6-Amino-3-methyl-4-(3,4,5-tri­meth­oxy­phen­yl)-2,4-di­hydro­pyrano[2,3-c]pyrazole-5-carbo­nitrile

Naresh Sharma; Goutam Brahmachari; Bubun Banerjee; Rajni Kant; Vivek K Gupta

doi:10.1107/S1600536814015670

. 2014 Jul 23;70(Pt 8):o875–o876. doi: 10.1107/S1600536814015670

6-Amino-3-methyl-4-(3,4,5-trimethoxyphenyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile

Naresh Sharma ^a, Goutam Brahmachari ^b, Bubun Banerjee ^b, Rajni Kant ^a, Vivek K Gupta ^a,^*

PMCID: PMC4158517 PMID: 25249920

Abstract

In the title compound, C₁₇H₁₈N₄O₄, the dihedral angle between the benzene ring and 2,4-dihydropyrano[2,3-c]pyrazole ring system is 89.41 (7)°. The pyran moiety adopts a strongly flattened boat conformation. In the crystal, molecules are linked by N—H⋯N, N—H⋯O, C—H⋯N and C—H⋯O hydrogen bonds into an infinite two-dimensional network parallel to (110). There are π–π interactions between the pyrazole rings in neighbouring layers [centroid–centroid distance = 3.621 (1) Å].

Keywords: crystal structure

Related literature

For background to the biological activity of synthetic pyrano[2,3-c] pyrazole compounds, see: Zaki et al. (2006 ▶); Abdelrazek et al. (2007 ▶); Mohamed et al. (2010 ▶); Bhavanarushi et al. (2013 ▶). For the synthesis of the title compound, see: Brahmachari & Banerjee (2014 ▶). For a related structure, see: Low et al. (2004 ▶).

Experimental

Crystal data

C₁₇H₁₈N₄O₄
M _r = 342.35
Triclinic,
a = 7.6168 (6) Å
b = 9.9967 (5) Å
c = 11.7888 (6) Å
α = 105.283 (5)°
β = 99.416 (5)°
γ = 92.221 (5)°
V = 851.05 (9) Å³
Z = 2
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 293 K
0.30 × 0.20 × 0.20 mm

Data collection

Oxford Diffraction Xcalibur Sapphire3 diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2010 ▶) T _min = 0.805, T _max = 1.000
6228 measured reflections
3344 independent reflections
2201 reflections with I > 2σ(I)
R _int = 0.030

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.125
S = 1.00
3344 reflections
242 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Data collection: CrysAlis PRO (Oxford Diffraction, 2010 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, New_Global_Publ_Block. DOI: 10.1107/S1600536814015670/gk2612sup1.cif

e-70-0o875-sup1.cif^{(25.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814015670/gk2612Isup2.hkl

e-70-0o875-Isup2.hkl^{(160.7KB, hkl)}

Click here for additional data file.^{(6.8KB, cml)}

Supporting information file. DOI: 10.1107/S1600536814015670/gk2612Isup3.cml

CCDC reference: 973484

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

Cg3 is the centroid of the phenyl ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H30⋯O20ⁱ	0.94 (2)	1.96 (2)	2.882 (2)	165 (2)
N11—H40⋯N1ⁱⁱ	0.95 (2)	2.11 (2)	3.030 (3)	163 (2)
N11—H50⋯N10ⁱⁱⁱ	0.91 (2)	2.25 (2)	3.156 (3)	172 (2)
C8—H8C⋯O18ⁱ	0.96	2.52	3.305 (3)	139
C19—H19B⋯N1^iv	0.96	2.52	3.455 (4)	165
C21—H21A⋯Cg3^v	0.96	2.85	3.55	130

Open in a new tab

Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) .

