3-Chloro-2-ethyl-6-nitro-2H-indazole

Mohamed Abdelahi, M.M.; El Bakri, Y.; Minnih, M.S.; Benchidmi, M.; Essassi, E.M.; Mague, J.T.

doi:10.1107/S2414314617006526

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 2| Part 5| May 2017| x170652

https://doi.org/10.1107/S2414314617006526

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access

3-Chloro-2-ethyl-6-nitro-2H-indazole

Mohamed Mokhtar Mohamed Abdelahi,^a ^* Youness El Bakri,^a Mohamed Said Minnih,^b Mohammed Benchidmi,^a El Mokhtar Essassi ^a and Joel T. Mague ^c

^aLaboratoire de Chimie Organique Hétérocyclique, URAC 21, Pôle de Compétence Pharmacochimie, Av Ibn Battouta, BP 1014, Faculté des Sciences, Mohammed V University, Rabat, Morocco, ^bFaculté des Sciences et Techniques, Université de Sciences, de Technologie et de Medecine Nouakchott, Mauritania, and ^cDepartment of Chemistry, Tulane University, New Orleans, LA 70118, USA
^*Correspondence e-mail: mmohamedabdelahi@gmail.com

Edited by J. Simpson, University of Otago, New Zealand (Received 30 April 2017; accepted 1 May 2017; online 5 May 2017)

In the title compound, C₉H₈ClN₃O₂, the orientation of the ethyl substituent is partly determined by an intramolecular C—H⋯Cl hydrogen bond. The indazole moiety is slightly folded with an angle of 0.70 (8)° between the five- and six-membered rings. In the crystal, molecules pack in layers parallel to [100] through C—H⋯π(ring) and N O⋯π(ring) interactions.

Keywords: crystal structure; indazole; hydrogen bond; π-stacking.

CCDC reference: 1547138

Structure description

The indazole nucleus is important pharmaceutically and is a key subunit in many drugs that display a broad range of pharmacological properties. These include HIV protease inhibition (Patel et al., 1999 ) and antiarrhythmic, analgesic and antitumor activities (Mosti et al., 2000 ) together with antihypertensive properties (Bouissane et al., 2006 ; Abbassi et al., 2012 ). As a continuation of our studies of indazole derivatives (Mohamed Abdelahi et al., 2017 ), we report the synthesis and structure of the title compound.

In the title molecule, the indazole portion is very slightly folded, as indicated by the dihedral angle of 0.70 (8)° between the five- and six-membered rings. The orientation of the ethyl substituent is determined, in part, by an intramolecular C8—H8B⋯Cl1 hydrogen bond (Table 1 and Fig. 1). Head-to-tail offset π–π-stacking interactions between indazole ring systems [centroid–centroid distance = 3.5291 (7) Å, dihedral angle = 0.70 (6)°] form dimers that are connected into layers parallel to [100] by a combination of C5—H5⋯Cg2 (Table 1) and N3 O1⋯Cg1 interactions [Cg1 is the centroid of the C1/C6/C7/N1/N2 ring; O1⋯Cg1 = 3.421 (1) Å and N3 O1⋯Cg1 = 126.66 (8)°] (Fig. 2). The ethyl substituents protrude from the faces of the layers.

Table 1
Hydrogen-bond geometry (Å, °)

Cg2 is the centroid of the C1–C6 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C8—H8B⋯Cl1	0.938 (18)	2.689 (17)	3.2158 (15)	116.3 (12)
C5—H5⋯Cg2ⁱ	0.961 (16)	2.698 (15)	3.5418 (13)	147 (1)
Symmetry code: (i) $[-x+1, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

Figure 1
The structure of the title molecule, showing the atom-labelling scheme, with ellipsoids drawn at the 50% probability level. The intramolecular C—H⋯Cl hydrogen bond is shown as a dashed line.

Figure 2
Packing projected onto [010] giving a side view of one sheet of molecules. The π–π stacking, C—H⋯π(ring) and N O⋯π(ring) interactions are shown, respectively, as orange, green and purple dashed lines.

Synthesis and crystallization

To a solution of 6-nitro-1H-indazole (0.8 g, 5 mmol) in tetrahydrofuran (30 ml) was added bromoethane (0.8 g, 5 mmol), potassium carbonate (1.24 g, 9 mmol) and a catalytic quantity of tetra-n-butylammonium iodide. The mixture was stirred at room temperature for 48 h. The solution was filtered and the solvent removed under reduced pressure. The residue was recrystallized from ethanol solution to afford the title compound as colourless crystals (yield: 66%).

