02095nas a2200217   4500008004100000022001400041245017100055210006900226260011000295300001400405490000700419520116900426100002501595700002001620700002001640700002301660700002201683700002101705700002601726856012501752       2015                        eng d  a1463-926200aHighly efficient regioselective synthesis of pyrroles via a tandem enamine formation-Michael addition-cyclization sequence under catalyst- and solvent-free conditions0 aHighly efficient regioselective synthesis of pyrroles via a tand  aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcAPR  a3415-34230 v173 a<p>A convenient catalyst-free, three-component procedure was developed for the synthesis of tetrasubstituted pyrroles under solvent-free conditions and in green solvents glycerol, PEG-200 and water. A sequential enamine-formation, Michael addition and intramolecular cyclization of primary amines, 1,3-dicarbonyl compounds and isatin-derived Michael acceptors afforded 3-(1H-pyrrol-3-yl)indolin-2-ones in excellent yields. In this simple one-pot transformation the requirement of column chromatography purification of the products was completely avoided. Besides, the method is highly environmentally benign and atom-economical, and the only side product of this reaction was two molecules of water. A comparative study for the four developed conditions showed that the solvent-free conditions were superior regardless of the nature of the starting materials, and the green solvents were effective for alkyl and benzylamines affording higher yields compared to arylamines. The preliminary in vitro cytotoxic studies of a representative compound against Ehrlich's ascites carcinoma (EAC) tumor cells showed significant activity with a CTC50 value of 15.64 mu M.</p>1 aVivekanand, Thavaraj1 aVinoth, Perumal1 aAgieshkumar, B.1 aSampath, Natarajan1 aSudalai, Arumugam1 aMenendez, Carlos1 aSridharan, Vellaisamy  uhttps://library.ncl.res.in/content/highly-efficient-regioselective-synthesis-pyrroles-tandem-enamine-formation-michael-0