1-Allyl-5-(2,5-dimethyl-1H-pyrrol-1-yl)-1H-indazole

El Ghozlani, M.; Rais, A.; Rakib, E.M.; Mojahidi, S.; Saadi, M.; El Ammari, L.

doi:10.1107/S2414314616011214

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 1| Part 7| July 2016| x161121

https://doi.org/10.1107/S2414314616011214

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access

1-Allyl-5-(2,5-dimethyl-1H-pyrrol-1-yl)-1H-indazole

Mohamed El Ghozlani,^a ^* Adiba Rais,^a El Mostapha Rakib,^a Souad Mojahidi,^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: m_elghozlani@yahoo.fr

Edited by H. Stoeckli-Evans, University of Neuchâtel, Switzerland (Received 29 June 2016; accepted 10 July 2016; online 15 July 2016)

In the title compound, C₁₆H₁₇N₃, the indazole ring system makes a dihedral angle of 64.73 (12)° with the pyrrole ring. The atoms of the allyl group are disordered over two sets of sites, with a refined occupancy ratio of 0.70 (3):0.30 (3). The mean plane through the major component of the allyl group is nearly perpendicular to the indazole ring, as indicated by the N—C—C=C torsion angle of −114 (1)°. In the crystal, molecules are linked by C—H⋯π interactions, forming undulating sheets parallel to the ab plane.

Keywords: crystal structure; 2,5-dimethylpyrrole; indazole; hydrogen bonds.

CCDC reference: 1491842

Structure description

Indazole is recognized to be a highly effective pharmacophore in medicinal chemistry as well as being the core of important nitrogen-containing heterocycles that show a broad range of biological activities (Cerecetto et al., 2005 ; Gaikwad et al., 2015 ; Jennings & Tennant, 2007 ). Previously, our group has researched indazole derivatives with potential anticancer activity. Some of them exert pharmacologically interesting antiproliferative/apoptotic activity against human and murine cell lines (Bouissane et al., 2006 ; Abbassi et al., 2012 , 2014 ).

The molecule of the title compound is built up from an indazole ring system (C1–C7/N2/N3) linked to an allyl group and to a 2,5-dimethyl-pyrrol-1-yl moiety, as shown in Fig. 1. The mean plane of the major component of the allyl group, which is disordered over two positions, is almost perpendicular to the indazole ring as indicated by the N3—C14—C15A=C16A torsion angle of −114 (1)°. The pyrrole ring makes a dihedral angle of 64.73 (12)° with the indazole ring system.

Figure 1
A view of the molecular structure of the title compound, showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level. The atoms of the allyl group (C15A/16A and C15B/16B) are disordered over two sets of sites.

In the crystal, molecules are linked by C14—H14B⋯π and C16A—H16B⋯π interactions (Table 1), forming undulating sheets parallel to (001), as shown in Fig. 2.

Table 1
Hydrogen-bond geometry (Å, °)

Cg1 and Cg3 are the centroids of the N1/C2–C5 and C7–C13 rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C14—H14B⋯Cg1ⁱ	0.97	2.92	3.860 (3)	162
C16A—H16B⋯Cg3ⁱⁱ	0.93	2.98	3.783 (14)	145
Symmetry codes: (i) $[-x+1, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (ii) x+1, y, z.

Figure 2
A view along the a axis of the crystal packing of the title compound, with the C—H⋯π interactions represented by dashed lines (see Table 1

). For clarity, only the H atoms involved in these interactions (grey balls), and the atoms of the major component of the disordered allyl group, have been included.

Synthesis and crystallization

1-Allyl-5-nitroindazole (1.0 mmol) was added to a mixture of anhydrous SnCl₂ powder (460 mg, 4.0 mmol), and acetic acid (0.572 ml, 10 mmol) in tetrahydrofuran (10 ml), followed by the addition of 2,5-hexadione (1.0 mmol) in THF (15 ml). The reaction mixture was stirred at 353 K for 4 h. After the reaction was completed, the mixture was diluted with ethyl acetate (30 ml), poured into 10% NaHCO₃ (30 ml), and then extracted with ethyl acetate (3 × 50 ml). The combined organic extracts were dried over MgSO₄, filtered and concentrated. The residue was purified by column chromatography on silica gel using ethyl acetate/hexane (3:7) to afford the title compound indazole in good yield. The title compound was recrystallized from ethyl ether at room temperature giving colourless crystals (m.p. 360 K, yield 68%).

