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 R22(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 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 interaction
Citation
Becerra , D , Castillo , J , Insuasty , B , Cobo , J & Glidewell , C 2020 , ' 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 ' , Acta Crystallographica Section C Structural Chemistry , vol. 76 , no. 5 , C76 . https://doi.org/10.1107/S2053229620004143
Publication
Acta Crystallographica Section C Structural Chemistry
Status
Peer reviewed
ISSN
2053-2296Type
Journal article
Description
The authors thank `Centro de Instrumentación Científico-Técnica' of Universidad de Jaén and its staff for data collection. They also thank Universidad del Valle, Universidad Pedagógica y Tecnológica de Colombia (project SGI-2829), Universidad de Jaén and the Consejería de Innovación, Ciencia y Empresa (Junta de Andalucía, Spain), for financial support. DB also thanks the Asociación Universitaria Iberoamericana de Postgrado for financial support.Collections
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