An Efficient and Rapid Microwave-Assisted Synthesis of 1-acetyl-1Hindol- 3-yl Acetates

Author(s): Jay P. Parshotam , John A. Brazier , Richard Bovill , Helen M.I. Osborn .

Journal Name: Current Microwave Chemistry

Volume 3 , Issue 3 , 2016

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Background: The synthesis of indoles, which are often derived from 1-acetyl-1H-indol-3-yl acetates, is of considerable synthetic interest, for example due to their medicinal properties, and their applications within microbiology. Whilst several chemical routes are available for accessing indoles, many are lengthy, and their scope for accessing a range of derivatives has not always been demonstrated. Herein, an optimised method for the synthesis of 1-acetyl-1H-indol-3-yl acetates is presented that is rapid and efficient, and allows entry to a range of functionalised indoxyls.

Methods: 1-Acetyl-1H-indol-3-yl acetates 1 and 7 have been prepared via the microwave-assisted cyclisation and decarboxylation of 2-[(carboxymethyl)amino]benzoic acids 5. The latter were reacted with acetic anhydride using triethylamine as the base and were subjected to microwave irradiation for 1 minute, at 80 °C with initial power of 300 W. Two chemical routes were investigated for access to the key 2-[(carboxymethyl)amino]benzoic acid intermediates 5.

Results: The target 1-acetyl-1H-indol-3-yl acetates 1 and 7 were isolated in 34-71% yield. In particular, synthesis of 1-acetyl-6-(trifluoromethyl)-1H-indol-3-yl acetate 7f and 1-acetyl-7-methyl-1H-indol-3-yl acetate 7h is reported for the first time. Access to the key 2-[(carboxymethyl)amino]benzoic acid intermediates 5 was achieved via two complementary routes, with a two step synthesis that used 2-aminobenzoic acids 4 as the starting materials being the preferred strategy.

Conclusion: The synthesis of 1-acetyl-1H-indol-3-yl acetates 1 and 7 from 2-[(carboxymethyl)amino]benzoic acids 5 has been optimised. By using microwave irradiation, and altering the base, solvent and reaction time, rapid entry to a range of indoxyl derivatives 1 and 7 proved possible, in good yield.

Keywords: Cyclisation, indoxyls, indoles, microwave, synthesis.

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Article Details

Year: 2016
Page: [247 - 257]
Pages: 11
DOI: 10.2174/2213335603666160108001556
Price: $58

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PDF: 18