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Acta Cryst. (2009). E65, o39    [ doi:10.1107/S160053680804052X ]

Ethyl 6-amino-5-cyano-4-isopropyl-2-methyl-4H-pyran-3-carboxylate

M. Messaâd, B. Hamdi, F. Chabchoub, A. Ben Salah and M. Salem

Abstract top

In the title compound, C13H18N2O3, the two H atoms of the NH2 group are engaged in hydrogen bonding with the N atom of the cyano group and with one O atom of the ethoxycarbonyl group, building a chain parallel to the [100] direction. The N-H...N hydrogen bonds assemble the molecules around inversion centres, forming dimers with an R22(12) graph-set motif.

Comment top

The analysis of the bibliographical data shows that pyrans are biologically interesting compounds (Bloxham et al., 1994; Wang et al., 1996). In fact, some pyran derivatives present antibacterial activities (Zamocka et al., 1992; Ohira & Yatagai, 1993); antifungal activities (Mohr et al., 1975); antitumor activity (Tandon et al., 1991) and they can have an hypotensive effect (Elagamey et al., 1993). 2-amino-3-cyano-4H-pyrans are useful biphilic agents that lead to polycondensed pyranopyrimidines (Khafagy et al., 2002; Messaâd et al., 2005, 2006). In this paper we report for the first time the synthesis of 2-amino-3-cyano-5-ethoxycarbonyl-4-isopropyl-6-methyl-4H-pyran (3). This product was prepared via a standard addition of Michael of ethylacetoacetate (1) on α,β-ethylenic nitrile (2) in the presence of pyridine as a base (Scheme).

A view of the molecule is represented in Fig. 1. The two H atoms of the NH2 group are engaged in hydrogen bondings with the nitrogen of the cyano group and with one O atom of the ethoxy group then building a chain developing parallel to the [100] direction (Table 1, Fig. 2). The N—H···N hydrogen bonds assemble the molecules around inversion centres to form pseudo-dimers with a R22(12) graph set motif (Etter, 1990; Bernstein et al., 1994).

Related literature top

For general background, see: Messaâd et al. (2005, 2006); Mohr et al. (1975); Ohira & Yatagai (1993); Tandon et al. (1991); Wang et al. (1996); Zamocka et al. (1992); Bloxham et al. (1994); Elagamey et al. (1993); Khafagy et al. (2002). For graph-set notation, see: Etter (1990); Bernstein et al. (1994).

Experimental top

A mixture containing 1.3 g (0.01 mol) of ethylacetoacetate and 1.2 g (0.01 mol) of α,β-ethylenic nitrile in 50 ml of ethanol was heated to reflux for 3 h. The solvent was removed under rotary evaporation. The crude product was washed with ether then filtered and recrystallized from ethanol to give analytically pure crystals. Yield 75%; m.p. 118°C. Spectroscopic analysis, IR: νCN: 2183 cm-1; νNH2: 3334–3398 cm-1; νC═O:1692 cm-1; 1H NMR (300 MHz; CDCl3, p.p.m.): 1.29 (t, 3 J = 7.5, 3H); 4.21 (q, 3 J = 7.5, 2H); 2.29 (s, 1H); 4.48 (s, 2H); 3.37(d, 3 J = 4.5, 1H); 1.82 (m, 1H); 0.81–0.97 (2 d, 3 J = 9, 6H); 13 C NMR (75 MHz; CDCl3, p.p.m.): 14.16; 16.93; 18.27; 19.62; 34.58; 38.66; 57.20; 60.71; 108.42; 120.42; 157.64; 160.23; 166.62.

Refinement top

All H atoms attached to C atoms were fixed geometrically and treated as riding with C—H = 0.98 Å (C methine), 0.97 Å (C methylene), 0.96 Å (C methyl) and 0.86 Å (NH) with Uiso(H) = 1.2 Ueq(C methine, C methylene and NH) and Uiso(H) = 1.5 Ueq(C methyl).

In the absence of significant anomalous scattering, the absolute configuration could not be reliably determined and then the Friedel pairs were merged and any references to the Flack parameter were removed.

