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Substituted benzoic acid and cinnamic acid esters are of inter­est as tyrosinase inhibitors and the development of such inhibitors may help in diminishing many dermatological disorders. The tyrosinase enzyme has also been linked to Parkinson's disease. In view of hy­droxy­lated compounds having ester and amide functionalities to potentially inhibit tyrosinase, we herein report the synthesis and crystal structures of two amide-based derivatives, namely N-(4-acetyl­phen­yl)-2-chloro­acetamide, C10H10ClNO2, (I), and 2-(4-acetyl­anilino)-2-oxoethyl cinnamate, C19H17NO4, (II). In compound (I), the acetyl­phenyl ring and the N—(C=O)—C unit of the acetamide group are almost coplanar, with a dihedral angle of 7.39 (18)°. Instead of esterification, a cheaper and more efficient synthetic method has been developed for the preparation of compound (II). The mol­ecular geometry of compound (II) is a V-shape. The acetamide and cinnamate groups are almost planar, with mean deviations of 0.088 and 0.046 Å, respectively; the dihedral angle between these groups is 77.39 (7)°. The carbonyl O atoms are positioned syn and anti to the amide carbonyl O atom. In the crystals of (I) and (II), N—H...O, C—H...O and C—H...π inter­actions link the mol­ecules into a three-dimensional network.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S205322961502433X/cu3092sup1.cif
Contains datablocks I, II, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S205322961502433X/cu3092Isup2.hkl
Contains datablock I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S205322961502433X/cu3092IIsup3.hkl
Contains datablock II

CCDC references: 1443110; 1443109

Introduction top

The synthesis and bioevaluation of substituted benzoic acid and cinnamic acid esters as tyrosinase inhibitors is currently ongoing research in our laboratory (Ashraf et al., 2014, 2015). A number of hy­droxy-substituted aromatic acids and esters have been reported as potent tyrosinase inhibitors (Menezes et al., 2011; Miliovsky et al., 2013; Liu et al., 2003; Chen et al., 2005). Takahashi & Miyazawa (2011) also reported the potential of hy­droxy­lated amides and analogues to potentially inhibit tyrosinase. The development of potent tyrosinase inhibitors may help in diminishing many dermatological disorders such as melasma, lentigosenilis, hyperpigmentation etc. (Urabe et al., 1998; Lynde et al., 2006; Cullen, 1998). Zhu et al. (2011) reported that tyrosinase enzyme has also been linked to Parkinson's disease.

In view of hy­droxy­lated compounds having ester and amide functionalities to potentially inhibit tyrosinase, we herein report the synthesis and crystal structures of the amide inter­mediate N-(4-acetyl­phenyl)-2-chloro­acetamide, (I), and the amide compound having a cinnamate ester moiety, namely 2-(4-acetyl­anilino)-2-oxo­ethyl­cinnamate, (II). Inter­mediate compound (I) possesses a 4-acetyl group and a halogen atom (Cl) at the α-methyl group. The chloro group can easily be replaced by nucleophilic substitution, while the acetyl group can undergo a nucleophilic addition reaction potentially resulting in a number of imine derivatives. Cinnamate ester (II) has been synthesized by nucleophilic substitution of a chloro group with cinnamic acid (see Scheme 1).

Experimental top

Synthesis and crystallization top

The amide inter­mediate N-(4-acetyl­phenyl)-2-chloro­acetamide, (I), was synthesized in a three-step synthesis from the acetanilide. In the first step, the acetanilide was treated with acetyl chloride and AlCl3 under Friedal–Crafts acyl­ation conditions to get the 4-acetyl­acetanilide. The latter was then subjected to acidic hydrolysis in the presence of 70% H2SO4 to get 4-amino­aceto­phenone. The free amino group in 4-amino­aceto­phenone was then reacted with chloro­acetyl chloride in the presence of dry CH2Cl2 and tri­ethyl amine at 273 K to afford inter­mediate (I). The progress of the reaction was monitored by thin-layer chromatography (TLC) (n-hexane–ethyl acetate = 2:1 v/v as eluent). After the completion of the reaction, the mixture was poured into ice-cold water. Inter­mediate (I) was extracted with ethyl acetate. On evaporation of the solvent under reduced pressure, a light-yellow precipitate was obtained (yield 84%, m.p. 430–431 K). Needle-shaped crystals were obtained from a mixture of ethyl acetate and n-hexane (1:0.5 v/v) upon slow evaporation at room temperature. FT–IR νmax cm-1: 3462 (N–H), 3072 (sp2 C—H), 2851 (sp3 C—H), 1715 (CO keto), 1631 (CO amide),1600 (CC aromatic), 1167 (C—O amide).

