4-(Benz­yloxy)benzaldehyde

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.

Key indicators

• Single-crystal X-ray study
• T = 123 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.039
• wR factor = 0.071
• Data-to-parameter ratio = 10.5

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT910_ALERT_3_C Missing # of FCF Reflections Below Th(Min) .....          1
PLAT125_ALERT_4_C No _symmetry_space_group_name_Hall Given .......          ?
PLAT912_ALERT_4_C Missing # of FCF Reflections Above STh/L=  0.600         87

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           29.98
           From the CIF: _reflns_number_total               1579
           Count of symmetry unique reflns         1678
           Completeness (_total/calc)             94.10%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   3 ALERT level C = Check and explain
   1 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   3 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. 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 °).

Related literature

For discussion of C—H···O contacts in a related methoxy derivative, see: Gerkin (1999). For other related structures, see: Allwood et al. (1985); Li & Chen (2008); Liu et al. (2006, 2007); Zhen et al. (2006). For background to the antiretroviral treatment programme of AIDS, see: 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). For the need for new small molecules that target HIV-1 binding sites, see: Christer et al. (1998); Himmel et al. (2006). For related literature [on what subject?], see: Hunter et al. (2007); Muhanji (2006);

S2. 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.

S3. Refinement

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

Computing details

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

Figures

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

4-(Benzyloxy)benzaldehyde

Crystal data

C14H12O2	Dx = 1.312 Mg m^−3
Mr = 212.24	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pna21	Cell parameters from 2444 reflections
a = 11.4772 (11) Å	θ = 2.8–29.9°
b = 12.9996 (12) Å	µ = 0.09 mm^−1
c = 7.2032 (6) Å	T = 123 K
V = 1074.71 (17) Å^3	Block, colourless
Z = 4	0.42 × 0.20 × 0.14 mm
F(000) = 448

Data collection

Oxford Diffraction Gemini S diffractometer	Rint = 0.049
Radiation source: fine-focus sealed tube	θmax = 30.0°, θmin = 3.1°
Graphite monochromator	h = −15→15
ω scans	k = −18→13
8432 measured reflections	l = −9→9
1579 independent reflections	3 standard reflections every 240 min
1130 reflections with I > 2σ(I)	intensity decay: none

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.039	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.071	w = 1/[σ^2(Fo^2) + (0.0342P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 0.91	(Δ/σ)max < 0.001
1579 reflections	Δρmax = 0.18 e Å^−3
150 parameters	Δρmin = −0.17 e Å^−3
1 restraint	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction 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 (Ų)

	x	y	z	Uiso*/Ueq
O1	0.63724 (11)	0.04432 (8)	0.81224 (19)	0.0256 (3)
O2	0.81066 (12)	−0.42284 (9)	0.8002 (2)	0.0360 (4)
C1	0.53896 (16)	0.08862 (13)	0.9065 (2)	0.0232 (4)
H1A	0.5446	0.0748	1.0413	0.028*
H1B	0.4660	0.0573	0.8599	0.028*
C2	0.53725 (17)	0.20292 (13)	0.8725 (2)	0.0212 (4)
C3	0.62873 (17)	0.25573 (12)	0.7892 (3)	0.0235 (4)
H3	0.6963	0.2195	0.7503	0.028*
C4	0.62149 (18)	0.36164 (13)	0.7626 (3)	0.0276 (5)
H4	0.6838	0.3974	0.7045	0.033*
C5	0.52362 (18)	0.41501 (14)	0.8205 (3)	0.0294 (5)
H5	0.5186	0.4872	0.8019	0.035*
C6	0.43353 (18)	0.36301 (14)	0.9054 (3)	0.0293 (5)
H6	0.3670	0.3998	0.9469	0.035*
C7	0.43932 (18)	0.25775 (14)	0.9304 (2)	0.0251 (4)
H7	0.3762	0.2225	0.9874	0.030*
C8	0.65609 (17)	−0.05854 (13)	0.8365 (3)	0.0219 (4)
C9	0.75866 (17)	−0.09649 (14)	0.7567 (2)	0.0231 (4)
H9	0.8097	−0.0512	0.6926	0.028*
C10	0.78550 (16)	−0.19922 (13)	0.7712 (3)	0.0232 (4)
H10	0.8551	−0.2250	0.7170	0.028*
C11	0.71047 (16)	−0.26592 (13)	0.8657 (2)	0.0211 (4)
C12	0.60968 (17)	−0.22681 (14)	0.9451 (2)	0.0234 (4)
H12	0.5590	−0.2720	1.0102	0.028*
C13	0.58121 (17)	−0.12411 (13)	0.9319 (2)	0.0236 (4)
H13	0.5118	−0.0985	0.9869	0.028*
C14	0.73311 (19)	−0.37705 (14)	0.8791 (3)	0.0271 (5)
H14	0.6736 (19)	−0.4158 (13)	0.961 (3)	0.033 (6)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0262 (7)	0.0207 (6)	0.0301 (8)	0.0024 (6)	0.0083 (6)	0.0016 (6)
O2	0.0320 (9)	0.0287 (8)	0.0474 (9)	0.0057 (6)	0.0023 (8)	−0.0033 (7)
C1	0.0216 (11)	0.0224 (10)	0.0255 (11)	0.0029 (8)	0.0033 (8)	0.0005 (8)
C2	0.0210 (10)	0.0224 (10)	0.0201 (10)	−0.0017 (8)	−0.0036 (8)	−0.0005 (7)
C3	0.0202 (10)	0.0248 (10)	0.0256 (11)	0.0000 (8)	0.0003 (8)	−0.0017 (9)
C4	0.0260 (12)	0.0279 (11)	0.0288 (12)	−0.0055 (8)	0.0000 (9)	0.0008 (9)
C5	0.0339 (12)	0.0203 (10)	0.0340 (11)	0.0003 (9)	−0.0044 (10)	−0.0012 (9)
C6	0.0274 (12)	0.0288 (10)	0.0316 (12)	0.0049 (9)	−0.0009 (9)	−0.0058 (9)
C7	0.0224 (11)	0.0275 (11)	0.0254 (10)	−0.0003 (8)	0.0027 (9)	−0.0002 (8)
C8	0.0234 (10)	0.0224 (10)	0.0199 (10)	0.0006 (8)	−0.0008 (8)	−0.0002 (8)
C9	0.0211 (11)	0.0243 (10)	0.0239 (10)	−0.0043 (8)	0.0033 (8)	0.0010 (8)
C10	0.0212 (10)	0.0270 (10)	0.0213 (10)	0.0006 (8)	0.0014 (8)	−0.0027 (8)
C11	0.0222 (10)	0.0216 (10)	0.0195 (9)	−0.0009 (8)	−0.0034 (8)	0.0004 (8)
C12	0.0230 (11)	0.0254 (10)	0.0217 (10)	−0.0045 (9)	0.0012 (8)	0.0044 (8)
C13	0.0217 (11)	0.0266 (10)	0.0225 (10)	0.0014 (8)	0.0028 (8)	0.0024 (8)
C14	0.0261 (12)	0.0261 (11)	0.0290 (11)	−0.0021 (9)	−0.0046 (9)	0.0009 (9)

