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Acta Crystallogr Sect E Struct Rep Online. 2010 April 1; 66(Pt 4): o731.
Published online 2010 March 3. doi:  10.1107/S1600536810006896
PMCID: PMC2983934

2-Hydr­oxy-10-propargylpyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione monohydrate

Abstract

The title compound, C15H14N2O3·H2O, 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). In the crystal, adjacent mol­ecules are linked by O—H(...)O hydrogen bonds into sheets parallel to (102). In addition, Cacetyl­inic—H(...)O hydrogen bonds occur.

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 and 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-66-0o731-scheme1.jpg

Experimental

Crystal data

  • C15H14N2O3·H2O
  • M r = 288.30
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-0o731-efi1.jpg
  • a = 6.8977 (1) Å
  • b = 7.9761 (1) Å
  • c = 13.0680 (2) Å
  • β = 99.194 (1)°
  • V = 709.72 (2) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.10 mm−1
  • T = 293 K
  • 0.3 × 0.3 × 0.3 mm

Data collection

  • Bruker APEXII diffractometer
  • 9524 measured reflections
  • 1744 independent reflections
  • 1680 reflections with I > 2σ(I)
  • R int = 0.021

Refinement

  • R[F 2 > 2σ(F 2)] = 0.029
  • wR(F 2) = 0.094
  • S = 1.10
  • 1744 reflections
  • 202 parameters
  • 4 restraints
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.18 e Å−3
  • Δρmin = −0.16 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/S1600536810006896/bt5199sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810006896/bt5199Isup2.hkl

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

Acknowledgments

We thank Université Mohammed V-Agdal and 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), propargyl bromide (0.26 g, 2.15 mmol) and 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 72 h. The solid material was removed by filtration and the solvent evaporated under vacuum. The residue was separated by chromatography on silica gel with an n-hexane:ethyl acetate (1:9) solvent system. The compound was obtained as colorless crystals in 50% yield upon evaporation of the solvent.

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 1.2U(C). The oxygen-bound H-atoms were located in a difference Fourier map, and were 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 C15H14N2O3.H2O at the 50% probability level; hydrogen atoms are drawn as spheres of an arbitrary radius.

Crystal data

C15H14N2O3·H2OF(000) = 304
Mr = 288.30Dx = 1.349 Mg m3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ybCell parameters from 6455 reflections
a = 6.8977 (1) Åθ = 2.5–34.3°
b = 7.9761 (1) ŵ = 0.10 mm1
c = 13.0680 (2) ÅT = 293 K
β = 99.194 (1)°Block, colorless
V = 709.72 (2) Å30.3 × 0.3 × 0.3 mm
Z = 2

Data collection

Bruker APEXII diffractometer1680 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.021
graphiteθmax = 27.5°, θmin = 1.6°
[var phi] and ω scansh = −8→8
9524 measured reflectionsk = −10→10
1744 independent reflectionsl = −16→16

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)] = 0.029Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.094H atoms treated by a mixture of independent and constrained refinement
S = 1.10w = 1/[σ2(Fo2) + (0.0656P)2 + 0.0541P] where P = (Fo2 + 2Fc2)/3
1744 reflections(Δ/σ)max = 0.001
202 parametersΔρmax = 0.18 e Å3
4 restraintsΔρmin = −0.16 e Å3

