Crystal structure of ethyl 4-(2-fluoro­phen­yl)-6-methyl-2-sulfanyl­idene-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate

M S Krishnamurthy; Noor Shahina Begum

doi:10.1107/S2056989015015145

. 2015 Sep 12;71(Pt 10):o699–o700. doi: 10.1107/S2056989015015145

Crystal structure of ethyl 4-(2-fluorophenyl)-6-methyl-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carboxylate

M S Krishnamurthy ^a, Noor Shahina Begum ^a,^*

PMCID: PMC4647406 PMID: 26594430

Abstract

The title compound, C₁₄H₁₅FN₂O₂S, crystallizes with two molecules in the asymmetric unit. In each molecule, the pyrimidine ring adopts a sofa conformation with the sp ³-hybridized C atom forming the flap and the fluoro-substituted ring in an axial position. In the crystal, molecules are linked via N—H⋯S hydrogen bonds, forming chains of R ₂ ²(8) rings along [100]. In one independent molecule, an intramolecular C—H⋯O hydrogen bond is observed.

Keywords: crystal structure; ester; pyrimidine; hydrogen bonding; 3,4-dihydropyrimidin-2(1H)-one; therapeutic properties; pharmacological properties

Related literature

For the therapeutic and pharmacological properties of 3,4-dihydropyrimidin-2(1H)-ones, see: Kappe (2000 ▸); Hurst & Hull (1961 ▸); Mayer et al. (1999 ▸); Atwal et al. (1991 ▸). For their applications in calcium-channel modulators, see: Kappe (1998 ▸); Jauk et al. (2000 ▸); Krishnamurthy & Begum (2015 ▸). For the bioactivity of organo–fluorine compounds, see: Hermann et al. (2003 ▸); Ulrich (2004 ▸). For examples of fluorine-directed crystal packing, see: Prasanna & Guru Row (2001 ▸). For related structures, see: Qin et al. (2006 ▸); Krishnamurthy & Begum (2015 ▸). For hydrogen-bond graph-set notation, see: Bernstein et al. (1995 ▸). graphic file with name e-71-0o699-scheme1.jpg

Experimental

Crystal data

C₁₄H₁₅FN₂O₂S
M _r = 294.34
Triclinic,
a = 8.9298 (6) Å
b = 11.5870 (8) Å
c = 15.7459 (11) Å
α = 100.940 (2)°
β = 104.804 (2)°
γ = 98.153 (2)°
V = 1515.11 (18) Å³
Z = 4
Mo Kα radiation
μ = 0.23 mm⁻¹
T = 100 K
0.18 × 0.16 × 0.16 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1998 ▸) T _min = 0.960, T _max = 0.965
17808 measured reflections
5328 independent reflections
3389 reflections with I > 2σ(I)
R _int = 0.039

Refinement

R[F ² > 2σ(F ²)] = 0.075
wR(F ²) = 0.228
S = 0.98
5328 reflections
365 parameters
H-atom parameters constrained
Δρ_max = 1.04 e Å⁻³
Δρ_min = −0.36 e Å⁻³

Data collection: SMART (Bruker, 1998 ▸); cell refinement: SMART; 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 ▸), CAMERON (Watkin et al., 1996 ▸) and DIAMOND (Brandenburg & Berndt, 1999 ▸); software used to prepare material for publication: WinGX (Farrugia, 2012 ▸).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989015015145/lh5781sup1.cif

e-71-0o699-sup1.cif^{(25.6KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015015145/lh5781Isup2.hkl

e-71-0o699-Isup2.hkl^{(255.6KB, hkl)}

Click here for additional data file.^{(5.5KB, cml)}

Supporting information file. DOI: 10.1107/S2056989015015145/lh5781Isup3.cml

Click here for additional data file.^{(1.3MB, tif)}

. DOI: 10.1107/S2056989015015145/lh5781fig1.tif

The asymmetric unit of the title compound with displacement ellipsoids drawn at the 50% probability level. H atoms are presented as small spheres of arbitrary radius.

Click here for additional data file.^{(1.4MB, tif)}

. DOI: 10.1107/S2056989015015145/lh5781fig2.tif

Part of the crystal structure with hydrogen bonds shown as dashed lines.

CCDC reference: 1418668

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (, ).

DHA	DH	HA	D A	DHA
N1H1S1ⁱ	0.88	2.83	3.703(4)	170
N1H1S1	0.88	2.84	3.711(4)	171
N2H2S1	0.88	2.52	3.337(4)	155
N2H2S1ⁱⁱ	0.88	2.50	3.335(5)	158
C1H11O1	0.98	2.14	2.861(6)	129

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

MSK thanks for the University Grants Commission (UGC), India, for the UGC–BSR Meritorious fellowship.

supplementary crystallographic information

S1. Comment

The Biginelli reaction is a three-component condensation of ethyl acetoacetate, benzaldehyde and urea for the synthesis of 3,4-dihydropyrimidine-2(1H) -ones (abbreviated as DHPMs). DHPMs have recently emerged as important target molecules because of their therapeutic and pharmacological properties (Kappe, 2000), such as antiviral (Hurst & Hull, 1961), antimitotic (Mayer et al., 1999), anticarcinogenic and antihypertensive (Atwal et al., 1991). They are also noteworthy as calcium channel modulators (Kappe, 1998; Jauk et al., 2000). In addition, compounds that contain fluorine have special bioactivity, e.g. flumioxazin is a widely used herbicide (Hermann et al., 2003; Ulrich, 2004). Guru Row and co-workers have extensively studied the structural property of fluorine and they have presented several elegant examples of fluorine directed crystal packing (Prasanna & Guru Row, 2001). Herein, we report the crystal structure of the title compound.

The asymmetric unit of the title compound is shown in Fig. 1. There are two indpendent molecules in the asymmetric unit. The bond lengths and bond angles are in good agreement with the corresponding bond distances and angles reported in closely related structures (Qin et al., 2006; Krishnamurthy & Begum, 2015). In each molecule, the pyrimidine ring adopts a sofa conformation with the sp³ hybridized carbon atom [C4 and C4'] forming the flap and the fluoro-substituted ring in an axial position. The carbonyl group of the exocyclic ester at C5 and C5' adopts a cis orientation with respect to the C5═C6 and C5'═C6 double bond. The fluoro-substituted benzene ring adopts an syn periplanar conformation with respect to the C4—H4 and C4'—H4' bonds. In the crystal, molecules are linked via N—H···S hydrogen bonds forming chains of R₂²(8) rings (Bernstein et al., 1995) along [100] (Fig. 2). In one independent molecule an intramolecular C—H···O hydrogen bond is observed.

S2. Experimental

The title compound was synthesized by the reaction of 2-fluorobenzaldehyde (1.24 g, 10 mmol), ethylacetoacetate (1.52 g, 12 mmol) and thiourea (1.14 g, 15 mmol) in 15 ml ethanol was refluxed for 6 h in the presence of concentrated hydrochloric acid as a catalyst. The reaction was monitored with TLC and the reaction medium was quenched in ice cold water. The precipitate obtained was filtered and dried. The compound was recrystallized from ethanol solvent by slow evaporation method, yielding colorless blocks suitable for X-ray diffraction studies (yield 76%; m.p. 485 K).