supplementary materials


is5318 scheme

Acta Cryst. (2013). E69, o1757-o1758    [ doi:10.1107/S1600536813030390 ]

Ethyl 4-anilino-2-methyl-5-oxo-1-phenyl-2,5-di­hydro-1H-pyrrole-2-carboxyl­ate

M. Akkurt, S. K. Mohamed, M. A. A. Elremaily, F. Santoyo-Gonzalez and M. R. Albayati

Abstract top

In the title compound, C20H20N2O3, the central 2,5-di­hydro-1H-pyrrole ring [r.m.s. deviation = 0.014 (1) Å] is oriented at dihedral angles of 77.81 (6) and 25.33 (6)°, respectively, to the attached phenyl ring and the aniline phenyl ring. An intra­molecular N-H...O hydrogen bond occurs. In the crystal, mol­ecules are linked through pairs of N-H...O hydrogen bonds, forming inversion dimers with an R22(10) ring motif. Two weak C-H...[pi] inter­actions are also observed.

Comment top

Dihydropyrrolone compounds have been reported to display importantant biological activities with better hydrolytic stability. Dihydropyrrolones are known as lactams such as Pulchellalactam, which inhibits CD45 protein, a receptor-like transmembrane protein tyrosine phosphatase, and therefore could be of therapeutic value targeting autoimmune and chronic anti-inflammatory diseases (Alvi et al., 1998; Li et al., 2002). γ-Lactam PI-091 has been reported to display potent activity against platelet aggregation (Shiraki et al., 1996) and jatropham has been proven to be an antitumor alkaloid (Mase et al., 1999; Wiedhopf et al., 1973). Numerous methods to synthesize pyrrol-2-ones have been reported in the literature and the majority of these require multiple steps with low yields. However, one direct conversion strategy has been demonstrated in synthesis of γ-lactam PI-091 (Shiraki et al., 1996). Based on this concept, we herein report the synthesis and crystal structure of the title compound.

In the title compound, the central 2,5-dihydro-1H-pyrrole ring (N1/C4–C7) makes dihedral angles of 77.81 (6) and 25.33 (6)° with the two phenyl rings (C8–C13 and C15–C20), respectively (Fig. 1). All bond lengths and bond angles are normal (Allen et al., 1987).

In the crystal structure, pairs of adjacent molecules are linked through intermolecular N—H···O hydrogen bonds (Table 1), forming inversion dimers with R22(10) ring motifs (Bernstein et al., 1995; Fig. 2). Two weak C—H···π interactions are observed.

Related literature top

For the synthesis of pyrrolone compounds, see: Shiraki et al. (1996). For the biological activity of lactams, see: Alvi et al. (1998); Li et al. (2002); Mase et al. (1999); Wiedhopf et al. (1973). For bond-length data, see: Allen et al. (1987). For hydrogen-bond motifs, see: Bernstein et al. (1995).

Experimental top

In a 50 ml round bottom flask, a mixture of 186 mg of aniline (2 mmol) and 232 mg of ethyl pyruvate (2 mmol) were taken in presence of 8 mol % of Fe3O4 nanoparticles in 15 ml ethanol/water (v/v) or glacial acetic acid was stirred well and irradited in microwave for 30 minutes. The progress of the reaction was monitored by TLC. After completion, the solid product was filtered off, washed with water and recrystallized from ethanol. Single crystals suitable for X-ray analysis were obtained by slow evaporation method of an ethanolic solution of the title compound at room temperature.

Refinement top

The C-bound H-atoms were positioned geometrically, with C—H = 0.95, 0.98 and 0.99 Å for aromatic, methyl and methylene H, respectively, and allowed to ride on their respective parent atoms, with Uiso(H) = xUeq(C), where x = 1.5 for methyl H, and x = 1.2 for the other H atoms. The N-bound H-atom was located in a difference Fourier map and refined freely.

