A facile and environmentally benign polyethylene glycol 600-mediated method for the synthesis of densely functionalized 2-aminothiophene derivatives under ultrasonication

Abstract

A green and efficient protocol for the synthesis of densely functionalized 2-aminothiophene derivatives is described by the one-pot three-component Gewald reaction from enolizable carbonyl compounds, malononitrile (or ethyl cyanoacetate) and elemental sulfur in polyethylene glycol 600, as an eco-friendly reaction medium, without using any basic compounds under ultrasonic be recovered and reused at least five times without significant loss of its activity. The merits of this protocol are mild reaction conditions, good yields, short reaction time, simple work-up procedure and recyclability of the reaction medium as well as avoiding the use of any basic catalyst at ambient temperature. ARTICLE HISTORY

Green methodologies for the synthesis of 2-aminothiophene

“…Another methodology reporting alternative solvents was described in 2017 by Akbarzadeh and Dekamin and is disclosed in Fig. 16 (Akbarzadeh and Dekamin 2017 ). They applied alkyl ketones 24a – i in the reaction with corresponding nitriles 2a,b and elemental sulfur S 8 in eco-friendly PEG-600 under ultrasonic conditions at room temperature for 10 to 50 min to form 2-aminothiophenes 25aa – bi in 29–98% yields after filtration and recrystallization from ethanol (Fig.…”

Ultrasound-assisted transition-metal-free catalysis: a sustainable route towards the synthesis of bioactive heterocycles

“…59 Because of their importance, a rapid and eco-compatible strategy for the assembly of diverse polysubstituted thiophenes 15 via a three-component Gewald reaction of carbonyl compounds 12, active methylene compounds 13, and elemental sulfur 14 in the presence of polyethylene glycol-600 (PEG-600) under ultrasound irradiation at room temperature was developed by Akbarzadeh and Dekamin in 2017 (Scheme 4). 60 Using this catalyst-free protocol, 16 target compounds were accomplished in poor to excellent yield in comparatively short reaction durations.…”

Synthesis and analgesic activity evaluation of derivatives of 2-[(1,4-dioxo-1-amino-4-arylbutyl-2-en-2-yl)amino]-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid

“…The Gewald aminothiophene fragment is a promising pharmacophore group, since it was found in both natural and synthetic physiologically active compounds [1][2][3][4][5][6]. The synthesis of substituted Gewald aminothiophenes can be carried out using the Gewald reaction [7][8][9]. In turn, 3imino(hydrazono)-3H-furan-2-ones have high reactivity, leading to the production of compounds of various structures [10][11][12][13][14][15][16][17].…”