (2010); Hans et al. (2010); Cordova et al. (2006). For the synthesis of derivatives of the title compound, see: Ashraf et al. (2014, 2015).

Structure description top

For the background to alcoholic hydroxy compounds and their applications, see: Patrick (2001); Yasohara et al. (2001); Rodríguez-Barrios & Gago (2004); Wu et al. (2008); Matteelli et al. (2010); Coimbra et al. (2010); Hans et al. (2010); Cordova et al. (2006). For the synthesis of derivatives of the title compound, see: Ashraf et al. (2014, 2015).

Synthesis and crystallization top

Refinement details top

Computing details top

Data collection: SMART (Bruker, 2002); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT (Bruker, 2002); program(s) used to solve structure: SHELXS2013 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: WinGX (Farrugia, 2012).

Figures top

	Fig. 1. The molecular structure of the title compound, showing the atom-numbering scheme and 30% probability ellipsoids.
	Fig. 2. Part of the crystal structure of the title compound, showing the 3-D network of molecules linked by intermolecular O—H···O hydrogen bonds (dashed lines).

5-Hydroxymethyl-2-methoxyphenol top

Crystal data top

C₈H₁₀O₃	F(000) = 656
M_r = 154.16	D_x = 1.344 Mg m⁻³
Orthorhombic, Pbca	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 7746 reflections
a = 15.011 (4) Å	θ = 2.5–28.2°
b = 6.1354 (18) Å	µ = 0.10 mm⁻¹
c = 16.543 (5) Å	T = 296 K
V = 1523.6 (7) Å³	Block, brown
Z = 8	0.28 × 0.25 × 0.23 mm

Data collection top

Bruker SMART CCD area-detector diffractometer	R_int = 0.025
Radiation source: fine-focus sealed tube	θ_max = 28.4°, θ_min = 2.5°
φ and ω scans	h = −20→19
28952 measured reflections	k = −8→8
1900 independent reflections	l = −22→20
1530 reflections with I > 2σ(I)

Refinement top

Refinement on F²	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.051	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.149	w = 1/[σ²(F_o²) + (0.0668P)² + 0.6464P] where P = (F_o² + 2F_c²)/3
S = 1.07	(Δ/σ)_max < 0.001
1900 reflections	Δρ_max = 0.38 e Å⁻³
108 parameters	Δρ_min = −0.42 e Å⁻³

Crystal data top

C₈H₁₀O₃	V = 1523.6 (7) Å³
M_r = 154.16	Z = 8
Orthorhombic, Pbca	Mo Kα radiation
a = 15.011 (4) Å	µ = 0.10 mm⁻¹
b = 6.1354 (18) Å	T = 296 K
c = 16.543 (5) Å	0.28 × 0.25 × 0.23 mm

Data collection top

Bruker SMART CCD area-detector diffractometer	1530 reflections with I > 2σ(I)
28952 measured reflections	R_int = 0.025
1900 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.051	0 restraints
wR(F²) = 0.149	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	Δρ_max = 0.38 e Å⁻³
1900 reflections	Δρ_min = −0.42 e Å⁻³
108 parameters

