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

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ISSN: 2056-9890

(11aS)-7-Bromo-2,3,5,10,11,11a-hexa­hydro-1H-pyrrolo­[2,1-c][1,4]benzodiazepine-3,11-dione

aSchool of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China, and bJiangsu Kanion Pharmaceutical Co. Ltd, Lianyungang 222001, People's Republic of China
*Correspondence e-mail: machao@syphu.edu.cn

(Received 5 December 2011; accepted 8 December 2011; online 14 December 2011)

The title compound, C12H11BrN2O2, was prepared by an intra-cyclization reaction of (S)-1-(5-bromo-2-nitro­benz­yl)-5-oxopyrrolidine-2-carb­oxy­lic acid methyl ester in the presence of EtOH/Fe. The five-membered pyrrolidinone ring adopts an approximate envelope conformation, while the seven-membered diazepanone ring displays a twisted boat conformation. Inter­molecular classical N—H⋯O hydrogen bonds and weak C—H⋯O inter­actions help to stabilize the crystal structure.

Related literature

For applications of pyrrolo­[2,1-c][1,4]benzodiazepines, see: Bose et al. (1992[Bose, D. S., Jones, G. B. & Thurston, D. E. (1992). Tetrahedron, 48, 751-758.]); Hu et al. (2001[Hu, W.-P., Wang, J.-J., Lin, F.-L., Lin, Y.-C., Lin, S.-R. & Hsu, M.-H. (2001). J. Org. Chem. 66, 2881-2883.]); Jitendra et al. (2007[Jitendra, K. M., Puja, G., Preeti, D., Ashutosh, K., Mohammad, I. S., Madhur, R. & Gautam, P. (2007). Bioorg. Med. Chem. Lett. 17, 1326-1331.]); Kamal et al. (2002[Kamal, A., Rao, M. V., Laxman, N., Ramesh, G. & Reddy, G. S. K. (2002). Curr. Med. Chem. Anti-Cancer Agent. 2, 215-254.]); Thurston & Bose (1994[Thurston, D. E. & Bose, D. S. (1994). Chem. Rev. 94, 433-465.]). For a related structure, see: Cheng et al. (2007[Cheng, M.-S., Ma, C., Liu, J.-H., Sha, Y. & Wang, Q.-H. (2007). Acta Cryst. E63, o4605.]).

[Scheme 1]

Experimental

Crystal data
  • C12H11BrN2O2

  • Mr = 295.14

  • Orthorhombic, P 21 21 21

  • a = 4.3880 (4) Å

  • b = 13.1210 (11) Å

  • c = 19.8722 (16) Å

  • V = 1144.14 (17) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 3.58 mm−1

  • T = 185 K

  • 0.22 × 0.18 × 0.07 mm

Data collection
  • Bruker APEX CCD area-detector diffractometer

  • Absorption correction: multi-scan (SADABS; Bruker, 2001[Bruker (2001). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.506, Tmax = 0.788

  • 7012 measured reflections

  • 2244 independent reflections

  • 2074 reflections with I > 2σ(I)

  • Rint = 0.021

Refinement
  • R[F2 > 2σ(F2)] = 0.022

  • wR(F2) = 0.057

  • S = 1.02

  • 2244 reflections

  • 154 parameters

  • H-atom parameters constrained

  • Δρmax = 0.49 e Å−3

  • Δρmin = −0.21 e Å−3

  • Absolute structure: Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]), 884 Friedel pairs

  • Flack parameter: −0.007 (9)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N2—H2⋯O1i 0.88 2.00 2.864 (2) 169
C5—H5A⋯O2ii 0.99 2.38 3.328 (3) 160
Symmetry codes: (i) [-x+2, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]; (ii) [-x+2, y-{\script{1\over 2}}, -z+{\script{3\over 2}}].

Data collection: SMART (Bruker, 2007[Bruker (2007). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2007[Bruker (2007). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Supporting information


