Crystal structure of 2-acetyl-5-(3,4-di­meth­oxy­phen­yl)-6-eth­oxy­carbonyl-3,7-dimethyl-5H-thia­zolo[3,2-a]pyrimidin-8-ium chloride

N L Prasad; M S Krishnamurthy; Noor Shahina Begum

doi:10.1107/S2056989015016229

. 2015 Sep 17;71(Pt 10):o764–o765. doi: 10.1107/S2056989015016229

Crystal structure of 2-acetyl-5-(3,4-dimethoxyphenyl)-6-ethoxycarbonyl-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidin-8-ium chloride

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

PMCID: PMC4647379 PMID: 26594466

Abstract

The title molecular salt, C₂₁H₂₅N₂O₅S⁺·Cl⁻, crystallizes with two ion pairs in the asymmetric unit. The cations have similar conformations (r.m.s. overlay fit = 0.40 Å), with one of them showing disorder of the terminal methyl group of the ester in a 0.72 (2):0.28 (2) ratio. In the first cation, the 3,4-dimethoxy-substituted phenyl ring subtends a dihedral angle of 88.38 (7)° with the pyrimidine ring and 6.79 (8)° with the thiazole ring. The equivalent data for the second cation are 89.97 (3) and 6.42 (7)°, respectively. The pyrimidine ring adopts a sofa conformation in each cation. In the crystal, the components are linked by N—H⋯Cl hydrogen bonds, generating isolated ion pairs. The ion pairs are are linked by C—H⋯O interactions, generating a three-dimensional network. In addition, a weak C—H⋯π interaction is observed.

Keywords: crystal structure, salt, pyrimidinium, chloride, pyrimidine derivatives, pharmacological properties, biological activity, hydrogen bonding, C—H⋯π interactions

Related literature

For the pharmacological properties of pyrimidine derivatives, see: Ashok et al. (2007 ▸); Alam et al. (2010 ▸); Kulakov et al. (2009 ▸); Zhi et al. (2008 ▸). For conformational effects on biological activity, see: Rovnyak et al. (1995 ▸). For related structures, see: Prasad et al. (2014 ▸); Nagarajaiah et al. (2012 ▸). graphic file with name e-71-0o764-scheme1.jpg

Experimental

Crystal data

C₂₁H₂₅N₂O₅S⁺·Cl⁻
M _r = 452.94
Triclinic,
a = 9.9000 (6) Å
b = 11.8563 (7) Å
c = 19.0377 (11) Å
α = 80.827 (2)°
β = 83.999 (2)°
γ = 86.071 (2)°
V = 2190.9 (2) Å³
Z = 4
Mo Kα radiation
μ = 0.31 mm⁻¹
T = 100 K
0.40 × 0.35 × 0.30 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1998 ▸) T _min = 0.947, T _max = 0.953
26782 measured reflections
7693 independent reflections
4545 reflections with I > 2σ(I)
R _int = 0.077

Refinement

R[F ² > 2σ(F ²)] = 0.055
wR(F ²) = 0.134
S = 0.97
7693 reflections
565 parameters
H-atom parameters constrained
Δρ_max = 0.46 e Å⁻³
Δρ_min = −0.39 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/S2056989015016229/hb7484sup1.cif

e-71-0o764-sup1.cif^{(36.6KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015016229/hb7484Isup2.hkl

e-71-0o764-Isup2.hkl^{(368.8KB, hkl)}

Click here for additional data file.^{(8.4KB, cml)}

Supporting information file. DOI: 10.1107/S2056989015016229/hb7484Isup3.cml

Click here for additional data file.^{(1.7MB, tif)}

. DOI: 10.1107/S2056989015016229/hb7484fig1.tif

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

Click here for additional data file.^{(1.3MB, tif)}

. DOI: 10.1107/S2056989015016229/hb7484fig2.tif

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

Click here for additional data file.^{(1.7MB, tif)}

. DOI: 10.1107/S2056989015016229/hb7484fig3.tif

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

CCDC reference: 1421372

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

Table 1. Hydrogen-bond geometry (, ).

Cg3 is the centroid of the C9BC14B ring.

DHA	DH	HA	D A	DHA
N1AH1ACl1A	0.88	2.20	2.993(1)	151
N1BH1BCl1B ⁱ	0.88	2.20	2.992(2)	150
C11AH11AO5B ⁱⁱ	0.95	2.58	3.523(1)	173
C15BH15CO5A ⁱⁱⁱ	0.98	2.58	3.456(6)	148
C21AH21DO3B ⁱⁱⁱ	0.98	2.50	3.459(6)	166
C4AH4A2Cg3	0.98	2.63	3.551(2)	157

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

Acknowledgments

NLP thanks for the University Grants Commission (UGC), India, for a CSIR–NET fellowship and MSK thanks the UGC for a UGC–BSR Meritorious fellowship.

supplementary crystallographic information

S1. Comment

Pyrimidine derivatives are of interest because of their useful biological and therapeutic activities (Ashok et al., 2007). The presence of both pyrimidine and thiazole rings results in enhanced activity (Alam et al., 2010; Kulakov et al., 2009). Thiazolo [3,2-a]pyrimidine derivatives generate enzyme inhibitors as novel therapeutical entities for severe neurodegenerative diseases (Zhi et al., 2008). In continuation to our research interests on thiazolo[3,2-a]pyrimidine derivatives (Prasad et al., 2014; Nagarajaiah et al., 2012), we report the crystal structure of the title compound. During the synthesis of one of the thiazolopyrimidine derivatives, an intermediate [C₂₁H₂₅N₂O₅S]⁺ Cl^- (I) was isolated and the structure was confirmed by X-ray diffraction.

The molecular structure of the compound is shown in Fig. 1. The title compound, [C₂₁H₂₅N₂O₅S]⁺ Cl^-, crystallizes in the triclinic space group with two molecules in the asymmetric unit. In molecules A and B, the 3,4- dimethoxy substituted phenyl ring form dihedral angle of 88.38 (7)° / 89.97 (3)° with mean plane of the pyrimidine ring and 6.79 (8)° / 6.42 (7)° with thiazole ring respectively. The two values separated by / corresponds to the two molecules in the asymmetric unit. The pyrimidine ring adopts a sofa conformation with atom C5A displaced by -0.2637 (3) Å from the mean plane of the other five atoms (N1A/C2A/N2A/C6A/C7A). The carbonyl group of the exocyclic ester at C6A and C6B adopts a cis orientation with respect to C6A=C7A and C6B=C6B double bond and the 3,4-dimethoxy substituted phenyl ring shows an syn periplanar conformation with respect to C5A—H5A and C5B—H5B bond of the pyrimidine ring. Phenyl ring at C5A and C5B in both the molecules shows antagonist (aryl-group up) conformation (Rovnyak et al., 1995). The packing features C—H···O interactions. The weak C11A—H11A···O5B hydrogen bonds forms supramolecular assembly along the crystallographic [101], which are inturn linked by another two C—H···O interactions (C15B—H15C···O5A & C21A—H21D···O3B) resulting in a ring with the graph set R²₂(7) notation (Table. 1; Fig. 2). The crystal packing also features N1A—H1A···Cl1A & N1B—H1B···Cl1B interactions. In addition, a weak C—H···π interaction of the type C4A-H4A2···Cg (Cg being the centroid of the phenyl ring) at a distance of 2.628 Å is also observed (Fig. 3).

S2. Experimental

A mixture of 4-(3,4-dimethoxy-phenyl)-6-methyl-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.