Ethyl 4-oxo-1,4-di­hydro­pyridine-3-carboxyl­ate

Gao, J.; Long, S.

doi:10.1107/S2414314621005551

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 6| Part 6| June 2021| x210555

https://doi.org/10.1107/S2414314621005551

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Ethyl 4-oxo-1,4-dihydropyridine-3-carboxylate

Jun Gao ^a and Sihui Long ^a ^*

^aSchool of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, Hubei 430205, People's Republic of China
^*Correspondence e-mail: longsihui@yahoo.com

Edited by S. Parkin, University of Kentucky, USA (Received 20 May 2021; accepted 30 May 2021; online 4 June 2021)

The title compound, C₈H₉NO₃, likely generated through hydrolysis and esterification of 3′-carboxy-3-methyl-(1,4′-bipyridin)-1-ium chloride by ethanol, which contained water, has a nearly planar conformation. The crystal structure is sustained by one-dimensional chains along the a-axis direction based on bifurcated N—H⋯(O,O) hydrogen bonds between the NH group of the 4-oxo-1,4-dihydropyridine ring and the two carbonyl O atoms.

Keywords: crystal structure; bifurcated hydrogen bonds.

CCDC reference: 2086773

Structure description

The title compound (Fig. 1) was first synthesized by Ross (1966 ). It may be a potential inhibitor of the glycolytic process by which many cancer cells derive an appreciable proportion of their energy requirement (Ross, 1966). Balogh et al. (1980 ) demonstrated that the compound exhibited antimicrobial activity. In our study, the compound was obtained serendipitously during an attempt to grow single crystals of 3′-carboxy-3-methyl-(1,4′-bipyridin)-1-ium chloride in ethanol. The compound has a nearly planar conformation, as evidenced by the dihedral angle between the 4-oxo-1,4-dihydropyridine ring and the ester moiety [2.3 (2)°]. In the crystal, the molecules form chains propagating parallel to the a-axis through bifurcated hydrogen bonds between the NH group and the two carbonyl oxygen atoms. The hydrogen bond parameters for NH⋯O=C (ring) are: 1.96 (2) Å for bond length, and 134.9 (17)° for the bond angle. The corresponding parameters for NH⋯O=C (ester) are 2.15 (2) Å and 139.6 (17)° (Fig. 2, Table 1).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O1ⁱ	0.90 (2)	1.96 (2)	2.6771 (15)	134.9 (17)
N1—H1⋯O2ⁱ	0.90 (2)	2.15 (2)	2.9002 (17)	139.6 (17)
Symmetry code: (i) .

Figure 1
The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level.

Figure 2
(a) Packing of the molecules in the title compound viewed along the a axis; (b) Chain sustained by bifurcated hydrogen bonds between the NH group and two carbonyl O atoms (blue dashed lines).

Synthesis and crystallization

The title compound was obtained during an attempt to grow single crystals of 3′-carboxy-3-methyl-(1,4′-bipyridin)-1-ium chloride by slow evaporation of an ethanolic solution. 3′-Carboxy-3-methyl-(1,4′-bipyridin)-1-ium chloride was dissolved in bulk ethanol at 343 K, and then the resulting solution was left in a refrigerator. Colorless plate-shaped crystals (Fig. 3) were harvested after several days. Structure determination by single-crystal X-ray diffraction revealed the identity of the crystals to be ethyl 4-oxo-1,4-dihydropyridine-3-carboxylate. Hydrolysis and esterification of 3′-carboxy-3-methyl-[1,4′-bipyridin]-1-ium chloride may have led to the title compound (Fig. 4).

Figure 3
A representative crystal of I.

Figure 4
Reaction scheme.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₈H₉NO₃
M_r	167.16
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	6.4973 (2), 11.5323 (5), 11.2908 (5)
β (°)	91.500 (4)
V (Å³)	845.72 (6)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	0.86
Crystal size (mm)	0.07 × 0.03 × 0.02

Data collection
Diffractometer	Rigaku Oxford Diffraction, Synergy Custom system, HyPix
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2020 )
T_min, T_max	0.311, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	5379, 1693, 1456
R_int	0.022
(sin θ/λ)_max (Å⁻¹)	0.633

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.046, 0.129, 1.11
No. of reflections	1693
No. of parameters	114
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.21, −0.22
Computer programs: CrysAlis PRO (Rigaku OD, 2020), SHELXS (Sheldrick, 2008 ), SHELXL (Sheldrick, 2015 ), Mercury (Macrae et al., 2020 ) and OLEX2 (Dolomanov et al., 2009 ).

Structural data

CCDC reference: 2086773

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2414314621005551/pk4034sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314621005551/pk4034Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314621005551/pk4034Isup3.cml

checkCIF report

Computing details top

Data collection: CrysAlis PRO (Rigaku OD, 2020); cell refinement: CrysAlis PRO (Rigaku OD, 2020); data reduction: CrysAlis PRO (Rigaku OD, 2020); program(s) used to solve structure: SHELXS (Sheldrick, 2008); program(s) used to refine structure: SHELXL (Sheldrick, 2015); molecular graphics: Mercury (Macrae et al., 2020); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Ethyl 4-oxo-1,4-dihydropyridine-3-carboxylate top

Crystal data top

C₈H₉NO₃	F(000) = 352
M_r = 167.16	D_x = 1.313 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54184 Å
a = 6.4973 (2) Å	Cell parameters from 3630 reflections
b = 11.5323 (5) Å	θ = 6.8–76.4°
c = 11.2908 (5) Å	µ = 0.86 mm⁻¹
β = 91.500 (4)°	T = 293 K
V = 845.72 (6) Å³	Needle, clear light colourless
Z = 4	0.07 × 0.03 × 0.02 mm

