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

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4-(3,5-Dioxo-10-oxa-4-aza­tri­cyclo­[5.2.1.02,6]decan-4-yl)-10-oxa-4-aza­tri­cyclo­[5.2.1.02,6]decane-3,5-dione

aZhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces, Institute of Physical Chemistry, Zhejiang Normal University, Jinhua, Zhejiang 321004, People's Republic of China, and bCollege of Chemistry and Life Science, Zhejiang Normal University, Jinhua 321004, Zhejiang, People's Republic of China
*Correspondence e-mail: sky51@zjnu.cn

(Received 30 December 2011; accepted 6 January 2012; online 14 January 2012)

In the title compound, C16H16N2O6, the dihedral angle between the two pyrrolidine rings is 79.38 (14)°.

Related literature

Norcantharidin [systematic name: 7-oxabicyclo­(2.2.1)heptane-2,3-dicarb­oxy­lic anhydride] and its derivatives are of significant inter­est as serine/threonine protein phosphatase 1 and 2A inhibitors, see: Hill et al. (2008[Hill, T. A., Stewart, S. G., Gordon, C. P., Ackland, S. P., Gilbert, J., Sauer, B., Sakoff, J. A. & McCluskey, A. (2008). ChemMedChem, 3, 1878-1892.]). For related structures, see: Li et al. (2011[Li, S.-K., Zhang, F., Lv, T.-X. & Lin, Q.-Y. (2011). Acta Cryst. E67, o1974.]); Zhu & Lin (2009[Zhu, W.-Z. & Lin, Q.-Y. (2009). Acta Cryst. E65, o287.]).

[Scheme 1]

Experimental

Crystal data
  • C16H16N2O6

  • Mr = 332.31

  • Orthorhombic, P b c a

  • a = 10.2342 (6) Å

  • b = 10.5673 (6) Å

  • c = 27.3485 (17) Å

  • V = 2957.7 (3) Å3

  • Z = 8

  • Mo Kα radiation

  • μ = 0.12 mm−1

  • T = 296 K

  • 0.14 × 0.09 × 0.08 mm

Data collection
  • Bruker P4 diffractometer

  • Absorption correction: multi-scan (SADABS; Sheldrick, 1996[Sheldrick, G. M. (1996). SADABS. University of Göttingen, Germany.]) Tmin = 0.987, Tmax = 0.991

  • 43071 measured reflections

  • 3423 independent reflections

  • 1581 reflections with I > 2σ(I)

  • Rint = 0.163

Refinement
  • R[F2 > 2σ(F2)] = 0.083

  • wR(F2) = 0.224

  • S = 1.07

  • 3423 reflections

  • 217 parameters

  • H-atom parameters constrained

  • Δρmax = 0.24 e Å−3

  • Δρmin = −0.21 e Å−3

Data collection: SMART (Bruker, 2004[Bruker (2004). SAINT and SMART. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2004[Bruker (2004). SAINT and SMART. 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

Norcantharidin and its derivatives are of significant interest as serine/threonine protein phosphatase 1 and 2A inhibitors (Hill et al., 2008); norcantharidin has been used in the treatment of primary hepatoma and upper gastrointestinal carcinomas, and it does not display the nephrotoxicity of cantharidin. Related norcantharidin imides were reported by Zhu & Lin (2009) and Li et al. (2011).

X-ray crystallography confirmed the molecular structure and the atom connectivity for the title compound, as illustrated in Fig. 1. In the molecule, the dihedral angle between the two pyrrolidine rings is 79.38 (14)°. The pyrrolidine rings are linked via N—N bond. The bond angles of C7—N1—N2, C8—N1—N2 and C7—N1—C8 are 121.8 (3),123.4 (3) and 114.6 (3), respectively.

Related literature top

Norcantharidin [systematic name: 7-oxabicyclo(2.2.1)heptane-2,3-dicarboxylic anhydride] and its derivatives are of significant interest as serine/threonine protein phosphatase 1 and 2A inhibitors, see: Hill et al. (2008). For related structures, see: Li et al. (2011); Zhu & Lin (2009).

Experimental top

A mixture of 0.5 mmol norcantharidin, 0.5 mmol 2-amino-1,3,4-thiadiazole, 0.5 mmol palladium chloride as a promoter, and 10 mL distilled water was sealed in a 25 mL stainless steel reactor with a Telflon liner and heated at 393 K for 3 d. The reactor was cooled slowly to room temperature over 3 d. The solution was filtered and after 3 weeks, crystals with suitable size for single-crystal X-ray diffraction were obtained.

Refinement top

The H atoms were positioned geometrically and refined using a riding model [aliphatic of tertiary carbon C—H = 0.98 Å, aliphatic of secondary carbon C—H = 0.97 Å, Uiso(H) = 1.2Ueq(C)].