Inter­mediate (I) was then reacted with cinnamic acid in an equimolar ratio in the presence of tri­ethyl­amine and potassium iodide in di­methyl­formamide. The reaction mixture was stirred overnight at room temperature and then extracted with ethyl acetate. It was washed with 5% HCl and 5% NaHCO3, and finally with brine. Evaporation of the solvent afforded compound (II) (yield 78%, m.p. 435–437 K). FT–IR νmax cm-1: 3321 (N—H), 2918 (sp2 C—H), 2820 (sp3 C—H), 1739 (CO ester), 1728 (CO keto), 1650 (CO amide), 1593 (CC aromatic), 1146 (C—O, ester); 1H NMR (DMSO-d6): δ 10.5 (s, 1H, —NH), 7.96 (d, J = 4.0 Hz, 2H, H-3', H-5'), 7.70–7.77 (m, 5H, H-2–H-6), 7.47 (d, J = 3.6, 2.0 Hz, 2H, H-2',6'), 7.46 (d, J = 16.0 Hz, 1H, H-2"), 6.75 (d, J = 16.0 Hz, 1H, H-1"), 4.85 (s, 2H, —CH2), 2.54 (s, 3H, —CH3).

Refinement top

Crystal data, data collection and structure refinement details are summarized in Table 1. In the two title compounds, H atoms on N atoms were located in a difference Fourier map and refined freely [N—H = 0.80 (3) Å for (I) and 0.89 (4) Å for (II)]. All other H atoms were included as riding atoms, with C—H = 0.93–0.97 Å and Uiso(H) = 1.5Ueq(C) for methyl H atoms or 1.2Ueq(C) otherwise.

Results and discussion top

A nubmer of cinnamic acid derivatives have been reported as potent tyrosinase inhihitors (Dayan & Riemer, 2007). 2-(4-Acetyl­anilino)-2-oxo­ethyl­cinnamate, (II), which can be used as tyrosinase inhibitor, was synthesized by using a simple reaction in which the nucleophilic replacement of the halogen Cl atom of N-(4-acetyl­phenyl)-2-chloro­acetamide, (I), was replaced with the carb­oxy­lic acid O atom of cinnamic acid. This reaction was carried out at room temperature and gave a good yield (yield 78%). Another way to synthesize compound (II) is by esterification of hy­droxy-substituted inter­mediate (I) instead of replacing a [OK?] the halogen with a cinnamic acid group. Esterification reactions are reversible, which means that reflux temperatures must be achieved and sustained for a longer period of time (e.g. 6–10 h) and the yields are not as good (Soda et al., 2012). The method reported here for the preparation of (II) is cheaper and provides a good yield.

Compound (I) crystallized in the orthorhombic noncentrosymmetric P212121 space group. The acetyl­phenyl (atoms O1/C1–C9) and the N—(CO)—C plane of the acetamide group are almost coplanar, with a dihedral angel of 7.39 (18)° (Fig. 1). The carbonyl O1 atom is positioned anti with respect to the carbonyl O12 atom, with bond lengths of 1.219 (3) (C3—O1) and 1.201 (3) Å (C11—O12). The crystal structure of (I) is stabilized by three kinds of inter­molecular hydrogen bonds. Both N—H···O and C—H···π hydrogen bonds (H8···Cg1 = 3.650 Å; Cg1 is the centroid of the C4–C9 ring) link the molecules into zigzag chains extending along the b axis (Fig. 2). The third hydrogen bond is of the C—H···O type (Table 2), with the carbonyl O12 atom functioning as a hydrogen-bond acceptor to connect the components into a three-dimensional network (Fig. 3)

In compound (II), the molecular geometry is a V-shape because of the sp3-hybridization of the central C13 atom (Fig. 4). The acetamide group (atoms O1/O12/N10/C2–C9/C11) is almost planar, as at compound (I), with a mean deviation of 0.088 Å from the corresponding least-squares plane defined by the 12 constituent atoms. The cinnamate group (atoms O14/O16/C15/C17–C24) is also planar, with a mean deviation of 0.046 Å from the least-squares plane of the 11 constituent atoms. The dihedral angle between the two planes is 77.39 (7)°. The carbonyl O12 atom is positioned syn with respect to the carbonyl O1 atom, which has been changed from that of compound (I). This change of configuration is possible because of the single-bond character of C2—C3 [1.478 (6) Å]. However, the carbonyl O16 atom is positioned anti with respect to the carbonyl O12 atom. The CO bond lengths are in the range 1.196 (4)–1.221 (5) Å. The C17—C18 bond length [1.319 (5) Å] is consistent with a double-bond character and it is in a trans conformation. In the crystal, there are three kinds of hydrogen bonds (Table 3), viz. N—H···O, C—H···O and C—H···π (H4C···Cg2 = 3.010 Å; Cg2 is the centroid of the C19–C24 ring). These inter­molecular inter­actions link the molecules into a three-dimensional network (Fig. 5).

Structure description top

The synthesis and bioevaluation of substituted benzoic acid and cinnamic acid esters as tyrosinase inhibitors is currently ongoing research in our laboratory (Ashraf et al., 2014, 2015). A number of hy­droxy-substituted aromatic acids and esters have been reported as potent tyrosinase inhibitors (Menezes et al., 2011; Miliovsky et al., 2013; Liu et al., 2003; Chen et al., 2005). Takahashi & Miyazawa (2011) also reported the potential of hy­droxy­lated amides and analogues to potentially inhibit tyrosinase. The development of potent tyrosinase inhibitors may help in diminishing many dermatological disorders such as melasma, lentigosenilis, hyperpigmentation etc. (Urabe et al., 1998; Lynde et al., 2006; Cullen, 1998). Zhu et al. (2011) reported that tyrosinase enzyme has also been linked to Parkinson's disease.

