Ethyl 3-(4-chloro­phen­yl)-5-(ethoxy­carbon­yl)-1H-pyrazole-1-acetate

Dong, W.-L.; Dong, W.-L.; Xia, Y.; Ge, Y.-Q.; Zhao, B.-X.

doi:10.1107/S1600536807052208

Ethyl 3-(4-chlorophenyl)-5-(ethoxycarbonyl)-1H-pyrazole-1-acetate

W.-L. Dong, W.-L. Dong, Y. Xia, Y.-Q. Ge and B.-X. Zhao

In the title compound, C₁₆H₁₇ClN₂O₄, all bond lengths and angles show normal values. The dihedral angle between the pyrazole ring and the benzene ring is 5.75 (8)°. The molecules are linked into a network by intermolecular C—Cl

π interactions.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807052208/fj2060sup1.cif Contains datablocks I, global
	Structure factor file (CIF format) https://doi.org/10.1107/S1600536807052208/fj2060Isup2.hkl Contains datablock I

CCDC reference: 667465

checkCIF report

Key indicators

Single-crystal X-ray study
T = 296 K
Mean (C-C) = 0.002 Å
R factor = 0.038
wR factor = 0.108
Data-to-parameter ratio = 18.0

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT154_ALERT_1_C The su's on the Cell Angles are Equal  (x 10000)        100 Deg.
PLAT180_ALERT_3_C Check Cell Rounding: # of Values Ending with 0 =          4

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   2 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

Comment top

The pyrazole unit is one of the core structures in a number of natural products. Many pyrazole derivatives are known to exhibit a wide range of biological properties such as antagonists (Sehon et al., 2006), anti-inflammatory (Cheng et al., 2006), inhibitors of the Hsp90 (Brough et al., 2005), antitumor (Wei et al., 2006, Xia et al., 2007). We report here the crystal structure of the title compound, (I).

In compound (I) (Fig. 1), all bond lengths and angles are normal (Allen et al., 1987). The dihedral angle between the rings of the pyrazole and the benzene ring is 5.75 (8)°. The two ethyl carboxylate groups are inclined to the attached pyrazole ring by 1.09 (7)° and 78.21 (9)°, respectively. The molecules are linked into a network parallel by C—H···π interactions (Table 1) involving the pyrazole ring (centroid Cg1).

Related literature top

For related literature, see: Allen et al. (1987); Brough et al. (2005); Cheng et al. (2006); Sehon et al. (2006); Wei et al. (2006); Xia et al. (2007).

Experimental top

A mixture of ethyl 3-(4-chlorophenyl)-1H-pyrazole-5-carboxylate (0.01 mol), ethyl chloroacetate (0.015 mol) and potassium carbonate (0.02 mol) in acetonitrile (50 ml) was heated to reflux for 15 h. The solvent was removed under reduced pressure, and the residue was dissolved in the mixture of water (50 ml) and ethyl acetate (50 ml). After separated, the water phase was extracted with ethyl acetate (25 ml), and then the organic phase was combined, dried over anhydrous magnesium sulfate and filtered. The solvent was removed under reduced pressure. The solid product was recrystallized from ethyl acetate (yield 64%). Crystals of (I) suitable for X-ray diffraction were obtained by slow evaporation of a solution of the solid in ethyl acetate at room temperature for 4 d.

Structure description top

For related literature, see: Allen et al. (1987); Brough et al. (2005); Cheng et al. (2006); Sehon et al. (2006); Wei et al. (2006); Xia et al. (2007).

Computing details top

Data collection: APEX2 (Bruker, 2005); cell refinement: APEX2 (Bruker, 2005); data reduction: APEX2 (Bruker, 2005); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999) and PLATON (Spek, 2003).

Figures top

	Fig. 1. The structure of the title molecule showing displacement ellipsoids drawn at the 50% probability level. Hydrogen atoms have been omitted for clarity.
	Fig. 2. Packing view of (I), shown down the a axis.

