Ethyl 4-(4-chloro-3-fluoro­phen­yl)-6-methyl-2-sulfanyl­idene-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate

Shraddha, K.N.; Devika, S.; Begum, N.S.

doi:10.1107/S241431461900960X

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 4| Part 7| July 2019| x190960

https://doi.org/10.1107/S241431461900960X

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Ethyl 4-(4-chloro-3-fluorophenyl)-6-methyl-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carboxylate

K. N. Shraddha,^a S. Devika ^a and Noor Shahina Begum ^a ^*

^aDepartment of Studies in Chemistry, Gnana Bharathi Campus, Bangalore University, Bangalore-560 056, Karnataka, India
^*Correspondence e-mail: noorsb05@gmail.com

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 10 June 2019; accepted 4 July 2019; online 12 July 2019)

In the title compound, C₁₄H₁₄ClFN₂O₂S, the dihydropyrimidine ring adopts a shallow-boat conformation and subtends a dihedral angle of 81.91 (17)° with the phenyl ring. In the crystal, N—H⋯O, N—H⋯S and C—H⋯F hydrogen bonds and C—H⋯π interactions are found.

Keywords: crystal structure.

CCDC reference: 1835185

Structure description

The title compound is a dihydropyrimidine derivative (Kappe, 2000 ). Some of these compounds have therapeutic and pharmacological properties, such as anticarcinogenic (Mayer et al., 1999 ) activity. They have also emerged as integral backbones of several calcium-channel modulators (Jauk et al., 2000 ). As part of our studies in this area, we now describe the synthesis and structure of the title compound (Fig. 1).

Figure 1
The molecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level.

The phenyl ring atttached to chiral atom C4 is positioned axially and bisects the pyrimidine ring with a dihedral angle of 81.91 (17)°. The pyrimidine ring adopts a shallow-boat conformation, with atoms N1 and C4 displaced from the mean plane of the other four atoms (C5/C6/C2/N2) by −0.0982 (7) and −0.0393 (1) Å, respectively. The O atom of the carbonyl group is in an anti conformation with respect to the C5—C6 bond.

The crystal structure features pairwise N2—H2⋯S1ⁱ hydrogen bonds (Table 1), resulting in centrosymmetric R₂²(8) loops and also displays [100] chains linked by N1—H1⋯O1ⁱⁱ hydrogen bonds (Fig. 2). In addition, the packing is consolidated by a C1—H1A⋯F1ⁱⁱⁱ interaction along the [110] direction (Fig. 3) and a C7—H7B⋯Cg^iv interaction (Cg being the centroid of the C8–C13 ring), with a H⋯Cg distance of 2.62 Å (Fig. 4).

Table 1
Hydrogen-bond geometry (Å, °)

Cg is the centroid of the C8–C13 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2⋯S1ⁱ	0.86	2.47	3.301 (1)	163
N1—H1⋯O1ⁱⁱ	0.86	2.17	2.998 (2)	160
C1—H1A⋯F1ⁱⁱⁱ	0.96	2.60	3.368 (3)	137
C7—H7B⋯Cg^iv	0.96	2.62	3.577 (1)	168
Symmetry codes: (i) -x+1, -y, -z+2; (ii) x+1, y, z; (iii) x+1, y+1, z; (iv) x, y-1, z.

Figure 2
Unit-cell packing of the title compound, showing N—H⋯O and N—H⋯S interactions as dotted lines. H atoms not involved in hydrogen bonding have been excluded. See Table 1

for symmetry codes.

Figure 3
Unit-cell packing of the title compound, showing C—H⋯F interactions with dotted lines. H atoms not involved in hydrogen bonding have been excluded. See Table 1

for symmetry code.

Figure 4
Unit-cell packing depicting the C—H⋯π interaction as a dotted line.

