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Acta Crystallogr Sect E Struct Rep Online. 2010 August 1; 66(Pt 8): o2110.
Published online 2010 July 24. doi:  10.1107/S1600536810027200
PMCID: PMC3007533

4-(Benz­yloxy)benzaldehyde

Abstract

The title compound, C14H12O2, has an essentially planar conformation with the two aromatic rings forming a dihedral angle of 5.23 (9)° and the aldehyde group lying in the plane of its aromatic group [maximum deviation = 0.204 (3) Å]. Weak inter­molecular C—H(...)O contacts are found to be shortest between the aldehyde O-atom acceptor and the H atoms of the methyl­ene group.

Related literature

For discussion of C—H(...)O contacts in a related meth­oxy derivative, see: Gerkin (1999 [triangle]). For other related structures, see: Allwood et al. (1985 [triangle]); Li & Chen (2008 [triangle]); Liu et al. (2006 [triangle], 2007 [triangle]); Zhen et al. (2006 [triangle]). For background to the anti­retroviral treatment programme of AIDS, see: UNAIDS/WHO (2009 [triangle]). The established non-nucleoside reverse transcriptase inhibitors (NNRTIs) are susceptible to the development of viral resistance, emanating from mutations of amino acids in RT enzymes (Jones et al., 2006 [triangle]). For the need for new small mol­ecules that target HIV-1 binding sites, see: Christer et al. (1998 [triangle]); Himmel et al. (2006 [triangle]). For related literature on our work in this area, see: Hunter et al. (2007 [triangle]); Muhanji (2006 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o2110-scheme1.jpg

Experimental

Crystal data

  • C14H12O2
  • M r = 212.24
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-66-o2110-efi1.jpg
  • a = 11.4772 (11) Å
  • b = 12.9996 (12) Å
  • c = 7.2032 (6) Å
  • V = 1074.71 (17) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 123 K
  • 0.42 × 0.20 × 0.14 mm

Data collection

  • Oxford Diffraction Gemini S diffractometer
  • 8432 measured reflections
  • 1579 independent reflections
  • 1130 reflections with I > 2σ(I)
  • R int = 0.049

Refinement

  • R[F 2 > 2σ(F 2)] = 0.039
  • wR(F 2) = 0.071
  • S = 0.91
  • 1579 reflections
  • 150 parameters
  • 1 restraint
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.18 e Å−3
  • Δρmin = −0.17 e Å−3

Data collection: CrysAlis CCD (Oxford Diffraction, 2007 [triangle]); cell refinement: CrysAlis CCD; data reduction: CrysAlis RED (Oxford Diffraction, 2007 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 (Farrugia, 1997 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810027200/gw2083sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810027200/gw2083Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

MOO thanks the Commonwealth Scholarship Commission and the British Council for funding and Moi University for sabatical leave.

supplementary crystallographic information

Comment

A critical strategy for mitigating the impact of the Acquired Immunodeficiency Syndrome (AIDS) epidemic is the antiretroviral treatment programme (UNAIDS/WHO, 2009). The established non-nucleoside reverse transcriptase inhibitors (NNRTIs) are susceptible to the development of viral resistance, emanating from mutations of amino acids in RT enzymes (Jones et al., 2006). The effectiveness of the drugs that have already been developed is thus affected by the emergence of drug resistant strains. Consequently, NNRTIs having a good activity against wild-type RT and the most prevalent mutant viral strains are needed. There is therefore the need to look for new compounds that are highly potent and less susceptible to mutations of RT- enzyme (Christer et al., 1998). According to Himmel et al. (2006), new lead compounds that target novel binding sites are needed because of rapid emergence of these drug resistant variants of HIV-1 which has limited the efficacy of AIDS treatment. This study was therefore limited to the use of Wiener's topological index, a theoretical approach used in theoretical chemistry to predict the anti-HIV activity of phenylethylthiazolylthiourea (PETT) analogues.

The title compound, 4-(benzyloxy)benzaldehyde, was an intermediate in the production of such target compounds. It was found to exist as discrete molecules (Figure 1), although there are some non-classical hydrogen bonding C—H···O interactions involving the aldehyde O atom and both the methylene H atoms (H···O 2.50 and 2.53 Å) and aromatic H atoms (2.69 and 2.80 Å). Similar interactions are described for the similar 2-methoxy vanillin derivitive by Gerkin (1999). All contacts to the ether O atom are longer than these.

