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Acta Crystallographica Section E: Structure Reports Online logoLink to Acta Crystallographica Section E: Structure Reports Online
. 2007 Dec 21;64(Pt 1):o334. doi: 10.1107/S1600536807065154

Isopropyl 2-[2-(2,6-dichloro­anilino)phen­yl]acetate

Hamid Nawaz a, M Khawar Rauf b, Masahiro Ebihara b, Amin Badshah a,*
PMCID: PMC2915375  PMID: 21200895

Abstract

In the title compound, C17H17Cl2NO2, the NH group exhibits an intra­molecular hydrogen bond to the carbonyl O atom and no inter­molecular hydrogen bonding, in contrast with previous studies. The dihedral angle between the two benzene rings is 58.57 (5)°. The ester group is planar, the greatest deviation from planarity being 0.0135 (11) Å for the ether O atom.

Related literature

For related literature, see: Abo-Ghalia et al. (1999 ▶); Alvarez-Larena et al. (1992 ▶); Corell et al. (1979 ▶); Evens (1979 ▶); Kass (1982 ▶); Lipka (1978 ▶, 1980 ▶); Moser et al. (1990 ▶); Robinson (1977 ▶); Scherrer & Whitehouse (1974 ▶).graphic file with name e-64-0o334-scheme1.jpg

Experimental

Crystal data

  • C17H17Cl2NO2

  • M r = 338.22

  • Monoclinic, Inline graphic

  • a = 17.548 (6) Å

  • b = 9.443 (3) Å

  • c = 9.719 (3) Å

  • β = 93.959 (4)°

  • V = 1606.7 (9) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.41 mm−1

  • T = 123 (2) K

  • 0.45 × 0.25 × 0.15 mm

Data collection

  • Rigaku/MSC Mercury CCD diffractometer

  • Absorption correction: none

  • 12744 measured reflections

  • 3670 independent reflections

  • 3428 reflections with I > 2σ(I)

  • R int = 0.061

Refinement

  • R[F 2 > 2σ(F 2)] = 0.038

  • wR(F 2) = 0.093

  • S = 1.10

  • 3670 reflections

  • 205 parameters

  • H atoms treated by a mixture of independent and constrained refinement

  • Δρmax = 0.31 e Å−3

  • Δρmin = −0.32 e Å−3

Data collection: CrystalClear (Molecular Structure Corporation & Rigaku, 2001 ▶); cell refinement: CrystalClear; data reduction: TEXSAN (Molecular Structure Corporation & Rigaku, 2004 ▶); program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997 ▶); molecular graphics: ORTEPII (Johnson, 1976 ▶); software used to prepare material for publication: SHELXL97 and TEXSAN.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536807065154/ez2110sup1.cif

e-64-0o334-sup1.cif (18KB, cif)

Structure factors: contains datablocks I. DOI: 10.1107/S1600536807065154/ez2110Isup2.hkl

e-64-0o334-Isup2.hkl (180KB, hkl)

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A D—H H⋯A D⋯A D—H⋯A
N1—H1⋯O1 0.90 (2) 2.05 (2) 2.859 (2) 149 (2)
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Acknowledgments

MKR is grateful to the Higher Education Commission of Pakistan for financial support under the International Support Initiative Program for Pre-doctoral Fellowships at Gifu University, Japan.

supplementary crystallographic information

Comment

The anti-phlogistic nonsteroidal anti-inflammatory drug (NSAID) (2-[(2,6-Dichlorophenyl)amino]-phenylacetic acid, common name diclofenac, is a potent cyclo-oxygenase inhibitor. It therapeutically interferes with the arachidonic acid cascade prior to the biosynthesis of the inflammatory prostaglandins. Consequently, the drug has a universal anti-phlogistic potency represented by generalized anti-inflammatory, anti-pyretic, anti-rheumatic and analgesic characteristics (Robinson, 1977; Kass, 1982; Evens, 1979; Scherrer & Whitehouse, 1974). However, several undesired side effects of the drug, particularly its ulcerogenicity, frequently restrict its remedial recommendation and it is contra-indicated for patients with a high risk of gastro-intestinal ulcers (Corell et al., 1979). New non-proteinogenic amino acid conjugates of diclofenac have been synthesized and biologically screened for their anti-inflammatory, analgesic and ulcerogenic activity in rats (Abo-Ghalia et al., 1999). We are interested in the synthesis of more potent, less ulcerogenic drugs that hopefully replace diclofenac, and present here the crystal structure of the title compound (I).

