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In the title compound, C15H18N2O4S, the packing is consolidated by an intra/inter­molecular bifurcated O—H...(O,O) and inter­molecular N—H...S hydrogen bonds. The tetrahydropyrimidin-2-one ring is twisted.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807046752/hb2552sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536807046752/hb2552Isup2.hkl
Contains datablock I

CCDC reference: 664215

Key indicators

  • Single-crystal X-ray study
  • T = 294 K
  • Mean [sigma](C-C) = 0.004 Å
  • R factor = 0.040
  • wR factor = 0.107
  • Data-to-parameter ratio = 12.8

checkCIF/PLATON results

No syntax errors found



Alert level C PLAT066_ALERT_1_C Predicted and Reported Transmissions Identical . ? PLAT154_ALERT_1_C The su's on the Cell Angles are Equal (x 10000) 400 Deg. PLAT222_ALERT_3_C Large Non-Solvent H Ueq(max)/Ueq(min) ... 3.11 Ratio
Alert level G PLAT793_ALERT_1_G Check the Absolute Configuration of C4 = ... S PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints ....... 2
0 ALERT level A = In general: serious problem 0 ALERT level B = Potentially serious problem 3 ALERT level C = Check and explain 2 ALERT level G = General alerts; check 3 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 0 ALERT type 2 Indicator that the structure model may be wrong or deficient 2 ALERT type 3 Indicator that the structure quality may be low 0 ALERT type 4 Improvement, methodology, query or suggestion 0 ALERT type 5 Informative message, check

Comment top

Dihydropyrimidinones (DHPMs) and their derivatives exhibit a wide range of pharmacological and biological activities such as antibacterial, antiviral, antitumor and anti-inflamatory actions (Kappe, 1993).

The title compound, (I), (Fig. 1), was synthesized by the one-pot reaction of 4-hydroxy-3-methoxybenzaldehyde, thiourea and ethyl 3-oxobutanoate in ethanol under reflux. In the arbitrarily chosen asymmetric molecule, C4 has S configuration, but crystal symmetry generates a racemic mixture of enantiomers. The tetrahydropyrimidin-2-one ring is significantly twisted [C3—N2—C4—C5 = 32.8 (3)°]; the phenyl ring is almost perpendicular to the tetrahydropyrimidin-2-one ring [C3—N2—C4—C9 = -93.5 (2)° and C9—C4—C5—C2 = 99.7 (2)°]. The crystal structure is stabilized mainly through intermolecular N—H···S and O—H···O hydrogen bonds (Table 1).

Related literature top

For background, see: Kappe (1993).

Experimental top

A solution of ethyl 3-oxobutanoate (1.95 g, 15 mmol), 4-hydroxy-3-methoxybenzaldehyde (1.52 g, 10.0 mmol) and thiourea (0.76 g, 10 mmol) in ethanol (10 ml) was heated under reflux in the presence of a catalytic amount of HCl for 5 h. The reaction mixture was cooled and filtered. The solid product was recrystallized from ethanol to afford the pure product which was then dissolved in 100 ml absolute ethanol and crystals suitable for X-ray analysis were grown by slow evaporation over a period of 15 d.

Refinement top

The C and O-bound H atoms were positioned geometrically, with C—H = 0.93–0.97 Å and O—H = 0.82 Å, and refined in a riding model, with Uiso(H)= 1.2Ueq(C, O) or 1.5Ueq(methyl C). The positional parameters of the nitrogen-bound H atoms were refined freely, with Uiso(H) = 1.2Ueq(N).

Structure description top

Dihydropyrimidinones (DHPMs) and their derivatives exhibit a wide range of pharmacological and biological activities such as antibacterial, antiviral, antitumor and anti-inflamatory actions (Kappe, 1993).