Computing details top

Data collection: SMART (Bruker, 2004); cell refinement: SAINT (Bruker, 2004); data reduction: SAINT (Bruker, 2004); 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. A view of the molecule of the title compound showing the atom-labelling scheme with displacement ellipsoids drawn at 30% probability. Hydrogen atoms were omitted for clarity.
4-(3,5-Dioxo-10-oxa-4-azatricyclo[5.2.1.02,6]decan-4-yl)-10-oxa-4- azatricyclo[5.2.1.02,6]decane-3,5-dione top
Crystal data top
C16H16N2O6F(000) = 1392
Mr = 332.31Dx = 1.493 Mg m3
Orthorhombic, PbcaMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2abCell parameters from 2007 reflections
a = 10.2342 (6) Åθ = 1.5–27.6°
b = 10.5673 (6) ŵ = 0.12 mm1
c = 27.3485 (17) ÅT = 296 K
V = 2957.7 (3) Å3Block, colourless
Z = 80.14 × 0.09 × 0.08 mm
Data collection top
Bruker P4
diffractometer
3423 independent reflections
Radiation source: fine-focus sealed tube1581 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.163
ω scansθmax = 27.6°, θmin = 1.5°
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)
h = 1313
Tmin = 0.987, Tmax = 0.991k = 1313
43071 measured reflectionsl = 3535
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)] = 0.083Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.224H-atom parameters constrained
S = 1.07 w = 1/[σ2(Fo2) + (0.0862P)2 + 1.8201P]
where P = (Fo2 + 2Fc2)/3
3423 reflections(Δ/σ)max = 0.002
217 parametersΔρmax = 0.24 e Å3
0 restraintsΔρmin = 0.21 e Å3
Crystal data top
C16H16N2O6V = 2957.7 (3) Å3
Mr = 332.31Z = 8
Orthorhombic, PbcaMo Kα radiation
a = 10.2342 (6) ŵ = 0.12 mm1
b = 10.5673 (6) ÅT = 296 K
c = 27.3485 (17) Å0.14 × 0.09 × 0.08 mm
Data collection top
Bruker P4
diffractometer
3423 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)
1581 reflections with I > 2σ(I)
Tmin = 0.987, Tmax = 0.991Rint = 0.163
43071 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0830 restraints
wR(F2) = 0.224H-atom parameters constrained
S = 1.07Δρmax = 0.24 e Å3
3423 reflectionsΔρmin = 0.21 e Å3
217 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
xyzUiso*/Ueq
O40.4418 (3)0.1479 (3)0.03560 (11)0.0595 (8)
O10.5405 (3)0.4020 (3)0.13629 (11)0.0643 (9)
N10.5287 (3)0.0942 (3)0.15182 (13)0.0517 (9)
O20.3401 (3)0.1174 (3)0.10792 (12)0.0658 (9)
O30.7107 (3)0.1261 (3)0.19883 (14)0.0784 (11)
O50.6972 (3)0.0800 (3)0.07064 (12)0.0701 (10)
C160.5130 (4)0.1318 (4)0.14002 (15)0.0484 (10)
C110.6499 (4)0.1471 (3)0.06726 (14)0.0486 (10)
H11A0.73840.18210.06540.058*
N20.5691 (3)0.0145 (3)0.12856 (13)0.0496 (9)
C120.5594 (4)0.2230 (3)0.10115 (14)0.0446 (10)
H12A0.60210.29790.11490.054*
O60.4401 (3)0.1492 (3)0.17385 (11)0.0654 (9)
C70.4108 (4)0.1543 (4)0.13968 (16)0.0498 (10)
C10.5826 (4)0.3963 (4)0.18576 (17)0.0557 (12)
H1A0.67760.40210.18960.067*
C80.6043 (4)0.1584 (4)0.18598 (16)0.0502 (11)
C100.4465 (4)0.2567 (4)0.06668 (16)0.0542 (11)
H10A0.36400.27420.08360.065*
C150.6466 (4)0.0144 (4)0.08651 (16)0.0510 (11)
C30.5256 (4)0.2710 (4)0.20309 (16)0.0491 (10)
H3A0.51050.26980.23850.059*
C20.4016 (5)0.3919 (4)0.14670 (18)0.0622 (13)
H2A0.34590.39560.11760.075*
C140.4899 (5)0.3623 (4)0.03254 (17)0.0622 (12)
H14A0.41650.39860.01500.075*
H14B0.53570.42860.05010.075*
C90.5756 (4)0.1560 (4)0.01894 (16)0.0545 (11)
H9A0.59950.09010.00460.065*
C130.5819 (5)0.2898 (4)0.00196 (16)0.0623 (13)
H13A0.67000.32350.00070.075*
H13B0.55070.29230.03540.075*
C40.3968 (4)0.2652 (4)0.17362 (16)0.0500 (11)
H4A0.31990.25790.19480.060*
C60.3774 (5)0.4990 (4)0.18326 (18)0.0640 (13)
H6A0.30510.47950.20490.077*
H6B0.36020.57850.16670.077*
C50.5080 (5)0.5027 (4)0.21108 (18)0.0626 (13)
H5A0.55170.58350.20710.075*
H5B0.49610.48560.24560.075*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O40.057 (2)0.0543 (18)0.0669 (19)0.0109 (15)0.0062 (16)0.0045 (15)
