Ethyl 1-(2,6-difluoro­benz­yl)-1H-1,2,3-triazole-4-carboxyl­ate

Jia, J.; Lu, D.

doi:10.1107/S1600536810050014

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 67| Part 1| January 2011| Page o127

https://doi.org/10.1107/S1600536810050014

Open

access

Ethyl 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylate

Jing Jia ^a and Dingqiang Lu ^a ^*

^aSchool of Pharmaceutical Sciences, Nanjing University of Technology, No. 5 Xinmofan Road, Nanjing 210009, People's Republic of China and Jiangsu Provincial Institute of Materia Medica, Nanjing University of Technology, No. 26 Majia Street, Nanjing 210009, People's Republic of China
^*Correspondence e-mail: jiajing.jj@gmail.com

(Received 25 November 2010; accepted 30 November 2010; online 15 December 2010)

In the title compound, C₁₂H₁₁F₂N₃O₂, the dihedral angle between the triazole and phenyl rings is 73.74 (9)°. In the crystal, molecules are linked into chains along [010] via weak C—H⋯O and C—H⋯N hydrogen bonds.

Related literature

The title compound is an intermediate in the synthesis of rufinamide, a new anti-epilepsy drug (Herranz, 2008 ). For synthetic procedures, see: Abu-Orabi et al. (1989 ); Wang & Xie (2004 ). For a related structure, see: Xiao et al. (2008 ).

Experimental

Crystal data

C₁₂H₁₁F₂N₃O₂
M_r = 267.24
Monoclinic, P 2₁ /c
a = 9.4540 (19) Å
b = 10.963 (2) Å
c = 12.167 (2) Å
β = 93.21 (3)°
V = 1259.1 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.12 mm⁻¹
T = 293 K
0.30 × 0.20 × 0.20 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: ψ scan (North et al., 1968 ) T_min = 0.965, T_max = 0.977
3270 measured reflections
2316 independent reflections
1629 reflections with I > 2σ(I)
R_int = 0.026
3 standard reflections every 200 reflections intensity decay: 1%

Refinement

R[F² > 2σ(F²)] = 0.055
wR(F²) = 0.163
S = 1.03
2316 reflections
174 parameters
H-atom parameters constrained
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C7—H7B⋯O1ⁱ	0.97	2.47	3.415 (3)	166
C8—H8⋯N3ⁱ	0.93	2.61	3.536 (3)	172
Symmetry code: (i) $[-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994 ); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995 ); 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: PLATON (Spek, 2009 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536810050014/pv2364sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810050014/pv2364Isup2.hkl

checkCIF report

Comment top

Epilepsia has been a common disease for a long time and has been on an increase year after year. Rufinamide is a new drug to cure epilepsia; it is a triazole derivative (Herranz et al., 2008). We report herein the crystal structure of the title compound which is a key intermediate in the synthesis of rufinamide. In the title compound (Fig. 1), the planes of the triazole and phenyl rings are not coplanar [dihedral angle 73.74 (9)°]. The discrete molecules are linked through weak C—H···O and C—H···N hydrogen bonds, forming one-dimensional chains along [010] direction (Fig. 2 and Tab. 1). In the structure of the title compound, the bond lengths and angles agree with the corresponding values reported for a related compound (Xiao et al., 2008).

Related literature top

The title compound is an intermediate in the synthesis of rufinamide, a new anti-epilepsy drug (Herranz, 2008). For synthetic procedures, see: Abu-Orabi et al. (1989); Wang & Xie (2004). For a related structure, see: Xiao et al. (2008).

Experimental top

The title compound, was prepared by following procedures reported earlier (Wang et al., 2004; Abu-Orabi et al., 1989). To a solution of 2-(azidomethyl)-1,3-difluorobenzene (1.69 g, 10 mmol) in etanol (50 mL), ethyl propiolate (0.98 g, 10 mmol) was added and the mixture was heated under reflux for 10 h. After removing the solvent under reduced pressure the residue was dissolved and the title compound recrystallized from petroleum ether-methanol mixture (15:2), to provide crystals suitable for X-ray diffraction (yield 2.31 g, 86.3%).

