4-(2-Oxa-6-aza­spiro­[3.3]hept-6-yl)­benzo­nitrile

Li, J.; Xu, T.; Wu, P.-B.; Lu, J.; Tang, Y.

doi:10.1107/S1600536810012936

organic compounds

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ISSN: 2056-9890

Volume 66| Part 5| May 2010| Page o1179

https://doi.org/10.1107/S1600536810012936

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4-(2-Oxa-6-azaspiro[3.3]hept-6-yl)benzonitrile

Jian Li,^a Ting Xu,^a Peng-Bo Wu,^a Jing Lu ^a and Yao Tang ^a ^*

^aDepartment of Pharmacy, West China Hospital of Sichuan University, Chengdu 610041, People's Republic of China
^*Correspondence e-mail: hxyylj@163.com

(Received 19 March 2010; accepted 7 April 2010; online 28 April 2010)

In the title compound, C₁₂H₁₂N₂O, the azetidine ring (r.m.s. deviation = 0.021 Å) and the oxetane ring (r.m.s. deviation = 0.014 Å) are nearly perpendicular to each other [dihedral angle = 89.7 (1)°]. The azetidine ring is twisted out of the plane of the benzene ring by 18.3 (1)°. In the crystal structure, molecules are linked to form chains along the c axis by C—H⋯O hydrogen bonds.

Related literature

The title compound is a key intermediate to synthesize (pyrrolo[3,4-c]pyrazol-3-yl)benzamide derivatives. For the anti-tumor effect of these derivatives, see: Fancelli et al. (2005 $[Fancelli, D., Berta, D., Bindi, S., Cameron, A., Cappella, P., Carpinelli, P., Catana, C., Forte, B., Giordano, P., Giorgini, M. L., Mantegani, S., Marsiglio, A., Meroni, M., Moll, J., Pittal\'a, V., Roletto, F., Severino, D., Soncini, C., Storici, P., Tonani, R., Varasi, M., Vulpetti, A. & Vianello, P.et al. (2005). J. Med. Chem. 48, 3080-3084.]$ ).

Experimental

Crystal data

C₁₂H₁₂N₂O
M_r = 200.24
Monoclinic, P 2₁ /n
a = 9.484 (4) Å
b = 11.033 (4) Å
c = 10.419 (4) Å
β = 113.186 (5)°
V = 1002.2 (7) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 113 K
0.60 × 0.60 × 0.27 mm

Data collection

Rigaku AFC10/Saturn 724-Plus diffractometer
7662 measured reflections
2234 independent reflections
1872 reflections with I > 2σ(I)
R_int = 0.029

Refinement

R[F² > 2σ(F²)] = 0.041
wR(F²) = 0.099
S = 1.00
2234 reflections
136 parameters
H-atom parameters constrained
Δρ_max = 0.30 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C4—H4⋯O1ⁱ	0.95	2.47	3.371 (2)	159
Symmetry code: (i) x, y, z+1.

Data collection: CrystalClear (Rigaku, 2008 ); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009 ); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536810012936/ci5062sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810012936/ci5062Isup2.hkl

checkCIF report

Related literature top

The title compound is a key intermediate to synthesize (pyrrolo[3,4-c]pyrazol-3-yl)benzamide derivatives. For the anti-proliferation effect of these derivatives, see: Fancelli et al. (2005).

Experimental top

A DMSO solution of 2-oxa-6-azaspiro[3,3]heptane (0.99 g, 0.01 mol) with 4-fluorobenzonitrile (1.21 g, 0.01 mol) was heated to reflux for 5 h, then water (100 ml) was added into the solution. The mixture was extracted with CH₂Cl₂. Then the solvent was removed to give a red powder. Single crystals were obtained from a CH₂Cl₂ solution after 3 days.

Structure description top

The title compound is a key intermediate to synthesize (pyrrolo[3,4-c]pyrazol-3-yl)benzamide derivatives. For the anti-proliferation effect of these derivatives, see: Fancelli et al. (2005).

Computing details top

Data collection: CrystalClear (Rigaku, 2008); cell refinement: CrystalClear (Rigaku, 2008); data reduction: CrystalClear (Rigaku, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top

Fig. 1.