In view of hy­droxy­lated compounds having ester and amide functionalities to potentially inhibit tyrosinase, we herein report the synthesis and crystal structures of the amide inter­mediate N-(4-acetyl­phenyl)-2-chloro­acetamide, (I), and the amide compound having a cinnamate ester moiety, namely 2-(4-acetyl­anilino)-2-oxo­ethyl­cinnamate, (II). Inter­mediate compound (I) possesses a 4-acetyl group and a halogen atom (Cl) at the α-methyl group. The chloro group can easily be replaced by nucleophilic substitution, while the acetyl group can undergo a nucleophilic addition reaction potentially resulting in a number of imine derivatives. Cinnamate ester (II) has been synthesized by nucleophilic substitution of a chloro group with cinnamic acid (see Scheme 1).

A nubmer of cinnamic acid derivatives have been reported as potent tyrosinase inhihitors (Dayan & Riemer, 2007). 2-(4-Acetyl­anilino)-2-oxo­ethyl­cinnamate, (II), which can be used as tyrosinase inhibitor, was synthesized by using a simple reaction in which the nucleophilic replacement of the halogen Cl atom of N-(4-acetyl­phenyl)-2-chloro­acetamide, (I), was replaced with the carb­oxy­lic acid O atom of cinnamic acid. This reaction was carried out at room temperature and gave a good yield (yield 78%). Another way to synthesize compound (II) is by esterification of hy­droxy-substituted inter­mediate (I) instead of replacing a [OK?] the halogen with a cinnamic acid group. Esterification reactions are reversible, which means that reflux temperatures must be achieved and sustained for a longer period of time (e.g. 6–10 h) and the yields are not as good (Soda et al., 2012). The method reported here for the preparation of (II) is cheaper and provides a good yield.

Compound (I) crystallized in the orthorhombic noncentrosymmetric P212121 space group. The acetyl­phenyl (atoms O1/C1–C9) and the N—(CO)—C plane of the acetamide group are almost coplanar, with a dihedral angel of 7.39 (18)° (Fig. 1). The carbonyl O1 atom is positioned anti with respect to the carbonyl O12 atom, with bond lengths of 1.219 (3) (C3—O1) and 1.201 (3) Å (C11—O12). The crystal structure of (I) is stabilized by three kinds of inter­molecular hydrogen bonds. Both N—H···O and C—H···π hydrogen bonds (H8···Cg1 = 3.650 Å; Cg1 is the centroid of the C4–C9 ring) link the molecules into zigzag chains extending along the b axis (Fig. 2). The third hydrogen bond is of the C—H···O type (Table 2), with the carbonyl O12 atom functioning as a hydrogen-bond acceptor to connect the components into a three-dimensional network (Fig. 3)

In compound (II), the molecular geometry is a V-shape because of the sp3-hybridization of the central C13 atom (Fig. 4). The acetamide group (atoms O1/O12/N10/C2–C9/C11) is almost planar, as at compound (I), with a mean deviation of 0.088 Å from the corresponding least-squares plane defined by the 12 constituent atoms. The cinnamate group (atoms O14/O16/C15/C17–C24) is also planar, with a mean deviation of 0.046 Å from the least-squares plane of the 11 constituent atoms. The dihedral angle between the two planes is 77.39 (7)°. The carbonyl O12 atom is positioned syn with respect to the carbonyl O1 atom, which has been changed from that of compound (I). This change of configuration is possible because of the single-bond character of C2—C3 [1.478 (6) Å]. However, the carbonyl O16 atom is positioned anti with respect to the carbonyl O12 atom. The CO bond lengths are in the range 1.196 (4)–1.221 (5) Å. The C17—C18 bond length [1.319 (5) Å] is consistent with a double-bond character and it is in a trans conformation. In the crystal, there are three kinds of hydrogen bonds (Table 3), viz. N—H···O, C—H···O and C—H···π (H4C···Cg2 = 3.010 Å; Cg2 is the centroid of the C19–C24 ring). These inter­molecular inter­actions link the molecules into a three-dimensional network (Fig. 5).

Synthesis and crystallization top

The amide inter­mediate N-(4-acetyl­phenyl)-2-chloro­acetamide, (I), was synthesized in a three-step synthesis from the acetanilide. In the first step, the acetanilide was treated with acetyl chloride and AlCl3 under Friedal–Crafts acyl­ation conditions to get the 4-acetyl­acetanilide. The latter was then subjected to acidic hydrolysis in the presence of 70% H2SO4 to get 4-amino­aceto­phenone. The free amino group in 4-amino­aceto­phenone was then reacted with chloro­acetyl chloride in the presence of dry CH2Cl2 and tri­ethyl amine at 273 K to afford inter­mediate (I). The progress of the reaction was monitored by thin-layer chromatography (TLC) (n-hexane–ethyl acetate = 2:1 v/v as eluent). After the completion of the reaction, the mixture was poured into ice-cold water. Inter­mediate (I) was extracted with ethyl acetate. On evaporation of the solvent under reduced pressure, a light-yellow precipitate was obtained (yield 84%, m.p. 430–431 K). Needle-shaped crystals were obtained from a mixture of ethyl acetate and n-hexane (1:0.5 v/v) upon slow evaporation at room temperature. FT–IR νmax cm-1: 3462 (N–H), 3072 (sp2 C—H), 2851 (sp3 C—H), 1715 (CO keto), 1631 (CO amide),1600 (CC aromatic), 1167 (C—O amide).

