N-(2,3,4-Trifluoro­phen­yl)morpholine-4-carboxamide

Jie, L.; Shuchen, P.; Li, H.; Yong, W.

doi:10.1107/S1600536811051300

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 68| Part 1| January 2012| Page o13

doi:10.1107/S1600536811051300

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N-(2,3,4-Trifluorophenyl)morpholine-4-carboxamide

Li Jie,^a Pei Shuchen,^a Hai Li ^a and Wu Yong ^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 title molecule, C₁₁H₁₁F₃N₂O₂, the central –N—C(=O)—N– unit is essentially planar [maximum deviation = 0.013 (2) Å] and forms a dihedral angle of 57.33 (9)° with the benzene ring. The morpholine ring is in a chair conformation. In the crystal, molecules are linked into chains along [001] by N—H⋯O hydrogen bonds.

Related literature

For background to urea derivatives as antibacterial and antifungal agents, see: Zheng et al. (2010 ).

Experimental

Crystal data

C₁₁H₁₁F₃N₂O₂
M_r = 260.22
Monoclinic, P 2₁ /c
a = 7.8515 (4) Å
b = 17.8264 (6) Å
c = 8.6872 (4) Å
β = 109.790 (5)°
V = 1144.09 (8) Å³
Z = 4
Mo Kα radiation
μ = 0.14 mm⁻¹
T = 293 K
0.40 × 0.35 × 0.30 mm

Data collection

Agilent Xcalibur Eos diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011 ) T_min = 0.994, T_max = 1.000
4250 measured reflections
2009 independent reflections
1587 reflections with I > 2σ(I)
R_int = 0.016

Refinement

R[F² > 2σ(F²)] = 0.041
wR(F²) = 0.103
S = 1.07
2009 reflections
167 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.15 e Å⁻³
Δρ_min = −0.23 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O2ⁱ	0.843 (18)	2.120 (19)	2.9306 (19)	161.2 (17)
Symmetry code: (i) $[x, -y+{\script{3\over 2}}, z+{\script{1\over 2}}]$ .

Data collection: CrysAlis PRO (Agilent, 2011); 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 ) and PLATON (Spek, 2009 ); software used to prepare material for publication: OLEX2.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811051300/lh5385sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811051300/lh5385Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536811051300/lh5385Isup3.cdx

Supporting information file. DOI: 10.1107/S1600536811051300/lh5385Isup4.cml

checkCIF report

Comment top

The title compound (I) was made as part of our work on urea derivatives. Urea derivatives have been reported in the literature as antibacterial and antifungal agents (Zheng et al., 2010). The crystal structure of (I) is reported herein here.

The molecular structure of the title compound is shown in Fig. 1. The central -N—C(═O)—N- unit is essentially planar (the maximun deviation from atoms N2/C7/O2/O1 is 0.013Å for C7) and forms a dihedral angle of 57.33 (9)° with the benzene ring. The morpholine ring is in a chair conformation. In the crystal, molecules are linked into chains along [001] by N—H···O hydrogen bonds (Fig. 2).

Related literature top

For background to urea derivatives as antibacterial and antifungal agents, see: Zheng et al. (2010).

Experimental top

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, a solution of 2,3,4-trifluoroaniline (500 mg, 3.40 mmol) and triethylamine (680 mg, 6.80 mmol) in anhydrous acetonitrile (5 ml) was added dropwise. The mixture was stirred for 1 h. Then, a solition of morpholine (300 mg,3.40 mmol) and triethylamine (680 mg, 6.80 mmol) in anhydrous acetonitrile (5 ml) was 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 (1:8) yielded the white solid 670 mg (yield 76.2%) of N-(2,3,4-trifluorophenyl)morpholine-4-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 (Agilent, 2011); cell refinement: CrysAlis PRO (Agilent, 2011); data reduction: CrysAlis PRO (Agilent, 2011); 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) and PLATON (Spek, 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. Part of the crystal structure with hydrogen bonds shown as dashed lines.

