Methyl 4-(4-hy­droxy­phen­yl)-6-methyl-2-sulfanyl­idene-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate

Fathima, N.; Nagarajaiah, H.; Begum, N.S.

doi:10.1107/S1600536814002888

organic compounds

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doi:10.1107/S1600536814002888

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Methyl 4-(4-hydroxyphenyl)-6-methyl-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Nikhath Fathima,^a H. Nagarajaiah ^a and Noor Shahina Begum ^a ^*

^aDepartment of Studies in Chemistry, Bangalore University, Bangalore 560 001, India
^*Correspondence e-mail: noorsb@rediffmail.com

(Received 24 January 2014; accepted 8 February 2014; online 15 February 2014)

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

C₁₃H₁₄N₂O₃S
M_r = 278.32
Triclinic, $[P \overline 1]$
a = 7.3016 (12) Å
b = 7.6855 (13) Å
c = 11.4706 (19) Å
α = 88.337 (3)°
β = 84.870 (3)°
γ = 89.937 (3)°
V = 640.84 (18) Å³
Z = 2
Mo Kα radiation
μ = 0.26 mm⁻¹
T = 296 K
0.18 × 0.16 × 0.16 mm

Data collection

Bruker SMART APEX CCD detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1998 ) T_min = 0.955, T_max = 0.960
3897 measured reflections
2703 independent reflections
2084 reflections with I > 2σ(I)
R_int = 0.020

Refinement

R[F² > 2σ(F²)] = 0.067
wR(F²) = 0.224
S = 1.22
2703 reflections
175 parameters
H-atom parameters constrained
Δρ_max = 0.76 e Å⁻³
Δρ_min = −0.65 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

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.

Data collection: SMART (Bruker, 1998); cell refinement: 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

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536814002888/lh5689sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536814002888/lh5689Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536814002888/lh5689Isup3.cml

checkCIF report

Comment top

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).

Related literature top

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 top

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.

Computing details top

Data collection: SMART (Bruker, 1998); cell refinement: 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).

Figures top

	Fig. 1. The molecular structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level. H atoms are presented as small spheres of arbitrary radius.
	Fig. 2. Part of the crystal structure with hydrogen bonds shown as dashed lines.

Methyl 4-(4-hydroxyphenyl)-6-methyl-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carboxylate top

Crystal data top

C₁₃H₁₄N₂O₃S	Z = 2
M_r = 278.32	F(000) = 292
Triclinic, P1	D_x = 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

Data collection top

Bruker SMART APEX CCD detector diffractometer	2703 independent reflections
Radiation source: fine-focus sealed tube	2084 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.020
ω scans	θ_max = 27.0°, θ_min = 1.8°
Absorption correction: multi-scan (SADABS; Bruker, 1998)	h = −9→9
T_min = 0.955, T_max = 0.960	k = −9→9
3897 measured reflections	l = −10→14

Refinement top

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(F_o²) + (0.0743P)² + 1.681P] where P = (F_o² + 2F_c²)/3
2703 reflections	(Δ/σ)_max < 0.001
175 parameters	Δρ_max = 0.76 e Å⁻³
0 restraints	Δρ_min = −0.65 e Å⁻³

Crystal data top

C₁₃H₁₄N₂O₃S	γ = 89.937 (3)°
M_r = 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)°

Data collection top

Bruker SMART APEX CCD detector diffractometer	2703 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 1998)	2084 reflections with I > 2σ(I)
T_min = 0.955, T_max = 0.960	R_int = 0.020
3897 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.067	0 restraints
wR(F²) = 0.224	H-atom parameters constrained
S = 1.22	Δρ_max = 0.76 e Å⁻³
2703 reflections	Δρ_min = −0.65 e Å⁻³
175 parameters

Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
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)

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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)

Hydrogen-bond geometry (Å, º) top

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.

Hydrogen-bond geometry (Å, º) top

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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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Methyl 4-(4-hy­dr­oxy­phen­yl)-6-methyl-2-sulfanyl­­idene-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate

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Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

Methyl 4-(4-hydroxyphenyl)-6-methyl-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carboxylate