Ethyl 3-(4-chlorophenyl)-5-(ethoxycarbonyl)-1H-pyrazole-1-acetate top

Crystal data top

C₁₆H₁₇ClN₂O₄	Z = 2
M_r = 336.77	F(000) = 352
Triclinic, P1	D_x = 1.354 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 6.9912 (1) Å	Cell parameters from 6319 reflections
b = 10.8651 (2) Å	θ = 2.2–27.5°
c = 12.2528 (3) Å	µ = 0.25 mm⁻¹
α = 108.407 (1)°	T = 296 K
β = 99.878 (1)°	Block, colourless
γ = 103.834 (1)°	0.48 × 0.40 × 0.37 mm
V = 826.08 (3) Å³

Data collection top

Bruker APEX2 CCD area-detector diffractometer	3784 independent reflections
Radiation source: fine-focus sealed tube	3029 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.020
φ and ω scans	θ_max = 27.6°, θ_min = 1.8°
Absorption correction: multi-scan (APEX2; Bruker, 2005)	h = −9→9
T_min = 0.889, T_max = 0.913	k = −14→14
12665 measured reflections	l = −15→14

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)] = 0.038	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.108	H-atom parameters constrained
S = 1.06	w = 1/[σ²(F_o²) + (0.0497P)² + 0.1299P] where P = (F_o² + 2F_c²)/3
3784 reflections	(Δ/σ)_max = 0.001
210 parameters	Δρ_max = 0.17 e Å⁻³
0 restraints	Δρ_min = −0.26 e Å⁻³

Crystal data top

C₁₆H₁₇ClN₂O₄	γ = 103.834 (1)°
M_r = 336.77	V = 826.08 (3) Å³
Triclinic, P1	Z = 2
a = 6.9912 (1) Å	Mo Kα radiation
b = 10.8651 (2) Å	µ = 0.25 mm⁻¹
c = 12.2528 (3) Å	T = 296 K
α = 108.407 (1)°	0.48 × 0.40 × 0.37 mm
β = 99.878 (1)°

