2-[7-(3,5-Dibromo-2-hy­droxy­phen­yl)-6-eth­oxy­carbonyl-2-oxo-5H-2,3,6,7-tetra­hydro­thio­pyrano[2,3-d][1,3]thia­zol-6-yl]acetic acid ethanol monosolvate

M Kowiel; N Zelisko; D Atamanyuk; R Lesyk; A K Gzella

doi:10.1107/S1600536812035325

. 2012 Aug 15;68(Pt 9):o2721–o2722. doi: 10.1107/S1600536812035325

2-[7-(3,5-Dibromo-2-hydroxyphenyl)-6-ethoxycarbonyl-2-oxo-5H-2,3,6,7-tetrahydrothiopyrano[2,3-d][1,3]thiazol-6-yl]acetic acid ethanol monosolvate

M Kowiel ^a, N Zelisko ^b, D Atamanyuk ^b, R Lesyk ^b, A K Gzella ^a,^c,^*

PMCID: PMC3435735 PMID: 22969606

Abstract

The title compound, C₁₇H₁₅Br₂NO₆S₂·C₂H₅OH, is the esterification reaction product of 2-(8,10-dibromo-2,6-dioxo-3,5,5a,11b-tetrahydro-2H,6H-chromeno[4′,3′:4,5]thiopyrano[2,3-d]thiazol-5a-yl)acetic acid. Cleavage of the lactone ring and formation of ethoxycarbonyl and hydroxy groups from its structural elements were observed. On the other hand, the carboxymethyl group was not esterified. The H atom and carboxymethyl group, both at stereogenic centres, show a cis conformation. The six-membered dihydrothiopyran ring adopts a half-chair conformation. All NH and OH groups participate in the three-dimensional hydrogen-bond network, which is additionally strengthened by C—H⋯O and C—H⋯S interactions. Intramolecular O—H⋯Br and C—H⋯O interactions also occur.

Related literature

For the biological activity of 4-thiazolidinone and thiopyrano[2,3-d]thiazole-2-one derivatives, see: Lesyk & Zimenkovsky (2004 ▶); Lesyk et al. (2011 ▶); Kaminskyy et al. (2011 ▶); Matiychuk et al. (2008 ▶); Lesyk et al. (2006 ▶); Atamanyuk et al. (2008 ▶). For ring conformation analysis, see: Cremer & Pople (1975 ▶). For bond-length data, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C₁₇H₁₅Br₂NO₆S₂·C₂H₆O
M _r = 599.31
Monoclinic,
a = 16.8176 (9) Å
b = 8.1654 (4) Å
c = 18.3841 (9) Å
β = 113.303 (6)°
V = 2318.6 (2) Å³
Z = 4
Mo Kα radiation
μ = 3.72 mm⁻¹
T = 130 K
0.45 × 0.40 × 0.25 mm

Data collection

Oxford Diffraction Xcalibur Atlas diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009 ▶) T _min = 0.761, T _max = 1.000
15312 measured reflections
5539 independent reflections
4500 reflections with I > 2σ(I)
R _int = 0.022

Refinement

R[F ² > 2σ(F ²)] = 0.027
wR(F ²) = 0.073
S = 1.09
5539 reflections
298 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 1.08 e Å⁻³
Δρ_min = −0.87 e Å⁻³

Data collection: CrysAlis PRO (Oxford Diffraction, 2009 ▶); 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, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶) and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812035325/bt5997sup1.cif

e-68-o2721-sup1.cif^{(23.4KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812035325/bt5997Isup2.hkl

e-68-o2721-Isup2.hkl^{(265.8KB, hkl)}

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
O26—H26⋯Br1	0.98 (3)	2.55 (3)	3.1181 (15)	117 (2)
C6—H6A⋯O13	0.97	2.44	3.033 (2)	119
N3—H3⋯O27ⁱ	0.89 (2)	1.83 (2)	2.713 (2)	171 (3)
O14—H14⋯O13ⁱⁱ	0.85 (3)	1.80 (3)	2.645 (2)	171 (3)
O26—H26⋯O16ⁱⁱⁱ	0.98 (3)	1.96 (3)	2.7800 (19)	139 (2)
O27—H27⋯O10	0.87 (3)	1.86 (3)	2.724 (2)	174 (2)
C6—H6A⋯S1^iv	0.97	2.75	3.5659 (17)	142
C23—H23⋯O10^v	0.93	2.36	3.253 (2)	161

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

supplementary crystallographic information

Comment

The prominent success in thiazolidinone field is related to 4-thiazolidinone derivatives. Anticonvulsant, sedative, antidepressant, anti-inflammatory, antihypertensive, antihistaminic and anticancer activities are a few among many other biological responses shown by this scaffold (Lesyk & Zimenkovsky, 2004; Lesyk et al., 2011). Among mentioned heterocycles fused heterocyclic systems, particularly thiopyrano[2,3-d]thiazole-2-ones possess a special interest as cyclic isosteric mimics of their synthetic precursors namely 4-thiazolidones without Michael accepting functionalities (Kaminskyy et al., 2011; Matiychuk et al., 2008). Fixation of highly active 5-arylidene-4-thiazolidinone in thiopyranothiazole system usually allows save the activity vector and opens up new possibilities of obtained derivatives optimization. Following the fact of anticancer activity discovery for various thiopyrano[2,3-d]thiazole-2-ones (Lesyk et al., 2006; Atamanyuk et al., 2008) the introduction of exocyclic carboxylic group into the mentioned heterocycles can be considered as on the way of lead-structures optimization. This prompted us to synthesize title compound, (I).