Structure description top

The title compound is an intermediate in the synthesis of rufinamide, a new anti-epilepsy drug (Herranz, 2008). For synthetic procedures, see: Abu-Orabi et al. (1989); Wang & Xie (2004). For a related structure, see: Xiao et al. (2008).

Computing details top

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994); cell refinement: CAD-4 EXPRESS (Enraf–Nonius, 1994); data reduction: XCAD4 (Harms & Wocadlo, 1995); 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: PLATON (Spek, 2009).

Figures top

	Fig. 1. ORTEP view of the title compound. The dispalcement ellipsoids are drawn at 30% probability level.
	Fig. 2. A one-dimensional chain of the title compound.

Ethyl 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylate top

Crystal data top

C₁₂H₁₁F₂N₃O₂	F(000) = 552
M_r = 267.24	D_x = 1.410 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 25 reflections
a = 9.4540 (19) Å	θ = 9–13°
b = 10.963 (2) Å	µ = 0.12 mm⁻¹
c = 12.167 (2) Å	T = 293 K
β = 93.21 (3)°	Block, colorless
V = 1259.1 (4) Å³	0.30 × 0.20 × 0.20 mm
Z = 4

Data collection top

Enraf–Nonius CAD-4 diffractometer	1629 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.026
Graphite monochromator	θ_max = 25.4°, θ_min = 2.2°
ω/2θ scans	h = 0→11
Absorption correction: ψ scan (North et al., 1968)	k = −3→13
T_min = 0.965, T_max = 0.977	l = −14→14
3270 measured reflections	3 standard reflections every 200 reflections
2316 independent reflections	intensity decay: 1%

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.055	H-atom parameters constrained
wR(F²) = 0.163	w = 1/[σ²(F_o²) + (0.0873P)² + 0.337P] where P = (F_o² + 2F_c²)/3
S = 1.03	(Δ/σ)_max < 0.001
2316 reflections	Δρ_max = 0.32 e Å⁻³
174 parameters	Δρ_min = −0.22 e Å⁻³
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.029 (5)

Crystal data top

C₁₂H₁₁F₂N₃O₂	V = 1259.1 (4) Å³
M_r = 267.24	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 9.4540 (19) Å	µ = 0.12 mm⁻¹
b = 10.963 (2) Å	T = 293 K
c = 12.167 (2) Å	0.30 × 0.20 × 0.20 mm
β = 93.21 (3)°

