supplementary materials


rn2098 scheme

Acta Cryst. (2012). E68, o127    [ doi:10.1107/S1600536811052925 ]

(Z)-Ethyl 2-(2,4-dimethylbenzylidene)-7-methyl-3-oxo-5-phenyl-3,5-dihydro-2H-thiazolo[3,2-a]pyrimidine-6-carboxylate

X.-Y. Chen, H.-C. Wang, Q. Zhang, Z.-J. Song and F.-Y. Zheng

Abstract top

In the title compound, C25H24N2O3S, the dihedral angles between the thiazole ring and the phenyl and substituted benzene rings are 84.91 (11) and 11.58 (10)°, respectively. The dihydropyrimidine ring adopts a flattened boat conformation. The olefinic double bond is in a Z configuration.

Comment top

Pyrimidine has gained considerable attention because of its diversity in biological activity, such as anticarcinogenic and analgesic properties (Ashok et al., 2007). Thiazoles and their derivatives are also found to be associated with various biological activities such as antibacterial, antifungal and anti-inflammatory properties (Jang et al., 2011). Furthermore, the pyrimidines and thiazoles rings are found in the skeleton of many compounds with potent biological activity (Al-Rashood et al.,2010; Wichmann, et al., 1999). Since the two heterocyclic moieties constitute two active pharmacophores that are highly active against inflammation and pain, combining the two is expected to have a synergistic effect in dealing with diseases.

In this paper, we report the molecular and crystal structure of (Z)-ethyl 2-(2,4-dimethylbenzylidene)-7-methyl-3-oxo-5-phenyl-3,5-dihydro-2H-thiazolo [3,2-a]pyrimidine-6-carboxylate (I). The molecule (I), consists of one thiazole ring and two benzene rings. The fused pyrimidine ring has usual geometry as observed in other fused pyrimidine compounds (Kulakov, et al., 2009; Zhao, et al., 2011). The thiazole ring makes dihedral angles of 84.91 (11) and 11.58 (10)° with the benzene rings C7—C12 and C18–C23, respectively. The pyrimidine ring adopts a flattened boat conformation. The C2—C17 double bond exists in the Z configuration. The molecular structure of (I) is illustrated in Fig. 1.

Related literature top

For related structures, see: Kulakov et al. (2009); Zhao et al. (2011). For background to the biological properties of fused pyrimidine derivatives, see: Al-Rashood & Abdel-Aziz (2010); Ashok et al. (2007); Jang et al. (2011); Wichmann et al. (1999).

Experimental top

In a one pot Biginelli reaction, a mixture of 5 mmol of benzaldehyde, 6 mmol ethyl acetoacetate, 7.5 mmol thiourea and 10 ml of EtOH was stirred at 50°C in presence of sulfamic acid catalyst for 3 h to obtain 6-methyl-4-phenyl-2-thioxo-1,2,3,4- tetrahydropyrimidine-5-carboxylate. Then the product (2 mmol) was reacted with ethyl chloroacetate (2 mmol) in the presence of pyridine for 4 h; and 2,4-dimethylbenzaldehyde (2 mmol) and piperidine were added, and the mixture refluxed for 4 h until the TLC assay indicated that the reaction was completed. The reaction mixture was cooled and filtered to give crude product. The solid was collected and crystallized from acetic acid to obtain the final product. Single crystals of the title compound were grown in a CH2Cl2/CH3OH mixture (2:1 v/v) by slow evaporation.

Refinement top

The H atoms were positioned geometrically (C—H = 0.93 and 0.96 Å) and refined as riding with Uiso(H) = 1.2Ueq(C) or 1.5Ueq(methyl C).

