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

Wang, P.-P.; Lin, Q.-Y.; Zhang, F.

doi:10.1107/S1600536812000542

organic compounds

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ISSN: 2056-9890

Volume 68| Part 2| February 2012| Page o381

doi:10.1107/S1600536812000542

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4-(3,5-Dioxo-10-oxa-4-azatricyclo[5.2.1.0^2,6]decan-4-yl)-10-oxa-4-azatricyclo[5.2.1.0^2,6]decane-3,5-dione

Peng-Peng Wang,^a,^b Qiu-Yue Lin ^a,^b ^* and Fan Zhang ^b

^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 ). For related structures, see: Li et al. (2011 ); Zhu & Lin (2009 ).

Experimental

Crystal data

C₁₆H₁₆N₂O₆
M_r = 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 ) T_min = 0.987, T_max = 0.991
43071 measured reflections
3423 independent reflections
1581 reflections with I > 2σ(I)
R_int = 0.163

Refinement

R[F² > 2σ(F²)] = 0.083
wR(F²) = 0.224
S = 1.07
3423 reflections
217 parameters
H-atom parameters constrained
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Data collection: SMART (Bruker, 2004 ); cell refinement: SAINT (Bruker, 2004); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536812000542/ff2050sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812000542/ff2050Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812000542/ff2050Isup3.cml

checkCIF report

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.

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

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[5.2.1.0^2,6]decan-4-yl)-10-oxa-4- azatricyclo[5.2.1.0^2,6]decane-3,5-dione top

Crystal data top

C₁₆H₁₆N₂O₆	F(000) = 1392
M_r = 332.31	D_x = 1.493 Mg m⁻³
Orthorhombic, Pbca	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 2007 reflections
a = 10.2342 (6) Å	θ = 1.5–27.6°
b = 10.5673 (6) Å	µ = 0.12 mm⁻¹
c = 27.3485 (17) Å	T = 296 K
V = 2957.7 (3) Å³	Block, colourless
Z = 8	0.14 × 0.09 × 0.08 mm

Data collection top

Bruker P4 diffractometer	3423 independent reflections
Radiation source: fine-focus sealed tube	1581 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.163
ω scans	θ_max = 27.6°, θ_min = 1.5°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −13→13
T_min = 0.987, T_max = 0.991	k = −13→13
43071 measured reflections	l = −35→35

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)] = 0.083	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.224	H-atom parameters constrained
S = 1.07	w = 1/[σ²(F_o²) + (0.0862P)² + 1.8201P] where P = (F_o² + 2F_c²)/3
3423 reflections	(Δ/σ)_max = 0.002
217 parameters	Δρ_max = 0.24 e Å⁻³
0 restraints	Δρ_min = −0.21 e Å⁻³

Crystal data top

C₁₆H₁₆N₂O₆	V = 2957.7 (3) Å³
M_r = 332.31	Z = 8
Orthorhombic, Pbca	Mo Kα radiation
a = 10.2342 (6) Å	µ = 0.12 mm⁻¹
b = 10.5673 (6) Å	T = 296 K
c = 27.3485 (17) Å	0.14 × 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)
T_min = 0.987, T_max = 0.991	R_int = 0.163
43071 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.083	0 restraints
wR(F²) = 0.224	H-atom parameters constrained
S = 1.07	Δρ_max = 0.24 e Å⁻³
3423 reflections	Δρ_min = −0.21 e Å⁻³
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

