Synthesis of N -substituted 3-(2-aryl-2-oxoethyl) 3-hydroxyindolin-2-ones and their conversion to N -substituted (E)-3-(2-aryl-2-oxoethylidene)indolin-2-ones: synthetic sequence, spectroscopic characterization and structures of four 3-hydroxy compounds and five oxoethylidene products

An operationally simple and time -efficient approach has been developed for the synthesis of racemic N-substituted 3-(2-aryl-2-oxoethyl)-3-hydroxyindolin-2ones by a piperidine-catalysed aldol reaction between aryl methyl ketones and N-alkylisatins. These aldol products were used successfully as strategic intermediates for the preparation of N-substituted (E)-3-(2-hetary1-2-oxoethylidene)indolin-2-ones by a stereoselective dehydration reaction under acidic conditions. The products have all been fully characterized by 'H and 13C NMR spectroscopy, by mass spectrometry and, for a representative selection, by crystal structure analysis. In each of (RS)-1-benzy1-3-hydroxy 3 [2 (4 methoxypheny1)-2-oxoethyl]indolin-2-one, C24H21N04, (Ic), and (RS)-1-benzy1-3-{214(dimethylamino)pheny11-2-oxoethyll-3-hydroxyindolin-2-one, C25H24N203, (Id), inversion -related pairs of molecules are linked by 0 H" " "0 hydrogen bonds to form R22(10) rings, which are further linked into chains of rings by a combination of C H" " "0 and C H" " -7r(arene) hydrogen bonds in (Ic) and by C H" " " rr(arene) hydrogen bonds in (Id). The molecules of (RS)-1-benzy1-3-hydroxy-3[2-oxo-2-(pyridin-4-yl)ethyl]indolin-2-one, C22Hi8N203, (Ie), are linked into a three-dimensional framework structure by a combination of 0 H" " -N, C H- " "0 and C H" " -7r(arene) hydrogen bonds. (RS)-342-(Benzo[d][1,3]dioxo1-5y1)-2-oxoethy11-1-benzyl-3-hydroxyindolin-2-one, C24Hi9N05, (If), crystallizes with Z = 2 in the space group Pi and the molecules are linked into complex sheets by a combination of 0 H" " -0, C H" " "0 and C H" " -7r(arene) hydrogen bonds. In each of (E)-1-benzyl 3 [2 (4 fluoropheny1)-2-oxoethylidene]indolin-2one, C23H16FN02, (Ha), and (E)-1-benzy1-342-oxo-2-(thiophen-2-yl)ethylidene1indolin-2-one, C2iH15NO2S, (llg), the molecules are linked into simple chains by a single C H" " "0 hydrogen bond, while those of (E)-1-benzy1-342-oxo-2-(pyriclin4-yl)ethylidenelindolin-2-one, C22Hi6N202, (He), are linked by three C H" " "0 hydrogen bonds to form sheets which are further linked into a three-dimensional structure by C H" " -7r(arene) hydrogen bonds. There are no hydrogen bonds in the structures of either (E)-1-benzy1-342-(4-methoxypheny1)-2-oxoethylidene1indolin-2-one, C24Hi9NO3, (IIc), or (E)-1-benzy1-5-chloro 3 [2 (4 chloropheny1)-2oxoethylidene]indolin-2-one, C23H15C12NO2, (IIh), but the molecules of (IIh) are linked into chains of rr-stacked dimers by a combination of C Cl" " -7r(arene) and aromatic 7r rr stacking interactions.