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

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ISSN: 2414-3146

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

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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.

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

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[Patel, M., Rodgers, J. D., McHugh, R. J. Jr, Johnson, B. L., Cordova, B. C., Klabe, R. M., Bacheler, L. T., Erickson-Viitanen, S. & Ko, S. S. (1999). Bioorg. Med. Chem. Lett. 9, 3217-3220.]) and anti­arrhythmic, analgesic and anti­tumor activities (Mosti et al., 2000[Mosti, L., Menozzi, G., Fossa, P., Filippelli, W., Gessi, S., Rinaldi, B. & Falcone, G. (2000). Arzneim.-Forsch. Drug. Res. 50, 963-972.]) together with anti­hypertensive properties (Bouissane et al., 2006[Bouissane, L., El Kazzouli, S., Léonce, S., Pfeiffer, B., Rakib, M. E., Khouili, M. & Guillaumet, G. (2006). Bioorg. Med. Chem. 14, 1078-1088.]; Abbassi et al., 2012[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.]). As a continuation of our studies of indazole derivatives (Mohamed Abdelahi et al., 2017[Mohamed Abdelahi, M. M., El Bakri, Y., Benchidmi, M., Essassi, E. M. & Mague, J. T. (2017). IUCrData, 2, x170432.]), 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[link] and Fig. 1[link]). Head-to-tail offset ππ-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[link]) 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[link]). 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 DA 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]
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]
Figure 2
Packing projected onto [010] giving a side view of one sheet of mol­ecules. The ππ 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[link].

Table 2
Experimental details

Crystal data
Chemical formula C9H8ClN3O2
Mr 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)
V3) 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[Bruker (2016). APEX3, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.85, 0.94
No. of measured, independent and observed [I > 2σ(I)] reflections 17539, 2543, 2183
Rint 0.028
(sin θ/λ)max−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
Δρmax, Δρmin (e Å−3) 0.68, −0.20
Computer programs: APEX3 and SAINT (Bruker, 2016[Bruker (2016). APEX3, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXT (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2014 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), DIAMOND (Brandenburg & Putz, 2012[Brandenburg, K. & Putz, H. (2012). DIAMOND, Crystal Impact GbR, Bonn, Germany.]) and SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]).

