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In the course of a study on pyrrolidinone-derived anticancer agents, the crystal structure of the title compound, 1,1′-(4-methyl­benzyl­idene)­bis(5-oxopyrrolidine-2-carboxyl­ic acid), C18H20N2O6, was determined. In this compound, a π–π interaction brings the first carboxyl­ic acid group above the aromatic ring, whereas the second carboxyl­ic acid group is oriented above one of the pyrrolidine rings.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536801006493/ci6021sup1.cif
Contains datablocks I, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536801006493/ci6021Isup2.hkl
Contains datablock I

CCDC reference: 165662

Key indicators

  • Single-crystal X-ray study
  • T = 293 K
  • Mean [sigma](C-C) = 0.003 Å
  • R factor = 0.028
  • wR factor = 0.076
  • Data-to-parameter ratio = 8.2

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry

General Notes

REFLT_03 From the CIF: _diffrn_reflns_theta_max 71.90 From the CIF: _reflns_number_total 2499 Count of symmetry unique reflns 1945 Completeness (_total/calc) 128.48% TEST3: Check Friedels for noncentro structure Estimate of Friedel pairs measured 554 Fraction of Friedel pairs measured 0.285 Are heavy atom types Z>Si present no WARNING: CuKa measured Friedel data can be used to determine absolute structure in a light-atom study only if the Friedel fraction is large.

Comment top

Azatoxin, an anticancer drug, is an inhibitor of both topoisomerase II and tubulin polymerization (Leteurtre et al., 1995). Recently, the crystal structure of methyl N-[(4-methoxyphenyl)(3,4,5-trimethoxyphenyl)methyl]pyroglutamate, (I), an aryl derivative of a precursor of two azatoxin analogues, has been studied (Camus et al., 2000). This aryl compound presents mild anticancer properties (Bourry et al., 2001). During various attempts to obtain (I) stereoselectively, the reactivity of other reactants were tested and methyl 1-{[2-(methoxycarbonyl)-5-oxopyrrolidin-1-yl](3,4,5-trimethoxyphenyl)methyl}- pyroglutamate, (II), was obtained. The spatial structure of the diester (II) was confirmed by an X-ray analysis of a rather similar compound, NN-{[2-carboxy-5-oxopyrrolidin-1-yl](p-tolyl)methyl}pyroglutamic acid, (III).

In this compound, the sp2 hybridization of N9 and N15 is confirmed [sum of bond angles around N9 and N15 is 359.7 (1) and 359.8 (1)° respectively]. Moreover, the torsion angle C19—N15—C8—N9 of 45.5 (2)° brings the C20-carrying carboxylic acid function just above the second pyrrolidine cycle. Furhermore, a ππ interaction orients the C14-carried carboxylic acid group just above the aromatic ring, imposing a torsion angle C13—N9—C8—C5 of 28.8 (2)°.

Experimental top

The synthesize of (III) has been reported elsewhere (Bourry et al., 2001). Crystals were obtained by slow evaporation of a methanol solution at room temperature.

Computing details top

Data collection: CAD-4 EXPRESS (Enraf-Nonius, 1992); cell refinement: CAD-4 EXPRESS; data reduction: PLATON (Spek, 2001); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2001); software used to prepare material for publication: SHELXL97.

