Facile Method for the Combinatorial Synthesis of 2,2-Disubstituted Quinazolin-4(1H)-one Derivatives Catalyzed by Iodine in Ionic Liquids

Abstract

A mild and facile method for the combinatorial synthesis of quinazolin-4-(1H)-one derivatives, containing simple 2,2-disubstituted quinazolin-4-(1H)-ones, spirocyclic quinazolin-4-(1H)-ones, spiro-heterocyclic quinazolin-4-(1H)-ones, and dispirocyclic quinazolin-4-(1H)-ones, is described, which results in high yields by using ionic liquids as green media. The method involves the reaction of 2-aminobenzamides with various ketones catalyzed by iodine and provides new quinazolin-4-(1H)-one library for biomedical screening.

Practical approach to 2-thioxo-2,3-dihydroquinazolin-4(1 H )-one via dithiocarbamate–anthranilic acid reaction

“…However, ethanol can give an excellent isolated yield (95%) for this reaction (Table 1, entry 10) and appeared to be the best media for this reaction in term of yields and product separation. Under optimum conditions, the reaction time was also studied ( Table 1, entries [15][16][17][18]. About 8 hours of reaction was sufficient for the completion of reaction.…”

“…Given the importance of these nitrogen heterocyclic compounds, the development of mild, high yielding and clean synthesis of these important compounds is daunting challenge and has been extensively investigated in literatures [6][7][8][9][10][11][12]. The classical methods for the synthesis of quinazolinedione ring system are the reaction of anthranilic acid and their derivatives with isothiocyanates or their equivalents [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. However the difficult handling of unstable isothiocyanate as well as preparation of costly and toxic reagents, such as thiophosgene limits its practical applications.…”

Eco-friendly syntheses of 2,2-disubstituted- and 2-spiroquinazolinones

“…6 Some spiro[heterocycloalkyl-2′(1′H)-quinazolin]-4′(3′H)-ones demonstrate anti-amoebic activity in vitro 7 and have been investigated as central nervous system depressants. A number of green methods have been reported for the preparation of 2(2,2)-(di)substituted quinazolin-4(1H)-ones, based mainly on the cyclocondensation of anthranilamide with various aromatic aldehydes and (cyclo)alkanones in ionic liquids, 8 in/on water 9 or under solventless conditions, i.e. by heating at 60-70 °C 10 or by using a grinding technique 11 .…”

Green synthesis of polysubstituted quinoline and benzoquinoline derivatives in ionic liquid via a three-component reaction

“…As a continuation of our research devoted to the development of new methods for the preparation of heterocycles in ionic liquids [17][18][19][20][21], we would like to report the synthesis of 4-arylquinoline-3-carbonitrile and 4-arylbenzo[h]quinoline-3-carbonitrile derivatives under catalyst-free conditions. The method involved a threecomponent reaction of aldehyde, (E)-3-aminobut-2-enenitrile and dimedone or 2-hydroxynaphthalene-1,4-dione in ionic liquids.…”