2-Ethyl-3-hy­droxy-1-isopropyl-4-pyridone

Pule P Molokoane; M Schutte; G Steyl

doi:10.1107/S1600536812044091

. 2012 Oct 27;68(Pt 11):o3235–o3236. doi: 10.1107/S1600536812044091

2-Ethyl-3-hydroxy-1-isopropyl-4-pyridone

Pule P Molokoane ^a, M Schutte ^a,^*, G Steyl ^a

PMCID: PMC3515315 PMID: 23284535

Abstract

The title compound, C₁₀H₁₅NO₂, crystallized with three molecules in the asymmetric unit. These three molecules are quite similar except for slight differences in the torsion angles of the substituents on the ring. The isopropyl C—C—N—C torsion angles (towards the carbon next to the ethyl bound carbon), for example, are −150.63 (11), −126.77 (13) and −138.76 (11)° for molecules A, B and C, respectively, and the C—C—C—N torsion angles involving the ethyl C atoms are 102.90 (13), 87.81 (14) and 86.47 (13)°. The main difference between the three molecules lies in the way they are arranged in the solid-state structure. All three molecules form dimers that are connected through strong O—H⋯O hydrogen bonds with R ₂ ²(10) graph-set motifs. The symmetry of the dimers formed does however differ between molecules. Molecules B connect with each other to form inversion dimers. Molecules A and C, on the other hand, form dimers with local twofold symmetry, but the two molecules are crystallographically distinct. The B and C molecules are linked to themselves and to each other via C—H⋯O hydrogen bonds. This results in the formation of a three-dimensional network structure.

Related literature

For background on this type of ligand system, see: Fassihi et al. (2009 ▶); Weinberg (1994 ▶); Galanello, 2007 ▶); Scott et al. (2008 ▶). For similar structures, see: Xiao et al. (1992 ▶); Burgess et al. (1993 ▶); Hider et al. (1990 ▶); Dobbin et al. (1993 ▶); Brown et al. (1995 ▶).

Experimental

Crystal data

C₁₀H₁₅NO₂
M _r = 181.23
Orthorhombic,
a = 11.7408 (2) Å
b = 13.3554 (2) Å
c = 37.5523 (8) Å
V = 5888.32 (18) Å³
Z = 24
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 100 K
0.43 × 0.32 × 0.16 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.968, T _max = 0.986
66795 measured reflections
7343 independent reflections
5939 reflections with I > 2σ(I)
R _int = 0.041

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.111
S = 1.01
7343 reflections
373 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.31 e Å⁻³
Δρ_min = −0.28 e Å⁻³

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT-Plus (Bruker, 2008 ▶); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg & Putz, 2005 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Click here for additional data file.^{(27KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812044091/zl2508sup1.cif

e-68-o3235-sup1.cif^{(27KB, cif)}

Click here for additional data file.^{(352.2KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812044091/zl2508Isup2.hkl

e-68-o3235-Isup2.hkl^{(352.2KB, hkl)}

Click here for additional data file.^{(3.8KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536812044091/zl2508Isup3.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
O2A—H2A⋯O1C ⁱ	0.89 (2)	1.85 (2)	2.6503 (13)	149.9 (17)
O2B—H2B⋯O1B ⁱⁱ	0.882 (19)	1.859 (18)	2.6480 (13)	147.8 (17)
O2C—H2C⋯O1A ⁱⁱⁱ	0.869 (18)	1.796 (18)	2.5868 (12)	150.3 (17)
C5B—H5B⋯O1C ⁱⁱ	0.95	2.43	3.3237 (16)	156
C6C—H6C⋯O2C ^iv	1.00	2.59	3.4623 (15)	146
C9B—H9B1⋯O1B ^v	0.99	2.44	3.3548 (16)	153

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) .

Acknowledgments

The University of the Free State, the Chemistry Department, the NRF and Sasol Ltd and Inkaba yeAfrica are greatly acknowledged for funding.

supplementary crystallographic information

Comment

3-Hydroxypyridinones, which are derivatives of 3-hydroxypyranones, are known to have antimicrobial and antimalarial activity (Fassihi et al., 2009 and Weinberg, 1994). In addition to this, these compounds are non-toxic and they are approved for therapeutic use in some parts of the world (Galanello, 2007). Furthermore these organic compounds are metal ion chelators and they are used to prepare prodrugs with antioxidant characteristics and have brain targeting capabilities. These drugs have been suggested for the treatment of Alzheimer's disease and might possibly be more effective than treatments that just isolate metals (Scott et al., 2008).

