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

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

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.

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

The title compound is a di­hydro­pyrimidine derivative (Kappe, 2000[Kappe, C. O. (2000). Eur. J. Med. Chem. 35, 1043-1052.]). Some of these compounds have therapeutic and pharmacological properties, such as anti­carcinogenic (Mayer et al., 1999[Mayer, T. U., Kapoor, T. M., Haggarty, S. J., King, R. W., Schreiber, S. I. & Mitchison, T. (1999). Science, 286, 971-974.]) activity. They have also emerged as integral backbones of several calcium-channel modulators (Jauk et al., 2000[Jauk, B., Pernat, T. & Kappe, C. O. (2000). Molecules, 5, 227-239.]). As part of our studies in this area, we now describe the synthesis and structure of the title compound (Fig. 1[link]).

[Figure 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[link]), resulting in centrosymmetric R22(8) loops and also displays [100] chains linked by N1—H1⋯O1ii hydrogen bonds (Fig. 2[link]). In addition, the packing is consolidated by a C1—H1A⋯F1iii inter­action along the [110] direction (Fig. 3[link]) and a C7—H7BCgiv inter­action (Cg being the centroid of the C8–C13 ring), with a H⋯Cg distance of 2.62 Å (Fig. 4[link]).

Table 1
Hydrogen-bond geometry (Å, °)

Cg is the centroid of the C8–C13 ring.

D—H⋯A D—H H⋯A DA 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—H7BCgiv 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]
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[link] for symmetry codes.
[Figure 3]
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[link] for symmetry code.
[Figure 4]
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[link]. 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 Uiso(H) = 1.5Ueq(C) for methyl H atoms and 1.2Ueq(C) otherwise.

Table 2
Experimental details

Crystal data
Chemical formula C14H14ClFN2O2S
Mr 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)
V3) 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[Bruker (1998). SMART, SAINT-Plus and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.930, 0.941
No. of measured, independent and observed [I > 2σ(I)] reflections 9007, 2630, 2087
Rint 0.042
(sin θ/λ)max−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
Δρmax, Δρmin (e Å−3) 1.72, −0.58
Computer programs: SMART and SAINT (Bruker, 1998[Bruker (1998). SMART, SAINT-Plus and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2018 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]) and ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]).

