Ethyl 6-amino-5-cyano-4-phenyl-2,4-di­hydro­pyrano[2,3-c]pyrazole-3-carboxyl­ate dimethyl sulfoxide monosolvate

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

doi:10.1107/S1600536814013270

. 2014 Jun 18;70(Pt 7):o795–o796. doi: 10.1107/S1600536814013270

Ethyl 6-amino-5-cyano-4-phenyl-2,4-dihydropyrano[2,3-c]pyrazole-3-carboxylate dimethyl sulfoxide monosolvate

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

PMCID: PMC4120557 PMID: 25161577

Abstract

In the asymmetric unit of the title compound, C₁₆H₁₄N₄O₃·C₂H₆OS, there are two independent main molecules (A and B) and two dimethyl sulfoxide solvent molecules. In molecule A, the pyran ring is in a flattened sofa conformation, with the sp ³-hydridized C atom forming the flap. In molecule B, the pyran ring is in a flattened boat conformation, with the sp ³-hydridized C atom and the O atom deviating by 0.073 (3) and 0.055 (3) Å, respectively, from the plane of the other four atoms. The mean planes the pyrazole and phenyl rings form dihedral angles of 84.4 (2) and 84.9 (2)°, respectively, for molecules A and B. In the crystal, N—H⋯O and N—H⋯N hydrogen bonds link the components of the structure into chains along [010]. In both solvent molecules, the S atoms are disordered over two sites, with occupancy ratios of 0.679 (4):0.321 (4) and 0.546 (6):0.454 (6).

Related literature

For background to the biological activity of synthetic pyrano[2,3-c] pyrazole compounds, see: Nasr et al. (2002 ▶); Ismail et al. (2003 ▶); Foloppe et al. (2006 ▶); Mohamed et al. (2010 ▶); Zonouz et al. (2012 ▶); Kuo et al. (1984 ▶); Zaki et al. (2006 ▶); Ahluwalia et al. (1997 ▶); Bhavanarushi et al. (2013 ▶). For the synthesis of the title compound, see: Brahmachari & Banerjee (2014 ▶). For a related structure, see: Topno et al. (2011 ▶). For standard bond-length data, see: Allen et al. (1987 ▶). For ring conformations, see: Duax & Norton (1975 ▶). graphic file with name e-70-0o795-scheme1.jpg

Experimental

Crystal data

C₁₆H₁₄N₄O₃·C₂H₆OS
M _r = 388.44
Monoclinic,
a = 28.018 (5) Å
b = 9.196 (5) Å
c = 15.396 (5) Å
β = 93.376 (5)°
V = 3960 (3) Å³
Z = 8
Mo Kα radiation
μ = 0.19 mm⁻¹
T = 293 K
0.30 × 0.20 × 0.20 mm

Data collection

Oxford Diffraction Xcalibur Sapphire3 diffractometer
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2010 ▶) T _min = 0.805, T _max = 1.000
13653 measured reflections
6946 independent reflections
3460 reflections with I > 2σ(I)
R _int = 0.052

Refinement

R[F ² > 2σ(F ²)] = 0.068
wR(F ²) = 0.210
S = 1.00
6946 reflections
510 parameters
H-atom parameters constrained
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.24 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/S1600536814013270/lh5712sup1.cif

e-70-0o795-sup1.cif^{(48.7KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814013270/lh5712Isup2.hkl

e-70-0o795-Isup2.hkl^{(333.1KB, hkl)}

Click here for additional data file.^{(7.1KB, cml)}

Supporting information file. DOI: 10.1107/S1600536814013270/lh5712Isup3.cml

CCDC reference: 1006444

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

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

Cg is the centroid of the N1B–C9B/C8B ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2A—H2A⋯O1S	0.86	1.90	2.737 (4)	165
N2B—H2B⋯O2S ⁱ	0.86	1.90	2.750 (5)	168
N12A—H50A⋯N11B ⁱⁱ	0.86	2.19	3.024 (5)	164
N12A—H40A⋯O13A ⁱⁱⁱ	0.86	2.11	2.958 (4)	170
N12B—H50B⋯N11A ^iv	0.86	2.23	3.072 (5)	165
N12B—H40B⋯O13B ^v	0.86	2.10	2.945 (4)	168