Data collection top

Bruker APEX2 CCD area-detector diffractometer	3784 independent reflections
Absorption correction: multi-scan (APEX2; Bruker, 2005)	3029 reflections with I > 2σ(I)
T_min = 0.889, T_max = 0.913	R_int = 0.020
12665 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.038	0 restraints
wR(F²) = 0.108	H-atom parameters constrained
S = 1.06	Δρ_max = 0.17 e Å⁻³
3784 reflections	Δρ_min = −0.26 e Å⁻³
210 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
C1	1.4251 (2)	0.32582 (15)	0.55519 (14)	0.0539 (3)
C2	1.2529 (2)	0.21560 (17)	0.49049 (14)	0.0616 (4)
H2	1.2460	0.1574	0.4146	0.074*
C3	1.0909 (2)	0.19247 (15)	0.53954 (13)	0.0588 (4)
H3	0.9745	0.1181	0.4958	0.071*
C4	1.0977 (2)	0.27768 (13)	0.65283 (12)	0.0466 (3)
C5	1.2746 (2)	0.38795 (14)	0.71633 (13)	0.0556 (3)
H5	1.2832	0.4461	0.7925	0.067*
C6	1.4372 (2)	0.41210 (15)	0.66777 (14)	0.0592 (4)
H6	1.5543	0.4862	0.7108	0.071*
C7	0.9249 (2)	0.25142 (13)	0.70471 (12)	0.0472 (3)
C8	0.8980 (2)	0.33064 (13)	0.81219 (12)	0.0489 (3)
H8	0.9875	0.4138	0.8676	0.059*
C9	0.7116 (2)	0.25994 (13)	0.81884 (12)	0.0475 (3)
C10	0.6129 (2)	0.30064 (14)	0.91472 (13)	0.0535 (3)
C11	0.3153 (2)	0.24963 (19)	0.98225 (16)	0.0682 (4)
H11A	0.2796	0.3306	0.9823	0.082*
H11B	0.3955	0.2679	1.0618	0.082*
C12	0.1269 (3)	0.1310 (2)	0.9463 (2)	0.0836 (6)
H12A	0.0592	0.1055	0.8637	0.125*
H12B	0.0368	0.1557	0.9943	0.125*
H12C	0.1632	0.0553	0.9579	0.125*
C13	0.4440 (2)	0.03457 (14)	0.67921 (12)	0.0511 (3)
H13A	0.4209	−0.0216	0.5960	0.061*
H13B	0.3325	0.0728	0.6854	0.061*
C14	0.4434 (2)	−0.05372 (14)	0.75279 (13)	0.0545 (3)
C15	0.2261 (3)	−0.22815 (18)	0.79200 (18)	0.0764 (5)
H15A	0.2627	−0.1800	0.8778	0.092*
H15B	0.3126	−0.2854	0.7738	0.092*
C16	0.0075 (3)	−0.3130 (3)	0.7480 (3)	0.1160 (9)
H16A	−0.0768	−0.2549	0.7631	0.174*
H16B	−0.0169	−0.3752	0.7888	0.174*
H16C	−0.0251	−0.3638	0.6638	0.174*
Cl1	1.62997 (7)	0.35614 (5)	0.49404 (4)	0.07621 (16)
N1	0.76366 (17)	0.13804 (11)	0.64765 (10)	0.0512 (3)
N2	0.63518 (16)	0.14490 (11)	0.71761 (10)	0.0480 (3)
O1	0.69162 (19)	0.40359 (13)	1.00153 (11)	0.0874 (4)
O2	0.43116 (15)	0.21400 (10)	0.89587 (9)	0.0596 (3)
O3	0.59010 (18)	−0.05511 (14)	0.81726 (13)	0.0857 (4)
O4	0.25301 (15)	−0.13161 (10)	0.73253 (9)	0.0595 (3)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0528 (8)	0.0533 (8)	0.0604 (8)	0.0151 (6)	0.0205 (6)	0.0259 (7)
C2	0.0627 (9)	0.0606 (9)	0.0529 (8)	0.0138 (7)	0.0169 (7)	0.0132 (7)
C3	0.0524 (8)	0.0532 (8)	0.0526 (8)	0.0019 (6)	0.0083 (6)	0.0099 (6)
C4	0.0453 (7)	0.0425 (7)	0.0486 (7)	0.0075 (5)	0.0098 (5)	0.0185 (6)
C5	0.0537 (8)	0.0468 (7)	0.0522 (8)	0.0012 (6)	0.0145 (6)	0.0105 (6)
C6	0.0515 (8)	0.0495 (8)	0.0629 (9)	−0.0003 (6)	0.0157 (7)	0.0151 (7)
C7	0.0451 (7)	0.0405 (6)	0.0478 (7)	0.0025 (5)	0.0065 (5)	0.0170 (5)
C8	0.0441 (7)	0.0403 (6)	0.0490 (7)	0.0000 (5)	0.0074 (6)	0.0119 (5)
C9	0.0442 (7)	0.0403 (6)	0.0457 (7)	0.0015 (5)	0.0047 (5)	0.0125 (5)
C10	0.0465 (7)	0.0483 (7)	0.0512 (8)	0.0016 (6)	0.0080 (6)	0.0120 (6)
C11	0.0577 (9)	0.0780 (11)	0.0666 (10)	0.0143 (8)	0.0242 (8)	0.0249 (8)
C12	0.0686 (11)	0.0831 (12)	0.1117 (15)	0.0156 (9)	0.0442 (11)	0.0481 (12)
C13	0.0451 (7)	0.0447 (7)	0.0453 (7)	−0.0050 (5)	0.0035 (5)	0.0114 (5)
C14	0.0493 (8)	0.0452 (7)	0.0562 (8)	0.0006 (6)	0.0085 (6)	0.0158 (6)
C15	0.0759 (11)	0.0638 (10)	0.0924 (13)	0.0060 (8)	0.0235 (10)	0.0442 (10)
C16	0.0892 (15)	0.0949 (16)	0.151 (2)	−0.0211 (12)	0.0157 (15)	0.0742 (16)
Cl1	0.0705 (3)	0.0778 (3)	0.0866 (3)	0.0186 (2)	0.0411 (2)	0.0317 (2)
N1	0.0498 (6)	0.0456 (6)	0.0465 (6)	0.0000 (5)	0.0107 (5)	0.0140 (5)
N2	0.0445 (6)	0.0417 (6)	0.0442 (6)	−0.0021 (4)	0.0067 (5)	0.0124 (5)
O1	0.0672 (7)	0.0733 (8)	0.0718 (8)	−0.0138 (6)	0.0244 (6)	−0.0144 (6)
O2	0.0503 (5)	0.0571 (6)	0.0559 (6)	−0.0016 (4)	0.0160 (5)	0.0135 (5)
O3	0.0566 (7)	0.0860 (9)	0.1089 (10)	0.0010 (6)	−0.0037 (7)	0.0582 (8)
O4	0.0517 (6)	0.0514 (6)	0.0666 (6)	−0.0016 (4)	0.0129 (5)	0.0252 (5)