Bond lengths are similar to those found in the structures of related compounds and the aldehyde is coplanar with the ring in all cases (here C10C11C14O2 = -6.3 (3) °. However, two different conformations are found for these compounds. In common with three other derivatives (Li & Chen (2008); Liu et al. (2006); Zhen et al. (2006)), the two aromatic rings of 4-(benzyloxy)benzaldehyde approach coplanarity (C13C8C2C7 = -9.2 (3)°), whilst the similarly substituted species described by Gerkin (1999), Allwood et al. (1985) and Liu et al. (2007) are very twisted (torsion angle range 31.7 to 99.1 °).

Experimental

All reactions in the preparation of 4-(benzyloxy)benzaldehyde were performed under an atmosphere of nitrogen gas. 5.0 g of 4-hydroxybenzaldehyde (40.98 mmol), 5.0 ml of benzylbromide (42.05 mmol) and 20.0 g of anhydrous potassium carbonate (144.27 mmol) in ethanol were refluxed for 14 hours. Potassium carbonate was filtered out and large volumes of EtOAc were used to wash the residue. Rotavapour apparatus was used to remove the solvent. The residual mass was dissolved in 50 ml Et2O. Two portions of 50 mL saturated sodium chloride solution were used to wash the Et2O solution. Thereafter, it was washed with one portion of 5% sodium hydroxide solution. Finally, the Et2O solution was washed with distilled water. Anhydrous magnesium sulphate was used to dry the Et2O solution and the solvent removed under reduced pressure. The crude product was then recrystallized from ethanol to give colorless crystals (7.58 g, 87.4%). Mp: 338-339 K.

Refinement

The aldehyde H atom (H14) was refined freely, but all other atoms were placed in calculated positions and refined in riding modes with Uiso(H) = 1.2Ueq(C). C—H distances 0.95 and 0.99 Å for CH and CH2 respectively.

Figures

Fig. 1.
The molecular structure showing 50% probability displacement ellipsoids.
Fig. 2.
Packing diagram with view along the length of the b axis.

Crystal data

C14H12O2Dx = 1.312 Mg m3
Mr = 212.24Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pna21Cell parameters from 2444 reflections
a = 11.4772 (11) Åθ = 2.8–29.9°
b = 12.9996 (12) ŵ = 0.09 mm1
c = 7.2032 (6) ÅT = 123 K
V = 1074.71 (17) Å3Block, colourless
Z = 40.42 × 0.20 × 0.14 mm
F(000) = 448

Data collection

Oxford Diffraction Gemini S diffractometerRint = 0.049
Radiation source: fine-focus sealed tubeθmax = 30.0°, θmin = 3.1°
graphiteh = −15→15
ω scansk = −18→13
8432 measured reflectionsl = −9→9
1579 independent reflections3 standard reflections every 240 min
1130 reflections with I > 2σ(I) intensity decay: none

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.039H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.071w = 1/[σ2(Fo2) + (0.0342P)2] where P = (Fo2 + 2Fc2)/3
S = 0.91(Δ/σ)max < 0.001
1579 reflectionsΔρmax = 0.18 e Å3
150 parametersΔρmin = −0.17 e Å3
1 restraintExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0052 (11)

Special details

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.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

