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Acta Crystallogr Sect E Struct Rep Online. 2009 October 1; 65(Pt 10): o2322.
Published online 2009 September 5. doi:  10.1107/S1600536809034266
PMCID: PMC2970423

10-Allyl-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione

Abstract

The compound, C15H16N2O2, features a pyrroline ring fused with a seven-membered diazepine ring; the latter system adopts a boat conformation (with the methine C atom as the prow and the two C atoms of the aromatic ring as the stern). A CH2–CH2 segment of the pyrroline ring is disordered over two positions in a 1:1 ratio.

Related literature

Pyrrolo[2,1-c][1,4]benzodiazepines are potent, naturally occurring anti­tumor anti­biotics produced by Streptomyces species; see: Cargill et al. (1974 [triangle]); Thurston et al. (1993 [triangle]). For the design and synthesis of DNA inter-strand cross-linking as well as conjugate agents to enhance the sequence selectivity and to increase selectivity for tumor cells, see: Bose et al. (1992 [triangle]); Gregson et al. (2004 [triangle]).

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Object name is e-65-o2322-scheme1.jpg

Experimental

Crystal data

  • C15H16N2O2
  • M r = 256.30
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-65-o2322-efi1.jpg
  • a = 7.0988 (1) Å
  • b = 11.7166 (2) Å
  • c = 15.6592 (3) Å
  • V = 1302.44 (4) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 193 K
  • 0.30 × 0.30 × 0.20 mm

Data collection

  • Bruker APEXII diffractometer
  • Absorption correction: none
  • 20329 measured reflections
  • 2263 independent reflections
  • 1900 reflections with I > 2σ(I)
  • R int = 0.031

Refinement

  • R[F 2 > 2σ(F 2)] = 0.049
  • wR(F 2) = 0.146
  • S = 1.04
  • 2263 reflections
  • 178 parameters
  • 15 restraints
  • H-atom parameters constrained
  • Δρmax = 0.53 e Å−3
  • Δρmin = −0.30 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, 2009 [triangle]).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809034266/sj2637sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809034266/sj2637Isup2.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

2,3-Dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione (1 g, 4.6 mmol), allyl bromide (0.64 g, 4.6 mmol) and potassium carbonate (0.64 g, 4.6 mmol) along with a catalytic amount of tetra-n-butyammonium bromide were stirred in N,N-dimethylformamide (20 ml) for 12 h. After the completion of the reaction (as 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 dichloromethane to afford colorless crystals in 80% yield. The formulation was established by proton and carbon-13 NMR spectroscopy in CDCl3.

Refinement

Carbon-bound H-atoms were placed in calculated positions (C—H 0.95 to 0.99 Å) and were included in the refinement in the riding model approximation, with U(H) set to 1.2U(C).

Two of the carbon atoms in the tetrahydropyrrolyl ring are disordered over two positions; the occupancy cound not be refined, and was assumed to be 50:50. The pairs of carbon-carbon (C10–C11, C10'–C11') distances were restrained to within 0.01 Å of each other, and the temperature factors of the primed atoms were restrained to those of the unprimed ones. Their anisotropic temperature factors were restrained to nearly isotropic values.

In the absence of significant anomalous dispersion effects, Freidel pairs were merged.

Figures

Fig. 1.
Thermal ellipsoid plot (Barbour, 2001) of C15H16N2O2 at the 70% probability level; hydrogen atoms are drawn as spheres of arbitrary radius.

Crystal data

C15H16N2O2F(000) = 544
Mr = 256.30Dx = 1.307 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 7433 reflections
a = 7.0988 (1) Åθ = 2.2–25.3°
b = 11.7166 (2) ŵ = 0.09 mm1
c = 15.6592 (3) ÅT = 193 K
V = 1302.44 (4) Å3Block, colorless
Z = 40.30 × 0.30 × 0.20 mm

Data collection

Bruker APEXII diffractometer1900 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.031
graphiteθmax = 30.5°, θmin = 5.2°
[var phi] and ω scansh = −10→10
20329 measured reflectionsk = −16→14
2263 independent reflectionsl = −22→19

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)] = 0.049Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.146H-atom parameters constrained
S = 1.03w = 1/[σ2(Fo2) + (0.086P)2 + 0.2922P] where P = (Fo2 + 2Fc2)/3
2263 reflections(Δ/σ)max = 0.001
178 parametersΔρmax = 0.53 e Å3
15 restraintsΔρmin = −0.30 e Å3