Structural data


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
C14H14ClFN2O2SF(000) = 340
Mr = 328.78Dx = 1.465 Mg m3
Triclinic, P1Melting point: 696 K
a = 7.2599 (5) ÅMo Kα radiation, λ = 0.71073 Å
b = 9.4979 (7) ÅCell parameters from 2630 reflections
c = 11.9596 (8) Åθ = 2.4–25.0°
α = 106.149 (2)°µ = 0.41 mm1
β = 90.236 (2)°T = 446 K
γ = 108.939 (2)°Block, colorless
V = 745.18 (9) Å30.18 × 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 tubeRint = 0.042
ω scansθmax = 25.0°, θmin = 2.4°
Absorption correction: multi-scan
(SADABS; Bruker, 1998)
h = 88
Tmin = 0.930, Tmax = 0.941k = 1111
9007 measured reflectionsl = 1414
2630 independent reflections
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)] = 0.054Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.158H-atom parameters constrained
S = 1.03 w = 1/[σ2(Fo2) + (0.0909P)2 + 1.0474P]
where P = (Fo2 + 2Fc2)/3
2630 reflections(Δ/σ)max < 0.001
192 parametersΔρmax = 1.72 e Å3
0 restraintsΔρmin = 0.58 e Å3
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
xyzUiso*/Ueq
S10.80640 (12)0.09215 (10)0.95796 (7)0.0197 (3)
Cl10.03066 (14)0.26657 (11)0.39379 (8)0.0338 (3)
O20.4590 (3)0.5730 (3)0.7799 (2)0.0226 (6)
F10.0960 (3)0.2780 (3)0.6204 (2)0.0425 (6)
O10.1990 (3)0.4448 (3)0.8562 (2)0.0208 (5)
N20.4864 (4)0.1580 (3)0.9215 (2)0.0170 (6)
H20.4314510.0996670.9640270.020*
N10.7687 (4)0.3128 (3)0.8740 (2)0.0167 (6)
H10.8881140.3277710.8589400.020*
C130.1221 (5)0.0377 (4)0.7349 (3)0.0209 (8)
H130.0687250.0539840.8026810.025*
C80.2770 (5)0.0978 (4)0.7412 (3)0.0169 (7)
C30.3659 (5)0.4668 (4)0.8320 (3)0.0166 (7)
C40.3629 (5)0.2150 (4)0.8609 (3)0.0153 (7)
H40.2548750.2256530.9075900.018*
C20.6770 (5)0.1905 (4)0.9151 (3)0.0162 (7)
C10.8217 (5)0.5621 (4)0.8419 (3)0.0212 (8)
H1A0.8385510.5497690.7605580.032*
H1B0.9454100.5847070.8844590.032*
H1C0.7727050.6462420.8721130.032*
C70.4830 (6)0.7615 (5)0.6824 (4)0.0304 (9)
H7A0.6076190.8210850.7273040.046*
H7B0.4237670.8307290.6648190.046*
H7C0.5011900.6928820.6108050.046*
C50.4835 (5)0.3742 (4)0.8520 (3)0.0153 (7)
C100.2735 (5)0.0099 (4)0.5308 (3)0.0233 (8)
H100.3223060.0273420.4622350.028*
C140.3523 (5)0.6672 (4)0.7517 (3)0.0229 (8)
H14A0.3268260.7348640.8225770.027*
H14B0.2284630.6012710.7058370.027*
C60.6797 (5)0.4153 (4)0.8551 (3)0.0167 (7)
C90.3514 (5)0.1203 (4)0.6382 (3)0.0211 (8)
H90.4549700.2105540.6413120.025*
C120.0481 (5)0.1471 (4)0.6293 (3)0.0223 (8)
C110.1241 (5)0.1249 (4)0.5265 (3)0.0245 (8)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0175 (5)0.0224 (5)0.0247 (5)0.0090 (4)0.0040 (3)0.0128 (4)
Cl10.0348 (6)0.0350 (6)0.0249 (5)0.0135 (5)0.0060 (4)0.0033 (4)
O20.0191 (13)0.0245 (13)0.0328 (14)0.0114 (11)0.0069 (10)0.0173 (11)
F10.0379 (14)0.0399 (14)0.0399 (13)0.0011 (12)0.0066 (11)0.0109 (11)
O10.0150 (13)0.0251 (13)0.0251 (13)0.0092 (11)0.0039 (10)0.0090 (10)
N20.0165 (15)0.0187 (14)0.0180 (14)0.0052 (12)0.0029 (11)0.0098 (12)
N10.0134 (14)0.0196 (14)0.0226 (14)0.0080 (12)0.0079 (11)0.0121 (12)
C130.0156 (17)0.0267 (19)0.0230 (17)0.0080 (16)0.0036 (14)0.0106 (15)
C80.0132 (17)0.0203 (17)0.0203 (17)0.0090 (15)0.0009 (13)0.0070 (14)
C30.0161 (18)0.0151 (16)0.0144 (15)0.0029 (14)0.0010 (13)0.0008 (13)
C40.0135 (17)0.0198 (17)0.0163 (16)0.0077 (14)0.0032 (13)0.0084 (14)
C20.0182 (18)0.0153 (16)0.0134 (15)0.0037 (14)0.0013 (13)0.0037 (13)
C10.0159 (18)0.0209 (18)0.0291 (19)0.0063 (15)0.0019 (14)0.0112 (15)
C70.026 (2)0.031 (2)0.046 (2)0.0152 (18)0.0095 (18)0.0225 (19)
C50.0171 (18)0.0161 (16)0.0130 (15)0.0057 (14)0.0018 (13)0.0048 (13)
C100.027 (2)0.028 (2)0.0184 (17)0.0147 (17)0.0047 (15)0.0075 (15)
C140.0226 (19)0.0244 (19)0.0305 (19)0.0149 (16)0.0040 (15)0.0134 (16)
