2-Chloro-N-(4-hy­droxy­phen­yl)acetamide

El Moutaouakil Ala Allah, A.; Kariuki, B.M.; Ameziane El Hassani, I.; Alsubari, A.; Guerrab, W.; Said, M.; Ramli, Y.

doi:10.1107/S2414314624010150

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 9| Part 10| October 2024| x241015

https://doi.org/10.1107/S2414314624010150

Open

access

2-Chloro-N-(4-hydroxyphenyl)acetamide

Abderrazzak El Moutaouakil Ala Allah,^a Benson M. Kariuki,^b Issam Ameziane El Hassani,^a Abdulsalam Alsubari,^c ^* Walid Guerrab,^a Musa A. Said ^d and Youssef Ramli ^a ^*

^aLaboratory of Medicinal Chemistry, Drug Sciences Research Center, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Morocco, ^bSchool of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, United Kingdom, ^cLaboratory of Medicinal Chemistry, Faculty of Clinical Pharmacy, 21 September University, Yemen, and ^dDepartment of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah, 42351, Saudi Arabia
^*Correspondence e-mail: alsubaripharmaco@21umas.edu.ye, y.ramli@um5r.ac.ma

(Received 14 October 2024; accepted 17 October 2024; online 24 October 2024)

The title compound, C₈H₈ClNO₂, is significantly distorted from planarity, with a twist angle between the planes through the hydroxybenzene and acetamide groups being 23.5 (2)°. This conformation is supported by intramolecular C—H⋯O and N—H⋯Cl contacts. In the crystal, N—H⋯O hydrogen-bonding contacts between acetamide groups and O—H⋯O contacts between hydroxyl groups form tapes propagating parallel to [103].

Keywords: crystal structure; acetamide; hydrogen-bonding.

CCDC reference: 2392239

Structure description

N-arylacetamides are intermediates for the synthesis of medicinal, agrochemical and pharmaceutical compounds (Missioui et al., 2021 ). As part of our ongoing studies of these systems (Missioui et al., 2022 ), we now describe the synthesis and structure of the title compound, C₈H₈ClNO₂.

The molecule, Fig. 1, is almost planar as indicated by a twist angle between the planes through the hydroxybenzene (C1–C6, O1) and acetamide (C7, C8, N1, O2) groups being 23.5 (2)°; the acetamide group has an anti conformation. The chloro substituent deviates only slightly from the plane of the acetamide group as indicated by the N1—C7—C8—Cl1 torsion angle of 15.4 (4)°.

Figure 1
The molecule of 2-chloro-N-(4-hydroxyphenyl)acetamide showing the atom-numbering scheme and displacement parameters at the 50% probability level. The intramolecular C—H⋯O and N—H⋯Cl contacts are shown as green dotted lines.

Two types of close intramolecular contacts occur within the molecule. The first contact is of the type C—H⋯O with a C3—H3⋯O2 angle of 116° and a C3⋯O2 distance of 2.873 (4) Å, Table 1. Similar contacts are observed in related structures including 2-chloro-N-(4-fluorophenyl)acetamide (Kang et al., 2008 ), 2-chloro-N-phenylacetamide (Gowda et al., 2008 ) and 2-chloro-N-(4-chlorophenyl)acetamide (Gowda et al., 2007 ). The second contact is of the type N—H⋯Cl and has a N1—H1⋯Cl1 angle of 115° and a N1⋯Cl1 distance of 2.999 (2) Å.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C3—H3⋯O2	0.93	2.34	2.873 (4)	116
N1—H1⋯Cl1	0.86	2.53	2.999 (2)	115
N1—H1⋯O2ⁱ	0.86	2.28	3.025 (3)	145
O1—H1A⋯O1ⁱⁱ	0.82	2.06	2.8585 (17)	166
Symmetry codes: (i) ; (ii) $[-x+2, y+{\script{1\over 2}}, -z+2]$ .

