An efficient one-pot synthesis of polyfunctionalized 2H-pyrroline derivatives by reaction of β-enaminocarbonyls, arylglyoxals and amines

Abstract

Multi-component reactions (MCRs), especially threecomponent reactions, offer significant advantages over conventional linear-type syntheses, because the combination of the reaction components to generate new products in a single step is easy and economic [12,13].β-Enaminocarbonyls are important compounds used for selective alkylation and acylation of carbonyl compounds and valuable intermediates for the synthesis of biologically active compounds [14][15][16]. These compounds are useful starting points for the preparation of a variety of heterocyclic compounds [17] utilized for synthesis of pharmaceuticals [18] and are building blocks for amino acids [19], peptides [20] or alkaloids [21].Designing of multi-component reactions in water is another attractive area in chemistry, because water is a cheap, safe and an environmentally benign solvent [22].Multi-component reactions of arylglyoxals and enaminocarbonyls in the presence of different nucleophiles have been recently reported for synthesis of polyfunctionalized pyrroles [23][24][25]. However, to the best of our knowledge there are only a few reports on the simple addition of enaminocarbonyl compounds to arylglyoxals [26]. Caballero et al. reported the condensation of N-unsubstituted enaminoesters with phenylglyoxal to afford N-unsubstituted pyrroles. When N-phenyl-enaminoesters were used, they reported obtaining a complex mixture, from which the pyrrolinone derivative was isolated in 30 % yield. The mechanistic studies established the reversibility of the addition reaction between enaminoester and phenylglyoxal to afford the cyclic intermediate dihydroxy pyrrole and product pyrrolinone in reaction conditions [26]. In continuation of our previous studies on the application of arylglyoxals for the synthesis of heterocyclic compounds [27][28][29], here we wish to report a simple addition reaction between arylglyoxal monohydrates and enaminoketones in water as solvent at Abstract An efficient one-pot synthesis of 2H-pyrroline derivatives by a simple reaction of β-enaminocarbonyls with arylglyoxals in water at room temperature is reported. The addition reaction between arylglyoxal derivatives and β-enaminocarbonyls in water afforded 3,4-dihydroxy-2H-pyrrolines after about 10 min stirring at room temperature. When the reaction was done in the presence of aromatic amines, the corresponding 4-amino-5-hydroxy-2H-pyrroline derivatives were obtained in good yields. All reactions were performed in water at room temperature and the products were isolated by simple filtration.

A Facile and Effective Procedure for Synthesis of Polyfunctionalized Bis (imidazolyl) Pyrrole/Imidazolyl Indole from Pyrrole/Indole with Arylglyoxals and N‐aryl amidines

“…The imidazole/pyrrole pair has been subject to considerable studies, including analyses of binding in hundreds of various sequence contexts and crystal structures confirming the existence of a hydrogen bond between the exocyclic amine of guanine and the imidazole nitrogen . With this background in mind and in continuation of our previous works on the development of multicomponent approaches to heterocycles , we report a simple multicomponent reaction between pyrrole or indole with arylglyoxal monohydrates and N ‐aryl amidines in an environmentally favorable moderate (ethanol) under mild reaction conditions for the synthesis of 4‐(5‐(1 H ‐imidazol‐4‐yl)‐1 H ‐pyrrol‐2‐yl)‐1 H ‐imidazole (Scheme ) or 3‐(1 H ‐imidazol‐4‐yl)‐1 H ‐indole derivatives (Scheme ), respectively, in high yields.…”