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

xyzUiso*/UeqOcc. (<1)
O10.3349 (3)0.89582 (17)0.62000 (12)0.0545 (5)
O2−0.1387 (3)0.62142 (13)0.76109 (11)0.0423 (4)
N10.2785 (2)0.86934 (15)0.76059 (12)0.0312 (4)
N2−0.0624 (3)0.77145 (15)0.67775 (12)0.0327 (4)
C10.2213 (4)0.88657 (18)0.67841 (15)0.0355 (5)
C2−0.0695 (3)0.71719 (17)0.75353 (14)0.0301 (4)
C3−0.0008 (3)0.78280 (17)0.82960 (13)0.0280 (4)
C40.1542 (3)0.85792 (16)0.83096 (13)0.0279 (4)
C50.1940 (3)0.91758 (17)0.90646 (13)0.0333 (4)
H50.29890.96780.90830.040*
C60.0828 (4)0.9044 (2)0.97834 (14)0.0396 (5)
H60.10900.94761.02830.048*
C7−0.0675 (4)0.8278 (2)0.97772 (14)0.0407 (5)
H7−0.14250.81721.02740.049*
C8−0.1059 (3)0.76768 (19)0.90409 (14)0.0359 (5)
H8−0.20690.71440.90400.043*
C9−0.1524 (4)0.7262 (2)0.60032 (14)0.0399 (5)
H9A−0.26780.68230.61370.048*0.50
H9B−0.06510.67800.56670.048*0.50
H9C−0.27590.69160.61430.048*0.50
H9D−0.07190.66710.57360.048*0.50
C10−0.197 (3)0.8367 (11)0.5551 (12)0.059 (3)0.50
H10A−0.21870.82360.49350.071*0.50
H10B−0.31020.87320.58000.071*0.50
C11−0.025 (2)0.9097 (17)0.5692 (5)0.047 (2)0.50
H11A−0.05000.99120.55700.056*0.50
H11B0.08320.88350.53420.056*0.50
C10'−0.178 (3)0.8258 (11)0.5408 (12)0.059 (3)0.50
H10C−0.31240.84650.53660.071*0.50
H10D−0.13120.80610.48300.071*0.50
C11'−0.066 (2)0.9241 (16)0.5769 (5)0.047 (2)0.50
H11C−0.14750.99230.58230.056*0.50
H11D0.04000.94300.53840.056*0.50
C120.0096 (3)0.88869 (18)0.66551 (14)0.0339 (5)
H12−0.05510.94590.70270.041*0.50
H12'−0.04790.93940.70980.041*0.50
C130.4837 (3)0.8775 (2)0.77691 (19)0.0433 (6)
H13A0.55220.83220.73350.052*
H13B0.51210.84460.83370.052*
C140.5520 (4)1.0005 (2)0.7740 (2)0.0490 (6)
H140.50201.04900.73090.059*
C150.6751 (4)1.0438 (3)0.8269 (2)0.0565 (7)
H15A0.72780.99760.87070.068*
H15B0.71191.12140.82160.068*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0621 (12)0.0550 (11)0.0466 (10)−0.0140 (10)0.0231 (9)−0.0031 (9)
O20.0473 (9)0.0272 (7)0.0525 (10)−0.0097 (7)−0.0042 (8)0.0039 (7)
N10.0253 (7)0.0269 (8)0.0413 (10)−0.0014 (6)0.0036 (7)0.0012 (7)
N20.0361 (8)0.0276 (8)0.0345 (8)−0.0072 (7)−0.0013 (8)−0.0020 (7)
C10.0425 (11)0.0278 (9)0.0362 (10)−0.0075 (9)0.0072 (9)−0.0012 (8)
C20.0273 (8)0.0252 (8)0.0380 (10)−0.0003 (7)0.0003 (9)0.0007 (8)
C30.0266 (8)0.0245 (8)0.0331 (9)0.0012 (7)−0.0001 (8)0.0042 (7)
C40.0267 (8)0.0225 (8)0.0345 (9)0.0010 (7)−0.0026 (8)0.0043 (7)
C50.0358 (10)0.0277 (9)0.0362 (10)−0.0004 (8)−0.0083 (9)0.0034 (8)
C60.0487 (13)0.0388 (11)0.0312 (10)0.0040 (10)−0.0062 (10)0.0022 (9)
C70.0467 (12)0.0436 (12)0.0320 (10)0.0029 (11)0.0042 (10)0.0098 (9)
C80.0345 (10)0.0360 (10)0.0372 (10)−0.0027 (9)0.0015 (9)0.0095 (9)
C90.0446 (12)0.0394 (11)0.0357 (11)−0.0074 (10)−0.0010 (10)−0.0097 (9)
C100.088 (4)0.059 (3)0.031 (5)−0.015 (3)−0.015 (4)0.000 (3)
C110.061 (6)0.042 (4)0.0371 (16)−0.008 (4)−0.012 (3)0.010 (2)
C10'0.088 (4)0.059 (3)0.031 (5)−0.015 (3)−0.015 (4)0.000 (3)
C11'0.061 (6)0.042 (4)0.0371 (16)−0.008 (4)−0.012 (3)0.010 (2)
C120.0440 (11)0.0259 (9)0.0319 (10)−0.0067 (9)−0.0066 (9)0.0041 (8)
C130.0253 (9)0.0403 (12)0.0643 (16)0.0012 (9)0.0044 (10)−0.0007 (11)
C140.0315 (11)0.0506 (14)0.0648 (16)−0.0065 (11)0.0037 (12)0.0040 (13)
C150.0413 (13)0.0502 (14)0.078 (2)−0.0061 (12)0.0002 (15)−0.0023 (14)