In the crystal, neighbouring molecules are linked by N—H⋯O hydrogen-bonding between translationally related acetamide groups with a N1—H1⋯O2ⁱ [symmetry code: (i) x, y − 1, z] angle of 145° and a N1⋯O2ⁱ distance of 3.025 (3) Å, Table 1, to form linear chains parallel to the b axis (Fig. 2). The molecules are also bridged by O—H⋯O contacts with a O1—H1A⋯O1ⁱⁱ [symmetry code: (ii) −x + 2, y + $[{1\over 2}]$ , −z + 2] angle of 166° and an O1⋯O1ⁱⁱ distance of 2.8585 (17) Å which, by themselves assemble molecules along the 2₁ screw axis in the b-axis direction. The combined hydrogen-bonding interactions result in almost flat tapes of molecules parallel to [ $[\overline{1}]$ 03].

Figure 2
A segment of the packing in the crystal of 2-chloro-N-(4-hydroxyphenyl)acetamide showing the intermolecular N—H⋯O and O—H⋯O hydrogen bonds as green dotted lines.

Synthesis and crystallization

4-Aminophenol (1 mmol) was dissolved in pure acetic acid (30 ml) and placed in an ice-bath. Subsequently, chloroacetyl chloride (1.2 mmol) was added portion-wise under stirring. At the end of the reaction, a solution of sodium acetate (25 ml) was added, and a solid precipitate formed after 30 min of stirring at room temperature. The resulting solid was filtered, washed with cold water, dried and recrystallized from its ethanol solution to yield the title compound as colourless crystals.

Yield = 89%, colour:colourless, m.p. = 413–415 K. FT–IR (ATR, ν, cm⁻¹): 3385 (OH), 3200 (NH), 1640 (C=O). ¹H NMR (500 MHz, DMSO-d₆): δ p.p.m. 4.21 (s, 2H, CH₂), 6.76–7.34 (m, 4H, Ar—H), 9.20 (s, 1H, OH), 10.23 (s, 1H, NH). ¹³C NMR (500 MHz, DMSO-d₆): 43.42 (CH₂); 117.68, 122.20, 131.50, 132.63, 153.68 (C—Ar); 164.76 (C=O). HRMS (ESI): calculated for C₈H₈ClNO₂ [M - H]⁺ 186.0224, found 186.0328.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₈H₈ClNO₂
M_r	185.60
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	296
a, b, c (Å)	6.5088 (6), 5.1758 (5), 12.2175 (14)
β (°)	101.649 (10)
V (Å³)	403.11 (7)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	0.43
Crystal size (mm)	0.45 × 0.20 × 0.07

Data collection
Diffractometer	SuperNova, Dual, Cu at home/near, Atlas
Absorption correction	Gaussian (CrysAlis PRO; Rigaku OD, 2023 $[Rigaku OD (2023). CrysAlis PRO. Rigaku Oxford Diffraction.]$ )
T_min, T_max	0.642, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	3642, 1902, 1487
R_int	0.028
(sin θ/λ)_max (Å⁻¹)	0.697

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.039, 0.081, 1.06
No. of reflections	1902
No. of parameters	110
No. of restraints	1
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.16, −0.19
Absolute structure	Flack x determined using 510 quotients [(I⁺)−(I⁻)]/[(I⁺)+(I⁻)] (Parsons et al., 2013 )
Absolute structure parameter	0.11 (5)
Computer programs: CrysAlis PRO (Rigaku OD, 2023 $[Rigaku OD (2023). CrysAlis PRO. Rigaku Oxford Diffraction.]$ ), SHELXT (Sheldrick, 2015a ), SHELXL2019/2 (Sheldrick, 2015b ), Mercury (Macrae et al., 2020 ) and WinGX (Farrugia, 2012 ).

Structural data

CCDC reference: 2392239

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314624010150/tk4111sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314624010150/tk4111Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314624010150/tk4111Isup3.cml

checkCIF report

Computing details top

2-Chloro-N-(4-hydroxyphenyl)acetamide top

Crystal data top

C₈H₈ClNO₂	F(000) = 192
M_r = 185.60	D_x = 1.529 Mg m⁻³
Monoclinic, P2₁	Mo Kα radiation, λ = 0.71073 Å
a = 6.5088 (6) Å	Cell parameters from 1576 reflections
b = 5.1758 (5) Å	θ = 3.9–28.2°
c = 12.2175 (14) Å	µ = 0.43 mm⁻¹
β = 101.649 (10)°	T = 296 K
V = 403.11 (7) Å³	Plate, colourless
Z = 2	0.45 × 0.20 × 0.07 mm