The bond lengths and angles in (I) are normal for this kind of molecule (Lipka, 1978, 1980; Moser et al.; 1990). The bond angles C(6)—N(1)—H(1) and C(7)—N(1)—H(1) are both 113.0 (1)°. The bond length N(1)—C(7) [1.418 (2) Å] is larger than N(1)—C(6) [1.393 (2) Å] suggesting a greater delocalization of the N lone pair toward the chlorinated ring. The bond lengths C(14)—O(1) [1.209 (2) Å] and C(14)—O(2) [1.333 (2) Å] indicate double and partial double bond character, respectively. The dihedral angle between the two benzene rings is 58.57 (5)°. The N(1)—H(1) is involved in intramolecular H-bonding to the carbonylic O(1) (Alvarez-Larena et al.; 1992).

Experimental

Diclofenac sodium (1.0 g, 3.1 mmol) and anhydrous potassium carbonate (1.0 g, 7.2 mmol) were added to dry acetone (30 ml) and the mixture was stirred for 20 min. Neat isopropyl iodide (0.785 ml, 7.83 mmol) in excess was then added and the resulting mixture was heated under reflux for 6 h. The reaction mixture was filtered when hot. The resultant cakes were washed with dry acetone 5 × 2 ml. The combined filtrate and washings were evaporated under reduced pressure to afford compound (I) as an oily material which solidified after 5 d at room temperature (70% yield). Melting point 363–366 K. Block-shaped single crystals were obtained by recrystallization from acetone.

Refinement

The H atom on the N atom was refined isotropically. Other H atoms were placed in idealized positions and treated as riding atoms with the C—H distance in the range 0.95–0.99 Å and Uiso(H) = 1.2Ueq(C) or 1.5Ueq(Cmethyl).

Figures

Fig. 1.

Fig. 1.

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Molecular structure of (I) showing atom-labelling scheme and displacement ellipsoids at the 30% probability level. The intramolecular hydrogen bond is shown by a dashed line.

Crystal data

C17H17Cl2NO2 F000 = 704
Mr = 338.22 Dx = 1.398 Mg m−3
Monoclinic, P21/c Melting point: 363 K
Hall symbol: -P 2ybc Mo Kα radiation λ = 0.71070 Å
a = 17.548 (6) Å Cell parameters from 4977 reflections
b = 9.443 (3) Å θ = 3.0–27.5º
c = 9.719 (3) Å µ = 0.41 mm−1
β = 93.959 (4)º T = 123 (2) K
V = 1606.7 (9) Å3 Block, colorless
Z = 4 0.45 × 0.25 × 0.15 mm
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Data collection

Rigaku/MSC Mercury CCD diffractometer 3670 independent reflections
Radiation source: fine-focus sealed tube 3428 reflections with I > 2σ(I)
Monochromator: graphite Rint = 0.061
Detector resolution: 14.62 pixels mm-1 θmax = 27.5º
T = 123(2) K θmin = 3.0º
ω scans h = −16→22
Absorption correction: none k = −12→12
12744 measured reflections l = −11→12
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Refinement

Refinement on F2 Secondary atom site location: difference Fourier map
Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.038 H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.093   w = 1/[σ2(Fo2) + (0.0391P)2 + 0.7365P] where P = (Fo2 + 2Fc2)/3
S = 1.10 (Δ/σ)max = 0.002
3670 reflections Δρmax = 0.31 e Å−3
205 parameters Δρmin = −0.32 e Å−3
Primary atom site location: structure-invariant direct methods Extinction correction: none
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Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.
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Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

