organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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

aLaboratoire de Chimie Organique Hétérocyclique, Pôle de Compétences Pharmacochimie, Université Mohammed V-Agdal, BP 1014 Avenue Ibn Batout, Rabat, Morocco, bCNRST, Division of UATRS Angle Allal Fassi/FAR, BP 8027 Hay Riad, 10000 Rabat, Morocco, and cDepartment of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
*Correspondence e-mail: seikweng@um.edu.my

(Received 21 February 2010; accepted 23 February 2010; online 3 March 2010)

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[Cargill, C., Bachmann, E. & Zbinden, G. (1974). J. Natl. Cancer Inst. 53, 481- 486.]). 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[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.]).

[Scheme 1]

Experimental

Crystal data
  • C15H14N2O3·H2O

  • Mr = 288.30

  • Monoclinic, P 21

  • 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)

  • Rint = 0.021

Refinement
  • R[F2 > 2σ(F2)] = 0.029

  • wR(F2) = 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

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O3—H3⋯O1w 0.84 (1) 1.85 (1) 2.686 (2) 177 (3)
O1w—H11⋯O2i 0.84 (1) 1.92 (1) 2.7485 (19) 172 (4)
O1w—H12⋯O3ii 0.84 (1) 1.92 (1) 2.767 (2) 177 (3)
C15—H15⋯O1iii 0.93 2.29 3.166 (3) 157
Symmetry codes: (i) [-x+1, y-{\script{1\over 2}}, -z]; (ii) [-x+1, y+{\script{1\over 2}}, -z]; (iii) [-x+1, y+{\script{1\over 2}}, -z+1].

Data collection: APEX2 (Bruker, 2005[Bruker (2005). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2005[Bruker (2005). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: X-SEED (Barbour, 2001[Barbour, L. J. (2001). J. Supramol. Chem. 1, 189-191.]); software used to prepare material for publication: publCIF (Westrip, 2010[Westrip, S. P. (2010). publCIF. In preparation.]).

Supporting information


Related literature top

Pyrrolo[2,1-c][1,4]benzodiazepines are potent antibiotics produced by Streptomyces species; see: Cargill et al. (1974). 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).

Experimental top

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 top

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.

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, 2010).

