supplementary materials


bt5716 scheme

Acta Cryst. (2012). E68, o12    [ doi:10.1107/S1600536811051385 ]

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

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

Abstract top

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.

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.

Refinement top

H atoms bonded to C were positioned geometrically (C—H = 0.93–0.97 Å) and refined using a riding model, with Uiso(H) = 1.2Ueq(C). The amino H atom was freely refined.

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
[Figure 1] Fig. 1. The molecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level.
[Figure 2] Fig. 2. A packing diagram for the title compound.
N-(2,3,4-Trifluorophenyl)pyrrolidine-1-carboxamide top
Crystal data top
C11H11F3N2OF(000) = 504
Mr = 244.22Dx = 1.512 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.7107 Å
a = 6.0708 (4) ÅCell parameters from 1445 reflections
b = 24.2124 (15) Åθ = 2.9–28.9°
c = 7.4232 (6) ŵ = 0.13 mm1
β = 100.508 (7)°T = 293 K
V = 1072.83 (13) Å3Block, colorless
Z = 40.35 × 0.35 × 0.25 mm
Data collection top
Oxford Diffraction Xcalibur Eos
diffractometer
2190 independent reflections
Radiation source: Enhance (Mo) X-ray Source1374 reflections with I > 2σ(I)
graphiteRint = 0.018
Detector resolution: 16.0874 pixels mm-1θmax = 26.4°, θmin = 2.9°
ω scansh = 76
Absorption correction: multi-scan
(CrysAlis PRO; Oxford Diffraction, 2007)
k = 3027
Tmin = 0.964, Tmax = 1.000l = 89
4465 measured reflections
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)] = 0.054Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.151H atoms treated by a mixture of independent and constrained refinement
S = 1.04 w = 1/[σ2(Fo2) + (0.055P)2 + 0.3084P]
where P = (Fo2 + 2Fc2)/3
2190 reflections(Δ/σ)max < 0.001
158 parametersΔρmax = 0.24 e Å3
0 restraintsΔρmin = 0.22 e Å3
Crystal data top
C11H11F3N2OV = 1072.83 (13) Å3
Mr = 244.22Z = 4
Monoclinic, P21/nMo Kα radiation
a = 6.0708 (4) ŵ = 0.13 mm1
b = 24.2124 (15) ÅT = 293 K
c = 7.4232 (6) Å0.35 × 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)
Tmin = 0.964, Tmax = 1.000Rint = 0.018
4465 measured reflectionsθmax = 26.4°
Refinement top
R[F2 > 2σ(F2)] = 0.054H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.151Δρmax = 0.24 e Å3
S = 1.04Δρmin = 0.22 e Å3
2190 reflectionsAbsolute structure: ?
158 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
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
F10.1373 (2)0.04074 (6)0.1339 (2)0.0855 (6)
F20.2120 (3)0.14684 (7)0.2355 (3)0.0987 (7)
F30.6185 (3)0.17950 (6)0.4120 (2)0.0908 (6)
O10.7849 (3)0.08144 (8)0.2954 (3)0.0827 (6)
N10.4504 (4)0.03783 (9)0.2033 (3)0.0586 (6)
H10.325 (4)0.0407 (10)0.159 (4)0.061 (9)*
N20.4818 (3)0.13161 (8)0.1745 (3)0.0577 (6)
C10.3428 (4)0.05587 (11)0.2237 (3)0.0577 (6)
C20.3786 (5)0.10989 (11)0.2741 (4)0.0626 (7)
C30.5855 (5)0.12546 (11)0.3645 (4)0.0649 (7)
C40.7542 (5)0.08815 (11)0.4034 (4)0.0676 (7)
H40.89500.09920.46400.081*
C50.7159 (4)0.03335 (11)0.3522 (4)0.0645 (7)
H50.83150.00780.37990.077*
C60.5075 (4)0.01615 (10)0.2603 (3)0.0521 (6)
C70.5845 (4)0.08395 (10)0.2289 (3)0.0558 (6)
C80.2441 (4)0.13970 (10)0.1006 (4)0.0637 (7)
H8A0.15130.12380.18070.076*
H8B0.20320.12340.02030.076*
