organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2056-9890

Crystal structure of 5-hy­dr­oxy­methyl-2-meth­­oxy­phenol

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.

1. Related literature

For the background to alcoholic hy­droxy compounds and their applications, see: Patrick (2001[Patrick, G. L. (2001). In An Introduction to Medicinal Chemistry. Oxford: University Press.]); Yasohara et al. (2001[Yasohara, Y., Miyamoto, K., Kizaki, N. & Hasegawa, J. (2001). Tetrahedron Lett. 42, 3331-3333.]); Rodríguez-Barrios & Gago (2004[Rodríguez-Barrios, F. & Gago, F. (2004). Curr. Top. Med. Chem. 4, 991-1007.]); Wu et al. (2008[Wu, X., Öhrngren, P., Ekegren, J. K., Unge, J., Unge, T., Wallberg, H., Samuelsson, B., Hallberg, A. & Larhed, M. (2008). J. Med. Chem. 51, 1053-1057.]); Matteelli et al. (2010[Matteelli, A., Carvalho, A. C., Dooley, K. E. & Kritski, A. (2010). Future Microbiol. 5, 849-858.]); Coimbra et al. (2010[Coimbra, E. S., de Almeida, M. V., Jðnior, C. O. R., Taveira, A. F., da Costa, C. F., de Almeida, A. C., Reis, E. F. C. & da Silva, A. D. (2010). Chem. Biol. Drug Des. 75, 233-235.]); Hans et al. (2010[Hans, R. H., Gut, J., Rosenthal, P. J. & Chibale, K. (2010). Bioorg. Med. Chem. Lett. 20, 2234-2237.]); Cordova et al. (2006[Córdova, I., León, L. G., León, F., San Andrés, L., Luis, J. G. & Padrón, J. M. (2006). Eur. J. Med. Chem. 41, 1327-1332.]). For the synthesis of derivatives of the title compound, see: Ashraf et al. (2014[Ashraf, Z., Rafiq, M., Seo, S. Y., Babar, M. M. & Zaidi, N. S. S. (2014). J. Enzyme Inhib. Med. Chem. pp. 1-10.], 2015[Ashraf, Z., Rafiq, M., Seo, S. Y., Kwon, K. S., Babar, M. M. & Zaidi, N. U. S. (2015). Eur. J. Med. Chem. 98, 203-211.]).

[Scheme 1]

2. Experimental

2.1. Crystal data

  • C8H10O3

  • Mr = 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)

  • Rint = 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

  • Δρmax = 0.38 e Å−3

  • Δρmin = −0.42 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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[Bruker (2002). SAINT and SMART. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2002[Bruker (2002). SAINT and SMART. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXS2013 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]); software used to prepare material for publication: WinGX (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]).

Supporting information


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 Uiso(H) = 1.2Ueq(C) for phenyl-H and methyl­ene-H and 1.5Ueq(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

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.

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

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 details 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 Uiso(H) = 1.2Ueq(C) for phenyl-H and methyl­ene-H and 1.5Ueq(C) for methyl-H atoms.

