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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 67| Part 1| January 2011| Page o224
https://doi.org/10.1107/S1600536810051743

tert-Butyl 4-(4-chloro­anilino)-6-methyl-2-oxo­cyclo­hex-3-ene­carboxyl­ate

Mariano S. Alexander,a Henry North,a Kenneth R. Scotta and Ray J. Butcherb*

aDepartment of Pharmaceutical Sciences, Howard University, 2300 4th Street NW, Washington, DC 20059, USA, and bDepartment of Chemistry, Howard University, 525 College Street NW, Washington, DC 20059, USA
*Correspondence e-mail: rbutcher99@yahoo.com

(Received 10 November 2010; accepted 9 December 2010; online 24 December 2010)

In the title compound, C18H22ClNO3, the dihedral angle between the benzene ring and the conjugated part of the enaminone ring is 55.19 (9)°. The ester substituent makes a dihedral angle of 81.0 (2)° with this latter moiety. The crystal structure features N—H⋯O and weak C—H⋯O inter­molecular inter­actions.

Related literature

Our research on enamino­nes has led to several compounds possessing anti­convulsant properties, see: Edafiogho et al. (1992[Edafiogho, I. O., Hinko, C. N., Chang, H., Moore, J. A., Mulzac, D., Nicholson, J. M. & Scott, K. R. (1992). J. Med. Chem. 35, 2798-2805.]); Eddington et al. (2003[Eddington, N. D., Cox, D. S., Khurana, M., Salama, N. N., Stables, J. P., Harrison, S. J., Negussie, A., Taylor, R. S., Tran, U. Q., Moore, J. A., Barrow, J. C. & Scott, K. R. (2003). Eur. J. Med. Chem. 38, 49-64.]); Scott et al. (1993[Scott, K. R., Edafiogho, I. O., Richardson, E. R., Farrar, V. A., Moore, J. A., Tietz, E., Hinko, C. N., Chang, H., El-Assadi, A. & Nicholson, J. M. (1993). J. Med. Chem. 36, 1947-1955.], 1995[Scott, K. R., Rankin, G. O., Stables, J. P., Alexander, M. S., Edafiogho, I. O., Farrar, V. A., Kolen, K. R., Moore, J. A., Sims, L. D. & Tonnu, A. D. (1995). J. Med. Chem. 38, 4033-4043.]).

[Scheme 1]

Experimental

Crystal data

  • C18H22ClNO3

  • Mr = 335.82

  • Orthorhombic, P b c a

  • a = 11.0801 (3) Å

  • b = 10.9095 (3) Å

  • c = 29.2474 (7) Å

  • V = 3535.39 (16) Å3

  • Z = 8

  • Mo Kα radiation

  • μ = 0.23 mm−1

  • T = 295 K

  • 0.45 × 0.38 × 0.08 mm
Data collection

  • Oxford Diffraction Xcalibur Ruby Gemini diffractometer

  • Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2007[Oxford Diffraction (2007). CrysAlis PRO and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, England.]) Tmin = 0.93, Tmax = 0.98

  • 9798 measured reflections

  • 3708 independent reflections

  • 2925 reflections with I > 2σ(I)

  • Rint = 0.030
Refinement

  • R[F2 > 2σ(F2)] = 0.055

  • wR(F2) = 0.172

  • S = 1.09

  • 3708 reflections

  • 212 parameters

  • H-atom parameters constrained

  • Δρmax = 0.39 e Å−3

  • Δρmin = −0.25 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
N1—H1⋯O1i 0.86 2.24 2.909 (2) 135
C6—H6⋯O1i 0.93 2.63 3.363 (2) 137
C10—H10⋯O2ii 0.98 2.36 3.255 (2) 152
Symmetry codes: (i) [x-{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+1]; (ii) [-x+{\script{3\over 2}}, y+{\script{1\over 2}}, z].