The molecular structure of compound (I) and the atom-labelling scheme is illustrated in Fig. 1.

The X-ray analysis showed that the crystal exists as ethanolic solvate. The asymmetric part of the unit cell contains one molecule of the compound (I) (solute) and one molecule of ethanol (solvent).

The studies on the structure of (I) showed that refluxing of 2-(8,10-dibromo-2,6-dioxo-3,5,5a,11b-tetrahydro-2H,6H-chromeno[4',3':4,5]thiopyrano[2,3-d]thiazol-5a-yl)acetic acid for three hours in ethanol resulted in the cleavage of the lactone ring and formation of an ethoxycarbonyl moiety from its structural elements. On the other hand, the carboxymethyl group was not esterified under these conditions.

Investigations of the geometry of dihydrothiopyrano[2,3-d]thiazol-2-one showed that the six-membered dihydrothiopyran ring has a half-chair conformation [Cremer & Pople (1975) puckering parameters: Q = 0.5136 (19) Å, Θ = 49.7 (2)°, φ = 268.5 (2)°].

The C4═C9 bond length of 1.342 (2) Å confirmed the presence of a double bond between these carbons.

The C2—N3 interatomic distance of 1.356 (3) Å in the thiazol-2-one moiety is lengthened of about 7σ relative to the normal (O═ )C—NH bond length [1.331 (2) Å] of secondary amide group of γ-lactam (Allen et al., 1987).

The carboxymethyl and ethoxycarbonyl groups at C7 atom of dihydrothiopyran ring are in an axial and equatorial positions, respectively, while the 3,4-dibromo-2-hydroxyphenyl substituent at C8 atom is in a pseudoaxial position.

The carboxymethyl and ethoxycarbonyl groups are trans and cis, respectively, relative to the 3,4-dibromo-2-hydroxyphenyl substituent. The torsion angles C11—C7—C8—C20 and C15—C7—C8—C20 are 159.65 (15) and 45.32 (19)°, respectively.

The planar carboxymethyl and phenyl groups are approximately perpendicular to the least squares plane of the dihydrothiopyran ring; the dihedral angles are 83.10 (6) and 86.47 (6)°, respectively. The C12═O13 carbonyl group of the carboxymethyl substituent is synperiplanar (+sp) relative to the C7—C11 bond [torsion angle C7—C11—C12—O13: 2.3 (2)°]. On the other hand, the C11—C12 bond is antiperiplanar (-ap) in relation to the C7—C8 bond [torsion angle: C8—C7—C11—C12: -168.91 (14)°]. The C21 atom of the 3,4-dibromo-2-hydroxyphenyl substituent, at which the hydroxy group is attached, is anticlinal relative to the C7—C8 bond (-ac) [torsion angle C7—C8—C20—C21: -108.48 (18)°].

The flat fragment of the ethoxycarbonyl group, consisted of C15,O16,O17, and C18 atoms, forms a 55.18 (6)° dihedral angle with the best plane of dihydrothiopyran ring. The remaining C19 atom of the ethoxycarbonyl group, projected away of 1.367 (4) Å from the above atoms plane, is synclinal relative to the C15—O17 bond [torsion angle C15—O17—C18—C19: -81.1 (2)°]. Moreover, the C15═O16 carbonyl group is synclinal in relation to the C7—C8 bond [torsion angle C8—C7—C15—O16: 76.5 (2)°]. However, the torsion angles C15—O17—C18—C19 and C8—C7—C15—O16 are of different signs.

The molecules of (I) are interconnected with a screw axis and are linked by hydrogen bonds O26—H26···O16ⁱⁱⁱ in chains (Table 1, Fig. 2). The neighbouring chains exist in antiparallel arrangement and are connected by hydrogen bonds O14—H14···.O13ⁱⁱ in layers growing parallel to the (-101) plane (Table 1, Fig. 2). The ethanol molecules form hydrogen bonding O27—H27···O10 and N3—H3···O27ⁱ (Table 1, Fig. 2) being both proton donors and acceptors. They link the molecules from neighbouring layers that results in formation of a three-dimensional lattice of hydrogen bonds in the crystal.

Experimental

An equimolar mixture of 5-(2-hydroxy-3,5-dibromobenzylidene)-4-thioxo-2-thiazolidinone, itaconic anhydride and pinch of hydroquinone (2–3 mg, for preventing of polymerization) in acetic acid was refluxed for 2 hrs. The product formed was filtered, washed, dried and re-crystallized from mixture DMF–AcOH. Obtained 2-(8,10-dibromo-2,6-dioxo-3,5,5a,11b-tetrahydro-2H,6H-chromeno[4',3':4,5]thiopyrano[2,3-d]thiazol-5a-yl)acetic acid was refluxed in ethanol for 3 hrs. The product formed was filtered, washed, dried and recrystallized from ethanol.