4-Hy­droxy-6-methyl­pyridin-2(1H)-one

Reyes, H.; Aguirre, G.; Chávez, D.

doi:10.1107/S1600536813024240

organic compounds

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ISSN: 2056-9890

Volume 69| Part 10| October 2013| Page o1534

doi:10.1107/S1600536813024240

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4-Hydroxy-6-methylpyridin-2(1H)-one

Héctor Reyes,^a Gerardo Aguirre ^a and Daniel Chávez ^a ^*

^aCentro de Graduados e Investigación del Instituto Tecnológico de Tijuana, Apdo. Postal 1166, 22500, Tijuana, B.C., Mexico
^*Correspondence e-mail: dchavez@tectijuana.mx

(Received 15 July 2013; accepted 29 August 2013; online 12 September 2013)

In the crystal structure of the title compound, C₆H₇NO₂, N—H⋯O and O—H⋯O hydrogen bonds link the molecules, forming a zigzag array along [001] and a layer structure parallel to the ab plane.

Related literature

For the potential of related compounds in anti-HIV treatment, see: De Clercq (2005 ); Dollé et al. (1995 ); Medina-Franco et al. (2007 ).

Experimental

Crystal data

C₆H₇NO₂
M_r = 125.13
Monoclinic, P 2₁ /n
a = 4.7082 (5) Å
b = 12.2988 (8) Å
c = 10.0418 (7) Å
β = 91.303 (7)°
V = 581.32 (8) Å³
Z = 4
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 298 K
0.65 × 0.20 × 0.18 mm

Data collection

Bruker P4 diffractometer
Absorption correction: ψ scan (XSCANS; Siemens, 1996 ) T_min = 0.216, T_max = 0.259
2445 measured reflections
1701 independent reflections
1269 reflections with I > 2σ(I)
R_int = 0.026
3 standard reflections every 97 reflections intensity decay: 9.4%

Refinement

R[F² > 2σ(F²)] = 0.050
wR(F²) = 0.160
S = 1.06
1701 reflections
82 parameters
H-atom parameters constrained
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯O1ⁱ	0.86	1.98	2.835 (2)	175
O2—H2B⋯O1ⁱⁱ	0.82	1.79	2.609 (2)	180
Symmetry codes: (i) -x+2, -y+2, -z+1; (ii) $[x-{\script{1\over 2}}, -y+{\script{3\over 2}}, z-{\script{1\over 2}}]$ .

Data collection: XSCANS (Siemens, 1996); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablock I. DOI: 10.1107/S1600536813024240/im2437sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536813024240/im2437Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536813024240/im2437Isup3.cml

checkCIF report

Comment top

The acquired immunodeficiency syndrome (AIDS) is a disease of people who are infected with human immunodeficiency virus (HIV). The use of drugs to fight HIV are called antiretroviral drugs and are characterized by inhibiting essential enzymes for virus replication, such as reverse transcriptase (De Clercq, 2005).

Pyridin-2 (1H)-one hybrids are a kind of compounds that inhibit the reverse transcription process and have been shown, by molecular modeling, their good performance as non-nucleoside inhibitors of HIV-1 reverse transcriptase. Recent design of the pyridin-2(1H)-one hybrids has generated active molecules against wild type and mutant strains of HIV, as in the case of second-generation hybrid pyridinone-UC781 (Medina-Franco et al.., 2007). In this work, and as part of our ongoing research, we have synthesized pyridin-2 (1H)-one hybrids (Dollé et al., 1995) of second generation with different polar groups at C-3 and also with different olefinic groups at C-4, similar to pyridinone-UC781. The compound 4-hydroxy-6-methylpyridin-2 (1H)-one is an intermediate in the synthesis of second-generation hybrids with a polar nitro group at C-3.

We have synthesized the title compound (I) and report its crystal structure here (Fig. 1). In the crystal structure adjacent networks are linked together via intermolecular hydrogen bond interactions (table 1) [N1—H1A···O1ⁱ (2.8349 Å), symmetry codes: (i) –x + 2, –y + 2, - z + 1] and [O2—H2B···O1ⁱⁱ (2.6086 Å), symmetry codes: (ii) x – 1/2, - y + 3/2, z – 1/2] to form a zigzag array along the [001] direction and molecules are forming a layer structure parallel to the ab plane (Fig. 2).

Related literature top

For the potential of related compounds in anti-HIV treatment, see: De Clercq (2005); Dollé et al. (1995); Medina-Franco et al. (2007).