Figures top
[Figure 1] Fig. 1. ORTEPII (Johnson, 1976) representation of compound (III) with ellipsoids at the 50% probability level.
N-{[2-carboxy-5-oxopyrrolidin-1-yl](p-tolyl)methyl}pyroglutamic acid top
Crystal data top
C18H20N2O6Dx = 1.393 Mg m3
Mr = 360.36Cu Kα radiation, λ = 1.54178 Å
Orthorhombic, P212121Cell parameters from 25 reflections
a = 9.077 (1) Åθ = 38–42°
b = 11.065 (1) ŵ = 0.89 mm1
c = 17.106 (1) ÅT = 293 K
V = 1718.1 (3) Å3Prism, colorless
Z = 40.40 × 0.30 × 0.20 mm
F(000) = 760
Data collection top
Enraf Nonius CAD-4
diffractometer
2443 reflections with I > 2σ(I)
Radiation source: long fine-focus sealed tubeRint = 0.017
Graphite monochromatorθmax = 71.9°, θmin = 4.8°
θ/2θ scansh = 1111
Absorption correction: ψ scan
(North et al., 1968)
k = 013
Tmin = 0.718, Tmax = 0.843l = 021
2767 measured reflections3 standard reflections every 200 reflections
2499 independent reflections intensity decay: 2%
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.028H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.076 w = 1/[σ2(Fo2) + (0.048P)2 + 0.307P]
where P = (Fo2 + 2Fc2)/3
S = 1.03(Δ/σ)max = 0.002
2499 reflectionsΔρmax = 0.15 e Å3
304 parametersΔρmin = 0.15 e Å3
0 restraintsAbsolute structure: Flack (1983)
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.02 (19)
Crystal data top
C18H20N2O6V = 1718.1 (3) Å3
Mr = 360.36Z = 4
Orthorhombic, P212121Cu Kα radiation
a = 9.077 (1) ŵ = 0.89 mm1
b = 11.065 (1) ÅT = 293 K
c = 17.106 (1) Å0.40 × 0.30 × 0.20 mm
Data collection top
Enraf Nonius CAD-4
diffractometer
2443 reflections with I > 2σ(I)
Absorption correction: ψ scan
(North et al., 1968)
Rint = 0.017
Tmin = 0.718, Tmax = 0.8433 standard reflections every 200 reflections
2767 measured reflections intensity decay: 2%
2499 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.028H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.076Δρmax = 0.15 e Å3
S = 1.03Δρmin = 0.15 e Å3
2499 reflectionsAbsolute structure: Flack (1983)
304 parametersAbsolute structure parameter: 0.02 (19)
0 restraints
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) 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
O40.65292 (15)0.07332 (10)0.31666 (7)0.0417 (3)
O11.02055 (14)0.02901 (12)0.23901 (7)0.0456 (3)
O60.73025 (15)0.41152 (11)0.23706 (8)0.0442 (3)
O50.83230 (17)0.27203 (13)0.31446 (9)0.0571 (4)
O30.83223 (16)0.18354 (12)0.04648 (7)0.0452 (3)
O21.00349 (16)0.06747 (13)0.00935 (7)0.0525 (4)
N150.65467 (15)0.09593 (11)0.24057 (7)0.0308 (3)
N90.86115 (15)0.11939 (12)0.15461 (7)0.0300 (3)
C50.63993 (18)0.00644 (14)0.10766 (9)0.0310 (3)
C100.99349 (18)0.10759 (15)0.19085 (9)0.0340 (3)
C140.90850 (19)0.14268 (15)0.01317 (9)0.0333 (3)
C200.7383 (2)0.30329 (16)0.26952 (10)0.0362 (4)
