The title chiral compound, C
12H
12N
2O
2, was prepared by an intramolecular cyclization reaction of (
S)-methyl 1-(2-nitrobenzyl)-5-oxopyrrolidine-2-carboxylate in the presence of EtOH/Fe. In the molecule, the seven-membered ring adopts a twist-boat conformation, while the five-membered ring shows a typical envelope conformation. The crystal structure is stabilized by intermolecular N—H
O hydrogen bonding.
Supporting information
CCDC reference: 672866
Key indicators
- Single-crystal X-ray study
- T = 187 K
- Mean (C-C) = 0.004 Å
- R factor = 0.036
- wR factor = 0.093
- Data-to-parameter ratio = 7.5
checkCIF/PLATON results
No syntax errors found
Alert level C
PLAT089_ALERT_3_C Poor Data / Parameter Ratio (Zmax .LT. 18) ..... 7.51
PLAT125_ALERT_4_C No _symmetry_space_group_name_Hall Given ....... ?
PLAT152_ALERT_1_C Supplied and Calc Volume s.u. Inconsistent ..... ?
Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
correct. If it is not, please give the correct count in the
_publ_section_exptl_refinement section of the submitted CIF.
From the CIF: _diffrn_reflns_theta_max 25.62
From the CIF: _reflns_number_total 1089
Count of symmetry unique reflns 1093
Completeness (_total/calc) 99.63%
TEST3: Check Friedels for noncentro structure
Estimate of Friedel pairs measured 0
Fraction of Friedel pairs measured 0.000
Are heavy atom types Z>Si present no
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C4 = . S
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints ....... 1
0 ALERT level A = In general: serious problem
0 ALERT level B = Potentially serious problem
3 ALERT level C = Check and explain
3 ALERT level G = General alerts; check
2 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
0 ALERT type 2 Indicator that the structure model may be wrong or deficient
2 ALERT type 3 Indicator that the structure quality may be low
2 ALERT type 4 Improvement, methodology, query or suggestion
0 ALERT type 5 Informative message, check
(S)-1-(2-Nitrobenzyl)-5-oxopyrrolidine-2-carboxylic acid methyl ester
(5.56 g, 20 mmol) was dissolved in ethanol (100 ml). Fe (2.51 g, 45 mmol) was
added and the solution was heated to reflux for 30 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, 1:1). 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.
All H atoms were placed in geometrically idealized positions and constrained to
ride on their parent atoms, with N—H = 0.88 Å, C—H = 0.95, 0.99 and 1.00 Å for phenyl, methylene and tertiary H atoms, respectively, Uiso(H)
= 1.2Ueq(C,N). Based on known chirality of the equivalent atom
in the starting material, the S chirality at C4 was assigned. Friedels pairs
were merged.
Data collection: SMART (Bruker, 1997); cell refinement: SAINT (Bruker, 1999); data reduction: SAINT (Bruker, 1999); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL-Plus (Siemens, 1990); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997).
