Novel Route for Synthesis of Thiozolidine-2 , 4-Dione Derivatives as a Mannich Base

The Mannich base of Thiozolidine-2,4-dione derivatives has come to lime light due to their various pharmacological activities. Thiazolidine-2,4-dione is an extensively explored heterocyclic nucleus for designing of novel agents implicated for a wide variety of pathophysiological conditions, that is, diabetes, diabetic complications, cancer, arthritis, inflammation, microbial infection, and melanoma. In present work, synthesis quinoline attached imidazoline derivative using (3 + 2) cyclo-addition via imine of quinoline and TosMIC. These derivatives were converted to Mannich bases of thiozolidine-2,4-dione using Knoevenagel condensation. The sulfonamide analogues of thiozolidine-2,4-Dione were also synthesized and characterized by using alkylation conditions.

Nowadays, diabetes is a major metabolic disorder on human beings throughout International Journal of Organic Chemistry world.The Thiazolidine-2,4-dione (TZD) derivatives act as drug candidates such as, rosiglitazone, pioglitazone, lobiglitazone, englitazone, metolazone, ozoline, darglitazone and troglitazone etc. TZD derivatives not only confine for treatment of metabolic disorder diabetic, but also show as an inflammatory agent, anti-cancer and for treatment of melanoma.Due to importance of TZD derivatives, many scientists have developed various routes for synthesis.
Om Silakari et al. [2] developed different TZD derivatives and evolutes of their biological activity.The various pharmacological activity of Thiazolidine-2,4-dione was shown in Figure 1.
Various approaches have been developed for synthesis of thiazolidine-2,4-dione and there are many active sites for exploring new analogues.
As a part of research work, we synthesize novel Mannich base of thiazolidine-2,4-dione and sulfonamide analogues using an effective and feasible process compared to other approaches and designed to make easy to scale up.
We strongly believe these analogues are biologically active.

Materials and Methods
All reagents and starting material were procured from commercial sources (Aldrich, Alfa Aesar) and solvents, such as THF, DMF and toluene, which were thoroughly dried before use.THF and toluene were dried using sodium metal and Benzophenone, and DMF was dried using CaH.The synthesized analogues were fully characterized using Analytical methods like IR, NMR (Bruker).The melting points were recorded using on a WRS-1A digital Melting Point Apparatus without correction.Infrared spectra were taken using an AVATAR 370 FT-IR spectrometer. 1 HNMR, 13 CNMR spectra were recorded with a Bruker spectrometer operating at 400 MHz with Trimethylsilane reference and values were recorded in ppm.The progress of reaction was monitored using TLC system and I 2 spray and KMnO 4 TLC strain.The crude compounds were purified using column chromatography (100 -200 mesh silica) and Combi Flash Chromatography.The hydrogenolysis process was carried out using parr shaker.

Experimental Methods
Current research work, we prepared below compounds and described in step

Conclusion
In We are planning to make these derivatives check for biological evolution and details will include in next journal.

Figure 2 .
Figure 2. The Reaction mechanism for step 2.

2 N
current research work, we successfully synthesized and characterized Mannich bases of quinoline attached imidazoline containing thiozolidine-2,4-dione derivatives and sulfonamide analogues.In step 2, cyclization was achieved in good yield.In step 4, aldehyde was isolated with good yield.Step 7 & 8 avoid te-International Journal of Organic Chemistry dious work-up and gain good yields.We strongly believe this is a novel route for synthesis of Mannich bases of thiozolidne-2,4-dione and sulfonamide analogues.

Table 1 .
Summary of physical data for analogues 7(a-f).