Computing details top

Data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1998); data reduction: SAINT (Bruker, 1998); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPIII (Burnett & Johnson, 1996), ORTEP-3 for Windows (Farrugia, 1997) and PLATON (Spek, 2003); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top
[Figure 1] Fig. 1. Molecular view of the title compound with the atom-labelling scheme. Ellispsoids are drawn at the 50% probability level. H atoms are represented as small spheres of arbitrary radii.
[Figure 2] Fig. 2. Partial packing view showing the formation of pseudo dimer through N—H···O and O—H···O hydrogen bonds. Hydrogen bonds are shown as dashed lines. [Symmetry codes: (i) 1 + x, y, z; (ii) 1 - x, -y, 1 - z]
[Figure 3] Fig. 3. The formation of the title compound.
Ethyl 6-amino-5-cyano-4-isopropyl-2-methyl-4H-pyran-3-carboxylate top
Crystal data top
C13H18N2O3Z = 2
Mr = 250.29F(000) = 268
Triclinic, P1Dx = 1.243 Mg m−3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 8.0856 (1) ÅCell parameters from 2132 reflections
b = 9.3193 (2) Åθ = 2.3–21.2°
c = 10.4563 (2) ŵ = 0.09 mm−1
α = 65.652 (1)°T = 296 K
β = 69.679 (1)°Prism, colourless
γ = 76.105 (1)°0.44 × 0.36 × 0.18 mm
V = 668.80 (2) Å3
Data collection top
Bruker SMART CCD area-detector
diffractometer		4664 independent reflections
Radiation source: sealed tube3324 reflections with I > 2σ(I)
graphiteRint = 0.027
φ and ω scansθmax = 32.1°, θmin = 2.2°
Absorption correction: multi-scan
(SADABS; Bruker, 1998)		h = −12→12
Tmin = 0.959, Tmax = 0.982k = −13→12
17876 measured reflectionsl = −15→14
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)] = 0.046Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.143H-atom parameters constrained
S = 1.05 w = 1/[σ2(Fo2) + (0.0801P)2 + 0.026P]
where P = (Fo2 + 2Fc2)/3
4664 reflections(Δ/σ)max = 0.009
167 parametersΔρmax = 0.24 e Å−3
0 restraintsΔρmin = −0.24 e Å−3
Crystal data top
C13H18N2O3γ = 76.105 (1)°
Mr = 250.29V = 668.80 (2) Å3
Triclinic, P1Z = 2
a = 8.0856 (1) ÅMo Kα radiation
b = 9.3193 (2) ŵ = 0.09 mm−1
c = 10.4563 (2) ÅT = 296 K
α = 65.652 (1)°0.44 × 0.36 × 0.18 mm
β = 69.679 (1)°
Data collection top
Bruker SMART CCD area-detector
diffractometer		4664 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 1998)		3324 reflections with I > 2σ(I)
Tmin = 0.959, Tmax = 0.982Rint = 0.027
17876 measured reflectionsθmax = 32.1°
Refinement top
R[F2 > 2σ(F2)] = 0.046H-atom parameters constrained
wR(F2) = 0.143Δρmax = 0.24 e Å−3
S = 1.05Δρmin = −0.24 e Å−3
4664 reflectionsAbsolute structure: ?
167 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.36662 (8)0.54982 (7)0.29951 (8)0.03977 (18)
