N-(2,3,4-Trifluoro­phen­yl)pyrrolidine-1-carboxamide

Pei, S.; Li, J.; Qu, B.; Hai, L.; Wu, Y.

doi:10.1107/S1600536811051385

organic compounds

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ISSN: 2056-9890

Volume 68| Part 1| January 2012| Page o12

doi:10.1107/S1600536811051385

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N-(2,3,4-Trifluorophenyl)pyrrolidine-1-carboxamide

Shuchen Pei,^a Jie Li,^a Boyi Qu,^a Li Hai ^a and Yong Wu ^a ^*

^aKey Laboratory of Drug Targeting of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China
^*Correspondence e-mail: wyong@scu.edu.cn

(Received 19 November 2011; accepted 29 November 2011; online 3 December 2011)

In the title compound, C₁₁H₁₁F₃N₂O, a urea derivative, the best plane through the pyrrole ring makes a dihedral angle of 9.69 (13)° with the benzene ring. The amino H atom is shielded, so that it is not involved in any hydrogen-bonding interactions.

Related literature

For background to this class of compounds, see Zheng et al. (2010 ).

Experimental

Crystal data

C₁₁H₁₁F₃N₂O
M_r = 244.22
Monoclinic, P 2₁ /n
a = 6.0708 (4) Å
b = 24.2124 (15) Å
c = 7.4232 (6) Å
β = 100.508 (7)°
V = 1072.83 (13) Å³
Z = 4
Mo Kα radiation
μ = 0.13 mm⁻¹
T = 293 K
0.35 × 0.35 × 0.25 mm

Data collection

Oxford Diffraction Xcalibur Eos diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2007 $[Oxford Diffraction (2007). CrysAlis PRO. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.]$ ) T_min = 0.964, T_max = 1.000
4465 measured reflections
2190 independent reflections
1374 reflections with I > 2σ(I)
R_int = 0.018

Refinement

R[F² > 2σ(F²)] = 0.054
wR(F²) = 0.151
S = 1.04
2190 reflections
158 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Data collection: CrysAlis PRO (Oxford Diffraction, 2007 $[Oxford Diffraction (2007). CrysAlis PRO. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.]$ ); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009 ); software used to prepare material for publication: OLEX2.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811051385/bt5716sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811051385/bt5716Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536811051385/bt5716Isup3.cml

checkCIF report

Comment top

The compound N-(2,3,4-trifluorophenyl)pyrrolidine-1-carboxamide is one of urea derivatives. It has been established that urea derivatives have got a significant placein modern medicinal chemistry. Urea derivatives have been reported in the literature as anticancer agent, anticonvulsant, CXCR3 antagonist,antibacterial and so on. Our interests in synthesizing urea derivatives prompted us to develop an efficient methodology for synthesizing N-(2,3,4-trifluorophenyl)pyrrolidine-1-carboxamide. In our synthetic work, we obtained the title compound, and its crystal structure is reported here. The three fluorine atoms of the attached benzene ring are close to being coplanar with the ring, whereas the pyrrole ring is not coplanar with the benzene ring.

Related literature top

For background to this class of compounds, see Zheng et al. (2010).

Experimental top

The title compound was obtained as a derivative of urea. To a solution of triphosgene (350 mg, 1.19 mmol) and triethylamine (680 mg, 6.80 mmol) in anhydrous acetonitrile (5 ml) at ice bath, the solution of 2,3,4-trifluoroaniline (500 mg, 3.40 mmol) and triethylamine (680 mg, 6.80 mmol) in anhydrous acetonitrile (5 ml) were added dropwise.The mixture was stirred for 1 h. And then the solition of tetrahydropyrrole (240 mg,3.40 mmol) and triethylamine (680 mg, 6.80 mmol) in anhydrous acetonitrile (5 ml) were added dropwise. The reaction mixture was then removed from the cooling bath and stirred at room temperature overnight. On completion of the reaction, the mixture was poured into water. The aqueous layer was extracted with ethyl acetate and the organic layer was separated. The organic layers were washed with brine and dried over sodium sulfate, filtered, and concentrated in vacuo. The purification of the residue by silica gel column chromatography eluting with EtOAc-petroleum ether (1:10) yielded the white solid 660 mg (yield 86.7%) of N-(2,3,4-trifluorophenyl)pyrrolidine-1-carboxamide. Colorless crystals suitable for X-ray analysis were obtained by slow evaporation in ethyl acetate at room temperature.