(
S)-2,3,5,10,11,11
a-Hexahydro-1
H-pyrrolo[2,1-
c][1,4]benzodiazepine-3,11-dione
top
Crystal data top
C12H12N2O2 | F(000) = 456 |
Mr = 216.24 | Dx = 1.372 Mg m−3 |
Monoclinic, C2 | Mo Kα radiation, λ = 0.71073 Å |
a = 16.280 (2) Å | Cell parameters from 1769 reflections |
b = 6.2848 (9) Å | θ = 2.7–25.5° |
c = 11.1016 (15) Å | µ = 0.10 mm−1 |
β = 112.810 (2)° | T = 187 K |
V = 1047.0 (3) Å3 | Block, colorless |
Z = 4 | 0.36 × 0.17 × 0.13 mm |
Data collection top
Bruker SMART APEX CCD area-detector diffractometer | 1046 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.021 |
Graphite monochromator | θmax = 25.6°, θmin = 2.0° |
ϕ and ω scans | h = −19→16 |
2870 measured reflections | k = −7→7 |
1089 independent reflections | l = −8→13 |
Refinement top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.036 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.093 | H-atom parameters constrained |
S = 1.17 | w = 1/[σ2(Fo2) + (0.0528P)2 + 0.3158P] where P = (Fo2 + 2Fc2)/3 |
1089 reflections | (Δ/σ)max < 0.001 |
145 parameters | Δρmax = 0.20 e Å−3 |
1 restraint | Δρmin = −0.17 e Å−3 |
Crystal data top
C12H12N2O2 | V = 1047.0 (3) Å3 |
Mr = 216.24 | Z = 4 |
Monoclinic, C2 | Mo Kα radiation |
a = 16.280 (2) Å | µ = 0.10 mm−1 |
b = 6.2848 (9) Å | T = 187 K |
c = 11.1016 (15) Å | 0.36 × 0.17 × 0.13 mm |
β = 112.810 (2)° | |
Data collection top
Bruker SMART APEX CCD area-detector diffractometer | 1046 reflections with I > 2σ(I) |
2870 measured reflections | Rint = 0.021 |
1089 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.036 | 1 restraint |
wR(F2) = 0.093 | H-atom parameters constrained |
S = 1.17 | Δρmax = 0.20 e Å−3 |
1089 reflections | Δρmin = −0.17 e Å−3 |
145 parameters | |
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 | x | y | z | Uiso*/Ueq | |
C1 | 0.65320 (15) | 0.9090 (4) | 0.9102 (2) | 0.0281 (5) | |
C2 | 0.61760 (16) | 0.7804 (4) | 0.9947 (2) | 0.0313 (6) | |
H2A | 0.5689 | 0.8577 | 1.0083 | 0.038* | |
H2B | 0.6654 | 0.7504 | 1.0809 | 0.038* | |
C3 | 0.58320 (16) | 0.5751 (4) | 0.9194 (2) | 0.0308 (6) | |
H3A | 0.5181 | 0.5825 | 0.8688 | 0.037* | |
H3B | 0.5964 | 0.4517 | 0.9795 | 0.037* | |
C4 | 0.63361 (15) | 0.5576 (4) | 0.8278 (2) | 0.0249 (5) | |
H4 | 0.6886 | 0.4700 | 0.8700 | 0.030* | |
C5 | 0.57841 (15) | 0.4697 (4) | 0.6922 (2) | 0.0251 (5) | |
C6 | 0.71544 (15) | 0.4757 (4) | 0.6450 (2) | 0.0251 (5) | |
C7 | 0.76369 (16) | 0.3207 (4) | 0.6119 (2) | 0.0294 (5) | |
H7 | 0.7352 | 0.1945 | 0.5686 | 0.035* | |
C8 | 0.85484 (18) | 0.3519 (5) | 0.6431 (3) | 0.0342 (6) | |
H8 | 0.8885 | 0.2463 | 0.6212 | 0.041* | |
C9 | 0.89569 (16) | 0.5354 (5) | 0.7053 (3) | 0.0366 (6) | |
H9 | 0.9577 | 0.5556 | 0.7273 | 0.044* | |
C10 | 0.84635 (16) | 0.6912 (5) | 0.7360 (2) | 0.0330 (6) | |
H10 | 0.8749 | 0.8179 | 0.7783 | 0.040* | |
C11 | 0.75563 (15) | 0.6642 (4) | 0.7055 (2) | 0.0270 (5) | |
C12 | 0.70051 (17) | 0.8408 (4) | 0.7277 (2) | 0.0301 (5) | |
H12A | 0.7392 | 0.9658 | 0.7643 | 0.036* | |