Geometric parameters (Å, °)

O1—C11.224 (3)C9—H9C0.9900
O2—C21.231 (3)C9—H9D0.9900
N1—C11.365 (3)C10—C111.509 (9)
N1—C41.418 (3)C10—H10A0.9900
N1—C131.482 (3)C10—H10B0.9900
N2—C21.347 (3)C11—C121.547 (6)
N2—C91.470 (3)C11—H11A0.9900
N2—C121.478 (3)C11—H11B0.9900
C1—C121.517 (4)C10'—C11'1.507 (9)
C2—C31.499 (3)C10'—H10C0.9900
C3—C81.396 (3)C10'—H10D0.9900
C3—C41.409 (3)C11'—C121.545 (6)
C4—C51.402 (3)C11'—H11C0.9900
C5—C61.383 (3)C11'—H11D0.9900
C5—H50.9500C12—H121.0000
C6—C71.395 (4)C12—H12'1.0000
C6—H60.9500C13—C141.522 (3)
C7—C81.378 (3)C13—H13A0.9900
C7—H70.9500C13—H13B0.9900
C8—H80.9500C14—C151.306 (4)
C9—C10'1.504 (7)C14—H140.9500
C9—C101.510 (7)C15—H15A0.9500
C9—H9A0.9900C15—H15B0.9500
C9—H9B0.9900
C1—N1—C4124.17 (18)C11—C10—H10A110.9
C1—N1—C13116.5 (2)C9—C10—H10A110.9
C4—N1—C13118.9 (2)C11—C10—H10B110.9
C2—N2—C9122.70 (18)C9—C10—H10B110.9
C2—N2—C12124.44 (18)H10A—C10—H10B108.9
C9—N2—C12112.27 (18)C10—C11—C12100.3 (12)
O1—C1—N1121.5 (2)C10—C11—H11A111.7
O1—C1—C12123.5 (2)C12—C11—H11A111.7
N1—C1—C12115.02 (19)C10—C11—H11B111.7
O2—C2—N2122.0 (2)C12—C11—H11B111.7
O2—C2—C3121.4 (2)H11A—C11—H11B109.5
N2—C2—C3116.48 (18)C9—C10'—C11'107.4 (12)
C8—C3—C4118.96 (19)C9—C10'—H10C110.2
C8—C3—C2115.13 (18)C11'—C10'—H10C110.2
C4—C3—C2125.89 (18)C9—C10'—H10D110.2
C5—C4—C3118.78 (19)C11'—C10'—H10D110.2
C5—C4—N1118.87 (18)H10C—C10'—H10D108.5
C3—C4—N1122.21 (18)C10'—C11'—C12108.3 (12)
C6—C5—C4121.0 (2)C10'—C11'—H11C110.0
C6—C5—H5119.5C12—C11'—H11C110.0
C4—C5—H5119.5C10'—C11'—H11D110.0
C5—C6—C7120.2 (2)C12—C11'—H11D110.0
C5—C6—H6119.9H11C—C11'—H11D108.4
C7—C6—H6119.9N2—C12—C1108.08 (19)
C8—C7—C6119.1 (2)N2—C12—C11'104.2 (8)
C8—C7—H7120.5C1—C12—C11'117.9 (7)
C6—C7—H7120.5N2—C12—C11102.7 (8)
C7—C8—C3121.9 (2)C1—C12—C11106.7 (6)
C7—C8—H8119.1N2—C12—H12112.9
C3—C8—H8119.1C1—C12—H12112.9
N2—C9—C10'106.4 (8)C11'—C12—H12100.6
N2—C9—C1099.7 (8)C11—C12—H12112.9
N2—C9—H9A111.8N2—C12—H12'108.8
C10'—C9—H9A115.9C1—C12—H12'108.8
C10—C9—H9A111.8C11'—C12—H12'108.8
N2—C9—H9B111.8C11—C12—H12'121.1
C10'—C9—H9B100.8N1—C13—C14111.7 (2)
C10—C9—H9B111.8N1—C13—H13A109.3
H9A—C9—H9B109.6C14—C13—H13A109.3
N2—C9—H9C110.5N1—C13—H13B109.3
C10'—C9—H9C110.5C14—C13—H13B109.3
C10—C9—H9C105.6H13A—C13—H13B108.0