Figures top
[Figure 1] 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.
2-Hydroxy-10-propargylpyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione monohydrate top
Crystal data top
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 top
Bruker APEXII
diffractometer
1680 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.021
Graphite monochromatorθmax = 27.5°, θmin = 1.6°
ϕ and ω scansh = 88
9524 measured reflectionsk = 1010
1744 independent reflectionsl = 1616
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)] = 0.029Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.094H atoms treated by a mixture of independent and constrained refinement
S = 1.10 w = 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
Crystal data top
C15H14N2O3·H2OV = 709.72 (2) Å3
Mr = 288.30Z = 2
Monoclinic, P21Mo Kα radiation
a = 6.8977 (1) ŵ = 0.10 mm1
b = 7.9761 (1) ÅT = 293 K
c = 13.0680 (2) Å0.3 × 0.3 × 0.3 mm
β = 99.194 (1)°
Data collection top
Bruker APEXII
diffractometer
1680 reflections with I > 2σ(I)
9524 measured reflectionsRint = 0.021
1744 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0294 restraints
wR(F2) = 0.094H atoms treated by a mixture of independent and constrained refinement
S = 1.10Δρmax = 0.18 e Å3
1744 reflectionsΔρmin = 0.16 e Å3
202 parameters
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
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)
N10.0173 (2)0.7109 (2)0.37874 (10)0.0320 (3)
N20.1101 (2)0.74500 (19)0.17437 (11)0.0317 (3)
C10.1606 (2)0.8238 (2)0.32657 (12)0.0301 (3)
C20.3329 (2)0.8493 (3)0.36900 (14)0.0377 (4)
H20.35590.78500.42520.045*
C30.4683 (3)0.9684 (3)0.32844 (16)0.0456 (5)
H3A0.58160.98350.35760.055*
C40.4380 (3)1.0654 (3)0.24530 (15)0.0466 (5)
H40.52811.14780.21940.056*
C50.2715 (3)1.0388 (3)0.20077 (14)0.0410 (4)
H50.25121.10330.14420.049*
C60.1333 (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)
H11A0.11260.58410.19090.037*
C120.0799 (2)0.5931 (2)0.33103 (12)0.0319 (3)
C130.0327 (3)0.7196 (3)0.49276 (13)0.0362 (4)
H13A0.07580.77030.52040.043*
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) top
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, º) top
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—C647.5 (2)C7—N2—C8—C9171.01 (16)
C13—N1—C1—C6132.32 (17)C11—N2—C8—C918.65 (19)
C12—N1—C1—C2136.14 (18)N2—C8—C9—O3154.01 (16)
C13—N1—C1—C244.0 (2)N2—C8—C9—C1034.20 (19)
C6—C1—C2—C32.8 (3)O3—C9—C10—C11159.11 (16)
N1—C1—C2—C3173.70 (18)C8—C9—C10—C1137.66 (19)
C1—C2—C3—C40.0 (3)C7—N2—C11—C1274.4 (2)
C2—C3—C4—C51.8 (3)C8—N2—C11—C12115.58 (16)
C3—C4—C5—C60.6 (3)C7—N2—C11—C10165.40 (18)
C4—C5—C6—C12.2 (3)C8—N2—C11—C104.59 (18)
C4—C5—C6—C7177.42 (19)C9—C10—C11—N226.07 (18)
C2—C1—C6—C53.9 (2)C9—C10—C11—C1289.97 (17)
N1—C1—C6—C5172.45 (16)C1—N1—C12—O1179.99 (17)
C2—C1—C6—C7175.72 (16)C13—N1—C12—O10.2 (2)
N1—C1—C6—C78.0 (3)C1—N1—C12—C111.6 (2)
C8—N2—C7—O21.4 (3)C13—N1—C12—C11178.26 (14)
C11—N2—C7—O2170.47 (17)N2—C11—C12—O1109.22 (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—N1177.03 (14)
C1—C6—C7—O2150.25 (19)C12—N1—C13—C1481.9 (2)
C5—C6—C7—N2146.98 (17)C1—N1—C13—C1497.99 (19)
C1—C6—C7—N232.6 (3)N1—C13—C14—C15158 (6)
Hydrogen-bond geometry (Å, º) top
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, y1/2, z; (ii) x+1, y+1/2, z; (iii) x+1, y+1/2, z+1.

Experimental details

Crystal data
Chemical formulaC15H14N2O3·H2O
Mr288.30
Crystal system, space groupMonoclinic, P21
Temperature (K)293
a, b, c (Å)6.8977 (1), 7.9761 (1), 13.0680 (2)
β (°) 99.194 (1)
V3)709.72 (2)
Z2
Radiation typeMo Kα
µ (mm1)0.10
Crystal size (mm)0.3 × 0.3 × 0.3
Data collection
DiffractometerBruker APEXII
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
9524, 1744, 1680
Rint0.021
(sin θ/λ)max1)0.650
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.029, 0.094, 1.10
No. of reflections1744
No. of parameters202
No. of restraints4
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.18, 0.16

Computer programs: APEX2 (Bruker, 2005), SAINT (Bruker, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), X-SEED (Barbour, 2001), publCIF (Westrip, 2010).

Hydrogen-bond geometry (Å, º) top
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, y1/2, z; (ii) x+1, y+1/2, z; (iii) x+1, y+1/2, z+1.
 

Acknowledgements

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

References

First citationBarbour, L. J. (2001). J. Supramol. Chem. 1, 189–191.  CrossRef CAS
First citationBruker (2005). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.
First citationCargill, C., Bachmann, E. & Zbinden, G. (1974). J. Natl. Cancer Inst. 53, 481– 486.  CAS PubMed Web of Science
First citationGregson, 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.  Web of Science CrossRef PubMed CAS
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationWestrip, S. P. (2010). publCIF. In preparation.

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