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: WinGX (Farrugia, 2012) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound with the atom numbering scheme. Displacement ellipsoids for non-H atoms are drawn at the 50% probability level.
[Figure 2] Fig. 2. View of the molecular packing and hydrogen bonding (dotted lines) of the title compound along the a axis. H atoms not involved in H bonding are omitted for clarity.
Ethyl 4-anilino-2-methyl-5-oxo-1-phenyl-2,5-dihydro-1H-pyrrole-2-carboxylate top
Crystal data top
C20H20N2O3Z = 2
Mr = 336.38F(000) = 356
Triclinic, P1Dx = 1.309 Mg m3
Hall symbol: -P 1Cu Kα radiation, λ = 1.54178 Å
a = 5.9071 (6) ÅCell parameters from 9891 reflections
b = 11.3474 (12) Åθ = 3.5–72.5°
c = 14.1716 (14) ŵ = 0.72 mm1
α = 111.467 (2)°T = 100 K
β = 101.113 (3)°Cubs, colourless
γ = 95.328 (3)°0.34 × 0.29 × 0.21 mm
V = 853.45 (15) Å3
Data collection top
Bruker APEXII CCD
diffractometer
3367 independent reflections
Radiation source: sealed tube3156 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.035
φ and ω scansθmax = 72.6°, θmin = 3.5°
Absorption correction: multi-scan
(SADABS; Bruker, 2005)
h = 77
Tmin = 0.783, Tmax = 0.860k = 1414
18887 measured reflectionsl = 1717
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.037 w = 1/[σ2(Fo2) + (0.0487P)2 + 0.3108P] WHERE P = (Fo2 + 2Fc2)/3
wR(F2) = 0.096(Δ/σ)max < 0.001
S = 1.04Δρmax = 0.32 e Å3
3367 reflectionsΔρmin = 0.17 e Å3
232 parameters
Crystal data top
C20H20N2O3γ = 95.328 (3)°
Mr = 336.38V = 853.45 (15) Å3
Triclinic, P1Z = 2
a = 5.9071 (6) ÅCu Kα radiation
b = 11.3474 (12) ŵ = 0.72 mm1
c = 14.1716 (14) ÅT = 100 K
α = 111.467 (2)°0.34 × 0.29 × 0.21 mm
β = 101.113 (3)°
Data collection top
Bruker APEXII CCD
diffractometer
3367 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2005)
3156 reflections with I > 2σ(I)
Tmin = 0.783, Tmax = 0.860Rint = 0.035
18887 measured reflectionsθmax = 72.6°
Refinement top
R[F2 > 2σ(F2)] = 0.037H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.096Δρmax = 0.32 e Å3
S = 1.04Δρmin = 0.17 e Å3
3367 reflectionsAbsolute structure: ?
232 parametersAbsolute structure parameter: ?
0 restraintsRogers parameter: ?
Special details top