	x	y	z	U_iso*/U_eq
O4	0.4418 (3)	−0.1479 (3)	0.03560 (11)	0.0595 (8)
O1	0.5405 (3)	0.4020 (3)	0.13629 (11)	0.0643 (9)
N1	0.5287 (3)	0.0942 (3)	0.15182 (13)	0.0517 (9)
O2	0.3401 (3)	0.1174 (3)	0.10792 (12)	0.0658 (9)
O3	0.7107 (3)	0.1261 (3)	0.19883 (14)	0.0784 (11)
O5	0.6972 (3)	0.0800 (3)	0.07064 (12)	0.0701 (10)
C16	0.5130 (4)	−0.1318 (4)	0.14002 (15)	0.0484 (10)
C11	0.6499 (4)	−0.1471 (3)	0.06726 (14)	0.0486 (10)
H11A	0.7384	−0.1821	0.0654	0.058*
N2	0.5691 (3)	−0.0145 (3)	0.12856 (13)	0.0496 (9)
C12	0.5594 (4)	−0.2230 (3)	0.10115 (14)	0.0446 (10)
H12A	0.6021	−0.2979	0.1149	0.054*
O6	0.4401 (3)	−0.1492 (3)	0.17385 (11)	0.0654 (9)
C7	0.4108 (4)	0.1543 (4)	0.13968 (16)	0.0498 (10)
C1	0.5826 (4)	0.3963 (4)	0.18576 (17)	0.0557 (12)
H1A	0.6776	0.4021	0.1896	0.067*
C8	0.6043 (4)	0.1584 (4)	0.18598 (16)	0.0502 (11)
C10	0.4465 (4)	−0.2567 (4)	0.06668 (16)	0.0542 (11)
H10A	0.3640	−0.2742	0.0836	0.065*
C15	0.6466 (4)	−0.0144 (4)	0.08651 (16)	0.0510 (11)
C3	0.5256 (4)	0.2710 (4)	0.20309 (16)	0.0491 (10)
H3A	0.5105	0.2698	0.2385	0.059*
C2	0.4016 (5)	0.3919 (4)	0.14670 (18)	0.0622 (13)
H2A	0.3459	0.3956	0.1176	0.075*
C14	0.4899 (5)	−0.3623 (4)	0.03254 (17)	0.0622 (12)
H14A	0.4165	−0.3986	0.0150	0.075*
H14B	0.5357	−0.4286	0.0501	0.075*
C9	0.5756 (4)	−0.1560 (4)	0.01894 (16)	0.0545 (11)
H9A	0.5995	−0.0901	−0.0046	0.065*
C13	0.5819 (5)	−0.2898 (4)	−0.00196 (16)	0.0623 (13)
H13A	0.6700	−0.3235	−0.0007	0.075*
H13B	0.5507	−0.2923	−0.0354	0.075*
C4	0.3968 (4)	0.2652 (4)	0.17362 (16)	0.0500 (11)
H4A	0.3199	0.2579	0.1948	0.060*
C6	0.3774 (5)	0.4990 (4)	0.18326 (18)	0.0640 (13)
H6A	0.3051	0.4795	0.2049	0.077*
H6B	0.3602	0.5785	0.1667	0.077*
C5	0.5080 (5)	0.5027 (4)	0.21108 (18)	0.0626 (13)
H5A	0.5517	0.5835	0.2071	0.075*
H5B	0.4961	0.4856	0.2456	0.075*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O4	0.057 (2)	0.0543 (18)	0.0669 (19)	0.0109 (15)	−0.0062 (16)	−0.0045 (15)
O1	0.080 (3)	0.0474 (17)	0.065 (2)	−0.0046 (15)	0.0149 (18)	0.0010 (15)
N1	0.056 (2)	0.0350 (18)	0.064 (2)	0.0030 (16)	−0.0021 (18)	−0.0112 (16)
O2	0.058 (2)	0.0620 (19)	0.077 (2)	0.0033 (16)	−0.0110 (18)	−0.0143 (17)
O3	0.066 (2)	0.061 (2)	0.108 (3)	0.0160 (17)	−0.025 (2)	−0.0178 (19)
O5	0.074 (2)	0.0484 (17)	0.088 (2)	−0.0161 (16)	0.0124 (18)	0.0048 (17)
C16	0.057 (3)	0.041 (2)	0.046 (2)	0.004 (2)	0.002 (2)	0.001 (2)
C11	0.057 (3)	0.036 (2)	0.053 (2)	0.0058 (19)	0.004 (2)	0.0009 (18)
N2	0.056 (2)	0.0322 (17)	0.060 (2)	0.0004 (16)	0.0071 (19)	−0.0058 (16)
C12	0.050 (3)	0.0285 (19)	0.055 (2)	0.0028 (18)	0.000 (2)	0.0018 (17)
O6	0.085 (2)	0.0537 (18)	0.0576 (18)	−0.0048 (17)	0.0187 (18)	−0.0052 (15)
C7	0.047 (3)	0.042 (2)	0.061 (3)	−0.003 (2)	0.001 (2)	0.001 (2)
C1	0.051 (3)	0.039 (2)	0.078 (3)	−0.0008 (19)	−0.002 (2)	−0.003 (2)
C8	0.046 (3)	0.039 (2)	0.065 (3)	0.001 (2)	−0.005 (2)	0.000 (2)
C10	0.056 (3)	0.045 (2)	0.062 (3)	−0.005 (2)	0.005 (2)	−0.003 (2)
C15	0.047 (3)	0.043 (2)	0.063 (3)	−0.001 (2)	−0.002 (2)	0.003 (2)
C3	0.057 (3)	0.037 (2)	0.054 (2)	−0.0003 (19)	−0.001 (2)	−0.0046 (19)
C2	0.070 (3)	0.046 (2)	0.070 (3)	0.006 (2)	−0.010 (3)	0.002 (2)
C14	0.079 (3)	0.042 (2)	0.065 (3)	0.000 (2)	−0.003 (3)	−0.012 (2)
C9	0.062 (3)	0.048 (2)	0.053 (2)	0.007 (2)	0.002 (2)	0.005 (2)
C13	0.075 (3)	0.060 (3)	0.052 (3)	0.013 (2)	0.000 (2)	−0.009 (2)
C4	0.042 (2)	0.043 (2)	0.065 (3)	0.0022 (19)	0.001 (2)	−0.002 (2)
C6	0.064 (3)	0.041 (2)	0.087 (3)	0.010 (2)	−0.005 (3)	−0.004 (2)
C5	0.075 (3)	0.038 (2)	0.075 (3)	0.001 (2)	0.001 (3)	−0.011 (2)

