Methyl 12-hydroxy-10-[1-(4-meth­oxy­phen­yl)-2-oxo-3-phen­oxy­azetidin-4-yl]-11-oxa-3-aza­hexa­cyclo­[11.7.1.02,9.02,12.03,7.017,21]henicosa-1(20),13,15,17(21),18-penta­ene-9-carboxyl­ate

Sivasubramanian Suhitha; Thothadri Srinivasan; Raju Rajesh; Raghavachary Raghunathan; Devadasan Velmurugan

doi:10.1107/S1600536812045795

. 2012 Nov 10;68(Pt 12):o3329–o3330. doi: 10.1107/S1600536812045795

Methyl 12-hydroxy-10-[1-(4-methoxyphenyl)-2-oxo-3-phenoxyazetidin-4-yl]-11-oxa-3-azahexacyclo[11.7.1.0^2,9.0^2,12.0^3,7.0^17,21]henicosa-1(20),13,15,17(21),18-pentaene-9-carboxylate

Sivasubramanian Suhitha ^a, Thothadri Srinivasan ^a, Raju Rajesh ^b, Raghavachary Raghunathan ^b, Devadasan Velmurugan ^a,^*

PMCID: PMC3588933 PMID: 23476169

Abstract

In the title compound, C₃₇H₃₄N₂O₇, both pyrrolidine rings adopt envelope conformations. The β-lactam ring is close to planar (r.m.s. deviation = 0.0395 Å) and makes a dihedral angle of 83.35 (15)° with the furan ring. The O atom attached to the β-lactam ring deviates by 0.187 (2) Å from the mean plane of the ring. The β-lactam ring makes dihedral angles of 14.90 (15) and 27.72 (17)° with the methoxyphenyl and phenyl rings, respectively. The crystal packing features C—H⋯O hydrogen bonds.

Related literature

For general background and therapeutic applications of β-lactams, see: Banik & Becker (2000 ▶); Brakhage (1998 ▶). For a related structure, see: Sundaramoorthy et al. (2012 ▶).

Experimental

Crystal data

C₃₇H₃₄N₂O₇
M _r = 618.66
Orthorhombic,
a = 9.6545 (11) Å
b = 20.363 (2) Å
c = 31.804 (3) Å
V = 6252.5 (11) Å³
Z = 8
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 293 K
0.35 × 0.30 × 0.25 mm

Data collection

Bruker SMART APEXII area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.969, T _max = 0.978
26528 measured reflections
5614 independent reflections
3210 reflections with I > 2σ(I)
R _int = 0.062

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.127
S = 1.00
5614 reflections
421 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.14 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT (Bruker, 2008 ▶); 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, 2012) ▶; software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 ▶).

Supplementary Material

Click here for additional data file.^{(41.7KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812045795/pv2604sup1.cif

e-68-o3329-sup1.cif^{(41.7KB, cif)}

Click here for additional data file.^{(269.4KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812045795/pv2604Isup2.hkl

e-68-o3329-Isup2.hkl^{(269.4KB, hkl)}

Click here for additional data file.^{(12.2KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536812045795/pv2604Isup3.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
C33—H33⋯O4ⁱ	0.93	2.49	3.409 (3)	173
C37—H37C⋯O7ⁱⁱ	0.96	2.53	3.217 (3)	128

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

Acknowledgments

The authors thank the TBI X–ray facility, CAS in Crystallography and Biophysics, University of Madras, India for the data collection. TS thanks the DST for an Inspire fellowship.

supplementary crystallographic information

Comment

The role of β-lactam antibiotics is well known (Banik & Becker, 2000). The most commonly used β-lactam antibiotics for the therapy of infectious diseases are penicillin and cephalosporin (Brakhage, 1998). In view of potential applications of β-lactam derivatives, we have determined the crystal structure of the title compound and report it in this article.

In the title compound (Fig. 1), both pyrrolidine rings N2/C18–C20/C24 and N2/C20–C23 adopt C20- and C23-envelope conformations, respectively. The β lactam ring (N1/C8–C10) is essentially planar (rmsd = 0.0395 Å) and the O2 atom attached to it deviates by -0.187 (2)Å from its least-squares plane. The β lactam ring makes dihedral angles 14.90 (15)° and 27.72 (17)° with the methoxy phenyl and unsubstitued phenyl rings, respectively. The dihedral angle between the β lactam ring and the furan ring (O6/C17/C18/C24/C25) is 83.35 (15)°. The furan ring makes dihedral angles 81.84 (12)° and 72.24 (15)° with the two pyrrolidine rings. The dihedral angle between the furan ring and the cyclopentane ring (C24/C25/C26/C27/C28) is 71.56 (12)°. The bond distances and angles in the title compound agree very well with the corresponding bond distances and angles reported in a closely related compound (Sundaramoorthy et al., 2012). The packing of the crystal structure is stabilised by intermolecular C—H···O hydrogen bonds (Tab. 1 & Fig. 2).

Experimental

A solution of methyl 2-(hydroxy(1-(4-methoxyphenyl)-4-oxo-3-phenoxyazetidin -2-yl)methyl)acrylate (1.0 equiv.), acenaphthequinone (1.1 equiv.) and proline (1.1 equiv.) were refluxed in dry methanol. Completion of the reaction was evidenced by TLC analysis. The solvent was then removed under vacuum, diluted in dichloromethane and washed with brine and water. The organic layer was separated and removed and the residue subjected to column chromatography using ethyl acetate and hexane as an eluent (1:4) afforded the cycloadduct. The product was dissolved in chloroform and heated for two minutes. The resulting solution was subjected to crystallization by slow evaporation of the solvent for 48 hours resulting in the formation of single crystals.