Experimental top

The synthesis of 4-hydroxy-6-methylpyridin-2(1H)-one includes reagents and reagent grade solvents, which were used without further purification. In a round bottom flask of 500 ml equipped with a magnetic stirrer was placed 10.0 g of ethyl 4-hydroxy-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylate (0.05 mol) in 350 ml of hydrochloric acid 1 N. The mixture was stirred at reflux for 72 h. 4-Hydroxy-6-methylpyridin-2(1H)-one precipitated as a white solid (6.2 g, 99%, m. p. 273–275 °C, for analytical data, see _exptl_special_details section). Crystals of the title compound suitable for Xray diffraction were obtained by dissolving 100 mg of 4-hydroxy-6-methyl-pyridine-2 (1H)-one in 10 ml of methanol-diethylether (1:1, v / v) and placing the solution in a glass vial. The solution was allowed to stand at room temperature for 7 days and the crystals formed were filtered.

Computing details top

Data collection: XSCANS (Siemens, 1996); cell refinement: XSCANS (Siemens, 1996); data reduction: XSCANS (Siemens, 1996); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

	Fig. 1. Molecular structure of the title compound with displacement ellipsoids drawn at the 30% probability level.
	Fig. 2. Hydrogen-bond (indicated as dashed lines) network of the title compound leading to a two dimensional network along the ab plane.

4-Hydroxy-6-methylpyridin-2(1H)-one top

Crystal data top

C₆H₇NO₂	F(000) = 264
M_r = 125.13	D_x = 1.430 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 51 reflections
a = 4.7082 (5) Å	θ = 6.6–12.3°
b = 12.2988 (8) Å	µ = 0.11 mm⁻¹
c = 10.0418 (7) Å	T = 298 K
β = 91.303 (7)°	Prismatic, colorless
V = 581.32 (8) Å³	0.65 × 0.20 × 0.18 mm
Z = 4

Data collection top

Bruker P4 diffractometer	1269 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.026
Graphite monochromator	θ_max = 30.0°, θ_min = 2.6°
2θ/ω scans	h = −1→6
Absorption correction: ψ scan (XSCANS; Siemens, 1996)	k = −1→17
T_min = 0.216, T_max = 0.259	l = −14→14
2445 measured reflections	3 standard reflections every 97 reflections
1701 independent reflections	intensity decay: 9.4%

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)] = 0.050	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.160	H-atom parameters constrained
S = 1.06	w = 1/[σ²(F_o²) + (0.1P)²] where P = (F_o² + 2F_c²)/3
1701 reflections	(Δ/σ)_max < 0.001
82 parameters	Δρ_max = 0.32 e Å⁻³
0 restraints	Δρ_min = −0.25 e Å⁻³

Crystal data top

C₆H₇NO₂	V = 581.32 (8) Å³
M_r = 125.13	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 4.7082 (5) Å	µ = 0.11 mm⁻¹
b = 12.2988 (8) Å	T = 298 K
c = 10.0418 (7) Å	0.65 × 0.20 × 0.18 mm
β = 91.303 (7)°

Data collection top

Bruker P4 diffractometer	1269 reflections with I > 2σ(I)
Absorption correction: ψ scan (XSCANS; Siemens, 1996)	R_int = 0.026
T_min = 0.216, T_max = 0.259	3 standard reflections every 97 reflections
2445 measured reflections	intensity decay: 9.4%
1701 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.050	0 restraints
wR(F²) = 0.160	H-atom parameters constrained
S = 1.06	Δρ_max = 0.32 e Å⁻³
1701 reflections	Δρ_min = −0.25 e Å⁻³
82 parameters

Special details top

Experimental. IR: 3296, 3094, 2891, 1640 cm^-1. 1Ĥ NMR (CDCl~3~): δ 10.99 (s, NH-1), 10.40 (s, OH), 5.59 (s, H-3), 5.34 (s, H-5) 2.07 (s, 3H, CH~3~—C-6). ^13Ĉ NMR (CDCl~3~): δ 167.6, 164.8, 145.9, 98.2, 95.7, 18.5. MS m/e (int. rel): [M]^+^ 125 (100), 97 (16).

