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

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[De Clercq, E. (2005). J. Med. Chem. 48, 1297-1313.]); Dollé et al. (1995[Dollé, V., Fan, E., Nguyen, C. H., Aubertin, A.-M., Kirn, A., Andreola, M. L., Jamieson, G., Tarrago-Litvak, L. & Bisagni, E. (1995). J. Med. Chem. 38, 4679-4686.]); Medina-Franco et al. (2007[Medina-Franco, J. L., Martinez-Mayorga, K., Juárez-Gordiano, C. & Castillo, R. (2007). ChemMedChem, 2, 1141-1147.]).

[Scheme 1]

Experimental

Crystal data
  • C6H7NO2

  • Mr = 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[Siemens (1996). XSCANS. Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA.]) Tmin = 0.216, Tmax = 0.259

  • 2445 measured reflections

  • 1701 independent reflections

  • 1269 reflections with I > 2σ(I)

  • Rint = 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

  • Δρmax = 0.32 e Å−3

  • Δρmin = −0.25 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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[Siemens (1996). XSCANS. Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA.]); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXTL.

Supporting information


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.

Refinement top

All H atoms were positioned geometrically and refined using a riding model, with C—H = 0.93 Å for aryl and 0.96 Å for methyl H atoms. Isotropic thermal parameters were fixed to Uiso(H) = 1.2 Ueq(C) for aryl and Uiso(H) = 1.5 Ueq(C) for methyl H atoms.

