Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S205322961502433X/cu3092sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S205322961502433X/cu3092Isup2.hkl | |
Structure factor file (CIF format) https://doi.org/10.1107/S205322961502433X/cu3092IIsup3.hkl |
CCDC references: 1443110; 1443109
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).
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 (C═O keto), 1631 (C═O amide),1600 (C═C 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 (C═O ester), 1728 (C═O keto), 1650 (C═O amide), 1593 (C═C 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).
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.
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—(C═O)—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 C═O 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).
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—(C═O)—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 C═O 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).
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 (C═O keto), 1631 (C═O amide),1600 (C═C 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 (C═O ester), 1728 (C═O keto), 1650 (C═O amide), 1593 (C═C 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).
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.
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).
C10H10ClNO2 | Dx = 1.410 Mg m−3 |
Mr = 211.64 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, P212121 | Cell parameters from 9297 reflections |
a = 4.1713 (1) Å | θ = 2.5–27.9° |
b = 14.7792 (4) Å | µ = 0.36 mm−1 |
c = 16.1755 (4) Å | T = 296 K |
V = 997.19 (4) Å3 | Block, colourless |
Z = 4 | 0.29 × 0.27 × 0.25 mm |
F(000) = 440 |
Bruker SMART CCD area-detector diffractometer | 2189 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.025 |
φ and ω scans | θmax = 28.4°, θmin = 1.9° |
Absorption correction: multi-scan (SADABS; Bruker, 2012) | h = −4→5 |
Tmin = 0.890, Tmax = 0.905 | k = −19→19 |
21908 measured reflections | l = −21→21 |
2489 independent reflections |
Refinement on F2 | Hydrogen site location: mixed |
Least-squares matrix: full | H 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 = 1.05 | Δρmax = 0.34 e Å−3 |
2489 reflections | Δρmin = −0.21 e Å−3 |
132 parameters | Absolute structure: Flack x determined using 819 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons & Flack, 2004) |
0 restraints | Absolute structure parameter: 0.033 (14) |
C10H10ClNO2 | V = 997.19 (4) Å3 |
Mr = 211.64 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 4.1713 (1) Å | µ = 0.36 mm−1 |