H12B | 0.6540 | 0.8834 | 0.6428 | 0.036* | |
N1 | 0.65789 (13) | 0.7786 (3) | 0.81665 (19) | 0.0268 (5) | |
N2 | 0.62252 (12) | 0.4396 (4) | 0.61258 (18) | 0.0274 (5) | |
H2 | 0.5911 | 0.3934 | 0.5331 | 0.033* | |
O1 | 0.67442 (13) | 1.0953 (3) | 0.9227 (2) | 0.0395 (5) | |
O2 | 0.49882 (10) | 0.4306 (3) | 0.65628 (16) | 0.0328 (4) | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.0213 (10) | 0.0298 (14) | 0.0313 (12) | 0.0030 (10) | 0.0081 (9) | −0.0003 (10) |
C2 | 0.0262 (11) | 0.0376 (14) | 0.0336 (12) | −0.0003 (11) | 0.0155 (10) | −0.0049 (12) |
C3 | 0.0291 (12) | 0.0369 (14) | 0.0314 (12) | −0.0040 (11) | 0.0170 (10) | −0.0015 (11) |
C4 | 0.0241 (11) | 0.0252 (12) | 0.0261 (11) | −0.0006 (10) | 0.0105 (9) | 0.0013 (10) |
C5 | 0.0244 (11) | 0.0233 (11) | 0.0284 (11) | −0.0005 (9) | 0.0111 (9) | 0.0035 (10) |
C6 | 0.0250 (11) | 0.0316 (13) | 0.0207 (10) | −0.0004 (10) | 0.0110 (9) | 0.0025 (10) |
C7 | 0.0319 (12) | 0.0311 (14) | 0.0289 (11) | −0.0022 (11) | 0.0157 (9) | 0.0000 (10) |
C8 | 0.0323 (12) | 0.0407 (15) | 0.0353 (13) | 0.0066 (11) | 0.0193 (10) | 0.0057 (11) |
C9 | 0.0223 (11) | 0.0529 (18) | 0.0368 (13) | −0.0018 (12) | 0.0140 (10) | 0.0063 (13) |
C10 | 0.0291 (12) | 0.0385 (14) | 0.0317 (13) | −0.0098 (11) | 0.0121 (10) | 0.0011 (12) |
C11 | 0.0285 (12) | 0.0300 (14) | 0.0263 (11) | −0.0016 (11) | 0.0147 (9) | 0.0035 (10) |
C12 | 0.0363 (12) | 0.0253 (12) | 0.0328 (12) | −0.0040 (11) | 0.0178 (10) | 0.0013 (10) |
N1 | 0.0283 (10) | 0.0248 (10) | 0.0291 (10) | −0.0020 (8) | 0.0131 (8) | 0.0006 (9) |
N2 | 0.0223 (9) | 0.0354 (11) | 0.0235 (9) | −0.0055 (9) | 0.0078 (7) | −0.0047 (9) |
O1 | 0.0433 (11) | 0.0269 (10) | 0.0508 (11) | −0.0014 (8) | 0.0210 (9) | −0.0054 (9) |
O2 | 0.0199 (8) | 0.0461 (11) | 0.0329 (8) | −0.0053 (8) | 0.0107 (6) | −0.0001 (9) |
Geometric parameters (Å, º) top
C1—O1 | 1.213 (3) | C6—C11 | 1.393 (3) |
C1—N1 | 1.348 (3) | C6—N2 | 1.431 (3) |
C1—C2 | 1.514 (4) | C7—C8 | 1.401 (4) |
C2—C3 | 1.521 (4) | C7—H7 | 0.9500 |
C2—H2A | 0.9900 | C8—C9 | 1.376 (4) |
C2—H2B | 0.9900 | C8—H8 | 0.9500 |
C3—C4 | 1.538 (3) | C9—C10 | 1.390 (4) |
C3—H3A | 0.9900 | C9—H9 | 0.9500 |
C3—H3B | 0.9900 | C10—C11 | 1.392 (3) |
C4—N1 | 1.462 (3) | C10—H10 | 0.9500 |
C4—C5 | 1.527 (3) | C11—C12 | 1.507 (4) |
C4—H4 | 1.0000 | C12—N1 | 1.463 (3) |
C5—O2 | 1.224 (3) | C12—H12A | 0.9900 |
C5—N2 | 1.351 (3) | C12—H12B | 0.9900 |
C6—C7 | 1.387 (4) | N2—H2 | 0.8800 |
| | | |
O1—C1—N1 | 125.2 (3) | C6—C7—C8 | 119.4 (3) |
O1—C1—C2 | 127.2 (3) | C6—C7—H7 | 120.3 |
N1—C1—C2 | 107.6 (2) | C8—C7—H7 | 120.3 |
C1—C2—C3 | 105.10 (19) | C9—C8—C7 | 120.0 (2) |
C1—C2—H2A | 110.7 | C9—C8—H8 | 120.0 |
C3—C2—H2A | 110.7 | C7—C8—H8 | 120.0 |
C1—C2—H2B | 110.7 | C8—C9—C10 | 120.1 (2) |
C3—C2—H2B | 110.7 | C8—C9—H9 | 120.0 |
H2A—C2—H2B | 108.8 | C10—C9—H9 | 120.0 |
C2—C3—C4 | 104.26 (19) | C9—C10—C11 | 120.9 (3) |
C2—C3—H3A | 110.9 | C9—C10—H10 | 119.5 |
C4—C3—H3A | 110.9 | C11—C10—H10 | 119.5 |