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. The atoms of the allyl group are disordered over two sets of sites, with a refined occupancy ratio of 0.70 (3):0.30 (3).

Table 2
Experimental details

Crystal data
Chemical formula	C₁₆H₁₇N₃
M_r	251.32
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	296
a, b, c (Å)	7.5140 (2), 10.3737 (3), 17.8484 (5)
V (Å³)	1391.25 (7)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.07
Crystal size (mm)	0.37 × 0.32 × 0.27

Data collection
Diffractometer	Bruker X8 APEX
Absorption correction	Multi-scan (SADABS; Bruker, 2009 )
T_min, T_max	0.626, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections	23639, 3598, 2453
R_int	0.050
(sin θ/λ)_max (Å⁻¹)	0.676

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.045, 0.113, 1.03
No. of reflections	3598
No. of parameters	193
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.12, −0.16
Computer programs: APEX2 and SAINT (Bruker, 2009), SHELXT2014 (Sheldrick, 2015a ), SHELXL2014 (Sheldrick, 2015b ), ORTEPIII (Burnett & Johnson, 1996 ), ORTEP-3 for Windows (Farrugia, 2012 ), Mercury (Macrae et al., 2008 ) and publCIF (Westrip, 2010 ).

Structural data

CCDC reference: 1491842

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314616011214/su4060sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314616011214/su4060Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314616011214/su4060Isup3.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: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: ORTEPIII (Burnett & Johnson, 1996) and ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: Mercury (Macrae et al., 2008) and publCIF (Westrip, 2010).

1-Allyl-5-(2,5-dimethyl-1H-pyrrol-1-yl)-1H-indazole top

Crystal data top

C₁₆H₁₇N₃	D_x = 1.200 Mg m⁻³
M_r = 251.32	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 3598 reflections
a = 7.5140 (2) Å	θ = 2.3–28.7°
b = 10.3737 (3) Å	µ = 0.07 mm⁻¹
c = 17.8484 (5) Å	T = 296 K
V = 1391.25 (7) Å³	Block, colourless
Z = 4	0.37 × 0.32 × 0.27 mm
F(000) = 536

Data collection top

Bruker X8 APEX diffractometer	3598 independent reflections
Radiation source: fine-focus sealed tube	2453 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.050
φ and ω scans	θ_max = 28.7°, θ_min = 2.3°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −10→10
T_min = 0.626, T_max = 0.746	k = −13→14
23639 measured reflections	l = −22→24