Data collection top

SuperNova, Dual, Cu at home/near, Atlas diffractometer	1487 reflections with I > 2σ(I)
ω scans	R_int = 0.028
Absorption correction: gaussian (CrysAlis Pro; Rigaku OD, 2023)	θ_max = 29.7°, θ_min = 3.3°
T_min = 0.642, T_max = 1.000	h = −8→8
3642 measured reflections	k = −7→7
1902 independent reflections	l = −16→13

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.039	w = 1/[σ²(F_o²) + (0.0294P)² + 0.0021P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.081	(Δ/σ)_max < 0.001
S = 1.06	Δρ_max = 0.16 e Å⁻³
1902 reflections	Δρ_min = −0.18 e Å⁻³
110 parameters	Absolute structure: Flack x determined using 510 quotients [(I⁺)-(I^-)]/[(I⁺)+(I^-)] (Parsons et al., 2013)
1 restraint	Absolute structure parameter: 0.11 (5)

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
C1	0.7301 (4)	0.3699 (6)	0.8980 (2)	0.0311 (7)
C2	0.5982 (4)	0.5654 (6)	0.9179 (3)	0.0334 (7)
H2	0.645995	0.688449	0.972562	0.040*
C3	0.3940 (5)	0.5786 (6)	0.8563 (3)	0.0337 (7)
H3	0.305127	0.710757	0.869335	0.040*
C4	0.3236 (4)	0.3932 (6)	0.7754 (2)	0.0290 (7)
C5	0.4562 (5)	0.1964 (6)	0.7575 (3)	0.0335 (8)
H5	0.408280	0.070786	0.703994	0.040*
C6	0.6593 (5)	0.1844 (6)	0.8184 (3)	0.0348 (8)
H6	0.747984	0.051642	0.805778	0.042*
C7	−0.0065 (5)	0.6041 (7)	0.6835 (3)	0.0349 (7)
C8	−0.2181 (5)	0.5695 (7)	0.6051 (3)	0.0442 (9)
H8A	−0.238963	0.713348	0.553173	0.053*
H8B	−0.326264	0.580067	0.649112	0.053*
N1	0.1164 (3)	0.3959 (5)	0.7083 (2)	0.0331 (6)
H1	0.065971	0.250333	0.681401	0.040*
O1	0.9342 (3)	0.3507 (4)	0.9570 (2)	0.0433 (6)
H1A	0.967245	0.484830	0.991810	0.065*
O2	0.0363 (3)	0.8215 (4)	0.7186 (2)	0.0500 (6)
Cl1	−0.25580 (12)	0.27889 (19)	0.52655 (7)	0.0555 (3)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0250 (14)	0.0296 (17)	0.0360 (17)	−0.0017 (13)	−0.0002 (12)	0.0054 (14)
C2	0.0334 (17)	0.0289 (17)	0.0344 (17)	−0.0011 (14)	−0.0014 (13)	−0.0042 (14)
C3	0.0304 (16)	0.0303 (17)	0.0383 (18)	0.0034 (14)	0.0022 (13)	−0.0025 (14)
C4	0.0251 (15)	0.0268 (15)	0.0329 (16)	−0.0010 (13)	0.0006 (12)	0.0036 (13)
C5	0.0326 (16)	0.0266 (17)	0.0386 (18)	−0.0022 (13)	0.0007 (13)	−0.0037 (13)
C6	0.0293 (15)	0.0254 (16)	0.050 (2)	0.0063 (12)	0.0079 (14)	−0.0008 (14)
C7	0.0279 (16)	0.0337 (18)	0.0412 (18)	0.0000 (14)	0.0022 (13)	0.0041 (15)
C8	0.0340 (17)	0.0336 (19)	0.058 (2)	0.0014 (15)	−0.0066 (15)	0.0046 (17)
N1	0.0279 (13)	0.0259 (13)	0.0407 (15)	−0.0005 (11)	−0.0047 (11)	−0.0030 (12)
O1	0.0293 (10)	0.0387 (15)	0.0545 (14)	0.0005 (10)	−0.0093 (9)	−0.0015 (12)
O2	0.0407 (12)	0.0297 (14)	0.0705 (16)	0.0019 (11)	−0.0105 (11)	−0.0033 (12)
Cl1	0.0505 (5)	0.0519 (5)	0.0530 (5)	−0.0009 (5)	−0.0155 (4)	−0.0056 (5)