Computing details top

Data collection: CrysAlis PRO (Oxford Diffraction, 2007); cell refinement: CrysAlis PRO (Oxford Diffraction, 2007); data reduction: CrysAlis PRO (Oxford Diffraction, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Figures top

	Fig. 1. The molecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level.
	Fig. 2. A packing diagram for the title compound.

N-(2,3,4-Trifluorophenyl)pyrrolidine-1-carboxamide top

Crystal data top

C₁₁H₁₁F₃N₂O	F(000) = 504
M_r = 244.22	D_x = 1.512 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.7107 Å
a = 6.0708 (4) Å	Cell parameters from 1445 reflections
b = 24.2124 (15) Å	θ = 2.9–28.9°
c = 7.4232 (6) Å	µ = 0.13 mm⁻¹
β = 100.508 (7)°	T = 293 K
V = 1072.83 (13) Å³	Block, colorless
Z = 4	0.35 × 0.35 × 0.25 mm

Data collection top

Oxford Diffraction Xcalibur Eos diffractometer	2190 independent reflections
Radiation source: Enhance (Mo) X-ray Source	1374 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.018
Detector resolution: 16.0874 pixels mm^-1	θ_max = 26.4°, θ_min = 2.9°
ω scans	h = −7→6
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2007)	k = −30→27
T_min = 0.964, T_max = 1.000	l = −8→9
4465 measured 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)] = 0.054	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.151	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	w = 1/[σ²(F_o²) + (0.055P)² + 0.3084P] where P = (F_o² + 2F_c²)/3
2190 reflections	(Δ/σ)_max < 0.001
158 parameters	Δρ_max = 0.24 e Å⁻³
0 restraints	Δρ_min = −0.22 e Å⁻³

Crystal data top

C₁₁H₁₁F₃N₂O	V = 1072.83 (13) Å³
M_r = 244.22	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 6.0708 (4) Å	µ = 0.13 mm⁻¹
b = 24.2124 (15) Å	T = 293 K
c = 7.4232 (6) Å	0.35 × 0.35 × 0.25 mm
β = 100.508 (7)°

