5-Amino-3-methyl-1,2-oxazole-4-carbonitrile

Abstract

In the title compound, C₅H₅N₃O, the isoxazole ring is essentially planar, with a maximum deviation of 0.007 (1) Å from the least-squares plane. The N atom of the amine group exhibits sp ² character (sum of bond angles around this atom = 358°). In the crystal, mol­ecules are aggregated by two kinds of N—H⋯N hydrogen bonds into fused R ₂ ²(12) and R ₆ ⁶(26) rings, forming a slightly puckered two-dimensional array lying parallel to (101).

Related literature  

For the biological activities of isoxazole derivatives, see: Mantegani et al. (2011 ▶); Ali et al. (2011 ▶); Panda et al. (2009 ▶); Özdemir et al. (2007 ▶); Banerjee et al. (1994 ▶); Makoto et al. (2011 ▶). For background to push–pull nitriles, see: Ziao et al. (2001 ▶); Hao et al. (2005 ▶). For hydrogen-bond motif definitions, see: Bernstein et al. (1995 ▶).

Experimental  

Crystal data  

• C₅H₅N₃O

• M _r = 123.12

• Monoclinic,

• a = 3.8779 (2) Å

• b = 18.8518 (11) Å

• c = 8.2015 (4) Å

• β = 100.780 (2)°

• V = 588.99 (5) ų

• Z = 4

• Mo Kα radiation

• μ = 0.10 mm⁻¹

• T = 296 K

• 0.56 × 0.26 × 0.20 mm

Data collection  

• Bruker APEXII CCD diffractometer

• Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.674, T _max = 0.745

• 5275 measured reflections

• 1277 independent reflections

• 1072 reflections with I > 2σ(I)

• R _int = 0.020

Refinement  

• R[F ² > 2σ(F ²)] = 0.035

• wR(F ²) = 0.107

• S = 1.07

• 1277 reflections

• 91 parameters

• H atoms treated by a mixture of independent and constrained refinement

• Δρ_max = 0.19 e Å⁻³

• Δρ_min = −0.16 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: XPW (Siemens, 1996 ▶); software used to prepare material for publication: SHELXTL (Sheldrick, 2008 ▶) and enCIFer (Allen et al., 2004 ▶).

Supplementary Material

Supplementary material file. DOI: 10.1107/S1600536812032667/gk2513Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2A⋯N1i	0.842 (19)	2.118 (19)	2.9567 (16)	174.2 (16)
N2—H2B⋯N3ii	0.870 (18)	2.174 (18)	3.0402 (17)	173.8 (15)

Symmetry codes: (i) ; (ii) .

supplementary crystallographic information

Comment

Isoxazoles are an important class of heterocyclic compounds which are widely used in medicinal chemistry. A number of isoxazole derivatives are known to act as anti-tumor (Mantegani et al., 2011), anti-HIV (Ali et al., 2011), anti-inflammatory, antibacterial (Panda et al., 2009), antidepressant, anticonvulsant (Özdemir et al., 2007) and anthelmintic (Banerjee et al., 1994) agents. Isoxazole derivatives are also utilized in therapy in the treatment of diabetes, obesity or hyperlipemia (Makoto et al., 2011). Considering the potential of the title compound as a pharmaceutical intermediate, its crystal structure is reported here.

The title molecule (Fig. 1) exhibits a planar isoxazole ring with a maximum deviation of 0.007 (1) Å for atom C2. The sum of the bond angles around the N atom of the amine group (358°) is in accordance with sp² hybridization.

As has been described for related push–pull nitriles (Ziao et al., 2001; Hao et al., 2005), there is a conjugative interaction between the amino nitrogen lone pair and the nitrile nitrogen via the C1═C2 bond which increases the hydrogen-bonding acceptor capability of the nitrile nitrogen. Thus, the amino nitrogen lone pair is not available for a hydrogen-bond interaction and it does not form any hydrogen bond as an acceptor. In addition, the C4≡N3 bond length [1.1424 (16) Å] is typical of the nitrile bond lengths found in push–pull nitriles.

