Ethyl 2-(6-nitro-2H-indazol-2-yl)acetate

Rejouani, F.-Z.; Mojahidi, S.; Rakib, E.M.; Mdeghri Alaoui, A.; Saadi, M.; El Ammari, L.

doi:10.1107/S2414314616010749

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 1| Part 7| July 2016| x161074

https://doi.org/10.1107/S2414314616010749

Open

access

Ethyl 2-(6-nitro-2H-indazol-2-yl)acetate

Fatima-Zahra Rejouani,^a ^* Souad Mojahidi,^a El Mostapha Rakib,^a Abdelouahed Mdeghri Alaoui,^a Mohamed Saadi ^b and Lahcen El Ammari ^b

^aLaboratoire de Chimie Organique et Analytique, Université Sultan Moulay Slimane, Faculté des Sciences et Techniques, Béni-Mellal, BP 523, Morocco, and ^bLaboratoire de Chimie du Solide Appliquée, Faculty of Sciences, Mohammed V University in Rabat, Avenue Ibn Battouta, BP 1014, Rabat, Morocco
^*Correspondence e-mail: f_rejouani@yahoo.com

Edited by E. R. T. Tiekink, Sunway University, Malaysia (Received 29 June 2016; accepted 2 July 2016; online 7 July 2016)

In the title compound, C₁₁H₁₁N₃O₄, the indazolyl ring and the nitro group are nearly coplanar, with the greatest deviation from their mean plane being 0.103 (2) Å. The mean plane through the acetate group is almost perpendicular to the indazolyl ring, subtending a dihedral angle of 88.05 (7)°. In the crystal, molecules are linked by C—H⋯O and C—H⋯N non-classical hydrogen bonds to form supramolecular layers that stack along the a axis.

Keywords: crystal structure; 6-nitro-2H-indazolyl; ester; hydrogen bonds.

CCDC reference: 1489667

Structure description

Indazolyl derivatives have been used widely in medicinal chemistry (Gaikwad et al., 2015 ) and drug discovery (Jennings & Tennant et al., 2007 ). They exhibit a broad range of biological activities including HIV protease inhibition (Han et al., 1998 ), anti-inflammatory (Rosati et al., 2007 ) anti-microbial (Li et al., 2003 ), antispermatogenic (Takahashi et al., 2011 ) antiplatelet (Lee et al., 2001 ) and anticancer activities (Abbassi et al., 2012 , 2014 ).

The molecule of the title compound is built up from an indazolyl ring (C1–C7/N2/N3) linked to a nitro group and to an ethyl acetate groups as shown in Fig. 1. The nitro group and indazolyl cycle are nearly coplanar with the greatest deviation from the mean plane being 0.103 (2) Å for the O1 atom. The mean plan through the acetate moieties is almost perpendicular to the indazolyl ring as indicated by the dihedral angle of 88.05 (7)° between them.

Figure 1
Plot of the molecule of the title compound with the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are represented as small circles.

The crystal structure cohesion is ensured by C—H⋯O and C—H⋯N hydrogen interactions (Table 1), which form supramolecular layers that stack along the a axis.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C7—H7⋯O3ⁱ	0.93	2.54	3.2743 (18)	137
C8—H8A⋯N2ⁱⁱ	0.97	2.59	3.4650 (19)	149
C8—H8B⋯O3ⁱⁱⁱ	0.97	2.34	3.2525 (18)	157
Symmetry codes: (i) $[-x+{\script{1\over 2}}, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (ii) $[-x+{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+1]$ ; (iii) x, y-1, z.

Synthesis and crystallization

To a solution of 6-nitroindazole (6.13 mmol) in THF (30 ml) was added K₂CO₃ (9.2 mmol). After 15 min at 298 K, ethyl bromoacetate (6.13 mmol) was added dropwise. The solution was refluxed with stirring for 6 h and the resulting mixture was evaporated. The crude material was dissolved with EtOAc (50 ml), washed with water and brine, dried over MgSO₄ and the solvent evaporated in vacuo. The resulting residue was purified by column chromatography (EtOAc/ hexane 3/7). The title compound was recrystallized from ethanol at room temperature giving colourless crystals (m.p. 338 K, yield 65%).