Data collection: CrysAlis PRO (Oxford Diffraction, 2007[Oxford Diffraction (2007). CrysAlis PRO and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, England.]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536810051743/om2378sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810051743/om2378Isup2.hkl

checkCIF report


Comment top

Our research on enaminones has led to several compounds possessing anticonvulsant properties (Edafiogho et al., 1992; Eddington et al., 2003; Scott et al., 1993, 1995). The present work is part of a structural study of enaminones. Our group has extensively studied the effects of modification of the enaminone with substitutions at the methyl ester, ethyl ester, and without the ester group. We synthesized a series of carbo-tert-butoxy esters to evaluate the effect of added bulk and lipophilicity to the ester functionality. These compounds showed significant anticonvulsant activity. The title compound, tert-butyl- 4-(4-chlorophenlyamino)-6-methyl-2-oxocyclohex-3-enecarboxylate is highly active, with activity at <100 mg kg-1. The compound was active in maximal electroshock seizure evaluation (MES) in mice, indicative of protection against tonic-clonic convulsions in humans (1/4 rats protected at 1 h, 2 h and 4 h post dose at 50 mg kg dose). Toxicity tests showed no toxicity in rats (oral) up to 4 h at 50 mg/kg per dose. The MES study in mice showed 1/1 animals were protected at 300 mg/kg at 30 minutes. In 4 h testing, 3/3 animals were protected at 100 mg/kg and 1/1 animals protected at 300 mg/kg dose. In toxicity studies, at 15 min, 2/8 mice (ip = interperitoneal) showed toxicity at 500 mg/kg dose. A 2 h MES protection test in mice (ip) displayed 3/8 animals protected at 85 mg/kg dose, 4/8 animals protected at 100 mg/kg, and 7/8 animals were protected at 170 mg/kg (optimum dose). In mice, the MES ED50 (median effective dose) of 106.34 mg kg-1 and TD50 (median toxic dose) of 500 mg kg-1 TD, 95% confidence inteval. The scMET (subcuntaneous metrazole) test showed no protection at 250 or 500 mg/kg during a 2 h range.

In view of the therapeutic interest in this compound its structure was determined. The conformation adopted by the molecule is such that the dihedral angle between the phenyl ring and conjugated part of the enaminone ring is 55.19 (9)°. The ester substituent makes a dihedral angle of 81.0 (2)° with this latter moiety. The crystal structure is held together by strong N—H···O and weak C—H···O intermolecular interactions.

Related literature top

Our research on enaminones has led to several compounds possessing

anticonvulsant properties, see: Edafiogho et al. (1992); Eddington et al. (2003); Scott et al. (1993, 1995).

Experimental top

4-Carbo-tert-butoxy-5-methylcyclohexane-1,3-dione (6. 11 g, 27 mmol), mp 145–146° C (lit. mp 130–131.5°C),7 and 4-chloroaniline (4.21 g, 33 mmol) were added to a mixture of absolute EtOH (100 ml) and EtOAc (100 ml), and the solution was refluxed and stirred for 6 h. Evaporation under reduced pressure yielded a yellow solid which was recrystallized from 2-PrOH: yield 3.96 g (43%); mp 190–192° C; 1H NMR (CDC13) 6 1.10 (3H, d, J = 6.3 Hz, CH3), 1.48 (9H, s, 3 x CH3 of tert-butyl group), 2.22–2.63 (3H, m, CH2 + CH of cyclohexene ring), 2.90 (lH, d, J =11.0 Hz, CHI, 5.45 (lH, 8, =CHI, 6.90 (lH, bs, NH), 7.05–7.30 (4H, m, C6H4).

Refinement top

H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms with a C—H distance of 0.93 and 0.98 Å Uiso(H) = 1.2Ueq(C) and 0.96 Å for CH3 [Uiso(H) = 1.5Ueq(C)]. The H atoms attached to N were idealized with an N–H distance of 0.86 Å.

