105119-82-2Relevant academic research and scientific papers
Studies of Chiral Indoles. Part I. Indoles with Chiral 1- and 3-Substituents. Synthesis and Preparative Enantiomeric Separation by Chromatography on Microcrystalline Triacetylcellulose
Nilsson, Ingemar,Isaksson, Roland
, p. 531 - 548 (2007/10/02)
A number of indole derivatives with chiral substituents in position 1 or 3 and with substituents of varying size in position 2 have been prepared.The chiral rotors are 1-N,N-dimethylcarbamoylethyl and N'-methylpiperidin-2'-on-3'-yl and their corresponding thioanalogues, and 1-phenylethyl.The reaction conditions required to obtain preferential 1- or 3-alkylation are discussed in terms of the HSAB principle and the extent of ion pair formation.Three 1-(N,N-dimethylcarbamoylethyl-indoles (R2=H and Me, and R2=Me, R3=CO2Me, R5=OMe) and one 1-(1-phenylethyl)indole (R2=Me, R3=CO2Me, R5=OMe) were obtained optically pure by stereospecific pathways.The other compounds were obtained in racemic forms.Most of the racemic compounds were conveniently resolved by liquid chromatography on swollen, microcrystalline triacetylcellulose (TAC).In some cases rather remarkable separations were obtained.Attempts were made to prepare the optically active 1- and 3-(N'-methylpiperidin-2'-on-3'-yl)indoles by hydrolysis of the methylthioimmonium salts prepared from chromatographically resolved thioamides.The 3-substituted analogues were partly racemized in this process, while the 1-substituted ones were completely racemized.A possible explanation is proposed.
