1-(4-Amino­phen­yl)-2-ethyl-3-hydr­oxy-1,4-dihydro­pyridin-4-one monohydrate

In the title compound, C₁₃H₁₄N₂O₂·H₂O, the dihedral angle between the benzene and pyridinone rings is 74.86 (7)°. In the crystal structure, the mol­ecules are linked by a pair of O—H...O hydrogen bonds [O...O = 2.662 (2) Å], forming a centrosymmetric dimer. In addition, the mol­ecules are linked via O—H...O, O—H...N and N—H...O inter­molecular hydrogen bonds involving the water mol­ecules, and C—H...O inter­actions.

Key indicators

• Single-crystal X-ray study
• T = 298 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.043
• wR factor = 0.125
• Data-to-parameter ratio = 12.6

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S1. Comment

A number of hydroxypyrones and hydroxypyridinones are being assessed or considered as orally effective chelators for treatment iron or aluminium overload (Burgess, 1993; Clevette et al., 1990). In our continuing research on the hydroxypyridinone (Lu et al., 2003), we present here the crystal structure of the title compound, (I).

Bond distances (Table 1) in compound (I) agree with those observed for the N-benzyl analogues (Burgess, Fawcett, Russell & Zaisheng, 1998;

Burgess, Fawcett, Russell & Waltham, 1998). The dihedral angle between the benzene and pyridinone rings is 74.86 (7)°.

Molecules of compound (I) are linked by a pair of O2—H2···O1(1 - x, -y, -z) hydrogen bonds into a centrosymmetric dimer (Fig. 1). This type of dimeric structure is commonly found in anhydrous or hydrous 3-hydroxypyridin-4-one (Xiao et al., 1992; Burgess et al., 1993; Burgess, Fawcett, Russell & Zaisheng, 1998; Burgess, Fawcett, Russell & Waltham, 1998 and 3-hydroxypyran-4-one compounds (Brown et al., 1995). In the crystal structure, there is a water molecule associated with each pyridinone molecule, which are linked through N2—H2B···O3 hydrogen bonds (Fig. 1). The water molecule links the O1 and N2 atoms of adjacent pyridinones through O—H···O and O—H···O hydrogen bonds, with O3···O1(x, 1 + y, 1 + z) and O3···N2(-x, 2 - y, 1 - z) distances of 2.857 (2) and 2.987 (3) Å, respectively. In addition, the molecules are linked by weak C—H···O contacts of ca C···O 3.3 Å, as previously observed for this type of compounds (Burgess et al., 1996; Burgess, Fawcett, Russell & Zaisheng, 1998; Burgess, Fawcett, Russell & Waltham, 1998).

Related literature

O—H···O hydrogen-bonded dimer formation is observed in 3-hydroxypyridin-4-one and 3-hydroxypyran-4-one compounds (Xiao et al., 1992; Burgess et al., 1993; Burgess, Fawcett, Russell & Zaisheng, 1998; Burgess, Fawcett, Russell & Waltham, 1998; Brown et al., 1995). For related literature, see: Burgess (1993); Burgess et al. (1996); Chan et al. (1992); Clevette & Orvig (1990); Lu et al. (2003).

S2. Experimental

The title compound was prepared according to the literature method of Lu et al. (2003). Crystals suitable for X-ray analysis were obtained by slow evaporation of a methanol-water solution at room temperature after several weeks.

S3. Refinement

H atoms of amino group were located in a difference map and refined freely. The remaining H atoms were placed in calculated positions, with C—H = 0.93–0.97 Å and O—H = 0.82–0.85 Å, and included in the final cycles of refinement using a riding model, with U_iso(H) = 1.2U_eq(C) and 1.5U_eq(O).

Computing details

Data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1999); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1999); software used to prepare material for publication: SHELXTL.

Figures

	Fig. 1. A view of the hydrogen-bonded (dashed lines) dimer of (I). Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. The packing diagram of (I). Hydrogen bonds are shown as dashed lines.