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 (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.7844 (3)	0.91089 (9)	0.60053 (9)	0.0364 (3)
O2	0.2045 (2)	0.68616 (10)	0.32761 (10)	0.0396 (3)
H2B	0.2292	0.6556	0.2562	0.059*
N1	0.7786 (3)	0.93124 (10)	0.37596 (11)	0.0301 (3)
H1A	0.9049	0.9813	0.3858	0.036*
C1	0.6811 (3)	0.88072 (12)	0.48782 (12)	0.0288 (3)
C2	0.4786 (3)	0.79830 (13)	0.46911 (13)	0.0326 (3)
H2A	0.4026	0.7638	0.5426	0.039*
C3	0.3912 (3)	0.76793 (12)	0.34229 (13)	0.0303 (3)
C4	0.4958 (3)	0.82420 (12)	0.23072 (14)	0.0321 (3)
H4A	0.4353	0.8053	0.1450	0.038*
C5	0.6858 (3)	0.90624 (12)	0.25012 (13)	0.0293 (3)
C6	0.8049 (4)	0.97389 (15)	0.14088 (15)	0.0403 (4)
H6D	0.7267	0.9501	0.0567	0.060*
H6A	1.0078	0.9662	0.1411	0.060*
H6B	0.7566	1.0488	0.1548	0.060*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0491 (7)	0.0370 (6)	0.0227 (5)	−0.0064 (5)	−0.0062 (4)	0.0009 (4)
O2	0.0483 (7)	0.0407 (6)	0.0297 (5)	−0.0133 (5)	0.0024 (5)	−0.0057 (4)
N1	0.0360 (6)	0.0315 (6)	0.0227 (5)	−0.0037 (5)	−0.0032 (5)	0.0022 (4)
C1	0.0352 (7)	0.0297 (7)	0.0214 (6)	0.0034 (6)	−0.0013 (5)	0.0010 (5)
C2	0.0399 (8)	0.0340 (7)	0.0238 (6)	−0.0026 (6)	0.0015 (5)	0.0009 (5)
C3	0.0324 (7)	0.0311 (7)	0.0273 (6)	0.0002 (6)	0.0000 (5)	−0.0014 (5)
C4	0.0380 (8)	0.0357 (8)	0.0224 (6)	0.0007 (6)	−0.0021 (5)	−0.0023 (5)
C5	0.0341 (7)	0.0319 (7)	0.0218 (6)	0.0027 (6)	−0.0004 (5)	0.0016 (5)
C6	0.0534 (10)	0.0420 (9)	0.0255 (6)	−0.0049 (8)	0.0007 (6)	0.0068 (6)

Geometric parameters (Å, º) top

O1—C1	1.2768 (16)	C2—H2A	0.9300
O2—C3	1.3418 (18)	C3—C4	1.415 (2)
O2—H2B	0.8200	C4—C5	1.359 (2)
N1—C5	1.3629 (17)	C4—H4A	0.9300
N1—C1	1.3719 (17)	C5—C6	1.496 (2)
N1—H1A	0.8600	C6—H6D	0.9600
C1—C2	1.401 (2)	C6—H6A	0.9600
C2—C3	1.3809 (19)	C6—H6B	0.9600

C3—O2—H2B	109.5	C5—C4—C3	119.30 (13)
C5—N1—C1	123.42 (13)	C5—C4—H4A	120.4
C5—N1—H1A	118.3	C3—C4—H4A	120.4
C1—N1—H1A	118.3	C4—C5—N1	119.76 (13)
O1—C1—N1	117.79 (14)	C4—C5—C6	124.34 (13)
O1—C1—C2	124.99 (13)	N1—C5—C6	115.90 (14)
N1—C1—C2	117.21 (12)	C5—C6—H6D	109.5
C3—C2—C1	120.46 (13)	C5—C6—H6A	109.5
C3—C2—H2A	119.8	H6D—C6—H6A	109.5
C1—C2—H2A	119.8	C5—C6—H6B	109.5
O2—C3—C2	119.01 (13)	H6D—C6—H6B	109.5
O2—C3—C4	121.24 (12)	H6A—C6—H6B	109.5
C2—C3—C4	119.74 (14)

C5—N1—C1—O1	179.84 (14)	O2—C3—C4—C5	−179.71 (13)
C5—N1—C1—C2	1.0 (2)	C2—C3—C4—C5	1.3 (2)
O1—C1—C2—C3	−176.62 (15)	C3—C4—C5—N1	1.8 (2)
N1—C1—C2—C3	2.2 (2)	C3—C4—C5—C6	−178.05 (15)
C1—C2—C3—O2	177.69 (13)	C1—N1—C5—C4	−3.0 (2)
C1—C2—C3—C4	−3.3 (2)	C1—N1—C5—C6	176.88 (14)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O1ⁱ	0.86	1.98	2.835 (2)	175
O2—H2B···O1ⁱⁱ	0.82	1.79	2.609 (2)	180

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

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O1ⁱ	0.86	1.98	2.835 (2)	175.4
O2—H2B···O1ⁱⁱ	0.82	1.79	2.609 (2)	179.8

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

Acknowledgements

We gratefully acknowledge support for this project by the Dirección General de Educación Superior Tecnológica (DGEST grants 2535.09P and 3604.10-P).

References

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