N-(4-Chloro­phen­yl)-4-meth­oxy-3-(propanamido)­benzamide cyclo­hexane hemisolvate

Zhaojin Zhong; Zhuorong Li; Ningbo Gong; Yanping Li

doi:10.1107/S1600536812016480

. 2012 Apr 21;68(Pt 5):o1480. doi: 10.1107/S1600536812016480

N-(4-Chlorophenyl)-4-methoxy-3-(propanamido)benzamide cyclohexane hemisolvate

Zhaojin Zhong ^a, Zhuorong Li ^a,^*, Ningbo Gong ^b, Yanping Li ^a

PMCID: PMC3344590 PMID: 22590352

Abstract

The title compound, C₁₇H₁₇ClN₂O₃·0.5C₆H₁₂, was prepared by the condensation reaction of 4-methoxy-3-(propanamido)benzoic acid with 4-chloroaniline. The Cl atom, the propionyl CH₃ group and the cyclohexyl CH₂ group are disordered over two sets of sites of equal occupancy in both molecules. The cyclohexane solvent molecule is disordered over two orientations which were modelled with relative occupancies of 0.484 (4) and 0.516 (4). In the crystal, there are a number of N—H⋯O hydrogen bonds, forming layers perpendicular to (001).

Related literature

N-(4-chlorophenyl)-4-methoxy-3-(propanamido) benzamide is a lead compound with antiviral activity targeting APOBEC3G. For the synthesis and properties of the compound and its derivatives, see: Jiang et al. (2009 ▶). For APOBEC3G as a target for antiviral drugs, see: Cullen (2006 ▶); Mamgeat et al. (2003 ▶); Cen et al.(2004 ▶).

Experimental

Crystal data

C₁₇H₁₇ClN₂O₃·0.5C₆H₁₂
M _r = 374.86
Monoclinic,
a = 16.005 (3) Å
b = 18.953 (4) Å
c = 14.811 (3) Å
β = 120.08 (3)°
V = 3887.8 (18) Å³
Z = 8
Cu Kα radiation
μ = 1.92 mm⁻¹
T = 295 K
0.48 × 0.13 × 0.08 mm

Data collection

Rigaku MicroMax 002+ diffractometer
Absorption correction: multi-scan (REQAB; Blessing, 1995 ▶) T _min = 0.743, T _max = 0.860
22780 measured reflections
5742 independent reflections
5349 reflections with I > 2σ(I)
R _int = 0.037

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.139
S = 1.11
5742 reflections
561 parameters
68 restraints
H-atom parameters constrained
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.24 e Å⁻³

Data collection: CrystalClear (Rigaku, 2008 ▶); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEPII (Johnson,1976 ▶) and PLATON (Spek, 2009 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812016480/rn2093sup1.cif

e-68-o1480-sup1.cif^{(34.1KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812016480/rn2093Isup2.hkl

e-68-o1480-Isup2.hkl^{(281.1KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812016480/rn2093Isup4.cdx

Supplementary material file. DOI: 10.1107/S1600536812016480/rn2093Isup4.cml

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
N2A—H2AA⋯O1B	0.86	2.25	3.082 (4)	164
N2B—H2BA⋯O1A	0.86	2.26	3.091 (5)	163
N1A—H1AA⋯O2Bⁱ	0.86	2.28	3.040 (4)	147
N1B—H1BA⋯O2Aⁱⁱ	0.86	2.33	3.077 (4)	145

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

This research was supported by the National Natural Science Foundation of China (30873138).

supplementary crystallographic information

Comment

APOBEC3G (or hA3G, human apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like-3 G) is a target for antiviral drugs (Cullen, 2006; Mamgeat et al., 2003; Cen et al., 2004). In this research area, N-(4-chlorophenyl)-4-methoxy-3-(propanamido) benzamide is a lead compound and displays various biological activities (Jiang et al., 2009).

In the molecule of the title compound (I), there are two crystallographically independent benzamide molecules and one cyclohexane molecule in the asymmetric unit. The chlorine, the propionyl CH₃and cyclohexyl CH₂ are disordered. The isotropic displacement parameters of Cl1 (0.1177), Cl2 (0.1153), C16A (0.123) and C16B (0.156) are slightly higher than the average equivalent isotropic displacement parameters (0.065). No restraints were used. The occupancies of Cl1, Cl2, C16A and C16B are all equal to 1. The cyclohexane is disordered having two orientations which have been modelled with relative occupancies of 0.484 (4):0.516 (4). The dihedral angle between the benzene rings in molecule A is 7.86 (25) and this is very similar to that found in molecule B [7.76 (25)]. In the crystal structure, there are a number of N—H···O hydrogen bonds forming layers which are perpendicular to (001). (Table1, Fig. 1).

Experimental

To a solution of 4-methoxy-3-(propanamido)benzoic acid (10 g, 45 mmol) in N,N-dimethylformamide (150 ml) was added 1-hydroxybenzotriazole (9 g, 66.6 mmol) and N,N'-diisopropylcarbodiimide (8.5 ml). After stirring for 30 min at room temperature, p-chloroaniline (9 g, 70 mmol) was added. The solution was stirred at room temperature until no starting material was presented by TLC. The crude product was poured into water (200 ml), extracted with dichloromethane (300 ml) and washed with 5% NaOH (100 ml), 5% HCl (100 ml) and water. The organic layer was dried over anhydrous Na₂SO₄and filtered. After the removal of the dichloromethane under reduced pressure, the residue was treated with cyclohexane and filtered. The product, recrystallized with cyclohexane: dichloromethane (1:10), dried in vacuo to give N-(4-chlorophenyl)-4-methoxy-3-(propanamido) benzamide as a colourless crystalline solid (11.9 g, 79.8%; mp: 423–424 K). ¹H NMR (CDCl₃, δ): 8.89 (1H, s, –CONH), 8.19 (1H, s, 2-H), 7.811 (1H, s, –NHCOR), 7.74 (1H, d, 6-H), 7.60 (2H, d, 2',6'-H), 7.27 (2H, d, 3',5'-H), 6.94 (1H, d, 5-H), 3.94 (3H, s, –OCH₃), 2.44 (2H, q, –CH₂–), 1.24 (3H, t, –CH₃). MS (EI, m/z): 332 (M)⁺.

Single crystals suitable for X-ray analysis were obtained by slow evaporation of a mixed solvent of dichloromethane and cyclohexane (3:1 v/v).