Ethyl 1-(4-chloro­phen­yl)-3-[1-(4-meth­oxy­phen­yl)-4-oxo-3-phenyl­azetidin-2-yl]-2-nitro-2,3,10,10a-tetra­hydro-1H,5H-pyr­rolo[1,2-b]isoquinoline-10a-carboxyl­ate

S Sundaresan; P Ramesh; N Arumugam; R Raghunathan; M N Ponnuswamy

doi:10.1107/S1600536808030961

. 2008 Sep 30;64(Pt 10):o2042. doi: 10.1107/S1600536808030961

Ethyl 1-(4-chlorophenyl)-3-[1-(4-methoxyphenyl)-4-oxo-3-phenylazetidin-2-yl]-2-nitro-2,3,10,10a-tetrahydro-1H,5H-pyrrolo[1,2-b]isoquinoline-10a-carboxylate

S Sundaresan ^a, P Ramesh ^b, N Arumugam ^c, R Raghunathan ^c, M N Ponnuswamy ^a,^*

PMCID: PMC2959299 PMID: 21201234

Abstract

In the title compound, C₃₇H₃₄ClN₃O₆, the pyrrolidine and piperidine rings adopt envelope and boat conformations, respectively. The β-lactam ring is planar and forms dihedral angles of 21.3 (2) and 73.9 (2)°, respectively, with the attached methoxyphenyl and phenyl rings. Intramolecular C—H⋯O and C—H⋯N hydrogen bonds are observed. Centrosymmetrically related molecules are linked together by weak C—H⋯O hydrogen bonds to form dimers.

Related literature

For the biological properties of β-lactam derivatives, see: Borthwick et al. (1998 ▶); Brakhage (1998 ▶); Burnett (1994 ▶); Han et al. (1995 ▶); Vaccaro & Davis (1998 ▶); Vaccaro et al. (1998 ▶). For puckering and asymmetry parameters, see: Cremer & Pople (1975 ▶); Nardelli (1983 ▶).

Experimental

Crystal data

C₃₇H₃₄ClN₃O₆
M _r = 652.12
Monoclinic,
a = 9.1723 (2) Å
b = 18.0452 (4) Å
c = 19.7475 (5) Å
β = 100.638 (1)°
V = 3212.35 (13) Å³
Z = 4
Mo Kα radiation
μ = 0.17 mm⁻¹
T = 293 (2) K
0.22 × 0.20 × 0.17 mm

Data collection

Bruker kappa APEXII area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2001 ▶) T _min = 0.963, T _max = 0.971
30325 measured reflections
5582 independent reflections
3760 reflections with I > 2σ(I)
R _int = 0.034

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.135
S = 1.02
5582 reflections
426 parameters
H-atom parameters constrained
Δρ_max = 0.34 e Å⁻³
Δρ_min = −0.27 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: SAINT (Bruker, 2004 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2003 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808030961/ci2676sup1.cif

e-64-o2042-sup1.cif^{(30.6KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808030961/ci2676Isup2.hkl

e-64-o2042-Isup2.hkl^{(267.8KB, 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
C2—H2A⋯N27	0.97	2.53	3.196 (3)	126
C24—H24⋯O3	0.98	2.58	3.186 (3)	121
C25—H25⋯O6ⁱ	0.98	2.60	3.479 (3)	150
C35—H35⋯O5	0.93	2.60	3.157 (3)	119
C40—H40A⋯O4ⁱ	0.96	2.49	3.232 (4)	134

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Symmetry code: (i) Inline graphic .

Acknowledgments

SS thanks Dr Babu Varghese, SAIF, IIT Madras, Chennai, India, for his help with the data collection.

supplementary crystallographic information

Comment

β-Lactams have been shown to exhibit high antibacterial activity. 1,3,4-Trisubstituted β-lactams are potent cholesterol absorption inhibitors (Vaccaro & Davis, 1998; Vaccaro et al., 1998; Burnett, 1994), human cylomegalonims and protease inhibitors (Borthwick et al., 1998) and thrombin inhibitors (Han et al., 1995). The most commonly used β-lactam antibiotics for the therapy of infectious diseases are penicillin and cephalosporins (Brakhage, 1998). In view of these importance, the crystal structure determination of the title compound was carried out.

The pyrrolidine and piperidine rings in the molecule adopt envelope and boat conformations, respectively. The puckering parameters (Cremer & Pople, 1975) and the asymmetry parameter (Nardelli, 1983) for the pyrrolidine ring are q₂ = 0.292 (3) Å, π = 99.6 (5)° and Δ_S(C12) = 4.4 (3)°, and for the piperidine ring q₂ = 0.630 (3) Å, q₃ = 0.004 (3) Å, π = 61.2 (2)° and Δ_S(C2) = Δ_S(C9) = 1.2 (2)°. The ethylcarboxylate group adopts an extended conformation. The sum of angles at atom N27 of the β-lactam ring system [356.9°] is in accordance with sp² hybridization. The β-lactam ring is planar and the keto O5 atom deviates from this plane by -0.005 (2) Å. The methoxyphenyl (C34—C39) and (C28—C33) phenyl rings form dihedral angles of 21.3 (2) and 73.9 (2)°, respectively, with the β-lactam ring. C—H···O and C—H···N types of intramolecular hydrogen bonds are observed.

In the crystal structure, atoms C25 and C40 of the molecule at (x, y, z) donate one proton each to atoms O6 and O4 of the molecule at (- x, 1 - y, -z), forming a cyclic centrosymmetric dimer.

Experimental

To a stirred solution of 5-[1'-N-(p-methoxyphenyl-azetidine-2'-one]-4-nitro-3-(p-chloro)-phenyl-2-ethoxycarbonyl-2-benzyl-pyrrlolidine (1 mmol) in dry chloroform (20 ml) para formaldehyde (1 mmol) and then trifluroacetic acid (0.1 mmol) were added at room temperature. After completion of the reaction, the mixture was washed with water and dried over. The solvent was removed under the reduced pressure and the crude product was subjected to column chromatography with hexane-ethyl acetate (9:1) to obtain pure cyclized product. The compound was recrystallized from ethyl acetate