Structure description top

Our research on enaminones has led to several compounds possessing anticonvulsant properties (Edafiogho et al., 1992; Eddington et al., 2003; Scott et al., 1993, 1995). The present work is part of a structural study of enaminones. Our group has extensively studied the effects of modification of the enaminone with substitutions at the methyl ester, ethyl ester, and without the ester group. We synthesized a series of carbo-tert-butoxy esters to evaluate the effect of added bulk and lipophilicity to the ester functionality. These compounds showed significant anticonvulsant activity. The title compound, tert-butyl- 4-(4-chlorophenlyamino)-6-methyl-2-oxocyclohex-3-enecarboxylate is highly active, with activity at <100 mg kg-1. The compound was active in maximal electroshock seizure evaluation (MES) in mice, indicative of protection against tonic-clonic convulsions in humans (1/4 rats protected at 1 h, 2 h and 4 h post dose at 50 mg kg dose). Toxicity tests showed no toxicity in rats (oral) up to 4 h at 50 mg/kg per dose. The MES study in mice showed 1/1 animals were protected at 300 mg/kg at 30 minutes. In 4 h testing, 3/3 animals were protected at 100 mg/kg and 1/1 animals protected at 300 mg/kg dose. In toxicity studies, at 15 min, 2/8 mice (ip = interperitoneal) showed toxicity at 500 mg/kg dose. A 2 h MES protection test in mice (ip) displayed 3/8 animals protected at 85 mg/kg dose, 4/8 animals protected at 100 mg/kg, and 7/8 animals were protected at 170 mg/kg (optimum dose). In mice, the MES ED50 (median effective dose) of 106.34 mg kg-1 and TD50 (median toxic dose) of 500 mg kg-1 TD, 95% confidence inteval. The scMET (subcuntaneous metrazole) test showed no protection at 250 or 500 mg/kg during a 2 h range.

In view of the therapeutic interest in this compound its structure was determined. The conformation adopted by the molecule is such that the dihedral angle between the phenyl ring and conjugated part of the enaminone ring is 55.19 (9)°. The ester substituent makes a dihedral angle of 81.0 (2)° with this latter moiety. The crystal structure is held together by strong N—H···O and weak C—H···O intermolecular interactions.

Our research on enaminones has led to several compounds possessing

anticonvulsant properties, see: Edafiogho et al. (1992); Eddington et al. (2003); Scott et al. (1993, 1995).