Geometric parameters (Å, º) top

C1—C6	1.378 (4)	C5—H5	0.9300
C1—C2	1.379 (4)	C6—H6	0.9300
C1—O1	1.381 (3)	C7—O2	1.216 (4)
C2—C3	1.391 (4)	C7—N1	1.340 (4)
C2—H2	0.9300	C7—C8	1.520 (4)
C3—C4	1.387 (4)	C8—Cl1	1.774 (4)
C3—H3	0.9300	C8—H8A	0.9700
C4—C5	1.381 (4)	C8—H8B	0.9700
C4—N1	1.430 (3)	N1—H1	0.8600
C5—C6	1.382 (4)	O1—H1A	0.8200

C6—C1—C2	120.3 (3)	C1—C6—H6	120.1
C6—C1—O1	117.8 (3)	C5—C6—H6	120.1
C2—C1—O1	121.9 (3)	O2—C7—N1	125.5 (3)
C1—C2—C3	120.1 (3)	O2—C7—C8	116.4 (3)
C1—C2—H2	119.9	N1—C7—C8	118.1 (3)
C3—C2—H2	119.9	C7—C8—Cl1	116.7 (2)
C4—C3—C2	119.6 (3)	C7—C8—H8A	108.1
C4—C3—H3	120.2	Cl1—C8—H8A	108.1
C2—C3—H3	120.2	C7—C8—H8B	108.1
C5—C4—C3	119.8 (3)	Cl1—C8—H8B	108.1
C5—C4—N1	117.6 (3)	H8A—C8—H8B	107.3
C3—C4—N1	122.6 (3)	C7—N1—C4	126.0 (3)
C4—C5—C6	120.6 (3)	C7—N1—H1	117.0
C4—C5—H5	119.7	C4—N1—H1	117.0
C6—C5—H5	119.7	C1—O1—H1A	109.5
C1—C6—C5	119.7 (3)

N1—C7—C8—Cl1	−15.4 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C3—H3···O2	0.93	2.34	2.873 (4)	116
N1—H1···Cl1	0.86	2.53	2.999 (2)	115
N1—H1···O2ⁱ	0.86	2.28	3.025 (3)	145
O1—H1A···O1ⁱⁱ	0.82	2.06	2.8585 (17)	166

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

Acknowledgements

YR is thankful to the National Center for Scientific and Technical Research of Morocco (CNRST) for its continuous support. The contributions of the authors are as follows: conceptualization, YR; methodology, AA; investigation, AEMAA and IAEH; writing (original draft), AEMAA; writing (review and editing of the manuscript), YR; formal analysis, YR and BMK; supervision, YR; crystal structure determination, BMK.

References

Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854. Web of Science CrossRef CAS IUCr Journals Google Scholar
Gowda, B. T., Foro, S. & Fuess, H. (2007). Acta Cryst. E63, o4488. CrossRef IUCr Journals Google Scholar
Gowda, B. T., Kožíšek, J., Tokarčík, M. & Fuess, H. (2008). Acta Cryst. E64, o987. Web of Science CSD CrossRef IUCr Journals Google Scholar
Kang, S., Zeng, H., Li, H. & Wang, H. (2008). Acta Cryst. E64, o1194. Web of Science CSD CrossRef IUCr Journals Google Scholar
Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226–235. Web of Science CrossRef CAS IUCr Journals Google Scholar
Missioui, M., Guerrab, W., Nchioua, I., El Moutaouakil Ala Allah, A., Kalonji Mubengayi, C., Alsubari, A., Mague, J. T. & Ramli, Y. (2022). Acta Cryst. E78, 687–690. Web of Science CSD CrossRef IUCr Journals Google Scholar
Missioui, M., Mortada, S., Guerrab, W., Serdaroğlu, G., Kaya, S., Mague, J. T., Essassi, E. M., Faouzi, M. E. A. & Ramli, Y. (2021). J. Mol. Struct. 1239, 130484. Web of Science CSD CrossRef Google Scholar
Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Rigaku OD (2023). CrysAlis PRO. Rigaku Oxford Diffraction. 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

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.