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‐2‐ones 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‐hetaryl‐2‐oxoethylidene)indolin‐2‐ones by a stereoselective dehydration reaction under acidic conditions. The products have all been fully characterized by 1 H and 13 C NMR spectroscopy, by mass spectrometry and, for a representative selection, by crystal structure analysis. In each of ( RS )‐1‐benzyl‐3‐hydroxy‐3‐[2‐(4‐methoxyphenyl)‐2‐oxoethyl]indolin‐2‐one, C 24 H 21 NO 4 , (I c ), and ( RS )‐1‐benzyl‐3‐{2‐[4‐(dimethylamino)phenyl]‐2‐oxoethyl}‐3‐hydroxyindolin‐2‐one, C 25 H 24 N 2 O 3 , (I d ), inversion‐related pairs of molecules are linked by O—H…O hydrogen bonds to form R 2 2 (10) rings, which are further linked into chains of rings by a combination of C—H…O and C—H…π(arene) hydrogen bonds in (I c ) and by C—H…π(arene) hydrogen bonds in (I d ). The molecules of ( RS )‐1‐benzyl‐3‐hydroxy‐3‐[2‐oxo‐2‐(pyridin‐4‐yl)ethyl]indolin‐2‐one, C 22 H 18 N 2 O 3 , (I e ), are linked into a three‐dimensional framework structure by a combination of O—H…N, C—H…O and C—H…π(arene) hydrogen bonds. ( RS )‐3‐[2‐(Benzo[ d ][1,3]dioxol‐5‐yl)‐2‐oxoethyl]‐1‐benzyl‐3‐hydroxyindolin‐2‐one, C 24 H 19 NO 5 , (I f ), crystallizes with Z ′ = 2 in the space group P and the molecules are linked into complex sheets by a combination of O—H…O, C—H…O and C—H…π(arene) hydrogen bonds. In each of ( E )‐1‐benzyl‐3‐[2‐(4‐fluorophenyl)‐2‐oxoethylidene]indolin‐2‐one, C 23 H 16 FNO 2 , (II a ), and ( E )‐1‐benzyl‐3‐[2‐oxo‐2‐(thiophen‐2‐yl)ethylidene]indolin‐2‐one, C 21 H 15 NO 2 S, (II g ), the molecules are linked into simple chains by a single C—H…O hydrogen bond, while those of ( E )‐1‐benzyl‐3‐[2‐oxo‐2‐(pyridin‐4‐yl)ethylidene]indolin‐2‐one, C 22 H 16 N 2 O 2 , (II e ), are linked by three C—H…O hydrogen bonds to form sheets which are further linked into a three‐dimensional structure by C—H…π(arene) hydrogen bonds. There are no hydrogen bonds in the structures of either ( E )‐1‐benzyl‐3‐[2‐(4‐methoxyphenyl)‐2‐oxoethylidene]indolin‐2‐one, C 24 H 19 NO 3 , (II c ), or ( E )‐1‐benzyl‐5‐chloro‐3‐[2‐(4‐chlorophenyl)‐2‐oxoethylidene]indolin‐2‐one, C 23 H 15 Cl 2 NO 2 , (II h ), but the molecules of (II h ) are linked into chains of π‐stacked dimers by a combination of C—Cl…π(arene) and aromatic π–π stacking interactions.