Computing details top

Data collection: SMART (Bruker, 2002); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT (Bruker, 2002); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound, showing 30% displacement ellipsoids for the non-hydrogen atoms. Hydrogen atoms are drawn as spheres of arbitrary radius.
(Z)-Ethyl 2-(2,4-dimethylbenzylidene)-7-methyl-3-oxo-5-phenyl- 3,5-dihydro-2H-thiazolo[3,2-a]pyrimidine-6-carboxylate top
Crystal data top
C25H24N2O3SF(000) = 912
Mr = 432.52Dx = 1.287 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
a = 9.690 (5) ÅCell parameters from 2729 reflections
b = 10.620 (5) Åθ = 5.4–56.3°
c = 21.692 (12) ŵ = 0.17 mm1
β = 90.682 (10)°T = 293 K
V = 2232 (2) Å3Prismatic, green
Z = 40.32 × 0.27 × 0.16 mm
Data collection top
Bruker SMART CCD area-detector
diffractometer
4257 independent reflections
Radiation source: fine-focus sealed tube3096 reflections with I > 2σ(I)
graphiteRint = 0.026
phi and ω scansθmax = 26.0°, θmin = 1.9°
Absorption correction: multi-scan
(SADABS; Bruker, 2002)
h = 1111
Tmin = 0.675, Tmax = 1.000k = 1311
8761 measured reflectionsl = 1526
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)] = 0.050Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.155H-atom parameters constrained
S = 1.01 w = 1/[σ2(Fo2) + (0.0949P)2]
where P = (Fo2 + 2Fc2)/3
4257 reflections(Δ/σ)max = 0.003
284 parametersΔρmax = 0.31 e Å3
0 restraintsΔρmin = 0.26 e Å3
Crystal data top
C25H24N2O3SV = 2232 (2) Å3
Mr = 432.52Z = 4
Monoclinic, P21/nMo Kα radiation
a = 9.690 (5) ŵ = 0.17 mm1
b = 10.620 (5) ÅT = 293 K
c = 21.692 (12) Å0.32 × 0.27 × 0.16 mm
β = 90.682 (10)°
Data collection top
Bruker SMART CCD area-detector
diffractometer
4257 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2002)
3096 reflections with I > 2σ(I)
Tmin = 0.675, Tmax = 1.000Rint = 0.026
8761 measured reflectionsθmax = 26.0°
Refinement top
R[F2 > 2σ(F2)] = 0.050H-atom parameters constrained
wR(F2) = 0.155Δρmax = 0.31 e Å3
S = 1.01Δρmin = 0.26 e Å3
4257 reflectionsAbsolute structure: ?
284 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
S10.39630 (6)0.68577 (5)1.02581 (2)0.0468 (2)
N10.51571 (17)0.71961 (14)0.92082 (7)0.0387 (4)
N20.58867 (19)0.85690 (16)1.00033 (8)0.0473 (4)
O10.43929 (16)0.55550 (13)0.86185 (6)0.0527 (4)
O20.8683 (2)1.0158 (2)0.86481 (10)0.0999 (7)
O30.78414 (18)0.86963 (17)0.80152 (7)0.0651 (5)
C10.4398 (2)0.61190 (18)0.91047 (9)0.0397 (5)
C20.3609 (2)0.57762 (18)0.96664 (9)0.0402 (5)
C30.5139 (2)0.76745 (18)0.97952 (9)0.0412 (5)
C40.6868 (2)0.90740 (19)0.95937 (10)0.0472 (5)
C50.6901 (2)0.87651 (19)0.89920 (10)0.0461 (5)
C60.5836 (2)0.78885 (18)0.87051 (9)0.0422 (5)
H60.63120.72810.84420.051*
C70.4768 (2)0.8581 (2)0.83166 (9)0.0440 (5)
C80.4347 (3)0.8122 (2)0.77469 (10)0.0634 (7)
H80.47380.73890.75920.076*
C90.3338 (3)0.8758 (3)0.74073 (11)0.0804 (9)
H90.30560.84450.70260.097*
C100.2761 (3)0.9832 (3)0.76279 (13)0.0779 (8)
H100.20891.02530.73980.093*
C110.3176 (3)1.0286 (3)0.81878 (13)0.0758 (8)
H110.27801.10180.83410.091*
C120.4174 (3)0.9670 (2)0.85291 (11)0.0588 (6)
H120.44510.99960.89090.071*
C130.7847 (3)0.9961 (2)0.99124 (12)0.0617 (6)
H13A0.87500.98710.97410.093*
H13B0.78830.97701.03450.093*
H13C0.75331.08110.98550.093*
C140.7908 (2)0.9298 (2)0.85547 (12)0.0584 (6)
C150.8700 (3)0.9143 (3)0.75156 (13)0.0813 (9)
H15A0.96390.92760.76610.098*
H15B0.83460.99330.73540.098*
C160.8664 (4)0.8162 (4)0.70314 (14)0.1146 (14)
H16A0.90100.73850.71980.172*
H16B0.92270.84200.66930.172*
H16C0.77300.80450.68890.172*
C170.2755 (2)0.47861 (18)0.96532 (9)0.0441 (5)
H170.27440.43520.92810.053*
C180.1845 (2)0.42670 (18)1.01130 (9)0.0431 (5)
C190.0866 (2)0.33502 (19)0.99376 (10)0.0473 (5)
C200.0026 (2)0.2895 (2)1.03827 (11)0.0540 (6)
H200.06800.22981.02650.065*
C210.0007 (2)0.3284 (2)1.09903 (11)0.0536 (6)
C220.0988 (3)0.4159 (2)1.11590 (11)0.0581 (6)
H220.10480.44261.15670.070*
C230.1885 (2)0.4647 (2)1.07309 (10)0.0531 (6)
H230.25330.52431.08560.064*
C240.0761 (3)0.2857 (2)0.92891 (11)0.0661 (7)
H24A0.00260.22530.92610.099*
H24B0.16150.24610.91800.099*
H24C0.05750.35410.90110.099*
C250.1005 (3)0.2774 (3)1.14450 (13)0.0756 (8)
H25A0.18770.31911.13900.113*
H25B0.06660.29201.18560.113*
H25C0.11210.18861.13800.113*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0540 (4)0.0431 (3)0.0435 (3)0.0012 (2)0.0112 (2)0.0006 (2)
N10.0400 (10)0.0354 (8)0.0408 (8)0.0022 (7)0.0049 (7)0.0019 (7)
N20.0497 (11)0.0405 (9)0.0519 (10)0.0045 (8)0.0026 (8)0.0055 (8)
O10.0612 (10)0.0505 (8)0.0468 (8)0.0109 (8)0.0111 (7)0.0067 (7)
O20.0972 (16)0.0951 (15)0.1080 (16)0.0585 (13)0.0217 (13)0.0015 (12)
O30.0577 (11)0.0771 (11)0.0608 (10)0.0177 (9)0.0164 (8)0.0117 (9)
C10.0376 (12)0.0378 (11)0.0438 (10)0.0017 (9)0.0021 (9)0.0017 (8)
C20.0400 (12)0.0369 (10)0.0439 (10)0.0044 (9)0.0060 (9)0.0021 (8)
C30.0415 (12)0.0366 (10)0.0456 (10)0.0046 (9)0.0022 (9)0.0005 (8)
C40.0413 (12)0.0371 (11)0.0632 (13)0.0003 (9)0.0019 (10)0.0001 (9)
C50.0373 (12)0.0406 (11)0.0603 (13)0.0037 (9)0.0015 (10)0.0049 (9)
C60.0418 (12)0.0397 (10)0.0452 (10)0.0054 (9)0.0100 (9)0.0007 (8)
C70.0407 (12)0.0499 (12)0.0415 (10)0.0111 (10)0.0068 (9)0.0074 (9)
C80.0696 (18)0.0719 (16)0.0489 (12)0.0138 (14)0.0042 (12)0.0001 (11)
C90.081 (2)0.114 (2)0.0459 (13)0.025 (2)0.0126 (13)0.0155 (15)
C100.0650 (18)0.099 (2)0.0694 (17)0.0022 (17)0.0061 (14)0.0363 (16)
C110.0722 (19)0.0745 (18)0.0805 (18)0.0164 (15)0.0016 (15)0.0167 (14)
C120.0576 (15)0.0614 (15)0.0575 (13)0.0065 (12)0.0022 (11)0.0037 (11)
C130.0550 (15)0.0507 (13)0.0792 (16)0.0102 (11)0.0052 (12)0.0043 (12)
C140.0442 (14)0.0568 (14)0.0743 (16)0.0075 (12)0.0021 (12)0.0128 (12)
C150.0662 (18)0.104 (2)0.0741 (17)0.0152 (16)0.0208 (14)0.0375 (16)
C160.136 (3)0.149 (3)0.0596 (17)0.023 (3)0.036 (2)0.0160 (19)
C170.0451 (12)0.0391 (11)0.0481 (11)0.0002 (9)0.0053 (9)0.0026 (9)
C180.0418 (12)0.0353 (10)0.0522 (11)0.0026 (9)0.0071 (9)0.0063 (9)
C190.0460 (13)0.0367 (10)0.0593 (12)0.0020 (9)0.0045 (10)0.0072 (9)
C200.0431 (13)0.0434 (12)0.0756 (15)0.0036 (10)0.0054 (11)0.0103 (11)
C210.0441 (14)0.0498 (13)0.0672 (14)0.0066 (11)0.0131 (11)0.0167 (11)
C220.0598 (15)0.0613 (14)0.0533 (13)0.0009 (12)0.0116 (11)0.0082 (11)
C230.0547 (14)0.0499 (12)0.0548 (12)0.0096 (11)0.0084 (10)0.0041 (10)
C240.0727 (18)0.0569 (14)0.0688 (15)0.0175 (13)0.0074 (13)0.0034 (12)
C250.0597 (17)0.0840 (18)0.0836 (18)0.0012 (15)0.0216 (14)0.0293 (15)
Geometric parameters (Å, °) top
S1—C21.753 (2)C12—H120.9300
S1—C31.757 (2)C13—H13A0.9600
N1—C31.371 (3)C13—H13B0.9600
N1—C11.377 (3)C13—H13C0.9600
N1—C61.477 (2)C15—C161.480 (4)
N2—C31.274 (3)C15—H15A0.9700
N2—C41.415 (3)C15—H15B0.9700
O1—C11.213 (2)C16—H16A0.9600
O2—C141.198 (3)C16—H16B0.9600
O3—C141.334 (3)C16—H16C0.9600
O3—C151.454 (3)C17—C181.448 (3)
C1—C21.491 (3)C17—H170.9300
C2—C171.338 (3)C18—C231.400 (3)
C4—C51.347 (3)C18—C191.409 (3)
C4—C131.500 (3)C19—C201.390 (3)
C5—C141.481 (3)C19—C241.504 (3)
C5—C61.518 (3)C20—C211.381 (3)
C6—C71.517 (3)C20—H200.9300
C6—H60.9800C21—C221.376 (3)
C7—C121.374 (3)C21—C251.501 (3)
C7—C81.385 (3)C22—C231.380 (3)
C8—C91.392 (4)C22—H220.9300
C8—H80.9300C23—H230.9300
C9—C101.360 (4)C24—H24A0.9600
C9—H90.9300C24—H24B0.9600
C10—C111.363 (4)C24—H24C0.9600
C10—H100.9300C25—H25A0.9600
C11—C121.377 (3)C25—H25B0.9600
C11—H110.9300C25—H25C0.9600
C2—S1—C391.59 (10)H13B—C13—H13C109.5
C3—N1—C1116.53 (16)O2—C14—O3122.5 (2)
C3—N1—C6120.82 (16)O2—C14—C5126.8 (2)
C1—N1—C6122.33 (16)O3—C14—C5110.7 (2)
C3—N2—C4116.34 (17)O3—C15—C16106.9 (2)
C14—O3—C15118.4 (2)O3—C15—H15A110.3
O1—C1—N1123.26 (18)C16—C15—H15A110.3
O1—C1—C2126.39 (19)O3—C15—H15B110.3
N1—C1—C2110.34 (16)C16—C15—H15B110.3
C17—C2—C1119.81 (18)H15A—C15—H15B108.6
C17—C2—S1130.25 (16)C15—C16—H16A109.5
C1—C2—S1109.90 (14)C15—C16—H16B109.5
N2—C3—N1126.29 (19)H16A—C16—H16B109.5
N2—C3—S1122.38 (16)C15—C16—H16C109.5
N1—C3—S1111.30 (15)H16A—C16—H16C109.5
C5—C4—N2122.71 (19)H16B—C16—H16C109.5
C5—C4—C13125.3 (2)C2—C17—C18131.74 (19)
N2—C4—C13112.00 (19)C2—C17—H17114.1
C4—C5—C14123.4 (2)C18—C17—H17114.1
C4—C5—C6121.52 (19)C23—C18—C19117.94 (19)
C14—C5—C6114.95 (19)C23—C18—C17122.7 (2)
N1—C6—C7110.19 (17)C19—C18—C17119.39 (19)
N1—C6—C5108.00 (16)C20—C19—C18118.4 (2)
C7—C6—C5112.74 (17)C20—C19—C24119.5 (2)
N1—C6—H6108.6C18—C19—C24122.1 (2)
C7—C6—H6108.6C21—C20—C19123.4 (2)
C5—C6—H6108.6C21—C20—H20118.3
C12—C7—C8118.4 (2)C19—C20—H20118.3
C12—C7—C6120.47 (18)C22—C21—C20117.6 (2)
C8—C7—C6121.1 (2)C22—C21—C25121.6 (2)
C7—C8—C9119.9 (3)C20—C21—C25120.7 (2)
C7—C8—H8120.0C21—C22—C23120.9 (2)
C9—C8—H8120.0C21—C22—H22119.6
C10—C9—C8120.7 (3)C23—C22—H22119.6
C10—C9—H9119.7C22—C23—C18121.7 (2)
C8—C9—H9119.7C22—C23—H23119.1
C9—C10—C11119.5 (3)C18—C23—H23119.1
C9—C10—H10120.3C19—C24—H24A109.5
C11—C10—H10120.3C19—C24—H24B109.5
C10—C11—C12120.6 (3)H24A—C24—H24B109.5
C10—C11—H11119.7C19—C24—H24C109.5
C12—C11—H11119.7H24A—C24—H24C109.5
C7—C12—C11120.9 (2)H24B—C24—H24C109.5
C7—C12—H12119.5C21—C25—H25A109.5
C11—C12—H12119.5C21—C25—H25B109.5
C4—C13—H13A109.5H25A—C25—H25B109.5
C4—C13—H13B109.5C21—C25—H25C109.5
H13A—C13—H13B109.5H25A—C25—H25C109.5
C4—C13—H13C109.5H25B—C25—H25C109.5
H13A—C13—H13C109.5
C3—N1—C1—O1175.24 (19)N1—C6—C7—C8102.7 (2)
C6—N1—C1—O111.3 (3)C5—C6—C7—C8136.6 (2)
C3—N1—C1—C25.0 (2)C12—C7—C8—C90.5 (3)
C6—N1—C1—C2168.54 (17)C6—C7—C8—C9178.3 (2)
O1—C1—C2—C172.7 (3)C7—C8—C9—C100.2 (4)
N1—C1—C2—C17177.07 (17)C8—C9—C10—C110.1 (4)
O1—C1—C2—S1179.15 (18)C9—C10—C11—C120.2 (4)
N1—C1—C2—S11.1 (2)C8—C7—C12—C110.6 (3)
C3—S1—C2—C17180.0 (2)C6—C7—C12—C11178.1 (2)
C3—S1—C2—C12.08 (15)C10—C11—C12—C70.5 (4)
C4—N2—C3—N12.9 (3)C15—O3—C14—O22.9 (4)
C4—N2—C3—S1174.98 (15)C15—O3—C14—C5176.3 (2)
C1—N1—C3—N2171.51 (19)C4—C5—C14—O210.0 (4)
C6—N1—C3—N214.9 (3)C6—C5—C14—O2166.5 (2)
C1—N1—C3—S16.6 (2)C4—C5—C14—O3170.8 (2)
C6—N1—C3—S1166.99 (14)C6—C5—C14—O312.6 (3)
C2—S1—C3—N2173.40 (18)C14—O3—C15—C16167.7 (3)
C2—S1—C3—N14.81 (15)C1—C2—C17—C18177.9 (2)
C3—N2—C4—C59.0 (3)S1—C2—C17—C180.2 (4)
C3—N2—C4—C13170.39 (18)C2—C17—C18—C2311.2 (4)
N2—C4—C5—C14179.09 (19)C2—C17—C18—C19168.2 (2)
C13—C4—C5—C141.6 (4)C23—C18—C19—C201.5 (3)
N2—C4—C5—C62.8 (3)C17—C18—C19—C20177.96 (19)
C13—C4—C5—C6178.0 (2)C23—C18—C19—C24178.5 (2)
C3—N1—C6—C7100.3 (2)C17—C18—C19—C242.0 (3)
C1—N1—C6—C773.0 (2)C18—C19—C20—C210.8 (3)
C3—N1—C6—C523.3 (3)C24—C19—C20—C21179.2 (2)
C1—N1—C6—C5163.48 (17)C19—C20—C21—C220.6 (3)
C4—C5—C6—N117.7 (3)C19—C20—C21—C25178.7 (2)
C14—C5—C6—N1165.70 (18)C20—C21—C22—C231.3 (3)
C4—C5—C6—C7104.3 (2)C25—C21—C22—C23178.0 (2)
C14—C5—C6—C772.3 (2)C21—C22—C23—C180.6 (4)
N1—C6—C7—C1276.0 (2)C19—C18—C23—C220.9 (3)
C5—C6—C7—C1244.7 (3)C17—C18—C23—C22178.6 (2)
Acknowledgements top

The X-ray crystallographic facility at the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, is gratefully acknowledged.

references
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