Catalyst-Free Synthesis of Highly Biologically Active 5-Arylidene Rhodanine and 2,4-Thiazolidinedione Derivatives Using Aldonitrones in Polyethylene Glycol

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. 1. Introduction 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 1) such as epalrestat, ciglitazone, AD-5061, pioglitazone, rosiglitazone, and so forth. Figure 1: Clinically used molecules having 5-arylidene rhodanines and 2,4-thiazolidenediones. Furthermore, rhodanine derivatives possess anticonvulsant, antibacterial, antiviral, and antidiabetic activities [1–3] Some of rhodanine-based derivatives act as hepatitis C virus (HCV) protease inhibitor [4], uridine diphospho-N-acetylmuramate/L-alanine ligase inhibitor [5], aldose reductase [6], β-lactamase [7], and JNK-stimulating phosphatase-1 (JSP-1) [8], while some of its derivatives are used for the analysis of certain noble metal ions [9]. Therefore, the synthesis of rhodanine derivatives currently is of much importance and a variety of methods and catalysts have been used [10–12]. Unlike rhodanine, 2,4-thiazolidinedione derivatives also have remarkable biological activities like antidiabetic [13], antibacterial [14], antifungal [15], antiproliferative effect on vascular smooth muscle [16], aldose reductase inhibitors [17], 15-hydroxyprostaglandin dehydrogenase inhibitors [18] instead of these biological activities 5-benzylidene-thiazolidine-2,4-dione derivatives act as inhibitors of MurD ligase [19]. In the literature several methods have been reported to synthesize these privileged molecules [20–24]. Therefore, significant biological activities prompt us to synthesize thiozolidine derivatives. 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 [25–27]. Apart from this major utility their general chemistry is little studied.[27] There are few reports of successful 1,3-additions of nitrones [28, 29]. Yousif et al. reported reactions of heterocyclic N-oxides under acidic conditions and obtained only condensed products [30]. In contrast, their counterpart imines are extensively explored to expose their utility as aldehyde equivalent [31–33]. Present