O10.080 (3)0.0474 (17)0.065 (2)0.0046 (15)0.0149 (18)0.0010 (15)
N10.056 (2)0.0350 (18)0.064 (2)0.0030 (16)0.0021 (18)0.0112 (16)
O20.058 (2)0.0620 (19)0.077 (2)0.0033 (16)0.0110 (18)0.0143 (17)
O30.066 (2)0.061 (2)0.108 (3)0.0160 (17)0.025 (2)0.0178 (19)
O50.074 (2)0.0484 (17)0.088 (2)0.0161 (16)0.0124 (18)0.0048 (17)
C160.057 (3)0.041 (2)0.046 (2)0.004 (2)0.002 (2)0.001 (2)
C110.057 (3)0.036 (2)0.053 (2)0.0058 (19)0.004 (2)0.0009 (18)
N20.056 (2)0.0322 (17)0.060 (2)0.0004 (16)0.0071 (19)0.0058 (16)
C120.050 (3)0.0285 (19)0.055 (2)0.0028 (18)0.000 (2)0.0018 (17)
O60.085 (2)0.0537 (18)0.0576 (18)0.0048 (17)0.0187 (18)0.0052 (15)
C70.047 (3)0.042 (2)0.061 (3)0.003 (2)0.001 (2)0.001 (2)
C10.051 (3)0.039 (2)0.078 (3)0.0008 (19)0.002 (2)0.003 (2)
C80.046 (3)0.039 (2)0.065 (3)0.001 (2)0.005 (2)0.000 (2)
C100.056 (3)0.045 (2)0.062 (3)0.005 (2)0.005 (2)0.003 (2)
C150.047 (3)0.043 (2)0.063 (3)0.001 (2)0.002 (2)0.003 (2)
C30.057 (3)0.037 (2)0.054 (2)0.0003 (19)0.001 (2)0.0046 (19)
C20.070 (3)0.046 (2)0.070 (3)0.006 (2)0.010 (3)0.002 (2)
C140.079 (3)0.042 (2)0.065 (3)0.000 (2)0.003 (3)0.012 (2)
C90.062 (3)0.048 (2)0.053 (2)0.007 (2)0.002 (2)0.005 (2)
C130.075 (3)0.060 (3)0.052 (3)0.013 (2)0.000 (2)0.009 (2)
C40.042 (2)0.043 (2)0.065 (3)0.0022 (19)0.001 (2)0.002 (2)
C60.064 (3)0.041 (2)0.087 (3)0.010 (2)0.005 (3)0.004 (2)
C50.075 (3)0.038 (2)0.075 (3)0.001 (2)0.001 (3)0.011 (2)
Geometric parameters (Å, º) top
O4—C101.431 (5)C1—H1A0.9800
O4—C91.446 (5)C8—C31.511 (6)
O1—C11.421 (5)C10—C141.520 (6)
O1—C21.454 (6)C10—H10A0.9800
N1—N21.376 (4)C3—C41.547 (6)
N1—C81.390 (5)C3—H3A0.9800
N1—C71.404 (5)C2—C41.529 (6)
O2—C71.196 (5)C2—C61.530 (6)
O3—C81.194 (5)C2—H2A0.9800
O5—C151.205 (5)C14—C131.537 (6)
C16—O61.203 (5)C14—H14A0.9700
C16—N21.402 (5)C14—H14B0.9700
C16—C121.511 (5)C9—C131.526 (6)
C11—C151.498 (6)C9—H9A0.9800
C11—C91.527 (6)C13—H13A0.9700
C11—C121.536 (5)C13—H13B0.9700
C11—H11A0.9800C4—H4A0.9800
N2—C151.397 (5)C6—C51.539 (7)
C12—C101.533 (6)C6—H6A0.9700
C12—H12A0.9800C6—H6B0.9700
C7—C41.502 (6)C5—H5A0.9700
C1—C31.523 (6)C5—H5B0.9700
C1—C51.525 (6)
C10—O4—C996.2 (3)C1—C3—C4101.5 (3)
C1—O1—C296.2 (3)C8—C3—H3A112.3
N2—N1—C8123.4 (3)C1—C3—H3A112.3
N2—N1—C7121.8 (3)C4—C3—H3A112.3
C8—N1—C7114.6 (3)O1—C2—C4101.0 (3)
O6—C16—N2124.1 (4)O1—C2—C6103.4 (4)
O6—C16—C12129.7 (4)C4—C2—C6109.1 (4)
N2—C16—C12106.1 (3)O1—C2—H2A114.0
C15—C11—C9110.5 (3)C4—C2—H2A114.0
C15—C11—C12105.3 (3)C6—C2—H2A114.0
C9—C11—C12101.0 (3)C10—C14—C13101.0 (3)
C15—C11—H11A113.1C10—C14—H14A111.6
C9—C11—H11A113.1C13—C14—H14A111.6
C12—C11—H11A113.1C10—C14—H14B111.6
N1—N2—C15123.4 (3)C13—C14—H14B111.6
N1—N2—C16120.8 (3)H14A—C14—H14B109.4
C15—N2—C16114.6 (3)O4—C9—C13102.3 (3)
C16—C12—C10110.1 (3)O4—C9—C11101.2 (3)
C16—C12—C11106.3 (3)C13—C9—C11111.1 (3)
C10—C12—C11101.8 (3)O4—C9—H9A113.7
C16—C12—H12A112.6C13—C9—H9A113.7
C10—C12—H12A112.6C11—C9—H9A113.7
C11—C12—H12A112.6C9—C13—C14101.9 (3)
O2—C7—N1123.0 (4)C9—C13—H13A111.4
O2—C7—C4130.2 (4)C14—C13—H13A111.4
N1—C7—C4106.8 (4)C9—C13—H13B111.4
O1—C1—C3102.5 (3)C14—C13—H13B111.4
O1—C1—C5104.4 (4)H13A—C13—H13B109.3
C3—C1—C5107.9 (4)C7—C4—C2112.5 (4)
O1—C1—H1A113.7C7—C4—C3105.7 (3)
C3—C1—H1A113.7C2—C4—C3100.9 (3)
C5—C1—H1A113.7C7—C4—H4A112.3
O3—C8—N1124.5 (4)C2—C4—H4A112.3
O3—C8—C3128.3 (4)C3—C4—H4A112.3
N1—C8—C3107.2 (4)C2—C6—C5101.6 (4)
O4—C10—C14103.6 (3)C2—C6—H6A111.4
O4—C10—C12101.7 (3)C5—C6—H6A111.4
C14—C10—C12109.1 (4)C2—C6—H6B111.4
O4—C10—H10A113.8C5—C6—H6B111.4
C14—C10—H10A113.8H6A—C6—H6B109.3
C12—C10—H10A113.8C1—C5—C6101.1 (4)
O5—C15—N2122.7 (4)C1—C5—H5A111.6
O5—C15—C11129.7 (4)C6—C5—H5A111.6
N2—C15—C11107.5 (3)C1—C5—H5B111.6
C8—C3—C1112.6 (4)C6—C5—H5B111.6
C8—C3—C4105.2 (3)H5A—C5—H5B109.4

