organic compounds
Methyl 4-(4-hydroxyphenyl)-6-methyl-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carboxylate
aDepartment of Studies in Chemistry, Bangalore University, Bangalore 560 001, India
*Correspondence e-mail: noorsb@rediffmail.com
In the title molecule, C13H14N2O3S, the dihydropyrimidine ring is in a flattened sofa conformation, with the methine C atom forming the flap. The dihedral angle between the mean plane of the five essentially planar atoms of the dihydropyrimidine ring [maximum deviation = 0.056 (4) Å] and the benzene ring is 89.4 (2)°. The O atom of the carbonyl group is in a trans conformation with respect to the C=C bond of the dihydropyrimidine ring. In the crystal, N—H⋯O and O—H⋯S hydrogen bonds connect molecules, forming a two-dimensional network parallel to (001).
CCDC reference: 914631
Related literature
For general background and the biological activity of dihydropyrimidines, see: Kappe (2000); Jauk et al. (2000); Mayer et al. (1999); For a related structure, see: Liu et al. (2008).
Experimental
Crystal data
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Data collection: SMART (Bruker, 1998); cell SAINT-Plus (Bruker, 1998); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and PLATON (Spek, 2009); software used to prepare material for publication: WinGX (Farrugia, 2012).
Supporting information
CCDC reference: 914631
10.1107/S1600536814002888/lh5689sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536814002888/lh5689Isup2.hkl
Supporting information file. DOI: 10.1107/S1600536814002888/lh5689Isup3.cml
A mixture of methyl acetoacetate (3.12 g, 25 mmol), 4-hydroxy benzaldehyde (3.02 g, 20 mmol), thiourea (1.83 g, 24 mmol) and LiBr (0.175 g, 2mM) in acetonitrile (25 ml) was heated under reflux for 5 h. After cooling, the reaction mixture was poured onto crushed ice. Stirring was continued for several minutes. The solid product was filtered, washed with cold water, dried and recrystallized from ethanol (yield 85%; m.p.485 K). Single crystals were grown from a chloroform solution of the title compound by slow evaporation at room temperature.
H atoms were placed in calculated positions in the riding-model approximation with N—H = 0.86° A, O—H = 0.82° A, C—H = 0.93, 0.96 and 0.98 Å for aryl, methyl and methine H-atoms respectively, with Uiso(H) = 1.2Ueq(N/C) or 1.5Ueq(Cmethyl/O).
Data collection: SMART (Bruker, 1998); cell
SAINT-Plus (Bruker, 1998); data reduction: SAINT-Plus (Bruker, 1998); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and PLATON (Spek, 2009); software used to prepare material for publication: WinGX (Farrugia, 2012).C13H14N2O3S | Z = 2 |