1-(4-Aminophenyl)-2-ethyl-3-hydroxy-1,4-dihydropyridin-4-one monohydrate

Crystal data

C13H14N2O2·H2O	Z = 2
Mr = 248.28	F(000) = 264
Triclinic, P1	Dx = 1.331 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.8992 (14) Å	Cell parameters from 1277 reflections
b = 8.0162 (15) Å	θ = 2.9–27.8°
c = 11.4759 (19) Å	µ = 0.10 mm^−1
α = 96.835 (2)°	T = 298 K
β = 106.273 (2)°	Plate, yellow
γ = 113.143 (3)°	0.58 × 0.47 × 0.22 mm
V = 619.43 (19) Å^3

Data collection

Bruker SMART CCD area-detector diffractometer	2155 independent reflections
Radiation source: fine-focus sealed tube	1494 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.019
φ and ω scans	θmax = 25.0°, θmin = 1.9°
Absorption correction: multi-scan (SADABS: Sheldrick, 1996)	h = −9→9
Tmin = 0.947, Tmax = 0.979	k = −9→6
3228 measured reflections	l = −12→13

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.043	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.125	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	w = 1/[σ^2(Fo^2) + (0.058P)^2 + 0.141P] where P = (Fo^2 + 2Fc^2)/3
2155 reflections	(Δ/σ)max = 0.001
171 parameters	Δρmax = 0.15 e Å^−3
0 restraints	Δρmin = −0.19 e Å^−3

