Ethyl 2-(2-acetoxy­benzyl­idene)-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; Edward R T Tiekink

doi:10.1107/S1600536810007853

. 2010 Mar 6;66(Pt 4):o762–o763. doi: 10.1107/S1600536810007853

Ethyl 2-(2-acetoxybenzylidene)-7-methyl-3-oxo-5-phenyl-2,3-dihydro-5H-1,3-thiazolo[3,2-a]pyrimidine-6-carboxylate¹

Mukesh M Jotani ^a, Bharat B Baldaniya ^b, Edward R T Tiekink ^c,^*

PMCID: PMC2983806 PMID: 21580607

Abstract

In the title molecule, C₂₅H₂₂N₂O₅S, the atoms of the thiazolopyrimidine ring system, with the exception of the phenyl-bearing C atom [deviation = 0.177 (2) Å], are essentially planar [r.m.s deviation = 0.100 (2) °] and the mean plane of these atoms forms dihedral angles of 89.86 (10) and 7.97 (8)° with the phenyl and benzene rings, respectively. In the crystal, co-operative C—H⋯O and C—H⋯π interactions lead to a supramolecular chain along the a axis. These chains are connected via π–π interactions [centroid–centroid = 3.7523 (13) Å].

Related literature

For background to the pharmacological activity of thiazolo[3,2-a]pyrimidine derivatives, see: Winter et al. (1962 ▶); Atwal et al. (1990 ▶); Kappe (2000 ▶); Adams et al. (2005 ▶). For related structures, see: Jotani & Baldaniya (2007 ▶, 2008 ▶); Baldaniya & Jotani (2008 ▶); Jotani et al. (2009 ▶). For additional geometric analysis, see: Cremer & Pople (1975 ▶). Semi-empirical Quantum Chemical Calculations were performed with the MOPAC2009 program (Stewart, 2009 ▶).

Experimental

Crystal data

C₂₅H₂₂N₂O₅S
M _r = 462.51
Triclinic,
a = 8.4236 (3) Å
b = 9.6807 (3) Å
c = 14.3345 (5) Å
α = 87.939 (2)°
β = 89.680 (2)°
γ = 75.287 (2)°
V = 1129.86 (7) Å³
Z = 2
Mo Kα radiation
μ = 0.18 mm⁻¹
T = 293 K
0.47 × 0.35 × 0.20 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.920, T _max = 0.965
20701 measured reflections
3969 independent reflections
3438 reflections with I > 2σ(I)
R _int = 0.024

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.137
S = 1.06
3969 reflections
301 parameters
H-atom parameters constrained
Δρ_max = 0.36 e Å⁻³
Δρ_min = −0.31 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: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶) and PLATON (Spek, 2009 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and DIAMOND (Brandenburg, 2006 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810007853/lh5004sup1.cif

e-66-0o762-sup1.cif^{(23.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810007853/lh5004Isup2.hkl

e-66-0o762-Isup2.hkl^{(190.6KB, hkl)}

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

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

Cg1 is the centroid of the S1/C1/N2/C15/C16 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C2—H2⋯O5ⁱ	0.98	2.58	3.532 (3)	163
C12—H12a⋯Cg1ⁱ	0.97	2.98	3.902 (3)	160

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank the Department of Science and Technology (DST) and the SAIF, IIT Madras, Chennai, India, for the X-ray data collection. MMJ is grateful to the University Grant Commission (Western Regional Office), India, for Minor Research Project F. No.47-254/07.

supplementary crystallographic information

Comment

The absolute stereochemistry at C2 stereocentre in fused dihydropyrimidine rings is a critical factor for their biological activity and provides an additional opportunity to study the effect of chirality on biological activities (Atwal et al., 1990; Kappe, 2000). The title compound, (I), exhibits anti-cancer (Adams et al., 2005) and anti-inflammatory activities (Winter et al., 1962). In continuation of our structural studies of these pharmacologically interesting thiazolo[3,2-a]pyrimidine derivatives, designed to ascertain the influence of substitution patterns upon crystal packing (Jotani & Baldaniya, 2007; Jotani & Baldaniya, 2008; Baldaniya & Jotani, 2008; Jotani et al., 2009), the synthesis and crystal structure of the title compound, (I), is described herein.

The thiazole ring is essentially planar [maximum deviation of 0.0181 (17) for the N2 atom]. By contrast, the pyrimidine ring is non-planar with the sp ³-C2 atom lying well out of the approximate plane defined by the remaining atoms. The distortion is quantified by the ring puckering parameters (Cremer & Pople, 1975): Q = 0.1721 (19) Å, θ = 67.8 (7) °, and φ₂ = 164.3 (7) °. The dihedral angle formed between the fused rings is nevertheless small at 6.05 (9) °. The planarity in the molecule extends to the C3-bound acetyl group [the C4–C3–C11–O1 torsion angle is 9.3 (4) °] on one side of the fused-ring system, and on the other through the C16═C17 double bond [1.336 (3) Å] and adjacent benzene ring as seen in the C15–C16–C17–C18 and C16–C17–C18–C19 torsion angles of 174.58 (18) and -174.4 (2) °, respectively. Each of the remaining substituents, i.e. the C5–C10 benzene ring and O4-acetyl groups lie to the same side of the molecule and occupy positions defined by the N2–C2–C5–C6 and C18–C19–O4–C24 torsion angles of -64.7 (2) and 94.9 (2) °, respectively. Allowing for the presence of distinct substituents, the molecular framework in (I) resembles closely those found in related derivatives (Jotani & Baldaniya, 2007; Jotani & Baldaniya, 2008; Baldaniya & Jotani, 2008; Jotani et al., 2009)

The crystal structure is stabilised by a variety of weak intermolecular interactions. A supramolecular chain aligned along the a axis is formed through the agency of C–H···O and C–H···π interactions, Fig. 2 and Table 1. These are connected via π–π interactions formed between centrosymmetrically related C18–C23 rings [ring centroid(C18–C23)···ring centroid(C18–C23)ⁱ = 3.7523 (13) Å for i: -x, -y, -z], Fig. 3.

Semi-empirical Quantum Chemical Calculations were performed with the MOPAC2009 program (Stewart, 2009) in order to optimize the experimental structure with the Austin Model 1 (AM1) approximation together with the restricted Hartree-Fock closed-shell wavefunction; minimisations were terminated at a r.m.s. gradient of less than 1.0 kJ mol^-1 Å^-1. The heat of formation was calculated to be -313.14 kJ mol^-1. The ionization potential, dipole moment and self consistency field (SCF) factor were calculated as 8.633 eV, 3.880 Debye, and 121, respectively.

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 2-acetyloxy benzaldehyde (0.01 mol) was refluxed for 3 to 3.5 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 (75 % yield, m.pt. 438 K). The compound was crystallized by slow evaporation of benzene-ethanol (1:1) solution yielding yellow blocks.