In the crystal structure (Fig. 2), molecules are linked by N—H···N_cyano (N2···N3 = 3.0402 (17) Å) and N—H···N_isoxazole (N2···N1 = 2.9567 (16) Å) hydrogen bonds (Table 1) building R₂²(12) and R₆⁶(26) rings (Bernstein et al., 1995) in a two-dimensional arrangement along the (101) plane.

Experimental

To a solution of hydroxylamine hydrochloride (13.9 g, 0.2 mol) in 10% sodium hydroxide (80 ml), (1-ethoxyethylidene)malononitrile (27.23 g, 0.2 mol) was added dropwise at 323 K under vigorous stirring condition. The temperature was kept below 323 K by making this addition slowly and by addition of small amount of ice. After stirring for an additional 1.5 h at approximately 293 K, the resulting solid was filtered and washed with water. Single crystals of title compound were obtained from a solution of aqueous ethanol after slow evaporation at room temperature.

Refinement

All H atoms were located on a final ΔF map. The positions of H atoms from the methyl group were determined geometrically (C—H = 0.96 Å) and these atoms were refined as riding with U_iso(H) = 1.5U_eq(C). The H atoms of the amine group were freely refined.

Figures

Fig. 1.

The molecular structure of title compound, showing the atom-numbering scheme and displacement ellipsoids at the 50% probability level.

Fig. 2.

A view of two-dimensional structure in the title compound showing the R22(12) and R66(26) graph-set motifs, built from N—H···N hydrogen bonds (dashed lines).

Crystal data

C5H5N3O	F(000) = 256
Mr = 123.12	Dx = 1.388 Mg m−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 2187 reflections
a = 3.8779 (2) Å	θ = 2.8–26.2°
b = 18.8518 (11) Å	µ = 0.10 mm−1
c = 8.2015 (4) Å	T = 296 K
β = 100.780 (2)°	Irregular, colourless
V = 588.99 (5) Å3	0.56 × 0.26 × 0.20 mm
Z = 4

Data collection

Bruker APEXII CCD diffractometer	1277 independent reflections
Radiation source: fine-focus sealed tube	1072 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.020
φ and ω scans	θmax = 27.0°, θmin = 3.3°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −4→4
Tmin = 0.674, Tmax = 0.745	k = −24→23
5275 measured reflections	l = −10→10

Refinement

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.035	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.107	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ2(Fo2) + (0.0631P)2 + 0.0596P] where P = (Fo2 + 2Fc2)/3
1277 reflections	(Δ/σ)max = 0.001
91 parameters	Δρmax = 0.19 e Å−3
0 restraints	Δρmin = −0.16 e Å−3

Special details

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s 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 > 2σ(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 (Ų)

