N-(2-Nitro­oxyeth­yl)picolinamide

Abstract

In the title mol­ecule, C₈H₉N₃O₄, the amide group is involved in the formation of an intra­molecular N—H⋯N hydrogen bond. In the crystal, mol­ecules related by translation along the a axis are linked into chains via weak inter­molecular C—H⋯O inter­actions.

Related literature

For related structures, see: Eremenko et al. (1996 ▶); Fedorov et al. (2001 ▶). For further synthetic details, see: Samejima (1960 ▶); Jiao et al. (1990 ▶).

Experimental

Crystal data

• C₈H₉N₃O₄

• M _r = 211.18

• Orthorhombic,

• a = 5.5075 (2) Å

• b = 13.6114 (5) Å

• c = 12.6822 (4) Å

• V = 950.72 (6) ų

• Z = 4

• Mo Kα radiation

• μ = 0.12 mm⁻¹

• T = 295 K

• 0.49 × 0.21 × 0.19 mm

Data collection

• Nonius KappaCCD diffractometer

• 4037 measured reflections

• 1265 independent reflections

• 1039 reflections with I > 2σ(I)

• R _int = 0.020

Refinement

• R[F ² > 2σ(F ²)] = 0.038

• wR(F ²) = 0.108

• S = 1.07

• 1265 reflections

• 137 parameters

• H-atom parameters constrained

• Δρ_max = 0.23 e Å⁻³

• Δρ_min = −0.15 e Å⁻³

Data collection: COLLECT (Nonius, 2000 ▶); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997 ▶); data reduction: DENZO/SCALEPACK; 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: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Supplementary material file. DOI: 10.1107/S1600536811039572/cv5154Isup3.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—H⋯N1	0.86	2.31	2.692 (3)	107
C8—H8B⋯O1i	0.97	2.39	3.239 (3)	145

Symmetry code: (i) .

supplementary crystallographic information

Comment

The title compound (I) can be considered as a potential nitric oxide donating drug. Herewith we present its crystal structure.

The molecule of (I) adopts a folded conformation and contains a planar pyridine cycle (NC₅H₄) bearing a CO group attached to the α-carbon atom (Fig. 1). The dihedral angle between the pyridine ring and the O1/C6/N2 plane is 11.3 (2)°. This angle is smaller than that in the nicorandyl [22.8 (2)°] (Eremenko et al., 1996).The dihedral angle between the mean planes O1/C6/N2/C7 and C8/O2/N3/O3/O4 is 44.74 (7)°. The C═O and CH₂–ONO₂ bonds are oriented trans to the pyridine nitrogen atom. In the nicorandyl compound these groups were found in the cis position (Eremenko et al., 1996). Another structural isomer (Fedorov et al., 2001), [N-(2-nitrooxyethyl)isonicotinamide], displays a different molecular conformation and crystallizes in the same centrosymmetric space group P2₁/c as nicorandil.

The crystal structure of (I) is stabilized through weak non-classical intermolecular H-bonds of the type C—H···O in [100] direction, involving the carbon atom of the nitrooxyethyl group and the oxygen atom of carbonylamide. Moreover, were observed one intramolecular interactions of the type N—H···N (Table 1). On the other hand, the compound nicorandil has only one intermolecular interaction of the type N—H···O. The results for compound (I) and its structural isomers show that the position of the ligand in pyridine ring affects the conformation of the molecule and the interactions present in the crystal packing.

Experimental

The title product was synthesized by heating ethylnicotinate with an excess 2-ethanolamine to give N-(2-hydroxyethyl)picolinamide in 92% yield (Samejima, 1960). The nitration of N-(2-hydroxyethyl)picolinamide (0.10 mmol) was held by mixing it with fuming nitric acid (1.00 mmol) at -5°C and stirred for 2 h.

The reaction mixture was poured into water and ice, and the pH was adjusted to 6.0 adding (CaCO₃). The white solid obtained was filtered at reduced pressure and recrystallized in ethanol, forming the N-(2-nitrooxyethyl)picolinamide in 63% yield (Jiao et al., 1990). MP: 61.2–63.0°C. ¹H-NMR (200 MHz, CDCl₃): 3.85 (2H, q, J = 5.6 Hz), 4.67 (2H, t, J = 5.2 Hz),7.42–7.48 (¹H, m), 7.83–7.90 (¹H, m), 8.19 (¹H, d, J = 7.9 Hz), 8.39 (¹H, br s), 8.56 (¹H, d, J = 4.4 Hz). ¹³C-NMR (200 MHz, CDCl₃): 36.7, 71.7, 122.2, 126.4, 137.4, 148.1, 149.11, 164.7.

