research communications
Synthesis and
of 2-chloro-1-(3-hydroxyphenyl)ethanoneaDepartment of Chemistry, B. N. M. Institute of Technology, Bengaluru-560 070, India, bDepartment of Studies in Chemistry, University of Mysore, Manasagangotri, Mysuru-570 006, India, cDepartment of Chemistry, Yuvaraja's College, University of Mysore, Mysore-570 005, India, dT. John Institute of Technology, Bengaluru-560 083, India, and eDepartment of Chemistry, University of Kentucky, Lexington, KY, 40506-0055, USA
*Correspondence e-mail: yathirajan@hotmail.com
The structure of 2-chloro-1-(3-hydroxyphenyl)ethanone, C8H7ClO2, an α-haloketone is described. The molecule is planar (r.m.s. deviation = 0.0164 Å) and in the crystal, inversion-symmetric dimers are formed as a result of pairs of strong O—H⋯O and weak C—H⋯O hydrogen bonds. A brief comparison is made with structurally related compounds deposited in the CSD. In addition, the synthesis and some spectroscopic details are presented.
Keywords: crystal structure; α-haloketone; chlorinated acetophenone.
CCDC reference: 2211527
1. Chemical context
α-Haloketones have proven to be useful building blocks for the preparation of compounds of various classes because of their high reactivity and selective transformations with a variety of reagents (Erian et al., 2003). Chlorinated acetophenones are widely used in organic synthesis as intermediates for the manufacture of active pharmaceutical ingredients (Ott-Dombrowski et al., 2019). For example, 2-chloro-1-(4-hydroxyphenyl)ethanone is a reagent that is used in the preparation of hydroxypyrimidine derivatives for their HDAC (histone deacetylase) inhibitory activity (Kemp et al., 2011). In light of the importance of α-haloketones, this paper reports the synthesis, and some spectroscopic details for the title compound, C8H7O2Cl, (I).
2. Structural commentary
The molecule of I (Fig. 1) is planar (r.m.s. deviation = 0.0164 Å), with the largest deviation being for Cl1, which is 0.0346 (5) Å from the mean plane through all non-H atoms due to the O2—C7—C8—Cl1 torsion angle of −2.07 (14)°. The hydroxyl hydrogen atom, H1O, which was refined freely, lies 0.045 (16) Å out of the mean plane, with a C2—C3—O1—H1O torsion angle of 1.8 (12)°, its position being mandated by intermolecular hydrogen bonding (see section 3, Supramolecular details). All bond lengths and angles fall within the expected ranges for organic structures.
3. Supramolecular features
The main supramolecular feature is an inversion dimer resulting from a pair of symmetrically equivalent hydrogen bonds, O1—H1O⋯O2i and O1i—H1Oi⋯O2 [symmetry code: (i) −x + 1, −y + 1, −z + 1], giving an R22(14) motif. The cohesion of this dimer is augmented by a pair of weak hydrogen bonds, C2—H2⋯O2i and C2i—H2i⋯O2 (Table 1). It also, however, brings inversion-related H2 atoms into unfavourably close proximity [H2⋯H2i = 2.22 (3) Å]. These interactions are all illustrated in Fig. 2. Other noteworthy intermolecular contacts are weak C8—H8⋯O1ii [symmetry code: (ii) −x + , y − , −z + ] interactions between 21 screw-related molecules, which loosely connect the dimers into layers parallel to (10). Almost all of the atom–atom contact coverages quantified in a Hirshfeld-surface analysis using CrystalExplorer (Spackman et al., 2021) involve hydrogen (H⋯H = 26.6%, H⋯O/O⋯H = 23.7%, H⋯Cl/Cl⋯H = 21.2%, H⋯C/C⋯H = 15.8%), with all other contact types being <5%. Further details are given in individual Hirshfeld-surface fingerprint plots (Fig. 3).
4. Database survey
A search of the Cambridge Structure Database (v5.43 with updates as of June 2022; Groom et al., 2016) for a search fragment consisting of the structure of I but with the OH and Cl groups replaced by `any non-H' gave 71 hits. If the Cl site is specified as `any halogen', there are just four hits, only three of which are unique, and all have Br as the halogen. Structure AWOCAS (Aldeborgh et al., 2014) is chemically a Br analogue of I, but its is quite different (triclinic P vs P21/n for I). QAJNAS (Jasinski et al., 2011) [and QAJNAS01 (Mounir et al., 2013)] has NO2 in place of the hydroxyl. Lastly, MEXCOJ (Ambekar et al., 2013) has OC=OPh in place of the OH in I. Other similar structures in the literature include: LEFNAN (Fun et al., 2012), which is the 4-hydroxyphenyl analogue of I and crystallizes with the symmetry of P21/c; FUHHOG (Qing & Zhang, 2009), which is the bromo analogue of LEFNAN; and CUYDOR (Mei et al., 2015), which has 4-fluorophenyl in place of the halogen of LEFNAN and FUHHOG.
