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

M S Krishnamurthy; Noor Shahina Begum

doi:10.1107/S2056989015018873

. 2015 Oct 14;71(Pt 11):o838–o839. doi: 10.1107/S2056989015018873

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

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

PMCID: PMC4645072 PMID: 26594554

Abstract

In the title compound, C₁₃H₁₃FN₂O₂S, the pyrimidine ring adopts a twist-boat conformation with the MeCN and methine-C atoms displaced by 0.0938 (6) and 0.2739 (3) Å, respectively, from the mean plane through the other four atoms of the ring. The 2-fluorobenzene ring is positioned axially and forms a dihedral angle of 89.13 (4)° with the mean plane through the pyrimidine ring. The crystal structure features N—H⋯O, N—H⋯S and C—H⋯O hydrogen bonds that link molecules into supramolecular chains along the b axis. These chains are linked into a layer parallel to (10-1) by C—H⋯π interactions; layers stack with no specific interactions between them.

Keywords: crystal structure; pyrimidine derivative; hydrogen bonding,C—H⋯π interactions

Related literature

For the bioactivity of organo-fluorine compounds, see: Guru Row, (1999 ▸); Yamazaki et al., (2009 ▸). For biological activity of pyrimidine derivatives, see: Kappe (2000 ▸) and of dihydropyrimidines (DHPMs) and their derivatives, see; Jauk et al. (2000 ▸); Kappe (1998 ▸); Mayer et al. (1999 ▸). For the Biginelli reaction, see: Biginelli (1893 ▸). For bond length data, see: Qin et al. (2006 ▸). For related structures, see: Krishnamurthy & Begum (2015a ▸,b ▸). graphic file with name e-71-0o838-scheme1.jpg

Experimental

Crystal data

C₁₃H₁₃FN₂O₂S
M _r = 280.31
Monoclinic,
a = 13.3298 (15) Å
b = 7.1509 (8) Å
c = 14.5703 (17) Å
β = 109.854 (4)°
V = 1306.3 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.26 mm⁻¹
T = 100 K
0.24 × 0.22 × 0.18 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1998 ▸) T _min = 0.955, T _max = 0.960
9937 measured reflections
2296 independent reflections
1340 reflections with I > 2σ(I)
R _int = 0.112

Refinement

R[F ² > 2σ(F ²)] = 0.064
wR(F ²) = 0.133
S = 0.95
2296 reflections
174 parameters
H-atom parameters constrained
Δρ_max = 0.42 e Å⁻³
Δρ_min = −0.26 e Å⁻³

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 CAMERON (Watkin et al., 1996 ▸); software used to prepare material for publication: WinGX (Farrugia, 2012 ▸).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989015018873/tk5392sup1.cif

e-71-0o838-sup1.cif^{(17.4KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015018873/tk5392Isup2.hkl

e-71-0o838-Isup2.hkl^{(110.6KB, hkl)}

Click here for additional data file.^{(5.2KB, cml)}

Supporting information file. DOI: 10.1107/S2056989015018873/tk5392Isup3.cml

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

. DOI: 10.1107/S2056989015018873/tk5392fig1.tif

The molecular structure of the title compound with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are presented as small spheres of arbitrary radius.

Click here for additional data file.^{(4.2MB, tif)}

. DOI: 10.1107/S2056989015018873/tk5392fig2.tif

Unit cell packing of the title compound showing intermolecular C—H⋯O, N—H⋯O and N—H⋯S interactions as dotted lines. H atoms not involved in hydrogen bonding have been excluded.

CCDC reference: 1430034

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

Table 1. Hydrogen-bond geometry (, ).

Cg is the centroid of the C8C13 ring.

DHA	DH	HA	D A	DHA
N1H1O1ⁱ	0.88	2.14	2.977(4)	159
N2H2S1ⁱⁱ	0.88	2.55	3.386(2)	159
C1H1BO1ⁱ	0.98	2.52	3.262(5)	133
C10H10Cg ⁱⁱⁱ	0.95	2.86	3.648(2)	141

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

Acknowledgments

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

supplementary crystallographic information

S1. Comment

In recent years, dihydropyrimidines (DHPMs) and their derivatives have attracted considerable attention in synthetic organic chemistry because of their wide range of biological activities (Kappe et al., 2000), such as antibacterial, antiviral, antitumor and anti-inflammatory activities (Mayer et al., 1999). The Biginelli reaction (Biginelli et al., 1893), a one-pot condensation of aldehyde, acetoacetate and urea under strongly acidic conditions, is one of the most useful multicomponent reactions (MCRs), gaining increasing importance in organic and medicinal chemistry because of its capacity to generate multifunctionalized products including 3,4-dihydropyrimidin-2-ones, their thione analogs, and other related heterocyclic compounds. They are also noteworthy as calcium channel modulators (Kappe, 1998; Jauk et al., 2000). The presence of a fluorine atom in the molecule can have profound and unexpected results on the biological activity of the compound (Guru Row, 1999; Yamazaki et al., 2009). Herein, we report the crystal structure of the title compound. It is one of the analogue of our previously reported fluoro-DHPMs (Krishnamurthy & Begum, 2015a; Krishnamurthy & Begum, 2015b). The bond lengths and angles in the title compound are in good agreement with the corresponding bond distances and angles reported in closely related structures (Quin et al., 2006).

In the title compound, Fig. 1, the 2-fluorobenzene ring at chiral carbon atom C4 is positioned axially and bisects the pyrimidine ring with a dihedral angle of 89.13 (4)°. The pyrimidine ring adopts a twist-boat conformation with atoms C4 and N1 displaced by 0.2739 (3) Å and 0.0938 (6) Å from the mean plane of the other four atoms (C5/C6/C2/N2) respectively. The carbonyl group of the exocyclic ester at C5 adopts a trans orientation with respect to C5=C6 double bond. The 2-fluorobenzene ring shows an anti periplanar conformation with respect to C4—H4 bond of the pyrimidine ring. The molecular structure is stabilized by intermolecular C1—H1B···O1 and N1—H1···O1 interactions generating bifurcated bonds from two donor atoms C1 and N1, to the same acceptor O1 to form an R²₂(6) ring motif, which are in turn linked to form a molecular chain along crystallographic b axis. The packing is further stabilized by intermolecular N—H···S hydrogen bonds (N2—H2···S1) resulting in a centrosymmetric head to head dimer with graph set R²₂(8) notation (Table 1; Fig. 2). In addition, the crystal structure is stabilized by C10—H10···Cg (Cg is the centroid of aryl ring C8—C13) interaction (Table 1).

S2. Experimental

The title compound was synthesized by the reaction of 2-fluorobenzaldehyde (1.24 g, 10 mmol), methylacetoacetate (1.38 g, 12 mmol) and thiourea (1.14 g, 15 mmol) in 15 ml ethanol. The solution 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 72%; m.p. 476 K).