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
N1	0.2932 (2)	0.4626 (2)	0.13373 (15)	0.0410 (4)
N2	0.2456 (4)	1.0252 (4)	0.4479 (2)	0.0598 (6)
O1	0.3004 (2)	0.02104 (19)	−0.07892 (12)	0.0487 (4)
O2	0.6375 (2)	0.2808 (2)	0.11625 (14)	0.0555 (4)
H2	0.6220	0.1884	0.0671	0.083*
O3	0.0972 (2)	0.8939 (2)	0.65506 (14)	0.0663 (5)
H14	0.1591	0.9252	0.7339	0.100*
H15	−0.0016	0.9169	0.6437	0.100*
C1	0.4659 (3)	0.4445 (3)	0.15894 (17)	0.0376 (5)
C2	0.4666 (3)	0.2958 (3)	0.08741 (17)	0.0392 (5)
C3	0.2953 (3)	0.1587 (3)	−0.01476 (17)	0.0386 (5)
C4	0.1269 (3)	0.1900 (3)	−0.03696 (19)	0.0465 (5)
H4	0.0120	0.1085	−0.1040	0.056*
C5	0.1280 (3)	0.3360 (3)	0.0369 (2)	0.0476 (5)
H5	0.0128	0.3498	0.0209	0.057*
C6	0.2799 (3)	0.6082 (3)	0.21302 (18)	0.0390 (5)
C7	0.1834 (3)	0.5618 (3)	0.2967 (2)	0.0485 (5)
H7	0.1250	0.4377	0.3004	0.058*
C8	0.1741 (3)	0.6998 (3)	0.3745 (2)	0.0502 (5)
H8	0.1093	0.6679	0.4307	0.060*
C9	0.2597 (3)	0.8856 (3)	0.37046 (18)	0.0444 (5)
C10	0.3514 (3)	0.9284 (3)	0.28396 (19)	0.0465 (5)
H10	0.4068	1.0518	0.2784	0.056*
C11	0.3620 (3)	0.7914 (3)	0.20597 (18)	0.0430 (5)
H11	0.4246	0.8226	0.1486	0.052*
C12	0.6474 (3)	0.5818 (3)	0.26744 (18)	0.0449 (5)
H12A	0.6434	0.7017	0.2829	0.054*
H12B	0.7629	0.6010	0.2461	0.054*
C13	0.6645 (4)	0.5139 (4)	0.3857 (2)	0.0671 (7)
H13A	0.7824	0.6047	0.4528	0.101*
H13B	0.6702	0.3961	0.3711	0.101*
H13C	0.5519	0.4978	0.4083	0.101*
H2A	0.346 (5)	1.136 (5)	0.464 (3)	0.091 (11)*
H2B	0.214 (4)	0.983 (4)	0.513 (2)	0.071 (8)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0404 (10)	0.0359 (9)	0.0441 (9)	0.0184 (8)	0.0109 (8)	0.0073 (7)
N2	0.0670 (15)	0.0683 (15)	0.0520 (12)	0.0413 (13)	0.0205 (11)	0.0054 (11)
O1	0.0524 (9)	0.0468 (9)	0.0433 (8)	0.0258 (7)	0.0108 (7)	0.0023 (7)
O2	0.0439 (9)	0.0527 (9)	0.0588 (9)	0.0254 (7)	0.0058 (7)	−0.0070 (7)
O3	0.0696 (11)	0.0737 (11)	0.0486 (9)	0.0372 (9)	0.0089 (8)	0.0027 (8)
C1	0.0385 (11)	0.0363 (11)	0.0388 (10)	0.0174 (9)	0.0128 (8)	0.0121 (8)
C2	0.0397 (11)	0.0417 (11)	0.0391 (10)	0.0208 (9)	0.0130 (9)	0.0138 (9)
C3	0.0457 (11)	0.0361 (11)	0.0327 (10)	0.0177 (9)	0.0126 (9)	0.0095 (8)
C4	0.0424 (12)	0.0417 (12)	0.0438 (11)	0.0173 (9)	0.0031 (9)	0.0060 (9)
C5	0.0397 (11)	0.0442 (12)	0.0537 (12)	0.0218 (10)	0.0067 (10)	0.0081 (10)
C6	0.0404 (11)	0.0385 (11)	0.0413 (10)	0.0210 (9)	0.0144 (9)	0.0100 (9)
C7	0.0477 (12)	0.0453 (12)	0.0602 (13)	0.0230 (10)	0.0234 (11)	0.0223 (11)
C8	0.0527 (13)	0.0649 (15)	0.0512 (12)	0.0349 (12)	0.0281 (10)	0.0239 (11)
C9	0.0427 (11)	0.0537 (13)	0.0405 (11)	0.0309 (10)	0.0080 (9)	0.0086 (9)
C10	0.0498 (12)	0.0389 (11)	0.0525 (12)	0.0213 (10)	0.0185 (10)	0.0119 (10)
C11	0.0472 (12)	0.0416 (12)	0.0436 (11)	0.0201 (10)	0.0199 (9)	0.0139 (9)
C12	0.0424 (11)	0.0401 (11)	0.0478 (12)	0.0197 (9)	0.0109 (9)	0.0049 (9)
C13	0.0633 (15)	0.0707 (17)	0.0441 (13)	0.0200 (13)	0.0051 (11)	0.0052 (12)

Geometric parameters (Å, º)

