1-(Morpholin-4-yl)-4-(2-nitro­phen­yl)spiro­[azetidine-3,9′-xanthen]-2-one

Zeliha Atioğlu; Mehmet Akkurt; Aliasghar Jarrahpour; Roghayeh Heiran; Namık Özdemir

doi:10.1107/S1600536814013464

. 2014 Jun 14;70(Pt 7):o772–o773. doi: 10.1107/S1600536814013464

1-(Morpholin-4-yl)-4-(2-nitrophenyl)spiro[azetidine-3,9′-xanthen]-2-one

Zeliha Atioğlu ^a, Mehmet Akkurt ^b,^*, Aliasghar Jarrahpour ^c, Roghayeh Heiran ^c, Namık Özdemir ^d

PMCID: PMC4120553 PMID: 25161561

Abstract

In the title compound, C₂₂H₂₁N₃O₅, the β-lactam (azetidin-2-one) ring is nearly planar [maximum deviation = 0.010 (1) Å] and makes dihedral angles of 69.22 (5), 55.32 (5) and 89.42 (4)° with the least-squares planes formed by the four C atoms of the morpholine ring, which adopts a chair conformation, the benzene ring and the xanthene ring system, respectively. In the crystal, C—H⋯O hydrogen-bond contacts connect neighbouring molecules into infinite zigzag chains running parallel to the b axis.

Related literature

For general background to β-lactams, see: Arya et al. (2014 ▶); Ebrahimi & Jarrahpour (2014 ▶); Singh & Sudheesh (2014 ▶); Zeng et al. (2014 ▶); Zarei et al. (2013 ▶); Jarrahpour & Ebrahimi (2010 ▶); Mehta et al. (2010 ▶); Singh et al. (2011 ▶). For geometric analysis, see: Cremer & Pople (1975 ▶); Nardelli (1995 ▶). For similar structures, see: Akkurt et al. (2008a ▶,b ▶); Yalçın et al. (2009 ▶); Çelik et al. (2009a ▶,b ▶, 2014 ▶). graphic file with name e-70-0o772-scheme1.jpg

Experimental

Crystal data

C₂₅H₂₁N₃O₅
M _r = 443.45
Monoclinic,
a = 9.4272 (5) Å
b = 18.8525 (8) Å
c = 12.4345 (6) Å
β = 95.443 (4)°
V = 2199.97 (18) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 296 K
0.50 × 0.44 × 0.40 mm

Data collection

Stoe IPDS 2 diffractometer
Absorption correction: integration (X-RED32; Stoe & Cie, 2002 ▶) T _min = 0.956, T _max = 0.974
13801 measured reflections
5223 independent reflections
3421 reflections with I > 2σ(I)
R _int = 0.195

Refinement

R[F ² > 2σ(F ²)] = 0.045
wR(F ²) = 0.098
S = 1.00
5223 reflections
299 parameters
H-atom parameters constrained
Δρ_max = 0.15 e Å⁻³
Δρ_min = −0.11 e Å⁻³

Data collection: X-AREA (Stoe & Cie, 2002 ▶); cell refinement: X-AREA; data reduction: X-RED32 (Stoe & Cie, 2002 ▶); program(s) used to solve structure: SHELXS2013 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▶); software used to prepare material for publication: WinGX (Farrugia, 2012 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536814013464/sj5411sup1.cif

e-70-0o772-sup1.cif^{(32.1KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814013464/sj5411Isup2.hkl

e-70-0o772-Isup2.hkl^{(286.4KB, hkl)}

Click here for additional data file.^{(8.5KB, cml)}

Supporting information file. DOI: 10.1107/S1600536814013464/sj5411Isup3.cml

CCDC reference: 1007508

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C3—H3⋯O3ⁱ	0.98	2.55	3.5310 (16)	174
C6—H6⋯O1ⁱⁱ	0.93	2.56	3.3828 (17)	148
C11—H11⋯O2ⁱⁱⁱ	0.93	2.50	3.389 (2)	159

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

Acknowledgments

The authors acknowledge the Faculty of Arts and Sciences, Ondokuz Mayıs University, Turkey, for the use of the Stoe IPDS 2 diffractometer (purchased under grant F.279 of the University Research Fund).