Synthesis and crystallization

A mixture of 4-chloro-3-fluorobenzaldehyde (10 mmol), thiourea (10 mmol), ethyl acetoacetate (10 mmol) and a catalytic amount of concentrated hydrochloric acid in ethanol (20 ml) was refluxed for 8 h. The reaction mixture was allowed to stand overnight at room temperature. The solid thus separated was neutralized using an aqueous sodium carbonate solution and the obtained precipitate was filtered off and washed with a mixture of ethanol and water (1:1 v/v), and recrystallized from ethyl–acetate solution, yielding colourless blocks of the title compound (yield 80%; m.p. 422—425 °C). IR (KBr) (cm⁻¹): 3321 (CH), 1667 (C=O), 1572 (ester), 1487 (NH). ¹H NMR (CDCl₃): δ 1.2 (t, 3H), 2.5 (s, 3H), 4 (q, 3H), 5.3 (s, 1H), 7.05 (dd, 1H), 7.15 (dd, 1H), 7.52–7.60 (t, 3H). m/z: 328.086, (M + 2) 330.086, 331.06.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. H atoms were placed at calculated positions in the riding-model approximation, with C—H = 0.95, 1.00 and 0.96 Å for aromatic, methine and methyl H atoms, respectively, and with U_iso(H) = 1.5U_eq(C) for methyl H atoms and 1.2U_eq(C) otherwise.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₄H₁₄ClFN₂O₂S
M_r	328.78
Crystal system, space group	Triclinic, P $[\overline{1}]$
Temperature (K)	446
a, b, c (Å)	7.2599 (5), 9.4979 (7), 11.9596 (8)
α, β, γ (°)	106.149 (2), 90.236 (2), 108.939 (2)
V (Å³)	745.18 (9)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	0.41
Crystal size (mm)	0.18 × 0.16 × 0.15

Data collection
Diffractometer	Bruker SMART APEX CCD
Absorption correction	Multi-scan (SADABS; Bruker, 1998 )
T_min, T_max	0.930, 0.941
No. of measured, independent and observed [I > 2σ(I)] reflections	9007, 2630, 2087
R_int	0.042
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.054, 0.158, 1.03
No. of reflections	2630
No. of parameters	192
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	1.72, −0.58
Computer programs: SMART and SAINT (Bruker, 1998), SHELXS97 (Sheldrick, 2008 ), SHELXL2018 (Sheldrick, 2015 ) and ORTEP-3 for Windows (Farrugia, 2012 ).

Structural data

CCDC reference: 1835185

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S241431461900960X/hb4301sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S241431461900960X/hb4301Isup2.hkl

IR Supplementary file. DOI: https://doi.org/10.1107/S241431461900960X/hb4301sup3.pdf

NMR Supplementary file. DOI: https://doi.org/10.1107/S241431461900960X/hb4301sup4.tif

Mass Supplementary file. DOI: https://doi.org/10.1107/S241431461900960X/hb4301sup5.pdf

checkCIF report

Computing details top

Data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1998); data reduction: SAINT (Bruker, 1998); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015); molecular graphics: ORTEP-3 (Farrugia, 2012); software used to prepare material for publication: SHELXL2018 (Sheldrick, 2015).

Ethyl 4-(4-chloro-3-fluorophenyl)-6-methyl-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carboxylate top

Crystal data top

C₁₄H₁₄ClFN₂O₂S	F(000) = 340
M_r = 328.78	D_x = 1.465 Mg m⁻³
Triclinic, P1	Melting point: 696 K
a = 7.2599 (5) Å	Mo Kα radiation, λ = 0.71073 Å
b = 9.4979 (7) Å	Cell parameters from 2630 reflections
c = 11.9596 (8) Å	θ = 2.4–25.0°
α = 106.149 (2)°	µ = 0.41 mm⁻¹
β = 90.236 (2)°	T = 446 K
γ = 108.939 (2)°	Block, colorless
V = 745.18 (9) Å³	0.18 × 0.16 × 0.15 mm
Z = 2

Data collection top

Bruker SMART APEX CCD diffractometer	2087 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.042
ω scans	θ_max = 25.0°, θ_min = 2.4°
Absorption correction: multi-scan (SADABS; Bruker, 1998)	h = −8→8
T_min = 0.930, T_max = 0.941	k = −11→11
9007 measured reflections	l = −14→14
2630 independent reflections

