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Acta Crystallogr Sect E Struct Rep Online. 2009 December 1; 65(Pt 12): o3234.
Published online 2009 November 28. doi:  10.1107/S1600536809050284
PMCID: PMC2972029

N-Cyclo­hexyl-3,4,5-trimethoxy­benzamide

Abstract

The 3,5-meth­oxy groups in the title compound, C16H23NO4, are almost coplanar with the aromatic ring, whereas the 4-meth­oxy group is bent out of this plane. The three CH3—O—C—C torsion angles are −1.51 (18), 0.73 (19) and 75.33 (15)°. The cyclo­hexane ring adopts a chair conformation. In the crystal, mol­ecules are connected by inter­molecular N—H(...)O hydrogen bonds into chains running along the b axis.

Related literature

For the biological activity of benzanilides, see: Olsson et al. (2002 [triangle]); Lindgren et al. (2001 [triangle]); Calderone et al. (2006 [triangle]). For the use of benzamides in organic synthesis, see: Zhichkin et al. (2007 [triangle]); Beccalli et al. (2005 [triangle]). For related structures, see: Bowes et al. (2003 [triangle]); Chopra & Guru Row (2008 [triangle]); Kashino et al. (1979 [triangle]); Saeed et al. (2008 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o3234-scheme1.jpg

Experimental

Crystal data

  • C16H23NO4
  • M r = 293.35
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o3234-efi1.jpg
  • a = 23.4539 (19) Å
  • b = 5.2145 (6) Å
  • c = 12.4559 (10) Å
  • β = 92.886 (6)°
  • V = 1521.4 (2) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 173 K
  • 0.37 × 0.37 × 0.33 mm

Data collection

  • Stoe IPDSII two-circle diffractometer
  • Absorption correction: none
  • 6868 measured reflections
  • 2823 independent reflections
  • 2360 reflections with I > 2σ(I)
  • R int = 0.062

Refinement

  • R[F 2 > 2σ(F 2)] = 0.040
  • wR(F 2) = 0.109
  • S = 1.05
  • 2823 reflections
  • 198 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.27 e Å−3
  • Δρmin = −0.22 e Å−3

Data collection: X-AREA (Stoe & Cie, 2001 [triangle]); cell refinement: X-AREA; data reduction: X-AREA; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: XP in SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: PLATON (Spek, 2009 [triangle]) and SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809050284/fj2261sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809050284/fj2261Isup2.hkl

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

supplementary crystallographic information

Comment

N-substituted benzamides are well known anticancer compounds and the mechanism of action for N-substituted benzamide-induced apoptosis has been studied, using declopramide as a lead compound (Olsson et al., 2002). N-substituted benzamides inhibit the activity of nuclear factor- B and nuclear factor of activated T cells activity while inducing activator protein 1 activity in T lymphocytes (Lindgren et al., 2001). Heterocyclic analogs of benzanilide derivatives are potassium channel activators (Calderone et al., 2006). N-Alkylated 2-nitrobenzamides are intermediates in the synthesis of dibenzo[b,e][1,4]diazepines (Zhichkin et al., 2007) and N-Acyl-2-nitrobenzamides are precursors of 2,3-disubstitued 3H-quinazoline-4-ones (Beccalli et al., 2005).

The two m-methoxy groups the title compound are almost coplanar with the aromatic ring [CH3—O—C—C -1.51 (18)° and 0.73 (19)°] whereas the methoxy group in para position is bent out of the plane of the aromatic ring [CH3—O—C—C 75.33 (15)°]. The cyclohexyl ring adops a chair conformation. The molecules are connected by N—H···O hydrogen bonds to chains running along the b axis.

Experimental

3,4,5-Trimethoxybenzoyl chloride (1 mmol) in CHCl3 was treated with cyclohexylamine (3.5 mmol) under a nitrogen atmosphere at reflux for 3 h. Upon cooling, the reaction mixture was diluted with CHCl3 and washed consecutively with 1 M aq HCl and saturated aq NaHCO3. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Crystallization of the residue in methanol afforded the title compound (78%) as colourless crystals: Anal. calcd. for C16H23NO4: C, 65.51; H, 9.70; N, 4.77%; found: C, 65.58; H, 9.65; N, 4.81%.