Comment top

Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are of considerable interest because of their wide range of biological activities such as antitumor agents, gene regulators, DNA probes, and anti-ischemic agents (Bose et al., 1992; Hu et al., 2001; Jitendra et al.,2007; Kamal et al., 2002; Thurston & Bose, 1994). As PBDs compounds are of great pharmaceutical importance, we determined the title chiral compound's crystal structure. The molecular is shown in Fig. 1 and the bond lengths and angles are within normal ranges. PBD ring involes in a twisted conformation, similar to a related structure (Cheng et al., 2007). The seven-membered ring C5—C6—C7—N2—C8—C4—N1 (substituted diazepine) is far from planar, and its shape approximates to a twist boat. In this description applied to the title compound (Fig. 1), atoms C5, C8, N1 and N2 form the bottom of the boat (deviation from the mean N1/C5/N2/C8 plane = 0.138 (5) Å), C4 the prow, and C6 and C7 the stern [deviations from the C5/C8/N1/N2 mean plane = 0.641, 0.854, 0.952 Å, respectively]. The bond length of the carbonyl groups C8=O2 and C1=O1 of 1.221 (2) and 1.233 (3) Å, respectively, are somewhat longer than typical carbonyl bonds. This may be due to the fact that atoms O1 and O2 participate in intermolecular van der Waals forces. The five-membered ring N1—C1—C2—C3—C4 (substituted pyrrole) is non-planar and adopts nearly envelope conformation (deviation from the mean C4/N1/C1/C2 plane = 0.019 Å). The C3 atom is located above the plane [deviations from the C4/N1/C1/C2 mean plane = 0.322 Å]. Atom C4 of the title molecule is chiral: S configuration was assigned to this atom based on the known chirality of the equivalent atom in the starting material. In the crystal structure, intermolecular C—H···O and N—H···O hydrogen bonds link the molecules together (Table 1) and help to stabilize the structure.

Related literature top

For applications of pyrrolo[2,1-c][1,4]benzodiazepines, see: Bose et al. (1992); Hu et al. (2001); Jitendra et al. (2007); Kamal et al. (2002); Thurston & Bose (1994). For a related structure, see: Cheng et al. (2007).

Experimental top

(S)-1-(5-bromo-2-nitrobenzyl)-5-oxopyrrolidine-2-carboxylic acid methyl ester (10.68 g, 30 mmol) was dissolved in ethanol (200 ml). Fe (3.92 g, 70 mmol) was added and the solution was heated to reflux for 50 min. The mixture was filtered and the filtrate was concentrated under vacuum. The pure product was obtained through silica gel chromatography (eluant: petroleum ether/ethyl acetate, 2:1). Single crystals suitable for X-ray diffraction were obtained by slow evaporation of a dilute solution of the title compound in ethyl acetate at room temperature.

Refinement top

All H atoms were placed in geometrically idealized positions with N—H = 0.88 Å and C—H = 0.95–1.00 Å, and refined in riding mode with Uiso(H) = 1.2Ueq(C,N).

Computing details top

Data collection: SMART (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The structure of the title compound, showing 30% probability displacement ellipsoids and the atom-numbering scheme.
[Figure 2] Fig. 2. The molecular packing of the title compound.
(11aS)-7-Bromo-2,3,5,10,11,11a-hexahydro-1H- pyrrolo[2,1-c][1,4]benzodiazepine-3,11-dione top
Crystal data top
C12H11BrN2O2F(000) = 592
Mr = 295.14Dx = 1.713 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 3967 reflections
a = 4.3880 (4) Åθ = 2.6–26.0°
b = 13.1210 (11) ŵ = 3.58 mm1
c = 19.8722 (16) ÅT = 185 K
V = 1144.14 (17) Å3Plate, colorless
Z = 40.22 × 0.18 × 0.07 mm
Data collection top
Bruker APEX CCD area-detector
diffractometer
2244 independent reflections
Radiation source: fine-focus sealed tube2074 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.021
ϕ and ω scansθmax = 26.0°, θmin = 1.9°
Absorption correction: multi-scan
(SADABS; Bruker, 2001)
h = 55
Tmin = 0.506, Tmax = 0.788k = 1416
7012 measured reflectionsl = 2324
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.022H-atom parameters constrained
wR(F2) = 0.057 w = 1/[σ2(Fo2) + (0.0236P)2]
where P = (Fo2 + 2Fc2)/3
S = 1.02(Δ/σ)max = 0.001
2244 reflectionsΔρmax = 0.49 e Å3
154 parametersΔρmin = 0.21 e Å3
0 restraintsAbsolute structure: Flack (1983), 884 Friedel pairs
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.007 (9)
Crystal data top
C12H11BrN2O2V = 1144.14 (17) Å3
Mr = 295.14Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 4.3880 (4) ŵ = 3.58 mm1
b = 13.1210 (11) ÅT = 185 K
c = 19.8722 (16) Å0.22 × 0.18 × 0.07 mm
Data collection top
Bruker APEX CCD area-detector
diffractometer
2244 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2001)
2074 reflections with I > 2σ(I)
Tmin = 0.506, Tmax = 0.788Rint = 0.021
7012 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.022H-atom parameters constrained
wR(F2) = 0.057Δρmax = 0.49 e Å3
S = 1.02Δρmin = 0.21 e Å3
2244 reflectionsAbsolute structure: Flack (1983), 884 Friedel pairs
154 parametersAbsolute structure parameter: 0.007 (9)
0 restraints
Special details top