Refinement

H atoms were geometrically positioned (C—H 0.93-0.97 Å, N—H 0.86 Å) and refined as riding, with U_iso(H) = 1.2 U_eq of the parent atom. In the absence of significant anomalous scatterers in the molecule, attempts to confirm the absolute structure by refinement of the Flack parameter in the presence of 871 sets of Friedel equivalents led to an inconclusive value of -0.2 (13). Therefore, the Friedel pairs were merged before the final refinement.

Figures

Fig. 1.

The molecular structure of (I) showing the atom labeling. Displacement ellipsoids are drawn at the 30% probability level.

Crystal data

C8H9N3O4	Dx = 1.475 Mg m−3
Mr = 211.18	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121	Cell parameters from 2165 reflections
a = 5.5075 (2) Å	θ = 2.9–27.5°
b = 13.6114 (5) Å	µ = 0.12 mm−1
c = 12.6822 (4) Å	T = 295 K
V = 950.72 (6) Å3	Prism, colourless
Z = 4	0.49 × 0.21 × 0.19 mm
F(000) = 440

Data collection

Nonius KappaCCD diffractometer	1039 reflections with I > 2σ(I)
Radiation source: Enraf–Nonius	Rint = 0.020
graphite	θmax = 27.5°, θmin = 3.2°
Detector resolution: 9 pixels mm-1	h = −7→7
CCD rotation images, thick slices scans	k = −16→17
4037 measured reflections	l = −15→15
1265 independent reflections

Refinement

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.038	H-atom parameters constrained
wR(F2) = 0.108	w = 1/[σ2(Fo2) + (0.0654P)2 + 0.0645P] where P = (Fo2 + 2Fc2)/3
S = 1.07	(Δ/σ)max < 0.001
1265 reflections	Δρmax = 0.23 e Å−3
137 parameters	Δρmin = −0.15 e Å−3
0 restraints	Extinction correction: SHELXL
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.124 (13)

Special details

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

	x	y	z	Uiso*/Ueq
O1	−0.1820 (3)	0.49141 (13)	0.05722 (14)	0.0662 (5)
O2	0.2098 (3)	0.55263 (11)	−0.11459 (12)	0.0528 (4)
O3	−0.0499 (4)	0.67762 (12)	−0.11167 (15)	0.0705 (5)
O4	−0.1235 (4)	0.54631 (16)	−0.20249 (14)	0.0797 (6)
N1	0.1892 (3)	0.31135 (13)	0.17680 (14)	0.0509 (5)
N2	0.2136 (4)	0.49676 (13)	0.10379 (15)	0.0532 (5)
H	0.3331	0.4648	0.1308	0.064*
N3	−0.0061 (4)	0.59684 (13)	−0.14445 (15)	0.0532 (5)
C1	−0.0042 (4)	0.34497 (13)	0.12528 (15)	0.0430 (5)
C2	0.1867 (5)	0.21623 (15)	0.20374 (19)	0.0570 (6)
H2	0.3191	0.1914	0.2407	0.068*
C3	−0.0002 (5)	0.15319 (15)	0.17994 (18)	0.0565 (6)
H3	0.0066	0.0875	0.1998	0.068*
C4	−0.1974 (5)	0.18928 (16)	0.12612 (19)	0.0561 (6)
H4	−0.3265	0.1484	0.1086	0.067*
C5	−0.2003 (4)	0.28722 (15)	0.09855 (18)	0.0516 (5)
H5	−0.332	0.3138	0.0626	0.062*
C6	−0.0002 (4)	0.45146 (14)	0.09262 (15)	0.0459 (5)
C7	0.2509 (5)	0.59775 (15)	0.07192 (18)	0.0592 (6)
H7A	0.3618	0.629	0.1209	0.071*
H7B	0.0973	0.6325	0.0754	0.071*
C8	0.3520 (5)	0.60631 (17)	−0.03806 (19)	0.0595 (6)
H8A	0.3569	0.6751	−0.0581	0.071*
H8B	0.5171	0.5816	−0.0387	0.071*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O1	0.0545 (10)	0.0624 (10)	0.0817 (12)	0.0089 (8)	−0.0073 (9)	0.0174 (9)
O2	0.0556 (9)	0.0472 (7)	0.0555 (8)	0.0094 (7)	0.0037 (7)	0.0021 (6)
O3	0.0751 (12)	0.0563 (9)	0.0800 (12)	0.0189 (9)	0.0063 (10)	0.0087 (9)
O4	0.0799 (13)	0.0921 (13)	0.0672 (11)	−0.0228 (11)	−0.0137 (10)	0.0037 (10)
N1	0.0505 (10)	0.0471 (9)	0.0550 (10)	−0.0004 (8)	−0.0099 (9)	0.0039 (8)
N2	0.0585 (12)	0.0429 (8)	0.0581 (11)	−0.0035 (8)	−0.0129 (9)	0.0069 (8)
N3	0.0538 (11)	0.0526 (10)	0.0533 (11)	0.0014 (9)	0.0050 (9)	0.0093 (8)
C1	0.0447 (11)	0.0457 (10)	0.0385 (10)	0.0022 (9)	0.0016 (9)	−0.0010 (7)
C2	0.0584 (13)	0.0492 (11)	0.0633 (14)	0.0021 (10)	−0.0085 (12)	0.0074 (10)
C3	0.0685 (15)	0.0433 (10)	0.0577 (13)	−0.0026 (11)	0.0050 (12)	0.0021 (9)
C4	0.0574 (13)	0.0521 (12)	0.0588 (12)	−0.0105 (11)	0.0019 (11)	−0.0068 (10)
C5	0.0455 (11)	0.0559 (12)	0.0534 (12)	−0.0002 (9)	−0.0029 (10)	−0.0011 (9)
C6	0.0491 (12)	0.0459 (9)	0.0428 (10)	0.0022 (9)	−0.0026 (9)	0.0003 (8)
C7	0.0773 (17)	0.0433 (10)	0.0570 (13)	−0.0099 (11)	−0.0131 (12)	0.0011 (9)
C8	0.0519 (13)	0.0536 (12)	0.0728 (16)	−0.0090 (10)	−0.0059 (12)	0.0097 (11)