5. Synthesis, crystallization and spectroscopic details
Synthesis and crystallization: For the synthesis of I, sulfuryl chloride (150 mg, 1.1 mmol) was added dropwise to a stirred mixture of 3-hydroxyacetophenone (100 mg, 0.74 mmol) in 5 ml of methanol and 10 ml of ethyl acetate/dichloromethane at 293–303 K. After completion of the addition, it was allowed to return to RT with stirring for 1 h. The reaction was monitored by TLC. Then the solvent was removed under reduced pressure by rotary evaporation to give the desired product in 95% yield. An overall reaction scheme is depicted in Fig. 4. X-ray quality crystals were obtained by crystallization from ethanol (m.p. 352–354 K).
Spectroscopic data: Infrared and NMR spectroscopic details are as follows.
FTIR (γ in cm−1): 3400 (Ar—OH, broad), 2987 (C—H stretching), 1694 (C=C stretching), 1789 (s, C=O stretching), 832 (s, Ar-C—H bending).
1H NMR: CDCl3 (400 MHz, δ ppm): 4.7 (s, 2H, –CH2), 5.671 (s, 1H, –OH), 7.14 (d, 1H, Ar—H, J = 4.8 Hz), 7.36–7.4 (t, 2H, Ar—H, J = 16 Hz), 7.493–7.51 (m, 1H, Ar—H, J = 6.4 Hz).
6. Refinement
Crystal data, data collection, and structure . All hydrogen atoms were found in difference-Fourier maps, but subsequently, the carbon-bound hydrogens were included using riding models, with constrained distances set to 0.95 Å (Csp2—H) and 0.99 Å (R2CH2). The hydroxyl hydrogen atom coordinates were refined freely. In all cases, Uiso(H) values were set to 1.2Ueq of the attached atom.
details are given in Table 2Supporting information
CCDC reference: 2211527
https://doi.org/10.1107/S2056989022009835/vm2272sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989022009835/vm2272Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2056989022009835/vm2272Isup3.cml
Data collection: APEX3 (Bruker, 2016); cell
APEX3 (Bruker, 2016); data reduction: APEX3 (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2019/2 (Sheldrick, 2015b); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELX (Sheldrick, 2008) and publCIF (Westrip, 2010).C8H7ClO2 | F(000) = 352 |
Mr = 170.59 | Dx = 1.539 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
a = 4.9172 (2) Å | Cell parameters from 9994 reflections |
b = 12.7016 (4) Å | θ = 2.4–27.5° |
c = 11.8573 (3) Å | µ = 0.46 mm−1 |
β = 96.294 (1)° | T = 90 K |
V = 736.10 (4) Å3 | Cut block, colourless |
Z = 4 | 0.25 × 0.22 × 0.19 mm |
Bruker D8 Venture dual source diffractometer | 1685 independent reflections |
Radiation source: microsource | 1569 reflections with I > 2σ(I) |
Detector resolution: 7.41 pixels mm-1 | Rint = 0.028 |
φ and ω scans | θmax = 27.5°, θmin = 2.4° |
Absorption correction: multi-scan (SADABS; Krause et al., 2015) | h = −6→6 |
Tmin = 0.855, Tmax = 0.971 | k = −15→16 |
12264 measured reflections | l = −15→15 |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.024 | Hydrogen site location: mixed |
wR(F2) = 0.067 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.04 | w = 1/[σ2(Fo2) + (0.0323P)2 + 0.366P] where P = (Fo2 + 2Fc2)/3 |
1685 reflections | (Δ/σ)max < 0.001 |
106 parameters | Δρmax = 0.35 e Å−3 |
0 restraints | Δρmin = −0.18 e Å−3 |