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F2 for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The observed criterion of F2 > σ(F2) is used only for calculating -R-factor-obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.25546 (15)0.15386 (9)0.65884 (6)0.0278 (3)
O20.56211 (15)0.05034 (9)0.64918 (7)0.0284 (3)
O30.76449 (14)0.06561 (7)0.91641 (6)0.0245 (2)
N10.46752 (16)0.03089 (9)0.80378 (7)0.0188 (2)
N20.88879 (16)0.20496 (9)1.01844 (7)0.0198 (3)
C10.0420 (2)0.20985 (14)0.52705 (10)0.0347 (4)
C20.2691 (2)0.17212 (13)0.56318 (10)0.0321 (4)
C30.41016 (19)0.09001 (10)0.69110 (8)0.0202 (3)
C40.37187 (18)0.07904 (10)0.79249 (8)0.0185 (3)
C50.53286 (19)0.19157 (10)0.88320 (8)0.0186 (3)
C60.69734 (18)0.14945 (10)0.93602 (8)0.0174 (3)
C70.65363 (18)0.00576 (10)0.88708 (8)0.0179 (3)
C80.38731 (19)0.16263 (10)0.73392 (8)0.0195 (3)
C90.5140 (2)0.22001 (12)0.66212 (11)0.0326 (4)
C100.4452 (2)0.34902 (13)0.59739 (12)0.0386 (4)
C110.2505 (2)0.42071 (11)0.60400 (10)0.0279 (3)
C120.1241 (2)0.36303 (11)0.67556 (9)0.0262 (3)
C130.1920 (2)0.23334 (11)0.74107 (9)0.0241 (3)
C140.11531 (19)0.07087 (11)0.79771 (9)0.0235 (3)
C150.97223 (19)0.33611 (10)1.07830 (8)0.0189 (3)
C161.2078 (2)0.37409 (11)1.13371 (9)0.0229 (3)
C171.2957 (2)0.50213 (12)1.19811 (10)0.0258 (3)
C181.1522 (2)0.59446 (11)1.20871 (10)0.0263 (3)
C190.9195 (2)0.55647 (11)1.15397 (10)0.0273 (3)
C200.8280 (2)0.42848 (11)1.08897 (9)0.0233 (3)
H1A0.088200.140300.511900.0520*
H1B0.043400.225600.463600.0520*
H1C0.022200.288400.582000.0520*
H2A0.289600.091500.509300.0390*
H2B0.402800.240600.577300.0390*
H2N0.981 (3)0.1504 (14)1.0297 (11)0.025 (3)*
H50.519400.279300.900300.0220*
H90.647400.171000.657300.0390*
H100.532000.388600.548200.0460*
H110.203800.509300.559400.0340*
H120.009600.412200.680000.0310*
H130.105200.193700.790200.0290*
H14A0.018200.000300.734800.0350*
H14B0.064700.152100.802100.0350*
H14C0.098500.054900.859700.0350*
H161.307600.312001.127200.0270*
H171.455800.527201.235500.0310*
H181.213200.682201.252800.0320*
H190.820400.618901.160900.0330*
H200.667700.404001.051900.0280*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0344 (5)0.0343 (5)0.0224 (4)0.0158 (4)0.0085 (4)0.0168 (4)
O20.0282 (4)0.0362 (5)0.0246 (4)0.0117 (4)0.0100 (3)0.0131 (4)
O30.0252 (4)0.0189 (4)0.0263 (4)0.0053 (3)0.0017 (3)0.0091 (3)
N10.0187 (4)0.0161 (4)0.0194 (4)0.0038 (3)0.0006 (4)0.0064 (4)
N20.0209 (5)0.0171 (4)0.0189 (5)0.0058 (4)0.0009 (4)0.0057 (4)
C10.0423 (8)0.0358 (7)0.0282 (6)0.0081 (6)0.0000 (6)0.0190 (6)
C20.0427 (7)0.0380 (7)0.0222 (6)0.0129 (6)0.0085 (5)0.0176 (5)
C30.0206 (5)0.0180 (5)0.0183 (5)0.0022 (4)0.0009 (4)0.0053 (4)
C40.0191 (5)0.0172 (5)0.0192 (5)0.0051 (4)0.0031 (4)0.0074 (4)
C50.0210 (5)0.0162 (5)0.0178 (5)0.0041 (4)0.0048 (4)0.0057 (4)