Refinement

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

Table 2
Experimental details

Crystal data
Chemical formula	C₉H₈ClN₃O₂
M_r	225.63
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	100
a, b, c (Å)	11.2363 (7), 7.4063 (5), 12.1247 (8)
β (°)	111.051 (1)
V (Å³)	941.67 (11)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.39
Crystal size (mm)	0.34 × 0.19 × 0.16

Data collection
Diffractometer	Bruker SMART APEX CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2016 )
T_min, T_max	0.85, 0.94
No. of measured, independent and observed [I > 2σ(I)] reflections	17539, 2543, 2183
R_int	0.028
(sin θ/λ)_max (Å⁻¹)	0.686

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.036, 0.103, 1.13
No. of reflections	2543
No. of parameters	168
H-atom treatment	All H-atom parameters refined
Δρ_max, Δρ_min (e Å⁻³)	0.68, −0.20
Computer programs: APEX3 and SAINT (Bruker, 2016), SHELXT (Sheldrick, 2015a ), SHELXL2014 (Sheldrick, 2015b ), DIAMOND (Brandenburg & Putz, 2012 ) and SHELXTL (Sheldrick, 2008 ).

Structural data

CCDC reference: 1547138

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2414314617006526/sj4109sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314617006526/sj4109Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314617006526/sj4109Isup3.cdx

Supporting information file. DOI: https://doi.org/10.1107/S2414314617006526/sj4109Isup4.cml

checkCIF report

Computing details top

Data collection: APEX3 (Bruker, 2016); cell refinement: SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: DIAMOND (Brandenburg & Putz, 2012); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

3-Chloro-2-ethyl-6-nitro-2H-indazole top

Crystal data top

C₉H₈ClN₃O₂	F(000) = 464
M_r = 225.63	D_x = 1.592 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 11.2363 (7) Å	Cell parameters from 8820 reflections
b = 7.4063 (5) Å	θ = 3.3–29.1°
c = 12.1247 (8) Å	µ = 0.39 mm⁻¹
β = 111.051 (1)°	T = 100 K
V = 941.67 (11) Å³	Column, colourless
Z = 4	0.34 × 0.19 × 0.16 mm

Data collection top

Bruker SMART APEX CCD diffractometer	2543 independent reflections
Radiation source: fine-focus sealed tube	2183 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.028
Detector resolution: 8.3333 pixels mm^-1	θ_max = 29.2°, θ_min = 1.9°
φ and ω scans	h = −15→15
Absorption correction: multi-scan (SADABS; Bruker, 2016)	k = −10→10
T_min = 0.85, T_max = 0.94	l = −16→16
17539 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)] = 0.036	Hydrogen site location: difference Fourier map
wR(F²) = 0.103	All H-atom parameters refined
S = 1.13	w = 1/[σ²(F_o²) + (0.0702P)² + 0.0386P] where P = (F_o² + 2F_c²)/3
2543 reflections	(Δ/σ)_max < 0.001
168 parameters	Δρ_max = 0.68 e Å⁻³
0 restraints	Δρ_min = −0.20 e Å⁻³

Special details top

Experimental. The diffraction data were obtained from 3 sets of 400 frames, each of width 0.5° in ω, collected at φ = 0.00, 90.00 and 180.00° and 2 sets of 800 frames, each of width 0.45° in φ, collected at ω = –30.00 and 210.00°. The scan time was 15 sec/frame.

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.