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 | ||
O1 | 1.05641 (18) | 0.59830 (6) | 0.66167 (7) | 0.01786 (19) | |
H1O | 0.938 (3) | 0.6217 (12) | 0.6166 (14) | 0.021* | |
O2 | 0.38728 (17) | 0.32908 (6) | 0.48648 (7) | 0.01810 (19) | |
Cl1 | 0.22134 (5) | 0.10971 (2) | 0.48449 (2) | 0.01719 (10) | |
C1 | 0.7757 (2) | 0.33060 (8) | 0.62318 (9) | 0.0131 (2) | |
C2 | 0.8093 (2) | 0.43878 (9) | 0.60814 (9) | 0.0140 (2) | |
H2 | 0.686 (3) | 0.4757 (12) | 0.5553 (12) | 0.017* | |
C3 | 1.0190 (2) | 0.49212 (9) | 0.67174 (9) | 0.0139 (2) | |
C4 | 1.1997 (2) | 0.43790 (9) | 0.74969 (9) | 0.0151 (2) | |
H4 | 1.345037 | 0.474217 | 0.792591 | 0.018* | |
C5 | 1.1662 (2) | 0.33023 (9) | 0.76434 (9) | 0.0157 (2) | |
H5 | 1.289511 | 0.293235 | 0.817524 | 0.019* | |
C6 | 0.9546 (2) | 0.27607 (9) | 0.70220 (9) | 0.0147 (2) | |
H6 | 0.931888 | 0.202668 | 0.713351 | 0.018* | |
C7 | 0.5426 (2) | 0.27915 (8) | 0.55286 (9) | 0.0133 (2) | |
C8 | 0.5108 (2) | 0.16148 (9) | 0.56861 (10) | 0.0148 (2) | |
H8A | 0.493730 | 0.146717 | 0.649517 | 0.018* | |
H8B | 0.677307 | 0.125426 | 0.548476 | 0.018* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0212 (4) | 0.0116 (4) | 0.0191 (4) | −0.0027 (3) | −0.0048 (3) | 0.0006 (3) |
O2 | 0.0185 (4) | 0.0146 (4) | 0.0198 (4) | −0.0007 (3) | −0.0042 (3) | 0.0025 (3) |
Cl1 | 0.01466 (15) | 0.01477 (15) | 0.02144 (16) | −0.00314 (9) | −0.00114 (11) | −0.00204 (10) |
C1 | 0.0128 (5) | 0.0128 (5) | 0.0137 (5) | −0.0003 (4) | 0.0021 (4) | −0.0010 (4) |
C2 | 0.0143 (5) | 0.0132 (5) | 0.0141 (5) | 0.0006 (4) | −0.0001 (4) | 0.0008 (4) |
C3 | 0.0160 (5) | 0.0120 (5) | 0.0141 (5) | −0.0006 (4) | 0.0030 (4) | −0.0012 (4) |
C4 | 0.0142 (5) | 0.0162 (5) | 0.0146 (5) | −0.0004 (4) | −0.0004 (4) | −0.0032 (4) |
C5 | 0.0159 (5) | 0.0157 (5) | 0.0150 (5) | 0.0033 (4) | −0.0006 (4) | −0.0001 (4) |
C6 | 0.0161 (5) | 0.0121 (5) | 0.0159 (5) | 0.0010 (4) | 0.0020 (4) | 0.0000 (4) |
C7 | 0.0136 (5) | 0.0129 (5) | 0.0138 (5) | 0.0000 (4) | 0.0029 (4) | −0.0006 (4) |
C8 | 0.0125 (5) | 0.0126 (5) | 0.0184 (5) | −0.0011 (4) | −0.0020 (4) | 0.0005 (4) |
O1—C3 | 1.3682 (13) | C3—C4 | 1.3922 (16) |
O1—H1O | 0.803 (17) | C4—C5 | 1.3906 (16) |
O2—C7 | 1.2138 (14) | C4—H4 | 0.9500 |
Cl1—C8 | 1.7725 (11) | C5—C6 | 1.3892 (16) |
C1—C6 | 1.3967 (15) | C5—H5 | 0.9500 |
C1—C2 | 1.3978 (15) | C6—H6 | 0.9500 |
C1—C7 | 1.4921 (15) | C7—C8 | 1.5164 (15) |
C2—C3 | 1.3857 (15) | C8—H8A | 0.9900 |
C2—H2 | 0.945 (15) | C8—H8B | 0.9900 |
C3—O1—H1O | 109.2 (11) | C6—C5—H5 | 119.6 |
C6—C1—C2 | 119.91 (10) | C4—C5—H5 | 119.6 |
C6—C1—C7 | 123.12 (10) | C5—C6—C1 | 119.35 (10) |
C2—C1—C7 | 116.97 (10) | C5—C6—H6 | 120.3 |
C3—C2—C1 | 120.16 (10) | C1—C6—H6 | 120.3 |
C3—C2—H2 | 120.1 (9) | O2—C7—C1 | 121.59 (10) |
C1—C2—H2 | 119.7 (9) | O2—C7—C8 | 121.91 (10) |
O1—C3—C2 | 122.25 (10) | C1—C7—C8 | 116.50 (9) |
O1—C3—C4 | 117.6 (1) | C7—C8—Cl1 | 112.57 (8) |
C2—C3—C4 | 120.15 (10) | C7—C8—H8A | 109.1 |
C5—C4—C3 | 119.57 (10) | Cl1—C8—H8A | 109.1 |
C5—C4—H4 | 120.2 | C7—C8—H8B | 109.1 |
C3—C4—H4 | 120.2 | Cl1—C8—H8B | 109.1 |
C6—C5—C4 | 120.86 (10) | H8A—C8—H8B | 107.8 |
