A New Amphiphilic Brønsted Acid as Catalyst for the Friedel–Crafts Reactions of Indoles in Water

Abstract

A new amphiphile 1a featuring with two ‐NHSO2C4F9 sites is designed and synthesized as Brønsted diacid. The amphiphilicity arose from nano‐aggregations of hydrophobic fluorocarbon chains and extension of hydrophilic NH groups, confirmed by Tyndall effect and TEM. The acidity of 1a rivals to concentrated H2SO4, examined by the Hammett acidity function, 31P NMR and conductance titration. Compound 1a demonstrated excellent catalytic performance in the Friedel–Crafts alkylation of indoles in water. Reactive substrates, such as β‐monosubstituted vinyl ketones in 1,4‐addition and aldehydes in condensation, were quantitatively converted, and the products were easily isolated by filtration or extraction in 85–96 % yields. Additionally, there was no observation of effect of the acidity weakening of 1a on catalysis when poor‐reactive substrates were used, such as β,β‐disubstituted vinyl ketones in 1,4‐addition and ketones in condensation. The two kinds of reactions were practised very smoothly. The formed nano‐aggregations and the strong acidity of 1a were responsible for the highly efficient aqueous catalysis. Notably, 1a was recycled at least 3 times thanks to its amphiphilic structure. It was demonstrated the nano‐aggregations played a key role in the aqueous synthesis.

Highly Sensitive Colorimetric Detection of a Variety of Analytes via the Tyndall Effect

“…The red laser beam becomes invisible in deionized water without such particles (Figure 1B, middle). Some researchers have used TE to qualitatively evaluate nanolevel aggregation 30 or formation of colloidal catalysts. 31 However, the analytical advantages of the TE are far from being fully explored.…”

Solvent‐Assistant Purification for the Synthesis of Indole Derivatives Catalyzed by Solid Acid

“…The solubility control in the organic reactions can be implemented by the addition of water. Recently, many efforts have been devoted to the development of aqueous catalytic reactions from the perspective of green chemistry ,. However, the product purification via chromatography or recrystallization is still unavoidably solvent‐ and time‐consuming.…”

“…As a proof of concept, Michael addition reaction of indole ( 1 a ) with pent‐1‐en‐3‐one ( 2 a ) was carried out in water to construct 3‐substituted indoles, a type of important precursors in the synthesis of biologically active compounds and natural products ,, . However, the reaction was sluggish based on TLC analysis.…”

“…Furthermore, the simple purification workup by the product‐catalyst agglomeration in water‐containing system was investigated in another atom economic reaction, the condensation of indole with aldehyde. The product 3, 3’‐bis(indolyl)alkanes (BIAs), which were widely isolated from various natural sources, exhibit a range of biological activities ,. The investigations started with benzaldehyde ( 4 a ) and indole ( 1 a) in mixed EtOH/H 2 O solvents at 50 °C, and the results are shown in Table .…”

Operando laser scattering: probing the evolution of local pH gradients on complex electrode architectures

“…Named after the physicist John Tyndall, TE is a type of light scattering that takes place when visible light is passed through a colloidal solution with a particle size distribution that lies in the 400 to 750 nm range 21 . This phenomenon has already been used as a visual screening method to detect microprecipitates in blends of parental drug solutions 22,23 as well as to evaluate nanolevel aggregation and characterise colloidal catalyst and functional materials [24][25][26][27] . More recently, Xiao et al 28 added quantitative character to a TE-based colorimetry approach and demonstrated a ca.…”