xyzUiso*/Ueq
O10.63724 (11)0.04432 (8)0.81224 (19)0.0256 (3)
O20.81066 (12)−0.42284 (9)0.8002 (2)0.0360 (4)
C10.53896 (16)0.08862 (13)0.9065 (2)0.0232 (4)
H1A0.54460.07481.04130.028*
H1B0.46600.05730.85990.028*
C20.53725 (17)0.20292 (13)0.8725 (2)0.0212 (4)
C30.62873 (17)0.25573 (12)0.7892 (3)0.0235 (4)
H30.69630.21950.75030.028*
C40.62149 (18)0.36164 (13)0.7626 (3)0.0276 (5)
H40.68380.39740.70450.033*
C50.52362 (18)0.41501 (14)0.8205 (3)0.0294 (5)
H50.51860.48720.80190.035*
C60.43353 (18)0.36301 (14)0.9054 (3)0.0293 (5)
H60.36700.39980.94690.035*
C70.43932 (18)0.25775 (14)0.9304 (2)0.0251 (4)
H70.37620.22250.98740.030*
C80.65609 (17)−0.05854 (13)0.8365 (3)0.0219 (4)
C90.75866 (17)−0.09649 (14)0.7567 (2)0.0231 (4)
H90.8097−0.05120.69260.028*
C100.78550 (16)−0.19922 (13)0.7712 (3)0.0232 (4)
H100.8551−0.22500.71700.028*
C110.71047 (16)−0.26592 (13)0.8657 (2)0.0211 (4)
C120.60968 (17)−0.22681 (14)0.9451 (2)0.0234 (4)
H120.5590−0.27201.01020.028*
C130.58121 (17)−0.12411 (13)0.9319 (2)0.0236 (4)
H130.5118−0.09850.98690.028*
C140.73311 (19)−0.37705 (14)0.8791 (3)0.0271 (5)
H140.6736 (19)−0.4158 (13)0.961 (3)0.033 (6)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0262 (7)0.0207 (6)0.0301 (8)0.0024 (6)0.0083 (6)0.0016 (6)
O20.0320 (9)0.0287 (8)0.0474 (9)0.0057 (6)0.0023 (8)−0.0033 (7)
C10.0216 (11)0.0224 (10)0.0255 (11)0.0029 (8)0.0033 (8)0.0005 (8)
C20.0210 (10)0.0224 (10)0.0201 (10)−0.0017 (8)−0.0036 (8)−0.0005 (7)
C30.0202 (10)0.0248 (10)0.0256 (11)0.0000 (8)0.0003 (8)−0.0017 (9)
C40.0260 (12)0.0279 (11)0.0288 (12)−0.0055 (8)0.0000 (9)0.0008 (9)
C50.0339 (12)0.0203 (10)0.0340 (11)0.0003 (9)−0.0044 (10)−0.0012 (9)
C60.0274 (12)0.0288 (10)0.0316 (12)0.0049 (9)−0.0009 (9)−0.0058 (9)
C70.0224 (11)0.0275 (11)0.0254 (10)−0.0003 (8)0.0027 (9)−0.0002 (8)
C80.0234 (10)0.0224 (10)0.0199 (10)0.0006 (8)−0.0008 (8)−0.0002 (8)
C90.0211 (11)0.0243 (10)0.0239 (10)−0.0043 (8)0.0033 (8)0.0010 (8)
C100.0212 (10)0.0270 (10)0.0213 (10)0.0006 (8)0.0014 (8)−0.0027 (8)
C110.0222 (10)0.0216 (10)0.0195 (9)−0.0009 (8)−0.0034 (8)0.0004 (8)
C120.0230 (11)0.0254 (10)0.0217 (10)−0.0045 (9)0.0012 (8)0.0044 (8)
C130.0217 (11)0.0266 (10)0.0225 (10)0.0014 (8)0.0028 (8)0.0024 (8)
C140.0261 (12)0.0261 (11)0.0290 (11)−0.0021 (9)−0.0046 (9)0.0009 (9)

Geometric parameters (Å, °)