Mr = 278.32 | F(000) = 292 |
Triclinic, P1 | Dx = 1.442 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 7.3016 (12) Å | Cell parameters from 2703 reflections |
b = 7.6855 (13) Å | θ = 1.8–27.0° |
c = 11.4706 (19) Å | µ = 0.26 mm−1 |
α = 88.337 (3)° | T = 296 K |
β = 84.870 (3)° | Block, colourless |
γ = 89.937 (3)° | 0.18 × 0.16 × 0.16 mm |
V = 640.84 (18) Å3 |
Bruker SMART APEX CCD detector diffractometer | 2703 independent reflections |
Radiation source: fine-focus sealed tube | 2084 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.020 |
ω scans | θmax = 27.0°, θmin = 1.8° |
Absorption correction: multi-scan (SADABS; Bruker, 1998) | h = −9→9 |
Tmin = 0.955, Tmax = 0.960 | k = −9→9 |
3897 measured reflections | l = −10→14 |
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)] = 0.067 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.224 | H-atom parameters constrained |
S = 1.22 | w = 1/[σ2(Fo2) + (0.0743P)2 + 1.681P] where P = (Fo2 + 2Fc2)/3 |
2703 reflections | (Δ/σ)max < 0.001 |
175 parameters | Δρmax = 0.76 e Å−3 |
0 restraints | Δρmin = −0.65 e Å−3 |
C13H14N2O3S | γ = 89.937 (3)° |
Mr = 278.32 | V = 640.84 (18) Å3 |
Triclinic, P1 | Z = 2 |
a = 7.3016 (12) Å | Mo Kα radiation |
b = 7.6855 (13) Å | µ = 0.26 mm−1 |
c = 11.4706 (19) Å | T = 296 K |
α = 88.337 (3)° | 0.18 × 0.16 × 0.16 mm |
β = 84.870 (3)° |
Bruker SMART APEX CCD detector diffractometer | 2703 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 1998) | 2084 reflections with I > 2σ(I) |
Tmin = 0.955, Tmax = 0.960 | Rint = 0.020 |
3897 measured reflections |
R[F2 > 2σ(F2)] = 0.067 | 0 restraints |
wR(F2) = 0.224 | H-atom parameters constrained |
S = 1.22 | Δρmax = 0.76 e Å−3 |
2703 reflections | Δρmin = −0.65 e Å−3 |
175 parameters |
Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.3658 (6) | 0.2646 (6) | −0.0479 (4) | 0.0338 (9) | |
H1A | 0.4523 | 0.3220 | −0.1042 | 0.051* | |
H1B | 0.2455 | 0.3127 | −0.0541 | 0.051* | |
H1C | 0.3637 | 0.1424 | −0.0627 | 0.051* | |
C2 | 0.7615 (6) | 0.2492 (5) | 0.0356 (4) | 0.0304 (9) | |
C3 | 0.9034 (6) | 0.1552 (8) | −0.1446 (4) | 0.0438 (12) | |
H3A | 0.9746 | 0.2601 | −0.1569 | 0.066* | |
H3B | 0.8711 | 0.1151 | −0.2186 | 0.066* | |
H3C | 0.9744 | 0.0675 | −0.1079 | 0.066* | |
C4 | 0.6180 (5) | 0.2981 (5) | 0.2393 (4) | 0.0278 (8) | |
H4 | 0.7320 | 0.3627 | 0.2462 | 0.033* | |
C5 | 0.5918 (5) | 0.2811 (5) | 0.1099 (4) | 0.0270 (8) | |
C6 | 0.4216 (5) | 0.2909 (5) | 0.0729 (4) | 0.0299 (9) | |