Geometric parameters (Å, º) top

O4—C10	1.431 (5)	C1—H1A	0.9800
O4—C9	1.446 (5)	C8—C3	1.511 (6)
O1—C1	1.421 (5)	C10—C14	1.520 (6)
O1—C2	1.454 (6)	C10—H10A	0.9800
N1—N2	1.376 (4)	C3—C4	1.547 (6)
N1—C8	1.390 (5)	C3—H3A	0.9800
N1—C7	1.404 (5)	C2—C4	1.529 (6)
O2—C7	1.196 (5)	C2—C6	1.530 (6)
O3—C8	1.194 (5)	C2—H2A	0.9800
O5—C15	1.205 (5)	C14—C13	1.537 (6)
C16—O6	1.203 (5)	C14—H14A	0.9700
C16—N2	1.402 (5)	C14—H14B	0.9700
C16—C12	1.511 (5)	C9—C13	1.526 (6)
C11—C15	1.498 (6)	C9—H9A	0.9800
C11—C9	1.527 (6)	C13—H13A	0.9700
C11—C12	1.536 (5)	C13—H13B	0.9700
C11—H11A	0.9800	C4—H4A	0.9800
N2—C15	1.397 (5)	C6—C5	1.539 (7)
C12—C10	1.533 (6)	C6—H6A	0.9700
C12—H12A	0.9800	C6—H6B	0.9700
C7—C4	1.502 (6)	C5—H5A	0.9700
C1—C3	1.523 (6)	C5—H5B	0.9700
C1—C5	1.525 (6)