Refinement

Hydrogen atoms were located in difference syntheses, but those bonded to C were refined at idealized positions using a riding model with C–H = 0.95–1.00 Å) and with Uiso(H) = 1.2Ueq(C) or Uiso(H) = 1.5Ueq(Cmethyl). The methyl groups were allowed to rotate but not to tip. The H atom bonded to N was freely refined.

Figures

Fig. 1.
Molecular structure of title compound. Displacement ellipsoids are drawn at the 50% probability level.
Fig. 2.
Crystal packing viewed along [001] with intermolecular hydrogen bonds indicated as dashed lines. H-atoms not involved in hydrogen bonding are omitted.

Crystal data

C16H23NO4F(000) = 632
Mr = 293.35Dx = 1.281 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 6103 reflections
a = 23.4539 (19) Åθ = 3.4–26.0°
b = 5.2145 (6) ŵ = 0.09 mm1
c = 12.4559 (10) ÅT = 173 K
β = 92.886 (6)°Block, colourless
V = 1521.4 (2) Å30.37 × 0.37 × 0.33 mm
Z = 4

Data collection

Stoe IPDSII two-circle diffractometer2360 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.062
graphiteθmax = 25.6°, θmin = 3.4°
ω scansh = −28→23
6868 measured reflectionsk = −5→6
2823 independent reflectionsl = −15→15

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.040H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.109w = 1/[σ2(Fo2) + (0.0651P)2 + 0.0617P] where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max < 0.001
2823 reflectionsΔρmax = 0.27 e Å3
198 parametersΔρmin = −0.22 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.023 (3)

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
N10.19554 (5)0.4159 (2)0.53398 (9)0.0237 (3)
H10.2089 (8)0.579 (4)0.5241 (13)0.034 (4)*
O10.21507 (4)−0.01048 (18)0.53804 (8)0.0289 (3)
O20.42937 (4)0.00520 (19)0.45580 (7)0.0279 (3)
O30.43346 (4)0.36344 (18)0.30218 (7)0.0242 (2)
O40.34531 (4)0.66623 (18)0.25120 (7)0.0255 (2)
C10.22841 (6)0.2119 (2)0.51372 (10)0.0211 (3)
C110.28301 (5)0.2637 (2)0.45950 (9)0.0198 (3)
C120.32948 (6)0.1047 (2)0.48557 (9)0.0213 (3)
H120.3265−0.02650.53790.026*
C130.38033 (6)0.1395 (3)0.43442 (9)0.0211 (3)
C140.38357 (5)0.3267 (2)0.35373 (9)0.0202 (3)
C150.33712 (6)0.4871 (2)0.32918 (9)0.0198 (3)
C160.28646 (6)0.4586 (2)0.38262 (9)0.0201 (3)
H160.25500.56930.36710.024*
C170.42929 (6)−0.1910 (3)0.53660 (10)0.0268 (3)
H17A0.4199−0.11490.60550.040*
H17B0.4671−0.27070.54380.040*