b = 14.7792 (4) Å | T = 296 K |
c = 16.1755 (4) Å | 0.29 × 0.27 × 0.25 mm |
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 = 0.905 | Rint = 0.025 |
21908 measured reflections |
R[F2 > 2σ(F2)] = 0.038 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.106 | Δρmax = 0.34 e Å−3 |
S = 1.05 | Δρmin = −0.21 e Å−3 |
2489 reflections | Absolute structure: Flack x determined using 819 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons & Flack, 2004) |
132 parameters | Absolute structure parameter: 0.033 (14) |
0 restraints |
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 | 0.3090 (7) | 0.91692 (14) | 0.79553 (12) | 0.0734 (7) | |
C2 | 0.0351 (7) | 0.97312 (17) | 0.67865 (17) | 0.0565 (6) | |
H2A | 0.0171 | 1.0268 | 0.7117 | 0.085* | |
H2B | −0.1749 | 0.9531 | 0.6626 | 0.085* | |
H2C | 0.1594 | 0.9860 | 0.6301 | 0.085* | |
C3 | 0.1961 (7) | 0.90065 (16) | 0.72759 (14) | 0.0485 (6) | |
C4 | 0.2230 (6) | 0.80791 (16) | 0.69210 (13) | 0.0430 (5) | |
C5 | 0.3856 (7) | 0.74153 (17) | 0.73672 (14) | 0.0513 (6) | |
H5 | 0.4769 | 0.7560 | 0.7875 | 0.062* | |
C6 | 0.4122 (7) | 0.65528 (16) | 0.70661 (14) | 0.0504 (6) | |
H6 | 0.5211 | 0.6118 | 0.7372 | 0.061* | |
C7 | 0.2774 (6) | 0.63189 (15) | 0.63035 (13) | 0.0424 (5) | |
C8 | 0.1178 (7) | 0.69802 (16) | 0.58504 (13) | 0.0478 (5) | |
H8 | 0.0278 | 0.6838 | 0.5341 | 0.057* | |
C9 | 0.0933 (7) | 0.78470 (17) | 0.61582 (13) | 0.0471 (5) | |
H9 | −0.0123 | 0.8286 | 0.5849 | 0.056* | |
N10 | 0.3136 (6) | 0.54170 (14) | 0.60441 (12) | 0.0480 (5) | |
H10 | 0.413 (8) | 0.509 (2) | 0.6343 (19) | 0.055 (8)* | |
C11 | 0.1741 (7) | 0.50007 (17) | 0.53897 (15) | 0.0492 (6) | |
O12 | −0.0027 (7) | 0.53651 (14) | 0.49073 (13) | 0.0762 (7) | |
C13 | 0.2641 (9) | 0.40081 (19) | 0.53398 (18) | 0.0658 (8) | |
H13A | 0.1811 | 0.3697 | 0.5823 | 0.079* | |
H13B | 0.4958 | 0.3953 | 0.5347 | 0.079* | |
Cl14 | 0.1160 (3) | 0.34854 (5) | 0.44531 (5) | 0.0852 (3) |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.1087 (19) | 0.0584 (11) | 0.0532 (10) | −0.0123 (12) | −0.0182 (12) | −0.0073 (8) |
C2 | 0.0608 (15) | 0.0526 (14) | 0.0562 (14) | 0.0048 (12) | 0.0062 (13) | −0.0048 (11) |
C3 | 0.0543 (15) | 0.0503 (13) | 0.0409 (11) | −0.0112 (11) | 0.0045 (11) | −0.0002 (9) |
C4 | 0.0462 (12) | 0.0465 (11) | 0.0363 (10) | −0.0088 (10) | 0.0019 (9) | 0.0030 (8) |
C5 | 0.0652 (16) | 0.0517 (12) | 0.0369 (10) | −0.0127 (13) | −0.0107 (11) | 0.0053 (9) |
C6 | 0.0617 (16) | 0.0470 (12) | 0.0427 (11) | −0.0057 (12) | −0.0137 (11) | 0.0106 (9) |
C7 | 0.0470 (12) | 0.0446 (11) | 0.0356 (10) | −0.0059 (10) | 0.0016 (9) | 0.0047 (8) |
