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Acta Crystallogr Sect E Struct Rep Online. 2010 April 1; 66(Pt 4): o733.
Published online 2010 March 3. doi:  10.1107/S1600536810006914
PMCID: PMC2983942

Ethyl 2-hydr­oxy-5,11-dioxopyrrolo[2,1-c][1,4]benzodiazepine-10-acetate

Abstract

The title compound, C16H18N2O5, consists of a benzodiazepinedione system fused to a pyrrole system. The seven-membered ring adopts a boat-shaped conformation (with the methine C atom as the prow); the five-membered ring adopts an enveloped-shaped conformation (with the hydr­oxy-bearing C atom as the flap). The hydr­oxy group is hydrogen bonded to the carbonyl O atom of an adjacent mol­ecule generating a zigzag chain in the crystal structure.

Related literature

Pyrrolo[2,1-c][1,4]benzodiazepines are potent anti­biotics produced by Streptomyces species; see: Cargill et al. (1974 [triangle]). For the design of DNA inter-strand cross-linking as well as of conjugate agents to enhance the sequence selectivity and selectivity for tumor cells, see: Gregson et al. (2004 [triangle]).

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Object name is e-66-0o733-scheme1.jpg

Experimental

Crystal data

  • C16H18N2O5
  • M r = 318.32
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-66-0o733-efi1.jpg
  • a = 8.5503 (2) Å
  • b = 9.6580 (2) Å
  • c = 18.2734 (4) Å
  • V = 1509.00 (6) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.11 mm−1
  • T = 293 K
  • 0.3 × 0.3 × 0.3 mm

Data collection

  • Bruker APEXII diffractometer
  • 11809 measured reflections
  • 1907 independent reflections
  • 1765 reflections with I > 2σ(I)
  • R int = 0.024

Refinement

  • R[F 2 > 2σ(F 2)] = 0.032
  • wR(F 2) = 0.098
  • S = 1.04
  • 1907 reflections
  • 213 parameters
  • 1 restraint
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.21 e Å−3
  • Δρmin = −0.17 e Å−3

Data collection: APEX2 (Bruker, 2005 [triangle]); cell refinement: SAINT (Bruker, 2005 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: X-SEED (Barbour, 2001 [triangle]); software used to prepare material for publication: publCIF (Westrip, 2010 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810006914/bt5201sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810006914/bt5201Isup2.hkl

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

Acknowledgments

We thank Université Mohammed V-Agdaland the University of Malaya for supporting this study.

supplementary crystallographic information

Experimental

2-Hydroxy- pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione (0.5 g, 2.15 mmol), ethyl bromoacetate (0.45 ml, 4.3 mmol), potassium carbonate (0.6 g, 4.3 mmol) along with a catalytic amount of tetra-n-butyl ammonium bromide were stirred in N,N-dimethylformamide (20 ml) for 24 h. After the completion of the reaction (monitored by TLC), the solid material was removed by filtration and the solvent evaporated under vacuum. Dichloromethane (20 ml) was added and the solution filtered. The solvent was removed and the product purified by recrystallization from ethanol to afford colorless crystals in 80% yield.

Refinement

Carbon-bound H-atoms were placed in calculated positions (C—H 0.93-0.98 Å) and were included in the refinement in the riding model approximation, with U(H) set to 1.2–1.5U(C). The oxygen-bound H-atom was located in a difference Fourier map, and was refined isotropically with a distance restraint of O–H = 0.84±0.01 Å. Due to the absence of anomalous scatterers Friedel pairs were merged and the absolute configuration was arbitrarily set.

Figures

Fig. 1.
Anisotropic displacement ellipsoid plot (Barbour, 2001) of C16H18N2O5 at the 50% probability level; hydrogen atoms are drawn as arbitrary radius.

Crystal data

C16H18N2O5F(000) = 672
Mr = 318.32Dx = 1.401 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 6127 reflections
a = 8.5503 (2) Åθ = 2.2–32.7°
b = 9.6580 (2) ŵ = 0.11 mm1
c = 18.2734 (4) ÅT = 293 K
V = 1509.00 (6) Å3Block, colorless
Z = 40.3 × 0.3 × 0.3 mm

Data collection

Bruker APEXII diffractometer1765 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.024
graphiteθmax = 27.5°, θmin = 3.1°
[var phi] and ω scansh = −10→9
11809 measured reflectionsk = −12→12
1907 independent reflectionsl = −23→23

