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Review
. 2021 Nov:79:105778.
doi: 10.1016/j.ultsonch.2021.105778. Epub 2021 Oct 7.

Ultrasound-mediated radical cascade reactions: Fast synthesis of functionalized indolines from 2-(((N-aryl)amino)methyl)acrylates

Milene M Hornink  1 , Vinicius R Nascimento  1 , Julia L Couto  1 , Caroline S Santos  1 , Leandro H Andrade  2
Affiliations
Review

Ultrasound-mediated radical cascade reactions: Fast synthesis of functionalized indolines from 2-(((N-aryl)amino)methyl)acrylates

Milene M Hornink et al. Ultrason Sonochem. 2021 Nov.

Abstract

Novel functionalized indolines were synthesized from 2-(((N-aryl)amino)methyl)acrylates and formamides under ultrasonic irradiation for the first time. Aiming to develop a straightforward and easy-to-implement methodology for the synthesis of indolines, an instrumentation setup was designed, including ultrasound (US) equipment (Ultrasonic Horn; tip diameter of 12.7 mm, 20 kHz, maximum power of 400 W), an open reaction flask, and an inexpensive and green catalyst (1 mol%; FeSO4·7H2O; CAS: 7782-63-0) without the need for anhydrous conditions. The use of the sono-Fenton process in the presence of formamides and 2-(((N-aryl)amino)methyl)acrylates afforded a broad range of functionalized indolines within 60 s in high yields. Several experimental parameters of the ultrasound-assisted reaction were evaluated, such as amplitude (40-80%), sonication time (15-60 s), and pulsed ultrasonic irradiation. A 60 s silent reaction did not produce the desired indoline. The optimized conditions for US-mediated reactions allowed the production of functionalized indolines in high isolated yields (up to 99%, 60 s reaction, pulse ration 1 s:1 s, US amplitude 60 %).

Keywords: Functionalized indolines; Indolines; Organic synthesis; Pulsed ultrasound; Sono-Fenton; Ultrasound.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

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Graphical abstract
Fig. 1
Fig. 1
Indoline alkaloids and reported biological activities.
Fig. 2
Fig. 2
(a) Previous works involving radical cascade reactions for synthesis of indolines (b) Our work: a fast approach enabled by ultrasonic irradiation to construct novel functionalized indolines.
Fig. 3
Fig. 3
Combining ultrasound and the Fenton reaction in formamide for fast indoline construction. (a) Experimental setup; (b) Sequence of radical reactions: hydroxyl radical generation, carbamoyl radical generation and indoline formation.
Scheme 1
Scheme 1
Evaluation of the Fenton and sono-Fenton reaction in formamide for synthesis of indoline 2a.
Scheme 2
Scheme 2
Exploitation of ultrasonic irradiation and the Fenton reaction in formamide for indoline construction. aConversions were determined by GC–MS analysis.
Fig. 4
Fig. 4
Substrate scope for formamide. at-BuOH (0.9 mL), formamide (2.1 mL), 2 min.
Fig. 5
Fig. 5
Substrate scope for N-methylformamide.
Scheme 3
Scheme 3
Proposed reaction mechanism.
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See this image and copyright information in PMC

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