4-(2-Oxa-6-azaspiro[3.3]hept-6-yl)benzonitrile top

Crystal data top

C₁₂H₁₂N₂O	F(000) = 424
M_r = 200.24	D_x = 1.327 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
a = 9.484 (4) Å	Cell parameters from 2956 reflections
b = 11.033 (4) Å	θ = 3.1–27.5°
c = 10.419 (4) Å	µ = 0.09 mm⁻¹
β = 113.186 (5)°	T = 113 K
V = 1002.2 (7) Å³	Prism, colourless
Z = 4	0.60 × 0.60 × 0.27 mm

Data collection top

Rigaku AFC10/Saturn 724-Plus diffractometer	1872 reflections with I > 2σ(I)
Radiation source: rotating anode	R_int = 0.029
Graphite monochromator	θ_max = 27.5°, θ_min = 3.1°
Detector resolution: 28.5714 pixels mm^-1	h = −12→12
φ and ω scans	k = −14→11
7662 measured reflections	l = −12→12
2234 independent reflections

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)] = 0.041	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.099	H-atom parameters constrained
S = 1.00	w = 1/[σ²(F_o²) + (0.0456P)² + 0.36P] where P = (F_o² + 2F_c²)/3
2234 reflections	(Δ/σ)_max = 0.001
136 parameters	Δρ_max = 0.30 e Å⁻³
0 restraints	Δρ_min = −0.16 e Å⁻³

Crystal data top

C₁₂H₁₂N₂O	V = 1002.2 (7) Å³
M_r = 200.24	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 9.484 (4) Å	µ = 0.09 mm⁻¹
b = 11.033 (4) Å	T = 113 K
c = 10.419 (4) Å	0.60 × 0.60 × 0.27 mm
β = 113.186 (5)°

Data collection top

Rigaku AFC10/Saturn 724-Plus diffractometer	1872 reflections with I > 2σ(I)
7662 measured reflections	R_int = 0.029
2234 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.041	0 restraints
wR(F²) = 0.099	H-atom parameters constrained
S = 1.00	Δρ_max = 0.30 e Å⁻³
2234 reflections	Δρ_min = −0.16 e Å⁻³
136 parameters

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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
O1	0.53098 (12)	0.21116 (9)	−0.00129 (10)	0.0272 (3)
N1	0.81838 (14)	0.46062 (12)	1.07793 (13)	0.0275 (3)
N2	0.58259 (13)	0.37004 (10)	0.38573 (11)	0.0186 (3)
C1	0.74599 (15)	0.47583 (12)	0.59326 (14)	0.0178 (3)
H1	0.7933	0.5192	0.5421	0.021*
C2	0.79050 (15)	0.49646 (12)	0.73352 (14)	0.0186 (3)
H2	0.8679	0.5547	0.7788	0.022*
C3	0.72270 (15)	0.43219 (12)	0.81086 (14)	0.0177 (3)
C4	0.60810 (15)	0.34638 (12)	0.74350 (14)	0.0183 (3)
H4	0.5624	0.3022	0.7954	0.022*
C5	0.56183 (15)	0.32601 (12)	0.60278 (14)	0.0178 (3)
H5	0.4835	0.2683	0.5577	0.021*
C6	0.62984 (14)	0.39026 (12)	0.52463 (13)	0.0165 (3)
C7	0.49702 (15)	0.26581 (12)	0.30534 (14)	0.0178 (3)
H7A	0.3842	0.2751	0.2702	0.021*
H7B	0.5303	0.1871	0.3534	0.021*
C8	0.56407 (14)	0.29329 (12)	0.19522 (14)	0.0167 (3)
C9	0.65782 (15)	0.39702 (12)	0.28976 (13)	0.0177 (3)
H9A	0.7699	0.3827	0.3302	0.021*
H9B	0.6331	0.4782	0.2461	0.021*
C10	0.45979 (16)	0.31151 (12)	0.04116 (14)	0.0204 (3)
H10A	0.3499	0.2979	0.0208	0.024*
H10B	0.4749	0.3907	0.0037	0.024*
C11	0.63751 (16)	0.19237 (13)	0.14221 (14)	0.0226 (3)
H11A	0.7455	0.2092	0.1575	0.027*
H11B	0.6281	0.1114	0.1790	0.027*
C12	0.77569 (15)	0.44870 (12)	0.95891 (15)	0.0202 (3)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0353 (6)	0.0266 (6)	0.0202 (5)	0.0027 (5)	0.0113 (5)	−0.0041 (4)
N1	0.0257 (7)	0.0323 (7)	0.0231 (7)	−0.0015 (5)	0.0082 (5)	−0.0038 (6)
N2	0.0203 (6)	0.0187 (6)	0.0180 (6)	−0.0073 (4)	0.0086 (5)	−0.0027 (5)
C1	0.0179 (6)	0.0147 (6)	0.0217 (7)	−0.0007 (5)	0.0086 (5)	0.0028 (5)
C2	0.0156 (6)	0.0151 (6)	0.0223 (7)	0.0007 (5)	0.0043 (5)	−0.0017 (5)
C3	0.0165 (6)	0.0176 (6)	0.0177 (7)	0.0041 (5)	0.0054 (5)	−0.0004 (5)
C4	0.0177 (6)	0.0181 (6)	0.0212 (7)	0.0025 (5)	0.0098 (5)	0.0022 (5)
C5	0.0157 (6)	0.0163 (6)	0.0212 (7)	−0.0017 (5)	0.0069 (5)	−0.0012 (5)
C6	0.0151 (6)	0.0147 (6)	0.0188 (7)	0.0023 (5)	0.0058 (5)	0.0008 (5)
C7	0.0184 (6)	0.0157 (6)	0.0195 (7)	−0.0029 (5)	0.0076 (5)	−0.0014 (5)
C8	0.0161 (6)	0.0149 (6)	0.0193 (7)	0.0004 (5)	0.0071 (5)	0.0002 (5)
C9	0.0171 (6)	0.0186 (6)	0.0172 (6)	−0.0020 (5)	0.0065 (5)	0.0004 (5)
C10	0.0210 (7)	0.0184 (6)	0.0195 (7)	−0.0010 (5)	0.0057 (5)	−0.0002 (6)
C11	0.0257 (7)	0.0215 (7)	0.0227 (7)	0.0046 (6)	0.0117 (6)	0.0016 (6)
C12	0.0175 (6)	0.0195 (6)	0.0235 (8)	0.0024 (5)	0.0079 (5)	−0.0010 (6)