H9B—C9—H9C116.1C15—C14—C13124.2 (3)
N2—C9—H9D110.5C15—C14—H14117.9
C10'—C9—H9D110.5C13—C14—H14117.9
C10—C9—H9D121.5C14—C15—H15A120.0
H9A—C9—H9D101.8C14—C15—H15B120.0
H9C—C9—H9D108.6H15A—C15—H15B120.0
C11—C10—C9104.3 (14)
C4—N1—C1—O1−180.0 (2)C2—N2—C9—C10150.1 (10)
C13—N1—C1—O17.7 (3)C12—N2—C9—C10−21.4 (10)
C4—N1—C1—C12−2.2 (3)N2—C9—C10—C1141.2 (14)
C13—N1—C1—C12−174.50 (19)C10'—C9—C10—C11−87 (8)
C9—N2—C2—O26.1 (3)C9—C10—C11—C12−45.3 (16)
C12—N2—C2—O2176.6 (2)N2—C9—C10'—C11'11.4 (17)
C9—N2—C2—C3−169.74 (19)C10—C9—C10'—C11'65 (8)
C12—N2—C2—C30.8 (3)C9—C10'—C11'—C12−6.8 (19)
O2—C2—C3—C8−35.3 (3)C2—N2—C12—C170.3 (3)
N2—C2—C3—C8140.6 (2)C9—N2—C12—C1−118.3 (2)
O2—C2—C3—C4146.2 (2)C2—N2—C12—C11'−163.4 (7)
N2—C2—C3—C4−38.0 (3)C9—N2—C12—C11'7.9 (7)
C8—C3—C4—C5−1.9 (3)C2—N2—C12—C11−177.1 (6)
C2—C3—C4—C5176.60 (19)C9—N2—C12—C11−5.7 (6)
C8—C3—C4—N1173.72 (18)O1—C1—C12—N2107.3 (3)
C2—C3—C4—N1−7.8 (3)N1—C1—C12—N2−70.5 (3)
C1—N1—C4—C5−134.8 (2)O1—C1—C12—C11'−10.4 (9)
C13—N1—C4—C537.4 (3)N1—C1—C12—C11'171.8 (8)
C1—N1—C4—C349.6 (3)O1—C1—C12—C11−2.6 (8)
C13—N1—C4—C3−138.2 (2)N1—C1—C12—C11179.7 (8)
C3—C4—C5—C6−0.7 (3)C10'—C11'—C12—N2−0.5 (14)
N1—C4—C5—C6−176.43 (19)C10'—C11'—C12—C1119.3 (11)
C4—C5—C6—C72.4 (3)C10'—C11'—C12—C1185 (7)
C5—C6—C7—C8−1.4 (4)C10—C11—C12—N230.4 (12)
C6—C7—C8—C3−1.2 (4)C10—C11—C12—C1144.0 (10)
C4—C3—C8—C72.9 (3)C10—C11—C12—C11'−68 (6)
C2—C3—C8—C7−175.8 (2)C1—N1—C13—C1473.4 (3)
C2—N2—C9—C10'159.3 (10)C4—N1—C13—C14−99.4 (3)
C12—N2—C9—C10'−12.3 (10)N1—C13—C14—C15139.5 (3)

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: SJ2637).

References

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  • Bose, D. S., Thompson, A. S., Ching, J. A., Hartley, J. A., Berardini, M. D., Jenkins, T. C., Neidle, S., Hurley, L. H. & Thurston, D. E. (1992). J. Am. Chem. Soc.114, 4939–4941.
  • 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]
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  • Thurston, D. E., Neidle, S. & Waring, M. J. (1993). Molecular Aspects of Anticancer Drug-DNA Interactions, Vol. 1, pp. 54–88. New York: Macmillan Press.
  • Westrip, S. P. (2009). publCIF In preparation.

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