N-Cyclo­hexyl-3,4,5-trimethoxy­benzamide

Aamer Saeed; Muhammad Arshad; Rasheed Ahmad Khera; Michael Bolte

doi:10.1107/S1600536809050284

. 2009 Nov 28;65(Pt 12):o3234. doi: 10.1107/S1600536809050284

N-Cyclohexyl-3,4,5-trimethoxybenzamide

Aamer Saeed ^a,^*, Muhammad Arshad ^b, Rasheed Ahmad Khera ^a, Michael Bolte ^c

PMCID: PMC2972029 PMID: 21578939

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 ▶); Lindgren et al. (2001 ▶); Calderone et al. (2006 ▶). For the use of benzamides in organic synthesis, see: Zhichkin et al. (2007 ▶); Beccalli et al. (2005 ▶). For related structures, see: Bowes et al. (2003 ▶); Chopra & Guru Row (2008 ▶); Kashino et al. (1979 ▶); Saeed et al. (2008 ▶). graphic file with name e-65-o3234-scheme1.jpg

Experimental

Crystal data

C₁₆H₂₃NO₄
M _r = 293.35
Monoclinic,
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
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.22 e Å⁻³

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

Supplementary Material

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

e-65-o3234-sup1.cif^{(19.7KB, cif)}

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

e-65-o3234-Isup2.hkl^{(138.6KB, 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⋯O1ⁱ	0.916 (19)	2.153 (19)	3.0262 (15)	159.0 (15)

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Symmetry code: (i) Inline graphic .

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 C₁₆H₂₃N_O4: C, 65.51; H, 9.70; N, 4.77%; found: C, 65.58; H, 9.65; N, 4.81%.