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
[Figure 1] Fig. 1. Molecular structure of the title compound with displacement ellipsoids drawn at the 30% probability level.
[Figure 2] 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
C6H7NO2F(000) = 264
Mr = 125.13Dx = 1.430 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 51 reflections
a = 4.7082 (5) Åθ = 6.6–12.3°
b = 12.2988 (8) ŵ = 0.11 mm1
c = 10.0418 (7) ÅT = 298 K
β = 91.303 (7)°Prismatic, colorless
V = 581.32 (8) Å30.65 × 0.20 × 0.18 mm
Z = 4
Data collection top
Bruker P4
diffractometer
1269 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.026
Graphite monochromatorθmax = 30.0°, θmin = 2.6°
2θ/ω scansh = 16
Absorption correction: ψ scan
(XSCANS; Siemens, 1996)
k = 117
Tmin = 0.216, Tmax = 0.259l = 1414
2445 measured reflections3 standard reflections every 97 reflections
1701 independent reflections intensity decay: 9.4%
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.050Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.160H-atom parameters constrained
S = 1.06 w = 1/[σ2(Fo2) + (0.1P)2]
where P = (Fo2 + 2Fc2)/3
1701 reflections(Δ/σ)max < 0.001
82 parametersΔρmax = 0.32 e Å3
0 restraintsΔρmin = 0.25 e Å3
Crystal data top
C6H7NO2V = 581.32 (8) Å3
Mr = 125.13Z = 4
Monoclinic, P21/nMo Kα radiation
a = 4.7082 (5) ŵ = 0.11 mm1
b = 12.2988 (8) ÅT = 298 K
c = 10.0418 (7) Å0.65 × 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)
Rint = 0.026
Tmin = 0.216, Tmax = 0.2593 standard reflections every 97 reflections
2445 measured reflections intensity decay: 9.4%
1701 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0500 restraints
wR(F2) = 0.160H-atom parameters constrained
S = 1.06Δρmax = 0.32 e Å3
1701 reflectionsΔρmin = 0.25 e Å3
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
xyzUiso*/Ueq
O10.7844 (3)0.91089 (9)0.60053 (9)0.0364 (3)
O20.2045 (2)0.68616 (10)0.32761 (10)0.0396 (3)
H2B0.22920.65560.25620.059*
N10.7786 (3)0.93124 (10)0.37596 (11)0.0301 (3)
H1A0.90490.98130.38580.036*
C10.6811 (3)0.88072 (12)0.48782 (12)0.0288 (3)
C20.4786 (3)0.79830 (13)0.46911 (13)0.0326 (3)
H2A0.40260.76380.54260.039*
C30.3912 (3)0.76793 (12)0.34229 (13)0.0303 (3)
C40.4958 (3)0.82420 (12)0.23072 (14)0.0321 (3)
H4A0.43530.80530.14500.038*
C50.6858 (3)0.90624 (12)0.25012 (13)0.0293 (3)
C60.8049 (4)0.97389 (15)0.14088 (15)0.0403 (4)
H6D0.72670.95010.05670.060*
H6A1.00780.96620.14110.060*
H6B0.75661.04880.15480.060*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0491 (7)0.0370 (6)0.0227 (5)0.0064 (5)0.0062 (4)0.0009 (4)
O20.0483 (7)0.0407 (6)0.0297 (5)0.0133 (5)0.0024 (5)0.0057 (4)
N10.0360 (6)0.0315 (6)0.0227 (5)0.0037 (5)0.0032 (5)0.0022 (4)
C10.0352 (7)0.0297 (7)0.0214 (6)0.0034 (6)0.0013 (5)0.0010 (5)
C20.0399 (8)0.0340 (7)0.0238 (6)0.0026 (6)0.0015 (5)0.0009 (5)
C30.0324 (7)0.0311 (7)0.0273 (6)0.0002 (6)0.0000 (5)0.0014 (5)
C40.0380 (8)0.0357 (8)0.0224 (6)0.0007 (6)0.0021 (5)0.0023 (5)
C50.0341 (7)0.0319 (7)0.0218 (6)0.0027 (6)0.0004 (5)0.0016 (5)
C60.0534 (10)0.0420 (9)0.0255 (6)0.0049 (8)0.0007 (6)0.0068 (6)
Geometric parameters (Å, º) top
O1—C11.2768 (16)C2—H2A0.9300
O2—C31.3418 (18)C3—C41.415 (2)
O2—H2B0.8200C4—C51.359 (2)
N1—C51.3629 (17)C4—H4A0.9300
N1—C11.3719 (17)C5—C61.496 (2)
N1—H1A0.8600C6—H6D0.9600
C1—C21.401 (2)C6—H6A0.9600
C2—C31.3809 (19)C6—H6B0.9600
C3—O2—H2B109.5C5—C4—C3119.30 (13)
C5—N1—C1123.42 (13)C5—C4—H4A120.4
C5—N1—H1A118.3C3—C4—H4A120.4
C1—N1—H1A118.3C4—C5—N1119.76 (13)
O1—C1—N1117.79 (14)C4—C5—C6124.34 (13)
O1—C1—C2124.99 (13)N1—C5—C6115.90 (14)
N1—C1—C2117.21 (12)C5—C6—H6D109.5
C3—C2—C1120.46 (13)C5—C6—H6A109.5
C3—C2—H2A119.8H6D—C6—H6A109.5
C1—C2—H2A119.8C5—C6—H6B109.5
O2—C3—C2119.01 (13)H6D—C6—H6B109.5
O2—C3—C4121.24 (12)H6A—C6—H6B109.5
C2—C3—C4119.74 (14)
C5—N1—C1—O1179.84 (14)O2—C3—C4—C5179.71 (13)
C5—N1—C1—C21.0 (2)C2—C3—C4—C51.3 (2)
O1—C1—C2—C3176.62 (15)C3—C4—C5—N11.8 (2)
N1—C1—C2—C32.2 (2)C3—C4—C5—C6178.05 (15)
C1—C2—C3—O2177.69 (13)C1—N1—C5—C43.0 (2)
C1—C2—C3—C43.3 (2)C1—N1—C5—C6176.88 (14)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···O1i0.861.982.835 (2)175
O2—H2B···O1ii0.821.792.609 (2)180
Symmetry codes: (i) x+2, y+2, z+1; (ii) x1/2, y+3/2, z1/2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···O1i0.861.982.835 (2)175.4
O2—H2B···O1ii0.821.792.609 (2)179.8
Symmetry codes: (i) x+2, y+2, z+1; (ii) x1/2, y+3/2, z1/2.
 

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

First citationDe Clercq, E. (2005). J. Med. Chem. 48, 1297–1313.  Web of Science CrossRef PubMed CAS
First citationDollé, V., Fan, E., Nguyen, C. H., Aubertin, A.-M., Kirn, A., Andreola, M. L., Jamieson, G., Tarrago-Litvak, L. & Bisagni, E. (1995). J. Med. Chem. 38, 4679–4686.  CAS PubMed Web of Science
First citationMedina-Franco, J. L., Martinez-Mayorga, K., Juárez-Gordiano, C. & Castillo, R. (2007). ChemMedChem, 2, 1141–1147.  PubMed CAS
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationSiemens (1996). XSCANS. Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA.

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ISSN: 2056-9890
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