C8 | 0.0556 (14) | 0.0543 (13) | 0.0335 (10) | 0.0006 (12) | −0.0064 (10) | 0.0010 (9) |
C9 | 0.0541 (14) | 0.0494 (12) | 0.0377 (10) | 0.0010 (11) | −0.0035 (10) | 0.0051 (9) |
N10 | 0.0590 (13) | 0.0461 (10) | 0.0389 (9) | 0.0017 (10) | −0.0075 (9) | 0.0031 (8) |
C11 | 0.0542 (15) | 0.0525 (12) | 0.0409 (11) | 0.0015 (11) | 0.0003 (11) | −0.0023 (9) |
O12 | 0.0970 (18) | 0.0670 (12) | 0.0647 (12) | 0.0196 (12) | −0.0374 (12) | −0.0151 (10) |
C13 | 0.080 (2) | 0.0589 (16) | 0.0586 (15) | 0.0105 (15) | −0.0172 (15) | −0.0145 (12) |
Cl14 | 0.1245 (8) | 0.0599 (4) | 0.0713 (5) | −0.0088 (5) | −0.0269 (5) | −0.0142 (3) |
O1—C3 | 1.219 (3) | C7—C8 | 1.391 (3) |
C2—C3 | 1.492 (4) | C7—N10 | 1.405 (3) |
C2—H2A | 0.9600 | C8—C9 | 1.378 (3) |
C2—H2B | 0.9600 | C8—H8 | 0.9300 |
C2—H2C | 0.9600 | C9—H9 | 0.9300 |
C3—C4 | 1.490 (3) | N10—C11 | 1.356 (3) |
C4—C9 | 1.390 (3) | N10—H10 | 0.80 (3) |
C4—C5 | 1.394 (3) | C11—O12 | 1.201 (3) |
C5—C6 | 1.369 (4) | C11—C13 | 1.516 (4) |
C5—H5 | 0.9300 | C13—Cl14 | 1.742 (3) |
C6—C7 | 1.399 (3) | C13—H13A | 0.9700 |
C6—H6 | 0.9300 | C13—H13B | 0.9700 |
C3—C2—H2A | 109.5 | C6—C7—N10 | 117.0 (2) |
C3—C2—H2B | 109.5 | C9—C8—C7 | 119.9 (2) |
H2A—C2—H2B | 109.5 | C9—C8—H8 | 120.1 |
C3—C2—H2C | 109.5 | C7—C8—H8 | 120.1 |
H2A—C2—H2C | 109.5 | C8—C9—C4 | 121.4 (2) |
H2B—C2—H2C | 109.5 | C8—C9—H9 | 119.3 |
O1—C3—C4 | 120.0 (2) | C4—C9—H9 | 119.3 |
O1—C3—C2 | 120.7 (2) | C11—N10—C7 | 128.1 (2) |
C4—C3—C2 | 119.3 (2) | C11—N10—H10 | 115 (2) |
C9—C4—C5 | 118.4 (2) | C7—N10—H10 | 117 (2) |
C9—C4—C3 | 122.6 (2) | O12—C11—N10 | 124.6 (2) |
C5—C4—C3 | 119.0 (2) | O12—C11—C13 | 123.4 (2) |
C6—C5—C4 | 120.7 (2) | N10—C11—C13 | 112.0 (2) |
C6—C5—H5 | 119.7 | C11—C13—Cl14 | 112.6 (2) |
C4—C5—H5 | 119.7 | C11—C13—H13A | 109.1 |
C5—C6—C7 | 120.7 (2) | Cl14—C13—H13A | 109.1 |
C5—C6—H6 | 119.6 | C11—C13—H13B | 109.1 |
C7—C6—H6 | 119.6 | Cl14—C13—H13B | 109.1 |
C8—C7—C6 | 118.9 (2) | H13A—C13—H13B | 107.8 |
C8—C7—N10 | 124.1 (2) |
Cg1 is the centroid of the C4–C9 ring. |
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2C···O12i | 0.96 | 2.43 | 3.353 (3) | 161 |
C8—H8···O12 | 0.93 | 2.29 | 2.877 (3) | 121 |
N10—H10···O1ii | 0.80 (3) | 2.11 (3) | 2.915 (3) | 176 (3) |
C8—H8···Cg1iii | 0.93 | 3.65 | 4.434 (3) | 144 |
Symmetry codes: (i) x+1/2, −y+3/2, −z+1; (ii) −x+1, y−1/2, −z+3/2; (iii) x−1/2, −y+3/2, −z+1. |
C19H17NO4 | Dx = 1.292 Mg m−3 |
Mr = 323.33 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, Pca21 | Cell parameters from 2290 reflections |
a = 9.7969 (15) Å | θ = 3.1–19.4° |
b = 17.594 (3) Å | µ = 0.09 mm−1 |
c = 9.6425 (15) Å | T = 296 K |
V = 1662.1 (4) Å3 | Plate, colourless |