C190.61078 (18)0.22276 (15)0.24416 (10)0.0337 (4)
C130.86715 (19)0.20578 (15)0.08980 (9)0.0312 (3)
C120.9975 (2)0.28767 (16)0.11357 (10)0.0378 (4)
C20.4604 (2)0.08132 (17)0.01366 (11)0.0430 (4)
C160.61977 (18)0.03318 (15)0.30564 (9)0.0336 (4)
C60.4916 (2)0.03643 (16)0.10346 (11)0.0396 (4)
C80.73798 (17)0.04173 (15)0.17618 (9)0.0295 (3)
C170.5348 (2)0.11439 (18)0.35939 (11)0.0427 (4)
C111.0951 (2)0.20481 (19)0.16222 (11)0.0427 (4)
C70.4044 (2)0.00690 (19)0.04351 (13)0.0461 (4)
C40.6967 (2)0.06930 (17)0.05058 (11)0.0400 (4)
C30.6090 (2)0.11197 (19)0.00953 (11)0.0463 (5)
C180.4913 (2)0.22025 (17)0.30842 (11)0.0429 (4)
C10.3655 (3)0.1274 (2)0.07933 (12)0.0612 (6)
H1A0.27910.16520.05810.092*
H1B0.42000.18520.10960.092*
H1C0.33680.06110.11220.092*
H5010.7800 (19)0.0312 (16)0.1973 (10)0.027 (4)*
H5020.449 (2)0.0796 (19)0.1425 (12)0.042 (5)*
H5030.394 (3)0.207 (2)0.2831 (12)0.051 (6)*
H5040.957 (2)0.355 (2)0.1456 (12)0.047 (5)*
H5050.306 (3)0.012 (2)0.0440 (14)0.057 (6)*
H5060.800 (2)0.0943 (18)0.0533 (11)0.044 (5)*
H5070.576 (2)0.2520 (15)0.1947 (11)0.030 (4)*
H5081.047 (2)0.3168 (19)0.0683 (12)0.048 (6)*
H5090.776 (2)0.2496 (15)0.0843 (11)0.029 (4)*
H5100.854 (3)0.146 (2)0.0888 (13)0.052 (6)*
H5111.140 (2)0.2421 (18)0.2059 (13)0.047 (6)*
H5120.647 (3)0.1681 (19)0.0488 (12)0.052 (6)*
H5131.172 (3)0.164 (2)0.1314 (14)0.065 (7)*
H5140.491 (3)0.294 (2)0.3353 (13)0.058 (6)*
H5150.815 (3)0.455 (2)0.2473 (14)0.067 (7)*
H5160.463 (3)0.077 (2)0.3791 (13)0.058 (7)*
H5170.595 (3)0.137 (2)0.4025 (14)0.061 (7)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O40.0551 (7)0.0347 (6)0.0352 (6)0.0043 (6)0.0087 (6)0.0066 (5)
O10.0415 (7)0.0525 (7)0.0429 (6)0.0090 (6)0.0066 (6)0.0120 (6)
O60.0425 (7)0.0330 (6)0.0571 (8)0.0037 (6)0.0077 (6)0.0023 (6)
O50.0598 (9)0.0501 (8)0.0615 (8)0.0040 (7)0.0244 (8)0.0071 (7)
O30.0597 (8)0.0449 (7)0.0309 (6)0.0079 (7)0.0107 (6)0.0007 (6)
O20.0512 (7)0.0657 (8)0.0407 (7)0.0206 (7)0.0054 (6)0.0103 (6)
N150.0339 (6)0.0288 (6)0.0296 (6)0.0012 (6)0.0031 (6)0.0009 (5)
N90.0293 (6)0.0331 (7)0.0275 (6)0.0010 (6)0.0004 (5)0.0030 (5)
C50.0335 (8)0.0279 (7)0.0315 (7)0.0046 (7)0.0017 (7)0.0040 (6)
C100.0322 (8)0.0407 (8)0.0292 (7)0.0048 (8)0.0009 (7)0.0032 (7)
C140.0329 (8)0.0355 (8)0.0315 (8)0.0024 (7)0.0026 (7)0.0039 (7)
C200.0401 (9)0.0342 (8)0.0343 (8)0.0039 (7)0.0019 (8)0.0025 (7)
C190.0365 (9)0.0309 (8)0.0338 (8)0.0042 (7)0.0004 (7)0.0006 (7)
C130.0301 (8)0.0319 (8)0.0316 (8)0.0022 (7)0.0011 (7)0.0042 (7)
C120.0390 (9)0.0351 (8)0.0392 (9)0.0050 (8)0.0043 (8)0.0005 (8)
C20.0478 (10)0.0436 (9)0.0376 (9)0.0129 (8)0.0036 (8)0.0032 (8)
C160.0336 (8)0.0366 (8)0.0305 (8)0.0007 (7)0.0008 (7)0.0002 (7)
C60.0384 (9)0.0390 (9)0.0415 (9)0.0031 (8)0.0016 (8)0.0050 (8)
