supplementary materials


ng2761 scheme

Acta Cryst. (2010). E66, o1242    [ doi:10.1107/S1600536810015540 ]

Ethyl 2-(6-amino-5-cyano-3,4-dimethyl-2H,4H-pyrano[2,3-c]pyrazol-4-yl)acetate

M. Kannan, K. Kumaravel, G. Vasuki and R. Krishna

Abstract top

In he title compound, C13H16N4O3, the pyrazole ring is planar (r.m.s. deviation = 0.054 Å). The pyran ring is not planar; the mean plane makes a dihedral angle of 1.9 (1)° with the pyrazole ring. In the crystal structure, intermolecular N-H...N and N-H...O interactions lead to a linear chain motif.

Comment top

Pyrazole, Pyranopyrazoles and its derivates possess antimicrobial (Velaparthi et al.,2008),anticancer (Magedov et al.,2007) and anti-inflammatory (Rovnyak et al.,1982) properties,which made them to be used as a medicines and as biodegradable agrochemiclas (Wamhoff et al., 1993).Wide variety of biological importances of these molecules made the quest for their crystal study and accordingly we have synthesized the title compound by multi-component reaction which compiles with the principles of green chemistry and reported the crystal structure of the title compound.

The compound was crystallized by slow evaporation technique using ethanol as solvent at room temperature. The title compound, (I) was centrosymmetric and it has triclinic crystal system with the space group of P-1. The pyrazole groups are essentially planar, with a mean deviation of 0.0542 Å from the least square plane defined by the five atoms (N1 to C1). The pyran ring deviates significantly from the plane and it has dihedral angle of 1.93 (0.06)° with pyrazole ring. The ethyl acetate group has dihedral angle of 49.99 (0.07)° with pyran ring to which it is attached (Fig. 1). The intermolecular hydrogen bond was formed between N2···N1, N3···N4, N2—H···O2 and N3—H···O3 with distance of 2.956 (2), 3.012 (2), 3.274 (2) and 3.192 (2) Å respectively (Table.1). These intermolecular interactions help in theformation three-dimensional network and crystal packing (Fig. 2) of (I).

Related literature top

For biological applications of pyrazole and pyranopyrazole derivatives, see: Wamhoff et al. (1993).; Velaparthi et al. (2008); Magedov et al. (2007); Rovnyak et al. (1982). For the synthesis, see: Vasuki & Kumaravel (2008).

Experimental top

The titled compound was prepared bythe successive addition of malononitrile (0.132 g, 2 mmol) and piperidine (5 mol%) to a stirred aqueous mixture of hydrazine hydrate 96% 1 (0.107 g, 2 mmol)and ethyl acetoacetate 2 (0.520 g, 4 mmol) at room temperature under an openatmosphere with vigorous stirring for 5–10 min. The precipitated solid wasfiltered, washed with water and then with a mixture of ethyl acetate/hexane(20:80) (Vasuki & Kumaravel, 2008). The product obtained was pure by TLCand 1H NMR spectroscopy. However, the products were further purifiedby recrystallization from ethanol. Analysis calculated for ethyl2-(6-amino-5-cyano-3,4-dimethyl-2,4-dihydropyrano[2,3-c]pyrazol-4-yl) acetate showed that it has C13, H16,N4, O3.

Refinement top

The non-hydrogen atoms where refined anisotropically whereas hydrogen atoms were refined isotropically. The H atoms were geometrically placed (N—H = 0.86 Å, and C—H=0.93-0.97 Å) and refined as riding with Uiso(H) = 1.2-1.5 Ueq (parent atom).