Data collection top

Enraf–Nonius CAD-4 diffractometer	1629 reflections with I > 2σ(I)
Absorption correction: ψ scan (North et al., 1968)	R_int = 0.026
T_min = 0.965, T_max = 0.977	3 standard reflections every 200 reflections
3270 measured reflections	intensity decay: 1%
2316 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.055	0 restraints
wR(F²) = 0.163	H-atom parameters constrained
S = 1.03	Δρ_max = 0.32 e Å⁻³
2316 reflections	Δρ_min = −0.22 e Å⁻³
174 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	0.94152 (18)	0.27880 (14)	0.02828 (16)	0.0890 (6)
F2	0.78127 (17)	0.61613 (15)	0.22000 (14)	0.0829 (6)
O1	0.4165 (2)	0.20776 (17)	0.46337 (16)	0.0744 (6)
O2	0.3594 (2)	0.39959 (17)	0.41799 (17)	0.0776 (6)
N1	0.62925 (19)	0.35347 (16)	0.16945 (17)	0.0537 (5)
N2	0.6558 (3)	0.2343 (2)	0.1898 (2)	0.0751 (7)
N3	0.5829 (2)	0.20178 (19)	0.2728 (2)	0.0709 (7)
C1	0.9678 (3)	0.3771 (2)	0.0933 (2)	0.0618 (7)
C2	1.1060 (3)	0.4031 (3)	0.1262 (3)	0.0733 (8)
H2	1.1796	0.3538	0.1049	0.088*
C3	1.1325 (3)	0.5034 (3)	0.1910 (3)	0.0751 (8)
H3	1.2252	0.5220	0.2146	0.090*
C4	1.0243 (3)	0.5767 (3)	0.2217 (2)	0.0687 (7)
H4	1.0426	0.6459	0.2644	0.082*
C5	0.8887 (3)	0.5456 (2)	0.1878 (2)	0.0583 (6)
C6	0.8534 (2)	0.4459 (2)	0.12140 (19)	0.0522 (6)
C7	0.7032 (3)	0.4176 (2)	0.0843 (2)	0.0593 (7)
H7B	0.6538	0.4930	0.0658	0.071*
H7A	0.7023	0.3676	0.0185	0.071*
C8	0.5379 (2)	0.3966 (2)	0.2397 (2)	0.0524 (6)
H8	0.5015	0.4753	0.2428	0.063*
C9	0.5093 (2)	0.3001 (2)	0.3059 (2)	0.0538 (6)
C10	0.4248 (3)	0.2941 (2)	0.4032 (2)	0.0577 (6)
C11	0.2781 (4)	0.4100 (3)	0.5169 (3)	0.1053 (13)
H11A	0.2056	0.3473	0.5162	0.126*
H11B	0.3404	0.3988	0.5822	0.126*
C12	0.2137 (4)	0.5286 (3)	0.5186 (3)	0.0955 (11)
H12A	0.1482	0.5373	0.4559	0.143*
H12C	0.2857	0.5901	0.5163	0.143*
H12B	0.1641	0.5376	0.5849	0.143*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0929 (12)	0.0560 (10)	0.1202 (14)	−0.0053 (8)	0.0250 (10)	−0.0258 (9)
F2	0.0797 (11)	0.0754 (11)	0.0936 (12)	0.0159 (9)	0.0056 (9)	−0.0255 (9)
O1	0.0857 (13)	0.0520 (11)	0.0853 (13)	−0.0042 (9)	0.0038 (10)	0.0175 (10)
O2	0.0897 (14)	0.0537 (11)	0.0929 (14)	0.0125 (10)	0.0351 (11)	0.0150 (10)
N1	0.0500 (11)	0.0360 (10)	0.0751 (13)	−0.0006 (8)	0.0039 (9)	−0.0005 (9)
N2	0.0744 (15)	0.0421 (12)	0.1107 (18)	0.0101 (11)	0.0221 (14)	0.0037 (12)
N3	0.0678 (14)	0.0404 (12)	0.1064 (18)	0.0058 (10)	0.0220 (13)	0.0086 (12)
C1	0.0709 (17)	0.0402 (12)	0.0759 (16)	−0.0045 (12)	0.0198 (13)	−0.0027 (11)
C2	0.0581 (16)	0.0583 (17)	0.105 (2)	0.0027 (13)	0.0198 (15)	0.0076 (15)
C3	0.0602 (16)	0.0719 (19)	0.093 (2)	−0.0104 (15)	0.0015 (15)	0.0048 (16)
C4	0.0718 (17)	0.0629 (16)	0.0706 (17)	−0.0111 (14)	−0.0030 (13)	−0.0067 (13)
C5	0.0621 (15)	0.0524 (14)	0.0607 (14)	0.0023 (12)	0.0061 (12)	−0.0008 (11)
C6	0.0562 (13)	0.0444 (12)	0.0563 (13)	−0.0040 (11)	0.0066 (10)	0.0055 (10)
C7	0.0614 (15)	0.0506 (14)	0.0658 (15)	−0.0042 (11)	0.0018 (12)	−0.0001 (12)
C8	0.0439 (12)	0.0359 (12)	0.0769 (16)	0.0018 (9)	−0.0008 (11)	−0.0022 (11)
C9	0.0460 (12)	0.0375 (12)	0.0775 (16)	−0.0028 (10)	−0.0004 (11)	0.0011 (11)
C10	0.0534 (13)	0.0434 (13)	0.0759 (16)	−0.0046 (11)	−0.0003 (12)	0.0039 (12)
C11	0.141 (3)	0.077 (2)	0.103 (3)	0.020 (2)	0.058 (2)	0.0216 (19)
C12	0.105 (2)	0.095 (3)	0.088 (2)	0.018 (2)	0.0283 (18)	0.0080 (19)