Data collection top

Rigaku Oxford Diffraction, Synergy Custom system, HyPix diffractometer	1693 independent reflections
Radiation source: Rotating-anode X-ray tube, Rigaku (Cu) X-ray Source	1456 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.022
Detector resolution: 10.0000 pixels mm^-1	θ_max = 77.4°, θ_min = 6.8°
ω scans	h = −8→7
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2020)	k = −14→5
T_min = 0.311, T_max = 1.000	l = −13→14
5379 measured reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.046	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.129	w = 1/[σ²(F_o²) + (0.0674P)² + 0.1472P] where P = (F_o² + 2F_c²)/3
S = 1.11	(Δ/σ)_max < 0.001
1693 reflections	Δρ_max = 0.21 e Å⁻³
114 parameters	Δρ_min = −0.22 e Å⁻³
0 restraints

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.52166 (14)	0.40585 (10)	0.20366 (11)	0.0600 (4)
O2	0.57531 (15)	0.62403 (10)	0.09977 (11)	0.0584 (4)
O3	0.28325 (16)	0.71651 (9)	0.05152 (11)	0.0555 (3)
N1	−0.08871 (17)	0.47182 (12)	0.17157 (11)	0.0471 (3)
C1	0.25305 (18)	0.53513 (12)	0.14051 (12)	0.0388 (3)
C2	0.33512 (19)	0.42840 (13)	0.19022 (13)	0.0436 (4)
C3	0.1821 (2)	0.34638 (14)	0.22568 (15)	0.0538 (4)
H3	0.224295	0.274979	0.255937	0.065*
C4	−0.0203 (2)	0.36993 (15)	0.21635 (15)	0.0517 (4)
H4	−0.114786	0.315080	0.241186	0.062*
C5	0.04315 (19)	0.55121 (13)	0.13385 (13)	0.0421 (3)
H5	−0.008399	0.619967	0.101877	0.051*
C6	0.3901 (2)	0.62675 (12)	0.09660 (13)	0.0421 (3)
C7	0.3996 (3)	0.81144 (16)	0.00264 (19)	0.0663 (5)
H7A	0.470155	0.786241	−0.067519	0.080*
H7B	0.501453	0.839160	0.060290	0.080*
C8	0.2495 (4)	0.90531 (19)	−0.0281 (2)	0.0899 (7)
H8A	0.317924	0.965688	−0.070384	0.135*
H8B	0.194250	0.936516	0.043203	0.135*
H8C	0.139659	0.874119	−0.076909	0.135*
H1	−0.224 (3)	0.4880 (17)	0.1645 (17)	0.071 (6)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0234 (5)	0.0609 (7)	0.0956 (9)	0.0027 (4)	0.0007 (5)	0.0191 (6)
O2	0.0296 (5)	0.0541 (7)	0.0918 (9)	−0.0041 (4)	0.0038 (5)	0.0110 (6)
O3	0.0411 (6)	0.0456 (6)	0.0799 (8)	0.0017 (4)	0.0029 (5)	0.0130 (5)
N1	0.0211 (5)	0.0596 (8)	0.0608 (7)	−0.0002 (5)	0.0018 (5)	0.0002 (6)
C1	0.0255 (6)	0.0448 (8)	0.0460 (7)	0.0000 (5)	0.0022 (5)	−0.0028 (6)
C2	0.0241 (6)	0.0512 (8)	0.0555 (8)	−0.0001 (5)	0.0018 (5)	0.0018 (6)
C3	0.0321 (7)	0.0519 (9)	0.0774 (11)	−0.0012 (6)	0.0020 (7)	0.0147 (8)
C4	0.0288 (7)	0.0588 (9)	0.0678 (10)	−0.0075 (6)	0.0045 (6)	0.0075 (7)
C5	0.0279 (6)	0.0467 (8)	0.0517 (8)	0.0028 (5)	0.0006 (5)	−0.0024 (6)
C6	0.0307 (6)	0.0423 (7)	0.0532 (8)	0.0010 (5)	0.0016 (5)	−0.0022 (6)
C7	0.0674 (11)	0.0478 (9)	0.0842 (12)	−0.0088 (8)	0.0079 (9)	0.0110 (8)
C8	0.1063 (19)	0.0616 (13)	0.1014 (17)	0.0040 (11)	−0.0053 (14)	0.0288 (11)

Geometric parameters (Å, º) top

O1—C2	1.2450 (16)	C1—C2	1.449 (2)
O2—C6	1.2032 (16)	C1—C5	1.3765 (17)
O3—C6	1.3395 (17)	C1—C6	1.4760 (19)
O3—C7	1.448 (2)	C2—C3	1.437 (2)
N1—C4	1.350 (2)	C3—C4	1.344 (2)
N1—C5	1.3314 (19)	C7—C8	1.492 (3)

C6—O3—C7	117.28 (12)	C4—C3—C2	121.85 (15)
C5—N1—C4	120.66 (12)	C3—C4—N1	121.15 (14)
C2—C1—C6	121.28 (11)	N1—C5—C1	122.33 (13)
C5—C1—C2	119.33 (12)	O2—C6—O3	122.66 (13)
C5—C1—C6	119.40 (12)	O2—C6—C1	125.66 (13)
O1—C2—C1	124.89 (13)	O3—C6—C1	111.68 (11)
O1—C2—C3	120.46 (14)	O3—C7—C8	107.00 (16)
C3—C2—C1	114.65 (12)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1ⁱ	0.90 (2)	1.96 (2)	2.6771 (15)	134.9 (17)
N1—H1···O2ⁱ	0.90 (2)	2.15 (2)	2.9002 (17)	139.6 (17)

Symmetry code: (i) x−1, y, z.

Funding information

The authors thank the Natural Science Foundation of Hubei Province for financial support (2014CFB787).

References

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