Cyrene™ as a Neoteric Bio‐Based Solvent for Catalyst‐Free Microwave‐Assisted Construction of Diverse Bipyridine Analogues for Heavy‐Metal Sensing

Abstract

An environment-friendly synthetic protocol was developed to access polyfunctionalized bipyridines from readily available amines, chromone-3-carboxaldehydes, and pyridinylacetonitriles under catalyst-and additive-free conditions using the biorenewable neoteric solvent dihydrolevoglucosenone (Cyrene™). In this strategy, amines served as both a mild-base promoter and a substrate. In addition, water was the only by-product of this reaction. This multi-component protocol provided highly diverse 2,3-, 3,3-, and 3,4-bipyridines in good-to-excellent yields. Operational simplicity, short reaction time, excellent atom economy, and easily obtainable substrates are among the features of this microwave-assisted synthesis. Additionally, the compounds synthesized via this method have demonstrated the ability to detect heavy metals, specifically mercury(II), copper(II), and iron (III) ions.

Cyrene: a bio-based novel and sustainable solvent for organic synthesis

“…Under the elevated temperature conditions (150 °C), an impressive yield of 94% was obtained (entry 7, Table 7). 38 It is interesting that the authors did not observe any by-product derived from Cyrene. It was also reported that Cyrene's recovery was easily succeeded from the reaction mixture, just by removing water in vacuo .…”

“…Expanding the scope of the protocol, the authors employed 3-( pyridinyl)acetonitrile and 4-( pyridine)acetonitrile, leading to the desired dipyridine analogue in good yields (72% and 64%, respectively). 38 Adhering to this logic, the authors introduced other cyano-containing molecules, such as benzyl cyanides, instead of the pyridinyl acetonitriles. Excellent results were also afforded in the presence of electron-deficient groups on the aromatic ring, whereas benzyl cyanide, as well as 4-methyl derivative, did not afford the desired product.…”

“…In 2021, Lee and coworkers suggested the formation of bipyridine derivatives through a multicomponent reaction under microwave irradiation (Table 7). 38 Towards this aim, they initially used aniline ( 42 ), 3-formylchromone ( 66 ) and 2-pyridineacetonitrile ( 67 ) under catalyst-free conditions. The use of Cyrene as the solvent enabled the researchers to attain an even higher yield than what was previously documented using DMF, as the temperature could be elevated, without further problems.…”

“…To explore in which extend this reaction could be efficient, a great variety of aromatic amines was tested. 38 Excellent yields were obtained using ortho -, meta - or para -substituted anilines bearing either electron-withdrawing or electron-donating substituents. Excellent results were also afforded using aliphatic and cyclic amines irrespective of whether they were primary, secondary, or even heteroaromatic.…”

Cyrene: a bio-based solvent for the Mizoroki–Heck reaction of aryl iodides

“…The dimerization reaction of sinapic ester 12 and the difluoromethylation reaction of heteroarenes or terminal alkynes 13 highlighted the beneficial use of Cyrene instead of other hazardous solvents. In many syntheses of different classes of molecules, such as isothiocyanates, 14 ureas, 15 bipyridines 16 and benzothiazoles, 17 Cyrene outperformed all other suitable solvents, offering a greener approach. Its industrial applicability was demonstrated when it was utilized in a large-scale Baylis–Hillman reaction.…”