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

xyzUiso*/Ueq
O10.2007 (2)0.5000 (2)0.37937 (11)0.0464 (4)
O20.0918 (2)1.01924 (19)0.13444 (13)0.0503 (4)
O30.4060 (2)0.4426 (2)0.06723 (14)0.0561 (4)
O1W0.6986 (2)0.6295 (2)0.01457 (11)0.0465 (4)
N1−0.0173 (2)0.7109 (2)0.37874 (10)0.0320 (3)
N20.1101 (2)0.74500 (19)0.17437 (11)0.0317 (3)
C1−0.1606 (2)0.8238 (2)0.32657 (12)0.0301 (3)
C2−0.3329 (2)0.8493 (3)0.36900 (14)0.0377 (4)
H2−0.35590.78500.42520.045*
C3−0.4683 (3)0.9684 (3)0.32844 (16)0.0456 (5)
H3A−0.58160.98350.35760.055*
C4−0.4380 (3)1.0654 (3)0.24530 (15)0.0466 (5)
H4−0.52811.14780.21940.056*
C5−0.2715 (3)1.0388 (3)0.20077 (14)0.0410 (4)
H5−0.25121.10330.14420.049*
C6−0.1333 (2)0.9169 (2)0.23914 (12)0.0311 (3)
C70.0340 (3)0.8983 (2)0.17963 (13)0.0330 (3)
C80.2643 (3)0.7095 (2)0.11252 (15)0.0392 (4)
H8A0.37340.78670.12900.047*
H8B0.21410.71610.03890.047*
C90.3253 (3)0.5312 (2)0.14444 (15)0.0380 (4)
H90.41950.53290.20910.046*
C100.1339 (3)0.4509 (2)0.16327 (16)0.0387 (4)
H10A0.15900.35530.20940.046*
H10B0.05620.41460.09860.046*
C110.0298 (2)0.5904 (2)0.21314 (12)0.0308 (3)
H11A−0.11260.58410.19090.037*
C120.0799 (2)0.5931 (2)0.33103 (12)0.0319 (3)
C130.0327 (3)0.7196 (3)0.49276 (13)0.0362 (4)
H13A−0.07580.77030.52040.043*
H13B0.05020.60670.52040.043*
C140.2105 (3)0.8159 (3)0.52714 (13)0.0402 (4)
C150.3548 (3)0.8909 (4)0.55819 (18)0.0568 (6)
H150.46890.95010.58270.068*
H30.498 (3)0.499 (4)0.049 (2)0.065 (8)*
H110.760 (4)0.587 (4)−0.0291 (19)0.065 (8)*
H120.663 (4)0.725 (2)−0.009 (2)0.058 (8)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0455 (7)0.0516 (9)0.0432 (7)0.0169 (7)0.0107 (6)0.0127 (6)
O20.0618 (9)0.0320 (7)0.0644 (9)0.0021 (7)0.0322 (7)0.0110 (7)
O30.0670 (10)0.0393 (8)0.0728 (11)−0.0023 (8)0.0442 (9)−0.0149 (8)
O1W0.0522 (8)0.0481 (9)0.0430 (7)0.0059 (7)0.0196 (6)0.0032 (6)
N10.0346 (7)0.0360 (8)0.0258 (6)0.0029 (6)0.0058 (5)0.0028 (6)
N20.0376 (7)0.0276 (7)0.0324 (7)−0.0025 (6)0.0138 (6)−0.0006 (5)
C10.0315 (7)0.0298 (7)0.0288 (7)0.0000 (6)0.0046 (6)−0.0032 (6)
C20.0358 (8)0.0443 (10)0.0344 (8)0.0016 (8)0.0098 (6)0.0005 (7)
C30.0353 (9)0.0591 (13)0.0434 (9)0.0101 (9)0.0097 (7)−0.0037 (9)
C40.0435 (9)0.0510 (12)0.0439 (9)0.0178 (9)0.0024 (7)0.0002 (9)
C50.0481 (10)0.0391 (10)0.0360 (8)0.0083 (8)0.0072 (7)0.0042 (8)
C60.0341 (7)0.0290 (8)0.0305 (7)0.0003 (6)0.0060 (6)−0.0019 (6)
C70.0377 (8)0.0304 (8)0.0324 (7)−0.0006 (7)0.0106 (6)0.0011 (6)
C80.0488 (10)0.0324 (9)0.0416 (9)−0.0030 (8)0.0233 (8)−0.0029 (7)
C90.0418 (9)0.0337 (9)0.0419 (9)0.0012 (7)0.0169 (7)−0.0049 (7)
C100.0466 (9)0.0272 (8)0.0455 (10)−0.0029 (7)0.0169 (8)−0.0051 (7)
C110.0339 (7)0.0262 (7)0.0334 (7)−0.0019 (6)0.0089 (6)−0.0001 (6)
C120.0307 (7)0.0324 (8)0.0338 (7)−0.0001 (7)0.0086 (6)0.0043 (7)
C130.0412 (9)0.0408 (9)0.0265 (7)0.0014 (8)0.0054 (6)0.0031 (7)
C140.0420 (9)0.0468 (11)0.0313 (7)0.0063 (8)0.0040 (7)0.0016 (8)
C150.0472 (10)0.0728 (16)0.0483 (11)−0.0071 (12)0.0014 (8)−0.0078 (12)

Geometric parameters (Å, °)

