(Z)-2-Amino-5-[2,4-dimeth­oxy-6-(4-methoxy­styr­yl)benzyl­idene]-1,3-thia­zol-4(5H)-one methanol solvate

Nikhil Reddy Madadi; Thirupathi Reddy Yerram Reddy; Narsimha Reddy Penthala; Sean Parkin; Peter A Crooks

doi:10.1107/S1600536810018520

. 2010 Jun 26;66(Pt 7):o1792. doi: 10.1107/S1600536810018520

(Z)-2-Amino-5-[2,4-dimethoxy-6-(4-methoxystyryl)benzylidene]-1,3-thiazol-4(5H)-one methanol solvate

Nikhil Reddy Madadi ^a, Thirupathi Reddy Yerram Reddy ^a, Narsimha Reddy Penthala ^a, Sean Parkin ^b, Peter A Crooks ^a,^*

PMCID: PMC3006841 PMID: 21588002

Abstract

In the crystal structure of the title compound, C₂₁H₂₀N₂O₄S·CH₃OH, molecules are linked into chains by a series of intermolecular N—H⋯O, N—H⋯N and O—H⋯O hydrogen bonds. The molecular structure shows a double bond with Z geometry, connecting the thiazolone and resveratrol units. The dihedral angle between the thiazolone ring and the nearest dimethoxybenzene ring is 53.02 (7)°.

Related literature

For related structure–activitystudies, see; Aggarwal et al. (2004 ▶); Pettit et al. (1995 ▶); Cushman et al. (1991 ▶).

Experimental

Crystal data

C₂₁H₂₀N₂O₄S·CH₄O
M _r = 428.49
Monoclinic,
a = 10.6243 (2) Å
b = 22.2530 (5) Å
c = 9.0562 (2) Å
β = 93.028 (1)°
V = 2138.10 (8) Å³
Z = 4
Cu Kα radiation
μ = 1.65 mm⁻¹
T = 90 K
0.15 × 0.08 × 0.02 mm

Data collection

Bruker X8 Proteum diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2006 ▶) T _min = 0.777, T _max = 0.968
31098 measured reflections
3911 independent reflections
3631 reflections with I > 2σ(I)
R _int = 0.044

Refinement

R[F ² > 2σ(F ²)] = 0.043
wR(F ²) = 0.112
S = 1.13
3911 reflections
276 parameters
H-atom parameters constrained
Δρ_max = 0.51 e Å⁻³
Δρ_min = −0.30 e Å⁻³

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: SAINT (Bruker, 2006 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: XP in SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97 and local procedures.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810018520/fj2286sup1.cif

e-66-o1792-sup1.cif^{(22.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810018520/fj2286Isup2.hkl

e-66-o1792-Isup2.hkl^{(191.7KB, 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
N2—H2A⋯O4ⁱ	0.88	2.07	2.926 (2)	163
N2—H2A⋯N1ⁱ	0.88	2.64	3.175 (2)	120
N2—H2B⋯O1Sⁱⁱ	0.88	2.05	2.872 (2)	154
O1S—H1S⋯O4	0.84	1.88	2.716 (2)	172

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

Acknowledgments

This investigation was supported by NIH/National Cancer Institute grant PO1 CA104457 (PAC) and by NSF MRI grant CHE 0319176 (SP).

supplementary crystallographic information

Comment

Many natural products possessing a trimethoxybenzene ring, e.g., colchicines, and podophyllotoxins, are potent cytotoxic agents and exert their antitumor properties by their antitubulin activity. In view of the activity of such trimethoxybenzenes, similar structurally related stilbene moieties have been studied. The trihydroxy compound, resveratrol, a naturally occurring phytoalexin (trans-3, 4, 5-trihydroxystilbene) present in grapes, berries, peanuts,and red wine [Aggarwal et al.,2004, Pettit et al., 1995) is reported to be a potential cancer chemotherapeutic agent based on its striking inhibitory effects on cellular events associated with cancer initiation, promotion, and progression. (Cushman et al., 1991). These observations encouraged us to design and synthesise a series of novel trimethoxy resveratrol analogs that were expected to function as potent cytotoxic agents against lung and breast cancer cells. The structural characterization of the title compound by x-ray analysis was performed to determine the geometry (E vs Z) of the double bond connecting the thiozolone ring and the resveratrol moiety, which cannot be easily determined by NMR spectroscopic analysis, and to obtain detailed information on the structural conformation of the molecule, that may be useful in structure-activity relationship (SAR) analysis. The title compound was synthesized in two steps. In step one, the formylation of (E)-1, 3-dimethoxy-5- (4-methoxystyryl)benzene with a slight excess of phosphorous oxychloride in dimethylformamide at 0 °C resulted the formation of trans-2-formyl-3, 4', 5-trimethoxystilbene. In step two, the reaction of trans-2-formyl-3, 4', 5-trimethoxystilbene with the active methelene compound, 2-aminothiazol-4(5H)-one in presence of ammonium acetate in acetic acid under microwave irradiation conditions yielded the title compound, (Z)-2-amino-5-[2,4-dimethoxy-6- (4-methoxystyryl)benzylidene]thiazol-4(5H)-one in 90% yield. The x-ray analysis studies revealed that the double bond connecting the thiazolone and resveratrol moieties has the Z geometry. The dihedral angle between the plane of the thiazolone ring and the plane of the nearest phenyl ring is 53.02 (7)°. The crystal packing is stabilized by a series of N—H···O, N—H···N and O—H···O intermolecular hydrogen bonds.

Experimental

A mixture of trans-2-formyl-3,4',5-trimethoxystilbene (50 mg, 1 mmol), 2-aminothiazol-4(5H)-one (20.44 mg, 1.1 mmol), ammonium acetate (13.56 mg, 1.1 mmol) and acetic acid (0.25 ml) was irradiated in a domestic microwave oven for 60 sec with intermittent cooling to room temperature every 20 sec. The reaction mixture was allowed to cool to room temperature, and treated with saturated aqueous sodium bicarbonate solution. The precipitate thus obtained was collected by filtration, washed with cold water and dried, to afford the crude product. Crystallization from methanol gave a white crystalline product of (Z)-2-amino-5-[2,4-dimethoxy-6-(4-methoxystyryl) benzylidene]thiazol-4(5H)-one methanolate, which was suitable for x-ray analysis. ¹H NMR (DMSO-d₆): δ 3.77 (s, 3H, -OCH₃), 3.82 (s, 3H, -OCH₃), 3.86 (s, 3H, -OCH₃), 6.54-6.55 (d, J=2 Hz, 1H), 6.90-6.91 (m, 1H), 6.93-6.95 (d, J=2 Hz, 3H), 7.20-7.23 (d, J=16 Hz, 1H), 7.47-7.49 (d, J=9 Hz, 2H), 7.61 (s, 1H), 8.83 (s, 1H), 9.12 (s, 1H) ppm. ¹³C NMR (DMSO-d₆): δ 55.6, 55.9, 56.3, 98.1, 102.8, 114.9, 115.9, 124.2,125.7, 128.6, 130.2, 131.6, 134.6, 138.4, 150.5, 158.9, 159.9, 161.6, 176.6, 180.3, 181.3. M. P: 172-175 °C