Crystal structure of ethyl 2-acetyl-3,7-dimethyl-5-(thio­phen-2-yl)-5H-thia­zolo[3,2-a]pyrimidine-6-carboxyl­ate

N L Prasad; M S Krishnamurthy; Noor Shahina Begum

doi:10.1107/S2056989015010981

. 2015 Jun 13;71(Pt 7):o477–o478. doi: 10.1107/S2056989015010981

Crystal structure of ethyl 2-acetyl-3,7-dimethyl-5-(thiophen-2-yl)-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate

N L Prasad ^a, M S Krishnamurthy ^a, Noor Shahina Begum ^a,^*

PMCID: PMC4518970 PMID: 26279917

Abstract

In the title compound, C₁₇H₁₈N₂O₃S₂, the pyrimidine ring adopts a shallow sofa conformation, with the C atom bearing the axially-oriented thiophene ring as the flap [deviation = 0.439 (3) Å]. The plane of the thiophene ring lies almost normal to the pyrimidine ring, making a dihedral angle of 79.36 (19)°. In the crystal, pairs of very weak C—H⋯O hydrogen bonds link the molecules related by twofold rotation axes, forming R ₂ ²(18) rings, which are in turn linked by another C—H⋯O interaction, forming chains of rings along [010]. In addition, weak C—H⋯π(thiophene) interactions link the chains into layers parallel to [001] and π–π interactions with a centroid–centroid distance of 3.772 (10) Å connect these layers into a three-dimensional network.

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

Related literature

For the biological activities of fused pyrimidine derivatives, see: Atwal et al. (1991 ▸); Kappe et al. (1997 ▸); Singh et al. (2011 ▸); Ozair et al. (2010 ▸); Hayam et al. (2010 ▸). For related structures, see: Prasad et al. (2014 ▸); Nagarajaiah et al. (2012 ▸). graphic file with name e-71-0o477-scheme1.jpg

Experimental

Crystal data

C₁₇H₁₈N₂O₃S₂
M _r = 362.45
Monoclinic,
a = 7.8835 (10) Å
b = 14.4041 (19) Å
c = 15.231 (2) Å
β = 94.940 (4)°
V = 1723.2 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.33 mm⁻¹
T = 100 K
0.18 × 0.16 × 0.16 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1998 ▸) T _min = 0.944, T _max = 0.950
12021 measured reflections
3038 independent reflections
1984 reflections with I > 2σ(I)
R _int = 0.046

Refinement

R[F ² > 2σ(F ²)] = 0.065
wR(F ²) = 0.189
S = 1.00
3038 reflections
221 parameters
H-atom parameters constrained
Δρ_max = 0.51 e Å⁻³
Δρ_min = −0.28 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/S2056989015010981/hb7433sup1.cif

e-71-0o477-sup1.cif^{(19.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015010981/hb7433Isup2.hkl

e-71-0o477-Isup2.hkl^{(146.1KB, hkl)}

Click here for additional data file.^{(6.7KB, cml)}

Supporting information file. DOI: 10.1107/S2056989015010981/hb7433Isup3.cml

Click here for additional data file.^{(1.2MB, tif)}

. DOI: 10.1107/S2056989015010981/hb7433fig1.tif

The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level.

Click here for additional data file.^{(3.9MB, tif)}

. DOI: 10.1107/S2056989015010981/hb7433fig2.tif

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

Click here for additional data file.^{(2.3MB, tif)}

. DOI: 10.1107/S2056989015010981/hb7433fig3.tif

Unit-cell packing depicting the C—H⋯π and π–π interactions with dotted lines.

CCDC reference: 1405373

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

Table 1. Hydrogen-bond geometry (, ).

Cg1 is the centroid of the S2/C12C15 ring.

DHA	DH	HA	D A	DHA
C1H1CO1ⁱ	0.98	2.64	3.598(6)	166
C13H13O2ⁱⁱ	0.95	2.63	3.269(8)	125
C11H11A Cg1ⁱⁱⁱ	0.98	2.89	3.693(2)	139

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

Acknowledgments

NLP is thankful to the University Grants Commission (UGC), India for the UGC–JRF and MSK thanks the UGC for the UGC–BSR Meritorious Fellowship.

supplementary crystallographic information

S1. Comment

Pyrimidine derivatives are important class of compounds which display number of pharmacological properties including antiviral, antitumour, antibacterial and antihypertensive effects (Atwal et al., 1991; Kappe et al., 1997). Pyrimidine has been subjected to a large variety of structural modifications in order to synthesize derivatives (Singh et al., 2011) with different biological properties, among which, thiazole ring fused to pyrimidine ring resulting in thiazolopyrimidine is found to be more active (Ozair et al., 2010; Hayam et al., 2010). Herein, we report the crystal structure of the title compound (1). 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 (Nagarajaiah et al., 2012; Prasad et al., 2014). The molecular structure of the compound C₁₇H₁₈N₂O₃S₂ is shown in Fig. 1. The thiophenyl ring at chiral carbon C5 is positioned axially and exactly bisects the pyrimidine ring with a dihedral angle of 82.973 (1)°. The thiazine and pyrimidine ring form a dihedral angle of 5.975 (1)°. In the central pyrimidine ring, the chiral carbon atom C6 is displaced by 0.3130 (4) Å and adopts a flattened sofa conformation. The exocyclic ester group at C6 adopts cis orientation with respect to C6=C7 double bond and the carboxyl group (C11/C10/O3/C16) is slightly deviating from the thiozolopyrimidine plane at -87.946 (6)°. The crystal structure is mainly stabilized by a variety of intermolecular C—H···O interactions. C1—H1C···O1 hydrogen bonds link the molecules related by twofold rotation axes, forming R²₂(18) loops, which are in turn linked by C13—H13···O2 interactions to form chains of rings along [010] (Table.1; Fig. 2). In addition, weak C—H···π (thiophene) interactions of the type C11—H11A···Cg link the chains into layers parallel to [001] and π–π interactions between inversion-related thiazolopyrimidine rings with a centroid—centroid distance of 3.772 (10) Å connect these layers into a three-dimensional network (Fig. 3).

S2. Experimental

A mixture of 6-methyl-4-thiophen-2-yl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5- carboxylic acid ethyl ester (10 mmol) and 3-chloro-2,4-pentanedione (10 mmol) was refluxed in dry ethanol (20 mmol) for 12 h. The excess of solvent was distilled off and the solid hydrochloride salt that separated was collected by filtration, suspended in water and neutralized by aqueous sodium carbonate solution to yield the free base. The solution was filtered, the solid washed with water, dried and recrystallized from ethyl acetate to give the title compound (74% yield, mp 385 K). The compound was recrystallized by slow evaporation from 1:1 mixture of ethyl acetate and methanol, yielding pale- yellow blocks of the title compound.