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 > 2sigma(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
Cl1	0.74446 (3)	0.21393 (4)	0.48713 (3)	0.02049 (12)
O1	0.24410 (9)	0.46570 (14)	0.76126 (8)	0.0248 (2)
O2	0.13166 (8)	0.34576 (15)	0.59292 (8)	0.0278 (2)
N1	0.68668 (9)	0.49160 (14)	0.73487 (9)	0.0163 (2)
N2	0.75445 (9)	0.42256 (14)	0.67233 (9)	0.0164 (2)
N3	0.23394 (9)	0.39466 (14)	0.66663 (9)	0.0183 (2)
C1	0.56070 (11)	0.31391 (15)	0.58095 (10)	0.0139 (2)
C2	0.44490 (11)	0.23172 (16)	0.50971 (10)	0.0156 (2)
H2	0.4420 (13)	0.161 (2)	0.4443 (13)	0.016 (3)*
C3	0.33951 (11)	0.26044 (16)	0.53900 (11)	0.0162 (2)
H3	0.2548 (13)	0.211 (2)	0.4925 (12)	0.017 (4)*
C4	0.34978 (10)	0.36817 (16)	0.63905 (10)	0.0148 (2)
C5	0.45943 (11)	0.45167 (16)	0.70990 (10)	0.0144 (2)
H5	0.4606 (15)	0.530 (2)	0.7734 (14)	0.024 (4)*
C6	0.56820 (11)	0.42364 (15)	0.67937 (10)	0.0138 (2)
C7	0.68450 (11)	0.31794 (16)	0.58110 (10)	0.0155 (2)
C8	0.89008 (11)	0.4693 (2)	0.70924 (12)	0.0224 (3)
H8A	0.8929 (17)	0.595 (3)	0.7003 (16)	0.040 (5)*
H8B	0.9192 (16)	0.408 (2)	0.6562 (15)	0.032 (4)*
C9	0.96158 (12)	0.4151 (2)	0.83598 (12)	0.0252 (3)
H9A	1.0501 (16)	0.443 (2)	0.8538 (14)	0.028 (4)*
H9B	0.9544 (18)	0.279 (3)	0.8467 (18)	0.042 (5)*
H9C	0.9260 (16)	0.479 (2)	0.8872 (15)	0.030 (4)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.02732 (18)	0.01884 (19)	0.02015 (18)	0.00613 (10)	0.01440 (13)	0.00185 (11)
O1	0.0233 (5)	0.0309 (5)	0.0238 (5)	−0.0004 (4)	0.0127 (4)	−0.0047 (4)
O2	0.0150 (4)	0.0373 (6)	0.0277 (5)	−0.0025 (4)	0.0037 (4)	−0.0031 (4)
N1	0.0164 (4)	0.0199 (5)	0.0135 (5)	−0.0013 (4)	0.0064 (4)	−0.0008 (4)
N2	0.0157 (5)	0.0203 (5)	0.0141 (5)	0.0002 (4)	0.0064 (4)	0.0018 (4)
N3	0.0165 (5)	0.0183 (5)	0.0204 (5)	0.0007 (4)	0.0069 (4)	0.0025 (4)
C1	0.0185 (5)	0.0115 (5)	0.0118 (5)	0.0020 (4)	0.0054 (4)	0.0024 (4)
C2	0.0206 (5)	0.0129 (6)	0.0113 (5)	0.0010 (4)	0.0033 (4)	0.0001 (4)
C3	0.0178 (5)	0.0140 (5)	0.0137 (5)	−0.0014 (4)	0.0020 (4)	0.0010 (4)
C4	0.0151 (5)	0.0146 (6)	0.0149 (5)	0.0009 (4)	0.0056 (4)	0.0025 (4)
C5	0.0172 (5)	0.0139 (6)	0.0123 (5)	0.0007 (4)	0.0055 (4)	0.0011 (4)
C6	0.0166 (5)	0.0127 (5)	0.0114 (5)	−0.0005 (4)	0.0043 (4)	0.0015 (4)
C7	0.0195 (5)	0.0151 (6)	0.0126 (5)	0.0027 (4)	0.0067 (4)	0.0028 (4)
C8	0.0159 (5)	0.0301 (8)	0.0228 (6)	−0.0025 (5)	0.0086 (5)	0.0032 (5)
C9	0.0160 (6)	0.0361 (8)	0.0221 (7)	0.0018 (5)	0.0052 (5)	−0.0014 (6)

Geometric parameters (Å, º) top

Cl1—C7	1.7021 (12)	C2—H2	0.942 (15)
O1—N3	1.2297 (13)	C3—C4	1.4216 (17)
O2—N3	1.2299 (13)	C3—H3	0.986 (14)
N1—N2	1.3532 (14)	C4—C5	1.3704 (16)
N1—C6	1.3545 (14)	C5—C6	1.4138 (16)
N2—C7	1.3480 (15)	C5—H5	0.961 (16)
N2—C8	1.4672 (15)	C8—C9	1.5102 (19)
N3—C4	1.4687 (15)	C8—H8A	0.94 (2)
C1—C7	1.3907 (16)	C8—H8B	0.938 (18)
C1—C2	1.4151 (16)	C9—H9A	0.961 (17)
C1—C6	1.4210 (15)	C9—H9B	1.03 (2)
C2—C3	1.3696 (17)	C9—H9C	0.972 (17)

