Oligomerization of Indole Derivatives with Incorporation of Thiols

Felikss Mutulis,Jarl Wikberg,Edvards Liepinsh,Ilze Mutule,Adolf Gogoll,Aleh Yahorau,Sviatlana Yahorava

doi:10.3390/molecules13081846

Felikss Mutulis, Jarl Wikberg + Show 5 more

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https://doi.org/10.3390/molecules13081846

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Abstract

Two molecules of indole derivative, e.g. indole-5-carboxylic acid, reacted with one molecule of thiol, e.g. 1,2-ethanedithiol, in the presence of trifluoroacetic acid to yield adducts such as 3-[2-(2-amino-5-carboxyphenyl)-1-(2-mercaptoethylthio)ethyl]-1H-indole-5-carboxylic acid. Parallel formation of dimers, such as 2,3-dihydro-1H,1'H-2,3'-biindole-5,5'-dicarboxylic acid and trimers, such as 3,3'-[2-(2-amino-5-carboxy-phenyl)ethane-1,1-diyl]bis(1H-indole-5-carboxylic acid) of the indole derivatives was also observed. Reaction of a mixture of indole and indole-5-carboxylic acid with 2-phenylethanethiol proceeded in a regioselective way, affording 3-[2-(2-aminophenyl)-1-(phenethylthio)ethyl]-1H-indole-5-carboxylic acid. An additional product of this reaction was 3-[2-(2-aminophenyl)-1-(phenethylthio)ethyl]-2,3-dihydro-1H,1'H-2,3'-biindole-5'-carboxylic acid, which upon standing in DMSO-d6 solution gave 3-[2-(2-aminophenyl)-1-(phenethylthio)ethyl]-1H,1'H-2,3'-biindole-5'-carboxylic acid. Structures of all compounds were elucidated by NMR, and a mechanism for their formation was suggested.

Highlights

Multistage solid phase organic synthesis, which excludes isolation of intermediates steps, is an attractive method for the preparation of diverse chemical substances [1]
To investigate the aforementioned unknown side reaction, in the present study we tried to prepare a similar compound from indole-5-carboxylic acid itself
According to LC/MS, along with the dimer and trimer of indole-5-carboxylic acid, a product, whose molecular mass corresponded to the sum of mass of four molecules of indole-5-carboxylic acid and one molecule 1,2-ethanedithiol was detected

Summary

Introduction

Multistage solid phase organic synthesis, which excludes isolation of intermediates steps, is an attractive method for the preparation of diverse chemical substances [1]. A high yield of desired product at each synthetic stage is important for these methods [2], as various side reactions, lowering the chemical yield of the individual synthetic steps, are the main limitation of the method [3]. In order to make the method more efficient, a deeper understanding of these unwanted processes is desirable.

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