Synthesis and crystal structure of 2-chloro-1-(3-hy­droxy­phen­yl)ethanone

Priyanka, P.; Jayanna, B.K.; Vinaya; Shankara Prasad, H.J.; Divakara, T.R.; Yathirajan, H.S.; Parkin, S.

doi:10.1107/S2056989022009835

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ISSN: 2056-9890

Volume 78| Part 11| November 2022| Pages 1127-1130

https://doi.org/10.1107/S2056989022009835

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Synthesis and crystal structure of 2-chloro-1-(3-hydroxyphenyl)ethanone

Prabhakar Priyanka,^a Bidarur K. Jayanna,^a Vinaya,^b Holehundi J. Shankara Prasad,^c Thayamma R. Divakara,^d Hemmige S. Yathirajan ^b ^* and Sean Parkin ^e

^aDepartment 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

Edited by L. Van Meervelt, Katholieke Universiteit Leuven, Belgium (Received 3 October 2022; accepted 7 October 2022; online 20 October 2022)

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, crystal structure, 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.

Figure 1
An ellipsoid plot (50% probability) of I. Hydrogen atoms are drawn as small circles.

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 + $[{3\over 2}]$ , y − $[{1\over 2}]$ , −z + $[{3\over 2}]$ ] interactions between 2₁ screw-related molecules, which loosely connect the dimers into layers parallel to (10 $[\overline{1}]$ ). 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).

Table 1
Hydrogen-bond geometry (Å, °)

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) ; (ii) $[-x+{\script{3\over 2}}, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

Figure 2
A partial packing plot showing the main supramolecular motif in I: a hydrogen-bonded dimer between inversion-related [symmetry code: (i) −x + 1, −y + 1, −z + 1] molecules. Strong O—H⋯O hydrogen bonds are shown as thick dashed lines, weaker C—H⋯O interactions as open dashed lines, and an unfavourable, forced close contact between hydrogen atoms as a dotted line.

Figure 3
Hirshfeld surface fingerprint plots showing the relative contributions of various atom–atom contacts in the packing of I. (a) All contacts, (b) H⋯H (26.6%), (c) H⋯O/O⋯H (23.7%), (d) H⋯Cl/Cl⋯H (21.2%), (e) H⋯C/C⋯H (15.7%), (f) C⋯Cl/Cl⋯C (4.5%), (g) C⋯O/O⋯C (3.6%), (h) C⋯C (3.0%), (i) O⋯O (1.2%). All other contact types are <1%.

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 crystal structure is quite different (triclinic P $[\overline{1}]$ 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).

Figure 4
The overall reaction scheme for the synthesis of I.

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 refinement details are given in Table 2. 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, U_iso(H) values were set to 1.2U_eq of the attached atom.

Table 2
Experimental details

Crystal data
Chemical formula	C₈H₇ClO₂
M_r	170.59
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	90
a, b, c (Å)	4.9172 (2), 12.7016 (4), 11.8573 (3)
β (°)	96.294 (1)
V (Å³)	736.10 (4)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.46
Crystal size (mm)	0.25 × 0.22 × 0.19

Data collection
Diffractometer	Bruker D8 Venture dual source
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 )
T_min, T_max	0.855, 0.971
No. of measured, independent and observed [I > 2σ(I)] reflections	12264, 1685, 1569
R_int	0.028
(sin θ/λ)_max (Å⁻¹)	0.650

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.024, 0.067, 1.04
No. of reflections	1685
No. of parameters	106
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.35, −0.18
Computer programs: APEX3 (Bruker, 2016 ), SHELXT (Sheldrick, 2015a ), SHELXL2019/2 (Sheldrick, 2015b ), XP in SHELXTL and SHELX (Sheldrick, 2008 ) and publCIF (Westrip, 2010 ).

Supporting information

CCDC reference: 2211527

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2056989022009835/vm2272sup1.cif

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

checkCIF report

Computing details top

Data collection: APEX3 (Bruker, 2016); cell refinement: 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).

2-Chloro-1-(3-hydroxyphenyl)ethanone top

Crystal data top

C₈H₇ClO₂	F(000) = 352
M_r = 170.59	D_x = 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

Data collection top

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	R_int = 0.028
φ and ω scans	θ_max = 27.5°, θ_min = 2.4°
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	h = −6→6
T_min = 0.855, T_max = 0.971	k = −15→16
12264 measured reflections	l = −15→15

Refinement top

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(F_o²) + (0.0323P)² + 0.366P] where P = (F_o² + 2F_c²)/3
1685 reflections	(Δ/σ)_max < 0.001
106 parameters	Δρ_max = 0.35 e Å⁻³
0 restraints	Δρ_min = −0.18 e Å⁻³

Special details top

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.

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

	x	y	z	U_iso*/U_eq
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*

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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)

Hydrogen-bond geometry (Å, º) top

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).

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