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)] = 0.054	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.158	H-atom parameters constrained
S = 1.03	w = 1/[σ²(F_o²) + (0.0909P)² + 1.0474P] where P = (F_o² + 2F_c²)/3
2630 reflections	(Δ/σ)_max < 0.001
192 parameters	Δρ_max = 1.72 e Å⁻³
0 restraints	Δρ_min = −0.58 e Å⁻³

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

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

	x	y	z	U_iso*/U_eq
S1	0.80640 (12)	0.09215 (10)	0.95796 (7)	0.0197 (3)
Cl1	0.03066 (14)	−0.26657 (11)	0.39379 (8)	0.0338 (3)
O2	0.4590 (3)	0.5730 (3)	0.7799 (2)	0.0226 (6)
F1	−0.0960 (3)	−0.2780 (3)	0.6204 (2)	0.0425 (6)
O1	0.1990 (3)	0.4448 (3)	0.8562 (2)	0.0208 (5)
N2	0.4864 (4)	0.1580 (3)	0.9215 (2)	0.0170 (6)
H2	0.431451	0.099667	0.964027	0.020*
N1	0.7687 (4)	0.3128 (3)	0.8740 (2)	0.0167 (6)
H1	0.888114	0.327771	0.858940	0.020*
C13	0.1221 (5)	−0.0377 (4)	0.7349 (3)	0.0209 (8)
H13	0.068725	−0.053984	0.802681	0.025*
C8	0.2770 (5)	0.0978 (4)	0.7412 (3)	0.0169 (7)
C3	0.3659 (5)	0.4668 (4)	0.8320 (3)	0.0166 (7)
C4	0.3629 (5)	0.2150 (4)	0.8609 (3)	0.0153 (7)
H4	0.254875	0.225653	0.907590	0.018*
C2	0.6770 (5)	0.1905 (4)	0.9151 (3)	0.0162 (7)
C1	0.8217 (5)	0.5621 (4)	0.8419 (3)	0.0212 (8)
H1A	0.838551	0.549769	0.760558	0.032*
H1B	0.945410	0.584707	0.884459	0.032*
H1C	0.772705	0.646242	0.872113	0.032*
C7	0.4830 (6)	0.7615 (5)	0.6824 (4)	0.0304 (9)
H7A	0.607619	0.821085	0.727304	0.046*
H7B	0.423767	0.830729	0.664819	0.046*
H7C	0.501190	0.692882	0.610805	0.046*
C5	0.4835 (5)	0.3742 (4)	0.8520 (3)	0.0153 (7)
C10	0.2735 (5)	0.0099 (4)	0.5308 (3)	0.0233 (8)
H10	0.322306	0.027342	0.462235	0.028*
C14	0.3523 (5)	0.6672 (4)	0.7517 (3)	0.0229 (8)
H14A	0.326826	0.734864	0.822577	0.027*
H14B	0.228463	0.601271	0.705837	0.027*
C6	0.6797 (5)	0.4153 (4)	0.8551 (3)	0.0167 (7)
