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

Shoghpour, S.; Keykha, A.; Amiri Rudbari, H.; Rahimizadeh, M.; Bakavoli, M.; Pourayoubi, M.; Nicolò, F.

doi:10.1107/S1600536812032667

organic compounds

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Volume 68| Part 8| August 2012| Page o2530

https://doi.org/10.1107/S1600536812032667

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

Samad Shoghpour,^a ^* Amir Keykha,^a Hadi Amiri Rudbari,^b Mohammad Rahimizadeh,^a Mehdi Bakavoli,^a Mehrdad Pourayoubi ^a and Francesco Nicolò ^b

^aDepartment of Chemistry, Ferdowsi University of Mashhad, Mashhad 91779, Iran, and ^bDipartimento di Chimica Inorganica, Vill. S. Agata, Salita Sperone 31, Università di Messina, 98166 Messina, Italy
^*Correspondence e-mail: s.shoghpour@gmail.com

(Received 12 July 2012; accepted 18 July 2012; online 25 July 2012)

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 sp² 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 R₂²(12) and R₆⁶(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, P 2₁ /n
a = 3.8779 (2) Å
b = 18.8518 (11) Å
c = 8.2015 (4) Å
β = 100.780 (2)°
V = 588.99 (5) Å³
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[F² > 2σ(F²)] = 0.035
wR(F²) = 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

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) $[x-{\script{1\over 2}}, -y+{\script{3\over 2}}, z+{\script{1\over 2}}]$ ; (ii) -x+1, -y+2, -z+1.

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 ).

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536812032667/gk2513sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536812032667/gk2513Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S1600536812032667/gk2513Isup3.cml

checkCIF report

Comment top

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.

Related literature top

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 top

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.

Structure description top

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).

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); 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).

Figures top

	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).

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

Crystal data top

C₅H₅N₃O	F(000) = 256
M_r = 123.12	D_x = 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 top

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

Refinement top

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(F_o²) + (0.0631P)² + 0.0596P] where P = (F_o² + 2F_c²)/3
1277 reflections	(Δ/σ)_max = 0.001
91 parameters	Δρ_max = 0.19 e Å⁻³
0 restraints	Δρ_min = −0.16 e Å⁻³

Crystal data top

C₅H₅N₃O	V = 588.99 (5) Å³
M_r = 123.12	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 3.8779 (2) Å	µ = 0.10 mm⁻¹
b = 18.8518 (11) Å	T = 296 K
c = 8.2015 (4) Å	0.56 × 0.26 × 0.20 mm
β = 100.780 (2)°

Data collection top

Bruker APEXII CCD diffractometer	1277 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2008)	1072 reflections with I > 2σ(I)
T_min = 0.674, T_max = 0.745	R_int = 0.020
5275 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.035	0 restraints
wR(F²) = 0.107	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	Δρ_max = 0.19 e Å⁻³
1277 reflections	Δρ_min = −0.16 e Å⁻³
91 parameters

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
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 (Å²) top

	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) top

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) top

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.

Experimental details

Crystal data
Chemical formula	C₅H₅N₃O
M_r	123.12
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	296
a, b, c (Å)	3.8779 (2), 18.8518 (11), 8.2015 (4)
β (°)	100.780 (2)
V (Å³)	588.99 (5)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.56 × 0.26 × 0.20

Data collection
Diffractometer	Bruker APEXII CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2008)
T_min, T_max	0.674, 0.745
No. of measured, independent and observed [I > 2σ(I)] reflections	5275, 1277, 1072
R_int	0.020
(sin θ/λ)_max (Å⁻¹)	0.639

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.035, 0.107, 1.07
No. of reflections	1277
No. of parameters	91
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.19, −0.16

Computer programs: APEX2 (Bruker, 2007), SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), XPW (Siemens, 1996), SHELXTL (Sheldrick, 2008) and enCIFer (Allen et al., 2004).

Hydrogen-bond geometry (Å, º) top

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.

Acknowledgements

Support of this investigation by Ferdowsi University of Mashhad is gratefully acknowledged.

References

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