Z = 4 | 0.20 × 0.18 × 0.10 mm |
F(000) = 680 |
Bruker SMART CCD area-detector diffractometer | 1781 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.044 |
φ and ω scans | θmax = 28.3°, θmin = 2.3° |
Absorption correction: multi-scan (SADABS; Bruker, 2012) | h = −13→12 |
Tmin = 0.975, Tmax = 0.995 | k = −23→22 |
13763 measured reflections | l = −12→12 |
3879 independent reflections |
Refinement on F2 | 1 restraint |
Least-squares matrix: full | Hydrogen site location: mixed |
R[F2 > 2σ(F2)] = 0.057 | H 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 reflections | Δρmax = 0.11 e Å−3 |
222 parameters | Δρmin = −0.12 e Å−3 |
C19H17NO4 | V = 1662.1 (4) Å3 |
Mr = 323.33 | Z = 4 |
Orthorhombic, Pca21 | Mo Kα radiation |
a = 9.7969 (15) Å | µ = 0.09 mm−1 |
b = 17.594 (3) Å | T = 296 K |
c = 9.6425 (15) Å | 0.20 × 0.18 × 0.10 mm |
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 = 0.995 | Rint = 0.044 |
13763 measured reflections |
R[F2 > 2σ(F2)] = 0.057 | 1 restraint |
wR(F2) = 0.119 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.99 | Δρmax = 0.11 e Å−3 |
3879 reflections | Δρmin = −0.12 e Å−3 |
222 parameters |
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 | 0.8574 (4) | 0.3135 (2) | 0.4874 (4) | 0.1302 (15) | |
C2 | 0.7449 (7) | 0.2863 (2) | 0.4653 (5) | 0.0888 (15) | |
C3 | 0.7323 (5) | 0.2206 (2) | 0.3704 (4) | 0.0643 (11) | |
C4 | 0.6205 (6) | 0.3195 (3) | 0.5314 (6) | 0.1145 (19) | |
H4A | 0.6472 | 0.3529 | 0.6052 | 0.172* | |
H4B | 0.5646 | 0.2794 | 0.5679 | 0.172* | |
H4C | 0.5697 | 0.3476 | 0.4634 | 0.172* | |
C5 | 0.8482 (4) | 0.1850 (3) | 0.3212 (6) | 0.0826 (14) | |
H5 | 0.9328 | 0.2024 | 0.3512 | 0.099* | |
C6 | 0.8442 (4) | 0.1257 (2) | 0.2308 (5) | 0.0741 (13) | |
H6 | 0.9247 | 0.1026 | 0.2015 | 0.089* | |
C7 | 0.7192 (3) | 0.0999 (2) | 0.1828 (4) | 0.0538 (10) | |
C8 | 0.6030 (4) | 0.1343 (2) | 0.2313 (5) | 0.0738 (13) | |
H8 | 0.5182 | 0.1172 | 0.2013 | 0.089* | |
C9 | 0.6099 (4) | 0.1936 (2) | 0.3230 (5) | 0.0820 (13) | |
H9 | 0.5295 | 0.2160 | 0.3538 | 0.098* | |
N10 | 0.7033 (3) | 0.04028 (18) | 0.0870 (3) | 0.0569 (9) | |
H10 | 0.620 (4) | 0.025 (2) | 0.062 (5) | 0.100 (17)* | |
C11 | 0.7993 (4) | −0.0064 (2) | 0.0340 (5) | 0.0635 (11) | |
O12 | 0.9198 (2) | −0.00278 (15) | 0.0659 (4) | 0.0964 (11) | |
C13 | 0.7502 (5) | −0.0647 (2) | −0.0685 (4) | 0.0723 (12) | |
H13A | 0.6513 | −0.0672 | −0.0666 | 0.087* | |
H13B | 0.7783 | −0.0504 | −0.1613 | 0.087* | |
O14 | 0.8069 (3) | −0.13785 (15) | −0.0332 (3) | 0.0743 (8) | |
C15 | 0.7484 (4) | −0.1718 (2) | 0.0733 (5) | 0.0594 (10) | |
O16 | 0.6561 (3) | −0.14411 (17) | 0.1369 (4) | 0.0918 (10) | |