C60.0188 (5)0.0170 (5)0.0165 (5)0.0036 (4)0.0059 (4)0.0057 (4)
C70.0177 (5)0.0184 (5)0.0178 (5)0.0038 (4)0.0048 (4)0.0069 (4)
C80.0199 (5)0.0171 (5)0.0191 (5)0.0033 (4)0.0004 (4)0.0069 (4)
C90.0248 (6)0.0221 (6)0.0442 (8)0.0011 (5)0.0142 (5)0.0034 (5)
C100.0354 (7)0.0237 (6)0.0481 (8)0.0039 (5)0.0205 (6)0.0003 (6)
C110.0303 (6)0.0177 (5)0.0285 (6)0.0010 (5)0.0018 (5)0.0043 (5)
C120.0291 (6)0.0229 (6)0.0245 (6)0.0031 (5)0.0035 (5)0.0104 (5)
C130.0298 (6)0.0232 (6)0.0197 (5)0.0022 (5)0.0065 (5)0.0092 (5)
C140.0189 (5)0.0255 (6)0.0277 (6)0.0056 (4)0.0056 (4)0.0121 (5)
C150.0225 (5)0.0175 (5)0.0166 (5)0.0032 (4)0.0052 (4)0.0066 (4)
C160.0217 (5)0.0221 (6)0.0242 (6)0.0055 (4)0.0051 (4)0.0081 (5)
C170.0211 (5)0.0247 (6)0.0275 (6)0.0004 (4)0.0036 (5)0.0080 (5)
C180.0302 (6)0.0174 (5)0.0271 (6)0.0003 (5)0.0055 (5)0.0059 (5)
C190.0302 (6)0.0191 (6)0.0306 (6)0.0077 (5)0.0056 (5)0.0076 (5)
C200.0219 (5)0.0207 (6)0.0238 (6)0.0048 (4)0.0024 (4)0.0063 (5)
Geometric parameters (Å, º) top
O1—C21.4601 (16)C16—C171.3857 (19)
O1—C31.3317 (15)C17—C181.3920 (19)
O2—C31.2025 (15)C18—C191.3825 (18)
O3—C71.2237 (14)C19—C201.3904 (18)
N1—C41.4639 (16)C1—H1A0.9800
N1—C71.3530 (14)C1—H1B0.9800
N1—C81.4296 (15)C1—H1C0.9800
N2—C61.3638 (14)C2—H2A0.9900
N2—C151.3985 (16)C2—H2B0.9900
N2—H2N0.898 (17)C5—H50.9500
C1—C21.4991 (19)C9—H90.9500
C3—C41.5434 (15)C10—H100.9500
C4—C51.5130 (16)C11—H110.9500
C4—C141.5274 (16)C12—H120.9500
C5—C61.3418 (16)C13—H130.9500
C6—C71.4938 (17)C14—H14A0.9800
C8—C91.3851 (17)C14—H14B0.9800
C8—C131.3848 (17)C14—H14C0.9800
C9—C101.383 (2)C16—H160.9500
C10—C111.3845 (19)C17—H170.9500
C11—C121.3825 (17)C18—H180.9500
C12—C131.3912 (18)C19—H190.9500
C15—C201.3953 (17)C20—H200.9500
C15—C161.3994 (16)
C2—O1—C3116.61 (9)C2—C1—H1A110.00
C4—N1—C7112.22 (10)C2—C1—H1B109.00
C4—N1—C8125.67 (9)C2—C1—H1C109.00
C7—N1—C8122.05 (10)H1A—C1—H1B109.00
C6—N2—C15127.95 (10)H1A—C1—H1C109.00
C15—N2—H2N116.7 (10)H1B—C1—H1C109.00
C6—N2—H2N114.9 (10)O1—C2—H2A111.00
O1—C2—C1106.07 (10)O1—C2—H2B111.00
O1—C3—O2124.92 (11)C1—C2—H2A110.00
O2—C3—C4125.00 (11)C1—C2—H2B111.00
O1—C3—C4110.04 (9)H2A—C2—H2B109.00
N1—C4—C14111.56 (10)C4—C5—H5125.00
C3—C4—C5107.20 (9)C6—C5—H5125.00
N1—C4—C5102.09 (9)C8—C9—H9120.00
C5—C4—C14113.07 (9)C10—C9—H9120.00
C3—C4—C14112.87 (9)C9—C10—H10120.00
N1—C4—C3109.43 (9)C11—C10—H10120.00
C4—C5—C6110.17 (10)C10—C11—H11120.00
C5—C6—C7108.54 (9)C12—C11—H11120.00
N2—C6—C5135.95 (11)C11—C12—H12120.00
N2—C6—C7115.49 (10)C13—C12—H12120.00
O3—C7—N1126.32 (11)C8—C13—H13120.00
O3—C7—C6126.75 (10)C12—C13—H13120.00
N1—C7—C6106.93 (10)C4—C14—H14A109.00
N1—C8—C9118.96 (11)C4—C14—H14B109.00
C9—C8—C13120.50 (11)C4—C14—H14C109.00
N1—C8—C13120.48 (10)H14A—C14—H14B110.00
C8—C9—C10119.68 (12)H14A—C14—H14C109.00