O2−0.23592 (10)0.56365 (10)0.34370 (11)0.0559 (2)
O3−0.12340 (9)0.79434 (9)0.22760 (9)0.0463 (2)
N20.54618 (11)0.33268 (10)0.37642 (11)0.0440 (2)
H2A0.61610.39720.36310.053*
H2B0.57730.23210.40800.053*
N30.29885 (15)0.00436 (11)0.48430 (13)0.0583 (3)
C10.38924 (12)0.38872 (11)0.34801 (10)0.0340 (2)
C20.26177 (12)0.30627 (10)0.36205 (10)0.0341 (2)
C30.10119 (11)0.39019 (10)0.30733 (10)0.03172 (19)
H3−0.00200.33800.38010.038*
C40.07103 (11)0.55961 (10)0.29910 (10)0.03243 (19)
C50.19954 (12)0.63057 (10)0.29517 (10)0.0344 (2)
C6−0.11029 (12)0.63756 (12)0.29492 (11)0.0364 (2)
C7−0.29880 (14)0.87305 (14)0.21657 (15)0.0535 (3)
H7A−0.38190.85240.31330.064*
H7B−0.34090.83420.16180.064*
C8−0.2844 (2)1.04593 (17)0.14025 (19)0.0738 (4)
H8A−0.24951.08430.19820.111*
H8B−0.39731.10070.12640.111*
H8C−0.19721.06440.04690.111*
C90.28332 (13)0.13998 (11)0.42860 (12)0.0393 (2)
C100.19803 (15)0.79274 (12)0.28995 (14)0.0471 (3)
H10A0.07850.84390.30480.071*
H10B0.27000.85310.19630.071*
H10C0.24460.78590.36540.071*
C110.11157 (12)0.38374 (12)0.15880 (11)0.0382 (2)
H110.00710.44990.12970.046*
C120.27420 (17)0.45164 (17)0.03829 (13)0.0573 (3)
H12A0.37950.39030.06390.086*
H12B0.27280.55960.02660.086*
H12C0.27300.4479−0.05180.086*
C130.1026 (2)0.21704 (15)0.17254 (16)0.0614 (3)
H13A0.08520.22040.08500.092*
H13B0.00540.17280.25480.092*
H13C0.21160.15250.18650.092*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0361 (3)0.0241 (3)0.0613 (4)−0.0051 (2)−0.0227 (3)−0.0092 (3)
O20.0355 (4)0.0475 (5)0.0925 (6)−0.0084 (3)−0.0162 (4)−0.0320 (4)
O30.0353 (3)0.0343 (4)0.0665 (5)0.0028 (3)−0.0207 (3)−0.0140 (3)
N20.0393 (4)0.0292 (4)0.0672 (6)−0.0028 (3)−0.0279 (4)−0.0109 (4)
N30.0649 (6)0.0298 (5)0.0844 (8)−0.0039 (4)−0.0399 (6)−0.0098 (5)
C10.0358 (4)0.0255 (4)0.0421 (5)−0.0041 (3)−0.0164 (4)−0.0088 (3)
C20.0378 (4)0.0246 (4)0.0437 (5)−0.0043 (3)−0.0185 (4)−0.0100 (3)
C30.0322 (4)0.0248 (4)0.0417 (4)−0.0057 (3)−0.0146 (3)−0.0106 (3)
C40.0320 (4)0.0264 (4)0.0424 (5)−0.0030 (3)−0.0143 (3)−0.0128 (3)
C50.0357 (4)0.0258 (4)0.0450 (5)−0.0038 (3)−0.0171 (4)−0.0111 (3)
C60.0334 (4)0.0343 (5)0.0481 (5)−0.0018 (3)−0.0138 (4)−0.0204 (4)
C70.0398 (5)0.0505 (7)0.0749 (8)0.0106 (5)−0.0261 (5)−0.0276 (6)
C80.0675 (8)0.0544 (8)0.0838 (10)0.0189 (6)−0.0321 (7)−0.0150 (7)
C90.0413 (5)0.0289 (5)0.0525 (5)−0.0034 (4)−0.0224 (4)−0.0120 (4)
C100.0509 (5)0.0294 (5)0.0710 (7)−0.0048 (4)−0.0277 (5)−0.0188 (5)
C110.0393 (5)0.0369 (5)0.0472 (5)−0.0021 (4)−0.0200 (4)−0.0183 (4)
C120.0578 (7)0.0678 (8)0.0461 (6)−0.0139 (6)−0.0110 (5)−0.0195 (6)
C130.0818 (9)0.0518 (7)0.0718 (8)−0.0148 (6)−0.0272 (7)−0.0343 (6)
Geometric parameters (Å, °) top
O1—C11.3599 (11)C7—C81.4871 (18)
O1—C51.3855 (11)C7—H7A0.9700
