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Acta Cryst. (2009). E65, o2322    [ doi:10.1107/S1600536809034266 ]

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

H. Benzeid, E. M. Essassi, N. Saffon, B. Garrigues and S. W. Ng

Abstract top

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 top

Pyrrolo[2,1-c][1,4]benzodiazepines are potent, naturally occurring antitumor antibiotics produced by Streptomyces species; see: Cargill et al. (1974); Thurston et al. (1993). 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); Gregson et al. (2004).

Experimental top

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 top

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.

Computing details top

Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT (Bruker, 2005); data reduction: SAINT (Bruker, 2005); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: X-SEED (Barbour, 2001); software used to prepare material for publication: publCIF (Westrip, 2009).

Figures top
[Figure 1] Fig. 1. Thermal ellipsoid plot (Barbour, 2001) of C15H16N2O2 at the 70% probability level; hydrogen atoms are drawn as spheres of arbitrary radius.
\ 10-Allyl-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,\ 11(10H,11aH)-dione top
Crystal data top
C15H16N2O2F(000) = 544
Mr = 256.30Dx = 1.307 Mg m−3
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 mm−1
c = 15.6592 (3) ÅT = 193 K
V = 1302.44 (4) Å3Block, colorless
Z = 40.30 × 0.30 × 0.20 mm
Data collection top
Bruker APEXII
diffractometer		1900 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.031
graphiteθmax = 30.5°, θmin = 5.2°
φ and ω scansh = −10→10
20329 measured reflectionsk = −16→14
2263 independent reflectionsl = −22→19
Refinement top
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 = 1.03 w = 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 Å−3
15 restraintsΔρmin = −0.30 e Å−3
Crystal data top
C15H16N2O2V = 1302.44 (4) Å3
Mr = 256.30Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 7.0988 (1) ŵ = 0.09 mm−1
b = 11.7166 (2) ÅT = 193 K
c = 15.6592 (3) Å0.30 × 0.30 × 0.20 mm
Data collection top
Bruker APEXII
diffractometer		Rint = 0.031
20329 measured reflectionsθmax = 30.5°
2263 independent reflectionsStandard reflections: 0
1900 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.049H-atom parameters constrained
wR(F2) = 0.146Δρmax = 0.53 e Å−3
S = 1.03Δρmin = −0.30 e Å−3
2263 reflectionsAbsolute structure: ?
178 parametersFlack parameter: ?
15 restraintsRogers parameter: ?
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
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) top
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, °) top
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)
Acknowledgements top

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

references
References top

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