C9—C10—C11120.31 (12)H14B—C14—H14C109.00
C10—C11—C12119.85 (13)C15—C16—H16120.00
C11—C12—C13120.27 (12)C17—C16—H16120.00
C8—C13—C12119.38 (11)C16—C17—H17120.00
N2—C15—C16117.97 (11)C18—C17—H17120.00
C16—C15—C20119.22 (11)C17—C18—H18121.00
N2—C15—C20122.73 (10)C19—C18—H18121.00
C15—C16—C17120.08 (12)C18—C19—H19119.00
C16—C17—C18120.79 (11)C20—C19—H19119.00
C17—C18—C19118.93 (12)C15—C20—H20120.00
C18—C19—C20121.14 (12)C19—C20—H20120.00
C15—C20—C19119.84 (11)
C3—O1—C2—C1163.94 (11)O2—C3—C4—N125.34 (16)
C2—O1—C3—O22.26 (18)C3—C4—C5—C6113.96 (11)
C2—O1—C3—C4179.93 (10)C14—C4—C5—C6121.00 (11)
C7—N1—C8—C13101.78 (13)N1—C4—C5—C61.02 (12)
C7—N1—C4—C50.49 (12)C4—C5—C6—N2176.18 (12)
C8—N1—C4—C5176.44 (10)C4—C5—C6—C72.01 (13)
C7—N1—C4—C14120.55 (10)C5—C6—C7—O3177.72 (11)
C8—N1—C4—C1462.53 (13)N2—C6—C7—N1176.31 (9)
C4—N1—C8—C9101.29 (14)C5—C6—C7—N12.30 (12)
C7—N1—C4—C3113.83 (10)N2—C6—C7—O33.68 (17)
C8—N1—C4—C363.10 (13)N1—C8—C9—C10176.91 (12)
C4—N1—C7—C61.65 (12)C9—C8—C13—C120.19 (18)
C4—N1—C7—O3178.36 (11)C13—C8—C9—C100.23 (19)
C8—N1—C7—O34.58 (18)N1—C8—C13—C12176.91 (11)
C4—N1—C8—C1381.57 (14)C8—C9—C10—C110.1 (2)
C8—N1—C7—C6175.41 (9)C9—C10—C11—C120.1 (2)
C7—N1—C8—C975.36 (15)C10—C11—C12—C130.12 (19)
C15—N2—C6—C7179.61 (10)C11—C12—C13—C80.02 (19)
C6—N2—C15—C16158.37 (11)N2—C15—C16—C17176.86 (11)
C15—N2—C6—C51.5 (2)C20—C15—C16—C170.13 (18)
C6—N2—C15—C2025.02 (18)N2—C15—C20—C19176.70 (11)
O1—C3—C4—C593.17 (11)C16—C15—C20—C190.13 (17)
O1—C3—C4—N1156.85 (9)C15—C16—C17—C180.00 (19)
O2—C3—C4—C14150.20 (12)C16—C17—C18—C190.1 (2)
O1—C3—C4—C1431.99 (13)C17—C18—C19—C200.1 (2)
O2—C3—C4—C584.64 (14)C18—C19—C20—C150.00 (19)
Hydrogen-bond geometry (Å, º) top
Cg2 and Cg3 are the centroids of the C8–C13 and C15–C20 phenyl rings, respectively.
D—H···AD—HH···AD···AD—H···A
N2—H2N···O30.898 (17)2.443 (16)2.8247 (14)105.9 (12)
N2—H2N···O3i0.898 (17)2.033 (17)2.9135 (14)166.3 (14)
C1—H1B···Cg2ii0.982.913.6177 (15)130
C12—H12···Cg3iii0.952.843.4865 (14)126
Symmetry codes: (i) x+2, y, z+2; (ii) x, y, z+1; (iii) x+1, y, z+2.
Hydrogen-bond geometry (Å, º) top
Cg2 and Cg3 are the centroids of the C8–C13 and C15–C20 phenyl rings, respectively.
D—H···AD—HH···AD···AD—H···A
N2—H2N···O30.898 (17)2.443 (16)2.8247 (14)105.9 (12)
N2—H2N···O3i0.898 (17)2.033 (17)2.9135 (14)166.3 (14)
C1—H1B···Cg2ii0.982.913.6177 (15)130
C12—H12···Cg3iii0.952.843.4865 (14)126
Symmetry codes: (i) x+2, y, z+2; (ii) x, y, z+1; (iii) x+1, y, z+2.
Acknowledgements top

Manchester Metropolitan University, Erciyes University and Granada University are gratefully acknowledged for supporting this study. The authors also thank José Romero Garzón, Centro de Instrumentación Científica, Universidad de Granada, for the data collection.

references
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