research communications
Crystallographic and spectroscopic characterization of 3-chloro-5-fluorosalicylaldehyde
aDepartment of Chemistry, Vassar College, Poughkeepsie, NY 12604, USA
*Correspondence e-mail: jotanski@vassar.edu
The title compound (systematic name: 3-chloro-5-fluoro-2-hydroxybenzaldehyde), C7H4ClFO2, is a dihalogenated salicylaldehyde derivative that has been studied for its antibacterial characteristics. The salicylaldehyde engages in intramolecular hydrogen bonding with an O—H⋯O distance of 2.6231 (19) Å while the molecules pack together via weak intermolecular C—H⋯O, C—H⋯F and F⋯O interactions and offset face-to-face π-stacking.
CCDC reference: 2041401
1. Chemical context
Salicylaldehyde and its derivatives, including the title compound 3-chloro-5-fluoro-2-hydroxybenzaldehyde, (I), play an important role in the synthesis of novel antimicrobial complexes (Bozkır et al., 2012; Dahlgren et al., 2010; Sarı et al., 2013). The title compound, commonly known as 3-chloro-5-fluorosalicylaldehyde, may be synthesized by the formylation of 2-chloro-4-fluorophenol with chloroform through reflux with concentrated NaOH(aq) (Balko et al., 2007).
2. Structural commentary
The molecular structure of the title compound (Fig. 1) is planar, with an r.m.s. deviation from the plane of all non-hydrogen atoms of 0.0135 Å. The molecule engages in intramolecular hydrogen bonding between the phenol hydrogen atom and formyl oxygen with an O1⋯O2 distance of 2.6231 (19) Å characterizing the O1—H1⋯O2 interaction. The C3—Cl and C5—F bond lengths were found to be 1.7334 (16) and 1.3529 (19) Å, respectively.
3. Supramolecular features
The molecules pack together in the solid state with weak intermolecular C—H⋯O, C—H⋯F and F⋯O interactions and an offset face-to-face π-stacking geometrical relationship. Molecules of 3-chloro-5-fluorosalicylaldehyde form one-dimensional π-stacking chains (Fig. 2), which are characterized by a ring centroid-to-centroid distance of 3.7154 (3) Å, a centroid-to-plane distance of 3.3989 (8) Å, and a ring-offset slippage of 1.501 (2) Å. These π-stacking chains are linked together to form the three-dimensional structure through weak intermolecular C—H⋯O and C—H⋯F contacts (Table 1 and Fig. 3). Specifically, O1—H1⋯Fi, C4—H4A⋯O2ii, and C6—H6A⋯O1iii intermolecular interactions (symmetry codes as defined in Table 1), with donor–acceptor distances of 3.0101 (18), 3.254 (2) and 3.377 (2) Å, respectively. In addition, an O2⋯Fi contact with a distance of 2.880 (2) Å is observed. Notably, there are no close halogen–halogen interactions.
4. Database survey
The Cambridge Structural Database (Version 5.40, update of March 2020; Groom et al., 2016) contains many halogenated benzene structures and relatively few halogenated salicylaldehyde structures. Literature aryl C—Cl and C—F bond lengths, as seen in halogenated benzene crystal structures, are similar to those seen in the title compound. For example, the C—Cl distances in 1,2- and 1,3-dichlorobenzene range between 1.731 (3) and 1.756 (3) Å (ABUMIT and ABUMOZ; Boese et al., 2001), while the C—F distances in 1,3-difluorobenzene are found to be between 1.3486 (14) and 1.3553 (13) Å (PUGDAX; Kirchner et al., 2009). Related salicylaldehyde structures that differ in the number of halogen atoms include unsubstituted salicylaldehyde itself (YADJOE; Kirchner et al., 2011), 5-chlorosalicylaldehyde (RAJGOA01; Aitken et al., 2013; RAJGOA, Jin et al., 2011), and 3,5-dichlorosalicylaldehyde (MIXYEY; Azizul & Ng, 2008). As with the title compound, each of these structures exhibits strong intramolecular hydrogen bonding between the phenol hydrogen atom and formyl oxygen atom.
5. Synthesis and crystallization
3-Chloro-5-fluorosalicylaldehyde (I, 97%) was purchased from Aldrich Chemical Company, USA, and was used as received.