The title compound, (I), (Fig. 1), was synthesized by the one-pot reaction of 4-hydroxy-3-methoxybenzaldehyde, thiourea and ethyl 3-oxobutanoate in ethanol under reflux. In the arbitrarily chosen asymmetric molecule, C4 has S configuration, but crystal symmetry generates a racemic mixture of enantiomers. The tetrahydropyrimidin-2-one ring is significantly twisted [C3—N2—C4—C5 = 32.8 (3)°]; the phenyl ring is almost perpendicular to the tetrahydropyrimidin-2-one ring [C3—N2—C4—C9 = -93.5 (2)° and C9—C4—C5—C2 = 99.7 (2)°]. The crystal structure is stabilized mainly through intermolecular N—H···S and O—H···O hydrogen bonds (Table 1).

For background, see: Kappe (1993).

Computing details top

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

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), drawn with 50% probability ellipsoids (arbitrary spheres for the H atoms). The hydrogen bond is indicated by a double-dashed line.
[Figure 2] Fig. 2. The formation of the title compound.
Ethyl 4-(4-hydroxy-3-methoxyphenyl)-6-methyl-2-thioxo- 1,2,3,4-tetrahydropyrimidine-5-carboxylate top
Crystal data top
C15H18N2O4SZ = 2
Mr = 322.37F(000) = 340
Triclinic, P1Dx = 1.388 Mg m3
Hall symbol: -P 1Melting point = 518–520 K
a = 8.469 (2) ÅMo Kα radiation, λ = 0.71073 Å
b = 9.362 (3) ÅCell parameters from 1562 reflections
c = 11.183 (3) Åθ = 2.4–26.1°
α = 97.935 (4)°µ = 0.23 mm1
β = 107.783 (4)°T = 294 K
γ = 108.777 (4)°Prism, colorless
V = 771.4 (4) Å30.20 × 0.18 × 0.18 mm
Data collection top
Bruker SMART CCD
diffractometer
2693 independent reflections
Radiation source: fine-focus sealed tube2011 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.018
ω scansθmax = 25.0°, θmin = 2.0°
Absorption correction: multi-scan
(SADABS; Bruker, 1997)
h = 104
Tmin = 0.956, Tmax = 0.960k = 1111
3996 measured reflectionsl = 1213
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)] = 0.040Hydrogen site location: difmap and geom
wR(F2) = 0.107H atoms treated by a mixture of independent and constrained refinement
S = 1.02 w = 1/[σ2(Fo2) + (0.0443P)2 + 0.4122P]
where P = (Fo2 + 2Fc2)/3
2693 reflections(Δ/σ)max = 0.001
211 parametersΔρmax = 0.23 e Å3
2 restraintsΔρmin = 0.26 e Å3
Crystal data top
C15H18N2O4Sγ = 108.777 (4)°
Mr = 322.37V = 771.4 (4) Å3
Triclinic, P1Z = 2
a = 8.469 (2) ÅMo Kα radiation
b = 9.362 (3) ŵ = 0.23 mm1
c = 11.183 (3) ÅT = 294 K
α = 97.935 (4)°0.20 × 0.18 × 0.18 mm
β = 107.783 (4)°
Data collection top
Bruker SMART CCD
diffractometer
2693 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 1997)
2011 reflections with I > 2σ(I)
Tmin = 0.956, Tmax = 0.960Rint = 0.018
3996 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0402 restraints
wR(F2) = 0.107H atoms treated by a mixture of independent and constrained refinement
S = 1.02Δρmax = 0.23 e Å3
2693 reflectionsΔρmin = 0.26 e Å3
211 parameters
Special details top

