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

Volodymyr Horishny; Roman Lesyk; Andrzej K Gzella

doi:10.1107/S1600536813004236

. 2013 Feb 16;69(Pt 3):o391. doi: 10.1107/S1600536813004236

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

Volodymyr Horishny ^a, Roman Lesyk ^a, Andrzej K Gzella ^b,^c,^*

PMCID: PMC3588441 PMID: 23476576

Abstract

The structural analysis of the title compound, C₁₄H₁₄N₂O₄S, particularly the presence of an acetyl group at the exocyclic N atom and the C(H)—C(O₂CMe)—N acetoxy group in the thiazole ring, may indicate that one of the starting materials, i.e. 2-(4-methoxyanilino)-1,3-thiazol-4(5H)-one, exists in the reaction mixture, at least partially, as a tautomer with an exocyclic amine N atom and an enol group. The acetoxy and acetyl groups deviate from the thiazole plane by 69.17 (6) and 7.25 (19)°, respectively. The thiazole and benzene rings form a dihedral angle of 73.50 (4)°. In the crystal, centrosymmetrically related molecules are connected into dimeric aggregates via C—H⋯O interactions.

Related literature

For the biological activity of 2-aryl(heteryl)aminothiazol-4-one derivatives, see: Ates et al. (2000 ▶); Eleftheriou et al. (2012 ▶); Eriksson et al. (2007 ▶); Lesyk & Zimenkovsky (2004 ▶); Lesyk et al. (2003 ▶, 2011 ▶); Rout & Mahapatra (1955 ▶); Subtel’na et al. (2010 ▶). For prototropic tautomerism studies, see: Lesyk et al. (2003 ▶); Subtel’na et al. (2010 ▶). For bond-length data, see: Allen et al. (1987 ▶). For a related structural study, see: Horishny et al. (2013 ▶).

Experimental

Crystal data

C₁₄H₁₄N₂O₄S
M _r = 306.33
Triclinic,
a = 8.9445 (5) Å
b = 9.5736 (8) Å
c = 9.9078 (9) Å
α = 115.509 (9)°
β = 93.381 (6)°
γ = 108.144 (6)°
V = 708.95 (10) Å³
Z = 2
Mo Kα radiation
μ = 0.25 mm⁻¹
T = 130 K
0.50 × 0.50 × 0.10 mm

Data collection

Agilent Xcalibur Atlas diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011 ▶) T _min = 0.860, T _max = 1.000
12469 measured reflections
3445 independent reflections
3075 reflections with I > 2σ(I)
R _int = 0.022

Refinement

R[F ² > 2σ(F ²)] = 0.035
wR(F ²) = 0.095
S = 1.06
3445 reflections
193 parameters
H-atom parameters constrained
Δρ_max = 0.37 e Å⁻³
Δρ_min = −0.27 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2011 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; 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 ▶); software used to prepare material for publication: WinGX (Farrugia, 2012 ▶) and PLATON (Spek, 2009 ▶).

Supplementary Material

Click here for additional data file.^{(18.3KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536813004236/tk5195sup1.cif

e-69-0o391-sup1.cif^{(18.3KB, cif)}

Click here for additional data file.^{(165.5KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813004236/tk5195Isup2.hkl

e-69-0o391-Isup2.hkl^{(165.5KB, hkl)}

Click here for additional data file.^{(5.5KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813004236/tk5195Isup3.cml

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
C5—H5⋯O20ⁱ	0.93	2.53	3.200 (2)	129

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Symmetry code: (i) Inline graphic .

supplementary crystallographic information

Comment

Significant popularity of thiazolidine scaffolds in drug design is grounded on the broad spectrum of biological activity of their derivatives. Among thiazolidine derivatives the group of 2-aryl(heteryl)aminothiazol-4-one derivatives is one of the most promising (Lesyk & Zimenkovsky, 2004; Lesyk et al., 2011). 2-Aryl(heteryl)aminothiazol-4-one activities covers antibacterial (Ates et al., 2000), antifungal (Rout & Mahapatra, 1955), anti-inflammatory (Lesyk et al., 2003; Eleftheriou et al., 2012) and anticancer activities (Subtel'na et al., 2010; Eriksson et al., 2007). Moreover, literature reports indicate existence of prototropic tautomeric forms of 3-unsubstituted 2-aryl(heteryl)aminothiazol-4-ones both in solutions and solid phase which can be of significant importance for biological activity (Lesyk et al., 2003; Subtel'na et al., 2010). Dictated by these observations, the aim of the presented work was synthesis of the compound (I) as starting substance for further design of new biologically active compounds.

The investigations on the structure of the title compound, a product of the reaction of 2-(4-methoxyanilino)-1,3-thiazol-4-one with acetyl anhydride, showed the presence of an acetoxy group at C4 and an acetyl functionality at N6 (Fig. 1). Similar observations were made for the product obtained by the identical method from 2-(2,4-dimethoxyanilino)-1,3-thiazol-4-one. The presence of the C4 acetoxy and N6 acetyl groups in the structure of compound (I) and 2-[N-(2,4-dimethoxyphenyl)acetamido]-1,3-thiazol-4-yl acetate (Horishny et al., 2013) may indicate that the starting materials, i.e. 2-(4-methoxyanilino)-1,3-thiazol-4-one and 2-(2,4-dimethoxyanilino)-1,3-thiazol-4-one, exist in the reaction mixture at least partially as tautomers with an exocyclic amine nitrogen and an enol moiety (H—)C5═C4—OH within the five-membered heterocyclic ring.

The C4 acetoxy group and N6 acetyl functionality are oriented differently in relation to the planar thiazole ring. The first one forms a dihedral angle of 79.22 (5)° with the mean plane of this ring whereas the second one is tilted only slightly [dihedral angle: 7.25 (19)°] (Fig. 1).

Both the C7═O8 carbonyl group relative to the C2—N6 bond and the C21═ O22 carbonyl group in relation to the C4—O20 bond have the same synperiplanar conformation. The torsional angles C2—N6—C7—O8 and C4—O18—C19—O20 are 4.96 (19) and -1.67 (19)°, respectively. The C13 methoxy group is approximately coplanar with the phenyl ring – the torsion angle is 1.9 (2)°. The flat phenyl and thiazole rings form a dihedral angle of 73.50 (4)°.

The bond lengths and angles in compound (I) are similar to those observed in 2-[N-(2,4-dimethoxyphenyl)acetamido]-1,3-thiazol-4-yl acetate (Horishny et al., 2013). The N6—C7 distance [1.3876 (16) Å] is longer (by about 8σ) than the normal (O═)C—N tertiary amide distance [1.346 (5) Å, Allen et al., 1987].

In the crystal structure, the molecules of (I) are connected by the C5—H5···O21ⁱ hydrogen bonds into centrosymmetric dimers (Table 1, Fig. 2).

Experimental

2-(4-Methoxyanilino)thiazol-4-one in the medium of acetic anhydride was refluxed for 2 h. The obtained solution was evaporated in vacuum and the residue was recrystallized twice from benzene–hexane (1:1) mixtures.