Special details top

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

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

	x	y	z	U_iso*/U_eq
O1	0.56019 (17)	0.3078 (3)	0.91644 (10)	0.1025 (9)
H1	0.559 (2)	0.268 (6)	0.959 (2)	0.129 (13)*
C2	0.61335 (11)	0.1812 (3)	0.86876 (9)	0.0462 (4)
H2A	0.5895	0.0345	0.8663	0.055*
H2B	0.6727	0.1737	0.8919	0.055*
C3	0.61828 (10)	0.2752 (3)	0.78509 (9)	0.0383 (4)
C4	0.57178 (10)	0.1775 (3)	0.72196 (8)	0.0388 (4)
H4	0.5385	0.0524	0.7316	0.047*
C5	0.57476 (10)	0.2651 (3)	0.64505 (8)	0.0375 (3)
C6	0.62554 (10)	0.4516 (3)	0.62970 (9)	0.0368 (3)
C7	0.67100 (11)	0.5504 (3)	0.69227 (10)	0.0452 (4)
H7	0.7042	0.6757	0.6828	0.054*
C8	0.66682 (11)	0.4616 (3)	0.76955 (9)	0.0454 (4)
H8	0.6973	0.5292	0.8116	0.054*
O9	0.52924 (10)	0.1784 (2)	0.58164 (7)	0.0554 (4)
H9	0.498 (2)	0.060 (6)	0.5924 (18)	0.124 (12)*
O10	0.62581 (8)	0.5189 (2)	0.55089 (7)	0.0472 (3)
C11	0.67256 (15)	0.7139 (3)	0.53259 (12)	0.0588 (5)
H11A	0.6682	0.7433	0.4757	0.088*
H11B	0.7341	0.6976	0.5473	0.088*
H11C	0.647	0.8328	0.5624	0.088*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.1593 (19)	0.1051 (14)	0.0432 (8)	0.0824 (14)	0.0458 (10)	0.0312 (9)
C2	0.0512 (9)	0.0580 (10)	0.0293 (7)	0.0082 (7)	−0.0009 (6)	0.0039 (7)
C3	0.0371 (7)	0.0506 (9)	0.0272 (7)	0.0057 (6)	0.0004 (5)	0.0000 (6)
C4	0.0443 (8)	0.0425 (8)	0.0296 (7)	−0.0036 (6)	0.0043 (6)	−0.0003 (6)
C5	0.0429 (7)	0.0434 (8)	0.0263 (7)	−0.0021 (6)	0.0013 (5)	−0.0039 (6)
C6	0.0395 (7)	0.0431 (8)	0.0277 (7)	0.0011 (6)	0.0025 (5)	0.0014 (6)
C7	0.0469 (8)	0.0503 (9)	0.0384 (8)	−0.0110 (7)	−0.0005 (6)	−0.0007 (7)
C8	0.0443 (8)	0.0590 (10)	0.0327 (8)	−0.0063 (7)	−0.0063 (6)	−0.0050 (7)
O9	0.0752 (9)	0.0631 (8)	0.0279 (6)	−0.0280 (7)	−0.0037 (5)	−0.0024 (5)
O10	0.0610 (7)	0.0505 (7)	0.0302 (6)	−0.0110 (5)	0.0009 (5)	0.0060 (5)
C11	0.0761 (13)	0.0528 (11)	0.0476 (10)	−0.0137 (9)	0.0028 (9)	0.0127 (8)

Geometric parameters (Å, º) top

O1—C2	1.365 (2)	C6—O10	1.3677 (18)
O1—H1	0.74 (4)	C6—C7	1.380 (2)
C2—C3	1.501 (2)	C7—C8	1.391 (2)
C2—H2A	0.97	C7—H7	0.93
C2—H2B	0.97	C8—H8	0.93
C3—C8	1.380 (2)	O9—H9	0.88 (4)
C3—C4	1.392 (2)	O10—C11	1.420 (2)
C4—C5	1.382 (2)	C11—H11A	0.96
C4—H4	0.93	C11—H11B	0.96
C5—O9	1.3601 (18)	C11—H11C	0.96
C5—C6	1.398 (2)

C2—O1—H1	112 (3)	O10—C6—C5	114.96 (13)
O1—C2—C3	110.07 (15)	C7—C6—C5	119.54 (14)
O1—C2—H2A	109.6	C6—C7—C8	119.66 (16)
C3—C2—H2A	109.6	C6—C7—H7	120.2
O1—C2—H2B	109.6	C8—C7—H7	120.2
C3—C2—H2B	109.6	C3—C8—C7	121.29 (14)
H2A—C2—H2B	108.2	C3—C8—H8	119.4
C8—C3—C4	118.80 (14)	C7—C8—H8	119.4
C8—C3—C2	121.06 (14)	C5—O9—H9	116 (2)
C4—C3—C2	120.12 (15)	C6—O10—C11	117.34 (13)
C5—C4—C3	120.48 (15)	O10—C11—H11A	109.5
C5—C4—H4	119.8	O10—C11—H11B	109.5
C3—C4—H4	119.8	H11A—C11—H11B	109.5
O9—C5—C4	122.81 (14)	O10—C11—H11C	109.5
O9—C5—C6	116.99 (13)	H11A—C11—H11C	109.5
C4—C5—C6	120.20 (13)	H11B—C11—H11C	109.5
O10—C6—C7	125.50 (15)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O9ⁱ	0.74 (4)	2.11 (4)	2.773 (2)	150 (4)
O1—H1···O10ⁱ	0.74 (4)	2.54 (4)	3.152 (2)	142 (4)
O9—H9···O1ⁱⁱ	0.88 (4)	1.78 (4)	2.641 (2)	163 (3)

Symmetry codes: (i) x, −y+1/2, z+1/2; (ii) −x+1, y−1/2, −z+3/2.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O9ⁱ	0.74 (4)	2.11 (4)	2.773 (2)	150 (4)
O1—H1···O10ⁱ	0.74 (4)	2.54 (4)	3.152 (2)	142 (4)
O9—H9···O1ⁱⁱ	0.88 (4)	1.78 (4)	2.641 (2)	163 (3)

Symmetry codes: (i) x, −y+1/2, z+1/2; (ii) −x+1, y−1/2, −z+3/2.

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CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 71| Part 8| August 2015| Pages o540-o541

https://doi.org/10.1107/S205698901501230X

Open

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