N-(2,3,4-Trifluorophenyl)morpholine-4-carboxamide top

Crystal data top

C₁₁H₁₁F₃N₂O₂	F(000) = 536
M_r = 260.22	D_x = 1.511 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.7107 Å
a = 7.8515 (4) Å	Cell parameters from 1772 reflections
b = 17.8264 (6) Å	θ = 3.0–29.1°
c = 8.6872 (4) Å	µ = 0.14 mm⁻¹
β = 109.790 (5)°	T = 293 K
V = 1144.09 (8) Å³	Block, colorless
Z = 4	0.40 × 0.35 × 0.30 mm

Data collection top

Agilent Xcalibur Eos diffractometer	2009 independent reflections
Radiation source: Enhance (Mo) X-ray Source	1587 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.016
Detector resolution: 16.0874 pixels mm^-1	θ_max = 25.0°, θ_min = 3.0°
ω scans	h = −7→9
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011)	k = −13→21
T_min = 0.994, T_max = 1.000	l = −10→7
4250 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)] = 0.041	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.103	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ²(F_o²) + (0.044P)² + 0.1807P] where P = (F_o² + 2F_c²)/3
2009 reflections	(Δ/σ)_max < 0.001
167 parameters	Δρ_max = 0.15 e Å⁻³
0 restraints	Δρ_min = −0.23 e Å⁻³

Crystal data top

C₁₁H₁₁F₃N₂O₂	V = 1144.09 (8) Å³
M_r = 260.22	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 7.8515 (4) Å	µ = 0.14 mm⁻¹
b = 17.8264 (6) Å	T = 293 K
c = 8.6872 (4) Å	0.40 × 0.35 × 0.30 mm
β = 109.790 (5)°