Geometric parameters (Å, º) top

O1—C11	1.4525 (17)	C5—C6	1.4125 (19)
O1—C10	1.4534 (17)	C5—H5	0.95
N1—C12	1.1504 (18)	C7—C8	1.5451 (18)
N2—C6	1.3544 (17)	C7—H7A	0.99
N2—C7	1.4653 (17)	C7—H7B	0.99
N2—C9	1.4695 (17)	C8—C11	1.5274 (18)
C1—C2	1.3711 (19)	C8—C10	1.5314 (18)
C1—C6	1.4127 (18)	C8—C9	1.5431 (18)
C1—H1	0.95	C9—H9A	0.99
C2—C3	1.4049 (19)	C9—H9B	0.99
C2—H2	0.95	C10—H10A	0.99
C3—C4	1.4034 (19)	C10—H10B	0.99
C3—C12	1.4335 (19)	C11—H11A	0.99
C4—C5	1.3734 (19)	C11—H11B	0.99
C4—H4	0.95

C11—O1—C10	90.79 (9)	H7A—C7—H7B	111.1
C6—N2—C7	128.02 (11)	C11—C8—C10	85.12 (10)
C6—N2—C9	130.44 (11)	C11—C8—C9	122.78 (11)
C7—N2—C9	94.47 (10)	C10—C8—C9	122.94 (11)
C2—C1—C6	120.13 (12)	C11—C8—C7	120.34 (11)
C2—C1—H1	119.9	C10—C8—C7	121.30 (11)
C6—C1—H1	119.9	C9—C8—C7	88.49 (10)
C1—C2—C3	120.61 (12)	N2—C9—C8	88.40 (10)
C1—C2—H2	119.7	N2—C9—H9A	113.9
C3—C2—H2	119.7	C8—C9—H9A	113.9
C4—C3—C2	119.53 (12)	N2—C9—H9B	113.9
C4—C3—C12	119.89 (12)	C8—C9—H9B	113.9
C2—C3—C12	120.49 (12)	H9A—C9—H9B	111.1
C5—C4—C3	120.22 (12)	O1—C10—C8	91.91 (10)
C5—C4—H4	119.9	O1—C10—H10A	113.3
C3—C4—H4	119.9	C8—C10—H10A	113.3
C4—C5—C6	120.45 (12)	O1—C10—H10B	113.3
C4—C5—H5	119.8	C8—C10—H10B	113.3
C6—C5—H5	119.8	H10A—C10—H10B	110.6
N2—C6—C5	119.95 (12)	O1—C11—C8	92.11 (10)
N2—C6—C1	121.00 (12)	O1—C11—H11A	113.3
C5—C6—C1	119.05 (12)	C8—C11—H11A	113.3
N2—C7—C8	88.47 (10)	O1—C11—H11B	113.3
N2—C7—H7A	113.9	C8—C11—H11B	113.3
C8—C7—H7A	113.9	H11A—C11—H11B	110.6
N2—C7—H7B	113.9	N1—C12—C3	179.26 (15)
C8—C7—H7B	113.9