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
S11.28452 (8)0.56315 (7)0.51735 (7)0.0443 (2)
O10.7638 (2)0.18798 (19)0.30554 (17)0.0447 (4)
O21.0003 (2)0.20831 (18)0.26755 (18)0.0465 (5)
O30.5754 (2)0.1860 (3)0.18247 (17)0.0547 (5)
H30.48900.21020.18830.082*
O40.4557 (2)0.2693 (2)0.00204 (17)0.0524 (5)
N11.2645 (2)0.2813 (2)0.41844 (19)0.0345 (5)
N21.0002 (2)0.2943 (2)0.41542 (18)0.0329 (5)
C11.3338 (3)0.0517 (3)0.4109 (3)0.0441 (6)
H1A1.27970.05820.40250.066*
H1B1.42140.10290.49740.066*
H1C1.39140.06770.34930.066*
C21.1921 (3)0.1183 (2)0.3851 (2)0.0307 (5)
C31.1748 (3)0.3695 (3)0.4455 (2)0.0308 (5)
C40.8943 (3)0.1362 (2)0.3277 (2)0.0295 (5)
H40.79700.08550.35650.035*
C51.0128 (3)0.0437 (3)0.3421 (2)0.0300 (5)
C60.9129 (3)0.1276 (3)0.3051 (2)0.0323 (5)
C70.9108 (4)0.3780 (3)0.2279 (3)0.0479 (7)
H7A0.79050.40980.16380.058*
H7B0.90200.41760.30240.058*
C81.0197 (5)0.4392 (3)0.1721 (3)0.0728 (10)
H8A1.01800.40730.09390.109*
H8B0.97090.55130.15220.109*
H8C1.14120.39900.23370.109*
C90.8087 (3)0.1452 (2)0.1891 (2)0.0293 (5)
C100.6679 (3)0.1976 (3)0.1605 (2)0.0325 (5)
H100.62550.22130.22510.039*
C110.5909 (3)0.2150 (3)0.0391 (2)0.0349 (5)
C120.6507 (3)0.1751 (3)0.0592 (2)0.0366 (6)
C130.7897 (3)0.1247 (3)0.0315 (2)0.0401 (6)
H130.83110.09980.09630.048*
C140.8694 (3)0.1104 (3)0.0923 (2)0.0355 (5)
H140.96440.07710.10990.043*
C150.3902 (4)0.3151 (4)0.0975 (3)0.0637 (9)
H15A0.34060.22690.12840.096*
H15B0.29870.35280.05980.096*
H15C0.48720.39660.16890.096*
H20.937 (3)0.349 (3)0.435 (2)0.049 (7)*
H11.3834 (14)0.327 (3)0.443 (2)0.046 (7)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0291 (3)0.0336 (3)0.0617 (4)0.0114 (3)0.0146 (3)0.0064 (3)
O10.0307 (9)0.0437 (10)0.0550 (11)0.0108 (8)0.0130 (8)0.0142 (8)
O20.0449 (10)0.0259 (9)0.0694 (12)0.0104 (7)0.0286 (9)0.0058 (8)
O30.0470 (11)0.0894 (15)0.0380 (10)0.0360 (11)0.0156 (9)0.0246 (10)
O40.0481 (10)0.0796 (14)0.0451 (11)0.0438 (10)0.0160 (9)0.0205 (10)
N10.0229 (10)0.0318 (11)0.0484 (12)0.0126 (8)0.0137 (9)0.0033 (9)
N20.0233 (10)0.0351 (11)0.0372 (11)0.0142 (8)0.0090 (8)0.0012 (9)
C10.0322 (13)0.0393 (14)0.0563 (17)0.0185 (11)0.0088 (12)0.0051 (12)
C20.0309 (12)0.0303 (12)0.0316 (12)0.0156 (10)0.0105 (10)0.0041 (10)
C30.0270 (11)0.0355 (12)0.0307 (12)0.0149 (10)0.0105 (9)0.0053 (10)
C40.0227 (11)0.0304 (12)0.0330 (12)0.0091 (9)0.0099 (9)0.0048 (10)
C50.0286 (12)0.0322 (12)0.0289 (12)0.0131 (10)0.0092 (9)0.0075 (10)
C60.0323 (13)0.0364 (13)0.0277 (12)0.0150 (10)0.0075 (10)0.0114 (10)
C70.0550 (16)0.0281 (13)0.0557 (17)0.0090 (12)0.0226 (13)0.0081 (12)
C80.094 (3)0.0384 (16)0.088 (2)0.0178 (16)0.049 (2)0.0084 (16)
C90.0226 (11)0.0247 (11)0.0354 (13)0.0070 (9)0.0080 (9)0.0040 (9)
C100.0291 (12)0.0342 (12)0.0347 (13)0.0132 (10)0.0135 (10)0.0045 (10)
C110.0269 (12)0.0380 (13)0.0372 (14)0.0143 (10)0.0070 (10)0.0089 (10)
C120.0312 (12)0.0420 (14)0.0329 (13)0.0126 (11)0.0089 (10)0.0095 (11)
C130.0377 (13)0.0499 (15)0.0375 (14)0.0205 (12)0.0172 (11)0.0099 (12)
C140.0295 (12)0.0398 (13)0.0404 (14)0.0184 (10)0.0128 (10)0.0085 (11)