Inter­mediate (I) was then reacted with cinnamic acid in an equimolar ratio in the presence of tri­ethyl­amine and potassium iodide in di­methyl­formamide. The reaction mixture was stirred overnight at room temperature and then extracted with ethyl acetate. It was washed with 5% HCl and 5% NaHCO3, and finally with brine. Evaporation of the solvent afforded compound (II) (yield 78%, m.p. 435–437 K). FT–IR νmax cm-1: 3321 (N—H), 2918 (sp2 C—H), 2820 (sp3 C—H), 1739 (CO ester), 1728 (CO keto), 1650 (CO amide), 1593 (CC aromatic), 1146 (C—O, ester); 1H NMR (DMSO-d6): δ 10.5 (s, 1H, —NH), 7.96 (d, J = 4.0 Hz, 2H, H-3', H-5'), 7.70–7.77 (m, 5H, H-2–H-6), 7.47 (d, J = 3.6, 2.0 Hz, 2H, H-2',6'), 7.46 (d, J = 16.0 Hz, 1H, H-2"), 6.75 (d, J = 16.0 Hz, 1H, H-1"), 4.85 (s, 2H, —CH2), 2.54 (s, 3H, —CH3).

Refinement details top

Crystal data, data collection and structure refinement details are summarized in Table 1. In the two title compounds, H atoms on N atoms were located in a difference Fourier map and refined freely [N—H = 0.80 (3) Å for (I) and 0.89 (4) Å for (II)]. All other H atoms were included as riding atoms, with C—H = 0.93–0.97 Å and Uiso(H) = 1.5Ueq(C) for methyl H atoms or 1.2Ueq(C) otherwise.

Computing details top

For both compounds, data collection: SMART (Bruker, 2012); cell refinement: SAINT (Bruker, 2012); data reduction: SAINT (Bruker, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: publCIF (Westrip, 2010).