Data collection top

Oxford Diffraction Xcalibur Eos diffractometer	2190 independent reflections
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2007)	1374 reflections with I > 2σ(I)
T_min = 0.964, T_max = 1.000	R_int = 0.018
4465 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.054	0 restraints
wR(F²) = 0.151	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	Δρ_max = 0.24 e Å⁻³
2190 reflections	Δρ_min = −0.22 e Å⁻³
158 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
F1	0.1373 (2)	−0.04074 (6)	0.1339 (2)	0.0855 (6)
F2	0.2120 (3)	−0.14684 (7)	0.2355 (3)	0.0987 (7)
F3	0.6185 (3)	−0.17950 (6)	0.4120 (2)	0.0908 (6)
O1	0.7849 (3)	0.08144 (8)	0.2954 (3)	0.0827 (6)
N1	0.4504 (4)	0.03783 (9)	0.2033 (3)	0.0586 (6)
H1	0.325 (4)	0.0407 (10)	0.159 (4)	0.061 (9)*
N2	0.4818 (3)	0.13161 (8)	0.1745 (3)	0.0577 (6)
C1	0.3428 (4)	−0.05587 (11)	0.2237 (3)	0.0577 (6)
C2	0.3786 (5)	−0.10989 (11)	0.2741 (4)	0.0626 (7)
C3	0.5855 (5)	−0.12546 (11)	0.3645 (4)	0.0649 (7)
C4	0.7542 (5)	−0.08815 (11)	0.4034 (4)	0.0676 (7)
H4	0.8950	−0.0992	0.4640	0.081*
C5	0.7159 (4)	−0.03335 (11)	0.3522 (4)	0.0645 (7)
H5	0.8315	−0.0078	0.3799	0.077*
C6	0.5075 (4)	−0.01615 (10)	0.2603 (3)	0.0521 (6)
C7	0.5845 (4)	0.08395 (10)	0.2289 (3)	0.0558 (6)
C8	0.2441 (4)	0.13970 (10)	0.1006 (4)	0.0637 (7)
H8A	0.1513	0.1238	0.1807	0.076*
H8B	0.2032	0.1234	−0.0203	0.076*
C9	0.2219 (5)	0.20173 (12)	0.0924 (5)	0.0955 (11)
H9A	0.1181	0.2128	−0.0170	0.115*
H9B	0.1664	0.2153	0.1987	0.115*
C10	0.4431 (5)	0.22379 (13)	0.0893 (5)	0.0987 (11)
H10A	0.4614	0.2594	0.1501	0.118*
H10B	0.4652	0.2284	−0.0359	0.118*
C11	0.6072 (5)	0.18321 (11)	0.1877 (4)	0.0744 (8)
H11A	0.7371	0.1800	0.1293	0.089*
H11B	0.6562	0.1939	0.3146	0.089*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0581 (10)	0.0683 (10)	0.1208 (14)	−0.0094 (8)	−0.0083 (9)	0.0058 (9)
F2	0.0865 (13)	0.0638 (10)	0.1378 (17)	−0.0188 (9)	−0.0004 (11)	0.0062 (10)
F3	0.1087 (15)	0.0639 (11)	0.0979 (14)	0.0123 (9)	0.0135 (10)	0.0105 (9)
O1	0.0462 (11)	0.0746 (13)	0.1207 (18)	−0.0060 (9)	−0.0020 (10)	0.0012 (11)
N1	0.0477 (13)	0.0583 (14)	0.0662 (15)	−0.0060 (11)	0.0010 (11)	−0.0014 (10)
N2	0.0468 (12)	0.0521 (12)	0.0723 (14)	−0.0087 (10)	0.0060 (10)	−0.0041 (10)
C1	0.0524 (15)	0.0623 (16)	0.0570 (15)	−0.0028 (13)	0.0064 (11)	−0.0034 (12)
C2	0.0659 (17)	0.0541 (16)	0.0686 (17)	−0.0082 (14)	0.0147 (13)	−0.0042 (13)
C3	0.082 (2)	0.0562 (16)	0.0581 (16)	0.0061 (15)	0.0158 (14)	−0.0003 (12)
C4	0.0633 (17)	0.0739 (18)	0.0628 (17)	0.0100 (15)	0.0039 (13)	0.0012 (14)
C5	0.0563 (16)	0.0664 (17)	0.0675 (17)	−0.0033 (14)	0.0029 (12)	−0.0041 (13)
C6	0.0538 (15)	0.0576 (15)	0.0451 (14)	−0.0014 (12)	0.0097 (11)	−0.0049 (11)
C7	0.0506 (15)	0.0584 (15)	0.0588 (15)	−0.0065 (13)	0.0112 (11)	−0.0061 (12)
C8	0.0516 (15)	0.0632 (16)	0.0736 (18)	−0.0067 (13)	0.0045 (12)	0.0055 (13)
C9	0.069 (2)	0.069 (2)	0.144 (3)	−0.0005 (17)	0.007 (2)	0.0207 (19)
C10	0.082 (2)	0.0619 (19)	0.146 (3)	−0.0105 (18)	0.003 (2)	0.0102 (19)
C11	0.0585 (17)	0.0621 (17)	0.101 (2)	−0.0144 (14)	0.0086 (15)	−0.0058 (15)