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
[Figure 1] Fig. 1. The molecular structure of the title compound, showing the atom-numbering scheme and 30% probability ellipsoids.
[Figure 2] 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
C8H10O3F(000) = 656
Mr = 154.16Dx = 1.344 Mg m3
Orthorhombic, PbcaMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2abCell parameters from 7746 reflections
a = 15.011 (4) Åθ = 2.5–28.2°
b = 6.1354 (18) ŵ = 0.10 mm1
c = 16.543 (5) ÅT = 296 K
V = 1523.6 (7) Å3Block, brown
Z = 80.28 × 0.25 × 0.23 mm
Data collection top
Bruker SMART CCD area-detector
diffractometer
Rint = 0.025
Radiation source: fine-focus sealed tubeθmax = 28.4°, θmin = 2.5°
φ and ω scansh = 2019
28952 measured reflectionsk = 88
1900 independent reflectionsl = 2220
1530 reflections with I > 2σ(I)
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.051H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.149 w = 1/[σ2(Fo2) + (0.0668P)2 + 0.6464P]
where P = (Fo2 + 2Fc2)/3
S = 1.07(Δ/σ)max < 0.001
1900 reflectionsΔρmax = 0.38 e Å3
108 parametersΔρmin = 0.42 e Å3
Crystal data top
C8H10O3V = 1523.6 (7) Å3
Mr = 154.16Z = 8
Orthorhombic, PbcaMo Kα radiation
a = 15.011 (4) ŵ = 0.10 mm1
b = 6.1354 (18) ÅT = 296 K
c = 16.543 (5) Å0.28 × 0.25 × 0.23 mm
Data collection top
Bruker SMART CCD area-detector
diffractometer
1530 reflections with I > 2σ(I)
28952 measured reflectionsRint = 0.025
1900 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0510 restraints
wR(F2) = 0.149H atoms treated by a mixture of independent and constrained refinement
S = 1.07Δρmax = 0.38 e Å3
1900 reflectionsΔρmin = 0.42 e Å3
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
xyzUiso*/Ueq
O10.56019 (17)0.3078 (3)0.91644 (10)0.1025 (9)
H10.559 (2)0.268 (6)0.959 (2)0.129 (13)*
C20.61335 (11)0.1812 (3)0.86876 (9)0.0462 (4)
H2A0.58950.03450.86630.055*
H2B0.67270.17370.89190.055*
C30.61828 (10)0.2752 (3)0.78509 (9)0.0383 (4)
C40.57178 (10)0.1775 (3)0.72196 (8)0.0388 (4)
H40.53850.05240.73160.047*
C50.57476 (10)0.2651 (3)0.64505 (8)0.0375 (3)
C60.62554 (10)0.4516 (3)0.62970 (9)0.0368 (3)
C70.67100 (11)0.5504 (3)0.69227 (10)0.0452 (4)
H70.70420.67570.68280.054*
C80.66682 (11)0.4616 (3)0.76955 (9)0.0454 (4)
H80.69730.52920.81160.054*
O90.52924 (10)0.1784 (2)0.58164 (7)0.0554 (4)
H90.498 (2)0.060 (6)0.5924 (18)0.124 (12)*
O100.62581 (8)0.5189 (2)0.55089 (7)0.0472 (3)
C110.67256 (15)0.7139 (3)0.53259 (12)0.0588 (5)
H11A0.66820.74330.47570.088*
H11B0.73410.69760.54730.088*
H11C0.6470.83280.56240.088*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.1593 (19)0.1051 (14)0.0432 (8)0.0824 (14)0.0458 (10)0.0312 (9)
C20.0512 (9)0.0580 (10)0.0293 (7)0.0082 (7)0.0009 (6)0.0039 (7)
C30.0371 (7)0.0506 (9)0.0272 (7)0.0057 (6)0.0004 (5)0.0000 (6)
C40.0443 (8)0.0425 (8)0.0296 (7)0.0036 (6)0.0043 (6)0.0003 (6)
C50.0429 (7)0.0434 (8)0.0263 (7)0.0021 (6)0.0013 (5)0.0039 (6)
C60.0395 (7)0.0431 (8)0.0277 (7)0.0011 (6)0.0025 (5)0.0014 (6)
C70.0469 (8)0.0503 (9)0.0384 (8)0.0110 (7)0.0005 (6)0.0007 (7)
C80.0443 (8)0.0590 (10)0.0327 (8)0.0063 (7)0.0063 (6)0.0050 (7)
O90.0752 (9)0.0631 (8)0.0279 (6)0.0280 (7)0.0037 (5)0.0024 (5)
O100.0610 (7)0.0505 (7)0.0302 (6)0.0110 (5)0.0009 (5)0.0060 (5)
C110.0761 (13)0.0528 (11)0.0476 (10)0.0137 (9)0.0028 (9)0.0127 (8)
Geometric parameters (Å, º) top
O1—C21.365 (2)C6—O101.3677 (18)
O1—H10.74 (4)C6—C71.380 (2)
C2—C31.501 (2)C7—C81.391 (2)
C2—H2A0.97C7—H70.93
C2—H2B0.97C8—H80.93
C3—C81.380 (2)O9—H90.88 (4)
C3—C41.392 (2)O10—C111.420 (2)
C4—C51.382 (2)C11—H11A0.96
C4—H40.93C11—H11B0.96
C5—O91.3601 (18)C11—H11C0.96
C5—C61.398 (2)
C2—O1—H1112 (3)O10—C6—C5114.96 (13)
O1—C2—C3110.07 (15)C7—C6—C5119.54 (14)
O1—C2—H2A109.6C6—C7—C8119.66 (16)
C3—C2—H2A109.6C6—C7—H7120.2
O1—C2—H2B109.6C8—C7—H7120.2
C3—C2—H2B109.6C3—C8—C7121.29 (14)
H2A—C2—H2B108.2C3—C8—H8119.4
C8—C3—C4118.80 (14)C7—C8—H8119.4
C8—C3—C2121.06 (14)C5—O9—H9116 (2)
C4—C3—C2120.12 (15)C6—O10—C11117.34 (13)
C5—C4—C3120.48 (15)O10—C11—H11A109.5
C5—C4—H4119.8O10—C11—H11B109.5
C3—C4—H4119.8H11A—C11—H11B109.5
O9—C5—C4122.81 (14)O10—C11—H11C109.5
O9—C5—C6116.99 (13)H11A—C11—H11C109.5
C4—C5—C6120.20 (13)H11B—C11—H11C109.5
O10—C6—C7125.50 (15)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1···O9i0.74 (4)2.11 (4)2.773 (2)150 (4)
O1—H1···O10i0.74 (4)2.54 (4)3.152 (2)142 (4)
O9—H9···O1ii0.88 (4)1.78 (4)2.641 (2)163 (3)
Symmetry codes: (i) x, y+1/2, z+1/2; (ii) x+1, y1/2, z+3/2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1···O9i0.74 (4)2.11 (4)2.773 (2)150 (4)
O1—H1···O10i0.74 (4)2.54 (4)3.152 (2)142 (4)
O9—H9···O1ii0.88 (4)1.78 (4)2.641 (2)163 (3)
Symmetry codes: (i) x, y+1/2, z+1/2; (ii) x+1, y1/2, z+3/2.
 