Computing details top

Data collection: CrysAlis PRO (Oxford Diffraction, 2007); cell refinement: CrysAlis PRO (Oxford Diffraction, 2007); data reduction: CrysAlis PRO (Oxford Diffraction, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. Diagram of tert-butyl- 4-(4-chlorophenlyamino)-6-methyl-2-oxocyclohex-3-enecarboxylate showing atom labeling scheme. Thermal ellipsoids drawn at the 30% probability level.
[Figure 2] Fig. 2. The molecular packing for tert-butyl- 4-(4-chlorophenlyamino)-6-methyl-2-oxocyclohex-3-enecarboxylate viewed down the a axis. Intermolecular interactions are shown by dashed lines.
tert-Butyl 4-(4-chloroanilino)-6-methyl-2-oxocyclohex-3-enecarboxylate top
Crystal data top
C18H22ClNO3Dx = 1.262 Mg m−3
Mr = 335.82Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, PbcaCell parameters from 5335 reflections
a = 11.0801 (3) Åθ = 4.5–77.5°
b = 10.9095 (3) ŵ = 0.23 mm−1
c = 29.2474 (7) ÅT = 295 K
V = 3535.39 (16) Å3Plate, colorless
Z = 80.45 × 0.38 × 0.08 mm
F(000) = 1424
Data collection top
Oxford Diffraction Xcalibur Ruby Gemini
diffractometer		3708 independent reflections
Radiation source: Enhance (Cu) X-ray Source2925 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.030
Detector resolution: 10.5081 pixels mm-1θmax = 26.8°, θmin = 2.3°
ω scansh = −13→14
Absorption correction: multi-scan
(CrysAlis PRO; Oxford Diffraction, 2007)		k = −13→7
Tmin = 0.93, Tmax = 0.98l = −22→36
9798 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.055Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.172H-atom parameters constrained
S = 1.09 w = 1/[σ2(Fo2) + (0.1062P)2 + 0.3243P]
where P = (Fo2 + 2Fc2)/3
3708 reflections(Δ/σ)max < 0.001
212 parametersΔρmax = 0.39 e Å−3
0 restraintsΔρmin = −0.25 e Å−3
Crystal data top
C18H22ClNO3V = 3535.39 (16) Å3
Mr = 335.82Z = 8
Orthorhombic, PbcaMo Kα radiation
a = 11.0801 (3) ŵ = 0.23 mm−1
b = 10.9095 (3) ÅT = 295 K
c = 29.2474 (7) Å0.45 × 0.38 × 0.08 mm
Data collection top
Oxford Diffraction Xcalibur Ruby Gemini
diffractometer		3708 independent reflections
Absorption correction: multi-scan
(CrysAlis PRO; Oxford Diffraction, 2007)		2925 reflections with I > 2σ(I)
Tmin = 0.93, Tmax = 0.98Rint = 0.030
9798 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0550 restraints
wR(F2) = 0.172H-atom parameters constrained
S = 1.09Δρmax = 0.39 e Å−3
3708 reflectionsΔρmin = −0.25 e Å−3
212 parameters
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Cl10.91865 (8)0.65446 (7)0.66441 (3)0.0944 (3)
O10.91038 (13)0.17651 (17)0.43476 (6)0.0689 (4)
O20.7403 (2)0.01470 (14)0.37719 (6)0.0785 (5)
O30.78836 (13)0.16309 (12)0.32703 (4)0.0545 (3)
N10.63017 (13)0.40873 (17)0.52106 (5)0.0539 (4)
H10.55360.41800.52430.065*
C10.70410 (16)0.46315 (18)0.55484 (6)0.0492 (4)
C20.8068 (2)0.5287 (2)0.54365 (7)0.0628 (5)
H20.83140.53330.51330.075*
C30.8732 (2)0.5875 (2)0.57713 (8)0.0682 (6)
H30.94290.63050.56950.082*
C40.8349 (2)0.5817 (2)0.62193 (7)0.0621 (5)
C50.7323 (2)0.5180 (2)0.63334 (7)0.0659 (5)
H50.70680.51540.66360.079*