C17 | 0.8134 (4) | −0.2450 (2) | 0.1080 (5) | 0.0630 (10) | |
H17 | 0.8902 | −0.2609 | 0.0592 | 0.076* | |
C18 | 0.7634 (4) | −0.2880 (2) | 0.2077 (4) | 0.0654 (11) | |
H18 | 0.6871 | −0.2690 | 0.2535 | 0.078* | |
C19 | 0.8132 (4) | −0.3621 (2) | 0.2553 (4) | 0.0614 (11) | |
C20 | 0.9287 (4) | −0.3959 (2) | 0.1999 (5) | 0.0751 (12) | |
H20 | 0.9788 | −0.3709 | 0.1318 | 0.090* | |
C21 | 0.9695 (5) | −0.4671 (3) | 0.2463 (6) | 0.0895 (14) | |
H21 | 1.0464 | −0.4901 | 0.2082 | 0.107* | |
C22 | 0.8971 (6) | −0.5038 (3) | 0.3482 (6) | 0.0905 (15) | |
H22 | 0.9246 | −0.5516 | 0.3783 | 0.109* | |
C23 | 0.7852 (5) | −0.4703 (3) | 0.4052 (5) | 0.0920 (16) | |
H23 | 0.7373 | −0.4946 | 0.4755 | 0.110* | |
C24 | 0.7430 (5) | −0.3997 (2) | 0.3580 (5) | 0.0786 (14) | |
H24 | 0.6658 | −0.3773 | 0.3965 | 0.094* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.140 (3) | 0.099 (2) | 0.152 (4) | −0.027 (2) | −0.063 (3) | −0.015 (3) |
C2 | 0.123 (4) | 0.061 (3) | 0.083 (3) | −0.013 (4) | −0.043 (4) | 0.014 (3) |
C3 | 0.074 (3) | 0.055 (2) | 0.063 (3) | −0.009 (2) | −0.019 (3) | 0.011 (2) |
C4 | 0.167 (5) | 0.078 (4) | 0.099 (4) | 0.016 (4) | −0.022 (4) | −0.010 (3) |
C5 | 0.065 (3) | 0.084 (3) | 0.099 (4) | −0.025 (3) | −0.019 (3) | 0.006 (3) |
C6 | 0.045 (2) | 0.085 (3) | 0.092 (3) | −0.009 (2) | −0.005 (2) | 0.003 (3) |
C7 | 0.044 (2) | 0.053 (2) | 0.064 (3) | −0.0067 (19) | −0.007 (2) | 0.015 (2) |
C8 | 0.048 (2) | 0.074 (3) | 0.099 (4) | 0.001 (2) | −0.013 (2) | −0.015 (3) |
C9 | 0.063 (3) | 0.079 (3) | 0.104 (4) | 0.001 (2) | −0.013 (3) | −0.012 (3) |
N10 | 0.0448 (19) | 0.056 (2) | 0.070 (2) | −0.0002 (16) | −0.0057 (18) | 0.006 (2) |
C11 | 0.063 (2) | 0.055 (2) | 0.073 (3) | 0.005 (2) | 0.000 (2) | 0.014 (2) |
O12 | 0.0484 (15) | 0.091 (2) | 0.149 (3) | 0.0132 (15) | −0.0117 (18) | −0.006 (2) |
C13 | 0.087 (3) | 0.061 (3) | 0.069 (3) | 0.018 (2) | 0.003 (2) | 0.009 (3) |
O14 | 0.0895 (19) | 0.0603 (17) | 0.073 (2) | 0.0205 (14) | 0.0167 (16) | 0.0106 (17) |
C15 | 0.054 (2) | 0.059 (3) | 0.066 (3) | 0.003 (2) | 0.005 (2) | −0.003 (3) |
O16 | 0.0816 (19) | 0.088 (2) | 0.106 (3) | 0.0243 (16) | 0.0288 (19) | 0.0191 (19) |
C17 | 0.060 (2) | 0.058 (2) | 0.071 (3) | 0.001 (2) | 0.003 (2) | 0.003 (2) |
C18 | 0.059 (2) | 0.067 (3) | 0.070 (3) | 0.000 (2) | −0.003 (2) | 0.000 (3) |
C19 | 0.064 (3) | 0.057 (3) | 0.064 (3) | −0.005 (2) | 0.000 (2) | −0.001 (2) |
C20 | 0.079 (3) | 0.075 (3) | 0.071 (3) | 0.008 (2) | 0.003 (2) | 0.012 (3) |
C21 | 0.090 (3) | 0.086 (3) | 0.093 (4) | 0.021 (3) | 0.002 (3) | 0.014 (3) |
C22 | 0.106 (4) | 0.070 (3) | 0.096 (4) | 0.004 (3) | −0.012 (3) | 0.019 (3) |