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.032Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.098H atoms treated by a mixture of independent and constrained refinement
S = 1.04w = 1/[σ2(Fo2) + (0.0709P)2 + 0.1392P] where P = (Fo2 + 2Fc2)/3
1907 reflections(Δ/σ)max = 0.001
213 parametersΔρmax = 0.21 e Å3
1 restraintΔρmin = −0.17 e Å3

Special details

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
O1−0.0674 (2)1.16444 (16)−0.01855 (9)0.0502 (4)
O20.1577 (2)1.04456 (15)0.23744 (7)0.0480 (4)
O30.2180 (2)1.50177 (16)0.09188 (10)0.0577 (5)
H30.277 (3)1.452 (3)0.0664 (16)0.077 (10)*
O40.25606 (19)0.66847 (14)0.26892 (8)0.0426 (4)
O50.4250 (2)0.8107 (2)0.21372 (11)0.0677 (6)
N10.0805 (2)1.20584 (14)0.08027 (8)0.0306 (4)
N20.1825 (2)0.92800 (14)0.13177 (7)0.0299 (3)
C10.2136 (2)0.92042 (17)0.05498 (9)0.0275 (4)
C20.3094 (3)0.81259 (19)0.03067 (10)0.0386 (4)
H20.36050.75670.06450.046*
C30.3287 (3)0.7885 (2)−0.04302 (12)0.0478 (6)
H3A0.39320.7168−0.05860.057*
C40.2530 (3)0.8699 (2)−0.09410 (11)0.0495 (6)
H40.26380.8517−0.14380.059*
C50.1614 (3)0.9784 (2)−0.07053 (9)0.0395 (5)
H50.11161.0338−0.10500.047*
C60.1411 (2)1.00772 (17)0.00397 (8)0.0289 (4)
C70.0428 (2)1.13048 (18)0.02157 (9)0.0325 (4)
C80.0024 (3)1.33736 (19)0.09788 (12)0.0403 (4)
H8A−0.08901.32190.12820.048*
H8B−0.02921.38550.05370.048*
C90.1259 (3)1.41889 (18)0.13900 (11)0.0385 (5)
H90.07471.47840.17520.046*
C100.2186 (3)1.30721 (18)0.17856 (11)0.0383 (4)
H10A0.17171.28690.22570.046*
H10B0.32561.33710.18630.046*
C110.2141 (2)1.17906 (16)0.12901 (9)0.0270 (3)
H110.31111.17110.10080.032*
C120.1830 (2)1.04664 (17)0.17179 (8)0.0292 (4)
C130.1586 (3)0.79979 (17)0.17246 (10)0.0333 (4)
H13A0.13980.72490.13820.040*
H13B0.06630.80920.20290.040*
C140.2970 (3)0.76303 (19)0.22022 (10)0.0353 (4)
C150.3801 (3)0.6167 (3)0.31610 (14)0.0548 (6)
H15A0.42800.69290.34250.066*
H15B0.46020.57180.28690.066*
C160.3116 (4)0.5171 (3)0.36799 (15)0.0711 (9)
H16A0.39330.47650.39700.107*
H16B0.25800.44570.34140.107*
H16C0.23900.56410.39940.107*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0530 (10)0.0443 (7)0.0533 (8)0.0063 (8)−0.0280 (8)0.0017 (7)
O20.0756 (12)0.0458 (7)0.0226 (6)−0.0069 (8)0.0034 (6)0.0001 (5)
O30.0718 (13)0.0293 (6)0.0720 (11)−0.0031 (8)0.0311 (10)0.0004 (7)
O40.0435 (9)0.0418 (7)0.0425 (7)−0.0019 (7)−0.0044 (6)0.0179 (6)
O50.0443 (10)0.0727 (12)0.0861 (13)−0.0162 (10)−0.0148 (9)0.0430 (10)
N10.0319 (9)0.0271 (7)0.0328 (7)0.0039 (6)−0.0047 (6)0.0007 (5)
N20.0402 (10)0.0256 (6)0.0240 (6)−0.0003 (6)0.0007 (6)0.0043 (5)
C10.0333 (10)0.0243 (7)0.0250 (7)−0.0037 (7)0.0014 (6)−0.0006 (6)
C20.0468 (13)0.0303 (8)0.0387 (9)0.0031 (9)0.0036 (9)−0.0004 (7)
C30.0591 (16)0.0382 (9)0.0462 (11)0.0012 (10)0.0159 (11)−0.0116 (8)
C40.0744 (17)0.0461 (10)0.0279 (8)−0.0115 (11)0.0115 (10)−0.0091 (8)
C50.0553 (14)0.0376 (9)0.0255 (8)−0.0098 (9)−0.0031 (8)0.0026 (7)
C60.0348 (10)0.0267 (7)0.0250 (7)−0.0057 (7)−0.0024 (7)0.0008 (6)
C70.0371 (11)0.0287 (8)0.0316 (8)−0.0007 (7)−0.0070 (7)0.0061 (6)
C80.0391 (12)0.0301 (8)0.0516 (10)0.0083 (8)0.0007 (9)0.0006 (8)
C90.0464 (13)0.0264 (8)0.0428 (10)0.0008 (8)0.0135 (9)−0.0059 (7)
C100.0432 (12)0.0319 (8)0.0398 (9)−0.0016 (8)0.0003 (9)−0.0115 (7)
C110.0292 (10)0.0258 (7)0.0259 (7)−0.0001 (7)−0.0024 (6)−0.0019 (6)
C120.0322 (10)0.0314 (7)0.0239 (7)−0.0010 (7)−0.0028 (7)0.0007 (6)
C130.0387 (11)0.0300 (8)0.0311 (8)−0.0042 (7)−0.0018 (7)0.0077 (6)
C140.0365 (12)0.0328 (8)0.0366 (9)−0.0016 (8)−0.0015 (8)0.0095 (7)
C150.0501 (15)0.0564 (12)0.0579 (13)0.0070 (12)−0.0091 (11)0.0248 (11)
C160.080 (2)0.0770 (17)0.0566 (14)0.0242 (17)0.0073 (14)0.0332 (13)