C60.66736 (17)0.4583 (2)0.60016 (6)0.0584 (5)
H60.59850.41440.60810.070*
C70.66666 (15)0.34364 (17)0.48417 (5)0.0447 (4)
C80.56893 (15)0.32234 (19)0.44950 (6)0.0507 (4)
H8A0.56010.39560.43100.061*
H8B0.49330.30910.46540.061*
C90.59232 (15)0.21420 (18)0.41826 (6)0.0489 (4)
H90.58730.13910.43650.059*
C100.72128 (15)0.22487 (16)0.39930 (6)0.0447 (4)
H10A0.72700.30160.38200.054*
C110.81263 (14)0.23012 (17)0.43840 (6)0.0472 (4)
C120.78047 (15)0.29974 (18)0.47760 (6)0.0485 (4)
H120.83910.31590.49950.058*
C130.49731 (19)0.2070 (2)0.38044 (7)0.0635 (5)
H13A0.41840.20220.39390.095*
H13B0.51150.13550.36210.095*
H13C0.50240.27890.36160.095*
C140.75164 (18)0.12016 (16)0.36732 (6)0.0507 (4)
C150.8185 (2)0.0796 (2)0.28902 (6)0.0586 (5)
C160.9248 (3)0.0025 (4)0.30166 (10)0.1008 (11)
H16C0.9005−0.05850.32340.151*
H16D0.98630.05340.31490.151*
H16A0.9560−0.03680.27480.151*
C170.8512 (4)0.1665 (3)0.25068 (9)0.0955 (10)
H17A0.91440.22050.26070.143*
H17B0.78160.21390.24230.143*
H17C0.87830.12040.22470.143*
C180.7086 (3)0.0050 (4)0.27656 (11)0.1025 (11)
H18A0.6868−0.04650.30190.154*
H18B0.7264−0.04500.25040.154*
H18C0.64280.05900.26950.154*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.1084 (6)0.0928 (5)0.0821 (4)−0.0154 (4)−0.0342 (4)−0.0178 (4)
O10.0460 (7)0.0958 (11)0.0648 (9)0.0202 (7)−0.0022 (6)−0.0154 (8)
O20.1255 (15)0.0446 (8)0.0653 (9)0.0057 (8)0.0129 (9)0.0027 (7)
O30.0694 (8)0.0495 (7)0.0446 (6)0.0010 (6)0.0015 (6)−0.0036 (5)
N10.0414 (7)0.0721 (10)0.0481 (8)0.0038 (7)0.0036 (6)−0.0087 (7)
C10.0474 (8)0.0557 (10)0.0443 (8)0.0047 (7)0.0002 (6)−0.0028 (7)
C20.0743 (13)0.0642 (12)0.0499 (10)−0.0136 (10)0.0051 (9)0.0020 (9)
C30.0743 (13)0.0604 (12)0.0700 (12)−0.0195 (11)−0.0015 (10)0.0011 (10)
C40.0714 (12)0.0577 (11)0.0571 (10)0.0041 (9)−0.0161 (9)−0.0065 (9)
C50.0642 (11)0.0887 (15)0.0447 (9)0.0067 (11)−0.0011 (8)−0.0058 (10)
C60.0470 (9)0.0802 (13)0.0479 (9)0.0015 (9)0.0032 (7)−0.0037 (9)
C70.0413 (8)0.0528 (9)0.0399 (7)−0.0010 (7)0.0017 (6)0.0020 (7)
C80.0364 (7)0.0677 (11)0.0480 (8)0.0020 (7)−0.0013 (6)−0.0027 (8)
C90.0441 (8)0.0538 (10)0.0489 (9)−0.0056 (7)−0.0048 (7)0.0038 (7)
C100.0476 (8)0.0448 (8)0.0418 (8)−0.0005 (6)−0.0001 (6)0.0007 (7)
C110.0383 (7)0.0561 (9)0.0471 (8)0.0006 (7)0.0020 (6)0.0001 (7)
C120.0378 (7)0.0630 (10)0.0445 (8)0.0029 (7)−0.0034 (6)−0.0022 (7)
C130.0538 (10)0.0735 (13)0.0633 (11)−0.0086 (9)−0.0151 (9)−0.0045 (10)
C140.0575 (9)0.0469 (9)0.0478 (9)0.0033 (8)−0.0038 (7)−0.0005 (7)
C150.0693 (11)0.0613 (11)0.0451 (9)0.0034 (9)−0.0008 (8)−0.0103 (8)
C160.102 (2)0.126 (3)0.0742 (16)0.051 (2)0.0111 (15)−0.0059 (17)
C170.147 (3)0.0849 (17)0.0544 (13)−0.0033 (19)0.0192 (16)−0.0025 (12)
C180.102 (2)0.125 (3)0.0800 (17)−0.0311 (19)0.0000 (15)−0.0427 (18)
Geometric parameters (Å, º) top
Cl1—C41.742 (2)C9—C131.529 (2)
O1—C111.235 (2)C9—C101.537 (2)
O2—C141.193 (3)C9—H90.9800
O3—C141.332 (2)C10—C141.514 (2)
O3—C151.475 (2)C10—C111.528 (2)
N1—C71.353 (2)C10—H10A0.9800
N1—C11.414 (2)C11—C121.421 (2)
N1—H10.8600C12—H120.9300
