2-[N-(2,4-Dimethoxyphenyl)acetamido]-1,3-thiazol-4-yl acetate

The title compound, C15H16N2O5S, is a product of the reaction of 2-(2,4-dimethoxyphenylamino)-1,3-thiazol-4(5H)-one with acetic anhydride. The presence of the acetyl and acetoxy groups in the molecule indicates that the starting thiazole exists as a tautomer in the reaction mixture with exocyclic amino and enol moieties. The acetyl group is tilted slightly from the heterocyclic ring plane [dihedral angle = 4.46 (11)°], while the acetoxy group is almost perpendicular to this ring [dihedral angle = 88.14 (12)°]. An intramolecular acetyl–methoxy C—H⋯O interaction is noted. In the crystal, molecules are connected into a three-dimensional architecture by C—H⋯O interactions.

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: TK5194).

Comment
2-Arylaminothiazol-4-one derivatives are of great importance in modern medicinal chemistry of anticancer agents (Lesyk & Zimenkovsky, 2004;Lesyk et al., 2011). In particular, these heterocycles demonstrated inhibition of the HT29 cell line (colon cancer), characterized by a high COX-2 expression (Ottana et al., 2005), as well as CDK1/cyclin B inhibition (Chen et al., 2007). These effects were achieved by block of cell cycle progression at the G2/M phase border in reversible manner and induction of apoptosis (Vassilev et al., 2006). Antagonizing stimulatory effects of free fatty acids at cell proliferation (inhibitory effect on tumor survival) in human breast cancer cell line (MDA-MB-231) was reported as well for the benzylidene-2-arylaminothiazol-4-ones (Eriksson et al., 2007). Series of novel 5-arylidene-2-arylaminothiazol-4(5H)-ones were evaluated for the anticancer potential, in vitro, against the standard US National Cancer Institute's panel of 60 cancer cell lines. The majority of compounds showed significant cytotoxicity at micromolar and submicromolar concentrations; mean log(GI 50 ) range -5.77 to -4.35. Some of the most potent compounds possessed selectively high effects on all leukemia cell lines at the submicromolar level (Subtelna et al., 2010).
Prototropic tautomerism of 2-aminothiazol-4-ones presents an interesting target for studies of both molecular structures and spectroscopic properties (Subtelna et al., 2010;Lesyk et al., 2003;Vana et al., 2009). Motivated by previous research of 2-arylaminothiazol-4-one derivatives, the aim of the present work was to synthesize the title compound (I) as a starting substance for further design of new anticancer agents.
The studies on the structure of compound (I), a product of the reaction of 2-(2,4-dimethoxyphenylamino)-1,3-thiazol-4one with acetic anhydride, showed the presence of acetoxy and acetyl groups attached respectively at C4 and N6 positions of the compound (Fig. 1). This observation indicates that the starting material exists in the reaction mixture as a tautomer with an exocyclic amino nitrogen atom and additionally an enol moiety (H-)C5═C4-OH in the heterocyclic ring. The acetyl and acetoxy groups are oriented differently relative to the planar thiazole ring. The acetyl group at N6 is tilted only slightly [dihedral angle: 4.46 (11)°] whereas the acetoxy group at C4 is almost perpendicular to this ring [dihedral angle: 88.14 (12)°] (Fig. 1). Worthy of mention is the fact that the C7═ O8 and C21═O22 carbonyl groups are synperiplanar in relation to the C2-N6 and C4-O20, respectively. The torsion angles C2-N6-C7-O8 and C4-O20 -C21-O22 are -1.16 (19) and 12.0 (2)°, respectively.
The methoxy groups on C11 and C14 of the phenyl ring are tilted to a small but statistically significant extent. The torsional angles C12-C11-O16-C17 and C12-C13-O18-C19 have the same value of 11.2 (2)°.
In the crystal lattice, the molecules of compound (I) are connected by three-centre hydrogen bonds C17 i -H17C i ···O8···H15 ii -C15 ii into ribbons parallel to the a axis. According to the graph method for categorizing hydrogen bonds, this pattern can be classified as ring motifs R 2 2 (16) and R 2 2 (12) (Fig. 2) further through the C5-H5···O18 iii contacts into layers growing parallel to the (011) plane (Fig. 3).

Refinement
All H atoms were positioned into the idealized positions and were refined in the riding model approximation: C methyl -H = 0.96 Å, C(sp 2 )-H = 0.93 Å; U iso (H) = 1.2U eq (C) or 1.5U eq (C) for methyl H. The methyl groups were refined as rigid groups which were allowed to rotate.

Figure 1
The molecular structure of (I) together with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as spheres of arbitrary radii.   The hydrogen bonding (dotted lines) in (I), viewed approximately down the a axis. Symmetry code: (iii) x, -1 + y, 1 + z.
H atoms not involved in hydrogen bonds have been omitted for clarity.

Special details
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 F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.