A Simple, Effective, Green Method for the Regioselective 3-Acylation of Unprotected Indoles

Abstract

A fast and green method is developed for regioselective acylation of indoles in the 3-position without the need for protection of the NH position. The method is based on Friedel-Crafts acylation using acid anhydrides. The method has been optimized, and Y(OTf)3 in catalytic amounts is found to be the best catalyst together with the commercially available ionic liquid [BMI]BF4 (1-butyl-3-methylimidazolium tetrafluoro-borate) as solvent. The reaction is completed in a very short time using monomode microwave irradiation. The catalyst can be reused up to four times without significant loss of activity. A range of substituted indoles are investigated as substrates, and thirteen new compounds have been synthesized.

Greener Friedel‐Crafts Acylation Using Microwave‐Enhanced Reactivity of Bismuth Triflate in the Friedel‐Crafts Benzoylation of Aromatic Compounds with Benzoic Anhydride

“…The non‐substituted arenes such as benzene, naphthalene, anthracene, biphenyl and fluorene were also reactive yielding primarily p ‐substituted products (Table , entries 15–19). 3‐Benzoylindoles are considered to be interesting precursors for many organic transformations and regioselectivity in the 3‐benzoylation of indoles is a challenging subject in organic synthesis . Under current method, the benzoylation of indole and 5‐methylindole afforded in high yield, with over 90 % of 3‐benzoyindoles (Table , entries 20–21).…”

The Beneficial Sinergy of MW Irradiation and Ionic Liquids in Catalysis of Organic Reactions

“…Moreover, to further improve sustainability of the reaction, it was not necessary to protect the heterocyclic NH, thus eliminating the protection-deprotection steps, in agreement with the eighth principle of Green Chemistry [1]. Another metal triflate, Y(OTf) 3 , was the best catalyst for regioselective 3-acylation of indoles [91]. MW irradiation and IL solvent ([bmim]BF 4 ) contributed to obtain high yields in few minutes (Scheme 28).…”

“…Tb(OTf)3 emerged as the catalyst of choice after a screening of 19metal triflates; moreover, it could be recovered and re-used three times, with only slight decrease in product isolated yield. Another metal triflate, Y(OTf)3, was the best catalyst for regioselective 3-acylation of indoles [91]. MW irradiation and IL solvent ([bmim]BF4) contributed to obtain high yields in few minutes (Scheme 28).…”

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“…Electrophilic substitution in indoles occurs predominantly in the β-position, and when this is blocked, either at the nitrogen or at the α-position (Ibrahim, 2007). 3-acylindoles was prepared regioselectivity and in high yields, without protection of the NH position of Indoles using a green method (Tran et al, 2015).…”