C23 | 0.097 (4) | 0.079 (3) | 0.100 (4) | −0.018 (3) | 0.008 (3) | 0.018 (3) |
C24 | 0.080 (3) | 0.063 (3) | 0.093 (4) | −0.008 (3) | 0.009 (3) | 0.004 (3) |
O1—C2 | 1.221 (5) | C13—O14 | 1.443 (4) |
C2—C3 | 1.478 (6) | C13—H13A | 0.9700 |
C2—C4 | 1.495 (7) | C13—H13B | 0.9700 |
C3—C9 | 1.369 (5) | O14—C15 | 1.319 (5) |
C3—C5 | 1.380 (6) | C15—O16 | 1.196 (4) |
C4—H4A | 0.9600 | C15—C17 | 1.475 (5) |
C4—H4B | 0.9600 | C17—C18 | 1.319 (5) |
C4—H4C | 0.9600 | C17—H17 | 0.9300 |
C5—C6 | 1.361 (6) | C18—C19 | 1.465 (5) |
C5—H5 | 0.9300 | C18—H18 | 0.9300 |
C6—C7 | 1.385 (5) | C19—C24 | 1.375 (5) |
C6—H6 | 0.9300 | C19—C20 | 1.385 (5) |
C7—C8 | 1.372 (5) | C20—C21 | 1.390 (5) |
C7—N10 | 1.406 (5) | C20—H20 | 0.9300 |
C8—C9 | 1.369 (5) | C21—C22 | 1.372 (6) |
C8—H8 | 0.9300 | C21—H21 | 0.9300 |
C9—H9 | 0.9300 | C22—C23 | 1.361 (6) |
N10—C11 | 1.350 (4) | C22—H22 | 0.9300 |
N10—H10 | 0.89 (4) | C23—C24 | 1.386 (6) |
C11—O12 | 1.221 (4) | C23—H23 | 0.9300 |
C11—C13 | 1.502 (6) | C24—H24 | 0.9300 |
O1—C2—C3 | 119.4 (6) | O14—C13—H13A | 109.8 |
O1—C2—C4 | 120.5 (5) | C11—C13—H13A | 109.8 |
C3—C2—C4 | 120.1 (5) | O14—C13—H13B | 109.8 |
C9—C3—C5 | 116.6 (4) | C11—C13—H13B | 109.8 |
C9—C3—C2 | 123.5 (5) | H13A—C13—H13B | 108.3 |
C5—C3—C2 | 119.9 (5) | C15—O14—C13 | 114.8 (3) |
C2—C4—H4A | 109.5 | O16—C15—O14 | 122.9 (4) |
C2—C4—H4B | 109.5 | O16—C15—C17 | 124.4 (4) |
H4A—C4—H4B | 109.5 | O14—C15—C17 | 112.6 (4) |
C2—C4—H4C | 109.5 | C18—C17—C15 | 120.4 (4) |
H4A—C4—H4C | 109.5 | C18—C17—H17 | 119.8 |
H4B—C4—H4C | 109.5 | C15—C17—H17 | 119.8 |
C6—C5—C3 | 123.0 (4) | C17—C18—C19 | 128.0 (4) |
C6—C5—H5 | 118.5 | C17—C18—H18 | 116.0 |
C3—C5—H5 | 118.5 | C19—C18—H18 | 116.0 |
C5—C6—C7 | 119.4 (4) | C24—C19—C20 | 118.7 (4) |
C5—C6—H6 | 120.3 | C24—C19—C18 | 119.1 (4) |
C7—C6—H6 | 120.3 | C20—C19—C18 | 122.2 (4) |
C8—C7—C6 | 118.4 (4) | C19—C20—C21 | 119.9 (4) |
C8—C7—N10 | 117.5 (3) | C19—C20—H20 | 120.1 |
C6—C7—N10 | 124.2 (4) | C21—C20—H20 | 120.1 |
C9—C8—C7 | 121.1 (4) | C22—C21—C20 | 120.4 (4) |
C9—C8—H8 | 119.5 | C22—C21—H21 | 119.8 |
C7—C8—H8 | 119.5 | C20—C21—H21 | 119.8 |
C8—C9—C3 | 121.6 (4) | C23—C22—C21 | 120.1 (4) |
C8—C9—H9 | 119.2 | C23—C22—H22 | 119.9 |
C3—C9—H9 | 119.2 | C21—C22—H22 | 119.9 |
C11—N10—C7 | 128.7 (3) | C22—C23—C24 | 119.8 (5) |
C11—N10—H10 | 111 (3) | C22—C23—H23 | 120.1 |
C7—N10—H10 | 120 (3) | C24—C23—H23 | 120.1 |
O12—C11—N10 | 123.1 (4) | C19—C24—C23 | 121.2 (4) |
O12—C11—C13 | 120.8 (4) | C19—C24—H24 | 119.4 |
N10—C11—C13 | 116.1 (4) | C23—C24—H24 | 119.4 |
O14—C13—C11 | 109.3 (3) |
Cg2 is the centroid of the C19–C24 ring. |