supplementary crystallographic information

S1. Comment

2-Azetidinones, commonly known as β-lactams, constitute a most important class of antibiotics in both human and veterinary medicine (Arya et al., 2014; Singh & Sudheesh, 2014; Zeng et al., 2014; Zarei et al., 2013). In addition to their well recognized antibiotic activity, β-lactams exhibit various other biological activities such as thrombin, human, HIV-1 protease, human leukocyte elastase, cholesterol absorption inhibition and antifungal, anticancer, antidiabetic and potential antimalarial properties (Mehta et al., 2010; Singh et al., 2011; Ebrahimi & Jarrahpour, 2014). The synthesis and chemistry of spiro-fused 2-azetidinones has grown steadily over the years and many newly synthesized spiro-fused 2-azetidinones have been reported in the literature (Jarrahpour & Ebrahimi, 2010; Singh et al., 2011).

The β-lactam (azetidin-2-one) ring of the title compound (I, Fig. 1) is nearly planar, with a maximum deviation of -0.010 (1) Å for C1 from the mean plane. Atom O1 lies almost in the β-lactam plane, with a deviation of 0.069 (1) Å. The β-lactam ring makes a dihedral angle of 55.32 (5)° with the benzene ring C16—C21.

The xanthene ring system is V-shaped, with a dihedral angle between the (C4–C9) and (C10–C15) benzene rings of 19.07 (7)°. Its central ring, C2/C4/C9/O2/C10/C15, is not planar, with puckering parameters: Q_T = 0.2438 (13) Å, θ = 98.1 (3)° and φ = 2.0 (3)° (Cremer & Pople, 1975).

The mean plane of the xanthene ring system forms dihedral angles of 89.42 (4), 43.44 (3) and 22.80 (5)° (Nardelli, 1995), with the β-lactam ring, the benzene ring (C16–C21) and the least-squares plane formed by the four C atoms of the morpholine ring (N2/O5/C22–C25), respectively.

The bond lengths and angles in (I) are comparable with those observed in similar compounds that we have reported previously (Akkurt et al., 2008a,b; Çelik et al., 2009a,b; Çelik et al., 2014; Yalçın et al., 2009).

In the crystal structure, molecules are linked by C—H···O hydrogen contacts (Table 1) into infinite zigzag chains running parallel to the b axis. Figs. 2, 3 and 4 show the projections along the a, b and c axes of the crystal packing of (I), respectively.

S2. Experimental

A mixture of N-(2-nitrobenzylidene)morpholin-4-amine (0.24 g, 1.00 mmol), 9H-xanthen-9-carboxylic acid (0.34 g, 1.50 mmol), tosyl chloride (0.28 g, 1.50 mmol) and triethylamine (0.25 g, 2.50 mmol) was stirred in dry CH₂Cl₂ at room temperature. After 24 h, the mixture was washed with HCl 1 M (20 ml), saturated NaHCO₃ (20 ml), brine (20 ml), dried over Na₂SO₄ and the solvent was evaporated to give the crude product which was purified by column chromatography (eluent 2:1 n-hexane/EtOAc) as light yellow crystalline solid (yield 41%). mp: 471- 473 K. IR (KBr, cm^-1): 1759 (CO, β-lactam), 1346, 1523 (NO2). ¹H-NMR (CDCl3) δ (p.p.m.): 3.52–3.76 (CH₂ morpholine ring, m, 8H), 5.38 (H-3, s, 1H), 6.62–8.10 (ArH, m, 12H). ¹³C-NMR (CDCl₃) δ (p.p.m.): 53.8 (CH₂—N), 61.4 (C-3), 66.8 (CH₂—O), 73.9 (C-4), 114.9, 116.8, 116.9, 120.5, 122.2, 123.9, 124.8, 125.1, 127.8, 128.9, 129.3, 129.5, 131.1, 133.1, 147.5, 152.1, 152.3 (aromatic carbons), 169.7 (CO, β-lactam). Anal. calcd for C₂₅H₂₁N₃O₅: C 67.71, H 4.77, N 9.48%. Found: C 67.80, H 4.66, N 9.45%.