A green, efficient synthesis of 5-arylidene rhodanine and 2,4-thiazolidinedione derivatives without using any external catalyst in polyethylene glycol (PEG) at 80°C has been described. Reaction procedure is very simple, short, and obtained yields are very high.
Rhodanines and thiazolidinediones both are aprivileged class of molecule, and they show large number of biological activities. The most significant position of these molecules seems to be as they are asubset of commercially employed noninsulin-dependent diabetes mellitus (NIDDM), insulin sensitizing agents (Figure
Clinically used molecules having 5-arylidene rhodanines and 2,4-thiazolidenediones.
Furthermore, rhodanine derivatives possess anticonvulsant, antibacterial, antiviral, and antidiabetic activities [
Unlike rhodanine, 2,4-thiazolidinedione derivatives also have remarkable biological activities like antidiabetic [
Nitrones (imine oxides) are reputed as 1,3-dipoles and are extensively explored for the synthesis of five membered heterocycles by combining them with several types of multiple bonds [
Synthesis of 5-arylidene thiazolidinediones.
First of all, a series of nitrones was prepared using a variety of aldehyde and hydroxyl amine as per already reported method [
To check the effect of the solvent, a set of reactions was performed using different solvents such as MeOH, EtOH, H2O, THF, PEG, DMF, and so forth and in absence of solvent. Conclusively, in case of PEG best results were obtained with high yields in minimum reduced time. Keeping optimized reaction conditions, a variety of aldehydes with rhodanine/2,4-thiazolidinedione were reacted to afford 5-arylidenerhodanines
Synthesis of 5-arylidine rhodanine and 2,4-thiazolidinedione derivatives using aldonitrones in polyethylene glycol (PEG).
Entry | X | Y | Producta | Time (min) | Yield (%)b | Melting point (°C) reference |
---|---|---|---|---|---|---|
1 | H | S |
|
20 | 85 | 202-203 [ |
2 | 4-Cl | S |
|
20 | 93 | 230–232 [ |
3 | 4-Br | S |
|
20 | 89 | 229-230 [ |
4 | 4-NO2 | S |
|
25 | 94 | 254-255 [ |
5 | 4-CH3 | S |
|
30 | 78 | 224-225 [ |
6 | 4-CH3O | S |
|
30 | 83 | 250-251 [ |
7 | 4-OH | S |
|
30 | 79 | 184-185 [ |
8 | H | O |
|
25 | 92 | 240-241 [ |
9 | 3-Cl | O |
|
25 | 88 | 270-271 [ |
10 | 4-Cl | O |
|
25 | 85 | 224-225 [ |
11 | 4-NO2 | O |
|
25 | 75 | 260–262 [ |
12 | 4-CH3 | O |
|
25 | 86 | 224-225 [ |
13 | 4-CH3O | O |
|
35 | 88 | 234-235 [ |
14 | 4-OH | O |
|
35 | 90 | 280-281 [ |
aReaction conditions:
Active methylene compounds
Plausible reaction mechanism.
Next, the recyclability of the solvent was studied by using
As far as mechanism is concerned, reaction proceeds via nucleophilic addition of
In summary, the present protocol is an efficient and environmentally benign procedure for the synthesis of drug intermediate 5-arylidine rhodanine and 2,4-thiazolidinedione derivatives using aldonitrones in polyethylene glycol (PEG)
Reagent-grade chemicals were purchased from a commercial source and used without further purification. Yields refer to the yield of the isolated products. Melting points were determined in open capillaries in paraffin bath and are uncorrected. Infrared (IR) spectra were recorded in KBr discs on a Perkin-Elmer 240C analyzer. 1H NMR spectra were recorded on a BRUKER AVANCE II 400 NMR Spectrometer using tetramethylsilane (TMS) as internal standard. The progress of the reaction was monitored by thin layer chromatography (TLC) using silica gel G (Merck).
A mixture-nitrone (10 mmol) 1, rhodanine or 2,4-thiazolidinedione (10 mmol) 2, and polyethylene glycol (5 mL) was stirred at 80°C temperature for appropriate time (see Table
(5Z)-5-Benzylidene-2-thioxo-1,3-thiazolidine-4-one (
(5Z)-5-(4-Methoxybenzylidene)-2-thioxo-1,3-thiazolidine-4-one (
(5Z)-5-Benzylidene-1,3-thiazolidine-2,4-dione
(5Z)-5-(4-Methylbenzylidene)-1,3-thiazolidine-2,4-dione (
The authors are thankful to Sophisticated Analytical Instrument Facility Central Instrument Laboratory, Panjab University, Chandigarh, for spectral analysis.