x y z Uiso*/Ueq
N1 0.20829 (8) 0.00238 (14) 0.81278 (14) 0.0176 (3)
H1 0.2551 (14) −0.036 (2) 0.822 (2) 0.041 (6)*
C1 0.15347 (8) −0.07425 (15) 0.87884 (15) 0.0150 (3)
C2 0.07450 (9) −0.06102 (15) 0.84548 (15) 0.0152 (3)
C3 0.02096 (9) −0.13894 (16) 0.91175 (16) 0.0178 (3)
H3 −0.0320 −0.1244 0.8893 0.021*
C4 0.04477 (9) −0.23810 (16) 1.01071 (16) 0.0192 (3)
H4 0.0083 −0.2903 1.0577 0.023*
C5 0.12211 (9) −0.26066 (17) 1.04063 (16) 0.0188 (3)
H5 0.1390 −0.3313 1.1053 0.023*
C6 0.17464 (8) −0.17985 (16) 0.97592 (15) 0.0158 (3)
Cl1 0.04071 (2) 0.05250 (4) 0.71474 (4) 0.01864 (11)
Cl2 0.27143 (2) −0.21169 (4) 1.01691 (4) 0.02223 (11)
C7 0.20896 (8) 0.15202 (16) 0.80276 (15) 0.0163 (3)
C8 0.16317 (9) 0.23666 (17) 0.88131 (16) 0.0185 (3)
H8 0.1321 0.1938 0.9459 0.022*
C9 0.16256 (9) 0.38265 (17) 0.86589 (17) 0.0214 (3)
H9 0.1306 0.4390 0.9189 0.026*
C10 0.20854 (10) 0.44656 (17) 0.77316 (17) 0.0233 (3)
H10 0.2079 0.5465 0.7616 0.028*
C11 0.25537 (9) 0.36304 (17) 0.69773 (16) 0.0214 (3)
H11 0.2874 0.4071 0.6355 0.026*
C12 0.25671 (9) 0.21573 (16) 0.71063 (15) 0.0172 (3)
C13 0.30776 (9) 0.12827 (18) 0.62396 (16) 0.0201 (3)
H13A 0.2779 0.0492 0.5806 0.024*
H13B 0.3262 0.1880 0.5494 0.024*
C14 0.37563 (9) 0.06929 (17) 0.71054 (17) 0.0211 (3)
O1 0.37023 (7) −0.01740 (15) 0.80056 (15) 0.0362 (3)
O2 0.44207 (6) 0.12335 (12) 0.67675 (11) 0.0209 (2)
C15 0.51089 (9) 0.07400 (18) 0.75893 (17) 0.0225 (3)
H15 0.5055 −0.0287 0.7814 0.027*
C16 0.52004 (11) 0.1592 (2) 0.89044 (19) 0.0337 (4)
H16A 0.5287 0.2588 0.8681 0.051*
H16B 0.5638 0.1231 0.9482 0.051*
H16C 0.4736 0.1509 0.9404 0.051*
C17 0.57594 (10) 0.0941 (3) 0.6674 (2) 0.0390 (5)
H17A 0.5659 0.0396 0.5822 0.059*
H17B 0.6236 0.0611 0.7155 0.059*
H17C 0.5806 0.1948 0.6448 0.059*
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Atomic displacement parameters (Å2)

U11 U22 U33 U12 U13 U23
N1 0.0136 (6) 0.0152 (6) 0.0242 (7) 0.0011 (5) 0.0032 (5) 0.0029 (5)
C1 0.0168 (7) 0.0137 (7) 0.0148 (7) −0.0001 (5) 0.0019 (5) −0.0018 (5)
C2 0.0168 (7) 0.0130 (7) 0.0156 (7) 0.0017 (5) −0.0004 (5) −0.0017 (5)
C3 0.0141 (7) 0.0179 (7) 0.0213 (7) −0.0011 (6) 0.0013 (6) −0.0042 (6)
C4 0.0203 (8) 0.0180 (7) 0.0195 (7) −0.0039 (6) 0.0039 (6) −0.0009 (6)
C5 0.0234 (8) 0.0165 (7) 0.0163 (7) 0.0000 (6) 0.0005 (6) 0.0007 (6)
C6 0.0134 (7) 0.0171 (7) 0.0165 (7) 0.0015 (6) −0.0016 (5) −0.0023 (6)
Cl1 0.01741 (19) 0.01788 (18) 0.02003 (19) 0.00138 (13) −0.00299 (13) 0.00181 (13)
Cl2 0.01558 (19) 0.0220 (2) 0.0285 (2) 0.00267 (14) −0.00263 (14) 0.00416 (15)
C7 0.0132 (7) 0.0175 (7) 0.0174 (7) −0.0012 (6) −0.0041 (5) 0.0022 (6)
C8 0.0158 (7) 0.0205 (7) 0.0189 (7) −0.0024 (6) −0.0016 (6) −0.0004 (6)
C9 0.0195 (8) 0.0204 (7) 0.0235 (8) 0.0015 (6) −0.0052 (6) −0.0043 (6)
C10 0.0270 (9) 0.0158 (7) 0.0258 (8) −0.0025 (6) −0.0069 (7) 0.0021 (6)
C11 0.0211 (8) 0.0218 (8) 0.0207 (8) −0.0054 (6) −0.0043 (6) 0.0053 (6)
C12 0.0135 (7) 0.0219 (8) 0.0157 (7) −0.0011 (6) −0.0034 (5) 0.0022 (6)
C13 0.0151 (7) 0.0260 (8) 0.0191 (7) −0.0005 (6) 0.0013 (6) 0.0042 (6)
C14 0.0158 (7) 0.0252 (8) 0.0224 (8) −0.0001 (6) 0.0022 (6) 0.0021 (6)
O1 0.0168 (6) 0.0452 (8) 0.0467 (8) 0.0018 (6) 0.0022 (5) 0.0264 (7)
O2 0.0131 (5) 0.0285 (6) 0.0207 (6) −0.0007 (4) −0.0005 (4) 0.0053 (5)
C15 0.0133 (8) 0.0284 (8) 0.0252 (8) 0.0000 (6) −0.0037 (6) 0.0064 (7)
C16 0.0332 (10) 0.0355 (10) 0.0307 (10) −0.0012 (8) −0.0100 (8) 0.0013 (8)
C17 0.0145 (8) 0.0663 (14) 0.0363 (10) 0.0045 (9) 0.0022 (7) 0.0140 (10)
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Geometric parameters (Å, °)