Data collection top

Agilent Xcalibur Eos diffractometer	2009 independent reflections
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011)	1587 reflections with I > 2σ(I)
T_min = 0.994, T_max = 1.000	R_int = 0.016
4250 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.041	0 restraints
wR(F²) = 0.103	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	Δρ_max = 0.15 e Å⁻³
2009 reflections	Δρ_min = −0.23 e Å⁻³
167 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	0.88764 (17)	0.67437 (6)	0.52547 (15)	0.0574 (4)
F2	1.12312 (17)	0.76456 (7)	0.45200 (16)	0.0681 (4)
F3	1.11974 (18)	0.91342 (7)	0.50200 (18)	0.0764 (4)
O1	0.2304 (2)	0.51651 (8)	0.66738 (18)	0.0617 (4)
O2	0.50780 (18)	0.68346 (7)	0.37155 (14)	0.0427 (4)
N1	0.6148 (2)	0.73140 (8)	0.63043 (18)	0.0384 (4)
N2	0.4106 (2)	0.63276 (8)	0.56564 (16)	0.0370 (4)
C1	0.8741 (3)	0.74877 (10)	0.5421 (2)	0.0380 (4)
C2	0.9976 (3)	0.79446 (11)	0.5078 (2)	0.0434 (5)
C3	0.9947 (3)	0.87006 (11)	0.5337 (2)	0.0469 (5)
C4	0.8722 (3)	0.90070 (11)	0.5949 (2)	0.0471 (5)
H4	0.8739	0.9519	0.6159	0.057*
C5	0.7451 (3)	0.85485 (10)	0.6255 (2)	0.0397 (5)
H5	0.6604	0.8757	0.6662	0.048*
C6	0.7420 (2)	0.77841 (9)	0.59651 (19)	0.0331 (4)
C7	0.5081 (2)	0.68272 (9)	0.5135 (2)	0.0328 (4)
C8	0.2658 (3)	0.59059 (10)	0.4469 (2)	0.0422 (5)
H8A	0.2909	0.5865	0.3452	0.051*
H8B	0.1523	0.6173	0.4244	0.051*
C9	0.2489 (3)	0.51341 (11)	0.5100 (3)	0.0546 (6)
H9A	0.1442	0.4885	0.4342	0.065*
H9B	0.3553	0.4842	0.5165	0.065*
C10	0.3837 (3)	0.55182 (12)	0.7792 (2)	0.0587 (6)
H10A	0.4916	0.5240	0.7841	0.070*
H10B	0.3735	0.5512	0.8874	0.070*
C11	0.4023 (3)	0.63175 (11)	0.7304 (2)	0.0484 (5)
H11A	0.2996	0.6610	0.7340	0.058*
H11B	0.5115	0.6538	0.8063	0.058*
H1	0.576 (3)	0.7459 (10)	0.705 (2)	0.039 (5)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0633 (8)	0.0337 (6)	0.0872 (9)	0.0021 (5)	0.0412 (7)	−0.0068 (6)
F2	0.0613 (8)	0.0643 (8)	0.1001 (10)	0.0016 (6)	0.0552 (8)	−0.0071 (7)
F3	0.0789 (10)	0.0583 (8)	0.1138 (11)	−0.0191 (7)	0.0613 (9)	0.0059 (7)
O1	0.0655 (10)	0.0587 (10)	0.0722 (10)	−0.0197 (8)	0.0380 (9)	0.0057 (8)
O2	0.0571 (9)	0.0439 (8)	0.0345 (7)	−0.0081 (6)	0.0253 (6)	−0.0018 (5)
N1	0.0493 (10)	0.0379 (9)	0.0361 (8)	−0.0088 (7)	0.0252 (8)	−0.0071 (7)
N2	0.0437 (9)	0.0384 (8)	0.0333 (8)	−0.0090 (7)	0.0188 (7)	0.0005 (6)
C1	0.0448 (11)	0.0291 (9)	0.0438 (10)	0.0012 (8)	0.0199 (9)	−0.0017 (8)
C2	0.0428 (11)	0.0460 (12)	0.0497 (11)	0.0019 (9)	0.0266 (9)	−0.0013 (9)
C3	0.0494 (12)	0.0427 (11)	0.0549 (12)	−0.0112 (10)	0.0259 (10)	0.0050 (9)
C4	0.0572 (13)	0.0308 (10)	0.0576 (12)	−0.0045 (9)	0.0252 (11)	−0.0012 (9)
C5	0.0449 (11)	0.0349 (10)	0.0435 (10)	0.0010 (9)	0.0206 (9)	−0.0045 (8)
C6	0.0398 (10)	0.0326 (9)	0.0294 (8)	−0.0031 (8)	0.0150 (8)	−0.0008 (7)
C7	0.0379 (10)	0.0300 (9)	0.0338 (9)	0.0033 (8)	0.0165 (8)	0.0014 (7)
C8	0.0408 (11)	0.0433 (11)	0.0449 (11)	−0.0065 (9)	0.0177 (9)	−0.0050 (9)
C9	0.0563 (14)	0.0431 (12)	0.0725 (14)	−0.0106 (10)	0.0326 (12)	−0.0082 (10)
C10	0.0637 (15)	0.0638 (14)	0.0549 (13)	−0.0065 (12)	0.0283 (12)	0.0179 (11)
C11	0.0588 (13)	0.0536 (12)	0.0389 (10)	−0.0124 (10)	0.0247 (9)	0.0023 (9)

Geometric parameters (Å, º) top

F1—C1	1.342 (2)	C3—C4	1.361 (3)
F2—C2	1.347 (2)	C4—H4	0.9300
F3—C3	1.349 (2)	C4—C5	1.383 (3)
O1—C9	1.424 (2)	C5—H5	0.9300
O1—C10	1.413 (3)	C5—C6	1.384 (2)
O2—C7	1.232 (2)	C8—H8A	0.9700
N1—C6	1.409 (2)	C8—H8B	0.9700
N1—C7	1.383 (2)	C8—C9	1.504 (3)
N1—H1	0.843 (18)	C9—H9A	0.9700
N2—C7	1.349 (2)	C9—H9B	0.9700
N2—C8	1.459 (2)	C10—H10A	0.9700
N2—C11	1.455 (2)	C10—H10B	0.9700
C1—C2	1.374 (3)	C10—C11	1.508 (3)
C1—C6	1.382 (2)	C11—H11A	0.9700
C2—C3	1.368 (3)	C11—H11B	0.9700

