Title:An Efficient and Rapid Microwave-Assisted Synthesis of 1-acetyl-1Hindol- 3-yl Acetates
Volume: 3
Issue: 3
Author(s): Jay P. Parshotam, John A. Brazier, Richard Bovill and Helen M.I. Osborn
Affiliation:
Keywords:
Cyclisation, indoxyls, indoles, microwave, synthesis.
Abstract: 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.