Structural data


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
C9H8ClN3O2F(000) = 464
Mr = 225.63Dx = 1.592 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 11.2363 (7) ÅCell parameters from 8820 reflections
b = 7.4063 (5) Åθ = 3.3–29.1°
c = 12.1247 (8) ŵ = 0.39 mm1
β = 111.051 (1)°T = 100 K
V = 941.67 (11) Å3Column, colourless
Z = 40.34 × 0.19 × 0.16 mm
Data collection top
Bruker SMART APEX CCD
diffractometer
2543 independent reflections
Radiation source: fine-focus sealed tube2183 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.028
Detector resolution: 8.3333 pixels mm-1θmax = 29.2°, θmin = 1.9°
φ and ω scansh = 1515
Absorption correction: multi-scan
(SADABS; Bruker, 2016)
k = 1010
Tmin = 0.85, Tmax = 0.94l = 1616
17539 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.036Hydrogen site location: difference Fourier map
wR(F2) = 0.103All 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 parametersΔρmax = 0.68 e Å3
0 restraintsΔρmin = 0.20 e Å3
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
xyzUiso*/Ueq
Cl10.74446 (3)0.21393 (4)0.48713 (3)0.02049 (12)
O10.24410 (9)0.46570 (14)0.76126 (8)0.0248 (2)
O20.13166 (8)0.34576 (15)0.59292 (8)0.0278 (2)
N10.68668 (9)0.49160 (14)0.73487 (9)0.0163 (2)
N20.75445 (9)0.42256 (14)0.67233 (9)0.0164 (2)
N30.23394 (9)0.39466 (14)0.66663 (9)0.0183 (2)
C10.56070 (11)0.31391 (15)0.58095 (10)0.0139 (2)
C20.44490 (11)0.23172 (16)0.50971 (10)0.0156 (2)
H20.4420 (13)0.161 (2)0.4443 (13)0.016 (3)*
C30.33951 (11)0.26044 (16)0.53900 (11)0.0162 (2)
H30.2548 (13)0.211 (2)0.4925 (12)0.017 (4)*
C40.34978 (10)0.36817 (16)0.63905 (10)0.0148 (2)
C50.45943 (11)0.45167 (16)0.70990 (10)0.0144 (2)
H50.4606 (15)0.530 (2)0.7734 (14)0.024 (4)*
C60.56820 (11)0.42364 (15)0.67937 (10)0.0138 (2)
C70.68450 (11)0.31794 (16)0.58110 (10)0.0155 (2)
C80.89008 (11)0.4693 (2)0.70924 (12)0.0224 (3)
H8A0.8929 (17)0.595 (3)0.7003 (16)0.040 (5)*
H8B0.9192 (16)0.408 (2)0.6562 (15)0.032 (4)*
C90.96158 (12)0.4151 (2)0.83598 (12)0.0252 (3)
H9A1.0501 (16)0.443 (2)0.8538 (14)0.028 (4)*
H9B0.9544 (18)0.279 (3)0.8467 (18)0.042 (5)*
H9C0.9260 (16)0.479 (2)0.8872 (15)0.030 (4)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.02732 (18)0.01884 (19)0.02015 (18)0.00613 (10)0.01440 (13)0.00185 (11)
O10.0233 (5)0.0309 (5)0.0238 (5)0.0004 (4)0.0127 (4)0.0047 (4)
O20.0150 (4)0.0373 (6)0.0277 (5)0.0025 (4)0.0037 (4)0.0031 (4)
N10.0164 (4)0.0199 (5)0.0135 (5)0.0013 (4)0.0064 (4)0.0008 (4)
N20.0157 (5)0.0203 (5)0.0141 (5)0.0002 (4)0.0064 (4)0.0018 (4)
N30.0165 (5)0.0183 (5)0.0204 (5)0.0007 (4)0.0069 (4)0.0025 (4)
C10.0185 (5)0.0115 (5)0.0118 (5)0.0020 (4)0.0054 (4)0.0024 (4)
C20.0206 (5)0.0129 (6)0.0113 (5)0.0010 (4)0.0033 (4)0.0001 (4)
C30.0178 (5)0.0140 (5)0.0137 (5)0.0014 (4)0.0020 (4)0.0010 (4)
C40.0151 (5)0.0146 (6)0.0149 (5)0.0009 (4)0.0056 (4)0.0025 (4)
C50.0172 (5)0.0139 (6)0.0123 (5)0.0007 (4)0.0055 (4)0.0011 (4)
C60.0166 (5)0.0127 (5)0.0114 (5)0.0005 (4)0.0043 (4)0.0015 (4)
C70.0195 (5)0.0151 (6)0.0126 (5)0.0027 (4)0.0067 (4)0.0028 (4)
C80.0159 (5)0.0301 (8)0.0228 (6)0.0025 (5)0.0086 (5)0.0032 (5)
C90.0160 (6)0.0361 (8)0.0221 (7)0.0018 (5)0.0052 (5)0.0014 (6)
Geometric parameters (Å, º) top
Cl1—C71.7021 (12)C2—H20.942 (15)
O1—N31.2297 (13)C3—C41.4216 (17)
O2—N31.2299 (13)C3—H30.986 (14)
N1—N21.3532 (14)C4—C51.3704 (16)
N1—C61.3545 (14)C5—C61.4138 (16)
N2—C71.3480 (15)C5—H50.961 (16)
N2—C81.4672 (15)C8—C91.5102 (19)
N3—C41.4687 (15)C8—H8A0.94 (2)
C1—C71.3907 (16)C8—H8B0.938 (18)
C1—C21.4151 (16)C9—H9A0.961 (17)
C1—C61.4210 (15)C9—H9B1.03 (2)
C2—C31.3696 (17)C9—H9C0.972 (17)
N2—N1—C6103.39 (9)C4—C5—H5121.7 (10)
C7—N2—N1113.42 (9)C6—C5—H5122.3 (10)
C7—N2—C8128.42 (10)N1—C6—C5127.09 (11)
N1—N2—C8118.16 (10)N1—C6—C1112.40 (10)
O1—N3—O2123.60 (10)C5—C6—C1120.51 (10)
O1—N3—C4118.47 (10)N2—C7—C1107.55 (10)
O2—N3—C4117.93 (10)N2—C7—Cl1123.72 (9)
C7—C1—C2135.24 (11)C1—C7—Cl1128.73 (10)
C7—C1—C6103.24 (10)N2—C8—C9111.24 (10)
C2—C1—C6121.52 (10)N2—C8—H8A105.9 (11)
C3—C2—C1117.78 (11)C9—C8—H8A110.6 (11)
C3—C2—H2122.2 (9)N2—C8—H8B104.9 (10)
C1—C2—H2120.0 (9)C9—C8—H8B112.3 (10)
C2—C3—C4119.72 (11)H8A—C8—H8B111.6 (16)
C2—C3—H3122.7 (8)C8—C9—H9A107.5 (10)
C4—C3—H3117.5 (8)C8—C9—H9B110.7 (11)
C5—C4—C3124.56 (11)H9A—C9—H9B107.7 (14)
C5—C4—N3117.89 (10)C8—C9—H9C109.4 (10)
C3—C4—N3117.54 (10)H9A—C9—H9C112.6 (14)
C4—C5—C6115.90 (11)H9B—C9—H9C109.0 (15)
C6—N1—N2—C70.66 (13)C4—C5—C6—C10.31 (16)
C6—N1—N2—C8179.85 (10)C7—C1—C6—N10.68 (13)
C7—C1—C2—C3179.92 (13)C2—C1—C6—N1179.12 (10)
C6—C1—C2—C30.35 (17)C7—C1—C6—C5179.29 (10)
C1—C2—C3—C40.73 (17)C2—C1—C6—C50.91 (17)
C2—C3—C4—C51.40 (19)N1—N2—C7—C10.26 (14)
C2—C3—C4—N3179.97 (10)C8—N2—C7—C1179.68 (12)
O1—N3—C4—C511.20 (16)N1—N2—C7—Cl1179.83 (8)
O2—N3—C4—C5168.15 (11)C8—N2—C7—Cl10.40 (18)
O1—N3—C4—C3170.07 (11)C2—C1—C7—N2179.52 (13)
O2—N3—C4—C310.58 (16)C6—C1—C7—N20.25 (12)
C3—C4—C5—C60.82 (18)C2—C1—C7—Cl10.6 (2)
N3—C4—C5—C6179.46 (10)C6—C1—C7—Cl1179.66 (9)
N2—N1—C6—C5179.15 (11)C7—N2—C8—C9122.97 (13)
N2—N1—C6—C10.82 (13)N1—N2—C8—C957.62 (16)
C4—C5—C6—N1179.72 (11)
Hydrogen-bond geometry (Å, º) top
Cg2 is the centroid of the C1–C6 ring.
D—H···AD—HH···AD···AD—H···A
C8—H8B···Cl10.938 (18)2.689 (17)3.2158 (15)116.3 (12)
C5—H5···Cg2i0.961 (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