C7 | 0.2938 (6) | 0.3954 (5) | 0.2612 (4) | 0.0294 (9) | |
C8 | 0.6324 (5) | 0.1204 (5) | 0.3004 (3) | 0.0259 (8) | |
C9 | 0.4829 (6) | 0.0075 (5) | 0.3100 (4) | 0.0331 (10) | |
H9 | 0.3732 | 0.0437 | 0.2818 | 0.040* | |
C10 | 0.4930 (5) | −0.1559 (5) | 0.3601 (4) | 0.0331 (10) | |
H10 | 0.3905 | −0.2284 | 0.3665 | 0.040* | |
C11 | 0.6558 (5) | −0.2129 (5) | 0.4010 (3) | 0.0280 (8) | |
C12 | 0.8074 (6) | −0.1033 (6) | 0.3943 (4) | 0.0365 (10) | |
H12 | 0.9166 | −0.1396 | 0.4232 | 0.044* | |
C13 | 0.7924 (6) | 0.0628 (6) | 0.3433 (4) | 0.0335 (9) | |
H13 | 0.8938 | 0.1367 | 0.3381 | 0.040* | |
N1 | 0.2744 (5) | 0.3334 (5) | 0.1523 (3) | 0.0313 (8) | |
H1 | 0.1650 | 0.3200 | 0.1318 | 0.038* | |
N2 | 0.4641 (4) | 0.3976 (4) | 0.2940 (3) | 0.0265 (7) | |
H2 | 0.4851 | 0.4620 | 0.3514 | 0.032* | |
O1 | 0.9147 (4) | 0.2737 (5) | 0.0673 (3) | 0.0431 (8) | |
O2 | 0.7382 (4) | 0.1894 (4) | −0.0701 (3) | 0.0372 (8) | |
O3 | 0.6613 (4) | −0.3807 (4) | 0.4445 (3) | 0.0308 (7) | |
H3 | 0.7489 | −0.3919 | 0.4840 | 0.046* | |
S1 | 0.10843 (14) | 0.46706 (14) | 0.34469 (10) | 0.0335 (3) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.028 (2) | 0.039 (2) | 0.035 (2) | −0.0028 (17) | −0.0073 (17) | −0.0051 (18) |
C2 | 0.027 (2) | 0.030 (2) | 0.034 (2) | 0.0000 (16) | −0.0038 (16) | 0.0000 (17) |
C3 | 0.028 (2) | 0.071 (4) | 0.031 (2) | 0.000 (2) | 0.0023 (18) | −0.010 (2) |
C4 | 0.0247 (19) | 0.025 (2) | 0.034 (2) | −0.0010 (15) | −0.0027 (15) | −0.0020 (16) |
C5 | 0.0235 (19) | 0.025 (2) | 0.032 (2) | −0.0022 (15) | −0.0016 (15) | −0.0039 (16) |
C6 | 0.0227 (19) | 0.032 (2) | 0.035 (2) | −0.0038 (15) | −0.0033 (16) | −0.0035 (17) |
C7 | 0.029 (2) | 0.0203 (19) | 0.039 (2) | 0.0006 (15) | −0.0050 (17) | −0.0053 (16) |
C8 | 0.0261 (19) | 0.026 (2) | 0.026 (2) | −0.0014 (15) | −0.0001 (15) | −0.0064 (15) |
C9 | 0.027 (2) | 0.026 (2) | 0.047 (3) | 0.0016 (16) | −0.0090 (18) | 0.0005 (18) |
C10 | 0.0230 (19) | 0.029 (2) | 0.048 (3) | −0.0071 (16) | −0.0010 (17) | −0.0092 (18) |
C11 | 0.029 (2) | 0.029 (2) | 0.026 (2) | −0.0008 (16) | −0.0013 (15) | −0.0019 (16) |
C12 | 0.028 (2) | 0.036 (2) | 0.045 (3) | −0.0038 (17) | −0.0042 (18) | 0.0016 (19) |
C13 | 0.027 (2) | 0.036 (2) | 0.038 (2) | −0.0079 (17) | −0.0044 (17) | 0.0040 (18) |
N1 | 0.0225 (17) | 0.0339 (19) | 0.038 (2) | −0.0018 (14) | −0.0019 (14) | −0.0116 (15) |
N2 | 0.0163 (15) | 0.0261 (17) | 0.038 (2) | −0.0022 (12) | −0.0056 (13) | −0.0087 (14) |
O1 | 0.0195 (14) | 0.071 (2) | 0.0393 (19) | −0.0030 (14) | −0.0015 (12) | −0.0107 (16) |