N1—C5	1.358 (2)	C5—H5	0.93
N1—C1	1.382 (2)	C6—C11	1.376 (3)
N1—C6	1.449 (2)	C6—C7	1.384 (3)
N2—C9	1.404 (3)	C7—C8	1.375 (3)
N2—H2A	0.88 (3)	C7—H7	0.93
N2—H2B	0.92 (3)	C8—C9	1.386 (3)
O1—C3	1.273 (2)	C8—H8	0.93
O2—C2	1.354 (2)	C9—C10	1.384 (3)
O2—H2	0.82	C10—C11	1.376 (3)
O3—H14	0.85	C10—H10	0.93
O3—H15	0.85	C11—H11	0.93
C1—C2	1.367 (3)	C12—C13	1.512 (3)
C1—C12	1.500 (3)	C12—H12A	0.97
C2—C3	1.431 (3)	C12—H12B	0.97
C3—C4	1.409 (3)	C13—H13A	0.96
C4—C5	1.356 (3)	C13—H13B	0.96
C4—H4	0.93	C13—H13C	0.96
C5—N1—C1	120.00 (17)	C8—C7—H7	120.1
C5—N1—C6	118.45 (16)	C6—C7—H7	120.1
C1—N1—C6	121.45 (16)	C7—C8—C9	121.07 (19)
C9—N2—H2A	111.3 (19)	C7—C8—H8	119.5
C9—N2—H2B	109.7 (16)	C9—C8—H8	119.5
H2A—N2—H2B	119 (3)	C10—C9—C8	118.19 (19)
C2—O2—H2	109.5	C10—C9—N2	120.9 (2)
H14—O3—H15	107.1	C8—C9—N2	120.8 (2)
C2—C1—N1	119.21 (17)	C11—C10—C9	121.2 (2)
C2—C1—C12	120.64 (17)	C11—C10—H10	119.4
N1—C1—C12	120.09 (17)	C9—C10—H10	119.4
O2—C2—C1	117.57 (17)	C6—C11—C10	119.89 (18)
O2—C2—C3	119.97 (17)	C6—C11—H11	120.1
C1—C2—C3	122.46 (18)	C10—C11—H11	120.1
O1—C3—C4	124.17 (18)	C1—C12—C13	111.82 (17)
O1—C3—C2	120.92 (18)	C1—C12—H12A	109.3
C4—C3—C2	114.92 (17)	C13—C12—H12A	109.3
C5—C4—C3	121.69 (19)	C1—C12—H12B	109.3
C5—C4—H4	119.2	C13—C12—H12B	109.3
C3—C4—H4	119.2	H12A—C12—H12B	107.9
C4—C5—N1	121.67 (19)	C12—C13—H13A	109.5
C4—C5—H5	119.2	C12—C13—H13B	109.5
N1—C5—H5	119.2	H13A—C13—H13B	109.5
C11—C6—C7	119.82 (19)	C12—C13—H13C	109.5
C11—C6—N1	120.78 (17)	H13A—C13—H13C	109.5
C7—C6—N1	119.41 (18)	H13B—C13—H13C	109.5
C8—C7—C6	119.8 (2)
C5—N1—C1—C2	−1.6 (3)	C5—N1—C6—C11	−107.4 (2)
C6—N1—C1—C2	174.75 (17)	C1—N1—C6—C11	76.2 (2)
C5—N1—C1—C12	−178.74 (17)	C5—N1—C6—C7	72.6 (2)
C6—N1—C1—C12	−2.4 (3)	C1—N1—C6—C7	−103.8 (2)
N1—C1—C2—O2	−178.87 (16)	C11—C6—C7—C8	−1.5 (3)
C12—C1—C2—O2	−1.7 (3)	N1—C6—C7—C8	178.45 (18)
N1—C1—C2—C3	1.1 (3)	C6—C7—C8—C9	0.1 (3)
C12—C1—C2—C3	178.27 (17)	C7—C8—C9—C10	1.4 (3)
O2—C2—C3—O1	0.6 (3)	C7—C8—C9—N2	178.5 (2)
C1—C2—C3—O1	−179.44 (18)	C8—C9—C10—C11	−1.6 (3)
O2—C2—C3—C4	−179.23 (17)	N2—C9—C10—C11	−178.6 (2)
C1—C2—C3—C4	0.8 (3)	C7—C6—C11—C10	1.3 (3)
O1—C3—C4—C5	177.90 (19)	N1—C6—C11—C10	−178.65 (18)
C2—C3—C4—C5	−2.3 (3)	C9—C10—C11—C6	0.2 (3)
C3—C4—C5—N1	2.0 (3)	C2—C1—C12—C13	−84.4 (2)
C1—N1—C5—C4	0.1 (3)	N1—C1—C12—C13	92.7 (2)
C6—N1—C5—C4	−176.39 (18)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H15···N2^i	0.85	2.17	2.987 (3)	160
O3—H14···O1^ii	0.85	2.01	2.857 (2)	174
O2—H2···O1	0.82	2.34	2.7630 (19)	113
O2—H2···O1^iii	0.82	2.01	2.662 (2)	136
N2—H2B···O3	0.92 (3)	2.15 (3)	3.053 (3)	170 (2)
C11—H11···O1^iv	0.93	2.45	3.324 (3)	157

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