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₁H₁₁N₃O₄
M_r	249.23
Crystal system, space group	Monoclinic, C2/c
Temperature (K)	296
a, b, c (Å)	31.808 (3), 4.6312 (4), 19.0381 (16)
β (°)	122.839 (3)
V (Å³)	2356.3 (3)
Z	8
Radiation type	Mo Kα
μ (mm⁻¹)	0.11
Crystal size (mm)	0.35 × 0.31 × 0.25

Data collection
Diffractometer	Bruker X8 APEX
Absorption correction	Multi-scan (SADABS; Sheldrick, 2015b )
T_min, T_max	0.626, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections	25389, 3324, 2517
R_int	0.030
(sin θ/λ)_max (Å⁻¹)	0.694

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.044, 0.140, 1.03
No. of reflections	3324
No. of parameters	163
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.20, −0.19
Computer programs: APEX2 and SAINT (Bruker, 2009 ), SHELXT (Sheldrick, 2015a ), SHELXL2014 (Sheldrick, 2015b), ORTEP-3 for Windows (Farrugia, 2012 ), Mercury (Macrae et al., 2008 ) and publCIF (Westrip, 2010 ).

Structural data

CCDC reference: 1489667

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314616010749/tk4019sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314616010749/tk4019Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314616010749/tk4019Isup3.cml

checkCIF report

Computing details top

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: Mercury (Macrae et al., 2008) and publCIF (Westrip, 2010).

Ethyl 2-(6-nitro-2H-indazol-2-yl)acetate top

Crystal data top

C₁₁H₁₁N₃O₄	D_x = 1.405 Mg m⁻³
M_r = 249.23	Melting point: 338 K
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
a = 31.808 (3) Å	Cell parameters from 3324 reflections
b = 4.6312 (4) Å	θ = 2.1–29.6°
c = 19.0381 (16) Å	µ = 0.11 mm⁻¹
β = 122.839 (3)°	T = 296 K
V = 2356.3 (3) Å³	Block, colourless
Z = 8	0.35 × 0.31 × 0.25 mm
F(000) = 1040

Data collection top

Bruker X8 APEX diffractometer	3324 independent reflections
Radiation source: fine-focus sealed tube	2517 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.030
φ and ω scans	θ_max = 29.6°, θ_min = 2.1°
Absorption correction: multi-scan (SADABS; Sheldrick, 2015b)	h = −44→44
T_min = 0.626, T_max = 0.746	k = −6→6
25389 measured reflections	l = −24→26

Refinement top

Refinement on F²	0 restraints
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.044	H-atom parameters constrained
wR(F²) = 0.140	w = 1/[σ²(F_o²) + (0.0714P)² + 0.8343P] where P = (F_o² + 2F_c²)/3
S = 1.03	(Δ/σ)_max < 0.001
3324 reflections	Δρ_max = 0.20 e Å⁻³
163 parameters	Δρ_min = −0.19 e Å⁻³