Figures top
[Figure 1] Fig. 1. The molecular structure of compound, (I), showing the atom-numbering scheme and 30% probability displacement ellipsoids.
[Figure 2] Fig. 2. Part of the crystal structure of compound (I), showing molecules linked by intermolecular N—H···O and C—H···π interactions (dashed lines) along b axis forming a zigzag chain.
[Figure 3] Fig. 3. Part of the crystal structure of compound (I), showing the three-dimensional network of molecules linked by N—H···O and C—H···O hydrogen bonds (dashed lines).
[Figure 4] Fig. 4. The V-shape molecular structure of compound (II), showing the atom-numbering scheme and 30% probability displacement ellipsoids.
[Figure 5] Fig. 5. Part of the crystal structure of compound (II), showing the three-dimensional network of molecules linked by N—H···O and C—H···O hydrogen bonds (dashed lines).
(I) N-(4-Acetylphenyl)-2-chloroacetamide top
Crystal data top
C10H10ClNO2Dx = 1.410 Mg m3
Mr = 211.64Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121Cell parameters from 9297 reflections
a = 4.1713 (1) Åθ = 2.5–27.9°
b = 14.7792 (4) ŵ = 0.36 mm1
c = 16.1755 (4) ÅT = 296 K
V = 997.19 (4) Å3Block, colourless
Z = 40.29 × 0.27 × 0.25 mm
F(000) = 440
Data collection top
Bruker SMART CCD area-detector
diffractometer
2189 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.025
φ and ω scansθmax = 28.4°, θmin = 1.9°
Absorption correction: multi-scan
(SADABS; Bruker, 2012)
h = 45
Tmin = 0.890, Tmax = 0.905k = 1919
21908 measured reflectionsl = 2121
2489 independent reflections
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.038 w = 1/[σ2(Fo2) + (0.0511P)2 + 0.2203P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.106(Δ/σ)max < 0.001
S = 1.05Δρmax = 0.34 e Å3
2489 reflectionsΔρmin = 0.21 e Å3
132 parametersAbsolute structure: Flack x determined using 819 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons & Flack, 2004)
0 restraintsAbsolute structure parameter: 0.033 (14)
Crystal data top
C10H10ClNO2V = 997.19 (4) Å3
Mr = 211.64Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 4.1713 (1) ŵ = 0.36 mm1
b = 14.7792 (4) ÅT = 296 K
c = 16.1755 (4) Å0.29 × 0.27 × 0.25 mm
Data collection top
Bruker SMART CCD area-detector
diffractometer
2489 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2012)
2189 reflections with I > 2σ(I)
Tmin = 0.890, Tmax = 0.905Rint = 0.025
21908 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.038H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.106Δρmax = 0.34 e Å3
S = 1.05Δρmin = 0.21 e Å3
2489 reflectionsAbsolute structure: Flack x determined using 819 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons & Flack, 2004)
132 parametersAbsolute structure parameter: 0.033 (14)
0 restraints
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
xyzUiso*/Ueq
O10.3090 (7)0.91692 (14)0.79553 (12)0.0734 (7)
C20.0351 (7)0.97312 (17)0.67865 (17)0.0565 (6)
H2A0.01711.02680.71170.085*
H2B0.17490.95310.66260.085*
H2C0.15940.98600.63010.085*
C30.1961 (7)0.90065 (16)0.72759 (14)0.0485 (6)
C40.2230 (6)0.80791 (16)0.69210 (13)0.0430 (5)
C50.3856 (7)0.74153 (17)0.73672 (14)0.0513 (6)
H50.47690.75600.78750.062*
C60.4122 (7)0.65528 (16)0.70661 (14)0.0504 (6)
H60.52110.61180.73720.061*
C70.2774 (6)0.63189 (15)0.63035 (13)0.0424 (5)
C80.1178 (7)0.69802 (16)0.58504 (13)0.0478 (5)
H80.02780.68380.53410.057*
C90.0933 (7)0.78470 (17)0.61582 (13)0.0471 (5)
H90.01230.82860.58490.056*
N100.3136 (6)0.54170 (14)0.60441 (12)0.0480 (5)
H100.413 (8)0.509 (2)0.6343 (19)0.055 (8)*
C110.1741 (7)0.50007 (17)0.53897 (15)0.0492 (6)
O120.0027 (7)0.53651 (14)0.49073 (13)0.0762 (7)
C130.2641 (9)0.40081 (19)0.53398 (18)0.0658 (8)
H13A0.18110.36970.58230.079*
H13B0.49580.39530.53470.079*
Cl140.1160 (3)0.34854 (5)0.44531 (5)0.0852 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.1087 (19)0.0584 (11)0.0532 (10)0.0123 (12)0.0182 (12)0.0073 (8)
C20.0608 (15)0.0526 (14)0.0562 (14)0.0048 (12)0.0062 (13)0.0048 (11)
C30.0543 (15)0.0503 (13)0.0409 (11)0.0112 (11)0.0045 (11)0.0002 (9)
C40.0462 (12)0.0465 (11)0.0363 (10)0.0088 (10)0.0019 (9)0.0030 (8)
C50.0652 (16)0.0517 (12)0.0369 (10)0.0127 (13)0.0107 (11)0.0053 (9)
C60.0617 (16)0.0470 (12)0.0427 (11)0.0057 (12)0.0137 (11)0.0106 (9)
C70.0470 (12)0.0446 (11)0.0356 (10)0.0059 (10)0.0016 (9)0.0047 (8)
C80.0556 (14)0.0543 (13)0.0335 (10)0.0006 (12)0.0064 (10)0.0010 (9)