C1—C21.383 (3)C13—H13A0.9600
C1—C61.388 (3)C13—H13B0.9600
C2—C31.383 (3)C13—H13C0.9600
C2—H20.9300C15—C161.494 (3)
C3—C41.379 (3)C15—C181.509 (3)
C3—H30.9300C15—C171.512 (3)
C4—C51.373 (3)C16—H16C0.9600
C5—C61.373 (3)C16—H16D0.9600
C5—H50.9300C16—H16A0.9600
C6—H60.9300C17—H17A0.9600
C7—C121.363 (2)C17—H17B0.9600
C7—C81.502 (2)C17—H17C0.9600
C8—C91.515 (3)C18—H18A0.9600
C8—H8A0.9700C18—H18B0.9600
C8—H8B0.9700C18—H18C0.9600
C14—O3—C15121.26 (15)C11—C10—H10108.1
C7—N1—C1127.17 (15)C9—C10—H10108.1
C7—N1—H1116.4O1—C11—C12122.87 (17)
C1—N1—H1116.4O1—C11—C10119.88 (16)
C2—C1—C6119.15 (18)C12—C11—C10117.24 (15)
C2—C1—N1121.90 (17)C7—C12—C11122.28 (16)
C6—C1—N1118.77 (17)C7—C12—H12118.9
C3—C2—C1120.67 (19)C11—C12—H12118.9
C3—C2—H2119.7C9—C13—H13A109.5
C1—C2—H2119.7C9—C13—H13B109.5
C4—C3—C2119.2 (2)H13A—C13—H13B109.5
C4—C3—H3120.4C9—C13—H13C109.5
C2—C3—H3120.4H13A—C13—H13C109.5
C5—C4—C3120.60 (19)H13B—C13—H13C109.5
C5—C4—Cl1119.86 (17)O2—C14—O3125.85 (18)
C3—C4—Cl1119.54 (19)O2—C14—C10123.68 (18)
C6—C5—C4120.15 (19)O3—C14—C10110.43 (15)
C6—C5—H5119.9O3—C15—C16109.85 (18)
C4—C5—H5119.9O3—C15—C18109.42 (19)
C5—C6—C1120.22 (19)C16—C15—C18113.1 (3)
C5—C6—H6119.9O3—C15—C17103.07 (18)
C1—C6—H6119.9C16—C15—C17110.3 (2)
N1—C7—C12124.99 (16)C18—C15—C17110.6 (2)
N1—C7—C8113.84 (15)C15—C16—H16C109.5
C12—C7—C8121.18 (15)C15—C16—H16D109.5
C7—C8—C9113.86 (15)H16C—C16—H16D109.5
C7—C8—H8A108.8C15—C16—H16A109.5
C9—C8—H8A108.8H16C—C16—H16A109.5
C7—C8—H8B108.8H16D—C16—H16A109.5
C9—C8—H8B108.8C15—C17—H17A109.5
H8A—C8—H8B107.7C15—C17—H17B109.5
C8—C9—C13111.01 (16)H17A—C17—H17B109.5
C8—C9—C10108.52 (14)C15—C17—H17C109.5
C13—C9—C10112.52 (16)H17A—C17—H17C109.5
C8—C9—H9108.2H17B—C17—H17C109.5
C13—C9—H9108.2C15—C18—H18A109.5
C10—C9—H9108.2C15—C18—H18B109.5
C14—C10—C11110.08 (14)H18A—C18—H18B109.5
C14—C10—C9111.85 (15)C15—C18—H18C109.5
C11—C10—C9110.40 (14)H18A—C18—H18C109.5
C14—C10—H10108.1H18B—C18—H18C109.5
C7—N1—C1—C244.5 (3)C8—C9—C10—C1157.46 (19)
C7—N1—C1—C6−140.4 (2)C13—C9—C10—C11−179.30 (17)
C6—C1—C2—C30.8 (3)C14—C10—C11—O117.6 (2)
N1—C1—C2—C3175.9 (2)C9—C10—C11—O1141.56 (18)
C1—C2—C3—C4−1.0 (4)C14—C10—C11—C12−163.43 (16)
C2—C3—C4—C50.2 (4)C9—C10—C11—C12−39.5 (2)
C2—C3—C4—Cl1179.48 (19)N1—C7—C12—C11178.91 (18)
C3—C4—C5—C60.7 (4)C8—C7—C12—C11−1.1 (3)
Cl1—C4—C5—C6−178.60 (18)O1—C11—C12—C7−170.34 (19)
C4—C5—C6—C1−0.8 (3)C10—C11—C12—C710.7 (3)
C2—C1—C6—C50.1 (3)C15—O3—C14—O20.7 (3)
N1—C1—C6—C5−175.1 (2)C15—O3—C14—C10−177.35 (16)
C1—N1—C7—C1212.9 (3)C11—C10—C14—O270.1 (3)
C1—N1—C7—C8−167.05 (18)C9—C10—C14—O2−53.0 (3)
N1—C7—C8—C9−158.30 (16)C11—C10—C14—O3−111.80 (17)
C12—C7—C8—C921.7 (3)C9—C10—C14—O3125.08 (17)
C7—C8—C9—C13−173.31 (16)C14—O3—C15—C16−64.0 (3)
C7—C8—C9—C10−49.2 (2)C14—O3—C15—C1860.7 (3)
C8—C9—C10—C14−179.60 (14)C14—O3—C15—C17178.4 (2)
C13—C9—C10—C14−56.4 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.862.242.909 (2)135
C6—H6···O1i0.932.633.363 (2)137
C10—H10···O2ii0.982.363.255 (2)152
Symmetry codes: (i) x−1/2, −y+1/2, −z+1; (ii) −x+3/2, y+1/2, z.