Acknowledgments

RK acknowledges the Department of Science & Technology for the single-crystal X-ray diffractometer sanctioned as a National Facility under project No. SR/S2/CMP-47/2003. GB is thankful to the CSIR, New Delhi, for financial support [grant No. 02 (110)/12/EMR-II]. BB is grateful to the UGC, New Delhi for the award of a Senior Research Fellowship.

supplementary crystallographic information

S1. Comment

Pyrano[2,3-c]pyrazole scaffolds represent a "privileged" structural motif well distributed in bioactive natural products and pharmaceutically potent synthetic heterocycles possessing a wide range of activities (Abdelrazek et al., 2007; Zaki et al., 2006; Mohamed et al., 2010; Bhavanarushi et al., 2013). Hence, investigation of the structural features of biologically relevant pyrano[2,3-c]pyrazole derivatives is of both scientific and practical interest. In continuation of our efforts to develop useful synthetic protocols for biologically significant molecules, we herein report an efficient and environmentally benign synthesis and the crystal structure of the title compound. In this communication we wish to report the crystal structure of 6-amino-3-methyl-4-(3,4,5-trimethoxyphenyl)-2, 4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (1) synthesized via one-pot multicomponent reaction (MCR) at room temperature using commercially available urea as inexpensive and environmentally benign organo-catalyst. The structure of the title compound 1 was elucidated by spectral methods and X-ray diffraction studies. The bond distances in the title compound are comparable to the closely related structure (Low et al., 2004). In the title compound, C₁₇H₁₈N₄O₄, the dihedral angle between the benzene ring (C12/C13/C14/C15/C16/C17) and the pyrazole ring is 87.05 (7)° and between pyrano and pyrazole rings is 4.69 (8)°. The benzene ring and the pyrazole ring are nearly planar with a maximum deviation of 0.0018 Å for the phenyl C3 atom and 0.0227 Å for the pyrazole C15 atom. The pyran moiety adopts a strongly flattened boat conformation with one mirror plane passing through the atoms C4 and O7 and the other bisecting the bonds C3A—C7A and C5—C6. In the crystal, molecules are linked by N—H···N hydrogen bonds into infinite two-dimensional network parallel to (110) . There are π - π interactions between the pyrazole rings in neighbouring networks [centroid–centroid seperation = 3.621 (1) Å, interplanar spacing = 3.333 Å, centriod shift = 1.242 Å, symmetry code: 1 - x,1 - y,1 - z].

S2. Experimental

The synthesis of the title compound was carried out via one-pot multi-component reaction in aqueous ethanol using low-cost and environmentally benign urea as catalyst at room temperature. An oven-dried screw cap test tube was charged with a magnetic stir bar, ethyl acetoacetate (0.130 g, 1.0 mmol) and hydrazine hydrate (0.050 g, 1 mmol). The reaction mixture was then stirred at room temperature for about 10 min and 3,4,5-trimethoxybenzaldehyde (0.196 g, 1 mmol), malononitrile (0.066 g, 1.1 mmol), urea (0.007 g, 10 mol % as organo-catalyst) and EtOH:H2O (1:1 v/v; 4 ml) were added in a sequential manner (Brahmachari & Banerjee, 2014). The reaction mixture was then stirred vigorously at room temperature and the stirring was continued for 16 h. The progress of the reaction was monitored by TLC. On completion of the reaction, a solid was precipitated out, filtered off and repeatedly washed with aqueous ethanol to obtain a crude product which was purified by recrystallization from ethanol without carrying out column chromatography. The structure of the title compound was confirmed by analytical as well as spectral studies, including ¹H NMR, ¹³C NMR, and TOF-MS. Single crystal was obtained from DMSO. For crystallization 50 mg of compound was dissolved in 5 ml DMSO and left for several days at ambient temperature.

6-Amino-3-methyl-4-(3,4,5-trimethoxyphenyl)-2,4-dihydropyrano[2,3-c] pyrazole-5-carbonitrile (1). White solid. Yield 89%. Mp: 491–493 K. ¹H NMR (400 MHz, DMSO-d₆) δ /p.p.m.: 12.11(1H, s, NH), 6.87 (2H, s, NH₂), 6.47 (2H, s, aromatic H), 4.59 (1H, s, CH), 3.72 (6H, s, 2 \ OCH₃), 3.64 (3H, s, OCH₃), 1.87 (3H, s, CH₃). ¹³C NMR (100 MHz, DMSO-d₆) δ /p.p.m.: 161.39, 155.11, 153.20 (2 C), 140.49, 136.55, 136.20, 121.29, 104.98 (2 C), 97.74, 60.38, 57.33, 56.22 (2 C), 36.87, 10.34. TOF-MS: 365.1230 [M+Na]+. Elemental analysis: Calcd. (%) for C₁₇H₁₈N₄O₄: C, 59.64; H, 5.30; N, 16.37; found: C, 59.62; H, 5.28; N, 16.39.