C90.0541 (14)0.0494 (12)0.0377 (10)0.0010 (11)0.0035 (10)0.0051 (9)
N100.0590 (13)0.0461 (10)0.0389 (9)0.0017 (10)0.0075 (9)0.0031 (8)
C110.0542 (15)0.0525 (12)0.0409 (11)0.0015 (11)0.0003 (11)0.0023 (9)
O120.0970 (18)0.0670 (12)0.0647 (12)0.0196 (12)0.0374 (12)0.0151 (10)
C130.080 (2)0.0589 (16)0.0586 (15)0.0105 (15)0.0172 (15)0.0145 (12)
Cl140.1245 (8)0.0599 (4)0.0713 (5)0.0088 (5)0.0269 (5)0.0142 (3)
Geometric parameters (Å, º) top
O1—C31.219 (3)C7—C81.391 (3)
C2—C31.492 (4)C7—N101.405 (3)
C2—H2A0.9600C8—C91.378 (3)
C2—H2B0.9600C8—H80.9300
C2—H2C0.9600C9—H90.9300
C3—C41.490 (3)N10—C111.356 (3)
C4—C91.390 (3)N10—H100.80 (3)
C4—C51.394 (3)C11—O121.201 (3)
C5—C61.369 (4)C11—C131.516 (4)
C5—H50.9300C13—Cl141.742 (3)
C6—C71.399 (3)C13—H13A0.9700
C6—H60.9300C13—H13B0.9700
C3—C2—H2A109.5C6—C7—N10117.0 (2)
C3—C2—H2B109.5C9—C8—C7119.9 (2)
H2A—C2—H2B109.5C9—C8—H8120.1
C3—C2—H2C109.5C7—C8—H8120.1
H2A—C2—H2C109.5C8—C9—C4121.4 (2)
H2B—C2—H2C109.5C8—C9—H9119.3
O1—C3—C4120.0 (2)C4—C9—H9119.3
O1—C3—C2120.7 (2)C11—N10—C7128.1 (2)
C4—C3—C2119.3 (2)C11—N10—H10115 (2)
C9—C4—C5118.4 (2)C7—N10—H10117 (2)
C9—C4—C3122.6 (2)O12—C11—N10124.6 (2)
C5—C4—C3119.0 (2)O12—C11—C13123.4 (2)
C6—C5—C4120.7 (2)N10—C11—C13112.0 (2)
C6—C5—H5119.7C11—C13—Cl14112.6 (2)
C4—C5—H5119.7C11—C13—H13A109.1
C5—C6—C7120.7 (2)Cl14—C13—H13A109.1
C5—C6—H6119.6C11—C13—H13B109.1
C7—C6—H6119.6Cl14—C13—H13B109.1
C8—C7—C6118.9 (2)H13A—C13—H13B107.8
C8—C7—N10124.1 (2)
Hydrogen-bond geometry (Å, º) top
Cg1 is the centroid of the C4–C9 ring.
D—H···AD—HH···AD···AD—H···A
C2—H2C···O12i0.962.433.353 (3)161
C8—H8···O120.932.292.877 (3)121
N10—H10···O1ii0.80 (3)2.11 (3)2.915 (3)176 (3)
C8—H8···Cg1iii0.933.654.434 (3)144
Symmetry codes: (i) x+1/2, y+3/2, z+1; (ii) x+1, y1/2, z+3/2; (iii) x1/2, y+3/2, z+1.
(II) 2-(4-Acetylanilino)-2-oxoethyl cinnamate top
Crystal data top
C19H17NO4Dx = 1.292 Mg m3
Mr = 323.33Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pca21Cell parameters from 2290 reflections
a = 9.7969 (15) Åθ = 3.1–19.4°
b = 17.594 (3) ŵ = 0.09 mm1
c = 9.6425 (15) ÅT = 296 K
V = 1662.1 (4) Å3Plate, colourless
Z = 40.20 × 0.18 × 0.10 mm
F(000) = 680
Data collection top
Bruker SMART CCD area-detector
diffractometer
1781 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.044
φ and ω scansθmax = 28.3°, θmin = 2.3°
Absorption correction: multi-scan
(SADABS; Bruker, 2012)
h = 1312
Tmin = 0.975, Tmax = 0.995k = 2322
13763 measured reflectionsl = 1212
3879 independent reflections
Refinement top
Refinement on F21 restraint
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.057H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.119 w = 1/[σ2(Fo2) + (0.0459P)2]
where P = (Fo2 + 2Fc2)/3
S = 0.99(Δ/σ)max < 0.001
3879 reflectionsΔρmax = 0.11 e Å3
222 parametersΔρmin = 0.12 e Å3
Crystal data top
C19H17NO4V = 1662.1 (4) Å3
Mr = 323.33Z = 4
Orthorhombic, Pca21Mo Kα radiation
a = 9.7969 (15) ŵ = 0.09 mm1
b = 17.594 (3) ÅT = 296 K
c = 9.6425 (15) Å0.20 × 0.18 × 0.10 mm
Data collection top
Bruker SMART CCD area-detector
diffractometer
3879 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2012)
1781 reflections with I > 2σ(I)
Tmin = 0.975, Tmax = 0.995Rint = 0.044
13763 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0571 restraint
wR(F2) = 0.119H atoms treated by a mixture of independent and constrained refinement
S = 0.99Δρmax = 0.11 e Å3
3879 reflectionsΔρmin = 0.12 e Å3
222 parameters
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
xyzUiso*/Ueq
O10.8574 (4)0.3135 (2)0.4874 (4)0.1302 (15)
C20.7449 (7)0.2863 (2)0.4653 (5)0.0888 (15)
C30.7323 (5)0.2206 (2)0.3704 (4)0.0643 (11)
C40.6205 (6)0.3195 (3)0.5314 (6)0.1145 (19)
H4A0.64720.35290.60520.172*
H4B0.56460.27940.56790.172*
H4C0.56970.34760.46340.172*
C50.8482 (4)0.1850 (3)0.3212 (6)0.0826 (14)
H50.93280.20240.35120.099*
C60.8442 (4)0.1257 (2)0.2308 (5)0.0741 (13)
H60.92470.10260.20150.089*
C70.7192 (3)0.0999 (2)0.1828 (4)0.0538 (10)
C80.6030 (4)0.1343 (2)0.2313 (5)0.0738 (13)
H80.51820.11720.20130.089*
C90.6099 (4)0.1936 (2)0.3230 (5)0.0820 (13)
H90.52950.21600.35380.098*
N100.7033 (3)0.04028 (18)0.0870 (3)0.0569 (9)
H100.620 (4)0.025 (2)0.062 (5)0.100 (17)*
C110.7993 (4)0.0064 (2)0.0340 (5)0.0635 (11)
O120.9198 (2)0.00278 (15)0.0659 (4)0.0964 (11)
C130.7502 (5)0.0647 (2)0.0685 (4)0.0723 (12)
H13A0.65130.06720.06660.087*
H13B0.77830.05040.16130.087*