Experimental details

Crystal data
Chemical formulaC18H22ClNO3
Mr335.82
Crystal system, space groupOrthorhombic, Pbca
Temperature (K)295
a, b, c (Å)11.0801 (3), 10.9095 (3), 29.2474 (7)
V (Å3)3535.39 (16)
Z8
Radiation typeMo Kα
µ (mm−1)0.23
Crystal size (mm)0.45 × 0.38 × 0.08
Data collection
DiffractometerOxford Diffraction Xcalibur Ruby Gemini
Absorption correctionMulti-scan
(CrysAlis PRO; Oxford Diffraction, 2007)
Tmin, Tmax0.93, 0.98
No. of measured, independent and
observed [I > 2σ(I)] reflections		9798, 3708, 2925
Rint0.030
(sin θ/λ)max (Å−1)0.634
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.055, 0.172, 1.09
No. of reflections3708
No. of parameters212
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å−3)0.39, −0.25

Computer programs: CrysAlis PRO (Oxford Diffraction, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.862.242.909 (2)134.8
C6—H6···O1i0.932.633.363 (2)136.6
C10—H10···O2ii0.982.363.255 (2)152.0
Symmetry codes: (i) x−1/2, −y+1/2, −z+1; (ii) −x+3/2, y+1/2, z.
 

Acknowledgements

The authors are indebted to Mr James P. Stables, Epilepsy Branch, Division of Convulsive, Developmental and Neuromuscular Disorders, National Institute of Neurological Disorders and Stroke, for helpful discussions and initial data. The authors wish to acknowledge E. Jeannette Andrews, EdD Deputy Director of the Center of Excellence at Howard University College of Pharmacy, Nursing and Allied Health Sciences, for her generous assistance in completing this project. RJB wishes to acknowledge the NSF–MRI program (grant CHE-0619278) for funds to purchase the diffractometer.

References

First citationEdafiogho, I. O., Hinko, C. N., Chang, H., Moore, J. A., Mulzac, D., Nicholson, J. M. & Scott, K. R. (1992). J. Med. Chem. 35, 2798–2805.  CrossRef PubMed CAS Web of Science Google Scholar
 First citationEddington, N. D., Cox, D. S., Khurana, M., Salama, N. N., Stables, J. P., Harrison, S. J., Negussie, A., Taylor, R. S., Tran, U. Q., Moore, J. A., Barrow, J. C. & Scott, K. R. (2003). Eur. J. Med. Chem. 38, 49–64.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationOxford Diffraction (2007). CrysAlis PRO and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, England.  Google Scholar
 First citationScott, K. R., Edafiogho, I. O., Richardson, E. R., Farrar, V. A., Moore, J. A., Tietz, E., Hinko, C. N., Chang, H., El-Assadi, A. & Nicholson, J. M. (1993). J. Med. Chem. 36, 1947–1955.  CrossRef CAS PubMed Web of Science Google Scholar
 First citationScott, K. R., Rankin, G. O., Stables, J. P., Alexander, M. S., Edafiogho, I. O., Farrar, V. A., Kolen, K. R., Moore, J. A., Sims, L. D. & Tonnu, A. D. (1995). J. Med. Chem. 38, 4033–4043.  CrossRef CAS PubMed Web of Science Google Scholar
 First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS 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.

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ISSN: 2056-9890
Volume 67| Part 1| January 2011| Page o224
https://doi.org/10.1107/S1600536810051743
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