O2 | 0.0239 (15) | 0.056 (2) | 0.0317 (17) | −0.0016 (13) | −0.0015 (12) | −0.0081 (14) |
O3 | 0.0323 (16) | 0.0258 (15) | 0.0347 (17) | −0.0018 (12) | −0.0045 (12) | 0.0000 (12) |
S1 | 0.0259 (5) | 0.0338 (6) | 0.0405 (7) | 0.0020 (4) | −0.0001 (4) | −0.0079 (4) |
C1—C6 | 1.498 (6) | C7—N2 | 1.331 (5) |
C1—H1A | 0.9600 | C7—N1 | 1.370 (5) |
C1—H1B | 0.9600 | C7—S1 | 1.688 (4) |
C1—H1C | 0.9600 | C8—C13 | 1.376 (6) |
C2—O1 | 1.223 (5) | C8—C9 | 1.390 (5) |
C2—O2 | 1.334 (5) | C9—C10 | 1.370 (6) |
C2—C5 | 1.465 (6) | C9—H9 | 0.9300 |
C3—O2 | 1.443 (5) | C10—C11 | 1.382 (6) |
C3—H3A | 0.9600 | C10—H10 | 0.9300 |
C3—H3B | 0.9600 | C11—O3 | 1.371 (5) |
C3—H3C | 0.9600 | C11—C12 | 1.387 (6) |
C4—N2 | 1.463 (5) | C12—C13 | 1.398 (6) |
C4—C5 | 1.523 (6) | C12—H12 | 0.9300 |
C4—C8 | 1.525 (6) | C13—H13 | 0.9300 |
C4—H4 | 0.9800 | N1—H1 | 0.8600 |
C5—C6 | 1.350 (5) | N2—H2 | 0.8600 |
C6—N1 | 1.390 (5) | O3—H3 | 0.8200 |
C6—C1—H1A | 109.5 | N2—C7—S1 | 123.7 (3) |
C6—C1—H1B | 109.5 | N1—C7—S1 | 120.2 (3) |
H1A—C1—H1B | 109.5 | C13—C8—C9 | 117.7 (4) |
C6—C1—H1C | 109.5 | C13—C8—C4 | 122.3 (3) |
H1A—C1—H1C | 109.5 | C9—C8—C4 | 120.0 (4) |
H1B—C1—H1C | 109.5 | C10—C9—C8 | 121.7 (4) |
O1—C2—O2 | 121.7 (4) | C10—C9—H9 | 119.2 |
O1—C2—C5 | 123.1 (4) | C8—C9—H9 | 119.2 |
O2—C2—C5 | 115.2 (3) | C9—C10—C11 | 120.0 (4) |
O2—C3—H3A | 109.5 | C9—C10—H10 | 120.0 |
O2—C3—H3B | 109.5 | C11—C10—H10 | 120.0 |
H3A—C3—H3B | 109.5 | O3—C11—C10 | 117.5 (4) |
O2—C3—H3C | 109.5 | O3—C11—C12 | 122.3 (4) |
H3A—C3—H3C | 109.5 | C10—C11—C12 | 120.1 (4) |
H3B—C3—H3C | 109.5 | C11—C12—C13 | 118.5 (4) |
N2—C4—C5 | 108.7 (3) | C11—C12—H12 | 120.7 |
N2—C4—C8 | 110.9 (3) | C13—C12—H12 | 120.7 |
C5—C4—C8 | 111.5 (3) | C8—C13—C12 | 122.0 (4) |
N2—C4—H4 | 108.6 | C8—C13—H13 | 119.0 |
C5—C4—H4 | 108.6 | C12—C13—H13 | 119.0 |
C8—C4—H4 | 108.6 | C7—N1—C6 | 123.7 (3) |
C6—C5—C2 | 125.5 (4) | C7—N1—H1 | 118.1 |
C6—C5—C4 | 120.0 (4) | C6—N1—H1 | 118.1 |
C2—C5—C4 | 114.5 (3) | C7—N2—C4 | 124.6 (3) |
C5—C6—N1 | 119.0 (4) | C7—N2—H2 | 117.7 |
C5—C6—C1 | 128.1 (4) | C4—N2—H2 | 117.7 |
N1—C6—C1 | 112.8 (3) | C2—O2—C3 | 116.3 (3) |
N2—C7—N1 | 116.2 (4) | C11—O3—H3 | 109.5 |
O1—C2—C5—C6 | 165.7 (4) | C8—C9—C10—C11 | −1.0 (7) |
O2—C2—C5—C6 | −14.8 (6) | C9—C10—C11—O3 | −176.6 (4) |
O1—C2—C5—C4 | −16.3 (6) | C9—C10—C11—C12 | 1.8 (7) |
O2—C2—C5—C4 | 163.2 (3) | O3—C11—C12—C13 | 176.8 (4) |
N2—C4—C5—C6 | −25.1 (5) | C10—C11—C12—C13 | −1.5 (7) |
C8—C4—C5—C6 | 97.4 (4) | C9—C8—C13—C12 | 0.4 (7) |
N2—C4—C5—C2 | 156.8 (3) | C4—C8—C13—C12 | −177.0 (4) |
C8—C4—C5—C2 | −80.7 (4) | C11—C12—C13—C8 | 0.4 (7) |