O1—C81.3657 (18)C6—H60.9500
O1—C11.437 (2)C7—H70.9500
O2—C141.212 (2)C8—C131.392 (3)
C1—C21.506 (2)C8—C91.400 (2)
C1—H1A0.9900C9—C101.375 (2)
C1—H1B0.9900C9—H90.9500
C2—C31.391 (3)C10—C111.399 (2)
C2—C71.395 (3)C10—H100.9500
C3—C41.393 (2)C11—C121.387 (2)
C3—H30.9500C11—C141.471 (3)
C4—C51.385 (3)C12—C131.378 (2)
C4—H40.9500C12—H120.9500
C5—C61.378 (3)C13—H130.9500
C5—H50.9500C14—H141.03 (2)
C6—C71.382 (3)
C8—O1—C1117.15 (13)C6—C7—H7119.8
O1—C1—C2109.20 (14)C2—C7—H7119.8
O1—C1—H1A109.8O1—C8—C13124.39 (17)
C2—C1—H1A109.8O1—C8—C9115.20 (16)
O1—C1—H1B109.8C13—C8—C9120.41 (16)
C2—C1—H1B109.8C10—C9—C8119.99 (16)
H1A—C1—H1B108.3C10—C9—H9120.0
C3—C2—C7119.04 (16)C8—C9—H9120.0
C3—C2—C1123.18 (16)C9—C10—C11120.08 (17)
C7—C2—C1117.77 (16)C9—C10—H10120.0
C2—C3—C4120.15 (18)C11—C10—H10120.0
C2—C3—H3119.9C12—C11—C10119.13 (16)
C4—C3—H3119.9C12—C11—C14118.69 (16)
C5—C4—C3120.16 (18)C10—C11—C14122.15 (17)
C5—C4—H4119.9C13—C12—C11121.64 (16)
C3—C4—H4119.9C13—C12—H12119.2
C6—C5—C4119.76 (17)C11—C12—H12119.2
C6—C5—H5120.1C12—C13—C8118.75 (17)
C4—C5—H5120.1C12—C13—H13120.6
C5—C6—C7120.50 (19)C8—C13—H13120.6
C5—C6—H6119.7O2—C14—C11125.5 (2)
C7—C6—H6119.7O2—C14—H14120.9 (10)
C6—C7—C2120.38 (18)C11—C14—H14113.5 (10)
C8—O1—C1—C2176.49 (14)O1—C8—C9—C10−179.33 (17)
O1—C1—C2—C3−9.8 (2)C13—C8—C9—C100.5 (3)
O1—C1—C2—C7171.08 (16)C8—C9—C10—C110.0 (3)
C7—C2—C3—C4−0.7 (3)C9—C10—C11—C12−0.5 (3)
C1—C2—C3—C4−179.76 (16)C9—C10—C11—C14177.71 (18)
C2—C3—C4—C50.6 (3)C10—C11—C12—C130.5 (3)
C3—C4—C5—C60.3 (3)C14—C11—C12—C13−177.70 (17)
C4—C5—C6—C7−1.0 (3)C11—C12—C13—C8−0.1 (3)
C5—C6—C7—C20.9 (3)O1—C8—C13—C12179.39 (17)
C3—C2—C7—C6−0.1 (3)C9—C8—C13—C12−0.4 (3)
C1—C2—C7—C6179.06 (16)C12—C11—C14—O2171.8 (2)
C1—O1—C8—C136.0 (2)C10—C11—C14—O2−6.3 (3)
C1—O1—C8—C9−174.23 (17)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C1—H1A···O2i0.992.503.324 (2)141
C1—H1B···O2ii0.992.533.478 (2)160

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: GW2083).

References

  • Allwood, B. L., Kohnke, F. H., Slawin, A. M. Z., Stoddart, J. F. & Williams, D. J. (1985). Chem. Commun. pp. 311–314.
  • Christer, S., Rolf, N., Per, E., Marita, H., Jusii, K., Lotta, V. & Hong, Z. (1998). Bioorg. Med. Chem. Lett.8, 1511–1516.
  • Farrugia, L. J. (1997). J. Appl. Cryst.30, 565.
  • Gerkin, R. E. (1999). Acta Cryst. C55, 2140–2142. [PubMed]
  • Himmel, D. M., Sarafianos, S. G., Dharmasena, S., Hossain, M. M., McCoy-Simandle, K., Ilina, T., Clark, A. D. Jr, Knight, J. L., Julias, J. G., Clark, P. K., Krogh-Jespersen, K., Levy, R. M., Hughes, S. H., Parniak, M. A. & Arnold, E. (2006). ACS Chem. Biol.1, 702–712. [PMC free article] [PubMed]
  • Hunter, R., Muhanji, C. I., Hale, I., Bailey, M. C., Basavapathruni, A. & Anderson, S. K. (2007). Bioorg. Med. Chem. Lett.17, 2614–2617. [PubMed]
  • Jones, L. H., Dupont, T., Mowbray, C. E. & Newman, S. D. (2006). Org. Lett.8, 1725–1727. [PubMed]
  • Li, M. & Chen, X. (2008). Acta Cryst. E64, o2291. [PMC free article] [PubMed]
  • Liu, S.-X., Han, J.-R., Zhen, X.-L. & Tian, X. (2006). Acta Cryst. E62, o5643–o5644.
  • Liu, S.-X., Tian, X., Zhen, X.-L., Li, Z.-C. & Han, J.-R. (2007). Acta Cryst. E63, o4481.
  • Muhanji, C. I. (2006). PhD thesis, University of Cape Town, South Africa.
  • Oxford Diffraction (2007). CrysAlis CCD and CrysAlis RED Oxford Diffraction Ltd, Abingdon, England.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • UNAIDS/WHO (2009). UNAIDS/WHO Report on the global AIDS epidemic, 17th April 2009. http://www.unaids.org 2008
  • Zhen, X.-L., Han, J.-R., Wang, Q.-T., Tian, X. & Liu, S.-X. (2006). Acta Cryst. E62, o5794–o5795.

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