Crystal structure of 5-hy­droxy­methyl-2-meth­oxy­phenol

Mubashir Hassan; Zaman Ashraf; Sung-Yum Seo; Daeyoung Kim; Sung Kwon Kang

doi:10.1107/S205698901501230X

. 2015 Jul 4;71(Pt 8):o540–o541. doi: 10.1107/S205698901501230X

Crystal structure of 5-hydroxymethyl-2-methoxyphenol

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

PMCID: PMC4571386 PMID: 26396786

Abstract

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

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 ▸).

Experimental

Crystal data

C₈H₁₀O₃
M _r = 154.16
Orthorhombic,
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

Data collection

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

Refinement

R[F ² > 2σ(F ²)] = 0.051
wR(F ²) = 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

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 ▸).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S205698901501230X/tk5370sup1.cif

e-71-0o540-sup1.cif^{(15.6KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S205698901501230X/tk5370Isup2.hkl

e-71-0o540-Isup2.hkl^{(104.7KB, hkl)}

Click here for additional data file.^{(3.3KB, cml)}

Supporting information file. DOI: 10.1107/S205698901501230X/tk5370Isup3.cml

Click here for additional data file.^{(970KB, tif)}

. DOI: 10.1107/S205698901501230X/tk5370fig1.tif

The molecular structure of the title compound, showing the atom-numbering scheme and 30% probability ellipsoids.

Click here for additional data file.^{(2.5MB, tif)}

. DOI: 10.1107/S205698901501230X/tk5370fig2.tif

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).

CCDC reference: 1409010

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (, ).

DHA	DH	HA	D A	DHA
O1H1O9ⁱ	0.74(4)	2.11(4)	2.773(2)	150(4)
O1H1O10ⁱ	0.74(4)	2.54(4)	3.152(2)	142(4)
O9H9O1ⁱⁱ	0.88(4)	1.78(4)	2.641(2)	163(3)

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Symmetry codes: (i) Inline graphic ; (ii) .

supplementary crystallographic information

S1. Chemical context

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.

S2. Synthesis and crystallization

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.

S3. Refinement

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.