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.33711 (5)	0.4119 (3)	0.46597 (8)	0.0418 (3)
C2	0.37402 (5)	0.6087 (3)	0.52132 (8)	0.0466 (3)
H2	0.3723	0.7029	0.5628	0.056*
C3	0.41254 (5)	0.6530 (3)	0.51054 (8)	0.0472 (3)
C4	0.41682 (5)	0.5172 (4)	0.44835 (10)	0.0570 (4)
H4	0.4443	0.5553	0.4447	0.068*
C5	0.38093 (6)	0.3310 (4)	0.39402 (10)	0.0580 (4)
H5	0.3831	0.2427	0.3522	0.070*
C6	0.34001 (5)	0.2737 (3)	0.40226 (8)	0.0454 (3)
C7	0.29814 (5)	0.0965 (3)	0.36243 (9)	0.0508 (3)
H7	0.2884	−0.0244	0.3171	0.061*
C8	0.22800 (5)	0.0023 (3)	0.38266 (9)	0.0516 (3)
H8A	0.2282	−0.0198	0.4335	0.062*
H8B	0.2252	−0.1883	0.3594	0.062*
C9	0.18351 (5)	0.1819 (3)	0.32093 (8)	0.0432 (3)
C10	0.09600 (6)	0.2351 (4)	0.25660 (11)	0.0614 (4)
H10A	0.0955	0.4089	0.2845	0.074*
H10B	0.0940	0.2908	0.2058	0.074*
C11	0.05359 (6)	0.0510 (5)	0.23640 (13)	0.0792 (6)
H11A	0.0230	0.1540	0.2005	0.119*
H11B	0.0542	−0.1199	0.2084	0.119*
H11C	0.0557	−0.0022	0.2870	0.119*
N1	0.45222 (5)	0.8546 (3)	0.56789 (8)	0.0608 (3)
N2	0.29646 (4)	0.3270 (3)	0.46565 (7)	0.0482 (3)
N3	0.27453 (4)	0.1349 (2)	0.40251 (7)	0.0467 (3)
O1	0.48852 (5)	0.8813 (4)	0.56230 (9)	0.0909 (5)
O2	0.44763 (5)	0.9839 (4)	0.61888 (9)	0.0884 (4)
O3	0.18539 (4)	0.3901 (2)	0.28551 (7)	0.0644 (3)
O4	0.14227 (3)	0.0744 (2)	0.31126 (6)	0.0532 (3)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0379 (6)	0.0444 (6)	0.0440 (6)	0.0005 (5)	0.0229 (5)	0.0021 (5)
C2	0.0426 (6)	0.0519 (7)	0.0444 (6)	−0.0045 (5)	0.0231 (5)	−0.0024 (5)
C3	0.0372 (6)	0.0517 (7)	0.0465 (6)	−0.0025 (5)	0.0186 (5)	0.0082 (5)
C4	0.0456 (7)	0.0720 (9)	0.0616 (8)	0.0004 (7)	0.0345 (7)	0.0075 (7)
C5	0.0575 (8)	0.0695 (9)	0.0609 (8)	0.0013 (7)	0.0411 (7)	−0.0033 (7)
C6	0.0449 (7)	0.0453 (6)	0.0479 (7)	0.0034 (5)	0.0263 (6)	0.0013 (5)
C7	0.0528 (7)	0.0472 (7)	0.0520 (7)	−0.0009 (6)	0.0282 (6)	−0.0068 (6)
C8	0.0432 (7)	0.0446 (7)	0.0594 (8)	−0.0074 (5)	0.0229 (6)	0.0013 (6)
C9	0.0454 (7)	0.0394 (6)	0.0433 (6)	−0.0058 (5)	0.0230 (5)	−0.0063 (5)
C10	0.0529 (8)	0.0542 (8)	0.0715 (10)	0.0136 (7)	0.0301 (7)	0.0105 (7)
C11	0.0435 (8)	0.0896 (13)	0.0937 (13)	0.0143 (8)	0.0302 (9)	0.0275 (11)
N1	0.0453 (7)	0.0706 (8)	0.0555 (7)	−0.0128 (6)	0.0202 (6)	0.0064 (6)
N2	0.0430 (6)	0.0540 (6)	0.0507 (6)	−0.0083 (5)	0.0275 (5)	−0.0079 (5)
N3	0.0413 (5)	0.0433 (5)	0.0522 (6)	−0.0040 (4)	0.0231 (5)	−0.0022 (5)
O1	0.0569 (7)	0.1261 (12)	0.0900 (9)	−0.0356 (7)	0.0402 (7)	−0.0075 (8)
O2	0.0756 (8)	0.1017 (10)	0.0873 (9)	−0.0404 (8)	0.0438 (7)	−0.0381 (8)
O3	0.0602 (6)	0.0561 (6)	0.0687 (7)	−0.0068 (5)	0.0296 (6)	0.0132 (5)
O4	0.0417 (5)	0.0527 (5)	0.0620 (6)	0.0017 (4)	0.0260 (5)	0.0095 (4)

Geometric parameters (Å, º) top

C1—N2	1.3485 (15)	C8—C9	1.5073 (19)
C1—C2	1.4062 (18)	C8—H8A	0.9700
C1—C6	1.4182 (17)	C8—H8B	0.9700
C2—C3	1.3631 (17)	C9—O3	1.1964 (16)
C2—H2	0.9300	C9—O4	1.3195 (15)
C3—C4	1.411 (2)	C10—C11	1.460 (2)
C3—N1	1.4703 (18)	C10—O4	1.4634 (17)
C4—C5	1.355 (2)	C10—H10A	0.9700
C4—H4	0.9300	C10—H10B	0.9700
C5—C6	1.4177 (18)	C11—H11A	0.9600
C5—H5	0.9300	C11—H11B	0.9600
C6—C7	1.3881 (18)	C11—H11C	0.9600
C7—N3	1.3411 (17)	N1—O2	1.2150 (19)
C7—H7	0.9300	N1—O1	1.2218 (17)
C8—N3	1.4504 (16)	N2—N3	1.3468 (16)