Computing details top

Data collection: APEX2 (Bruker, 2004); cell refinement: APEX2 and SAINT (Bruker, 2004); data reduction: SAINT and XPREP (Bruker, 2004); 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, 1997); software used to prepare material for publication: PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. : The molecular structure of (I), showing the atom-numbering scheme and displacement ellipsoids drawn at the 30% probability level.
[Figure 2] Fig. 2. : The crystal packing of (I), showing intermolecular hydrogen bonding interactions as dashed lines.
Ethyl 2-(6-amino-5-cyano-3,4-dimethyl-2H,4H- pyrano[2,3-c]pyrazol-4-yl)acetate top
Crystal data top
C13H16N4O3Z = 2
Mr = 276.30F(000) = 292
Triclinic, P1Dx = 1.355 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71069 Å
a = 6.961 (5) ÅCell parameters from 7682 reflections
b = 7.373 (5) Åθ = 2.8–32.8°
c = 14.535 (5) ŵ = 0.10 mm1
α = 86.405 (5)°T = 293 K
β = 85.183 (5)°Block, colourless
γ = 65.726 (5)°0.25 × 0.20 × 0.20 mm
V = 677.3 (7) Å3
Data collection top
Bruker Kappa APEXII CCD
diffractometer
2385 independent reflections
Radiation source: fine-focus sealed tube2130 reflections with I > 2σ(I)
graphiteRint = 0.020
Detector resolution: 0 pixels mm-1θmax = 25.0°, θmin = 2.8°
ω and φ scanh = 88
Absorption correction: multi-scan
(SADABS; Bruker 2004)
k = 88
Tmin = 0.976, Tmax = 0.981l = 1717
12811 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)] = 0.041Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.117H-atom parameters constrained
S = 1.02 w = 1/[σ2(Fo2) + (0.0655P)2 + 0.2561P]
where P = (Fo2 + 2Fc2)/3
2378 reflections(Δ/σ)max = 0.001
184 parametersΔρmax = 0.30 e Å3
0 restraintsΔρmin = 0.26 e Å3
Crystal data top
C13H16N4O3γ = 65.726 (5)°
Mr = 276.30V = 677.3 (7) Å3
Triclinic, P1Z = 2
a = 6.961 (5) ÅMo Kα radiation
b = 7.373 (5) ŵ = 0.10 mm1
c = 14.535 (5) ÅT = 293 K
α = 86.405 (5)°0.25 × 0.20 × 0.20 mm
β = 85.183 (5)°
Data collection top
Bruker Kappa APEXII CCD
diffractometer
2385 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker 2004)
2130 reflections with I > 2σ(I)
Tmin = 0.976, Tmax = 0.981Rint = 0.020
12811 measured reflectionsθmax = 25.0°
Refinement top
R[F2 > 2σ(F2)] = 0.041H-atom parameters constrained
wR(F2) = 0.117Δρmax = 0.30 e Å3
S = 1.02Δρmin = 0.26 e Å3
2378 reflectionsAbsolute structure: ?
184 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
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.

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 > σ(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.