H17C0.4008−0.32140.51570.040*
C180.44384 (6)0.1648 (3)0.22488 (11)0.0294 (3)
H18A0.4411−0.00340.25930.044*
H18B0.48210.18630.19810.044*
H18C0.41540.17670.16470.044*
C190.29830 (6)0.8303 (3)0.22110 (10)0.0258 (3)
H19A0.26590.72630.19390.039*
H19B0.30950.94890.16490.039*
H19C0.28730.92820.28390.039*
C210.14322 (6)0.3901 (3)0.59287 (11)0.0247 (3)
H210.12610.21850.57550.030*
C220.15657 (7)0.4025 (4)0.71420 (11)0.0376 (4)
H22A0.17580.56700.73230.045*
H22B0.18310.26170.73570.045*
C230.10231 (7)0.3799 (4)0.77699 (12)0.0404 (4)
H23A0.08510.20820.76490.048*
H23B0.11220.39840.85480.048*
C240.05945 (7)0.5845 (3)0.74171 (12)0.0372 (4)
H24A0.07500.75570.76120.045*
H24B0.02390.55990.78000.045*
C250.04589 (7)0.5735 (4)0.62060 (12)0.0376 (4)
H25A0.01960.71530.59940.045*
H25B0.02640.40970.60230.045*
C260.10009 (6)0.5950 (3)0.55750 (11)0.0310 (3)
H26A0.09010.57570.47970.037*
H26B0.11730.76680.56920.037*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
N10.0193 (6)0.0209 (6)0.0316 (6)−0.0013 (5)0.0099 (4)0.0005 (4)
O10.0248 (5)0.0215 (5)0.0413 (6)−0.0004 (4)0.0099 (4)0.0034 (4)
O20.0198 (5)0.0365 (6)0.0277 (5)0.0075 (4)0.0047 (4)0.0091 (4)
O30.0189 (5)0.0278 (5)0.0266 (5)−0.0017 (4)0.0083 (4)−0.0024 (4)
O40.0250 (5)0.0272 (5)0.0248 (4)0.0026 (4)0.0065 (4)0.0070 (4)
C10.0188 (6)0.0230 (6)0.0215 (6)−0.0005 (5)0.0011 (5)−0.0006 (5)
C110.0184 (6)0.0221 (6)0.0192 (5)−0.0026 (5)0.0036 (5)−0.0048 (5)
C120.0218 (7)0.0225 (6)0.0197 (6)−0.0007 (5)0.0030 (5)0.0009 (5)
C130.0175 (6)0.0248 (6)0.0210 (6)0.0015 (5)0.0007 (5)−0.0025 (5)
C140.0172 (6)0.0240 (6)0.0197 (6)−0.0025 (5)0.0039 (5)−0.0035 (5)
C150.0214 (7)0.0205 (6)0.0178 (6)−0.0012 (5)0.0024 (5)−0.0011 (4)
C160.0176 (6)0.0212 (6)0.0215 (6)0.0018 (5)0.0009 (5)−0.0017 (5)
C170.0278 (7)0.0269 (7)0.0254 (6)0.0054 (6)−0.0003 (5)0.0037 (5)
C180.0293 (8)0.0299 (7)0.0301 (7)0.0031 (6)0.0125 (6)−0.0023 (6)
C190.0287 (7)0.0255 (7)0.0233 (6)0.0040 (6)0.0007 (5)0.0033 (5)
C210.0190 (7)0.0246 (7)0.0312 (7)−0.0017 (6)0.0086 (5)−0.0003 (5)
C220.0250 (8)0.0572 (10)0.0312 (8)0.0053 (7)0.0064 (6)0.0073 (7)
C230.0338 (9)0.0543 (10)0.0342 (8)0.0028 (8)0.0124 (7)0.0066 (7)
C240.0318 (8)0.0385 (9)0.0431 (8)−0.0008 (7)0.0184 (7)−0.0058 (7)
C250.0218 (8)0.0462 (9)0.0456 (9)0.0068 (7)0.0085 (6)0.0034 (7)
C260.0238 (8)0.0352 (8)0.0346 (7)0.0050 (6)0.0073 (6)0.0057 (6)