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

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Br10.25401 (6)0.050666 (16)0.521650 (10)0.04269 (9)
O11.0495 (4)0.02986 (12)0.85625 (8)0.0421 (4)
O20.9421 (4)0.41192 (12)0.82097 (8)0.0443 (4)
N10.8206 (4)0.16602 (12)0.80547 (8)0.0238 (4)
N20.7499 (5)0.35871 (11)0.72148 (7)0.0275 (3)
H20.80760.41630.70270.033*
C10.8919 (5)0.10757 (16)0.85843 (11)0.0301 (5)
C20.7399 (7)0.15233 (16)0.92027 (10)0.0388 (5)
H2A0.88260.15370.95880.047*
H2B0.55740.11230.93290.047*
C30.6517 (5)0.26009 (17)0.89928 (10)0.0322 (5)
H3A0.80330.31010.91570.039*
H3B0.44890.27850.91750.039*
C40.6457 (4)0.25772 (15)0.82215 (10)0.0253 (5)
H40.43100.25020.80600.030*
C50.9226 (5)0.14577 (17)0.73654 (10)0.0249 (4)
H5A0.95720.07170.73120.030*
H5B1.11950.18080.72890.030*
C60.6986 (4)0.18057 (14)0.68438 (9)0.0214 (4)
C70.6198 (5)0.28407 (15)0.67832 (10)0.0240 (4)
C80.7940 (5)0.35007 (14)0.78876 (10)0.0276 (4)
C90.5797 (5)0.11109 (15)0.63852 (10)0.0233 (4)
H90.62710.04070.64240.028*
C100.3923 (5)0.14489 (17)0.58721 (10)0.0267 (4)
C110.3113 (5)0.24598 (17)0.58081 (10)0.0295 (5)
H110.18050.26760.54550.035*
C120.4250 (5)0.31536 (17)0.62704 (11)0.0291 (5)
H120.36920.38510.62370.035*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Br10.06219 (16)0.03517 (14)0.03072 (13)0.00004 (16)0.01668 (12)0.00718 (8)
O10.0678 (12)0.0294 (9)0.0292 (9)0.0169 (9)0.0064 (8)0.0009 (7)
O20.0671 (12)0.0285 (9)0.0374 (10)0.0143 (9)0.0088 (9)0.0034 (7)
N10.0321 (10)0.0195 (8)0.0199 (8)0.0021 (7)0.0005 (7)0.0026 (6)
N20.0391 (9)0.0173 (7)0.0262 (8)0.0044 (10)0.0027 (9)0.0003 (6)
C10.0400 (12)0.0244 (11)0.0261 (12)0.0031 (10)0.0012 (10)0.0022 (9)
C20.0597 (13)0.0332 (11)0.0235 (10)0.0038 (16)0.0059 (14)0.0014 (8)
C30.0411 (13)0.0314 (12)0.0241 (11)0.0036 (9)0.0040 (9)0.0054 (9)
C40.0293 (11)0.0230 (10)0.0236 (10)0.0028 (8)0.0022 (8)0.0028 (8)
C50.0268 (11)0.0250 (10)0.0229 (10)0.0004 (9)0.0013 (8)0.0031 (9)
C60.0230 (11)0.0221 (9)0.0190 (9)0.0013 (8)0.0077 (8)0.0005 (7)
C70.0288 (10)0.0202 (10)0.0231 (10)0.0035 (8)0.0048 (9)0.0011 (8)
C80.0316 (12)0.0195 (9)0.0318 (11)0.0024 (10)0.0010 (9)0.0039 (8)
C90.0273 (10)0.0202 (10)0.0226 (10)0.0005 (8)0.0028 (9)0.0010 (8)
C100.0313 (10)0.0271 (11)0.0218 (11)0.0033 (9)0.0014 (9)0.0043 (9)
C110.0359 (13)0.0320 (11)0.0205 (10)0.0047 (10)0.0015 (9)0.0051 (8)
C120.0383 (12)0.0219 (11)0.0271 (12)0.0035 (9)0.0050 (10)0.0029 (9)
Geometric parameters (Å, º) top
Br1—C101.896 (2)C3—H3B0.9900
O1—C11.233 (3)C4—C81.527 (3)
O2—C81.221 (2)C4—H41.0000
N1—C11.339 (3)C5—C61.500 (3)
N1—C41.465 (2)C5—H5A0.9900
N1—C51.465 (3)C5—H5B0.9900
N2—C81.356 (2)C6—C91.391 (3)
N2—C71.422 (3)C6—C71.406 (3)
N2—H20.8800C7—C121.392 (3)
C1—C21.517 (3)C9—C101.383 (3)
C2—C31.524 (3)C9—H90.9500
C2—H2A0.9900C10—C111.379 (3)
C2—H2B0.9900C11—C121.386 (3)
C3—C41.533 (3)C11—H110.9500
C3—H3A0.9900C12—H120.9500
C1—N1—C4114.51 (16)N1—C5—C6113.00 (16)
C1—N1—C5124.01 (17)N1—C5—H5A109.0
C4—N1—C5121.36 (15)C6—C5—H5A109.0
C8—N2—C7126.49 (16)N1—C5—H5B109.0
C8—N2—H2116.8C6—C5—H5B109.0
C7—N2—H2116.8H5A—C5—H5B107.8
O1—C1—N1125.2 (2)C9—C6—C7118.99 (18)
O1—C1—C2126.5 (2)C9—C6—C5119.95 (17)
N1—C1—C2108.19 (18)C7—C6—C5120.95 (18)
C1—C2—C3104.43 (17)C12—C7—C6119.90 (19)
C1—C2—H2A110.9C12—C7—N2119.02 (18)
C3—C2—H2A110.9C6—C7—N2120.98 (18)
C1—C2—H2B110.9O2—C8—N2122.50 (19)
C3—C2—H2B110.9O2—C8—C4121.76 (18)
H2A—C2—H2B108.9N2—C8—C4115.73 (17)
C2—C3—C4105.02 (17)C10—C9—C6119.74 (19)
C2—C3—H3A110.7C10—C9—H9120.1
C4—C3—H3A110.7C6—C9—H9120.1
C2—C3—H3B110.7C11—C10—C9121.97 (19)
C4—C3—H3B110.7C11—C10—Br1118.79 (15)
H3A—C3—H3B108.8C9—C10—Br1119.20 (16)
N1—C4—C8109.27 (16)C10—C11—C12118.56 (19)
N1—C4—C3103.52 (16)C10—C11—H11120.7
C8—C4—C3114.27 (17)C12—C11—H11120.7
N1—C4—H4109.9C11—C12—C7120.8 (2)
C8—C4—H4109.9C11—C12—H12119.6
C3—C4—H4109.9C7—C12—H12119.6
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2···O1i0.882.002.864 (2)169
C5—H5A···O2ii0.992.383.328 (3)160
Symmetry codes: (i) x+2, y+1/2, z+3/2; (ii) x+2, y1/2, z+3/2.