C2—C3—H3B | 110.9 | C10—C11—C6 | 118.5 (2) |
C4—C3—H3B | 110.9 | C10—C11—C12 | 120.9 (2) |
H3A—C3—H3B | 108.9 | C6—C11—C12 | 120.5 (2) |
N1—C4—C5 | 109.59 (19) | N1—C12—C11 | 112.4 (2) |
N1—C4—C3 | 102.69 (19) | N1—C12—H12A | 109.1 |
C5—C4—C3 | 114.64 (18) | C11—C12—H12A | 109.1 |
N1—C4—H4 | 109.9 | N1—C12—H12B | 109.1 |
C5—C4—H4 | 109.9 | C11—C12—H12B | 109.1 |
C3—C4—H4 | 109.9 | H12A—C12—H12B | 107.8 |
O2—C5—N2 | 121.6 (2) | C1—N1—C12 | 122.7 (2) |
O2—C5—C4 | 122.5 (2) | C1—N1—C4 | 114.5 (2) |
N2—C5—C4 | 115.91 (18) | C12—N1—C4 | 121.72 (19) |
C7—C6—C11 | 121.1 (2) | C5—N2—C6 | 126.30 (18) |
C7—C6—N2 | 118.3 (2) | C5—N2—H2 | 116.9 |
C11—C6—N2 | 120.6 (2) | C6—N2—H2 | 116.9 |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2···O2i | 0.88 | 2.06 | 2.871 (2) | 153 |
Symmetry code: (i) −x+1, y, −z+1. |
Experimental details
Crystal data |
Chemical formula | C12H12N2O2 |
Mr | 216.24 |
Crystal system, space group | Monoclinic, C2 |
Temperature (K) | 187 |
a, b, c (Å) | 16.280 (2), 6.2848 (9), 11.1016 (15) |
β (°) | 112.810 (2) |
V (Å3) | 1047.0 (3) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.10 |
Crystal size (mm) | 0.36 × 0.17 × 0.13 |
|
Data collection |
Diffractometer | Bruker SMART APEX CCD area-detector diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2870, 1089, 1046 |
Rint | 0.021 |
(sin θ/λ)max (Å−1) | 0.608 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.036, 0.093, 1.17 |
No. of reflections | 1089 |
No. of parameters | 145 |
No. of restraints | 1 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.20, −0.17 |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2···O2i | 0.88 | 2.06 | 2.871 (2) | 153 |
Symmetry code: (i) −x+1, y, −z+1. |
Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are naturally occurring compounds isolated from various streptomyces (Kamal et al., 2002; Thurston & Bose, 1994). Such compounds have potential as regulators of gene expression with possible application as therapeutic agents in the treatment of certain genetic disorders including some cancers (Mishra et al., 2007; Mérour et al., 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. The bond lengths and angles are within normal ranges. PBD ring involves in a twisted conformation (Arora, 1979). The seven-membered ring C6—C11—C12—N1—C4—C5—N2 (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, C12, N1 and N2 form the bottom of the boat (deviation from the mean C5/N1/C12/N2 plane = 0.090 (2) Å), C4 the prow, and C6 and C11 the stern [deviations from the C5/C12/N1/N2 mean plane = 0.655, 0.951, 0.932 Å, respectively]. The bond length of the carbonyl groups C1=O1 and C5=O2 of 1.213 (3) and 1.224 (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 = 0.013 (5) Å). The C3 atom is located above the plane [deviations from the C4/N1/C1/C2 mean plane = 0.378 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.
The molecules are linked by an intermolecular hydrogen bond between N2–H2 and O2 (–X+1, y, z) (Table 1, Fig. 2).