C80.0315 (8)0.0270 (7)0.0299 (8)0.0025 (6)0.0017 (6)0.0027 (6)
C170.0430 (10)0.0477 (11)0.0376 (9)0.0021 (9)0.0099 (8)0.0012 (8)
C110.0348 (9)0.0512 (11)0.0421 (9)0.0067 (8)0.0042 (8)0.0008 (9)
C70.0362 (9)0.0505 (11)0.0514 (10)0.0012 (8)0.0063 (9)0.0022 (9)
C40.0345 (9)0.0400 (9)0.0454 (9)0.0044 (8)0.0050 (8)0.0070 (8)
C30.0481 (11)0.0487 (11)0.0421 (10)0.0127 (9)0.0067 (9)0.0140 (9)
C180.0396 (10)0.0409 (9)0.0483 (10)0.0056 (8)0.0088 (9)0.0033 (9)
C10.0625 (14)0.0718 (14)0.0493 (11)0.0168 (12)0.0105 (11)0.0028 (11)
Geometric parameters (Å, º) top
O4—C161.231 (2)C12—C111.522 (3)
O1—C101.223 (2)C12—H5041.00 (2)
O6—C201.322 (2)C12—H5080.95 (2)
O6—H5150.92 (3)C2—C71.376 (3)
O5—C201.199 (2)C2—C31.393 (3)
O3—C141.313 (2)C2—C11.505 (3)
O3—H5100.86 (2)C16—C171.499 (2)
O2—C141.200 (2)C6—C71.382 (3)
N15—C161.350 (2)C6—H5020.91 (2)
N15—C191.460 (2)C8—H5010.963 (18)
N15—C81.465 (2)C17—C181.513 (3)
N9—C101.358 (2)C17—H5160.84 (3)
N9—C81.458 (2)C17—H5170.95 (3)
N9—C131.465 (2)C11—H5110.95 (2)
C5—C41.386 (2)C11—H5130.99 (3)
C5—C61.388 (2)C7—H5050.91 (2)
C5—C81.523 (2)C4—C31.383 (3)
C10—C111.499 (3)C4—H5060.98 (2)
C14—C131.532 (2)C3—H5120.98 (2)
C20—C191.524 (2)C18—H5031.00 (2)
C19—C181.544 (2)C18—H5140.94 (2)
C19—H5070.959 (19)C1—H1A0.9600
C13—C121.545 (2)C1—H1B0.9600
C13—H5090.963 (19)C1—H1C0.9600
C20—O6—H515110.4 (15)N15—C16—C17108.55 (14)
C14—O3—H510111.4 (15)C7—C6—C5120.75 (18)
C16—N15—C19113.31 (13)C7—C6—H502119.2 (12)
C16—N15—C8122.06 (13)C5—C6—H502119.8 (12)
C19—N15—C8124.48 (13)N9—C8—N15110.18 (13)
C10—N9—C8120.42 (13)N9—C8—C5113.87 (12)
C10—N9—C13112.05 (13)N15—C8—C5112.47 (13)
C8—N9—C13127.21 (13)N9—C8—H501106.6 (10)
C4—C5—C6117.95 (16)N15—C8—H501105.3 (10)
C4—C5—C8118.68 (15)C5—C8—H501107.8 (10)
C6—C5—C8123.05 (15)C16—C17—C18104.17 (15)
O1—C10—N9123.62 (15)C16—C17—H516110.8 (17)
O1—C10—C11127.36 (15)C18—C17—H516113.9 (16)
N9—C10—C11109.02 (14)C16—C17—H517109.4 (15)
O2—C14—O3125.11 (16)C18—C17—H517113.4 (16)
O2—C14—C13122.59 (15)H516—C17—H517105 (2)
O3—C14—C13112.26 (14)C10—C11—C12104.65 (14)
O5—C20—O6124.75 (17)C10—C11—H511108.7 (12)
O5—C20—C19123.65 (16)C12—C11—H511114.9 (13)
O6—C20—C19111.59 (15)C10—C11—H513106.1 (14)
N15—C19—C20111.51 (14)C12—C11—H513113.5 (14)
N15—C19—C18101.78 (13)H511—C11—H513108.6 (19)
C20—C19—C18109.96 (14)C2—C7—C6121.54 (19)
N15—C19—H507112.2 (10)C2—C7—H505120.1 (15)
C20—C19—H507107.7 (10)C6—C7—H505118.3 (16)
C18—C19—H507113.7 (11)C3—C4—C5121.07 (18)
N9—C13—C14111.06 (13)C3—C4—H506119.4 (12)
N9—C13—C12102.24 (13)C5—C4—H506119.6 (12)
C14—C13—C12107.75 (14)C4—C3—C2120.78 (18)
N9—C13—H509111.7 (11)C4—C3—H512121.5 (14)
C14—C13—H509110.9 (11)C2—C3—H512117.6 (14)
C12—C13—H509112.8 (10)C17—C18—C19103.95 (14)