C6—C1—C2—C3	0.67 (19)	N2—C7—C8—C11	130.78 (12)
C1—C2—C3—C4	−0.17 (18)	N2—C7—C8—C10	−125.31 (12)
C1—C2—C3—C12	176.30 (12)	N2—C7—C8—C9	3.04 (9)
C2—C3—C4—C5	−0.45 (19)	C6—N2—C9—C8	154.66 (13)
C12—C3—C4—C5	−176.95 (12)	C7—N2—C9—C8	3.21 (10)
C3—C4—C5—C6	0.57 (19)	C11—C8—C9—N2	−128.76 (12)
C7—N2—C6—C5	−18.4 (2)	C10—C8—C9—N2	123.99 (12)
C9—N2—C6—C5	−161.23 (13)	C7—C8—C9—N2	−3.04 (9)
C7—N2—C6—C1	162.08 (12)	C11—O1—C10—C8	−2.22 (10)
C9—N2—C6—C1	19.3 (2)	C11—C8—C10—O1	2.12 (10)
C4—C5—C6—N2	−179.56 (12)	C9—C8—C10—O1	128.42 (12)
C4—C5—C6—C1	−0.07 (19)	C7—C8—C10—O1	−120.66 (12)
C2—C1—C6—N2	178.93 (12)	C10—O1—C11—C8	2.22 (10)
C2—C1—C6—C5	−0.55 (19)	C10—C8—C11—O1	−2.12 (10)
C6—N2—C7—C8	−155.71 (13)	C9—C8—C11—O1	−128.56 (12)
C9—N2—C7—C8	−3.21 (10)	C7—C8—C11—O1	121.54 (12)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C4—H4···O1ⁱ	0.95	2.47	3.371 (2)	159

Symmetry code: (i) x, y, z+1.

Experimental details

Crystal data
Chemical formula	C₁₂H₁₂N₂O
M_r	200.24
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	113
a, b, c (Å)	9.484 (4), 11.033 (4), 10.419 (4)
β (°)	113.186 (5)
V (Å³)	1002.2 (7)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.60 × 0.60 × 0.27

Data collection
Diffractometer	Rigaku AFC10/Saturn 724-Plus
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	7662, 2234, 1872
R_int	0.029
(sin θ/λ)_max (Å⁻¹)	0.649

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.041, 0.099, 1.00
No. of reflections	2234
No. of parameters	136
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.30, −0.16

Computer programs: CrystalClear (Rigaku, 2008), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C4—H4···O1ⁱ	0.95	2.47	3.371 (2)	159

Symmetry code: (i) x, y, z+1.

Acknowledgements

The authors thank Mr Kai-bei Yu of Beijing Institute of Technology for the X-ray data collection.

References

Fancelli, D., Berta, D., Bindi, S., Cameron, A., Cappella, P., Carpinelli, P., Catana, C., Forte, B., Giordano, P., Giorgini, M. L., Mantegani, S., Marsiglio, A., Meroni, M., Moll, J., Pittal\'a, V., Roletto, F., Severino, D., Soncini, C., Storici, P., Tonani, R., Varasi, M., Vulpetti, A. & Vianello, P.et al. (2005). J. Med. Chem. 48, 3080–3084. Google Scholar
Rigaku (2008). CrystalClear. Rigaku Corporation, The Woodlands, Texas, USA. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar