organic compounds
of methyl 4-(2-fluorophenyl)-6-methyl-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carboxylate
aDepartment of Studies in Chemistry, Bangalore University, Bangalore 560 001, Karnataka, India
*Correspondence e-mail: noorsb@rediffmail.com
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 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.
CCDC reference: 1430034
1. 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).
2. Experimental
2.1. Crystal data
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2.3. Refinement
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Data collection: SMART (Bruker, 1998); cell 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).
Supporting information
CCDC reference: 1430034
https://doi.org/10.1107/S2056989015018873/tk5392sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989015018873/tk5392Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2056989015018873/tk5392Isup3.cml
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).
The H atoms were placed at calculated positions in the riding-model approximation with N—H = 0.86 Å and C—H = 0.93–0.96 Å, and with Uiso(H) = 1.5Ueq(C) for methyl H atoms and Uiso(H) = 1.2Ueq(N, C) for the other hydrogen atoms.
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
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 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
is stabilized by C10—H10···Cg (Cg is the centroid of aryl ring C8—C13) interaction (Table 1).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).
Data collection: SMART (Bruker, 1998); cell
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 CAMERON (Watkin et al., 1996); software used to prepare material for publication: WinGX (Farrugia, 2012).Fig. 1. 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. | |
Fig. 2. 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. |
C13H13FN2O2S | F(000) = 584 |
Mr = 280.31 | Dx = 1.425 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2yn | Cell parameters from 2296 reflections |
a = 13.3298 (15) Å | θ = 3.0–25.0° |
b = 7.1509 (8) Å | µ = 0.26 mm−1 |
c = 14.5703 (17) Å | T = 100 K |
β = 109.854 (4)° | Block, colourless |
V = 1306.3 (3) Å3 | 0.24 × 0.22 × 0.18 mm |
Z = 4 |
Bruker SMART APEX CCD diffractometer | 2296 independent reflections |
Radiation source: fine-focus sealed tube | 1340 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.112 |
ω scans | θmax = 25.0°, θmin = 3.0° |
Absorption correction: multi-scan (SADABS; Bruker, 1998) | h = −15→15 |
Tmin = 0.955, Tmax = 0.960 | k = −8→8 |
9937 measured reflections | l = −15→17 |
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)] = 0.064 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.133 | H-atom parameters constrained |
S = 0.95 | w = 1/[σ2(Fo2) + (0.0421P)2 + 1.6067P] where P = (Fo2 + 2Fc2)/3 |
2296 reflections | (Δ/σ)max < 0.001 |
174 parameters | Δρmax = 0.42 e Å−3 |
0 restraints | Δρmin = −0.26 e Å−3 |
C13H13FN2O2S | V = 1306.3 (3) Å3 |
Mr = 280.31 | Z = 4 |
Monoclinic, P21/n | Mo Kα radiation |
a = 13.3298 (15) Å | µ = 0.26 mm−1 |
b = 7.1509 (8) Å | T = 100 K |
c = 14.5703 (17) Å | 0.24 × 0.22 × 0.18 mm |
β = 109.854 (4)° |
Bruker SMART APEX CCD diffractometer | 2296 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 1998) | 1340 reflections with I > 2σ(I) |
Tmin = 0.955, Tmax = 0.960 | Rint = 0.112 |
9937 measured reflections |
R[F2 > 2σ(F2)] = 0.064 | 0 restraints |
wR(F2) = 0.133 | H-atom parameters constrained |
S = 0.95 | Δρmax = 0.42 e Å−3 |
2296 reflections | Δρmin = −0.26 e Å−3 |
174 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
S1 | 0.95357 (8) | 0.77963 (14) | 0.05365 (8) | 0.0312 (3) | |
O1 | 0.6807 (2) | 0.0312 (4) | 0.0894 (2) | 0.0452 (9) | |
O2 | 0.5913 (2) | 0.2422 (3) | 0.1440 (2) | 0.0460 (8) | |
N1 | 0.7803 (2) | 0.6600 (4) | 0.0856 (2) | 0.0310 (9) | |
H1 | 0.7685 | 0.7788 | 0.0941 | 0.037* | |
N2 | 0.8688 (2) | 0.4407 (4) | 0.0289 (2) | 0.0243 (8) | |
H2 | 0.9267 | 0.4070 | 0.0170 | 0.029* | |
F1 | 0.64843 (18) | 0.5589 (3) | −0.10951 (18) | 0.0491 (7) | |
C1 | 0.6436 (4) | 0.6093 (5) | 0.1568 (4) | 0.0500 (14) | |
H1A | 0.5696 | 0.6128 | 0.1121 | 0.075* | |
H1B | 0.6672 | 0.7365 | 0.1789 | 0.075* | |
H1C | 0.6481 | 0.5311 | 0.2133 | 0.075* | |
C2 | 0.8628 (3) | 0.6175 (5) | 0.0542 (3) | 0.0257 (9) | |
C3 | 0.6629 (3) | 0.1929 (5) | 0.1031 (3) | 0.0305 (10) | |
C4 | 0.7879 (3) | 0.2971 (5) | 0.0189 (3) | 0.0229 (9) | |
H4 | 0.8262 | 0.1789 | 0.0469 | 0.027* | |
C5 | 0.7196 (3) | 0.3493 (5) | 0.0792 (3) | 0.0251 (9) | |
C6 | 0.7138 (3) | 0.5290 (5) | 0.1050 (3) | 0.0306 (10) | |
C7 | 0.5324 (4) | 0.0920 (6) | 0.1694 (4) | 0.0523 (14) | |
H7A | 0.4917 | 0.0232 | 0.1103 | 0.079* | |
H7B | 0.4833 | 0.1446 | 0.1997 | 0.079* | |
H7C | 0.5824 | 0.0068 | 0.2154 | 0.079* | |
C8 | 0.7244 (3) | 0.2591 (5) | −0.0870 (3) | 0.0237 (9) | |
C9 | 0.7339 (3) | 0.0877 (6) | −0.1298 (3) | 0.0323 (10) | |
H9 | 0.7803 | −0.0052 | −0.0914 | 0.039* | |
C10 | 0.6779 (3) | 0.0514 (7) | −0.2255 (3) | 0.0429 (12) | |
H10 | 0.6851 | −0.0666 | −0.2525 | 0.052* | |
C11 | 0.6117 (4) | 0.1832 (8) | −0.2826 (3) | 0.0550 (15) | |
H11 | 0.5737 | 0.1571 | −0.3494 | 0.066* | |
C12 | 0.5999 (3) | 0.3552 (8) | −0.2436 (3) | 0.0509 (14) | |
H12 | 0.5536 | 0.4478 | −0.2824 | 0.061* | |
C13 | 0.6574 (3) | 0.3874 (6) | −0.1470 (3) | 0.0343 (10) |
U11 | U22 | U33 | U12 | U13 | U23 | |
S1 | 0.0345 (6) | 0.0216 (5) | 0.0415 (6) | −0.0051 (5) | 0.0183 (5) | −0.0047 (5) |
O1 | 0.072 (2) | 0.0159 (16) | 0.070 (2) | 0.0026 (15) | 0.0524 (19) | −0.0029 (15) |
O2 | 0.058 (2) | 0.0187 (16) | 0.085 (2) | −0.0037 (14) | 0.0553 (19) | −0.0002 (15) |
N1 | 0.043 (2) | 0.0139 (17) | 0.048 (2) | 0.0005 (16) | 0.0300 (19) | 0.0032 (15) |
N2 | 0.0213 (18) | 0.0183 (18) | 0.036 (2) | 0.0019 (15) | 0.0136 (15) | −0.0013 (15) |
F1 | 0.0443 (16) | 0.0364 (15) | 0.0604 (17) | 0.0111 (13) | 0.0097 (13) | 0.0185 (13) |
C1 | 0.075 (4) | 0.014 (2) | 0.089 (4) | −0.003 (2) | 0.065 (3) | −0.004 (2) |
C2 | 0.030 (2) | 0.024 (2) | 0.026 (2) | 0.0024 (19) | 0.013 (2) | 0.0033 (18) |
C3 | 0.039 (3) | 0.022 (2) | 0.039 (2) | 0.001 (2) | 0.023 (2) | 0.002 (2) |
C4 | 0.027 (2) | 0.0146 (19) | 0.029 (2) | 0.0040 (18) | 0.0123 (18) | 0.0056 (18) |
C5 | 0.031 (2) | 0.014 (2) | 0.034 (2) | 0.0049 (18) | 0.017 (2) | 0.0040 (17) |
C6 | 0.041 (3) | 0.019 (2) | 0.042 (3) | 0.001 (2) | 0.027 (2) | 0.0048 (19) |
C7 | 0.067 (3) | 0.024 (2) | 0.095 (4) | −0.009 (2) | 0.065 (3) | −0.002 (3) |
C8 | 0.023 (2) | 0.024 (2) | 0.028 (2) | −0.0047 (19) | 0.0144 (18) | 0.0040 (19) |
C9 | 0.031 (3) | 0.038 (3) | 0.033 (3) | −0.006 (2) | 0.017 (2) | −0.006 (2) |
C10 | 0.034 (3) | 0.060 (3) | 0.041 (3) | −0.019 (3) | 0.022 (2) | −0.014 (3) |
C11 | 0.045 (3) | 0.090 (5) | 0.030 (3) | −0.031 (3) | 0.013 (3) | −0.012 (3) |
C12 | 0.027 (3) | 0.076 (4) | 0.042 (3) | −0.008 (3) | 0.000 (2) | 0.024 (3) |
C13 | 0.029 (2) | 0.030 (3) | 0.045 (3) | −0.003 (2) | 0.015 (2) | 0.002 (2) |
S1—C2 | 1.677 (4) | C4—C5 | 1.512 (5) |
O1—C3 | 1.211 (4) | C4—H4 | 1.0000 |
O2—C3 | 1.332 (4) | C5—C6 | 1.348 (5) |
O2—C7 | 1.451 (4) | C7—H7A | 0.9800 |
N1—C2 | 1.362 (4) | C7—H7B | 0.9800 |
N1—C6 | 1.383 (5) | C7—H7C | 0.9800 |
N1—H1 | 0.8800 | C8—C13 | 1.368 (5) |
N2—C2 | 1.327 (4) | C8—C9 | 1.400 (5) |
N2—C4 | 1.460 (4) | C9—C10 | 1.364 (5) |
N2—H2 | 0.8800 | C9—H9 | 0.9500 |
F1—C13 | 1.364 (5) | C10—C11 | 1.365 (7) |
C1—C6 | 1.502 (5) | C10—H10 | 0.9500 |
C1—H1A | 0.9800 | C11—C12 | 1.386 (7) |
C1—H1B | 0.9800 | C11—H11 | 0.9500 |
C1—H1C | 0.9800 | C12—C13 | 1.374 (6) |
C3—C5 | 1.457 (5) | C12—H12 | 0.9500 |
C4—C8 | 1.511 (5) | ||
C3—O2—C7 | 116.8 (3) | C5—C6—N1 | 119.1 (3) |
C2—N1—C6 | 124.4 (3) | C5—C6—C1 | 127.5 (4) |
C2—N1—H1 | 117.8 | N1—C6—C1 | 113.3 (3) |
C6—N1—H1 | 117.8 | O2—C7—H7A | 109.5 |
C2—N2—C4 | 125.8 (3) | O2—C7—H7B | 109.5 |
C2—N2—H2 | 117.1 | H7A—C7—H7B | 109.5 |
C4—N2—H2 | 117.1 | O2—C7—H7C | 109.5 |
C6—C1—H1A | 109.5 | H7A—C7—H7C | 109.5 |
C6—C1—H1B | 109.5 | H7B—C7—H7C | 109.5 |
H1A—C1—H1B | 109.5 | C13—C8—C9 | 116.1 (4) |
C6—C1—H1C | 109.5 | C13—C8—C4 | 123.3 (3) |
H1A—C1—H1C | 109.5 | C9—C8—C4 | 120.5 (3) |
H1B—C1—H1C | 109.5 | C10—C9—C8 | 121.4 (4) |
N2—C2—N1 | 116.0 (3) | C10—C9—H9 | 119.3 |
N2—C2—S1 | 123.1 (3) | C8—C9—H9 | 119.3 |
N1—C2—S1 | 120.9 (3) | C9—C10—C11 | 120.6 (5) |
O1—C3—O2 | 122.4 (3) | C9—C10—H10 | 119.7 |
O1—C3—C5 | 123.2 (4) | C11—C10—H10 | 119.7 |
O2—C3—C5 | 114.3 (3) | C10—C11—C12 | 120.1 (4) |
N2—C4—C8 | 111.5 (3) | C10—C11—H11 | 119.9 |
N2—C4—C5 | 109.8 (3) | C12—C11—H11 | 119.9 |
C8—C4—C5 | 113.5 (3) | C13—C12—C11 | 117.9 (4) |
N2—C4—H4 | 107.2 | C13—C12—H12 | 121.1 |
C8—C4—H4 | 107.2 | C11—C12—H12 | 121.1 |
C5—C4—H4 | 107.2 | F1—C13—C8 | 118.3 (4) |
C6—C5—C3 | 125.5 (3) | F1—C13—C12 | 117.8 (4) |
C6—C5—C4 | 120.1 (3) | C8—C13—C12 | 123.9 (4) |
C3—C5—C4 | 114.4 (3) | ||
C4—N2—C2—N1 | 9.1 (5) | C4—C5—C6—C1 | 174.3 (4) |
C4—N2—C2—S1 | −173.8 (3) | C2—N1—C6—C5 | −9.7 (6) |
C6—N1—C2—N2 | 9.3 (5) | C2—N1—C6—C1 | 168.7 (4) |
C6—N1—C2—S1 | −167.8 (3) | N2—C4—C8—C13 | −66.5 (4) |
C7—O2—C3—O1 | −1.7 (6) | C5—C4—C8—C13 | 58.1 (5) |
C7—O2—C3—C5 | −180.0 (4) | N2—C4—C8—C9 | 111.8 (4) |
C2—N2—C4—C8 | 103.4 (4) | C5—C4—C8—C9 | −123.5 (4) |
C2—N2—C4—C5 | −23.3 (5) | C13—C8—C9—C10 | −1.0 (5) |
O1—C3—C5—C6 | −170.2 (4) | C4—C8—C9—C10 | −179.4 (3) |
O2—C3—C5—C6 | 8.1 (6) | C8—C9—C10—C11 | 0.8 (6) |
O1—C3—C5—C4 | 10.8 (6) | C9—C10—C11—C12 | −0.7 (6) |
O2—C3—C5—C4 | −170.9 (3) | C10—C11—C12—C13 | 0.6 (6) |
N2—C4—C5—C6 | 21.7 (5) | C9—C8—C13—F1 | −177.7 (3) |
C8—C4—C5—C6 | −103.9 (4) | C4—C8—C13—F1 | 0.7 (5) |
N2—C4—C5—C3 | −159.3 (3) | C9—C8—C13—C12 | 1.0 (6) |
C8—C4—C5—C3 | 75.1 (4) | C4—C8—C13—C12 | 179.4 (4) |
C3—C5—C6—N1 | 173.6 (4) | C11—C12—C13—F1 | 177.9 (4) |
C4—C5—C6—N1 | −7.5 (6) | C11—C12—C13—C8 | −0.8 (6) |
C3—C5—C6—C1 | −4.6 (7) |
Cg is the centroid of the C8–C13 ring. |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O1i | 0.88 | 2.14 | 2.977 (4) | 159 |
N2—H2···S1ii | 0.88 | 2.55 | 3.386 (2) | 159 |
C1—H1B···O1i | 0.98 | 2.52 | 3.262 (5) | 133 |
C10—H10···Cgiii | 0.95 | 2.86 | 3.648 (2) | 141 |
Symmetry codes: (i) x, y+1, z; (ii) −x+2, −y+1, −z; (iii) −x, −y+1, −z. |
Cg is the centroid of the C8–C13 ring. |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O1i | 0.88 | 2.14 | 2.977 (4) | 159 |
N2—H2···S1ii | 0.88 | 2.55 | 3.386 (2) | 159 |
C1—H1B···O1i | 0.98 | 2.52 | 3.262 (5) | 133 |
C10—H10···Cgiii | 0.95 | 2.86 | 3.648 (2) | 141 |
Symmetry codes: (i) x, y+1, z; (ii) −x+2, −y+1, −z; (iii) −x, −y+1, −z. |
Acknowledgements
MSK thanks the University Grants Commission (UGC), India, for a UGC–BSR Meritorious Fellowship.
References
Biginelli, P. (1893). Gazz. Chim. Ital. 23, 360–413. Google Scholar
Bruker. (1998). SMART, SAINT-Plus and SADABS. Bruker Axs Inc., Madison, Wisconsin, USA. Google Scholar
Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854. Web of Science CrossRef CAS IUCr Journals Google Scholar
Guru Row, T. N. (1999). Chem. Rev. 183, 81–100. Google Scholar
Jauk, B., Pernat, T. & Kappe, C. O. (2000). Molecules, 5, 227–239. Web of Science CrossRef CAS Google Scholar
Kappe, C. O. (1998). Molecules, 3, 1–9. Web of Science CrossRef CAS Google Scholar
Kappe, C. O. (2000). Acc. Chem. Res. 33, 879–888. Web of Science CrossRef PubMed CAS Google Scholar
Krishnamurthy, M. S. & Begum, N. S. (2015a). Acta Cryst. E71, o268–o269. CSD CrossRef IUCr Journals Google Scholar
Krishnamurthy, M. S. & Begum, N. S. (2015b). Acta Cryst. E71, o699–o700. CSD CrossRef IUCr Journals Google Scholar
Mayer, T. U., Kapoor, T. M., Haggarty, S. J., King, R. W., Schreiber, S. I. & Mitchison, T. J. (1999). Science, 286, 971–974. Web of Science CrossRef PubMed CAS Google Scholar
Qin, Y.-Q., Ren, X.-Y., Liang, T.-L. & Jian, F.-F. (2006). Acta Cryst. E62, o5215–o5216. Web of Science CSD CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Watkin, D. J., Prout, C. K. & Pearce, L. J. (1996). CAMERON. Chemical Crystallography Laboratory, University of Oxford, England. Google Scholar
Yamazaki, T., Taguchi, T. & Ojima, I. (2009). Fluorine in Medicinal Chemistry and Chemical Biology, edited by I. Ojima, pp. 3–46. Weinheim: Wiley-Blackwell. Google Scholar
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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).