Experimental details

Crystal data
Chemical formulaC16H16N2O6
Mr332.31
Crystal system, space groupOrthorhombic, Pbca
Temperature (K)296
a, b, c (Å)10.2342 (6), 10.5673 (6), 27.3485 (17)
V3)2957.7 (3)
Z8
Radiation typeMo Kα
µ (mm1)0.12
Crystal size (mm)0.14 × 0.09 × 0.08
Data collection
DiffractometerBruker P4
diffractometer
Absorption correctionMulti-scan
(SADABS; Sheldrick, 1996)
Tmin, Tmax0.987, 0.991
No. of measured, independent and
observed [I > 2σ(I)] reflections
43071, 3423, 1581
Rint0.163
(sin θ/λ)max1)0.652
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.083, 0.224, 1.07
No. of reflections3423
No. of parameters217
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.24, 0.21

Computer programs: SMART (Bruker, 2004), SAINT (Bruker, 2004), SHELXTL (Sheldrick, 2008).

 

Acknowledgements

The authors thank the Natural Science Foundation of Zhejiang Province, China (grant No. Y407301) for financial support.

References

First citationBruker (2004). SAINT and SMART. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationHill, T. A., Stewart, S. G., Gordon, C. P., Ackland, S. P., Gilbert, J., Sauer, B., Sakoff, J. A. & McCluskey, A. (2008). ChemMedChem, 3, 1878–1892.  Web of Science CrossRef PubMed CAS Google Scholar
First citationLi, S.-K., Zhang, F., Lv, T.-X. & Lin, Q.-Y. (2011). Acta Cryst. E67, o1974.  Web of Science CSD CrossRef IUCr Journals Google Scholar
First citationSheldrick, G. M. (1996). SADABS. University of Göttingen, Germany.  Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationZhu, W.-Z. & Lin, Q.-Y. (2009). Acta Cryst. E65, o287.  Web of Science CSD CrossRef IUCr Journals Google Scholar

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