C10—O4—C9	96.2 (3)	C1—C3—C4	101.5 (3)
C1—O1—C2	96.2 (3)	C8—C3—H3A	112.3
N2—N1—C8	123.4 (3)	C1—C3—H3A	112.3
N2—N1—C7	121.8 (3)	C4—C3—H3A	112.3
C8—N1—C7	114.6 (3)	O1—C2—C4	101.0 (3)
O6—C16—N2	124.1 (4)	O1—C2—C6	103.4 (4)
O6—C16—C12	129.7 (4)	C4—C2—C6	109.1 (4)
N2—C16—C12	106.1 (3)	O1—C2—H2A	114.0
C15—C11—C9	110.5 (3)	C4—C2—H2A	114.0
C15—C11—C12	105.3 (3)	C6—C2—H2A	114.0
C9—C11—C12	101.0 (3)	C10—C14—C13	101.0 (3)
C15—C11—H11A	113.1	C10—C14—H14A	111.6
C9—C11—H11A	113.1	C13—C14—H14A	111.6
C12—C11—H11A	113.1	C10—C14—H14B	111.6
N1—N2—C15	123.4 (3)	C13—C14—H14B	111.6
N1—N2—C16	120.8 (3)	H14A—C14—H14B	109.4
C15—N2—C16	114.6 (3)	O4—C9—C13	102.3 (3)
C16—C12—C10	110.1 (3)	O4—C9—C11	101.2 (3)
C16—C12—C11	106.3 (3)	C13—C9—C11	111.1 (3)
C10—C12—C11	101.8 (3)	O4—C9—H9A	113.7
C16—C12—H12A	112.6	C13—C9—H9A	113.7
C10—C12—H12A	112.6	C11—C9—H9A	113.7
C11—C12—H12A	112.6	C9—C13—C14	101.9 (3)
O2—C7—N1	123.0 (4)	C9—C13—H13A	111.4
O2—C7—C4	130.2 (4)	C14—C13—H13A	111.4
N1—C7—C4	106.8 (4)	C9—C13—H13B	111.4
O1—C1—C3	102.5 (3)	C14—C13—H13B	111.4
O1—C1—C5	104.4 (4)	H13A—C13—H13B	109.3
C3—C1—C5	107.9 (4)	C7—C4—C2	112.5 (4)
O1—C1—H1A	113.7	C7—C4—C3	105.7 (3)
C3—C1—H1A	113.7	C2—C4—C3	100.9 (3)
C5—C1—H1A	113.7	C7—C4—H4A	112.3
O3—C8—N1	124.5 (4)	C2—C4—H4A	112.3
O3—C8—C3	128.3 (4)	C3—C4—H4A	112.3
N1—C8—C3	107.2 (4)	C2—C6—C5	101.6 (4)
O4—C10—C14	103.6 (3)	C2—C6—H6A	111.4
O4—C10—C12	101.7 (3)	C5—C6—H6A	111.4
C14—C10—C12	109.1 (4)	C2—C6—H6B	111.4
O4—C10—H10A	113.8	C5—C6—H6B	111.4
C14—C10—H10A	113.8	H6A—C6—H6B	109.3
C12—C10—H10A	113.8	C1—C5—C6	101.1 (4)
O5—C15—N2	122.7 (4)	C1—C5—H5A	111.6
O5—C15—C11	129.7 (4)	C6—C5—H5A	111.6
N2—C15—C11	107.5 (3)	C1—C5—H5B	111.6
C8—C3—C1	112.6 (4)	C6—C5—H5B	111.6
C8—C3—C4	105.2 (3)	H5A—C5—H5B	109.4

Experimental details

Crystal data
Chemical formula	C₁₆H₁₆N₂O₆
M_r	332.31
Crystal system, space group	Orthorhombic, Pbca
Temperature (K)	296
a, b, c (Å)	10.2342 (6), 10.5673 (6), 27.3485 (17)
V (Å³)	2957.7 (3)
Z	8
Radiation type	Mo Kα
µ (mm⁻¹)	0.12
Crystal size (mm)	0.14 × 0.09 × 0.08

Data collection
Diffractometer	Bruker P4 diffractometer
Absorption correction	Multi-scan (SADABS; Sheldrick, 1996)
T_min, T_max	0.987, 0.991
No. of measured, independent and observed [I > 2σ(I)] reflections	43071, 3423, 1581
R_int	0.163
(sin θ/λ)_max (Å⁻¹)	0.652

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.083, 0.224, 1.07
No. of reflections	3423
No. of parameters	217
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	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

Bruker (2004). SAINT and SMART. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
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. Web of Science CrossRef PubMed CAS Google Scholar
Li, S.-K., Zhang, F., Lv, T.-X. & Lin, Q.-Y. (2011). Acta Cryst. E67, o1974. Web of Science CSD CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (1996). SADABS. University of Göttingen, Germany. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Zhu, W.-Z. & Lin, Q.-Y. (2009). Acta Cryst. E65, o287. Web of Science CSD CrossRef IUCr Journals Google Scholar

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