organic compounds
3-Chloro-2-ethyl-6-nitro-2H-indazole
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
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.
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 .
details are summarized in Table 2Structural data
CCDC reference: 1547138
https://doi.org/10.1107/S2414314617006526/sj4109sup1.cif
contains datablocks global, I. DOI: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
Data collection: APEX3 (Bruker, 2016); cell
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).C9H8ClN3O2 | F(000) = 464 |
Mr = 225.63 | Dx = 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 |
Bruker SMART APEX CCD diffractometer | 2543 independent reflections |
Radiation source: fine-focus sealed tube | 2183 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.028 |
Detector resolution: 8.3333 pixels mm-1 | θmax = 29.2°, θmin = 1.9° |
φ and ω scans | h = −15→15 |
Absorption correction: multi-scan (SADABS; Bruker, 2016) | k = −10→10 |
Tmin = 0.85, Tmax = 0.94 | l = −16→16 |
17539 measured reflections |
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(Fo2) + (0.0702P)2 + 0.0386P] where P = (Fo2 + 2Fc2)/3 |
2543 reflections | (Δ/σ)max < 0.001 |
168 parameters | Δρmax = 0.68 e Å−3 |
0 restraints | Δρmin = −0.20 e Å−3 |
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. |
x | y | z | Uiso*/Ueq | ||
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)* |
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) |
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) |
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
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