C11—C12—C13103.66 (14)C17—C18—H503111.5 (13)
C11—C12—H504111.5 (12)C19—C18—H503108.6 (12)
C13—C12—H504107.4 (12)C17—C18—H514113.1 (13)
C11—C12—H508111.8 (13)C19—C18—H514109.6 (15)
C13—C12—H508110.4 (12)H503—C18—H514110 (2)
H504—C12—H508111.7 (17)C2—C1—H1A109.5
C7—C2—C3117.90 (17)C2—C1—H1B109.5
C7—C2—C1121.43 (19)H1A—C1—H1B109.5
C3—C2—C1120.7 (2)C2—C1—H1C109.5
O4—C16—N15124.16 (15)H1A—C1—H1C109.5
O4—C16—C17127.28 (16)H1B—C1—H1C109.5
C8—N9—C10—O14.5 (2)C10—N9—C8—N1588.46 (17)
C13—N9—C10—O1169.40 (15)C13—N9—C8—N1598.66 (17)
C8—N9—C10—C11175.30 (14)C10—N9—C8—C5144.11 (15)
C13—N9—C10—C1110.81 (19)C13—N9—C8—C528.8 (2)
C16—N15—C19—C2096.67 (16)C16—N15—C8—N9129.78 (15)
C8—N15—C19—C2079.00 (18)C19—N15—C8—N945.53 (19)
C16—N15—C19—C1820.52 (18)C16—N15—C8—C5102.01 (17)
C8—N15—C19—C18163.80 (15)C19—N15—C8—C582.68 (18)
O5—C20—C19—N1533.3 (2)C4—C5—C8—N967.95 (19)
O6—C20—C19—N15147.95 (15)C6—C5—C8—N9118.78 (16)
O5—C20—C19—C1878.9 (2)C4—C5—C8—N15165.81 (14)
O6—C20—C19—C1899.93 (16)C6—C5—C8—N157.5 (2)
C10—N9—C13—C1489.68 (16)O4—C16—C17—C18165.01 (18)
C8—N9—C13—C1483.70 (19)N15—C16—C17—C1814.4 (2)
C10—N9—C13—C1225.02 (17)O1—C10—C11—C12171.22 (17)
C8—N9—C13—C12161.60 (14)N9—C10—C11—C128.6 (2)
O2—C14—C13—N942.7 (2)C13—C12—C11—C1022.94 (18)
O3—C14—C13—N9139.52 (14)C3—C2—C7—C60.1 (3)
O2—C14—C13—C1268.5 (2)C1—C2—C7—C6179.37 (19)
O3—C14—C13—C12109.27 (16)C5—C6—C7—C20.3 (3)
N9—C13—C12—C1128.42 (17)C6—C5—C4—C31.1 (3)
C14—C13—C12—C1188.68 (16)C8—C5—C4—C3174.77 (16)
C19—N15—C16—O4176.29 (16)C5—C4—C3—C21.0 (3)
C8—N15—C16—O40.5 (3)C7—C2—C3—C40.4 (3)
C19—N15—C16—C174.3 (2)C1—C2—C3—C4179.70 (19)
C8—N15—C16—C17179.89 (15)C16—C17—C18—C1926.0 (2)
C4—C5—C6—C70.8 (3)N15—C19—C18—C1727.80 (18)
C8—C5—C6—C7174.15 (16)C20—C19—C18—C1790.51 (18)

Experimental details

Crystal data
Chemical formulaC18H20N2O6
Mr360.36
Crystal system, space groupOrthorhombic, P212121
Temperature (K)293
a, b, c (Å)9.077 (1), 11.065 (1), 17.106 (1)
V3)1718.1 (3)
Z4
Radiation typeCu Kα
µ (mm1)0.89
Crystal size (mm)0.40 × 0.30 × 0.20
Data collection
DiffractometerEnraf Nonius CAD-4
diffractometer
Absorption correctionψ scan
(North et al., 1968)
Tmin, Tmax0.718, 0.843
No. of measured, independent and
observed [I > 2σ(I)] reflections
2767, 2499, 2443
Rint0.017
(sin θ/λ)max1)0.617
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.028, 0.076, 1.03
No. of reflections2499
No. of parameters304
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.15, 0.15
Absolute structureFlack (1983)
Absolute structure parameter0.02 (19)

Computer programs: CAD-4 EXPRESS (Enraf-Nonius, 1992), CAD-4 EXPRESS, PLATON (Spek, 2001), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 1997), SHELXL97.

 

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