Ethyl 2-[(Z)-3-chloro­benzyl­idene]-7-methyl-3-oxo-5-phenyl-2,3-dihydro-5H-1,3-thia­zolo[3,2-a]pyrimidine-6-carboxyl­ate

Mukesh M Jotani; Bharat B Baldaniya

doi:10.1107/S1600536808007356

. 2008 Mar 29;64(Pt 4):o739. doi: 10.1107/S1600536808007356

Ethyl 2-[(Z)-3-chlorobenzylidene]-7-methyl-3-oxo-5-phenyl-2,3-dihydro-5H-1,3-thiazolo[3,2-a]pyrimidine-6-carboxylate

Mukesh M Jotani ^a,^*, Bharat B Baldaniya ^b

PMCID: PMC2961005 PMID: 21202129

Abstract

In the title compound, C₂₃H₁₉ClN₂O₃S, the central pyrimidine ring is significantly puckered, assuming almost a screw boat conformation. In addition to the usual intermolecular C—H⋯O hydrogen bonding, short intramolecular C—H⋯S contacts and π–π stacking interactions [centroid–centroid distance = 3.762 (2) Å] contribute to the crystal packing.

Related literature

For the crystal structures of similar compounds, see: Jotani & Baldaniya (2006 ▶, 2007 ▶); Sridhar et al., (2006 ▶); Fischer et al. (2007 ▶). For the biological activities, see: Kappe (2000 ▶); Rovnyak et al. (1995 ▶); Monks et al. (1991 ▶); Winter et al. (1962 ▶). For related literature, see: Allen, (2002 ▶); Bernstein et al. (1995 ▶); Cremer & Pople, (1975 ▶).

Experimental

Crystal data

C₂₃H₁₉ClN₂O₃S
M _r = 438.92
Triclinic,
a = 8.2650 (3) Å
b = 10.3291 (4) Å
c = 13.5655 (5) Å
α = 94.129 (2)°
β = 100.837 (2)°
γ = 111.812 (2)°
V = 1043.15 (7) Å³
Z = 2
Mo Kα radiation
μ = 0.31 mm⁻¹
T = 293 (2) K
0.47 × 0.35 × 0.2 mm

Data collection

Bruker Kappa APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2004 ▶) T _min = 0.867, T _max = 0.936
18826 measured reflections
3677 independent reflections
3111 reflections with I > 2σ(I)
R _int = 0.024

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.124
S = 1.06
3677 reflections
273 parameters
H-atom parameters constrained
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: APEX2 and SAINT (Bruker, 2004 ▶); data reduction: SAINT and XPREP (Bruker, 2004 ▶); program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and PLATON (Spek, 2003 ▶); software used to prepare material for publication: SHELXL97 and PLATON.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808007356/rk2081sup1.cif

e-64-0o739-sup1.cif^{(21.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808007356/rk2081Isup2.hkl

e-64-0o739-Isup2.hkl^{(176.6KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C23—H23⋯O1ⁱ	0.93	2.49	3.287 (3)	143
C19—H19⋯S1	0.93	2.50	3.210 (3)	133

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank the Department of Science and Technology (DST) and SAIF, IIT Madras, Chennai, India, for the intensity data collection.

supplementary crystallographic information

Comment

The remarkable biological activties of fused pyrimidines such as antiviral, antitumor, anticancer, antiinflammatory, antihypertensive etc. (Kappe, 2000; Rovnyak et al., 1995) bring this class of heterocyclic compounds of significant pharmacological interest. The title thiazolo [3,2-a] pyrimidine compound, (I), possesses anticancer and antiinflammatory activity. The anticancer drug screen is carried out using a diverse panel of cultured human tumor cell lines (Monks et al., 1991). The anti-inflammatory activity is determined by inhibition in the Carageena-induced rat paw edema method (Winter et al., 1962). In view of these properties and to study the effect of chlorine substituent at different positions of benzene ring on crystal packing, the crystal structure of I has been determined.

On Fig. 1 is shown the molecular structure of I with the atom numbering scheme. The pyrimidine ring adopts almost a screw boat conformation as indicated by the ring puckering parameters [q2 = 0.175 (2)Å, q3 = 0.077 (2)Å, θ = 66.2 (6)° and φ = 173.1 (7)°; Cremer & Pople, 1975]. The idealized values for the screw boat conformation are: θ = 67.5° and φ = (60k + 30)°, where k is an integer. The asymmetry parameters also support this information. All bond lengths and angles in the pyrimidine ring have normal values. The fused thiazole ring has usual geometry as observed in other fused thiazolopyrimidine compounds (Jotani & Baldaniya, 2006, 2007; Sridhar et al., 2006). The thiazole ring makes dihedral angles of 89.06 (11) and 6.56 (10)° with the benzene rings C11–C16 and C18–C23, respectively. The short C9–C10 bond distance is a consequence of slight liberation of the ethoxy group. The ethoxy group is in all–trans conformation as observed from the torsional angles C3–C8–O2–C9 and C8–O2–C9–C10 of -176.0 (2) and 117.2 (3)° respectively.

The crystal structure of I is also have an intermolecular C—H···O interaction (Fig. 2 and Table) similar to earlier reported ortho- and para-substituted compounds (Jotani & Baldaniya, 2006, 2007). In the structure a carbon C23 atom of C18–C23 benzene ring participates in the C—H···O interaction that forms R₂²(14) graph–set motif (Bernstein et al., 1995), where as in ortho- and para-substituted chlorine derivatives, the interaction is due to C14 atom of C11–C16 benzene ring. This may be the different symmetry of the crystal system as the title compound I crystallizes in triclinic system where as the previous two structures were crystallized in monoclinic space group. A PLATON analysis (Spek, 2003) of I indicated that a weak intramolecular C—H···S hydrogen bond (Fig. 1 and Table) forms a pseudo-six-membered ring of S(6) graph-set motif (Bernstein et al., 1995) also help to consolidate the crystal packing. There is a comparatively weak π–π stacking interaction between the C18–C23 benzene rings with symmetry codes: (x, y, z) and (1-x, 1-y, -z); their centroids are separated by 3.762 (2)Å and the rings have a slippage of 1.523Å (Fig. 3).

Experimental

A mixture of ethyl 6-methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (0.01 mol), chloroacetic acid (0.01 mol), fused sodium acetate (6 g) in glacial acetic acid (25 ml), acetic anhydride (10 ml) and 3-chlorobenzaldehyde (0.01 mol) was refluxed for 3 h. The reaction mixture was cooled and poured into cold water. The resulting solid was collected and crystallized from methanol to obtain the final product (82% yield, mp 444 K). The compound was recrystallized by slow evaporation of an ethanol solution, yielding yellow, Platlike single crystals suitable for X–ray diffraction.