C150.0586 (18)0.096 (2)0.0614 (19)0.0567 (18)0.0254 (15)0.0233 (18)
Geometric parameters (Å, º) top
S1—C31.689 (2)C4—H40.9800
O1—C61.208 (3)C5—C61.479 (3)
O2—C61.326 (3)C7—C81.470 (4)
O2—C71.456 (3)C7—H7A0.9700
O3—C121.364 (3)C7—H7B0.9700
O3—H30.8200C8—H8A0.9600
O4—C111.373 (3)C8—H8B0.9600
O4—C151.421 (3)C8—H8C0.9600
N1—C31.352 (3)C9—C141.375 (3)
N1—C21.395 (3)C9—C101.397 (3)
N1—H10.891 (10)C10—C111.372 (3)
N2—C31.325 (3)C10—H100.9300
N2—C41.471 (3)C11—C121.398 (3)
N2—H20.90 (3)C12—C131.371 (3)
C1—C21.494 (3)C13—C141.389 (3)
C1—H1A0.9600C13—H130.9300
C1—H1B0.9600C14—H140.9300
C1—H1C0.9600C15—H15A0.9600
C2—C51.343 (3)C15—H15B0.9600
C4—C51.510 (3)C15—H15C0.9600
C4—C91.524 (3)
C6—O2—C7117.25 (19)C8—C7—H7A110.3
C12—O3—H3109.5O2—C7—H7B110.3
C11—O4—C15117.87 (19)C8—C7—H7B110.3
C3—N1—C2123.52 (18)H7A—C7—H7B108.6
C3—N1—H1118.4 (17)C7—C8—H8A109.5
C2—N1—H1116.1 (17)C7—C8—H8B109.5
C3—N2—C4124.04 (18)H8A—C8—H8B109.5
C3—N2—H2118.4 (17)C7—C8—H8C109.5
C4—N2—H2116.3 (17)H8A—C8—H8C109.5
C2—C1—H1A109.5H8B—C8—H8C109.5
C2—C1—H1B109.5C14—C9—C10118.5 (2)
H1A—C1—H1B109.5C14—C9—C4122.74 (19)
C2—C1—H1C109.5C10—C9—C4118.7 (2)
H1A—C1—H1C109.5C11—C10—C9121.4 (2)
H1B—C1—H1C109.5C11—C10—H10119.3
C5—C2—N1118.47 (19)C9—C10—H10119.3
C5—C2—C1129.1 (2)C10—C11—O4126.0 (2)
N1—C2—C1112.37 (18)C10—C11—C12119.4 (2)
N2—C3—N1116.1 (2)O4—C11—C12114.6 (2)
N2—C3—S1123.25 (16)O3—C12—C13118.8 (2)
N1—C3—S1120.65 (16)O3—C12—C11121.8 (2)
N2—C4—C5108.71 (16)C13—C12—C11119.5 (2)
N2—C4—C9110.28 (17)C12—C13—C14120.8 (2)
C5—C4—C9114.55 (18)C12—C13—H13119.6
N2—C4—H4107.7C14—C13—H13119.6
C5—C4—H4107.7C9—C14—C13120.4 (2)
C9—C4—H4107.7C9—C14—H14119.8
C2—C5—C6126.0 (2)C13—C14—H14119.8
C2—C5—C4119.97 (19)O4—C15—H15A109.5
C6—C5—C4114.02 (18)O4—C15—H15B109.5
O1—C6—O2123.2 (2)H15A—C15—H15B109.5
O1—C6—C5123.2 (2)O4—C15—H15C109.5
O2—C6—C5113.57 (19)H15A—C15—H15C109.5
O2—C7—C8107.1 (2)H15B—C15—H15C109.5
O2—C7—H7A110.3
C3—N1—C2—C519.3 (3)C4—C5—C6—O2154.47 (19)
C3—N1—C2—C1157.4 (2)C6—O2—C7—C8171.4 (2)
C4—N2—C3—N116.1 (3)N2—C4—C9—C14106.3 (2)
C4—N2—C3—S1165.59 (17)C5—C4—C9—C1416.8 (3)
C2—N1—C3—N212.3 (3)N2—C4—C9—C1070.8 (2)
C2—N1—C3—S1166.09 (17)C5—C4—C9—C10166.18 (19)
C3—N2—C4—C532.8 (3)C14—C9—C10—C110.2 (3)
C3—N2—C4—C993.5 (2)C4—C9—C10—C11177.04 (19)
N1—C2—C5—C6178.7 (2)C9—C10—C11—O4178.2 (2)
C1—C2—C5—C62.5 (4)C9—C10—C11—C121.9 (3)
N1—C2—C5—C41.5 (3)C15—O4—C11—C101.3 (4)
C1—C2—C5—C4177.7 (2)C15—O4—C11—C12178.8 (2)
N2—C4—C5—C224.2 (3)C10—C11—C12—O3178.2 (2)
C9—C4—C5—C299.7 (2)O4—C11—C12—O31.8 (3)
N2—C4—C5—C6155.99 (18)C10—C11—C12—C132.4 (3)
C9—C4—C5—C680.2 (2)O4—C11—C12—C13177.7 (2)
C7—O2—C6—O11.3 (3)O3—C12—C13—C14179.4 (2)
C7—O2—C6—C5179.36 (19)C11—C12—C13—C141.1 (4)
C2—C5—C6—O1156.6 (2)C10—C9—C14—C131.1 (3)
C4—C5—C6—O123.6 (3)C4—C9—C14—C13178.2 (2)
C2—C5—C6—O225.3 (3)C12—C13—C14—C90.7 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3···O1i0.822.072.788 (2)147
O3—H3···O40.822.252.690 (3)114
N2—H2···S1ii0.90 (3)2.44 (3)3.326 (2)167 (2)
N1—H1···S1iii0.89 (1)2.53 (1)3.417 (2)173 (2)
Symmetry codes: (i) x+1, y, z; (ii) x+2, y+1, z+1; (iii) x+3, y+1, z+1.