N2—C1—C2	126.96 (11)	C9—C8—H8B	109.4
N2—C1—C6	111.80 (11)	H8A—C8—H8B	108.0
C2—C1—C6	121.23 (11)	O3—C9—O4	125.13 (13)
C3—C2—C1	115.98 (12)	O3—C9—C8	124.84 (12)
C3—C2—H2	122.0	O4—C9—C8	110.03 (11)
C1—C2—H2	122.0	C11—C10—O4	108.64 (13)
C2—C3—C4	124.25 (13)	C11—C10—H10A	110.0
C2—C3—N1	117.61 (13)	O4—C10—H10A	110.0
C4—C3—N1	118.14 (12)	C11—C10—H10B	110.0
C5—C4—C3	119.96 (12)	O4—C10—H10B	110.0
C5—C4—H4	120.0	H10A—C10—H10B	108.3
C3—C4—H4	120.0	C10—C11—H11A	109.5
C4—C5—C6	118.62 (13)	C10—C11—H11B	109.5
C4—C5—H5	120.7	H11A—C11—H11B	109.5
C6—C5—H5	120.7	C10—C11—H11C	109.5
C7—C6—C5	135.79 (13)	H11A—C11—H11C	109.5
C7—C6—C1	104.23 (11)	H11B—C11—H11C	109.5
C5—C6—C1	119.96 (12)	O2—N1—O1	123.26 (14)
N3—C7—C6	106.16 (12)	O2—N1—C3	118.66 (12)
N3—C7—H7	126.9	O1—N1—C3	118.08 (15)
C6—C7—H7	126.9	N3—N2—C1	103.17 (10)
N3—C8—C9	111.32 (11)	C7—N3—N2	114.63 (11)
N3—C8—H8A	109.4	C7—N3—C8	127.07 (12)
C9—C8—H8A	109.4	N2—N3—C8	118.25 (11)
N3—C8—H8B	109.4	C9—O4—C10	116.59 (11)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C7—H7···O3ⁱ	0.93	2.54	3.2743 (18)	137
C8—H8A···N2ⁱⁱ	0.97	2.59	3.4650 (19)	149
C8—H8B···O3ⁱⁱⁱ	0.97	2.34	3.2525 (18)	157

Symmetry codes: (i) −x+1/2, y−1/2, −z+1/2; (ii) −x+1/2, −y+1/2, −z+1; (iii) x, y−1, z.

Acknowledgements

The authors thank the Unit of Support for Technical and Scientific Research (UATRS, CNRST) for the X-ray measurements and the University Sultan Moulay Slimane, Beni-Mellal, Morocco, for the financial support.

References

Abbassi, N., Chicha, H., Rakib, el M., Hannioui, A., Alaoui, M., Hajjaji, A., Geffken, D., Aiello, C., Gangemi, R., Rosano, C. & Viale, M. (2012). Eur. J. Med. Chem. 57, 240–249. Web of Science CrossRef CAS PubMed Google Scholar
Abbassi, N., Rakib, E. M., Chicha, H., Bouissane, L., Hannioui, A., Aiello, C., Gangemi, R., Castagnola, P., Rosano, C. & Viale, M. (2014). Arch. Pharm. Chem. Life Sci. 347, 423–431. Web of Science CrossRef CAS Google Scholar
Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854. Web of Science CrossRef CAS IUCr Journals Google Scholar
Gaikwad, D. D., Chapolikar, A. D., Devkate, C. G., Warad, K. D., Tayade, A. P., Pawar, R. P. & Domb, A. J. (2015). Eur. J. Med. Chem. 90, 707–731. Web of Science CrossRef CAS PubMed Google Scholar
Han, W., Pelletier, J. C. & Hodge, C. N. (1998). Bioorg. Med. Chem. Lett. 8, 3615–3620. Web of Science CrossRef CAS PubMed Google Scholar
Jennings, A. & Tennant, M. (2007). J. Chem. Inf. Model. 47, 1829–1838. Web of Science CrossRef PubMed CAS Google Scholar
Lee, F. Y., Lien, J. C., Huang, L. J., Huang, T. M., Tsai, S. C., Teng, C. M., Wu, C. C., Cheng, F. C. & Kuo, S. C. (2001). J. Med. Chem. 44, 3746–3749. Web of Science CrossRef PubMed CAS Google Scholar
Li, X., Chu, S., Feher, V. A., Khalili, M., Nie, Z., Margosiak, S., Nikulin, V., Levin, J., Sprankle, K. G., Tedder, M. E., Almassy, R., Appelt, K. & Yager, K. M. (2003). J. Med. Chem. 46, 5663–5673. Web of Science CrossRef PubMed CAS Google Scholar
Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466–470. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Rosati, O., Curini, M., Marcotullio, M. C., Macchiarulo, A., Perfumi, M., Mattioli, L., Rismondo, F. & Cravotto, G. (2007). Bioorg. Med. Chem. 15, 3463–3473. Web of Science CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Takahashi, H., Shinoyama, M., Komine, T., Nagao, M., Suzuki, M., Tsuchida, H. & Katsuyama, K. (2011). Bioorg. Med. Chem. Lett. 21, 1758–1762. Web of Science CrossRef CAS PubMed Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

IUCrDATA

ISSN: 2414-3146

Volume 1| Part 7| July 2016| x161074

https://doi.org/10.1107/S2414314616010749

Open

access

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text
		Text

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text
		Text

Search IUCr Journals		doi		Advanced search
Author		volume	page

organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Ethyl 2-(6-nitro-2H-indazol-2-yl)acetate

Structure description

Synthesis and crystallization

Refinement

Structural data

Acknowledgements

References

organic compounds