Refinement top

Refinement on F²	0 restraints
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.045	H-atom parameters constrained
wR(F²) = 0.113	w = 1/[σ²(F_o²) + (0.0487P)² + 0.1215P] where P = (F_o² + 2F_c²)/3
S = 1.03	(Δ/σ)_max < 0.001
3598 reflections	Δρ_max = 0.12 e Å⁻³
193 parameters	Δρ_min = −0.16 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	Occ. (<1)
C1	0.0292 (4)	0.5717 (3)	0.39588 (19)	0.0704 (8)
H1A	−0.0924	0.6002	0.3952	0.106*
H1B	0.0483	0.5173	0.4386	0.106*
H1C	0.0542	0.5242	0.3509	0.106*
C2	0.1492 (3)	0.6855 (2)	0.40034 (14)	0.0526 (6)
C3	0.1113 (4)	0.8125 (3)	0.41117 (16)	0.0642 (7)
H3	−0.0015	0.8476	0.4177	0.077*
C4	0.2731 (4)	0.8816 (3)	0.41073 (16)	0.0637 (7)
H4	0.2849	0.9701	0.4173	0.076*
C5	0.4079 (3)	0.7978 (2)	0.39917 (14)	0.0508 (6)
C6	0.6036 (4)	0.8194 (3)	0.39599 (18)	0.0669 (8)
H6A	0.6458	0.8019	0.3463	0.100*
H6B	0.6618	0.7629	0.4309	0.100*
H6C	0.6294	0.9073	0.4088	0.100*
C7	0.4314 (3)	0.5599 (2)	0.38047 (12)	0.0425 (5)
C8	0.4341 (3)	0.4660 (2)	0.43402 (12)	0.0450 (5)
H8	0.3724	0.4760	0.4788	0.054*
C9	0.5322 (3)	0.3540 (2)	0.41963 (12)	0.0462 (5)
C10	0.5682 (5)	0.2378 (3)	0.45860 (15)	0.0653 (8)
H10	0.5227	0.2180	0.5057	0.078*
C11	0.6264 (3)	0.3416 (2)	0.35235 (12)	0.0438 (5)
C12	0.6233 (3)	0.4369 (2)	0.29737 (13)	0.0503 (6)
H12	0.6855	0.4278	0.2526	0.060*
C13	0.5245 (3)	0.5446 (2)	0.31236 (12)	0.0487 (6)
H13	0.5184	0.6096	0.2766	0.058*
C14	0.8354 (4)	0.1698 (3)	0.30186 (16)	0.0643 (7)
H14A	0.8083	0.0794	0.2938	0.077*
H14B	0.8243	0.2139	0.2542	0.077*
C15A	1.0165 (13)	0.1818 (11)	0.3286 (4)	0.070 (3)	0.70 (3)
H15A	1.0529	0.1368	0.3710	0.085*	0.70 (3)
C16A	1.1372 (15)	0.2616 (18)	0.2904 (7)	0.105 (4)	0.70 (3)
H16A	1.1006	0.3065	0.2480	0.126*	0.70 (3)
H16B	1.2536	0.2695	0.3074	0.126*	0.70 (3)
C15B	1.030 (6)	0.243 (5)	0.309 (3)	0.138 (19)	0.30 (3)
H15B	1.0336	0.3328	0.3071	0.166*	0.30 (3)
C16B	1.132 (8)	0.199 (3)	0.316 (2)	0.151 (17)	0.30 (3)
H16C	1.1299	0.1099	0.3183	0.181*	0.30 (3)
H16D	1.2390	0.2436	0.3199	0.181*	0.30 (3)
N1	0.3325 (3)	0.67630 (18)	0.39266 (10)	0.0462 (5)
N2	0.6734 (4)	0.1615 (2)	0.42016 (13)	0.0692 (7)
N3	0.7080 (3)	0.2236 (2)	0.35444 (12)	0.0563 (6)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0457 (16)	0.0734 (19)	0.092 (2)	−0.0031 (14)	0.0043 (15)	−0.0055 (16)
C2	0.0426 (13)	0.0607 (16)	0.0546 (14)	0.0065 (12)	0.0006 (11)	−0.0010 (12)
C3	0.0513 (16)	0.0661 (18)	0.0752 (17)	0.0171 (14)	−0.0004 (14)	−0.0065 (14)
C4	0.0691 (19)	0.0468 (14)	0.0752 (17)	0.0099 (14)	−0.0047 (16)	−0.0010 (12)
C5	0.0530 (15)	0.0449 (13)	0.0546 (14)	0.0015 (11)	−0.0004 (12)	0.0056 (11)
C6	0.0565 (16)	0.0588 (17)	0.0855 (19)	−0.0083 (14)	0.0088 (14)	0.0007 (15)
C7	0.0370 (12)	0.0438 (12)	0.0467 (12)	0.0006 (10)	0.0001 (10)	0.0013 (10)
C8	0.0476 (13)	0.0479 (13)	0.0396 (11)	−0.0006 (11)	0.0035 (10)	0.0000 (10)
C9	0.0496 (14)	0.0454 (13)	0.0437 (11)	0.0016 (11)	−0.0016 (10)	0.0002 (10)
C10	0.092 (2)	0.0473 (15)	0.0570 (14)	0.0094 (15)	0.0060 (15)	0.0055 (12)
C11	0.0381 (12)	0.0457 (13)	0.0475 (12)	0.0000 (11)	−0.0049 (9)	−0.0054 (10)
C12	0.0460 (14)	0.0629 (16)	0.0419 (12)	0.0034 (12)	0.0054 (10)	−0.0006 (11)
C13	0.0463 (14)	0.0561 (14)	0.0436 (11)	0.0024 (12)	0.0024 (10)	0.0095 (11)
C14	0.0605 (17)	0.0608 (16)	0.0715 (17)	0.0099 (14)	−0.0018 (14)	−0.0227 (14)
C15A	0.049 (4)	0.096 (6)	0.067 (3)	0.026 (4)	−0.006 (2)	−0.025 (3)
C16A	0.054 (5)	0.147 (11)	0.114 (6)	−0.022 (5)	0.020 (4)	−0.063 (6)
C15B	0.11 (3)	0.10 (2)	0.20 (4)	0.04 (2)	0.00 (3)	−0.07 (3)
C16B	0.20 (5)	0.078 (15)	0.17 (2)	−0.007 (19)	0.07 (3)	−0.008 (15)
N1	0.0425 (11)	0.0444 (11)	0.0516 (10)	0.0053 (9)	0.0010 (9)	0.0027 (9)
N2	0.0916 (18)	0.0497 (12)	0.0662 (13)	0.0146 (13)	−0.0013 (13)	0.0042 (11)
N3	0.0586 (14)	0.0523 (12)	0.0582 (13)	0.0122 (11)	−0.0016 (10)	−0.0087 (10)