Geometric parameters (Å, °)

N1—C11.3451 (17)C18—H18B0.9800
N1—C211.4670 (16)C18—H18C0.9800
N1—H10.916 (19)C19—H19A0.9800
O1—C11.2424 (16)C19—H19B0.9800
O2—C131.3615 (16)C19—H19C0.9800
O2—C171.4353 (16)C21—C261.521 (2)
O3—C141.3761 (15)C21—C221.529 (2)
O3—C181.4432 (16)C21—H211.0000
O4—C151.3681 (15)C22—C231.532 (2)
O4—C191.4307 (17)C22—H22A0.9900
C1—C111.5020 (17)C22—H22B0.9900
C11—C121.3945 (19)C23—C241.516 (2)
C11—C161.4015 (18)C23—H23A0.9900
C12—C131.3920 (18)C23—H23B0.9900
C12—H120.9500C24—C251.527 (2)
C13—C141.4058 (18)C24—H24A0.9900
C14—C151.3951 (19)C24—H24B0.9900
C15—C161.3988 (18)C25—C261.5320 (19)
C16—H160.9500C25—H25A0.9900
C17—H17A0.9800C25—H25B0.9900
C17—H17B0.9800C26—H26A0.9900
C17—H17C0.9800C26—H26B0.9900
C18—H18A0.9800
C1—N1—C21121.53 (11)H19A—C19—H19B109.5
C1—N1—H1120.3 (11)O4—C19—H19C109.5
C21—N1—H1117.0 (11)H19A—C19—H19C109.5
C13—O2—C17118.23 (10)H19B—C19—H19C109.5
C14—O3—C18112.80 (10)N1—C21—C26110.57 (11)
C15—O4—C19117.42 (10)N1—C21—C22110.82 (11)
O1—C1—N1122.58 (12)C26—C21—C22110.89 (12)
O1—C1—C11120.55 (12)N1—C21—H21108.1
N1—C1—C11116.87 (11)C26—C21—H21108.1
C12—C11—C16121.26 (11)C22—C21—H21108.2
C12—C11—C1117.54 (11)C21—C22—C23111.55 (13)
C16—C11—C1121.16 (11)C21—C22—H22A109.3
C13—C12—C11119.56 (11)C23—C22—H22A109.3
C13—C12—H12120.2C21—C22—H22B109.3
C11—C12—H12120.2C23—C22—H22B109.3
O2—C13—C12125.32 (11)H22A—C22—H22B108.0
O2—C13—C14114.92 (11)C24—C23—C22110.72 (13)
C12—C13—C14119.75 (12)C24—C23—H23A109.5
O3—C14—C15119.15 (11)C22—C23—H23A109.5
O3—C14—C13120.54 (12)C24—C23—H23B109.5
C15—C14—C13120.22 (11)C22—C23—H23B109.5
O4—C15—C14115.40 (11)H23A—C23—H23B108.1
O4—C15—C16124.30 (12)C23—C24—C25111.23 (13)
C14—C15—C16120.29 (11)C23—C24—H24A109.4
C15—C16—C11118.82 (12)C25—C24—H24A109.4
C15—C16—H16120.6C23—C24—H24B109.4
C11—C16—H16120.6C25—C24—H24B109.4
O2—C17—H17A109.5H24A—C24—H24B108.0
O2—C17—H17B109.5C24—C25—C26111.54 (13)
H17A—C17—H17B109.5C24—C25—H25A109.3
O2—C17—H17C109.5C26—C25—H25A109.3
H17A—C17—H17C109.5C24—C25—H25B109.3
H17B—C17—H17C109.5C26—C25—H25B109.3
O3—C18—H18A109.5H25A—C25—H25B108.0
O3—C18—H18B109.5C21—C26—C25110.91 (12)
H18A—C18—H18B109.5C21—C26—H26A109.5
O3—C18—H18C109.5C25—C26—H26A109.5
H18A—C18—H18C109.5C21—C26—H26B109.5
H18B—C18—H18C109.5C25—C26—H26B109.5
O4—C19—H19A109.5H26A—C26—H26B108.0
O4—C19—H19B109.5
C21—N1—C1—O14.06 (19)C19—O4—C15—C16−1.51 (18)
C21—N1—C1—C11−175.93 (11)O3—C14—C15—O42.05 (17)
O1—C1—C11—C12−32.62 (17)C13—C14—C15—O4178.53 (11)
N1—C1—C11—C12147.36 (12)O3—C14—C15—C16−178.18 (11)
O1—C1—C11—C16145.07 (13)C13—C14—C15—C16−1.70 (18)
N1—C1—C11—C16−34.94 (17)O4—C15—C16—C11178.64 (11)
C16—C11—C12—C13−0.02 (18)C14—C15—C16—C11−1.11 (18)
C1—C11—C12—C13177.67 (11)C12—C11—C16—C151.99 (18)
C17—O2—C13—C120.73 (19)C1—C11—C16—C15−175.62 (11)
C17—O2—C13—C14−179.46 (11)C1—N1—C21—C26−150.78 (12)
C11—C12—C13—O2177.00 (12)C1—N1—C21—C2285.85 (16)
C11—C12—C13—C14−2.81 (19)N1—C21—C22—C23179.14 (13)
C18—O3—C14—C15−108.20 (13)C26—C21—C22—C2355.95 (18)
C18—O3—C14—C1375.33 (15)C21—C22—C23—C24−56.00 (19)
O2—C13—C14—O30.29 (17)C22—C23—C24—C2555.59 (19)
C12—C13—C14—O3−179.89 (11)C23—C24—C25—C26−55.74 (19)
O2—C13—C14—C15−176.15 (11)N1—C21—C26—C25−178.60 (12)
C12—C13—C14—C153.68 (19)C22—C21—C26—C25−55.27 (17)
C19—O4—C15—C14178.25 (11)C24—C25—C26—C2155.42 (18)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.916 (19)2.153 (19)3.0262 (15)159.0 (15)

Symmetry codes: (i) x, y+1, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: FJ2261).

References

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