Some "bad" relections were omitted in the refinement.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.4375 (2)0.8266 (2)0.84125 (10)0.0288 (3)
C20.3125 (2)0.7231 (2)0.86328 (9)0.0271 (3)
C30.2551 (2)0.6151 (2)0.79351 (9)0.0271 (3)
C40.3682 (2)0.6404 (2)0.70213 (9)0.0282 (3)
C50.4908 (2)0.7439 (2)0.68793 (10)0.0306 (3)
C60.0126 (2)0.7009 (2)0.78369 (10)0.0329 (3)
H6A0.01640.62760.73750.040*
H6B0.05630.68180.84200.040*
C70.0780 (2)0.9167 (2)0.75667 (11)0.0378 (4)
C80.1525 (3)1.1488 (3)0.62848 (17)0.0654 (6)
H8A0.25281.24020.67240.078*
H8B0.22171.16360.57150.078*
C90.0317 (5)1.1990 (4)0.6104 (3)0.1088 (12)
H9A0.08871.20230.66790.163*
H9B0.01091.32710.57940.163*
H9C0.13751.10030.57220.163*
C100.2672 (2)0.7477 (2)0.95731 (10)0.0320 (3)
C110.1408 (3)0.6754 (3)1.02539 (11)0.0487 (5)
H11A0.21770.53561.03800.073*
H11B0.00910.69781.00060.073*
H11C0.11400.74611.08160.073*
C120.3282 (3)0.3931 (2)0.82003 (11)0.0385 (4)
H12A0.47800.33510.82610.058*
H12B0.29510.32700.77290.058*
H12C0.25740.37820.87770.058*
C130.3419 (2)0.5481 (2)0.62484 (10)0.0354 (4)
N10.4738 (2)0.9108 (2)0.91081 (8)0.0351 (3)
N20.3649 (2)0.8596 (2)0.98199 (8)0.0357 (3)
H20.35890.89541.03770.043*
N30.5923 (2)0.7662 (2)0.60839 (9)0.0474 (4)
H3A0.58310.71140.55940.057*
H3B0.66670.83520.60640.057*
N40.3189 (3)0.4715 (3)0.56322 (10)0.0555 (4)
O10.52556 (17)0.84545 (17)0.75515 (7)0.0367 (3)
O20.1338 (2)1.0482 (2)0.81014 (10)0.0659 (4)
O30.08990 (18)0.94621 (17)0.66504 (8)0.0450 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0306 (7)0.0354 (7)0.0243 (7)0.0169 (6)0.0013 (5)0.0047 (6)
C20.0271 (7)0.0322 (7)0.0246 (7)0.0142 (6)0.0018 (5)0.0038 (5)
C30.0277 (7)0.0322 (7)0.0250 (7)0.0153 (6)0.0012 (5)0.0050 (5)
C40.0269 (7)0.0353 (7)0.0253 (7)0.0148 (6)0.0007 (5)0.0071 (6)
C50.0307 (7)0.0399 (8)0.0245 (7)0.0172 (6)0.0006 (6)0.0069 (6)
C60.0291 (7)0.0450 (8)0.0312 (8)0.0213 (6)0.0005 (6)0.0068 (6)
C70.0250 (7)0.0454 (9)0.0434 (9)0.0128 (6)0.0036 (6)0.0124 (7)
C80.0592 (12)0.0478 (11)0.0810 (15)0.0144 (9)0.0116 (11)0.0124 (10)
C90.096 (2)0.0740 (17)0.171 (3)0.0526 (16)0.029 (2)0.0415 (19)
C100.0376 (8)0.0365 (8)0.0267 (7)0.0196 (6)0.0016 (6)0.0048 (6)
C110.0692 (12)0.0637 (11)0.0298 (8)0.0450 (10)0.0083 (8)0.0090 (8)
C120.0481 (9)0.0344 (8)0.0364 (8)0.0197 (7)0.0038 (7)0.0028 (6)
C130.0362 (8)0.0488 (9)0.0289 (8)0.0255 (7)0.0042 (6)0.0088 (7)
N10.0430 (7)0.0457 (7)0.0273 (6)0.0284 (6)0.0011 (5)0.0067 (5)
N20.0487 (8)0.0459 (7)0.0224 (6)0.0286 (6)0.0015 (5)0.0069 (5)
N30.0591 (9)0.0738 (10)0.0300 (7)0.0484 (8)0.0114 (6)0.0162 (7)
N40.0675 (10)0.0859 (12)0.0357 (8)0.0534 (9)0.0097 (7)0.0243 (8)
O10.0446 (6)0.0537 (7)0.0266 (6)0.0350 (5)0.0047 (4)0.0106 (5)
O20.0652 (9)0.0518 (8)0.0677 (9)0.0048 (7)0.0160 (7)0.0270 (7)
O30.0440 (7)0.0432 (6)0.0457 (7)0.0163 (5)0.0008 (5)0.0005 (5)
Geometric parameters (Å, °) top
C1—N11.3125 (19)C8—H8A0.9700
C1—O11.3714 (18)C8—H8B0.9700
C1—C21.383 (2)C9—H9A0.9600
C2—C101.383 (2)C9—H9B0.9600
C2—C31.5006 (19)C9—H9C0.9600
C3—C41.527 (2)C10—N21.346 (2)
C3—C121.535 (2)C10—C111.487 (2)
C3—C61.556 (2)C11—H11A0.9600
C4—C51.356 (2)C11—H11B0.9600
C4—C131.411 (2)C11—H11C0.9600
C5—N31.341 (2)C12—H12A0.9600
C5—O11.3616 (17)C12—H12B0.9600
C6—C71.490 (2)C12—H12C0.9600
C6—H6A0.9700C13—N41.144 (2)
C6—H6B0.9700N1—N21.3572 (18)
C7—O21.195 (2)N2—H20.8600
C7—O31.340 (2)N3—H3A0.8600
C8—O31.452 (2)N3—H3B0.8600
C8—C91.474 (4)
N1—C1—O1118.81 (13)H8A—C8—H8B108.0
N1—C1—C2115.28 (13)C8—C9—H9A109.5
O1—C1—C2125.90 (13)C8—C9—H9B109.5