N1—C1 1.3952 (19) C10—C11 1.385 (2)
N1—C7 1.416 (2) C10—H10 0.9500
N1—H1 0.90 (2) C11—C12 1.397 (2)
C1—C6 1.405 (2) C11—H11 0.9500
C1—C2 1.407 (2) C12—C13 1.516 (2)
C2—C3 1.387 (2) C13—C14 1.516 (2)
C2—Cl1 1.7354 (15) C13—H13A 0.9900
C3—C4 1.386 (2) C13—H13B 0.9900
C3—H3 0.9500 C14—O1 1.207 (2)
C4—C5 1.385 (2) C14—O2 1.3344 (19)
C4—H4 0.9500 O2—C15 1.4766 (19)
C5—C6 1.381 (2) C15—C17 1.507 (2)
C5—H5 0.9500 C15—C16 1.509 (3)
C6—Cl2 1.7438 (16) C15—H15 1.0000
C7—C8 1.397 (2) C16—H16A 0.9800
C7—C12 1.403 (2) C16—H16B 0.9800
C8—C9 1.387 (2) C16—H16C 0.9800
C8—H8 0.9500 C17—H17A 0.9800
C9—C10 1.388 (2) C17—H17B 0.9800
C9—H9 0.9500 C17—H17C 0.9800
C1—N1—C7 123.94 (13) C10—C11—H11 119.1
C1—N1—H1 113.5 (15) C12—C11—H11 119.1
C7—N1—H1 113.6 (15) C11—C12—C7 118.50 (14)
N1—C1—C6 121.23 (14) C11—C12—C13 119.98 (14)
N1—C1—C2 123.19 (14) C7—C12—C13 121.51 (14)
C6—C1—C2 115.36 (13) C14—C13—C12 111.31 (13)
C3—C2—C1 122.29 (14) C14—C13—H13A 109.4
C3—C2—Cl1 117.36 (12) C12—C13—H13A 109.4
C1—C2—Cl1 120.33 (11) C14—C13—H13B 109.4
C4—C3—C2 119.96 (14) C12—C13—H13B 109.4
C4—C3—H3 120.0 H13A—C13—H13B 108.0
C2—C3—H3 120.0 O1—C14—O2 123.47 (15)
C5—C4—C3 119.59 (14) O1—C14—C13 123.62 (15)
C5—C4—H4 120.2 O2—C14—C13 112.90 (13)
C3—C4—H4 120.2 C14—O2—C15 116.23 (12)
C6—C5—C4 119.65 (14) O2—C15—C17 105.38 (14)
C6—C5—H5 120.2 O2—C15—C16 108.97 (14)
C4—C5—H5 120.2 C17—C15—C16 113.10 (16)
C5—C6—C1 122.97 (14) O2—C15—H15 109.8
C5—C6—Cl2 118.09 (12) C17—C15—H15 109.8
C1—C6—Cl2 118.94 (12) C16—C15—H15 109.8
C8—C7—C12 119.65 (14) C15—C16—H16A 109.5
C8—C7—N1 121.69 (14) C15—C16—H16B 109.5
C12—C7—N1 118.66 (14) H16A—C16—H16B 109.5
C9—C8—C7 120.67 (15) C15—C16—H16C 109.5
C9—C8—H8 119.7 H16A—C16—H16C 109.5
C7—C8—H8 119.7 H16B—C16—H16C 109.5
C8—C9—C10 120.12 (15) C15—C17—H17A 109.5
C8—C9—H9 119.9 C15—C17—H17B 109.5
C10—C9—H9 119.9 H17A—C17—H17B 109.5
C11—C10—C9 119.25 (15) C15—C17—H17C 109.5
C11—C10—H10 120.4 H17A—C17—H17C 109.5
C9—C10—H10 120.4 H17B—C17—H17C 109.5
C10—C11—C12 121.78 (15)
C7—N1—C1—C6 −130.59 (16) N1—C7—C8—C9 −177.48 (14)
C7—N1—C1—C2 55.1 (2) C7—C8—C9—C10 −0.9 (2)
N1—C1—C2—C3 179.53 (14) C8—C9—C10—C11 −0.7 (2)
C6—C1—C2—C3 4.9 (2) C9—C10—C11—C12 1.1 (2)
N1—C1—C2—Cl1 1.1 (2) C10—C11—C12—C7 0.1 (2)
C6—C1—C2—Cl1 −173.52 (11) C10—C11—C12—C13 178.82 (14)
C1—C2—C3—C4 −2.7 (2) C8—C7—C12—C11 −1.7 (2)
Cl1—C2—C3—C4 175.78 (12) N1—C7—C12—C11 177.93 (13)
C2—C3—C4—C5 −1.3 (2) C8—C7—C12—C13 179.61 (13)
C3—C4—C5—C6 2.8 (2) N1—C7—C12—C13 −0.8 (2)
C4—C5—C6—C1 −0.3 (2) C11—C12—C13—C14 107.44 (16)
C4—C5—C6—Cl2 179.91 (12) C7—C12—C13—C14 −73.86 (18)
N1—C1—C6—C5 −178.14 (14) C12—C13—C14—O1 66.2 (2)
C2—C1—C6—C5 −3.4 (2) C12—C13—C14—O2 −113.82 (15)
N1—C1—C6—Cl2 1.62 (19) O1—C14—O2—C15 −1.5 (2)
C2—C1—C6—Cl2 176.35 (11) C13—C14—O2—C15 178.45 (13)
C1—N1—C7—C8 12.6 (2) C14—O2—C15—C17 155.43 (15)
C1—N1—C7—C12 −166.97 (14) C14—O2—C15—C16 −82.92 (17)
C12—C7—C8—C9 2.1 (2)
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Hydrogen-bond geometry (Å, °)

