2-(3,3,4,4-Tetra­fluoro­pyrrolidin-1-yl)aniline

Cao, W.; Zhong, J.; Wang, J.; Liu, P.; Zeng, Z.

doi:10.1107/S1600536811030339

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 67| Part 9| September 2011| Page o2220

doi:10.1107/S1600536811030339

Open

access

2-(3,3,4,4-Tetrafluoropyrrolidin-1-yl)aniline

Wanwan Cao,^a Jun-wen Zhong,^a Jin Wang,^a Pei-lian Liu ^a and Zhuo Zeng ^a,^b ^*

^aSchool of Chemistry and Environment, South China Normal University, Guangzhou 510006, People's Republic of China, and ^bKey Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, People's Republic of China
^*Correspondence e-mail: zhuosioc@yahoo.com.cn

(Received 1 July 2011; accepted 27 July 2011; online 2 August 2011)

In the title fluorinated pyrrolidine derivative, C₁₀H₁₀F₄N₂, the dihedral angle between the best planes of the benzene and pyrrolidine rings is 62.6 (1)°. The crystal packing features intermolecular N—H⋯F hydrogen bonds.

Related literature

For applications of fluorinated pyrrolidine derivatives, see: Hulin et al. (2005 ); Kerekes et al. (2011 ); Marson (2005 ); Santora et al. (2008 ).

Experimental

Crystal data

C₁₀H₁₀F₄N₂
M_r = 234.20
Orthorhombic, P 2₁ 2₁ 2₁
a = 6.791 (13) Å
b = 8.185 (16) Å
c = 18.66 (4) Å
V = 1037 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.14 mm⁻¹
T = 298 K
0.30 × 0.28 × 0.22 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ) T_min = 0.959, T_max = 0.970
6022 measured reflections
1342 independent reflections
748 reflections with I > 2σ(I)
R_int = 0.061

Refinement

R[F² > 2σ(F²)] = 0.041
wR(F²) = 0.112
S = 1.02
1342 reflections
153 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.14 e Å⁻³
Δρ_min = −0.15 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2A⋯F1ⁱ	0.84 (5)	2.59 (5)	3.295 (8)	142 (4)
Symmetry code: (i) $[-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Data collection: APEX2 (Bruker, 2008 ); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811030339/ld2018sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811030339/ld2018Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536811030339/ld2018Isup3.cml

checkCIF report

Comment top

Fluorinated pyrrolidine derivatives have attracted much attention due to their potential applications as dipeptidyl peptidase IV inhibitors (Hulin et al., 2005), asymmetric synthesis catalysts (Marson, 2005), aurora kinase inhibitors (Kerekes et al., 2011), and H3 receptor antagonists (Santora et al., 2008). Herein, we report the crystal structure of the title compound (Fig. 1), obtained by the reaction of o-phenylenediamine with trifluoromethanesulfonic acid 2,2,3,3-tretrafluoro-1,4-butanediyl ester.

The dihedral angle between the plane of phenyl ring and the least-squares plane of pyrrolidine ring is 62.63 (14)°. The pyrrolidine ring adopts a distorted N1-envelope conformation with folding angle 40.6 (2)°. The crystal packing (Fig. 2) is characterized by intermolecular N—H···F—C bonds linking molecules in zigzag chains along b.

Related literature top

For applications of fluorinated pyrrolidine derivatives, see: Hulin et al. (2005); Kerekes et al. (2011); Marson (2005); Santora et al. (2008).

Experimental top

A mixture of trifluoromethanesulfonic acid 2,2,3,3,-tretrafluoro-1,4-butanediyl ester(1 mmol), o-phenylenediamine (1.5 mmol), Et₃N (3 mmol) and ethanol(15 ml) was placed in a round-bottomed flask fitted with a reflux condenser, and then heated at reflux for 30 h. After cooling, the organic solvent was removed under reduced pressure and to the residue was solved in dichloromethane then washed with water, and the organic layer was dried over anhydrous Na₂SO₄. After the solvent was removed, the residue was purified by flash chromatography on silica gel to afford a purple solid (164 mg), yield 70%. Crystals suitable for X-ray structural analysis were grown from CH₃CN solution at room temperature.

Computing details top

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELTLX (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top

	Fig. 1. View of the title compound showing the atom-labelling scheme. Ellipsoids are drawn at the 50% probability level.
	Fig. 2. Perspective view of the crystal packing.