Geometric parameters (Å, °)

O1—C71.238 (2)C5—H50.9300
O2—C121.219 (2)C6—C71.489 (3)
O3—C91.415 (2)C8—C91.517 (3)
O3—H30.841 (10)C8—H8A0.9700
O4—C141.322 (2)C8—H8B0.9700
O4—C151.455 (3)C9—C101.521 (3)
O5—C141.193 (3)C9—H90.9800
N1—C71.336 (2)C10—C111.534 (2)
N1—C111.471 (2)C10—H10A0.9700
N1—C81.471 (2)C10—H10B0.9700
N2—C121.359 (2)C11—C121.522 (2)
N2—C11.430 (2)C11—H110.9800
N2—C131.459 (2)C13—C141.513 (3)
C1—C21.397 (3)C13—H13A0.9700
C1—C61.402 (2)C13—H13B0.9700
C2—C31.376 (3)C15—C161.472 (3)
C2—H20.9300C15—H15A0.9700
C3—C41.381 (3)C15—H15B0.9700
C3—H3A0.9300C16—H16A0.9600
C4—C51.377 (3)C16—H16B0.9600
C4—H40.9300C16—H16C0.9600
C5—C61.401 (2)
C9—O3—H3110 (2)C8—C9—H9109.1
C14—O4—C15116.28 (18)C10—C9—H9109.1
C7—N1—C11125.27 (15)C9—C10—C11106.17 (15)
C7—N1—C8122.48 (16)C9—C10—H10A110.5
C11—N1—C8111.83 (14)C11—C10—H10A110.5
C12—N2—C1124.78 (13)C9—C10—H10B110.5
C12—N2—C13116.22 (13)C11—C10—H10B110.5
C1—N2—C13118.86 (13)H10A—C10—H10B108.7
C2—C1—C6119.74 (15)N1—C11—C12108.85 (15)
C2—C1—N2117.34 (16)N1—C11—C10103.58 (14)
C6—C1—N2122.65 (16)C12—C11—C10112.28 (13)
C3—C2—C1120.47 (19)N1—C11—H11110.6
C3—C2—H2119.8C12—C11—H11110.6
C1—C2—H2119.8C10—C11—H11110.6
C4—C3—C2120.6 (2)O2—C12—N2120.99 (15)
C4—C3—H3A119.7O2—C12—C11123.37 (15)
C2—C3—H3A119.7N2—C12—C11115.62 (13)
C3—C4—C5119.21 (18)N2—C13—C14112.56 (16)
C3—C4—H4120.4N2—C13—H13A109.1
C5—C4—H4120.4C14—C13—H13A109.1
C4—C5—C6121.87 (19)N2—C13—H13B109.1
C4—C5—H5119.1C14—C13—H13B109.1
C6—C5—H5119.1H13A—C13—H13B107.8
C5—C6—C1118.02 (17)O5—C14—O4125.18 (19)
C5—C6—C7116.15 (16)O5—C14—C13124.73 (17)
C1—C6—C7125.82 (14)O4—C14—C13110.08 (18)
O1—C7—N1120.98 (18)O4—C15—C16108.4 (2)
O1—C7—C6120.85 (16)O4—C15—H15A110.0
N1—C7—C6118.12 (16)C16—C15—H15A110.0
N1—C8—C9103.94 (16)O4—C15—H15B110.0
N1—C8—H8A111.0C16—C15—H15B110.0
C9—C8—H8A111.0H15A—C15—H15B108.4
N1—C8—H8B111.0C15—C16—H16A109.5
C9—C8—H8B111.0C15—C16—H16B109.5
H8A—C8—H8B109.0H16A—C16—H16B109.5
O3—C9—C8112.32 (18)C15—C16—H16C109.5
O3—C9—C10113.62 (19)H16A—C16—H16C109.5
