Sustainable synthesis of Quinazolinones in Biobased solvent 2-MeTHF

What is it about?

An efficient method for the synthesis of quinazolinones by a domino cross-coupling reaction of 2-halobenzoic acids and amidines is demonstrated for the first time using a copper–glucose combination as an inexpensive catalytic system in a biomass-derived green solvent 2-methylTHF. Here, glucose plays a dual role, both as a reducing agent generating the low-valent copper ions from cupric precursors and as a chelating agent of the generated low-valent copper species, thereby impeding their deactivation. A wide variety of quinazolinones were synthesized in good to excellent yields. Notably, the activation of less reactive 2-bromo/chlorobenzoic acids by the catalyst not only advocates the efficiency of the developed protocol but also the broad substrate scope. Moreover, the developed methodology was successfully applied to the synthesis of the drug molecule diproqualone. The UV–vis spectrophotometric titration study of cupric and cuprous salts with glucose showed evidence of glucose playing the role as a ligand, thus it may act as a stabilizing agent for the low valent copper species formed in the reaction. The use of inexpensive and air stable cupric salts along with glucose for the synthesis of quinazolinones in a green solvent makes this a benign and sustainable method.

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Why is it important?

An efficient method for the synthesis of quinazolinones by a domino cross-coupling reaction of 2-halobenzoic acids and amidines is demonstrated for the first time using a copper–glucose combination as an inexpensive catalytic system in a biomass-derived green solvent 2-methylTHF. Here, glucose plays a dual role, both as a reducing agent generating the low-valent copper ions from cupric precursors and as a chelating agent of the generated low-valent copper species, thereby impeding their deactivation. A wide variety of quinazolinones were synthesized in good to excellent yields. Notably, the activation of less reactive 2-bromo/chlorobenzoic acids by the catalyst not only advocates the efficiency of the developed protocol but also the broad substrate scope. Moreover, the developed methodology was successfully applied to the synthesis of the drug molecule diproqualone. The UV–vis spectrophotometric titration study of cupric and cuprous salts with glucose showed evidence of glucose playing the role as a ligand, thus it may act as a stabilizing agent for the low valent copper species formed in the reaction. The use of inexpensive and air stable cupric salts along with glucose for the synthesis of quinazolinones in a green solvent makes this a benign and sustainable method.

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