Geometric parameters (Å, º) top

F1—C1	1.353 (3)	C4—C5	1.388 (4)
F2—C2	1.341 (3)	C5—H5	0.9300
F3—C3	1.360 (3)	C5—C6	1.387 (3)
O1—C7	1.228 (3)	C8—H8A	0.9700
N1—H1	0.77 (3)	C8—H8B	0.9700
N1—C6	1.398 (3)	C8—C9	1.508 (4)
N1—C7	1.375 (3)	C9—H9A	0.9700
N2—C7	1.338 (3)	C9—H9B	0.9700
N2—C8	1.461 (3)	C9—C10	1.449 (4)
N2—C11	1.457 (3)	C10—H10A	0.9700
C1—C2	1.367 (4)	C10—H10B	0.9700
C1—C6	1.378 (3)	C10—C11	1.492 (4)
C2—C3	1.365 (4)	C11—H11A	0.9700
C3—C4	1.357 (4)	C11—H11B	0.9700
C4—H4	0.9300

C6—N1—H1	112.6 (19)	N2—C7—N1	115.3 (2)
C7—N1—H1	120 (2)	N2—C8—H8A	111.2
C7—N1—C6	127.6 (2)	N2—C8—H8B	111.2
C7—N2—C8	127.1 (2)	N2—C8—C9	102.9 (2)
C7—N2—C11	120.7 (2)	H8A—C8—H8B	109.1
C11—N2—C8	112.3 (2)	C9—C8—H8A	111.2
F1—C1—C2	118.7 (2)	C9—C8—H8B	111.2
F1—C1—C6	118.6 (2)	C8—C9—H9A	110.3
C2—C1—C6	122.7 (2)	C8—C9—H9B	110.3
F2—C2—C1	120.2 (2)	H9A—C9—H9B	108.6
F2—C2—C3	120.7 (2)	C10—C9—C8	106.9 (2)
C3—C2—C1	119.0 (2)	C10—C9—H9A	110.3
F3—C3—C2	118.2 (3)	C10—C9—H9B	110.3
C4—C3—F3	121.0 (3)	C9—C10—H10A	110.4
C4—C3—C2	120.8 (3)	C9—C10—H10B	110.4
C3—C4—H4	120.1	C9—C10—C11	106.7 (3)
C3—C4—C5	119.7 (3)	H10A—C10—H10B	108.6
C5—C4—H4	120.1	C11—C10—H10A	110.4
C4—C5—H5	119.5	C11—C10—H10B	110.4
C6—C5—C4	120.9 (3)	N2—C11—C10	103.7 (2)
C6—C5—H5	119.5	N2—C11—H11A	111.0
C1—C6—N1	117.5 (2)	N2—C11—H11B	111.0
C1—C6—C5	116.8 (2)	C10—C11—H11A	111.0
C5—C6—N1	125.7 (2)	C10—C11—H11B	111.0
O1—C7—N1	122.3 (2)	H11A—C11—H11B	109.0
O1—C7—N2	122.5 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···F1	0.77 (3)	2.27 (3)	2.672 (3)	113 (2)

Experimental details

Crystal data
Chemical formula	C₁₁H₁₁F₃N₂O
M_r	244.22
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	293
a, b, c (Å)	6.0708 (4), 24.2124 (15), 7.4232 (6)
β (°)	100.508 (7)
V (Å³)	1072.83 (13)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.13
Crystal size (mm)	0.35 × 0.35 × 0.25

Data collection
Diffractometer	Oxford Diffraction Xcalibur Eos diffractometer
Absorption correction	Multi-scan (CrysAlis PRO; Oxford Diffraction, 2007)
T_min, T_max	0.964, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	4465, 2190, 1374
R_int	0.018
(sin θ/λ)_max (Å⁻¹)	0.625

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.054, 0.151, 1.04
No. of reflections	2190
No. of parameters	158
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.24, −0.22

Computer programs: CrysAlis PRO (Oxford Diffraction, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), OLEX2 (Dolomanov et al., 2009).

Acknowledgements

The authors thank the NSFC (81072532) for financial support and Professor Zhihua Mao (Sichuan University) for the X-ray measurements

References

Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Oxford Diffraction (2007). CrysAlis PRO. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Zheng, Q.-Z., Cheng, K., Zhang, X.-M., Liu, K., Jiao, Q.-C. & Zhu, H.-L. (2010). Eur. J. Med. Chem. 45, 3207–3212. Web of Science CSD CrossRef CAS PubMed Google Scholar