C2—C5—C6—N1 | −175.8 (4) | N2—C7—N1—C6 | −6.5 (6) |
C4—C5—C6—N1 | 6.3 (6) | S1—C7—N1—C6 | 172.3 (3) |
C2—C5—C6—C1 | 2.8 (7) | C5—C6—N1—C7 | 11.6 (6) |
C4—C5—C6—C1 | −175.1 (4) | C1—C6—N1—C7 | −167.2 (4) |
N2—C4—C8—C13 | −126.2 (4) | N1—C7—N2—C4 | −17.7 (6) |
C5—C4—C8—C13 | 112.5 (4) | S1—C7—N2—C4 | 163.6 (3) |
N2—C4—C8—C9 | 56.5 (5) | C5—C4—N2—C7 | 32.0 (5) |
C5—C4—C8—C9 | −64.8 (5) | C8—C4—N2—C7 | −90.9 (5) |
C13—C8—C9—C10 | −0.1 (7) | O1—C2—O2—C3 | 0.1 (6) |
C4—C8—C9—C10 | 177.3 (4) | C5—C2—O2—C3 | −179.4 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O1i | 0.86 | 2.06 | 2.923 (5) | 174 |
N2—H2···O3ii | 0.86 | 2.14 | 2.929 (4) | 152 |
O3—H3···S1iii | 0.82 | 2.36 | 3.122 (3) | 155 |
Symmetry codes: (i) x−1, y, z; (ii) x, y+1, z; (iii) −x+1, −y, −z+1. |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O1i | 0.860 | 2.060 | 2.923 (5) | 174 |
N2—H2···O3ii | 0.860 | 2.140 | 2.929 (4) | 152 |
O3—H3···S1iii | 0.820 | 2.360 | 3.122 (3) | 155 |
Symmetry codes: (i) x−1, y, z; (ii) x, y+1, z; (iii) −x+1, −y, −z+1. |
Acknowledgements
NSB is thankful to the University Grants Commission (UGC), India for financial assistance. NF thanks the UGC for a research fellowship under the RFSMS scheme.
References
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This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
The title compound is a member of the dihydropyrimidines (DHPM) (Kappe, 2000), which have emerged as important target molecules for therapeutic and pharmacological properties such as anticarcinogenic (Mayer et al., 1999) and more recently these compounds have emerged as the integral backbones of several calcium channel modulators (Jauk et al., 2000), anti-hypertensive agents. The title compound was chosen for X-ray diffraction studies with the intention of eliciting structural information which could facilitate further understanding of structural requirements for improved biological activity.
The molecular structure of the title compound is shown in Fig. 1. The dihydropyrimidine ring is in a flattened sofa conformation with atom C4 forming the flap. The dihedral angle between the mean plane of the five essentially planar atoms (N1/N2/C5/C6/C7) of the dihydropyrimidine ring [maximum deviation 0.056 (4) Å for C4] and the benzene ring (C8–C13) is 89.4 (2)°. The oxygen atom of the carbonyl group is in a trans configuration with respect to the C5═C6 bond of the dihydropyrimidine ring. In the crystal, N—H···O and O—H···S hydrogen bonds connect molecules forming a two-dimensional network parallel to (001) (Fig. 2).