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

Abstract

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 1H and 13C 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, C24H21NO4, (Ic), and (RS)-1-benzyl-3-{2-[4-(dimethylamino)phenyl]-2-oxoethyl}-3-hydroxyindolin-2-one, C25H24N2O3, (Id), 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 (Ic) and by C—H...π(arene) hydrogen bonds in (Id). The molecules of (RS)-1-benzyl-3-hydroxy-3-[2-oxo-2-(pyridin-4-yl)ethyl]indolin-2-one, C22H18N2O3, (Ie), 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, C24H19NO5, (If), crystallizes with Z′ = 2 in the space group P\overline{1} 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, C23H16FNO2, (IIa), and (E)-1-benzyl-3-[2-oxo-2-(thiophen-2-yl)ethylidene]indolin-2-one, C21H15NO2S, (IIg), 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, C22H16N2O2, (IIe), 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, C24H19NO3, (IIc), or (E)-1-benzyl-5-chloro-3-[2-(4-chlorophenyl)-2-oxoethylidene]indolin-2-one, C23H15Cl2NO2, (IIh), but the molecules of (IIh) are linked into chains of π-stacked dimers by a combination of C—Cl...π(arene) and aromatic π–π stacking interactions.