C8—C9—C10103.30 (14)H16B—C16—H16C109.5
O3—C9—H9109.1
C12—N2—C1—C2137.2 (2)N1—C8—C9—O390.74 (19)
C13—N2—C1—C2−38.4 (3)N1—C8—C9—C10−32.09 (19)
C12—N2—C1—C6−48.8 (3)O3—C9—C10—C11−90.0 (2)
C13—N2—C1—C6135.63 (19)C8—C9—C10—C1132.0 (2)
C6—C1—C2—C3−2.3 (3)C7—N1—C11—C12−69.2 (2)
N2—C1—C2—C3171.88 (19)C8—N1—C11—C12118.12 (16)
C1—C2—C3—C4−0.4 (3)C7—N1—C11—C10171.13 (18)
C2—C3—C4—C51.9 (4)C8—N1—C11—C10−1.53 (19)
C3—C4—C5—C6−0.8 (3)C9—C10—C11—N1−19.1 (2)
C4—C5—C6—C1−1.8 (3)C9—C10—C11—C12−136.39 (17)
C4—C5—C6—C7178.27 (19)C1—N2—C12—O2−178.8 (2)
C2—C1—C6—C53.3 (3)C13—N2—C12—O2−3.2 (3)
N2—C1—C6—C5−170.55 (18)C1—N2—C12—C112.2 (3)
C2—C1—C6—C7−176.78 (18)C13—N2—C12—C11177.84 (17)
N2—C1—C6—C79.4 (3)N1—C11—C12—O2−111.0 (2)
C11—N1—C7—O1−176.41 (17)C10—C11—C12—O23.1 (3)
C8—N1—C7—O1−4.5 (3)N1—C11—C12—N268.0 (2)
C11—N1—C7—C61.1 (3)C10—C11—C12—N2−177.93 (18)
C8—N1—C7—C6173.01 (16)C12—N2—C13—C14−69.9 (2)
C5—C6—C7—O132.0 (3)C1—N2—C13—C14106.03 (19)
C1—C6—C7—O1−147.9 (2)C15—O4—C14—O5−2.1 (3)
C5—C6—C7—N1−145.53 (19)C15—O4—C14—C13176.49 (19)
C1—C6—C7—N134.6 (3)N2—C13—C14—O5−17.2 (3)
C7—N1—C8—C9−151.47 (18)N2—C13—C14—O4164.23 (16)
C11—N1—C8—C921.4 (2)C14—O4—C15—C16177.9 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O3—H3···O1i0.84 (1)1.95 (1)2.782 (2)173 (4)

Symmetry codes: (i) x+1/2, −y+5/2, −z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BT5201).

References

  • Barbour, L. J. (2001). J. Supramol. Chem.1, 189–191.
  • Bruker (2005). APEX2 and SAINT Bruker AXS Inc., Madison, Wisconsin, USA.
  • Cargill, C., Bachmann, E. & Zbinden, G. (1974). J. Natl. Cancer Inst.53, 481– 486. [PubMed]
  • Gregson, S. T., Howard, P. W., Gullick, D. R., Hamaguchi, A., Corcoran, K. E., Brooks, N. A., Hartley, J. A., Jenkins, T. C., Patel, S., Guille, M. J. & Thurston, D. E. (2004). J. Med. Chem.47, 1161–1174. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Westrip, S. P. (2010). publCIF In preparation.

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