4-Hydr­oxy-5-(4-methoxy­phen­yl)pyrrolidin-2-one

M Fazli Mohammat; Zurina Shaameri; A Sazali Hamzah; Hoong-Kun Fun; Suchada Chantrapromma

doi:10.1107/S1600536808003899

. 2008 Feb 13;64(Pt 3):o578–o579. doi: 10.1107/S1600536808003899

4-Hydroxy-5-(4-methoxyphenyl)pyrrolidin-2-one

M Fazli Mohammat ^a, Zurina Shaameri ^a, A Sazali Hamzah ^a, Hoong-Kun Fun ^b,^*, Suchada Chantrapromma ^c,^‡

PMCID: PMC2960887 PMID: 21201918

Abstract

In the title compound, C₁₁H₁₃NO₃, the pyrrolidin-2-one ring is in an envelope conformation with the hydroxyl and 4-methoxyphenyl substituents mutually cis. The methoxy group is slighty twisted away from the mean plane of the attached benzene ring. The molecules are arranged into screw chains along the c axis. These chains are interconnected via intermolecular O—H⋯O and N—H⋯O hydrogen bonds into sheets parallel to the ac plane. The crystal structure is further stabilized by weak intermolecular C—H⋯O and C—H⋯π interactions.

Related literature

For details of ring conformations, see: Cremer & Pople (1975 ▶). For the biological properties of pyrrolidine alkaloids, see for example: Iida et al. (1986 ▶); Royles (1996 ▶). For the syntheses of compounds containing the tetramic acid ring, see for example: Chandrasekhar et al. (2006 ▶); Gurjar et al. (2006 ▶); Yoda et al. (1996 ▶). For bond-length data, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C₁₁H₁₃NO₃
M _r = 207.22
Orthorhombic,
a = 11.9862 (6) Å
b = 11.6251 (6) Å
c = 7.1539 (4) Å
V = 996.83 (9) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 100.0 (1) K
0.43 × 0.20 × 0.17 mm

Data collection

Bruker SMART APEX2 CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2005 ▶) T _min = 0.958, T _max = 0.983
8681 measured reflections
1562 independent reflections
1218 reflections with I > 2σ(I)
R _int = 0.066

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.109
S = 1.09
1562 reflections
145 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.24 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: APEX2; data reduction: SAINT (Bruker, 2005 ▶); program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2003 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808003899/sj2463sup1.cif

e-64-0o578-sup1.cif^{(16.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808003899/sj2463Isup2.hkl

e-64-0o578-Isup2.hkl^{(77KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

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

Cg1 is the centroid of the C5–C10 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N1⋯O2ⁱ	0.88 (4)	2.05 (4)	2.917 (3)	167 (4)
O2—H1O2⋯O3ⁱⁱ	0.90 (4)	1.98 (4)	2.800 (2)	152 (3)
C3—H3A⋯O1ⁱⁱⁱ	0.98	2.33	3.193 (3)	146
C11—H11A⋯O1^iv	0.96	2.49	3.395 (3)	158
C6—H6A⋯Cg1^v	0.93	2.81	3.514 (3)	133
C9—H9A⋯Cg1^vi	0.93	2.68	3.554 (3)	157

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

Acknowledgments

The authors acknowledge the generous support of both the Universiti Teknologi MARA and Universiti Sains Malaysia as well as the financial support of the Ministry of Science, Technology and Innovation (E-Science grant No. SF0050–02-01–01). HKF and SC thank the Malaysian Government and Universiti Sains Malaysia for the Scientific Advancement Grant Allocation (SAGA) grant No. 304/PFIZIK/653003/A118.

supplementary crystallographic information

Comment

Many naturally occurring compounds containing a tetramic acid ring system such as radicamine, fuligorobin and codonopsinine possess potent antibiotic, antiviral, antifungal, cytotoxic (Royles, 1996) as well as hypotensive activities (Iida et al., 1986). The title compound, C₁₁H₁₃NO₃, can act as an essential intermediate in the synthesis of such tetramic acid derivatives (Chandrasekhar et al., 2006; Gurjar et al., 2006; Yoda et al., 1996), which eventually can be used as a template in multi-step syntheses of biologically active natural products. We have synthesized the title compound (I) and its structure is reported here, Fig. 1.

In (I), the pyrrolidine-2-one ring adopts an envelope conformation with atom C3 displaced from the C1/C2/C3/N1 plane by 0.219 (3) Å, and with puckering parameters (Cremer & Pople, 1975) Q = 0.357 (3) Å and φ = 117.9 (4)°. The bond angles around C1 atom are indicative of sp² hybridization. The hydroxyl and 4-methoxyphenyl substituents are attached to the pyrrolidin-2-one ring at atom C3 and C4, respectively and is in cis-configuration (Fig. 1). The methoxy group is slightly twisted away from the mean plane of the phenyl ring as shown by the torsion angle C11–O3–C8–C7 = -5.2 (4)° All bond lengths and angles show normal values (Allen et al., 1987)

In the crystal packing of the title compound (Fig. 2), the molecules are arranged into screw chains along the c direction. These chains are interconnected via intermolecular O—H···O and N—H···O hydrogen bonds (Table 1) into sheets parallel to the ac plane. The crystal is further stabilized by weak intermolecular C—H···O and C—H···π interactions; C6—H6A···Cg₁ (symmetry code: 3/2 - x, y, 1/2 + z) and C9—H9A··· Cg₁ (symmetry code: 2 - x, 1 - y, -1/2 + z), Cg₁ is the centroid of C5–C10 phenyl ring.

Experimental

The synthetic approach to the title compound began with the esterification of p-hydroxyphenylglycine (10.00 g, 60.10 mmol) and thionyl chloride in methanol to give the ester product (10.30 g, 95%). Amine protection (10.00 g, 54.9 mmol) was then carried out using tert-butoxycarbonyl (Boc₂O) and triethylamine (Et₃N) in tetrahydrofuran (THF) to give the N-Boc protected product in 85% yield (13.12 g). The hydroxyl functional group (13.01 g, 46.66 mmol) was protected by converting it to the methyl ether using potassium carbonate and methyl iodide (12.72 g, 93%). Condensation between the N-Boc methyl ester (8.30 g, 28.30 mmol) and methyl malonyl chloride in equimolar amounts furnished an intermediate diester (10.60 g, 95%). Dieckmann cyclization of this intermediate diester (5.50 g, 13.99 mmol) with potassium tert-butoxide (t-BuOK) in toluene gave the carbon skeleton β,β diketoester in 45% yield (1.65 g). Demethoxycarbonylation of the β,β diketoester (0.30 g, 1.1 mmol) was successfully carried out by refluxing in 50 ml acetonitrile to give the basic pyrrolidinone ring skeleton (0.23 g, 99%). Reduction of this diketone (0.16 g, 0.77 mmol) was then carried out in sodium borohydride/methanol at 273 K to give the title compound (0.04 g, 24%). Single crystals suitable for X-ray structure determination were obtained by slow evaporation of an ethyl acetate-petroleum ether (2:1 v/v) solution after several days.