Experimental details

Crystal data
Chemical formulaC12H11BrN2O2
Mr295.14
Crystal system, space groupOrthorhombic, P212121
Temperature (K)185
a, b, c (Å)4.3880 (4), 13.1210 (11), 19.8722 (16)
V3)1144.14 (17)
Z4
Radiation typeMo Kα
µ (mm1)3.58
Crystal size (mm)0.22 × 0.18 × 0.07
Data collection
DiffractometerBruker APEX CCD area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2001)
Tmin, Tmax0.506, 0.788
No. of measured, independent and
observed [I > 2σ(I)] reflections
7012, 2244, 2074
Rint0.021
(sin θ/λ)max1)0.617
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.022, 0.057, 1.02
No. of reflections2244
No. of parameters154
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.49, 0.21
Absolute structureFlack (1983), 884 Friedel pairs
Absolute structure parameter0.007 (9)

Computer programs: SMART (Bruker, 2007), SAINT (Bruker, 2007), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2···O1i0.882.002.864 (2)168.6
C5—H5A···O2ii0.992.383.328 (3)160.1
Symmetry codes: (i) x+2, y+1/2, z+3/2; (ii) x+2, y1/2, z+3/2.
 

Acknowledgements

The work was supported by grants from the National Natural Science Foundation of China (No. 30973613) and the National Science Foundation for Post-doctoral Scientists of China (No. 2011M500578).

References

First citationBose, D. S., Jones, G. B. & Thurston, D. E. (1992). Tetrahedron, 48, 751–758.  CrossRef
First citationBruker (2001). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.
First citationBruker (2007). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.
First citationCheng, M.-S., Ma, C., Liu, J.-H., Sha, Y. & Wang, Q.-H. (2007). Acta Cryst. E63, o4605.  Web of Science CSD CrossRef IUCr Journals
First citationFlack, H. D. (1983). Acta Cryst. A39, 876–881.  CrossRef CAS Web of Science IUCr Journals
First citationHu, W.-P., Wang, J.-J., Lin, F.-L., Lin, Y.-C., Lin, S.-R. & Hsu, M.-H. (2001). J. Org. Chem. 66, 2881–2883.  Web of Science CrossRef PubMed CAS
First citationJitendra, K. M., Puja, G., Preeti, D., Ashutosh, K., Mohammad, I. S., Madhur, R. & Gautam, P. (2007). Bioorg. Med. Chem. Lett. 17, 1326–1331.  Web of Science PubMed
First citationKamal, A., Rao, M. V., Laxman, N., Ramesh, G. & Reddy, G. S. K. (2002). Curr. Med. Chem. Anti-Cancer Agent. 2, 215–254.  CrossRef CAS
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationThurston, D. E. & Bose, D. S. (1994). Chem. Rev. 94, 433–465.  CrossRef CAS Web of Science

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