C90.2219 (5)0.20173 (12)0.0924 (5)0.0955 (11)
H9A0.11810.21280.01700.115*
H9B0.16640.21530.19870.115*
C100.4431 (5)0.22379 (13)0.0893 (5)0.0987 (11)
H10A0.46140.25940.15010.118*
H10B0.46520.22840.03590.118*
C110.6072 (5)0.18321 (11)0.1877 (4)0.0744 (8)
H11A0.73710.18000.12930.089*
H11B0.65620.19390.31460.089*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0581 (10)0.0683 (10)0.1208 (14)0.0094 (8)0.0083 (9)0.0058 (9)
F20.0865 (13)0.0638 (10)0.1378 (17)0.0188 (9)0.0004 (11)0.0062 (10)
F30.1087 (15)0.0639 (11)0.0979 (14)0.0123 (9)0.0135 (10)0.0105 (9)
O10.0462 (11)0.0746 (13)0.1207 (18)0.0060 (9)0.0020 (10)0.0012 (11)
N10.0477 (13)0.0583 (14)0.0662 (15)0.0060 (11)0.0010 (11)0.0014 (10)
N20.0468 (12)0.0521 (12)0.0723 (14)0.0087 (10)0.0060 (10)0.0041 (10)
C10.0524 (15)0.0623 (16)0.0570 (15)0.0028 (13)0.0064 (11)0.0034 (12)
C20.0659 (17)0.0541 (16)0.0686 (17)0.0082 (14)0.0147 (13)0.0042 (13)
C30.082 (2)0.0562 (16)0.0581 (16)0.0061 (15)0.0158 (14)0.0003 (12)
C40.0633 (17)0.0739 (18)0.0628 (17)0.0100 (15)0.0039 (13)0.0012 (14)
C50.0563 (16)0.0664 (17)0.0675 (17)0.0033 (14)0.0029 (12)0.0041 (13)
C60.0538 (15)0.0576 (15)0.0451 (14)0.0014 (12)0.0097 (11)0.0049 (11)
C70.0506 (15)0.0584 (15)0.0588 (15)0.0065 (13)0.0112 (11)0.0061 (12)
C80.0516 (15)0.0632 (16)0.0736 (18)0.0067 (13)0.0045 (12)0.0055 (13)
C90.069 (2)0.069 (2)0.144 (3)0.0005 (17)0.007 (2)0.0207 (19)
C100.082 (2)0.0619 (19)0.146 (3)0.0105 (18)0.003 (2)0.0102 (19)
C110.0585 (17)0.0621 (17)0.101 (2)0.0144 (14)0.0086 (15)0.0058 (15)
Geometric parameters (Å, °) top
F1—C11.353 (3)C4—C51.388 (4)
F2—C21.341 (3)C5—H50.9300
F3—C31.360 (3)C5—C61.387 (3)
O1—C71.228 (3)C8—H8A0.9700
N1—H10.77 (3)C8—H8B0.9700
N1—C61.398 (3)C8—C91.508 (4)
N1—C71.375 (3)C9—H9A0.9700
N2—C71.338 (3)C9—H9B0.9700
N2—C81.461 (3)C9—C101.449 (4)
N2—C111.457 (3)C10—H10A0.9700
C1—C21.367 (4)C10—H10B0.9700
C1—C61.378 (3)C10—C111.492 (4)
C2—C31.365 (4)C11—H11A0.9700
C3—C41.357 (4)C11—H11B0.9700
C4—H40.9300
C6—N1—H1112.6 (19)N2—C7—N1115.3 (2)
C7—N1—H1120 (2)N2—C8—H8A111.2
C7—N1—C6127.6 (2)N2—C8—H8B111.2
C7—N2—C8127.1 (2)N2—C8—C9102.9 (2)
C7—N2—C11120.7 (2)H8A—C8—H8B109.1
C11—N2—C8112.3 (2)C9—C8—H8A111.2
F1—C1—C2118.7 (2)C9—C8—H8B111.2
F1—C1—C6118.6 (2)C8—C9—H9A110.3
C2—C1—C6122.7 (2)C8—C9—H9B110.3
F2—C2—C1120.2 (2)H9A—C9—H9B108.6
F2—C2—C3120.7 (2)C10—C9—C8106.9 (2)
C3—C2—C1119.0 (2)C10—C9—H9A110.3
F3—C3—C2118.2 (3)C10—C9—H9B110.3
C4—C3—F3121.0 (3)C9—C10—H10A110.4
C4—C3—C2120.8 (3)C9—C10—H10B110.4
C3—C4—H4120.1C9—C10—C11106.7 (3)
C3—C4—C5119.7 (3)H10A—C10—H10B108.6
C5—C4—H4120.1C11—C10—H10A110.4
C4—C5—H5119.5C11—C10—H10B110.4
C6—C5—C4120.9 (3)N2—C11—C10103.7 (2)
C6—C5—H5119.5N2—C11—H11A111.0
C1—C6—N1117.5 (2)N2—C11—H11B111.0
C1—C6—C5116.8 (2)C10—C11—H11A111.0
C5—C6—N1125.7 (2)C10—C11—H11B111.0
O1—C7—N1122.3 (2)H11A—C11—H11B109.0
O1—C7—N2122.5 (2)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···F10.77 (3)2.27 (3)2.672 (3)113 (2)
Acknowledgements top

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

references
References top

Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341.

Oxford Diffraction (2007). CrysAlis PRO. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Zheng, Q.-Z., Cheng, K., Zhang, X.-M., Liu, K., Jiao, Q.-C. & Zhu, H.-L. (2010). Eur. J. Med. Chem. 45, 3207–3212.