C1—C2—C10103.21 (13)H9A—C9—H9B109.5
C1—C2—C3123.21 (13)C8—C9—H9C109.5
C10—C2—C3133.58 (13)H9A—C9—H9C109.5
C2—C3—C4105.90 (12)H9B—C9—H9C109.5
C2—C3—C12111.39 (12)N2—C10—C2106.01 (13)
C4—C3—C12109.91 (12)N2—C10—C11122.04 (14)
C2—C3—C6112.12 (11)C2—C10—C11131.95 (14)
C4—C3—C6110.22 (12)C10—C11—H11A109.5
C12—C3—C6107.33 (12)C10—C11—H11B109.5
C5—C4—C13116.78 (13)H11A—C11—H11B109.5
C5—C4—C3126.29 (13)C10—C11—H11C109.5
C13—C4—C3116.93 (13)H11A—C11—H11C109.5
N3—C5—C4126.98 (14)H11B—C11—H11C109.5
N3—C5—O1109.58 (13)C3—C12—H12A109.5
C4—C5—O1123.44 (13)C3—C12—H12B109.5
C7—C6—C3112.62 (12)H12A—C12—H12B109.5
C7—C6—H6A109.1C3—C12—H12C109.5
C3—C6—H6A109.1H12A—C12—H12C109.5
C7—C6—H6B109.1H12B—C12—H12C109.5
C3—C6—H6B109.1N4—C13—C4178.79 (17)
H6A—C6—H6B107.8C1—N1—N2101.70 (12)
O2—C7—O3123.82 (17)C10—N2—N1113.80 (12)
O2—C7—C6124.23 (16)C10—N2—H2123.1
O3—C7—C6111.94 (13)N1—N2—H2123.1
O3—C8—C9111.08 (18)C5—N3—H3A120.0
O3—C8—H8A109.4C5—N3—H3B120.0
C9—C8—H8A109.4H3A—N3—H3B120.0
O3—C8—H8B109.4C5—O1—C1115.14 (12)
C9—C8—H8B109.4C7—O3—C8117.56 (15)
N1—C1—C2—C100.13 (17)C12—C3—C6—C7179.24 (12)
O1—C1—C2—C10179.38 (13)C3—C6—C7—O285.9 (2)
N1—C1—C2—C3179.36 (12)C3—C6—C7—O394.18 (15)
O1—C1—C2—C30.1 (2)C1—C2—C10—N20.13 (16)
C1—C2—C3—C42.14 (18)C3—C2—C10—N2179.54 (14)
C10—C2—C3—C4177.17 (15)C1—C2—C10—C11179.84 (17)
C1—C2—C3—C12121.60 (15)C3—C2—C10—C110.4 (3)
C10—C2—C3—C1257.7 (2)C5—C4—C13—N4169 (9)
C1—C2—C3—C6118.10 (15)C3—C4—C13—N411 (9)
C10—C2—C3—C662.6 (2)O1—C1—N1—N2179.63 (12)
C2—C3—C4—C51.37 (19)C2—C1—N1—N20.32 (17)
C12—C3—C4—C5121.80 (16)C2—C10—N2—N10.35 (17)
C6—C3—C4—C5120.10 (16)C11—C10—N2—N1179.63 (15)
C2—C3—C4—C13178.97 (12)C1—N1—N2—C100.41 (17)
C12—C3—C4—C1358.54 (17)N3—C5—O1—C1177.10 (12)
C6—C3—C4—C1359.56 (17)C4—C5—O1—C13.8 (2)
C13—C4—C5—N30.9 (2)N1—C1—O1—C5176.23 (12)
C3—C4—C5—N3179.41 (14)C2—C1—O1—C53.0 (2)
C13—C4—C5—O1178.03 (13)O2—C7—O3—C87.0 (2)
C3—C4—C5—O11.6 (2)C6—C7—O3—C8173.07 (14)
C2—C3—C6—C758.13 (16)C9—C8—O3—C787.2 (3)
C4—C3—C6—C759.57 (16)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N2—H2···O2i0.862.553.274 (2)142
N2—H2···N1ii0.862.372.956 (2)126
N3—H3A···N4iii0.862.193.012 (2)160
N3—H3B···O3iv0.862.403.192 (2)154
Symmetry codes: (i) −x, −y+2, −z+2; (ii) −x+1, −y+2, −z+2; (iii) −x+1, −y+1, −z+1; (iv) x+1, y, z.
Table 1
Hydrogen-bond geometry (Å, °)
top
D—H···AD—HH···AD···AD—H···A
N2—H2···O2i0.862.553.274 (2)142
N2—H2···N1ii0.862.372.956 (2)126
N3—H3A···N4iii0.862.193.012 (2)160
N3—H3B···O3iv0.862.403.192 (2)154
Symmetry codes: (i) −x, −y+2, −z+2; (ii) −x+1, −y+2, −z+2; (iii) −x+1, −y+1, −z+1; (iv) x+1, y, z.
Acknowledgements top

The authors acknowledge the Centre of Excellence in Bioinformatics, Pondicherry University, for providing the facilities and GV thanks the Department of Science and Technology, New Delhi, Government of India, (No. SR/S5/GC-22/2007) for financial support.

references
References top

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Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.

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Rovnyak, G. C., Millonig, R. C., Schwartz, J. & Shu, V. (1982). J. Med. Chem. 25, 1482–1488.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Spek, A. L. (2009). Acta Cryst. D65, 148–155.

Vasuki, G. & Kumaravel, K. (2008). Tetrahedron Lett. 49, 5636–5638.

Velaparthi, S., Brunsteiner, M., Uddin, R., Wan, B., Franzblau, S. G. & Petukhov, P. A. (2008). J. Med. Chem. 51, 1999–2002.

Wamhoff, H., Kroth, E. & Strauch, K. (1993). Synthesis, 11, 1129.