Geometric parameters (Å, º)

O1—C8	1.3657 (18)	C6—H6	0.9500
O1—C1	1.437 (2)	C7—H7	0.9500
O2—C14	1.212 (2)	C8—C13	1.392 (3)
C1—C2	1.506 (2)	C8—C9	1.400 (2)
C1—H1A	0.9900	C9—C10	1.375 (2)
C1—H1B	0.9900	C9—H9	0.9500
C2—C3	1.391 (3)	C10—C11	1.399 (2)
C2—C7	1.395 (3)	C10—H10	0.9500
C3—C4	1.393 (2)	C11—C12	1.387 (2)
C3—H3	0.9500	C11—C14	1.471 (3)
C4—C5	1.385 (3)	C12—C13	1.378 (2)
C4—H4	0.9500	C12—H12	0.9500
C5—C6	1.378 (3)	C13—H13	0.9500
C5—H5	0.9500	C14—H14	1.03 (2)
C6—C7	1.382 (3)
C8—O1—C1	117.15 (13)	C6—C7—H7	119.8
O1—C1—C2	109.20 (14)	C2—C7—H7	119.8
O1—C1—H1A	109.8	O1—C8—C13	124.39 (17)
C2—C1—H1A	109.8	O1—C8—C9	115.20 (16)
O1—C1—H1B	109.8	C13—C8—C9	120.41 (16)
C2—C1—H1B	109.8	C10—C9—C8	119.99 (16)
H1A—C1—H1B	108.3	C10—C9—H9	120.0
C3—C2—C7	119.04 (16)	C8—C9—H9	120.0
C3—C2—C1	123.18 (16)	C9—C10—C11	120.08 (17)
C7—C2—C1	117.77 (16)	C9—C10—H10	120.0
C2—C3—C4	120.15 (18)	C11—C10—H10	120.0
C2—C3—H3	119.9	C12—C11—C10	119.13 (16)
C4—C3—H3	119.9	C12—C11—C14	118.69 (16)
C5—C4—C3	120.16 (18)	C10—C11—C14	122.15 (17)
C5—C4—H4	119.9	C13—C12—C11	121.64 (16)
C3—C4—H4	119.9	C13—C12—H12	119.2
C6—C5—C4	119.76 (17)	C11—C12—H12	119.2
C6—C5—H5	120.1	C12—C13—C8	118.75 (17)
C4—C5—H5	120.1	C12—C13—H13	120.6
C5—C6—C7	120.50 (19)	C8—C13—H13	120.6
C5—C6—H6	119.7	O2—C14—C11	125.5 (2)
C7—C6—H6	119.7	O2—C14—H14	120.9 (10)
C6—C7—C2	120.38 (18)	C11—C14—H14	113.5 (10)
C8—O1—C1—C2	176.49 (14)	O1—C8—C9—C10	−179.33 (17)
O1—C1—C2—C3	−9.8 (2)	C13—C8—C9—C10	0.5 (3)
O1—C1—C2—C7	171.08 (16)	C8—C9—C10—C11	0.0 (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—C14	177.71 (18)
C2—C3—C4—C5	0.6 (3)	C10—C11—C12—C13	0.5 (3)
C3—C4—C5—C6	0.3 (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—C2	0.9 (3)	O1—C8—C13—C12	179.39 (17)
C3—C2—C7—C6	−0.1 (3)	C9—C8—C13—C12	−0.4 (3)
C1—C2—C7—C6	179.06 (16)	C12—C11—C14—O2	171.8 (2)
C1—O1—C8—C13	6.0 (2)	C10—C11—C14—O2	−6.3 (3)
C1—O1—C8—C9	−174.23 (17)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1A···O2^i	0.99	2.50	3.324 (2)	141
C1—H1B···O2^ii	0.99	2.53	3.478 (2)	160

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