Experimental details

Crystal data
Chemical formulaC15H18N2O4S
Mr322.37
Crystal system, space groupTriclinic, P1
Temperature (K)294
a, b, c (Å)8.469 (2), 9.362 (3), 11.183 (3)
α, β, γ (°)97.935 (4), 107.783 (4), 108.777 (4)
V3)771.4 (4)
Z2
Radiation typeMo Kα
µ (mm1)0.23
Crystal size (mm)0.20 × 0.18 × 0.18
Data collection
DiffractometerBruker SMART CCD
Absorption correctionMulti-scan
(SADABS; Bruker, 1997)
Tmin, Tmax0.956, 0.960
No. of measured, independent and
observed [I > 2σ(I)] reflections
3996, 2693, 2011
Rint0.018
(sin θ/λ)max1)0.595
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.040, 0.107, 1.02
No. of reflections2693
No. of parameters211
No. of restraints2
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.23, 0.26

Computer programs: SMART (Bruker, 1997), SAINT (Bruker, 1997), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL (Bruker, 1997).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3···O1i0.822.072.788 (2)147
O3—H3···O40.822.252.690 (3)114
N2—H2···S1ii0.90 (3)2.44 (3)3.326 (2)167 (2)
N1—H1···S1iii0.891 (10)2.531 (11)3.417 (2)173 (2)
Symmetry codes: (i) x+1, y, z; (ii) x+2, y+1, z+1; (iii) x+3, y+1, z+1.
 

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