O140.8069 (3)0.13785 (15)0.0332 (3)0.0743 (8)
C150.7484 (4)0.1718 (2)0.0733 (5)0.0594 (10)
O160.6561 (3)0.14411 (17)0.1369 (4)0.0918 (10)
C170.8134 (4)0.2450 (2)0.1080 (5)0.0630 (10)
H170.89020.26090.05920.076*
C180.7634 (4)0.2880 (2)0.2077 (4)0.0654 (11)
H180.68710.26900.25350.078*
C190.8132 (4)0.3621 (2)0.2553 (4)0.0614 (11)
C200.9287 (4)0.3959 (2)0.1999 (5)0.0751 (12)
H200.97880.37090.13180.090*
C210.9695 (5)0.4671 (3)0.2463 (6)0.0895 (14)
H211.04640.49010.20820.107*
C220.8971 (6)0.5038 (3)0.3482 (6)0.0905 (15)
H220.92460.55160.37830.109*
C230.7852 (5)0.4703 (3)0.4052 (5)0.0920 (16)
H230.73730.49460.47550.110*
C240.7430 (5)0.3997 (2)0.3580 (5)0.0786 (14)
H240.66580.37730.39650.094*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.140 (3)0.099 (2)0.152 (4)0.027 (2)0.063 (3)0.015 (3)
C20.123 (4)0.061 (3)0.083 (3)0.013 (4)0.043 (4)0.014 (3)
C30.074 (3)0.055 (2)0.063 (3)0.009 (2)0.019 (3)0.011 (2)
C40.167 (5)0.078 (4)0.099 (4)0.016 (4)0.022 (4)0.010 (3)
C50.065 (3)0.084 (3)0.099 (4)0.025 (3)0.019 (3)0.006 (3)
C60.045 (2)0.085 (3)0.092 (3)0.009 (2)0.005 (2)0.003 (3)
C70.044 (2)0.053 (2)0.064 (3)0.0067 (19)0.007 (2)0.015 (2)
C80.048 (2)0.074 (3)0.099 (4)0.001 (2)0.013 (2)0.015 (3)
C90.063 (3)0.079 (3)0.104 (4)0.001 (2)0.013 (3)0.012 (3)
N100.0448 (19)0.056 (2)0.070 (2)0.0002 (16)0.0057 (18)0.006 (2)
C110.063 (2)0.055 (2)0.073 (3)0.005 (2)0.000 (2)0.014 (2)
O120.0484 (15)0.091 (2)0.149 (3)0.0132 (15)0.0117 (18)0.006 (2)
C130.087 (3)0.061 (3)0.069 (3)0.018 (2)0.003 (2)0.009 (3)
O140.0895 (19)0.0603 (17)0.073 (2)0.0205 (14)0.0167 (16)0.0106 (17)
C150.054 (2)0.059 (3)0.066 (3)0.003 (2)0.005 (2)0.003 (3)
O160.0816 (19)0.088 (2)0.106 (3)0.0243 (16)0.0288 (19)0.0191 (19)
C170.060 (2)0.058 (2)0.071 (3)0.001 (2)0.003 (2)0.003 (2)
C180.059 (2)0.067 (3)0.070 (3)0.000 (2)0.003 (2)0.000 (3)
C190.064 (3)0.057 (3)0.064 (3)0.005 (2)0.000 (2)0.001 (2)
C200.079 (3)0.075 (3)0.071 (3)0.008 (2)0.003 (2)0.012 (3)
C210.090 (3)0.086 (3)0.093 (4)0.021 (3)0.002 (3)0.014 (3)
C220.106 (4)0.070 (3)0.096 (4)0.004 (3)0.012 (3)0.019 (3)
C230.097 (4)0.079 (3)0.100 (4)0.018 (3)0.008 (3)0.018 (3)
C240.080 (3)0.063 (3)0.093 (4)0.008 (3)0.009 (3)0.004 (3)
Geometric parameters (Å, º) top
O1—C21.221 (5)C13—O141.443 (4)
C2—C31.478 (6)C13—H13A0.9700
C2—C41.495 (7)C13—H13B0.9700
C3—C91.369 (5)O14—C151.319 (5)
C3—C51.380 (6)C15—O161.196 (4)
C4—H4A0.9600C15—C171.475 (5)
C4—H4B0.9600C17—C181.319 (5)
C4—H4C0.9600C17—H170.9300
C5—C61.361 (6)C18—C191.465 (5)
C5—H50.9300C18—H180.9300
C6—C71.385 (5)C19—C241.375 (5)
C6—H60.9300C19—C201.385 (5)
C7—C81.372 (5)C20—C211.390 (5)
C7—N101.406 (5)C20—H200.9300
C8—C91.369 (5)C21—C221.372 (6)
C8—H80.9300C21—H210.9300
C9—H90.9300C22—C231.361 (6)
N10—C111.350 (4)C22—H220.9300
N10—H100.89 (4)C23—C241.386 (6)
C11—O121.221 (4)C23—H230.9300
C11—C131.502 (6)C24—H240.9300
O1—C2—C3119.4 (6)O14—C13—H13A109.8
O1—C2—C4120.5 (5)C11—C13—H13A109.8
C3—C2—C4120.1 (5)O14—C13—H13B109.8
C9—C3—C5116.6 (4)C11—C13—H13B109.8
C9—C3—C2123.5 (5)H13A—C13—H13B108.3
C5—C3—C2119.9 (5)C15—O14—C13114.8 (3)
C2—C4—H4A109.5O16—C15—O14122.9 (4)
C2—C4—H4B109.5O16—C15—C17124.4 (4)
H4A—C4—H4B109.5O14—C15—C17112.6 (4)
C2—C4—H4C109.5C18—C17—C15120.4 (4)
H4A—C4—H4C109.5C18—C17—H17119.8
H4B—C4—H4C109.5C15—C17—H17119.8
C6—C5—C3123.0 (4)C17—C18—C19128.0 (4)
C6—C5—H5118.5C17—C18—H18116.0
C3—C5—H5118.5C19—C18—H18116.0
C5—C6—C7119.4 (4)C24—C19—C20118.7 (4)
C5—C6—H6120.3C24—C19—C18119.1 (4)
C7—C6—H6120.3C20—C19—C18122.2 (4)
C8—C7—C6118.4 (4)C19—C20—C21119.9 (4)
C8—C7—N10117.5 (3)C19—C20—H20120.1
C6—C7—N10124.2 (4)C21—C20—H20120.1
C9—C8—C7121.1 (4)C22—C21—C20120.4 (4)
C9—C8—H8119.5C22—C21—H21119.8
C7—C8—H8119.5C20—C21—H21119.8
C8—C9—C3121.6 (4)C23—C22—C21120.1 (4)
C8—C9—H9119.2C23—C22—H22119.9
C3—C9—H9119.2C21—C22—H22119.9
C11—N10—C7128.7 (3)C22—C23—C24119.8 (5)
C11—N10—H10111 (3)C22—C23—H23120.1
C7—N10—H10120 (3)C24—C23—H23120.1
O12—C11—N10123.1 (4)C19—C24—C23121.2 (4)
O12—C11—C13120.8 (4)C19—C24—H24119.4
N10—C11—C13116.1 (4)C23—C24—H24119.4
O14—C13—C11109.3 (3)
Hydrogen-bond geometry (Å, º) top
Cg2 is the centroid of the C19–C24 ring.
D—H···AD—HH···AD···AD—H···A
C6—H6···O120.932.272.860 (6)121
C6—H6···O16i0.932.463.203 (5)137
C8—H8···O12ii0.932.593.335 (5)138
N10—H10···O12ii0.89 (4)2.00 (4)2.862 (4)162 (4)
C4—H4C···Cg2ii0.963.013.948 (6)160
Symmetry codes: (i) x+1/2, y, z; (ii) x1/2, y, z.