Geometric parameters (Å, º) top

F1—C1	1.352 (3)	C4—C5	1.368 (4)
F2—C5	1.352 (3)	C4—H4	0.9300
O1—C10	1.202 (3)	C5—C6	1.390 (3)
O2—C10	1.329 (3)	C6—C7	1.498 (3)
O2—C11	1.468 (4)	C7—H7B	0.9700
N1—C8	1.335 (3)	C7—H7A	0.9700
N1—N2	1.351 (3)	C8—C9	1.366 (3)
N1—C7	1.462 (3)	C8—H8	0.9300
N2—N3	1.304 (3)	C9—C10	1.466 (4)
N3—C9	1.356 (3)	C11—C12	1.437 (4)
C1—C2	1.374 (4)	C11—H11A	0.9700
C1—C6	1.377 (3)	C11—H11B	0.9700
C2—C3	1.368 (4)	C12—H12A	0.9600
C2—H2	0.9300	C12—H12C	0.9600
C3—C4	1.369 (4)	C12—H12B	0.9600
C3—H3	0.9300

C10—O2—C11	116.6 (2)	C6—C7—H7B	109.3
C8—N1—N2	110.2 (2)	N1—C7—H7A	109.3
C8—N1—C7	129.4 (2)	C6—C7—H7A	109.3
N2—N1—C7	120.2 (2)	H7B—C7—H7A	108.0
N3—N2—N1	107.8 (2)	N1—C8—C9	105.03 (19)
N2—N3—C9	108.3 (2)	N1—C8—H8	127.5
F1—C1—C2	118.4 (2)	C9—C8—H8	127.5
F1—C1—C6	117.4 (2)	N3—C9—C8	108.6 (2)
C2—C1—C6	124.2 (2)	N3—C9—C10	121.0 (2)
C3—C2—C1	118.3 (3)	C8—C9—C10	130.2 (2)
C3—C2—H2	120.8	O1—C10—O2	123.7 (2)
C1—C2—H2	120.8	O1—C10—C9	125.8 (2)
C2—C3—C4	120.9 (3)	O2—C10—C9	110.4 (2)
C2—C3—H3	119.5	C12—C11—O2	108.9 (3)
C4—C3—H3	119.5	C12—C11—H11A	109.9
C5—C4—C3	118.2 (3)	O2—C11—H11A	109.9
C5—C4—H4	120.9	C12—C11—H11B	109.9
C3—C4—H4	120.9	O2—C11—H11B	109.9
F2—C5—C4	118.5 (2)	H11A—C11—H11B	108.3
F2—C5—C6	117.3 (2)	C11—C12—H12A	109.5
C4—C5—C6	124.2 (2)	C11—C12—H12C	109.5
C1—C6—C5	114.1 (2)	H12A—C12—H12C	109.5
C1—C6—C7	123.8 (2)	C11—C12—H12B	109.5
C5—C6—C7	122.0 (2)	H12A—C12—H12B	109.5
N1—C7—C6	111.7 (2)	H12C—C12—H12B	109.5
N1—C7—H7B	109.3