Geometric parameters (Å, º) top

C1—C2	1.488 (4)	C9—C10	1.418 (3)
C2—C3	1.361 (4)	C10—N2	1.312 (4)
C2—N1	1.387 (3)	C11—N3	1.370 (3)
C3—C4	1.411 (4)	C11—C12	1.393 (3)
C4—C5	1.350 (4)	C12—C13	1.368 (3)
C5—N1	1.387 (3)	C14—C15A	1.448 (9)
C5—C6	1.489 (4)	C14—N3	1.452 (3)
C7—C8	1.366 (3)	C14—C15B	1.65 (5)
C7—C13	1.412 (3)	C15A—C16A	1.40 (2)
C7—N1	1.434 (3)	C15B—C16B	0.90 (7)
C8—C9	1.399 (3)	N2—N3	1.364 (3)
C9—C11	1.400 (3)

C3—C2—N1	106.7 (2)	N3—C11—C12	131.4 (2)
C3—C2—C1	130.4 (2)	N3—C11—C9	106.6 (2)
N1—C2—C1	122.8 (2)	C12—C11—C9	122.0 (2)
C2—C3—C4	108.1 (2)	C13—C12—C11	116.8 (2)
C5—C4—C3	108.7 (2)	C12—C13—C7	122.0 (2)
C4—C5—N1	106.9 (2)	C15A—C14—N3	111.9 (4)
C4—C5—C6	130.5 (2)	N3—C14—C15B	110.6 (12)
N1—C5—C6	122.5 (2)	C16A—C15A—C14	119.8 (10)
C8—C7—C13	121.0 (2)	C16B—C15B—C14	122 (7)
C8—C7—N1	120.16 (19)	C5—N1—C2	109.6 (2)
C13—C7—N1	118.8 (2)	C5—N1—C7	124.47 (19)
C7—C8—C9	118.2 (2)	C2—N1—C7	126.0 (2)
C8—C9—C11	120.0 (2)	C10—N2—N3	106.2 (2)
C8—C9—C10	135.7 (2)	N2—N3—C11	111.1 (2)
C11—C9—C10	104.2 (2)	N2—N3—C14	120.0 (2)
N2—C10—C9	111.8 (2)	C11—N3—C14	128.4 (2)

Hydrogen-bond geometry (Å, º) top

Cg1 and Cg3 are the centroids of the N1/C2–C5 and C7–C13 rings, respectively.

D—H···A	D—H	H···A	D···A	D—H···A
C14—H14B···Cg1ⁱ	0.97	2.92	3.860 (3)	162
C16A—H16B···Cg3ⁱⁱ	0.93	2.98	3.783 (14)	145

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

References

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

1-Allyl-5-(2,5-di­methyl-1H-pyrrol-1-yl)-1H-indazole

Structure description

Synthesis and crystallization

Refinement

Structural data

Acknowledgements

References

organic compounds

1-Allyl-5-(2,5-dimethyl-1H-pyrrol-1-yl)-1H-indazole