	x	y	z	Uiso*/Ueq
O1	0.8940 (2)	0.77984 (4)	0.37710 (11)	0.0430 (3)
C2	0.8212 (3)	0.89315 (6)	0.30725 (13)	0.0343 (3)
N1	0.9900 (3)	0.78822 (6)	0.21727 (13)	0.0454 (3)
N2	0.6888 (4)	0.84546 (6)	0.57048 (14)	0.0463 (3)
N3	0.6449 (4)	1.02356 (6)	0.30830 (16)	0.0577 (4)
C4	0.7269 (3)	0.96534 (6)	0.30883 (14)	0.0384 (3)
C3	0.9420 (3)	0.85487 (7)	0.17972 (14)	0.0381 (3)
C5	1.0051 (4)	0.88260 (8)	0.01801 (16)	0.0518 (4)
H5A	1.1058	0.8459	−0.0394	0.078*
H5B	1.1637	0.9221	0.0372	0.078*
H5C	0.7866	0.8977	−0.0482	0.078*
C1	0.7919 (3)	0.84280 (6)	0.42663 (14)	0.0347 (3)
H2A	0.647 (4)	0.8074 (10)	0.617 (2)	0.063 (5)*
H2B	0.610 (4)	0.8842 (10)	0.608 (2)	0.061 (5)*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O1	0.0636 (6)	0.0243 (4)	0.0437 (5)	0.0043 (4)	0.0167 (4)	−0.0011 (3)
C2	0.0426 (6)	0.0264 (6)	0.0346 (6)	0.0016 (4)	0.0092 (5)	−0.0006 (4)
N1	0.0611 (7)	0.0367 (6)	0.0413 (6)	0.0057 (5)	0.0168 (5)	−0.0060 (4)
N2	0.0752 (8)	0.0257 (6)	0.0434 (6)	0.0018 (5)	0.0256 (6)	0.0023 (4)
N3	0.0844 (10)	0.0318 (6)	0.0616 (8)	0.0114 (6)	0.0260 (7)	0.0054 (5)
C4	0.0504 (7)	0.0306 (7)	0.0367 (6)	0.0018 (5)	0.0145 (5)	0.0021 (4)
C3	0.0420 (6)	0.0358 (6)	0.0369 (6)	0.0029 (5)	0.0083 (5)	−0.0038 (5)
C5	0.0622 (8)	0.0581 (9)	0.0384 (7)	0.0072 (7)	0.0180 (6)	0.0027 (6)
C1	0.0440 (6)	0.0237 (6)	0.0369 (6)	−0.0003 (4)	0.0090 (5)	−0.0026 (4)

Geometric parameters (Å, º)

O1—C1	1.3383 (13)	N2—H2A	0.842 (19)
O1—N1	1.4367 (13)	N2—H2B	0.870 (18)
C2—C1	1.3836 (16)	N3—C4	1.1424 (16)
C2—C4	1.4098 (16)	C3—C5	1.4877 (17)
C2—C3	1.4204 (16)	C5—H5A	0.9600
N1—C3	1.2988 (16)	C5—H5B	0.9600
N2—C1	1.3154 (16)	C5—H5C	0.9600
C1—O1—N1	108.74 (8)	C2—C3—C5	127.57 (12)
C1—C2—C4	126.86 (10)	C3—C5—H5A	109.5
C1—C2—C3	104.75 (10)	C3—C5—H5B	109.5
C4—C2—C3	128.25 (11)	H5A—C5—H5B	109.5
C3—N1—O1	105.83 (9)	C3—C5—H5C	109.5
C1—N2—H2A	119.3 (12)	H5A—C5—H5C	109.5
C1—N2—H2B	122.4 (11)	H5B—C5—H5C	109.5
H2A—N2—H2B	116.3 (16)	N2—C1—O1	117.57 (10)
N3—C4—C2	178.79 (15)	N2—C1—C2	133.44 (11)
N1—C3—C2	111.67 (11)	O1—C1—C2	109.00 (10)
N1—C3—C5	120.74 (11)
C1—O1—N1—C3	0.14 (14)	N1—O1—C1—N2	179.10 (11)
O1—N1—C3—C2	0.70 (14)	N1—O1—C1—C2	−0.94 (13)
O1—N1—C3—C5	−178.01 (10)	C4—C2—C1—N2	−2.8 (2)
C1—C2—C3—N1	−1.26 (14)	C3—C2—C1—N2	−178.75 (15)
C4—C2—C3—N1	−177.17 (12)	C4—C2—C1—O1	177.29 (12)
C1—C2—C3—C5	177.35 (12)	C3—C2—C1—O1	1.31 (13)
C4—C2—C3—C5	1.4 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···N1i	0.842 (19)	2.118 (19)	2.9567 (16)	174.2 (16)
N2—H2B···N3ii	0.870 (18)	2.174 (18)	3.0402 (17)	173.8 (15)

Symmetry codes: (i) x−1/2, −y+3/2, z+1/2; (ii) −x+1, −y+2, −z+1.