2-(3,3,4,4-Tetrafluoropyrrolidin-1-yl)aniline top

Crystal data top

C₁₀H₁₀F₄N₂	F(000) = 480
M_r = 234.20	D_x = 1.500 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
a = 6.791 (13) Å	µ = 0.14 mm⁻¹
b = 8.185 (16) Å	T = 298 K
c = 18.66 (4) Å	Block, purple
V = 1037 (3) Å³	0.30 × 0.28 × 0.22 mm
Z = 4

Data collection top

Bruker SMART APEXII CCD area-detector diffractometer	1342 independent reflections
Radiation source: fine-focus sealed tube	748 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.061
ϕ and ω scans	θ_max = 27.0°, θ_min = 2.2°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −8→7
T_min = 0.959, T_max = 0.970	k = −8→10
6022 measured reflections	l = −23→23

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) = 0.112	H atoms treated by a mixture of independent and constrained refinement
S = 1.02	w = 1/[σ²(F_o²) + (0.038P)² + 0.0935P] where P = (F_o² + 2F_c²)/3
1342 reflections	(Δ/σ)_max < 0.001
153 parameters	Δρ_max = 0.14 e Å⁻³
0 restraints	Δρ_min = −0.15 e Å⁻³

Crystal data top

C₁₀H₁₀F₄N₂	V = 1037 (3) Å³
M_r = 234.20	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 6.791 (13) Å	µ = 0.14 mm⁻¹
b = 8.185 (16) Å	T = 298 K
c = 18.66 (4) Å	0.30 × 0.28 × 0.22 mm

Data collection top

Bruker SMART APEXII CCD area-detector diffractometer	1342 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	748 reflections with I > 2σ(I)
T_min = 0.959, T_max = 0.970	R_int = 0.061
6022 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.041	0 restraints
wR(F²) = 0.112	H atoms treated by a mixture of independent and constrained refinement
S = 1.02	Δρ_max = 0.14 e Å⁻³
1342 reflections	Δρ_min = −0.15 e Å⁻³
153 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. Since this is a light atom structure (does not contain any atoms heavier than Si) and since the data collection was carried out using Mo radiation, it is not possible to unambiguously determine the absolute configuration of this molecule.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
F2	0.5502 (4)	0.9533 (4)	0.28755 (12)	0.0946 (9)
F4	0.9856 (4)	0.9465 (4)	0.22927 (13)	0.0938 (9)
F3	0.7878 (4)	1.1542 (3)	0.23004 (13)	0.0903 (9)
F1	0.7058 (4)	0.7458 (3)	0.24699 (12)	0.0897 (8)
C5	0.5124 (5)	0.9963 (4)	0.04139 (17)	0.0451 (8)
C6	0.3393 (5)	1.0854 (4)	0.02680 (18)	0.0491 (9)
C3	0.8125 (6)	1.0019 (5)	0.2037 (2)	0.0608 (10)
C2	0.6375 (6)	0.8962 (5)	0.22754 (19)	0.0595 (11)
C10	0.6062 (6)	0.9131 (5)	−0.01323 (19)	0.0575 (10)
H10	0.7199	0.8541	−0.0031	0.069*
C7	0.2663 (6)	1.0832 (5)	−0.0431 (2)	0.0605 (11)
H7	0.1501	1.1383	−0.0536	0.073*
C8	0.3635 (7)	1.0009 (5)	−0.0966 (2)	0.0688 (12)
H8	0.3133	1.0027	−0.1430	0.083*
C9	0.5346 (7)	0.9155 (5)	−0.0827 (2)	0.0716 (13)
H9	0.6004	0.8608	−0.1192	0.086*
C4	0.7993 (5)	0.9997 (5)	0.12353 (18)	0.0583 (10)
H4A	0.8623	1.0946	0.1025	0.070*
H4B	0.8569	0.9013	0.1036	0.070*
C1	0.5016 (6)	0.8845 (5)	0.16406 (19)	0.0665 (12)
H1A	0.5021	0.7752	0.1440	0.080*
H1B	0.3679	0.9136	0.1771	0.080*
N1	0.5854 (4)	1.0035 (4)	0.11341 (14)	0.0466 (7)
N2	0.2447 (6)	1.1710 (5)	0.0805 (2)	0.0653 (10)
H2A	0.312 (7)	1.201 (6)	0.116 (3)	0.091 (19)*
H2B	0.171 (9)	1.254 (9)	0.068 (3)	0.17 (3)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F2	0.093 (2)	0.123 (2)	0.0670 (14)	0.0049 (17)	0.0166 (15)	−0.0149 (14)
F4	0.0610 (15)	0.127 (2)	0.0934 (19)	0.0073 (16)	−0.0274 (15)	0.0235 (16)
F3	0.118 (2)	0.0611 (15)	0.0915 (17)	−0.0124 (16)	−0.0215 (16)	−0.0148 (13)
F1	0.111 (2)	0.0665 (15)	0.0915 (17)	0.0003 (16)	−0.0187 (16)	0.0234 (14)
C5	0.041 (2)	0.047 (2)	0.0470 (18)	−0.0033 (19)	−0.0009 (17)	0.0050 (16)
C6	0.047 (2)	0.046 (2)	0.054 (2)	−0.0019 (18)	−0.0030 (19)	0.0006 (18)
C3	0.056 (3)	0.058 (3)	0.068 (2)	0.007 (2)	−0.016 (2)	0.004 (2)
C2	0.069 (3)	0.062 (3)	0.048 (2)	0.006 (2)	−0.002 (2)	0.008 (2)
C10	0.058 (2)	0.055 (2)	0.059 (2)	0.004 (2)	0.003 (2)	−0.0032 (19)
C7	0.057 (3)	0.061 (2)	0.064 (2)	0.000 (2)	−0.016 (2)	0.009 (2)
C8	0.090 (3)	0.069 (3)	0.047 (2)	−0.013 (3)	−0.013 (2)	0.000 (2)
C9	0.087 (4)	0.069 (3)	0.058 (3)	−0.005 (3)	0.005 (2)	−0.011 (2)
C4	0.044 (2)	0.070 (3)	0.061 (2)	−0.004 (2)	−0.0026 (19)	0.010 (2)
C1	0.064 (3)	0.074 (3)	0.061 (2)	−0.017 (2)	−0.005 (2)	0.017 (2)
N1	0.0369 (16)	0.0548 (18)	0.0480 (16)	−0.0026 (15)	−0.0024 (14)	0.0073 (15)
N2	0.052 (2)	0.073 (2)	0.071 (2)	0.011 (2)	0.001 (2)	−0.004 (2)