6. Refinement
Crystal data, data collection and structure . All non-hydrogen atoms were refined anisotropically. Hydrogen atoms bonded to carbon were included in calculated positions and refined using a riding model with C—H = 0.95 and Uiso(H) = 1.2Ueq(C) for the aryl H atoms. The position of the phenolic hydrogen atom was found in the difference map and refined freely.
details are summarized in Table 27. Analytical Data
1H NMR (Bruker Avance III 400 MHz, CDCl3): δ 7.23 (dd, 1H, CarylH, Jmeta = 3.0 Hz, JH–F = 7.2 Hz), 7.42 (dd, 1H, CarylH, Jmeta = 3.0 Hz, JH–F = 7.8 Hz), 9.86 (s, 1H, OH), 11.21 (s, 1H, C(=O)H). 13C NMR (13C{1H}, 100.6 MHz, CDCl3): δ 116.90 (d, CarylH, JC–F = 22.6 Hz), 120.24 (d, Caryl, JC–F = 6.6 Hz), 123.15 (d, Caryl, JC–F = 9.1 Hz), 124.72 (d, CarylH, JC–F = 26.4 Hz), 153.85 (d, Caryl, JC–F = 2.2 Hz), 154.85 (d, CarylF, JC–F = 244.0 Hz), 194.97 (C(=O)H). 19F NMR (19F{1H}, 376.5 MHz, CDCl3): δ −121.50. IR (Thermo Nicolet iS50, ATR, cm−1) : 3081 (m br, O—H & Caryl—H str), 2859 [w, C(=O)—H fermi doublet str], 2733 [w, C(=O)—H fermi doublet str], 1803 (w), 1754 (w), 1664 (s, C=O str), 1623 (m), 1583 (w), 1524 (w), 1462 (m), 1436 (s), 1373 (m), 1351 (w), 1294 (s), 1238 (s), 1183 (s), 1119 (s), 982 (s), 902 (m), 894 (m), 875 (s), 802 (s), 727 (s), 708 (s), 578 (m), 530 (s), 493 (s), 458 (m). GC/MS (Agilent MS 5975/GC 7890): M+ = 174 (calc. exact mass 173.99).
Supporting information
CCDC reference: 2041401
https://doi.org/10.1107/S2056989020014425/pk2651sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989020014425/pk2651Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2056989020014425/pk2651Isup3.cml
Data collection: APEX2 (Bruker, 2017); cell
SAINT (Bruker, 2017); data reduction: SAINT (Bruker, 2017); program(s) used to solve structure: SHELXT2014/5 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2017/1 (Sheldrick, 2015b); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008), OLEX2 (Dolomanov et al., 2009), and Mercury (Macrae et al., 2020).C7H4ClFO2 | Dx = 1.720 Mg m−3 |
Mr = 174.55 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, Pna21 | Cell parameters from 9931 reflections |
a = 14.2730 (13) Å | θ = 2.9–30.5° |
b = 12.7102 (12) Å | µ = 0.52 mm−1 |
c = 3.7154 (3) Å | T = 125 K |
V = 674.02 (10) Å3 | Needle, colourless |
Z = 4 | 0.45 × 0.10 × 0.02 mm |
F(000) = 352 |
Bruker APEXII CCD diffractometer | 2052 independent reflections |
Radiation source: fine-focus sealed tube | 1985 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.030 |
Detector resolution: 8.3333 pixels mm-1 | θmax = 30.5°, θmin = 2.2° |
φ and ω scans | h = −20→20 |
Absorption correction: multi-scan (SADABS; Bruker, 2017) | k = −18→17 |
Tmin = 0.87, Tmax = 0.99 | l = −5→5 |
16131 measured reflections |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: mixed |
R[F2 > 2σ(F2)] = 0.023 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.066 | w = 1/[σ2(Fo2) + (0.0394P)2 + 0.1224P] where P = (Fo2 + 2Fc2)/3 |
S = 1.07 | (Δ/σ)max < 0.001 |
2052 reflections | Δρmax = 0.34 e Å−3 |
104 parameters | Δρmin = −0.19 e Å−3 |
1 restraint | Absolute structure: Flack x determined using 837 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) |
Primary atom site location: dual | Absolute structure parameter: 0.07 (2) |
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. |
x | y | z | Uiso*/Ueq | ||
Cl | 0.43892 (3) | 0.11149 (3) | 0.78847 (17) | 0.02049 (11) | |
F | 0.41791 (7) | 0.50784 (8) | 0.7158 (3) | 0.0246 (3) | |
O1 | 0.25167 (10) | 0.12611 (10) | 0.4770 (4) | 0.0204 (3) | |
H1 | 0.202 (2) | 0.137 (2) | 0.412 (8) | 0.036 (8)* | |
O2 | 0.11001 (9) | 0.23221 (11) | 0.2114 (4) | 0.0256 (3) | |
C1 | 0.24600 (12) | 0.31544 (12) | 0.4365 (4) | 0.0143 (3) | |
C2 | 0.29149 (11) | 0.22104 (12) | 0.5277 (4) | 0.0142 (3) | |
C3 | 0.38146 (11) | 0.22705 (12) | 0.6760 (4) | 0.0141 (3) | |
C4 | 0.42463 (11) | 0.32301 (13) | 0.7379 (4) | 0.0157 (3) | |
H4A | 0.485639 | 0.326265 | 0.8395 | 0.019* | |
C5 | 0.37672 (11) | 0.41404 (13) | 0.6482 (5) | 0.0160 (3) | |
C6 | 0.28892 (11) | 0.41307 (13) | 0.4973 (4) | 0.0157 (3) | |
H6A | 0.258084 | 0.476816 | 0.435752 | 0.019* | |
C7 | 0.15263 (10) | 0.31310 (13) | 0.2738 (6) | 0.0186 (3) | |
H7A | 0.123791 | 0.378134 | 0.213767 | 0.022* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl | 0.02085 (18) | 0.01654 (18) | 0.02407 (19) | 0.00416 (13) | −0.00540 (17) | 0.00218 (18) |
F | 0.0206 (5) | 0.0149 (5) | 0.0384 (7) | −0.0046 (4) | −0.0032 (5) | −0.0033 (5) |
O1 | 0.0189 (6) | 0.0142 (6) | 0.0281 (7) | −0.0017 (5) | −0.0059 (5) | 0.0005 (5) |
O2 | 0.0192 (5) | 0.0225 (6) | 0.0350 (9) | −0.0014 (5) | −0.0094 (6) | −0.0006 (5) |
C1 | 0.0138 (7) | 0.0147 (7) | 0.0145 (6) | 0.0007 (5) | −0.0012 (5) | 0.0000 (6) |
C2 | 0.0156 (7) | 0.0133 (7) | 0.0136 (6) | −0.0007 (5) | −0.0007 (6) | 0.0000 (6) |
C3 | 0.0153 (7) | 0.0133 (7) | 0.0139 (6) | 0.0024 (5) | −0.0015 (5) | 0.0006 (5) |
C4 | 0.0141 (6) | 0.0165 (7) | 0.0166 (8) | 0.0001 (5) | −0.0005 (6) | −0.0012 (6) |
C5 | 0.0160 (7) | 0.0135 (7) | 0.0185 (7) | −0.0025 (6) | 0.0011 (6) | −0.0017 (6) |
C6 | 0.0167 (7) | 0.0136 (7) | 0.0167 (7) | 0.0011 (6) | 0.0001 (6) | 0.0005 (6) |
C7 | 0.0162 (7) | 0.0192 (7) | 0.0205 (7) | 0.0022 (5) | −0.0031 (7) | 0.0008 (8) |
Cl—C3 | 1.7334 (16) | C2—C3 | 1.399 (2) |
F—C5 | 1.3529 (19) | C3—C4 | 1.386 (2) |
O1—C2 | 1.3470 (19) | C4—C5 | 1.385 (2) |
O1—H1 | 0.77 (3) | C4—H4A | 0.95 |
O2—C7 | 1.217 (2) | C5—C6 | 1.373 (2) |
C1—C6 | 1.402 (2) | C6—H6A | 0.95 |
C1—C2 | 1.406 (2) | C7—H7A | 0.95 |
C1—C7 | 1.464 (2) | ||
C2—O1—H1 | 106 (2) | C5—C4—H4A | 120.8 |
C6—C1—C2 | 120.99 (14) | C3—C4—H4A | 120.8 |
C6—C1—C7 | 118.83 (14) | F—C5—C6 | 118.71 (15) |
C2—C1—C7 | 120.18 (14) | F—C5—C4 | 118.49 (14) |
O1—C2—C3 | 119.41 (14) | C6—C5—C4 | 122.79 (15) |
O1—C2—C1 | 122.42 (14) | C5—C6—C1 | 118.19 (15) |
C3—C2—C1 | 118.17 (14) | C5—C6—H6A | 120.9 |
C4—C3—C2 | 121.43 (14) | C1—C6—H6A | 120.9 |
C4—C3—Cl | 119.70 (12) | O2—C7—C1 | 123.44 (15) |
C2—C3—Cl | 118.87 (12) | O2—C7—H7A | 118.3 |
C5—C4—C3 | 118.42 (15) | C1—C7—H7A | 118.3 |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···Fi | 0.77 (3) | 2.47 (3) | 3.0101 (18) | 128 (2) |
O1—H1···O2 | 0.77 (3) | 1.93 (3) | 2.6231 (19) | 150 (3) |
C4—H4A···O2ii | 0.95 | 2.37 | 3.254 (2) | 155 |
C6—H6A···O1iii | 0.95 | 2.55 | 3.377 (2) | 145 |
Symmetry codes: (i) −x+1/2, y−1/2, z−1/2; (ii) x+1/2, −y+1/2, z+1; (iii) −x+1/2, y+1/2, z−1/2. |
Funding information
This work was supported by Vassar College. X-ray facilities were provided by the US National Science Foundation (grants Nos. 0521237 and 0911324 to JMT). We acknowledge the Salmon Fund and Olin College Fund of Vassar College for funding publication expenses.
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