N2—N1—C6	103.39 (9)	C4—C5—H5	121.7 (10)
C7—N2—N1	113.42 (9)	C6—C5—H5	122.3 (10)
C7—N2—C8	128.42 (10)	N1—C6—C5	127.09 (11)
N1—N2—C8	118.16 (10)	N1—C6—C1	112.40 (10)
O1—N3—O2	123.60 (10)	C5—C6—C1	120.51 (10)
O1—N3—C4	118.47 (10)	N2—C7—C1	107.55 (10)
O2—N3—C4	117.93 (10)	N2—C7—Cl1	123.72 (9)
C7—C1—C2	135.24 (11)	C1—C7—Cl1	128.73 (10)
C7—C1—C6	103.24 (10)	N2—C8—C9	111.24 (10)
C2—C1—C6	121.52 (10)	N2—C8—H8A	105.9 (11)
C3—C2—C1	117.78 (11)	C9—C8—H8A	110.6 (11)
C3—C2—H2	122.2 (9)	N2—C8—H8B	104.9 (10)
C1—C2—H2	120.0 (9)	C9—C8—H8B	112.3 (10)
C2—C3—C4	119.72 (11)	H8A—C8—H8B	111.6 (16)
C2—C3—H3	122.7 (8)	C8—C9—H9A	107.5 (10)
C4—C3—H3	117.5 (8)	C8—C9—H9B	110.7 (11)
C5—C4—C3	124.56 (11)	H9A—C9—H9B	107.7 (14)
C5—C4—N3	117.89 (10)	C8—C9—H9C	109.4 (10)
C3—C4—N3	117.54 (10)	H9A—C9—H9C	112.6 (14)
C4—C5—C6	115.90 (11)	H9B—C9—H9C	109.0 (15)

C6—N1—N2—C7	0.66 (13)	C4—C5—C6—C1	−0.31 (16)
C6—N1—N2—C8	−179.85 (10)	C7—C1—C6—N1	0.68 (13)
C7—C1—C2—C3	179.92 (13)	C2—C1—C6—N1	−179.12 (10)
C6—C1—C2—C3	−0.35 (17)	C7—C1—C6—C5	−179.29 (10)
C1—C2—C3—C4	−0.73 (17)	C2—C1—C6—C5	0.91 (17)
C2—C3—C4—C5	1.40 (19)	N1—N2—C7—C1	−0.26 (14)
C2—C3—C4—N3	−179.97 (10)	C8—N2—C7—C1	−179.68 (12)
O1—N3—C4—C5	−11.20 (16)	N1—N2—C7—Cl1	179.83 (8)
O2—N3—C4—C5	168.15 (11)	C8—N2—C7—Cl1	0.40 (18)
O1—N3—C4—C3	170.07 (11)	C2—C1—C7—N2	179.52 (13)
O2—N3—C4—C3	−10.58 (16)	C6—C1—C7—N2	−0.25 (12)
C3—C4—C5—C6	−0.82 (18)	C2—C1—C7—Cl1	−0.6 (2)
N3—C4—C5—C6	−179.46 (10)	C6—C1—C7—Cl1	179.66 (9)
N2—N1—C6—C5	179.15 (11)	C7—N2—C8—C9	−122.97 (13)
N2—N1—C6—C1	−0.82 (13)	N1—N2—C8—C9	57.62 (16)
C4—C5—C6—N1	179.72 (11)

Hydrogen-bond geometry (Å, º) top

Cg2 is the centroid of the C1–C6 ring.

D—H···A	D—H	H···A	D···A	D—H···A
C8—H8B···Cl1	0.938 (18)	2.689 (17)	3.2158 (15)	116.3 (12)
C5—H5···Cg2ⁱ	0.961 (16)	2.698 (15)	3.5418 (13)	147 (1)

Symmetry code: (i) −x+1, y+1/2, −z+3/2.

Acknowledgements

JTM thanks Tulane University for support of the Tulane Crystallography Laboratory.

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
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ISSN: 2414-3146

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https://doi.org/10.1107/S2414314617006526

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

3-Chloro-2-ethyl-6-nitro-2H-indazole

Structure description

Synthesis and crystallization

Refinement

Structural data

Acknowledgements

References

organic compounds