Geometric parameters (Å, º) top

F2—C2	1.350 (5)	C7—C8	1.374 (6)
F4—C3	1.347 (5)	C7—H7	0.9300
F3—C3	1.350 (5)	C8—C9	1.380 (6)
F1—C2	1.365 (5)	C8—H8	0.9300
C5—C10	1.382 (5)	C9—H9	0.9300
C5—C6	1.409 (5)	C4—N1	1.465 (5)
C5—N1	1.434 (5)	C4—H4A	0.9700
C6—N2	1.381 (5)	C4—H4B	0.9700
C6—C7	1.395 (5)	C1—N1	1.472 (5)
C3—C4	1.498 (6)	C1—H1A	0.9700
C3—C2	1.536 (6)	C1—H1B	0.9700
C2—C1	1.505 (6)	N2—H2A	0.84 (5)
C10—C9	1.384 (6)	N2—H2B	0.87 (7)
C10—H10	0.9300

C10—C5—C6	119.8 (3)	C7—C8—C9	121.1 (4)
C10—C5—N1	123.5 (3)	C7—C8—H8	119.5
C6—C5—N1	116.6 (3)	C9—C8—H8	119.5
N2—C6—C7	121.3 (4)	C8—C9—C10	118.6 (4)
N2—C6—C5	120.7 (3)	C8—C9—H9	120.7
C7—C6—C5	118.1 (3)	C10—C9—H9	120.7
F4—C3—F3	106.8 (3)	N1—C4—C3	100.8 (3)
F4—C3—C4	113.7 (3)	N1—C4—H4A	111.6
F3—C3—C4	111.6 (3)	C3—C4—H4A	111.6
F4—C3—C2	112.5 (3)	N1—C4—H4B	111.6
F3—C3—C2	108.6 (3)	C3—C4—H4B	111.6
C4—C3—C2	103.7 (3)	H4A—C4—H4B	109.4
F2—C2—F1	103.9 (3)	N1—C1—C2	103.1 (3)
F2—C2—C1	113.9 (4)	N1—C1—H1A	111.2
F1—C2—C1	111.1 (3)	C2—C1—H1A	111.2
F2—C2—C3	112.7 (4)	N1—C1—H1B	111.2
F1—C2—C3	108.8 (3)	C2—C1—H1B	111.2
C1—C2—C3	106.4 (3)	H1A—C1—H1B	109.1
C5—C10—C9	121.5 (4)	C5—N1—C4	117.6 (3)
C5—C10—H10	119.3	C5—N1—C1	116.2 (3)
C9—C10—H10	119.3	C4—N1—C1	106.7 (3)
C8—C7—C6	121.0 (4)	C6—N2—H2A	117 (3)
C8—C7—H7	119.5	C6—N2—H2B	118 (4)
C6—C7—H7	119.5	H2A—N2—H2B	107 (5)