C9	0.3514 (5)	0.1203 (4)	0.6382 (3)	0.0211 (8)
H9	0.454970	0.210554	0.641312	0.025*
C12	0.0481 (5)	−0.1471 (4)	0.6293 (3)	0.0223 (8)
C11	0.1241 (5)	−0.1249 (4)	0.5265 (3)	0.0245 (8)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0175 (5)	0.0224 (5)	0.0247 (5)	0.0090 (4)	0.0040 (3)	0.0128 (4)
Cl1	0.0348 (6)	0.0350 (6)	0.0249 (5)	0.0135 (5)	−0.0060 (4)	−0.0033 (4)
O2	0.0191 (13)	0.0245 (13)	0.0328 (14)	0.0114 (11)	0.0069 (10)	0.0173 (11)
F1	0.0379 (14)	0.0399 (14)	0.0399 (13)	0.0011 (12)	0.0066 (11)	0.0109 (11)
O1	0.0150 (13)	0.0251 (13)	0.0251 (13)	0.0092 (11)	0.0039 (10)	0.0090 (10)
N2	0.0165 (15)	0.0187 (14)	0.0180 (14)	0.0052 (12)	0.0029 (11)	0.0098 (12)
N1	0.0134 (14)	0.0196 (14)	0.0226 (14)	0.0080 (12)	0.0079 (11)	0.0121 (12)
C13	0.0156 (17)	0.0267 (19)	0.0230 (17)	0.0080 (16)	0.0036 (14)	0.0106 (15)
C8	0.0132 (17)	0.0203 (17)	0.0203 (17)	0.0090 (15)	0.0009 (13)	0.0070 (14)
C3	0.0161 (18)	0.0151 (16)	0.0144 (15)	0.0029 (14)	−0.0010 (13)	0.0008 (13)
C4	0.0135 (17)	0.0198 (17)	0.0163 (16)	0.0077 (14)	0.0032 (13)	0.0084 (14)
C2	0.0182 (18)	0.0153 (16)	0.0134 (15)	0.0037 (14)	0.0013 (13)	0.0037 (13)
C1	0.0159 (18)	0.0209 (18)	0.0291 (19)	0.0063 (15)	0.0019 (14)	0.0112 (15)
C7	0.026 (2)	0.031 (2)	0.046 (2)	0.0152 (18)	0.0095 (18)	0.0225 (19)
C5	0.0171 (18)	0.0161 (16)	0.0130 (15)	0.0057 (14)	0.0018 (13)	0.0048 (13)
C10	0.027 (2)	0.028 (2)	0.0184 (17)	0.0147 (17)	0.0047 (15)	0.0075 (15)
C14	0.0226 (19)	0.0244 (19)	0.0305 (19)	0.0149 (16)	0.0040 (15)	0.0134 (16)
C6	0.0176 (17)	0.0194 (17)	0.0158 (16)	0.0075 (15)	0.0032 (13)	0.0076 (14)
C9	0.0189 (18)	0.0210 (18)	0.0245 (18)	0.0070 (15)	0.0026 (14)	0.0083 (15)
C12	0.0126 (17)	0.0141 (17)	0.036 (2)	0.0019 (15)	−0.0038 (15)	0.0046 (15)
C11	0.024 (2)	0.032 (2)	0.0192 (17)	0.0168 (18)	−0.0049 (15)	0.0010 (15)