C8—N1—N2—N3	−0.5 (3)	C8—N1—C7—C6	100.9 (3)
C7—N1—N2—N3	176.4 (2)	N2—N1—C7—C6	−75.2 (3)
N1—N2—N3—C9	0.0 (3)	C1—C6—C7—N1	99.0 (3)
F1—C1—C2—C3	179.3 (3)	C5—C6—C7—N1	−81.2 (3)
C6—C1—C2—C3	0.1 (4)	N2—N1—C8—C9	0.7 (3)
C1—C2—C3—C4	−0.6 (4)	C7—N1—C8—C9	−175.8 (2)
C2—C3—C4—C5	1.4 (4)	N2—N3—C9—C8	0.4 (3)
C3—C4—C5—F2	178.5 (3)	N2—N3—C9—C10	−175.6 (2)
C3—C4—C5—C6	−1.9 (4)	N1—C8—C9—N3	−0.7 (3)
F1—C1—C6—C5	−179.7 (2)	N1—C8—C9—C10	174.9 (2)
C2—C1—C6—C5	−0.5 (4)	C11—O2—C10—O1	2.7 (4)
F1—C1—C6—C7	0.1 (4)	C11—O2—C10—C9	−176.0 (3)
C2—C1—C6—C7	179.4 (2)	N3—C9—C10—O1	3.0 (4)
F2—C5—C6—C1	−179.0 (2)	C8—C9—C10—O1	−172.1 (3)
C4—C5—C6—C1	1.4 (4)	N3—C9—C10—O2	−178.3 (2)
F2—C5—C6—C7	1.2 (3)	C8—C9—C10—O2	6.6 (4)
C4—C5—C6—C7	−178.4 (2)	C10—O2—C11—C12	−179.3 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C7—H7A···F1	0.97	2.46	2.833 (3)	103
C7—H7B···O1ⁱ	0.97	2.47	3.415 (3)	166
C8—H8···N3ⁱ	0.93	2.61	3.536 (3)	172

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

Experimental details

Crystal data
Chemical formula	C₁₂H₁₁F₂N₃O₂
M_r	267.24
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	9.4540 (19), 10.963 (2), 12.167 (2)
β (°)	93.21 (3)
V (Å³)	1259.1 (4)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.12
Crystal size (mm)	0.30 × 0.20 × 0.20

Data collection
Diffractometer	Enraf–Nonius CAD-4
Absorption correction	ψ scan (North et al., 1968)
T_min, T_max	0.965, 0.977
No. of measured, independent and observed [I > 2σ(I)] reflections	3270, 2316, 1629
R_int	0.026
(sin θ/λ)_max (Å⁻¹)	0.603

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.055, 0.163, 1.03
No. of reflections	2316
No. of parameters	174
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.32, −0.22

Computer programs: CAD-4 EXPRESS (Enraf–Nonius, 1994), XCAD4 (Harms & Wocadlo, 1995), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008), PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C7—H7A···F1	0.97	2.46	2.833 (3)	102.6
C7—H7B···O1ⁱ	0.97	2.47	3.415 (3)	165.8
C8—H8···N3ⁱ	0.93	2.61	3.536 (3)	172.2

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

Acknowledgements

The authors thank the Center of Testing and Analysis, Nanjing University, for support.

References

Abu-Orabi, S. T., Atfah, M. A., Jibril, I., Mari'i, F. M. & Ali, A. A.-S. (1989). J. Heterocycl. Chem. 26, 1461–1468. CrossRef CAS Google Scholar
Enraf–Nonius (1994). CAD-4 Software. Enraf–Nonius, Delft, The Netherlands. Google Scholar
Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany. Google Scholar
Herranz, J. L. (2008). Rev. Neurol. 47, 369–373. Web of Science PubMed CAS Google Scholar
North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359. CrossRef IUCr Journals Web of Science 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
Wang, J. M. & Xie, Z. F. (2004). J. Med. Sci. Yanbian Univ. 27, 264-266. CAS Google Scholar
Xiao, J., Wang, W. X. & Zhao, H. (2008). Acta Cryst. E64, o2085. Web of Science CSD CrossRef IUCr Journals Google Scholar