First citationAbbassi, 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
First citationBouissane, L., El Kazzouli, S., Léonce, S., Pfeiffer, B., Rakib, M. E., Khouili, M. & Guillaumet, G. (2006). Bioorg. Med. Chem. 14, 1078–1088.  Web of Science CrossRef PubMed CAS Google Scholar
First citationBrandenburg, K. & Putz, H. (2012). DIAMOND, Crystal Impact GbR, Bonn, Germany.  Google Scholar
First citationBruker (2016). APEX3, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationMohamed Abdelahi, M. M., El Bakri, Y., Benchidmi, M., Essassi, E. M. & Mague, J. T. (2017). IUCrData, 2, x170432.  Google Scholar
First citationMosti, L., Menozzi, G., Fossa, P., Filippelli, W., Gessi, S., Rinaldi, B. & Falcone, G. (2000). Arzneim.-Forsch. Drug. Res. 50, 963–972.  CAS Google Scholar
First citationPatel, M., Rodgers, J. D., McHugh, R. J. Jr, Johnson, B. L., Cordova, B. C., Klabe, R. M., Bacheler, L. T., Erickson-Viitanen, S. & Ko, S. S. (1999). Bioorg. Med. Chem. Lett. 9, 3217–3220.  Web of Science CrossRef PubMed CAS Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar

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