C60.0176 (17)0.0194 (17)0.0158 (16)0.0075 (15)0.0032 (13)0.0076 (14)
C90.0189 (18)0.0210 (18)0.0245 (18)0.0070 (15)0.0026 (14)0.0083 (15)
C120.0126 (17)0.0141 (17)0.036 (2)0.0019 (15)0.0038 (15)0.0046 (15)
C110.024 (2)0.032 (2)0.0192 (17)0.0168 (18)0.0049 (15)0.0010 (15)
Geometric parameters (Å, º) top
S1—C21.688 (3)C4—C51.515 (4)
Cl1—C111.732 (3)C4—H40.9800
O2—C31.331 (4)C1—C61.491 (5)
O2—C141.460 (4)C1—H1A0.9600
F1—C121.316 (4)C1—H1B0.9600
O1—C31.211 (4)C1—H1C0.9600
N2—C21.324 (4)C7—C141.502 (5)
N2—C41.467 (4)C7—H7A0.9600
N2—H20.8600C7—H7B0.9600
N1—C21.361 (4)C7—H7C0.9600
N1—C61.395 (4)C5—C61.347 (5)
N1—H10.8600C10—C111.371 (5)
C13—C121.365 (5)C10—C91.390 (5)
C13—C81.391 (5)C10—H100.9300
C13—H130.9300C14—H14A0.9700
C8—C91.390 (5)C14—H14B0.9700
C8—C41.527 (4)C9—H90.9300
C3—C51.470 (5)C12—C111.391 (5)
C3—O2—C14117.4 (3)C14—C7—H7A109.5
C2—N2—C4124.3 (3)C14—C7—H7B109.5
C2—N2—H2117.8H7A—C7—H7B109.5
C4—N2—H2117.8C14—C7—H7C109.5
C2—N1—C6123.6 (3)H7A—C7—H7C109.5
C2—N1—H1118.2H7B—C7—H7C109.5
C6—N1—H1118.2C6—C5—C3126.0 (3)
C12—C13—C8120.1 (3)C6—C5—C4119.9 (3)
C12—C13—H13119.9C3—C5—C4113.9 (3)
C8—C13—H13119.9C11—C10—C9119.5 (3)
C9—C8—C13118.7 (3)C11—C10—H10120.2
C9—C8—C4122.2 (3)C9—C10—H10120.2
C13—C8—C4119.1 (3)O2—C14—C7105.4 (3)
O1—C3—O2123.5 (3)O2—C14—H14A110.7
O1—C3—C5123.5 (3)C7—C14—H14A110.7
O2—C3—C5113.0 (3)O2—C14—H14B110.7
N2—C4—C5108.9 (3)C7—C14—H14B110.7
N2—C4—C8109.9 (2)H14A—C14—H14B108.8
C5—C4—C8112.3 (3)C5—C6—N1118.7 (3)
N2—C4—H4108.5C5—C6—C1127.9 (3)
C5—C4—H4108.5N1—C6—C1113.3 (3)
C8—C4—H4108.5C10—C9—C8121.0 (3)
N2—C2—N1116.3 (3)C10—C9—H9119.5
N2—C2—S1123.4 (2)C8—C9—H9119.5
N1—C2—S1120.2 (2)F1—C12—C13121.7 (3)
C6—C1—H1A109.5F1—C12—C11117.3 (3)
C6—C1—H1B109.5C13—C12—C11121.0 (3)
H1A—C1—H1B109.5C10—C11—C12119.6 (3)
C6—C1—H1C109.5C10—C11—Cl1120.2 (3)
H1A—C1—H1C109.5C12—C11—Cl1120.3 (3)
H1B—C1—H1C109.5
C12—C13—C8—C91.1 (5)N2—C4—C5—C3159.6 (2)
C12—C13—C8—C4177.4 (3)C8—C4—C5—C378.4 (3)
C14—O2—C3—O10.3 (5)C3—O2—C14—C7173.6 (3)
C14—O2—C3—C5177.6 (3)C3—C5—C6—N1179.4 (3)
C2—N2—C4—C532.1 (4)C4—C5—C6—N14.0 (4)
C2—N2—C4—C891.4 (4)C3—C5—C6—C11.3 (5)
C9—C8—C4—N2102.3 (3)C4—C5—C6—C1176.7 (3)
C13—C8—C4—N276.1 (4)C2—N1—C6—C515.2 (5)
C9—C8—C4—C519.2 (4)C2—N1—C6—C1164.2 (3)
C13—C8—C4—C5162.4 (3)C11—C10—C9—C81.6 (5)
C4—N2—C2—N116.7 (4)C13—C8—C9—C100.1 (5)
C4—N2—C2—S1165.0 (2)C4—C8—C9—C10178.4 (3)
C6—N1—C2—N29.3 (4)C8—C13—C12—F1178.7 (3)
C6—N1—C2—S1169.1 (2)C8—C13—C12—C110.6 (5)
O1—C3—C5—C6162.2 (3)C9—C10—C11—C122.2 (5)
O2—C3—C5—C620.5 (5)C9—C10—C11—Cl1177.9 (3)
O1—C3—C5—C422.2 (4)F1—C12—C11—C10179.6 (3)
O2—C3—C5—C4155.2 (3)C13—C12—C11—C101.1 (5)
N2—C4—C5—C624.5 (4)F1—C12—C11—Cl10.4 (4)
C8—C4—C5—C697.6 (3)C13—C12—C11—Cl1179.0 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2···S1i0.862.473.301 (1)163
N1—H1···O1ii0.862.172.998 (2)160
C1—H1A···F1iii0.962.603.368 (3)137
C7—H7B···Cgiv0.962.623.577 (1)168
Symmetry codes: (i) x+1, y, z+2; (ii) x+1, y, z; (iii) x+1, y+1, z; (iv) x, y1, z.
 

References

First citationBruker (1998). SMART, SAINT-Plus and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationFarrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationJauk, B., Pernat, T. & Kappe, C. O. (2000). Molecules, 5, 227–239.  Web of Science CrossRef CAS Google Scholar
First citationKappe, C. O. (2000). Eur. J. Med. Chem. 35, 1043–1052.  Web of Science CrossRef PubMed CAS Google Scholar
First citationMayer, T. U., Kapoor, T. M., Haggarty, S. J., King, R. W., Schreiber, S. I. & Mitchison, T. (1999). Science, 286, 971–974.  Web of Science CrossRef PubMed CAS Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar

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