D—H···A | D—H | H···A | D···A | D—H···A |
C6—H6···O12 | 0.93 | 2.27 | 2.860 (6) | 121 |
C6—H6···O16i | 0.93 | 2.46 | 3.203 (5) | 137 |
C8—H8···O12ii | 0.93 | 2.59 | 3.335 (5) | 138 |
N10—H10···O12ii | 0.89 (4) | 2.00 (4) | 2.862 (4) | 162 (4) |
C4—H4C···Cg2ii | 0.96 | 3.01 | 3.948 (6) | 160 |
Symmetry codes: (i) x+1/2, −y, z; (ii) x−1/2, −y, z. |
Experimental details
(I) | (II) | |
Crystal data | ||
Chemical formula | C10H10ClNO2 | C19H17NO4 |
Mr | 211.64 | 323.33 |
Crystal system, space group | Orthorhombic, P212121 | Orthorhombic, Pca21 |
Temperature (K) | 296 | 296 |
a, b, c (Å) | 4.1713 (1), 14.7792 (4), 16.1755 (4) | 9.7969 (15), 17.594 (3), 9.6425 (15) |
V (Å3) | 997.19 (4) | 1662.1 (4) |
Z | 4 | 4 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.36 | 0.09 |
Crystal size (mm) | 0.29 × 0.27 × 0.25 | 0.20 × 0.18 × 0.10 |
Data collection | ||
Diffractometer | Bruker SMART CCD area-detector | Bruker SMART CCD area-detector |
Absorption correction | Multi-scan (SADABS; Bruker, 2012) | Multi-scan (SADABS; Bruker, 2012) |
Tmin, Tmax | 0.890, 0.905 | 0.975, 0.995 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 21908, 2489, 2189 | 13763, 3879, 1781 |
Rint | 0.025 | 0.044 |
(sin θ/λ)max (Å−1) | 0.668 | 0.667 |
Refinement | ||
R[F2 > 2σ(F2)], wR(F2), S | 0.038, 0.106, 1.05 | 0.057, 0.119, 0.99 |
No. of reflections | 2489 | 3879 |
No. of parameters | 132 | 222 |
No. of restraints | 0 | 1 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.34, −0.21 | 0.11, −0.12 |
Absolute structure | Flack x determined using 819 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons & Flack, 2004) | ? |
Absolute structure parameter | 0.033 (14) | ? |
Computer programs: SMART (Bruker, 2012), SAINT (Bruker, 2012), SHELXS97 (Sheldrick, 2008), SHELXL2013 (Sheldrick, 2015), ORTEP-3 for Windows (Farrugia, 2012), publCIF (Westrip, 2010).
Cg1 is the centroid of the C4–C9 ring. |
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2C···O12i | 0.96 | 2.43 | 3.353 (3) | 161 |
C8—H8···O12 | 0.93 | 2.29 | 2.877 (3) | 121 |
N10—H10···O1ii | 0.80 (3) | 2.11 (3) | 2.915 (3) | 176 (3) |
C8—H8···Cg1iii | 0.93 | 3.650 | 4.434 (3) | 144 |
Symmetry codes: (i) x+1/2, −y+3/2, −z+1; (ii) −x+1, y−1/2, −z+3/2; (iii) x−1/2, −y+3/2, −z+1. |
Cg2 is the centroid of the C19–C24 ring. |
D—H···A | D—H | H···A | D···A | D—H···A |
C6—H6···O12 | 0.93 | 2.27 | 2.860 (6) | 121 |
C6—H6···O16i | 0.93 | 2.46 | 3.203 (5) | 137 |
C8—H8···O12ii | 0.93 | 2.59 | 3.335 (5) | 138 |
N10—H10···O12ii | 0.89 (4) | 2.00 (4) | 2.862 (4) | 162 (4) |
C4—H4C···Cg2ii | 0.96 | 3.010 | 3.948 (6) | 160 |
Symmetry codes: (i) x+1/2, −y, z; (ii) x−1/2, −y, z. |