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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 naturally occurring compounds with a broad spectrum of significant biological activities. Recently, a series of synthetic pyrano[2,3-c] pyrazole compounds have been evaluated and possess potent bactericidal (Nasr et al., 2002), insecticidal (Ismail et al., 2003), molluscicidal (Zonouz et al., 2012), analgestic (Kuo et al., 1984), anti-inflammatory activities (Zaki et al., 2006), hypotensive (Ahluwalia et al., 1997), hypoglycemic, and anticancer agents (Mohamed et al., 2010; Bhavanarushi et al., 2013). They are also potential inhibitors of human Chk1 kinase (Foloppe et al., 2006). 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 report herein an efficient and environmentally benign synthesis and the crystal structure of the title compound (I)

The asymmetric unit of the title compound is shown in Fig. 1. There are two crystallographically independent molecules (A and B). The geometry of both molecules is similar and in terms of their bond lengths and bond angles and are in good agreement with the standard values (Allen et al., 1987) and corresponds to those observed in a related structure (Topno et al., 2011). The double bond length C13A═O13A [1.212 (5) Å] and C13B═O13B [1.210 (5) Å] indicates the C═O double bond slightly longer than that observed for carbonyl bonds, probably because atoms O13A and O13B are involved in intermolecular N—H···O hydrogen bonds. The pyran ring (ring II) adopts a flattned sofa conformation in molecule A and a flattened boat conformation in molecule B with asymmetry parameters [ΔCs(C4) = 2.73] (molecule A) and [ΔCs(C4)) = 1.03, ΔC2(C4—C5) = 1.14] (molecule B) (Duax & Norton, 1975). The mean planes the pyrazole (ring I) and phenyl (ring III) rings from dihedral angles of 84.4 (2)° and 84.9 (2)°, respectively for molecules A and B. In the crystal, N—H···O and N—H···N hydrogen bonds link the components of the structure into chains along [010] (Fig. 2). In both solvent molecules, the S atoms are disordered over two sites with occupancy ratios of 0.679 (4):0.321 (4) and 0.546 (6):0.454 (6).

S2. Experimental

The synthesis of the title compound, ethyl 6-amino-5-cyano-4-phenyl-2, 4-dihydropyrano[2,3-c]pyrazole-3-carboxylate (I), 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, diethyl acetylenedicarboxylate (0.170 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. After that, benzaldehyde (0.106 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) was added in a sequential manner (Brahmachari and Banerjee, 2014). The reaction mixture was then stirred vigorously at room temperature and the stirring was continued for 10 h. The progress of the reaction was monitored by TLC. On completion of the reaction, a solid mass was precipitated out, filtered off and repeatedly washed with aqueous ethanol to obtain a crude product which was purified just by recrystallization from ethanol without carrying out column chromatography. The structure of (I) was confirmed by analytical as well as spectral studies including ¹H NMR, ¹³C NMR, and TOF-MS. The single crystal was obtained from DMSO as a solvent. For crystallization 50 mg of (I) dissolved in 5 ml DMSO was left for several days at ambient temperature which yielded white block shaped crystals. Ethyl 6-amino-5-cyano-4-phenyl-2,4-dihydropyrano[2,3-c] pyrazole-3-carboxylate (1). White solid. Yield 91%. Mp: 521–523 K. ¹H NMR (400 MHz, DMSO-d₆) δ /p.p.m.: 13.76 (1H, s, NH), 7.28 (2H, t, J = 7.2 Hz, aromatic H), 7.19 (1H, t, J = 7.2 Hz, aromatic H), 7.10 (2H, d, J = 7.2 Hz, aromatic H), 7.03 (2H, s, NH₂), 4.76 (1H, s, CH), 4.07 (2H, q, J = 7.2 \ 6.8 Hz, CH₃), 1.03 (3H, t, J = 7.2 & 6.8 Hz, CH₃). ¹³C NMR (100 MHz, DMSO-d₆) δ /p.p.m.: 160.43, 158.56, 156.01, 145.31, 129.48, 128.66 (2 C), 127.73 (2 C), 127.04, 120.71, 104.03, 61.24, 58.32, 37.38, 14.14. TOF-MS: 333.0961 [M+Na]⁺. Elemental analysis: Calcd. (%) for C₁₆H₁₄N₄O₃: C, 61.93; H, 4.55; N, 18.06; found: C, C, 61.96; H, 4.53; N, 18.04.