O2—C61.2053 (11)C7—H7B0.9700
O3—C61.3308 (12)C8—H8A0.9600
O3—C71.4516 (12)C8—H8B0.9600
N2—C11.3367 (11)C8—H8C0.9600
N2—H2A0.8600C10—H10A0.9600
N2—H2B0.8600C10—H10B0.9600
N3—C91.1489 (13)C10—H10C0.9600
C1—C21.3625 (12)C11—C131.5172 (15)
C2—C91.4077 (13)C11—C121.5194 (15)
C2—C31.5113 (12)C11—H110.9800
C3—C41.5091 (12)C12—H12A0.9600
C3—C111.5513 (13)C12—H12B0.9600
C3—H30.9800C12—H12C0.9600
C4—C51.3404 (11)C13—H13A0.9600
C4—C61.4785 (12)C13—H13B0.9600
C5—C101.4868 (13)C13—H13C0.9600
C1—O1—C5119.76 (7)C7—C8—H8A109.5
C6—O3—C7116.29 (8)C7—C8—H8B109.5
C1—N2—H2A120.0H8A—C8—H8B109.5
C1—N2—H2B120.0C7—C8—H8C109.5
H2A—N2—H2B120.0H8A—C8—H8C109.5
N2—C1—O1110.47 (7)H8B—C8—H8C109.5
N2—C1—C2128.56 (8)N3—C9—C2179.11 (13)
O1—C1—C2120.97 (8)C5—C10—H10A109.5
C1—C2—C9118.33 (8)C5—C10—H10B109.5
C1—C2—C3121.20 (8)H10A—C10—H10B109.5
C9—C2—C3120.47 (7)C5—C10—H10C109.5
C4—C3—C2109.19 (7)H10A—C10—H10C109.5
C4—C3—C11110.66 (7)H10B—C10—H10C109.5
C2—C3—C11114.29 (8)C13—C11—C12110.81 (10)
C4—C3—H3107.5C13—C11—C3111.65 (9)
C2—C3—H3107.5C12—C11—C3112.53 (8)
C11—C3—H3107.5C13—C11—H11107.2
C5—C4—C6124.13 (8)C12—C11—H11107.2
C5—C4—C3121.99 (8)C3—C11—H11107.2
C6—C4—C3113.88 (7)C11—C12—H12A109.5
C4—C5—O1120.88 (8)C11—C12—H12B109.5
C4—C5—C10130.87 (9)H12A—C12—H12B109.5
O1—C5—C10108.23 (7)C11—C12—H12C109.5
O2—C6—O3122.42 (8)H12A—C12—H12C109.5
O2—C6—C4122.32 (9)H12B—C12—H12C109.5
O3—C6—C4115.19 (7)C11—C13—H13A109.5
O3—C7—C8107.55 (10)C11—C13—H13B109.5
O3—C7—H7A110.2H13A—C13—H13B109.5
C8—C7—H7A110.2C11—C13—H13C109.5
O3—C7—H7B110.2H13A—C13—H13C109.5
C8—C7—H7B110.2H13B—C13—H13C109.5
H7A—C7—H7B108.5
C5—O1—C1—N2−165.46 (8)C6—C4—C5—C101.72 (18)
C5—O1—C1—C214.55 (14)C3—C4—C5—C10−178.70 (10)
N2—C1—C2—C97.28 (17)C1—O1—C5—C4−18.29 (14)
O1—C1—C2—C9−172.73 (9)C1—O1—C5—C10160.34 (9)
N2—C1—C2—C3−172.47 (10)C7—O3—C6—O20.41 (16)
O1—C1—C2—C37.52 (15)C7—O3—C6—C4177.50 (9)
C1—C2—C3—C4−23.01 (13)C5—C4—C6—O2−155.83 (11)
C9—C2—C3—C4157.24 (9)C3—C4—C6—O224.56 (14)
C1—C2—C3—C11101.52 (11)C5—C4—C6—O327.08 (14)
C9—C2—C3—C11−78.22 (11)C3—C4—C6—O3−152.53 (9)
C2—C3—C4—C519.51 (13)C6—O3—C7—C8179.26 (11)
C11—C3—C4—C5−107.12 (10)C4—C3—C11—C13−167.94 (8)
C2—C3—C4—C6−160.87 (8)C2—C3—C11—C1368.32 (10)
C11—C3—C4—C672.50 (9)C4—C3—C11—C1266.72 (11)
C3—C4—C5—O1−0.42 (14)C2—C3—C11—C12−57.03 (11)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N2—H2A···O2i0.862.082.9411 (11)174
N2—H2B···N3ii0.862.193.0269 (13)164
Symmetry codes: (i) x+1, y, z; (ii) −x+1, −y, −z+1.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N2—H2A···O2i0.862.082.9411 (11)174
N2—H2B···N3ii0.862.193.0269 (13)164
Symmetry codes: (i) x+1, y, z; (ii) −x+1, −y, −z+1.
references
References top

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