C10—O1—C9	109.68 (15)	O2—C7—N2	122.31 (16)
C6—N1—H1	116.2 (13)	N2—C7—N1	116.05 (15)
C7—N1—C6	121.05 (14)	N2—C8—H8A	109.5
C7—N1—H1	118.2 (13)	N2—C8—H8B	109.5
C7—N2—C8	119.83 (14)	N2—C8—C9	110.94 (15)
C7—N2—C11	123.95 (15)	H8A—C8—H8B	108.0
C11—N2—C8	113.93 (15)	C9—C8—H8A	109.5
F1—C1—C2	118.37 (17)	C9—C8—H8B	109.5
F1—C1—C6	120.70 (16)	O1—C9—C8	111.42 (17)
C2—C1—C6	120.91 (17)	O1—C9—H9A	109.3
F2—C2—C1	119.96 (17)	O1—C9—H9B	109.3
F2—C2—C3	120.24 (18)	C8—C9—H9A	109.3
C3—C2—C1	119.78 (18)	C8—C9—H9B	109.3
F3—C3—C2	118.52 (18)	H9A—C9—H9B	108.0
F3—C3—C4	120.61 (18)	O1—C10—H10A	109.3
C4—C3—C2	120.83 (18)	O1—C10—H10B	109.3
C3—C4—H4	120.4	O1—C10—C11	111.65 (17)
C3—C4—C5	119.28 (18)	H10A—C10—H10B	108.0
C5—C4—H4	120.4	C11—C10—H10A	109.3
C4—C5—H5	119.5	C11—C10—H10B	109.3
C4—C5—C6	121.08 (18)	N2—C11—C10	109.20 (16)
C6—C5—H5	119.5	N2—C11—H11A	109.8
C1—C6—N1	120.74 (15)	N2—C11—H11B	109.8
C1—C6—C5	117.99 (17)	C10—C11—H11A	109.8
C5—C6—N1	121.17 (16)	C10—C11—H11B	109.8
O2—C7—N1	121.59 (16)	H11A—C11—H11B	108.3

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O2ⁱ	0.843 (18)	2.120 (19)	2.9306 (19)	161.2 (17)

Symmetry code: (i) x, −y+3/2, z+1/2.

Experimental details

Crystal data
Chemical formula	C₁₁H₁₁F₃N₂O₂
M_r	260.22
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	7.8515 (4), 17.8264 (6), 8.6872 (4)
β (°)	109.790 (5)
V (Å³)	1144.09 (8)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.14
Crystal size (mm)	0.40 × 0.35 × 0.30

Data collection
Diffractometer	Agilent Xcalibur Eos diffractometer
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2011)
T_min, T_max	0.994, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	4250, 2009, 1587
R_int	0.016
(sin θ/λ)_max (Å⁻¹)	0.594

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.041, 0.103, 1.07
No. of reflections	2009
No. of parameters	167
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.15, −0.23

Computer programs: CrysAlis PRO (Agilent, 2011), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), OLEX2 (Dolomanov et al., 2009) and PLATON (Spek, 2009), OLEX2 (Dolomanov et al., 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O2ⁱ	0.843 (18)	2.120 (19)	2.9306 (19)	161.2 (17)

Symmetry code: (i) x, −y+3/2, z+1/2.

Acknowledgements

The authors thank the NSFC(81102324) for financial support and Professor Zhihua Mao (Sichuan University) for the X-ray measurements

References

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