C6—C1—C2—C3 | −0.24 (16) | C2—C1—C6—C5 | −0.61 (16) |
C7—C1—C2—C3 | 179.06 (10) | C7—C1—C6—C5 | −179.86 (10) |
C1—C2—C3—O1 | −178.62 (10) | C6—C1—C7—O2 | 178.50 (11) |
C1—C2—C3—C4 | 0.97 (16) | C2—C1—C7—O2 | −0.77 (15) |
O1—C3—C4—C5 | 178.75 (10) | C6—C1—C7—C8 | −1.61 (15) |
C2—C3—C4—C5 | −0.85 (16) | C2—C1—C7—C8 | 179.11 (9) |
C3—C4—C5—C6 | 0.00 (17) | O2—C7—C8—Cl1 | −2.07 (14) |
C4—C5—C6—C1 | 0.73 (17) | C1—C7—C8—Cl1 | 178.05 (7) |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1O···O2i | 0.803 (17) | 2.004 (18) | 2.8029 (12) | 173.4 (16) |
C2—H2···O2i | 0.945 (15) | 2.547 (15) | 3.2633 (14) | 132.7 (11) |
C8—H8A···O1ii | 0.99 | 2.36 | 3.3485 (14) | 176 |
Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x+3/2, y−1/2, −z+3/2. |
Acknowledgements
PP is grateful to the B. N. M. Institute of Technology, Bengaluru for research facilities.
Funding information
HSY is grateful to UGC, New Delhi for a BSR Faculty Fellowship for three years. Funding for this research was provided by: NSF (MRI CHE1625732) and the University of Kentucky (Bruker D8 Venture diffractometer).
References
Aldeborgh, H., George, K., Howe, M., Lowman, H., Moustakas, H., Strunsky, N. & Tanski, J. M. (2014). J. Chem. Crystallogr. 44, 70–81. Web of Science CSD CrossRef CAS Google Scholar
Ambekar, S. P., Devarajegowda, H. C., ShylajaKumari, J., Kumar, K. M. & Kotresh, O. (2013). Acta Cryst. E69, o322. CSD CrossRef IUCr Journals Google Scholar
Bruker (2016). APEX3. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Erian, A. W., Sherif, S. M. & Gaber, H. M. (2003). Molecules, 8, 793–865. Web of Science CrossRef CAS Google Scholar
Fun, H.-K., Quah, C. K., Shetty, D. N., Narayana, B. & Sarojini, B. K. (2012). Acta Cryst. E68, o2424. CSD CrossRef IUCr Journals Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CrossRef IUCr Journals Google Scholar
Jasinski, J. P., Butcher, R. J., Praveen, A. S., Yathirajan, H. S. & Narayana, B. (2011). Acta Cryst. E67, o29–o30. CSD CrossRef IUCr Journals Google Scholar
Kemp, M. M., Wang, Q., Fuller, J. H., West, N., Martinez, N. M., Morse, E. M., Weïwer, M., Schreiber, S. L., Bradner, J. E. & Koehler, A. N. (2011). Bioorg. Med. Chem. Lett. 21, 4164–4169. CrossRef CAS PubMed Google Scholar
Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3–10. Web of Science CSD CrossRef ICSD CAS IUCr Journals Google Scholar
Mei, Q., Liu, H. & Han, B. (2015). CSD Communication (refcode CUYDOR). CCDC, Cambridge, England. Google Scholar
Mounir, F., Gandour, R. D. & Fronczek, F. (2013). CSD Communication (refcode QAJNAS01). CCDC, Cambridge, England. Google Scholar
Ott-Dombrowski, S., Rüter, H. & Ulrich, R. (2019). European patent EP3498687A1. Google Scholar
Qing, W.-X. & Zhang, W. (2009). Acta Cryst. E65, o2837. Web of Science CSD CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Spackman, P. R., Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Jayatilaka, D. & Spackman, M. A. (2021). J. Appl. Cryst. 54, 1006–1011. Web of Science CrossRef CAS IUCr Journals Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar
This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.