Diacetoxyiodobenzene mediated oxidative dethionation of N -substituted 5-arylmethylidene rhodanines: an efficient synthesis of N -substituted 5-arylmethylidene thiazolidine-2,4-diones

A simple and efficient synthesis of N -substituted-5-arylmethylidene thiazolidine-2,4-diones has been developed via oxidative dethionation of N -substituted-5-arylmethylidene rhodanines using diacetoxyiodobenzene (DIB) in ethanol at room temperature. This protocol is simple, mild, column free, obviates the need of acids and bases


Introduction
Thiazolidine-2,4-diones are important five membered N,S-heterocycles, which serve as the core components of numerous compounds that have been claimed to possess a wide range of interesting biological activities such as anti-inflammatory, 1 antidiabetic, 2 antimicrobial, 3 antimalarial, 4 and anticancer. 5They are building blocks of many commercially available drugs such as troglitazone, pioglitazone, and rosiglitazone. 6These derivatives are clinically used for treatment of type II diabetes mellitus.Further, thiazolidine-2,4-diones derivatives have been reported as inhibitors of targets such as glycogen synthase kinase-3 (GSK-3), 7 aldose reductase, 8 Pim protein kinases 9 and 15-hydroxyprostaglandin dehydrogenase. 10Because of the prominent biological activities of thiazolidine-2,4-dione derivatives, development of clean synthetic methods is of great significance.
Various methods have been developed to convert thioxo to oxo in 2-thioxo-4-thiazolidinones.The use of reagents such as hydrogen peroxide, 11 aqueous chloroacetic acid, 12 bromine in acetic acid, 13 and dimethyl sulfate 14 has been reported for this transformation.Moreover, N-substituted 5-arylmethylidene thiazolidine-2,4-diones are also prepared by alkylation of 5-arylmethylidene rhodanine with alkyl halide in presence of base. 15,16However, the conversion of thioxo group in N-substituted-5-arylmethylidene rhodanines into their corresponding oxo analogue has never been realized using hypervalent iodine compounds.

Results and Discussion
The desired N-substituted-5-arylmethylidene rhodanine (1a-k) were synthesized in good yields by condensation reaction of N-substituted rhodanines with aromatic aldehydes in the presence of piperidine using ethanol as solvent. 24Initially, a trial reaction was carried out by treating (Z)-3-benzyl-5-benzylidene-2thioxothiazolidin-4-one (1a) (0.5 mmol) with diacetoxyiodobenzene (DIB) (0.5 mmol) in acetonitrile at room temperature.A new product was detected after 1 h stirring at room temperature and then the solvent was evaporated under reduced pressure.The product was isolated (55%) by recrystallization from ethanol and spectroscopic analysis ( 1 H NMR, 13 C NMR, IR, HRMS) reveals its structure to be (Z)-3-benzyl-5benzylidenethiazolidine-2,4-dione (2a).

Conclusions
In summary, we have demonstrated a simple and efficient protocol for easy and facile access to N-substituted-5-arylmethylidene thiazolidine-2,4-diones derivatives by oxidative dethionation of N-substituted-5arylmethylidene rhodanines using diacetoxyiodobenzene (DIB).The reaction proceeded under mild condition and the desired product can be obtained by recrystallization from ethanol in good to high yields.

Experimental Section
General.All the compounds were commercial grade and were used without further purification.Solvents were removed in a rotary evaporator under reduced pressure.Reactions were monitored by TLC on silica gel 60 GF254 (0.25 mm).Silica gel (60−120 mesh size) was used for the column chromatography. 1 H NMR spectra were recorded on 400/600 MHz in CDCl3 and 13 C NMR spectra were recorded on 100/150 MHz in CDCl3 using TMS as internal standard.High-resolution mass spectral analysis (HRMS) data were recorded using ESI mode (Q-TOF type Mass Analyzer).

Table 1 .
Optimization of reaction conditions a,b b Isolated yield.c 0.6 mmol of DIB was used.