References

First citationAshraf, Z., Rafiq, M., Seo, S. Y., Babar, M. M. & Zaidi, N. S. S. (2014). J. Enzyme Inhib. Med. Chem. pp. 1–10.  Google Scholar
First citationAshraf, Z., Rafiq, M., Seo, S. Y., Kwon, K. S., Babar, M. M. & Zaidi, N. U. S. (2015). Eur. J. Med. Chem. 98, 203–211.  Web of Science CSD CrossRef CAS PubMed Google Scholar
First citationBruker (2002). SAINT and SMART. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationCoimbra, E. S., de Almeida, M. V., Jðnior, C. O. R., Taveira, A. F., da Costa, C. F., de Almeida, A. C., Reis, E. F. C. & da Silva, A. D. (2010). Chem. Biol. Drug Des. 75, 233–235.  Web of Science CrossRef CAS PubMed Google Scholar
First citationCórdova, I., León, L. G., León, F., San Andrés, L., Luis, J. G. & Padrón, J. M. (2006). Eur. J. Med. Chem. 41, 1327–1332.  Web of Science PubMed Google Scholar
First citationFarrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationHans, R. H., Gut, J., Rosenthal, P. J. & Chibale, K. (2010). Bioorg. Med. Chem. Lett. 20, 2234–2237.  Web of Science CrossRef CAS PubMed Google Scholar
First citationMatteelli, A., Carvalho, A. C., Dooley, K. E. & Kritski, A. (2010). Future Microbiol. 5, 849–858.  Web of Science CrossRef CAS PubMed Google Scholar
First citationPatrick, G. L. (2001). In An Introduction to Medicinal Chemistry. Oxford: University Press.  Google Scholar
First citationRodríguez-Barrios, F. & Gago, F. (2004). Curr. Top. Med. Chem. 4, 991–1007.  Web of Science PubMed Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationWu, X., Öhrngren, P., Ekegren, J. K., Unge, J., Unge, T., Wallberg, H., Samuelsson, B., Hallberg, A. & Larhed, M. (2008). J. Med. Chem. 51, 1053–1057.  Web of Science CrossRef PubMed CAS Google Scholar
First citationYasohara, Y., Miyamoto, K., Kizaki, N. & Hasegawa, J. (2001). Tetrahedron Lett. 42, 3331–3333.  Web of Science CrossRef CAS Google Scholar

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