Benzyl 2-{4-[2-(4-chloro­benzoyl­amino)­eth­yl]phen­oxy}-2-methyl­propionate

Ghulam Mustafa; Sania Tasneem; Islam Ullah Khan; Muhammad Ashfaq; Muhammad Nadeem Arshad

doi:10.1107/S1600536811039249

. 2011 Sep 30;67(Pt 10):o2803. doi: 10.1107/S1600536811039249

Benzyl 2-{4-[2-(4-chlorobenzoylamino)ethyl]phenoxy}-2-methylpropionate

Ghulam Mustafa ^a,^b,^*, Sania Tasneem ^a, Islam Ullah Khan ^b, Muhammad Ashfaq ^a, Muhammad Nadeem Arshad ^c,^‡

PMCID: PMC3201476 PMID: 22058827

Abstract

In the title compound, C₂₆H₂₆ClNO₄, the central phenylene ring is oriented at dihedral angles of 5.06 (14) and 64.14 (5)°, respectively, with respect to aromatic rings of the benzyl and chlorophenyl groups. The centroid–centroid distance between the central phenylene ring and the aromatic ring of the benzyl group is 4.028 (12) Å. In the crystal, intermolecular N—H⋯O hydrogen bond generate a chain along (100). C—H⋯O interactions are also observed.

Related literature

For background to the drug bezafibrate [systematic name: 2-(4-{2-[(4-chlorobenzoyl)amino]ethyl}phenoxy)-2-methylpropanoic acid], commonly used against hyperlipidemia, which has been found to decrease mRNA levels in adipocyte markers and increase fatty acid oxidation in primary cultures of adipocytes, see: Cabrero et al. (2001 ▶).

Experimental

Crystal data

C₂₆H₂₆ClNO₄
M _r = 451.93
Triclinic,
a = 5.5480 (1) Å
b = 11.0716 (3) Å
c = 18.9641 (5) Å
α = 82.247 (1)°
β = 86.915 (1)°
γ = 85.674 (1)°
V = 1149.81 (5) Å³
Z = 2
Mo Kα radiation
μ = 0.20 mm⁻¹
T = 296 K
0.41 × 0.19 × 0.13 mm

Data collection

Bruker Kappa APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2007 ▶) T _min = 0.923, T _max = 0.975
26646 measured reflections
5750 independent reflections
4355 reflections with I > 2σ(I)
R _int = 0.019

Refinement

R[F ² > 2σ(F ²)] = 0.049
wR(F ²) = 0.142
S = 1.05
5745 reflections
294 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.30 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶) and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811039249/ng5234sup1.cif

e-67-o2803-sup1.cif^{(22.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811039249/ng5234Isup2.hkl

e-67-o2803-Isup2.hkl^{(275.6KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811039249/ng5234Isup3.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
N1—H1N⋯O4ⁱ	0.848 (19)	2.540 (19)	3.350 (2)	160.3 (18)
C17—H17B⋯O4ⁱⁱ	0.97	2.57	3.532 (3)	172
C7—H7B⋯O2ⁱ	0.97	2.59	3.398 (3)	141

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

Acknowledgments

The authors acknowledge the Higher Education Commission of Pakistan for providing the grants under the project to strengthen the Materials Chemistry Laboratory.

supplementary crystallographic information

Comment

Among the fibrate family of drugs bezafibrate (2-(4-{2-[(4-chlorobenzoyl)amino]ethyl}phenoxy)-2-methylpropanoic acid) is well known for its use against hyperlipidemia. The drug has also found effective in decreases of mRNA levels in adipocyte markers and increases fatty acid oxidation in primary culture of adipocytes (Cabrero et al., 2001). Here in, we report the crystal structure of benzyl ester of bezafibrate (I).

The crysral structure of title compound consist of three aromatic rings. The aromatic ring (C1—C6) is oriented at dihedral angle of 5.06 (14)° with respect to other ring (C10—C15) and the centroid distance between these two rings is 4.028 Å. The chloro benzene ring (C19—C24) is twisted at dihedral angle of 64.14 (5)° with respect to the ring (C10—C15). The molecule is connected through only intermolecular hydrogen bonding of N—H···O and C—H···O type and generate an infinite chain along base vector (1 0 0).

Experimental

A weighed amount of bezafibrate (0.40 g, 0.001105 moles) was dissolved in DMF (10 cm³) taken in a 100 ml conical flask. Then sodium hydride (0.0530 g; 0.002210 moles) washed with n-hexane was added in reaction flask. The reaction mixture was stirred for about 1 hr at an ambient temperature until the NaH disappeared. An equivalent amount of benzyl chloride (0.14 g, 0.001105 moles) was then added in the reaction mixture and stirred until the solution became clear. The reaction was monitored after regular intervals by TLC. After the consumption of benzyl chloride, the reaction mixture was poured over the crushed ice. The crude precipitates were filtered, washed with distilled water and crystallized with methanol to get colorless crystals. Melting point of product was noted as 374K.