Geometric parameters (Å, º) top

S1—C2	1.688 (3)	C4—C5	1.515 (4)
Cl1—C11	1.732 (3)	C4—H4	0.9800
O2—C3	1.331 (4)	C1—C6	1.491 (5)
O2—C14	1.460 (4)	C1—H1A	0.9600
F1—C12	1.316 (4)	C1—H1B	0.9600
O1—C3	1.211 (4)	C1—H1C	0.9600
N2—C2	1.324 (4)	C7—C14	1.502 (5)
N2—C4	1.467 (4)	C7—H7A	0.9600
N2—H2	0.8600	C7—H7B	0.9600
N1—C2	1.361 (4)	C7—H7C	0.9600
N1—C6	1.395 (4)	C5—C6	1.347 (5)
N1—H1	0.8600	C10—C11	1.371 (5)
C13—C12	1.365 (5)	C10—C9	1.390 (5)
C13—C8	1.391 (5)	C10—H10	0.9300
C13—H13	0.9300	C14—H14A	0.9700
C8—C9	1.390 (5)	C14—H14B	0.9700
C8—C4	1.527 (4)	C9—H9	0.9300
C3—C5	1.470 (5)	C12—C11	1.391 (5)

C3—O2—C14	117.4 (3)	C14—C7—H7A	109.5
C2—N2—C4	124.3 (3)	C14—C7—H7B	109.5
C2—N2—H2	117.8	H7A—C7—H7B	109.5
C4—N2—H2	117.8	C14—C7—H7C	109.5
C2—N1—C6	123.6 (3)	H7A—C7—H7C	109.5
C2—N1—H1	118.2	H7B—C7—H7C	109.5
C6—N1—H1	118.2	C6—C5—C3	126.0 (3)
C12—C13—C8	120.1 (3)	C6—C5—C4	119.9 (3)
C12—C13—H13	119.9	C3—C5—C4	113.9 (3)
C8—C13—H13	119.9	C11—C10—C9	119.5 (3)
C9—C8—C13	118.7 (3)	C11—C10—H10	120.2
C9—C8—C4	122.2 (3)	C9—C10—H10	120.2
C13—C8—C4	119.1 (3)	O2—C14—C7	105.4 (3)
O1—C3—O2	123.5 (3)	O2—C14—H14A	110.7
O1—C3—C5	123.5 (3)	C7—C14—H14A	110.7
O2—C3—C5	113.0 (3)	O2—C14—H14B	110.7
N2—C4—C5	108.9 (3)	C7—C14—H14B	110.7
N2—C4—C8	109.9 (2)	H14A—C14—H14B	108.8
C5—C4—C8	112.3 (3)	C5—C6—N1	118.7 (3)
N2—C4—H4	108.5	C5—C6—C1	127.9 (3)
C5—C4—H4	108.5	N1—C6—C1	113.3 (3)
C8—C4—H4	108.5	C10—C9—C8	121.0 (3)
N2—C2—N1	116.3 (3)	C10—C9—H9	119.5
N2—C2—S1	123.4 (2)	C8—C9—H9	119.5
N1—C2—S1	120.2 (2)	F1—C12—C13	121.7 (3)
C6—C1—H1A	109.5	F1—C12—C11	117.3 (3)
C6—C1—H1B	109.5	C13—C12—C11	121.0 (3)
H1A—C1—H1B	109.5	C10—C11—C12	119.6 (3)
C6—C1—H1C	109.5	C10—C11—Cl1	120.2 (3)
H1A—C1—H1C	109.5	C12—C11—Cl1	120.3 (3)
H1B—C1—H1C	109.5

C12—C13—C8—C9	1.1 (5)	N2—C4—C5—C3	−159.6 (2)
C12—C13—C8—C4	−177.4 (3)	C8—C4—C5—C3	78.4 (3)
C14—O2—C3—O1	0.3 (5)	C3—O2—C14—C7	−173.6 (3)
C14—O2—C3—C5	177.6 (3)	C3—C5—C6—N1	−179.4 (3)
C2—N2—C4—C5	−32.1 (4)	C4—C5—C6—N1	−4.0 (4)
C2—N2—C4—C8	91.4 (4)	C3—C5—C6—C1	1.3 (5)
C9—C8—C4—N2	−102.3 (3)	C4—C5—C6—C1	176.7 (3)
C13—C8—C4—N2	76.1 (4)	C2—N1—C6—C5	−15.2 (5)
C9—C8—C4—C5	19.2 (4)	C2—N1—C6—C1	164.2 (3)
C13—C8—C4—C5	−162.4 (3)	C11—C10—C9—C8	−1.6 (5)
C4—N2—C2—N1	16.7 (4)	C13—C8—C9—C10	−0.1 (5)
C4—N2—C2—S1	−165.0 (2)	C4—C8—C9—C10	178.4 (3)
C6—N1—C2—N2	9.3 (4)	C8—C13—C12—F1	178.7 (3)
C6—N1—C2—S1	−169.1 (2)	C8—C13—C12—C11	−0.6 (5)
O1—C3—C5—C6	−162.2 (3)	C9—C10—C11—C12	2.2 (5)
O2—C3—C5—C6	20.5 (5)	C9—C10—C11—Cl1	−177.9 (3)
O1—C3—C5—C4	22.2 (4)	F1—C12—C11—C10	179.6 (3)
O2—C3—C5—C4	−155.2 (3)	C13—C12—C11—C10	−1.1 (5)
N2—C4—C5—C6	24.5 (4)	F1—C12—C11—Cl1	−0.4 (4)
C8—C4—C5—C6	−97.6 (3)	C13—C12—C11—Cl1	179.0 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···S1ⁱ	0.86	2.47	3.301 (1)	163
N1—H1···O1ⁱⁱ	0.86	2.17	2.998 (2)	160
C1—H1A···F1ⁱⁱⁱ	0.96	2.60	3.368 (3)	137
C7—H7B···Cg^iv	0.96	2.62	3.577 (1)	168

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

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