C10—C5—C6—N2	−179.2 (4)	C6—C7—C8—C9	1.1 (6)
N1—C5—C6—N2	−1.6 (5)	C7—C8—C9—C10	0.6 (6)
C10—C5—C6—C7	1.3 (5)	C5—C10—C9—C8	−1.3 (6)
N1—C5—C6—C7	178.9 (3)	F4—C3—C4—N1	159.5 (3)
F4—C3—C2—F2	93.9 (4)	F3—C3—C4—N1	−79.6 (4)
F3—C3—C2—F2	−24.1 (4)	C2—C3—C4—N1	37.0 (4)
C4—C3—C2—F2	−142.8 (3)	F2—C2—C1—N1	115.4 (4)
F4—C3—C2—F1	−20.8 (4)	F1—C2—C1—N1	−127.7 (4)
F3—C3—C2—F1	−138.8 (3)	C3—C2—C1—N1	−9.4 (4)
C4—C3—C2—F1	102.5 (3)	C10—C5—N1—C4	31.8 (5)
F4—C3—C2—C1	−140.6 (4)	C6—C5—N1—C4	−145.8 (4)
F3—C3—C2—C1	101.4 (4)	C10—C5—N1—C1	−96.3 (4)
C4—C3—C2—C1	−17.3 (4)	C6—C5—N1—C1	86.2 (4)
C6—C5—C10—C9	0.3 (5)	C3—C4—N1—C5	−177.7 (3)
N1—C5—C10—C9	−177.1 (4)	C3—C4—N1—C1	−45.2 (4)
N2—C6—C7—C8	178.5 (4)	C2—C1—N1—C5	167.3 (3)
C5—C6—C7—C8	−2.0 (6)	C2—C1—N1—C4	34.1 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···F1ⁱ	0.84 (5)	2.59 (5)	3.295 (8)	142 (4)

Symmetry code: (i) −x+1, y+1/2, −z+1/2.

Experimental details

Crystal data
Chemical formula	C₁₀H₁₀F₄N₂
M_r	234.20
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	298
a, b, c (Å)	6.791 (13), 8.185 (16), 18.66 (4)
V (Å³)	1037 (3)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.14
Crystal size (mm)	0.30 × 0.28 × 0.22

Data collection
Diffractometer	Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Sheldrick, 1996)
T_min, T_max	0.959, 0.970
No. of measured, independent and observed [I > 2σ(I)] reflections	6022, 1342, 748
R_int	0.061
(sin θ/λ)_max (Å⁻¹)	0.639

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.041, 0.112, 1.02
No. of reflections	1342
No. of parameters	153
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.14, −0.15

Computer programs: APEX2 (Bruker, 2008), SAINT (Bruker, 2008), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELTLX (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···F1ⁱ	0.84 (5)	2.59 (5)	3.295 (8)	142 (4)

Symmetry code: (i) −x+1, y+1/2, −z+1/2.

Acknowledgements

The authors gratefully acknowledge the support of the Department of Science and Technology, Guangdong Province (grant No. 2010 A020507001–76, 5300410, FIPL-05–003).

References

Bruker (2008). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Hulin, B., Cabral, S., Lopaze, M. G., Van Volkenburg, M. A., Andrews, K. M. & Parker, J. C. (2005). Bioorg. Med. Chem. Lett. 15, 4770–4773. CrossRef CAS Google Scholar
Kerekes, A. D., Esposite, S. J., Doll, R. J., Tagat, J. R., Yu, T., Xiao, Y. S., Zhang, Y. L., Prelusky, D. B., Tevar, S., Gray, K., Terracina, G. A., Lee, S. N., Jones, J., Liu, M., Basso, A. D. & Smith, E. B. (2011). J. Med. Chem. 54, 201–210. Web of Science CrossRef CAS Google Scholar
Marson, C. M. (2005). J. Org. Chem. 70, 9771–9779. CrossRef CAS Google Scholar
Santora, V. J., Covel, J. A., Hayashi, R., Hofilena, B. J., Ibarra, J. B., Pulley, M. D., Weinhouse, M. I., Sengupta, D., Duffield, J. J., Semple, G., Webb, R. R., Sage, C., Ren, A., Pereira, G., Knudsen, J., Edwards, J. E., Suarez, M., Frazer, J., Thomsen, W., Hauser, E., Whelan, K. & Grottick, A. J. (2008). Bioorg. Med. Chem. Lett. 18, 1490–1494. CSD CrossRef CAS 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