D—H···A D—H H···A D···A D—H···A
N1—H1···O1 0.90 (2) 2.05 (2) 2.859 (2) 149 (2)
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Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: EZ2110).

References

  1. Abo-Ghalia, M. H., Shalaby, A. M., El-Eraqi, W. I. & Awad, H. M. (1999). Amino Acids, 16, 425–440. [DOI] [PubMed]
  2. Altomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J. Appl. Cryst.32, 115–119.
  3. Alvarez-Larena, A., Piniella, J. F., Carrasco, E., Ginebreda, A., Julia, S. & Germain, G. (1992). J. Crystallogr. Spectrosc. Res.22, 323–328.
  4. Corell, T., Jensen, K. M. & Splawinski, J. (1979). Acta Pharmacol. Toxicol. (Copenh.), 45, 232–239. [DOI] [PubMed]
  5. Evens, R. P. (1979). Am. J. Hosp. Pharm.36, 622–633. [PubMed]
  6. Johnson, C. K. (1976). ORTEPII Report ORNL-5138. Oak Ridge National Laboratory, Tennessee, USA.
  7. Kass, E. (1982). Voltaren: New Findings pp. 14–30. Bern: Hans-Huber Verlag.
  8. Lipka, A. (1978). Z. Anorg. Allg. Chem.440, 224–230.
  9. Lipka, A. (1980). Z. Anorg. Allg. Chem.466, 195–202.
  10. Molecular Structure Corporation & Rigaku (2001). CrystalClear MSC, The Woodlands, Texas, USA, and Rigaku Corporation, Tokyo, Japan.
  11. Molecular Structure Corporation & Rigaku (2004). TEXSAN MSC, The Woodlands, Texas, USA, and Rigaku Corporation, Tokyo, Japan.
  12. Moser, P., Sallmann, A. & Wiesenberg, I. (1990). J. Med. Chem.33, 2358–2368. [DOI] [PubMed]
  13. Robinson, R. (1977). Clinical Experience with the New Geigy Antirheumatic ‘Voltaren’. Proceedings of 3rd Congress of the South-East Asia and Pacific Area League Against Rheumatism, Singapore, 1976. Bern: Hans-Huber Verlag.
  14. Scherrer, R. A. & Whitehouse, M. (1974). Anti-inflammatory Agents, Vol. 2. New York: Academic Press.
  15. Sheldrick, G. M. (1997). SHELXL97 University of Göttingen, Germany.

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536807065154/ez2110sup1.cif

e-64-0o334-sup1.cif (18KB, cif)

Structure factors: contains datablocks I. DOI: 10.1107/S1600536807065154/ez2110Isup2.hkl

e-64-0o334-Isup2.hkl (180KB, hkl)

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography

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