Experimental details

(I)(II)
Crystal data
Chemical formulaC10H10ClNO2C19H17NO4
Mr211.64323.33
Crystal system, space groupOrthorhombic, P212121Orthorhombic, Pca21
Temperature (K)296296
a, b, c (Å)4.1713 (1), 14.7792 (4), 16.1755 (4)9.7969 (15), 17.594 (3), 9.6425 (15)
V3)997.19 (4)1662.1 (4)
Z44
Radiation typeMo KαMo Kα
µ (mm1)0.360.09
Crystal size (mm)0.29 × 0.27 × 0.250.20 × 0.18 × 0.10
Data collection
DiffractometerBruker SMART CCD area-detectorBruker SMART CCD area-detector
Absorption correctionMulti-scan
(SADABS; Bruker, 2012)
Multi-scan
(SADABS; Bruker, 2012)
Tmin, Tmax0.890, 0.9050.975, 0.995
No. of measured, independent and
observed [I > 2σ(I)] reflections
21908, 2489, 2189 13763, 3879, 1781
Rint0.0250.044
(sin θ/λ)max1)0.6680.667
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.038, 0.106, 1.05 0.057, 0.119, 0.99
No. of reflections24893879
No. of parameters132222
No. of restraints01
H-atom treatmentH atoms treated by a mixture of independent and constrained refinementH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.34, 0.210.11, 0.12
Absolute structureFlack x determined using 819 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons & Flack, 2004)?
Absolute structure parameter0.033 (14)?

Computer programs: SMART (Bruker, 2012), SAINT (Bruker, 2012), SHELXS97 (Sheldrick, 2008), SHELXL2013 (Sheldrick, 2015), ORTEP-3 for Windows (Farrugia, 2012), publCIF (Westrip, 2010).

Hydrogen-bond geometry (Å, º) for (I) top
Cg1 is the centroid of the C4–C9 ring.
D—H···AD—HH···AD···AD—H···A
C2—H2C···O12i0.962.433.353 (3)161
C8—H8···O120.932.292.877 (3)121
N10—H10···O1ii0.80 (3)2.11 (3)2.915 (3)176 (3)
C8—H8···Cg1iii0.933.6504.434 (3)144
Symmetry codes: (i) x+1/2, y+3/2, z+1; (ii) x+1, y1/2, z+3/2; (iii) x1/2, y+3/2, z+1.
Hydrogen-bond geometry (Å, º) for (II) top
Cg2 is the centroid of the C19–C24 ring.
D—H···AD—HH···AD···AD—H···A
C6—H6···O120.932.272.860 (6)121
C6—H6···O16i0.932.463.203 (5)137
C8—H8···O12ii0.932.593.335 (5)138
N10—H10···O12ii0.89 (4)2.00 (4)2.862 (4)162 (4)
C4—H4C···Cg2ii0.963.0103.948 (6)160
Symmetry codes: (i) x+1/2, y, z; (ii) x1/2, y, z.
 

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