As part of an ongoing study, O,O'-donor bidentate ligands are obtained by functionalizing commercially available 3-hydroxy-2-methylpyran-4-one (maltol) and 3-hydroxy-2-ethylpyran-4-one (ethyl maltol) to the respective 3-hydroxy-2-methylpyrid-4-one and 3-hydroxy-2-ethylpyrid-4-one derivatives. The funtionalizations are performed in order to obtain an array of different electronic and steric properties imparted on the respective starting materials in order to study these effects. Coordination to copper(II) and designing a catalyst with a suitable support for oxidation and the kinetic study thereof are part of this study.

2-Ethyl-3-hydroxy-1-isopropylpyridinone crystallized in the orthorhombic Pbca space group with three molecules in the asymmetric unit. The average carbonyl distances (C=O) in the three molecules of 1.265 (4) Å are comparable to those of similar molecules that have been reported in the literature (Dobbin et al., 1993, Xiao et al., 1992, Burgess et al., 1993, Hider et al., 1990). These four structures differ only by the substituents on the N1 and C1 atoms and are reported as combinations of methyl and ethyl groups compared to ethyl (C1) and isopropyl (N1) for this structure. A distance of 1.265 (1) Å by Xiao et al. (1992), 1.275 (5) Å by Burgess et al. (1993), 1.271 (1) Å by Hider et al. (1990) and 1.264 (2) Å by Dobbin et al. (1993) have been reported. The three crystallograophically distinct molecules are quite similar, for instance the carbonyl distances for molecules A, B and C are 1.264 (1) Å, 1.261 (2) Å and 1.269 (1) Å respectively with r.m.s. values of 0.6447 Å (for an overlay of the complete molecule A and B), 0.6257 Å (for an overlay of the complete molecule B and C) and 0.1476 Å (for an overlay of the complete molecule A and C). Illustrated in Figure 3 is an overlay of all three molecules. As can be seen, the molecules are distinct by small variations in their torsion angles, C1—N1—C6—C7 and C10—C9—C1—N1. For molecule A, B and C respectively, C1—N1—C6—C7 and C10—C9—C1—N1 are -150.62 (11) °, -126.77 (13) ° and -138.76 (11) ° for the first and 102.90 (13) °, 87.81(154 ° and 86.47 (13) ° for the latter torsion angle. The main difference between the three molecules lies however in the way they are arranged in the solid state structure. All three molecules are forming dimers that are connected through strong O—H···O hydrogen bonds with graph set motifs of R₂²(10). The symmetry of the dimers formed does however differ between molecules. Molecules B connect with each other to form dimers with exact crystallographic inversion symmetry. Molecules A and C, on the other hand form dimers with local two fold symmetry, but the two molecules are crystallographically distinct within the crystal lattice. Two weaker C—H···O intramolecular hydrogen interactions are formed between the ethyl carbon (C9) and the hydroxyl oxygen (O2) in molecule B and C. Another intramolecular C—H···O interactions is formed between the aromatic carbon C5B and a neighboring molecule's ketone oxygen (O1C). Finally, an intermolecular hydrogen interaction is observed between ethyl carbon C9B and a ketone oxygen (O1B).

Experimental

2-Ethyl-3-hydroxy-1-isopropyl-4-pyridinone was prepared from the reflux of 2-ethyl-3-hydroxypyran-4-one (ethyl maltol) (5 g, 0,03568 mol) with 6 equivalents of aqueous isopropylamine (12.65 ml, 0,2141 mol, 99%) in 100 ml of water overnight. The mixture turned dark brown. Decolourizing charcoal was added after refluxing and the mixture was left to stand for 30 min. This was then filtered and the dark brown filtrate was evaporated in vacuo to yield a dark brown solid. Crystallization from cold acetone gave pink crystals of 2-ethyl-3-hydroxy-1-isopropyl-4-pyridinone (Yield - 2.5 g, 0.0138 mol, 50%). NMR (300 MHz)¹³C: 13.3, 18.5, 23.1, 51.5, 111.9, 133.4, 134.3, 145.2, 169.2. NMR (300 MHz) ¹H: 1.11(t), 1.38(d), 2.77(q), 4.48(m), 6.18(d), 7.70(d).