Geometric parameters (Å, º) top

C1—C6	1.376 (2)	C11—C12	1.491 (2)
C1—C2	1.377 (2)	C11—H11A	0.9700
C1—Cl1	1.7380 (15)	C11—H11B	0.9700
C2—C3	1.378 (2)	C12—H12A	0.9600
C2—H2	0.9300	C12—H12B	0.9600
C3—C4	1.390 (2)	C12—H12C	0.9600
C3—H3	0.9300	C13—N2	1.4515 (15)
C4—C5	1.3940 (19)	C13—C14	1.510 (2)
C4—C7	1.4693 (19)	C13—H13A	0.9700
C5—C6	1.380 (2)	C13—H13B	0.9700
C5—H5	0.9300	C14—O3	1.1885 (18)
C6—H6	0.9300	C14—O4	1.3287 (16)
C7—N1	1.3410 (16)	C15—O4	1.4499 (19)
C7—C8	1.3987 (19)	C15—C16	1.486 (3)
C8—C9	1.3757 (18)	C15—H15A	0.9700
C8—H8	0.9300	C15—H15B	0.9700
C9—N2	1.3639 (16)	C16—H16A	0.9600
C9—C10	1.466 (2)	C16—H16B	0.9600
C10—O1	1.1995 (17)	C16—H16C	0.9600
C10—O2	1.3205 (16)	N1—N2	1.3427 (16)
C11—O2	1.4532 (19)

C6—C1—C2	120.87 (14)	H11A—C11—H11B	108.5
C6—C1—Cl1	119.57 (11)	C11—C12—H12A	109.5
C2—C1—Cl1	119.56 (12)	C11—C12—H12B	109.5
C1—C2—C3	119.19 (14)	H12A—C12—H12B	109.5
C1—C2—H2	120.4	C11—C12—H12C	109.5
C3—C2—H2	120.4	H12A—C12—H12C	109.5
C2—C3—C4	121.51 (13)	H12B—C12—H12C	109.5
C2—C3—H3	119.2	N2—C13—C14	112.21 (11)
C4—C3—H3	119.2	N2—C13—H13A	109.2
C3—C4—C5	117.91 (13)	C14—C13—H13A	109.2
C3—C4—C7	121.07 (12)	N2—C13—H13B	109.2
C5—C4—C7	121.01 (12)	C14—C13—H13B	109.2
C6—C5—C4	120.96 (14)	H13A—C13—H13B	107.9
C6—C5—H5	119.5	O3—C14—O4	125.27 (14)
C4—C5—H5	119.5	O3—C14—C13	125.56 (13)
C1—C6—C5	119.56 (13)	O4—C14—C13	109.16 (12)
C1—C6—H6	120.2	O4—C15—C16	107.41 (16)
C5—C6—H6	120.2	O4—C15—H15A	110.2
N1—C7—C8	110.55 (12)	C16—C15—H15A	110.2
N1—C7—C4	120.44 (12)	O4—C15—H15B	110.2
C8—C7—C4	129.01 (12)	C16—C15—H15B	110.2
C9—C8—C7	105.64 (11)	H15A—C15—H15B	108.5
C9—C8—H8	127.2	C15—C16—H16A	109.5
C7—C8—H8	127.2	C15—C16—H16B	109.5
N2—C9—C8	106.38 (12)	H16A—C16—H16B	109.5
N2—C9—C10	126.65 (12)	C15—C16—H16C	109.5
C8—C9—C10	126.96 (12)	H16A—C16—H16C	109.5
O1—C10—O2	123.87 (14)	H16B—C16—H16C	109.5
O1—C10—C9	122.42 (13)	C7—N1—N2	105.61 (11)
O2—C10—C9	113.71 (12)	N1—N2—C9	111.82 (10)
O2—C11—C12	107.11 (14)	N1—N2—C13	118.63 (11)
O2—C11—H11A	110.3	C9—N2—C13	129.55 (12)
C12—C11—H11A	110.3	C10—O2—C11	117.87 (12)
O2—C11—H11B	110.3	C14—O4—C15	116.38 (12)
C12—C11—H11B	110.3