Geometric parameters (Å, °)

O1—C6	1.225 (3)	C2—C3	1.374 (3)
O2—N3	1.385 (3)	C2—H2	0.93
O2—C8	1.445 (3)	C3—C4	1.374 (4)
O3—N3	1.200 (2)	C3—H3	0.93
O4—N3	1.197 (3)	C4—C5	1.378 (3)
N1—C1	1.330 (3)	C4—H4	0.93
N1—C2	1.339 (3)	C5—H5	0.93
N2—C6	1.337 (3)	C7—C8	1.506 (3)
N2—C7	1.447 (3)	C7—H7A	0.97
N2—H	0.86	C7—H7B	0.97
C1—C5	1.378 (3)	C8—H8A	0.97
C1—C6	1.508 (3)	C8—H8B	0.97
N3—O2—C8	115.41 (16)	C5—C4—H4	120.6
C1—N1—C2	116.73 (19)	C4—C5—C1	118.7 (2)
C6—N2—C7	122.2 (2)	C4—C5—H5	120.7
C6—N2—H	118.9	C1—C5—H5	120.7
C7—N2—H	118.9	O1—C6—N2	123.66 (18)
O4—N3—O3	129.1 (2)	O1—C6—C1	121.03 (18)
O4—N3—O2	112.47 (19)	N2—C6—C1	115.30 (18)
O3—N3—O2	118.4 (2)	N2—C7—C8	112.60 (19)
N1—C1—C5	123.50 (19)	N2—C7—H7A	109.1
N1—C1—C6	116.99 (18)	C8—C7—H7A	109.1
C5—C1—C6	119.49 (19)	N2—C7—H7B	109.1
N1—C2—C3	123.7 (2)	C8—C7—H7B	109.1
N1—C2—H2	118.1	H7A—C7—H7B	107.8
C3—C2—H2	118.1	O2—C8—C7	112.49 (19)
C4—C3—C2	118.6 (2)	O2—C8—H8A	109.1
C4—C3—H3	120.7	C7—C8—H8A	109.1
C2—C3—H3	120.7	O2—C8—H8B	109.1
C3—C4—C5	118.8 (2)	C7—C8—H8B	109.1
C3—C4—H4	120.6	H8A—C8—H8B	107.8
C8—O2—N3—O4	−175.41 (19)	C7—N2—C6—O1	−1.7 (3)
C8—O2—N3—O3	5.3 (3)	C7—N2—C6—C1	177.33 (19)
C2—N1—C1—C5	−0.5 (3)	N1—C1—C6—O1	−170.5 (2)
C2—N1—C1—C6	−178.70 (19)	C5—C1—C6—O1	11.2 (3)
C1—N1—C2—C3	0.9 (3)	N1—C1—C6—N2	10.4 (3)
N1—C2—C3—C4	−0.5 (4)	C5—C1—C6—N2	−167.8 (2)
C2—C3—C4—C5	−0.3 (3)	C6—N2—C7—C8	−94.3 (3)
C3—C4—C5—C1	0.6 (3)	N3—O2—C8—C7	76.5 (2)
N1—C1—C5—C4	−0.2 (3)	N2—C7—C8—O2	52.7 (3)
C6—C1—C5—C4	177.95 (19)

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H···N1	0.86	2.31	2.692 (3)	107.
C8—H8B···O1i	0.97	2.39	3.239 (3)	145.

Symmetry codes: (i) x+1, y, z.