O1—C121.215 (2)C4—H40.9300
O2—C71.230 (2)C5—C61.398 (2)
O3—C91.416 (2)C5—H50.9300
O3—H30.838 (10)C6—C71.498 (2)
O1W—H110.835 (10)C8—C91.523 (3)
O1W—H120.843 (10)C8—H8A0.9700
N1—C121.362 (2)C8—H8B0.9700
N1—C11.428 (2)C9—C101.522 (3)
N1—C131.476 (2)C9—H90.9800
N2—C71.336 (2)C10—C111.526 (2)
N2—C81.463 (2)C10—H10A0.9700
N2—C111.474 (2)C10—H10B0.9700
C1—C61.400 (2)C11—C121.524 (2)
C1—C21.404 (2)C11—H11A0.9800
C2—C31.377 (3)C13—C141.456 (3)
C2—H20.9300C13—H13A0.9700
C3—C41.377 (3)C13—H13B0.9700
C3—H3A0.9300C14—C151.176 (3)
C4—C51.384 (3)C15—H150.9300
C9—O3—H3109 (2)N2—C8—H8B111.2
H11—O1W—H12106 (3)C9—C8—H8B111.2
C12—N1—C1124.80 (13)H8A—C8—H8B109.1
C12—N1—C13116.23 (14)O3—C9—C10110.79 (16)
C1—N1—C13118.96 (14)O3—C9—C8113.19 (16)
C7—N2—C8122.10 (15)C10—C9—C8103.21 (15)
C7—N2—C11125.15 (13)O3—C9—H9109.8
C8—N2—C11111.97 (14)C10—C9—H9109.8
C6—C1—C2118.58 (15)C8—C9—H9109.8
C6—C1—N1123.42 (14)C9—C10—C11103.99 (14)
C2—C1—N1117.90 (14)C9—C10—H10A111.0
C3—C2—C1120.83 (17)C11—C10—H10A111.0
C3—C2—H2119.6C9—C10—H10B111.0
C1—C2—H2119.6C11—C10—H10B111.0
C4—C3—C2120.81 (17)H10A—C10—H10B109.0
C4—C3—H3A119.6N2—C11—C12107.39 (14)
C2—C3—H3A119.6N2—C11—C10103.60 (12)
C3—C4—C5119.09 (19)C12—C11—C10113.32 (15)
C3—C4—H4120.5N2—C11—H11A110.8
C5—C4—H4120.5C12—C11—H11A110.8
C4—C5—C6121.35 (17)C10—C11—H11A110.8
C4—C5—H5119.3O1—C12—N1122.04 (15)
C6—C5—H5119.3O1—C12—C11122.86 (16)
C5—C6—C1119.23 (15)N1—C12—C11115.08 (14)
C5—C6—C7114.86 (15)C14—C13—N1112.68 (14)
C1—C6—C7125.91 (15)C14—C13—H13A109.1
O2—C7—N2122.21 (15)N1—C13—H13A109.1
O2—C7—C6120.45 (16)C14—C13—H13B109.1
N2—C7—C6117.27 (15)N1—C13—H13B109.1
N2—C8—C9102.88 (14)H13A—C13—H13B107.8
N2—C8—H8A111.2C15—C14—C13177.6 (2)
C9—C8—H8A111.2C14—C15—H15180.0
C12—N1—C1—C6−47.5 (2)C7—N2—C8—C9171.01 (16)
C13—N1—C1—C6132.32 (17)C11—N2—C8—C9−18.65 (19)
C12—N1—C1—C2136.14 (18)N2—C8—C9—O3154.01 (16)
C13—N1—C1—C2−44.0 (2)N2—C8—C9—C1034.20 (19)
C6—C1—C2—C3−2.8 (3)O3—C9—C10—C11−159.11 (16)
N1—C1—C2—C3173.70 (18)C8—C9—C10—C11−37.66 (19)
C1—C2—C3—C40.0 (3)C7—N2—C11—C12−74.4 (2)
C2—C3—C4—C51.8 (3)C8—N2—C11—C12115.58 (16)
C3—C4—C5—C6−0.6 (3)C7—N2—C11—C10165.40 (18)
C4—C5—C6—C1−2.2 (3)C8—N2—C11—C10−4.59 (18)
C4—C5—C6—C7177.42 (19)C9—C10—C11—N226.07 (18)
C2—C1—C6—C53.9 (2)C9—C10—C11—C12−89.97 (17)
N1—C1—C6—C5−172.45 (16)C1—N1—C12—O1−179.99 (17)
C2—C1—C6—C7−175.72 (16)C13—N1—C12—O10.2 (2)
N1—C1—C6—C78.0 (3)C1—N1—C12—C111.6 (2)
C8—N2—C7—O2−1.4 (3)C13—N1—C12—C11−178.26 (14)
C11—N2—C7—O2−170.47 (17)N2—C11—C12—O1−109.22 (19)
C8—N2—C7—C6175.64 (16)C10—C11—C12—O14.6 (2)
C11—N2—C7—C66.6 (3)N2—C11—C12—N169.19 (18)
C5—C6—C7—O230.1 (3)C10—C11—C12—N1−177.03 (14)
C1—C6—C7—O2−150.25 (19)C12—N1—C13—C1481.9 (2)
C5—C6—C7—N2−146.98 (17)C1—N1—C13—C14−97.99 (19)
C1—C6—C7—N232.6 (3)N1—C13—C14—C15−158 (6)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O3—H3···O1w0.84 (1)1.85 (1)2.686 (2)177 (3)
O1w—H11···O2i0.84 (1)1.92 (1)2.7485 (19)172 (4)
O1w—H12···O3ii0.84 (1)1.92 (1)2.767 (2)177 (3)
C15—H15···O1iii0.932.293.166 (3)157

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BT5199).

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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