C6—C1—C2—C3	0.3 (2)	N2—C9—C10—O2	−0.7 (2)
Cl1—C1—C2—C3	−179.86 (12)	C8—C9—C10—O2	178.45 (13)
C1—C2—C3—C4	−0.1 (2)	N2—C13—C14—O3	−15.2 (2)
C2—C3—C4—C5	−0.2 (2)	N2—C13—C14—O4	165.85 (12)
C2—C3—C4—C7	−179.46 (14)	C8—C7—N1—N2	0.17 (15)
C3—C4—C5—C6	0.4 (2)	C4—C7—N1—N2	179.97 (11)
C7—C4—C5—C6	179.66 (14)	C7—N1—N2—C9	−0.48 (15)
C2—C1—C6—C5	−0.1 (2)	C7—N1—N2—C13	−179.80 (11)
Cl1—C1—C6—C5	−179.95 (12)	C8—C9—N2—N1	0.60 (15)
C4—C5—C6—C1	−0.3 (2)	C10—C9—N2—N1	179.87 (13)
C3—C4—C7—N1	5.6 (2)	C8—C9—N2—C13	179.83 (13)
C5—C4—C7—N1	−173.64 (13)	C10—C9—N2—C13	−0.9 (2)
C3—C4—C7—C8	−174.68 (14)	C14—C13—N2—N1	108.02 (14)
C5—C4—C7—C8	6.1 (2)	C14—C13—N2—C9	−71.16 (19)
N1—C7—C8—C9	0.19 (16)	O1—C10—O2—C11	3.6 (2)
C4—C7—C8—C9	−179.59 (13)	C9—C10—O2—C11	−176.19 (13)
C7—C8—C9—N2	−0.46 (15)	C12—C11—O2—C10	−175.19 (14)
C7—C8—C9—C10	−179.73 (13)	O3—C14—O4—C15	−1.9 (2)
N2—C9—C10—O1	179.51 (16)	C13—C14—O4—C15	177.03 (13)
C8—C9—C10—O1	−1.4 (2)	C16—C15—O4—C14	−174.51 (17)

Experimental details

Crystal data
Chemical formula	C₁₆H₁₇ClN₂O₄
M_r	336.77
Crystal system, space group	Triclinic, P1
Temperature (K)	296
a, b, c (Å)	6.9912 (1), 10.8651 (2), 12.2528 (3)
α, β, γ (°)	108.407 (1), 99.878 (1), 103.834 (1)
V (Å³)	826.08 (3)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.25
Crystal size (mm)	0.48 × 0.40 × 0.37

Data collection
Diffractometer	Bruker APEX2 CCD area-detector
Absorption correction	Multi-scan (APEX2; Bruker, 2005)
T_min, T_max	0.889, 0.913
No. of measured, independent and observed [I > 2σ(I)] reflections	12665, 3784, 3029
R_int	0.020
(sin θ/λ)_max (Å⁻¹)	0.653

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.038, 0.108, 1.06
No. of reflections	3784
No. of parameters	210
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.17, −0.26

Computer programs: APEX2 (Bruker, 2005), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 1997), SHELXTL (Bruker, 1997), WinGX (Farrugia, 1999) and PLATON (Spek, 2003).

Y—X···π-ring interactions top

Y—X···Cg	Y—X	X···Cg	Y···Cg	Y—X···Cg
C1-Cl1···Cg1ⁱ	1.7378 (16)	3.8281 (8)	3.6952 (17)	72.42 (6)

Symmetry code: (i) -1+x, y, z. Cgⁱ is the centroid of the pyrazole ring (N1/N2/C7/C8/C9).

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Ethyl 3-(4-chloro­phen­yl)-5-(ethoxy­carbon­yl)-1H-pyrazole-1-acetate

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Ethyl 3-(4-chlorophenyl)-5-(ethoxycarbonyl)-1H-pyrazole-1-acetate