New three-component cyclocondensation reaction: microwave-assisted one-pot synthesis of 5-unsubstituted-3,4-dihydropyrimidin-2(1H)-ones under solvent-free conditions

The Three‐Component Biginelli Reaction: A Combined Experimental and Theoretical Mechanistic Investigation

“…Although it has been traditionally catalyzed by strong Brønsted acids, Lewis acids such as LiClO 4 , LaCl 3 , InCl 3 , BiA C H T U N G T R E N N U N G (OTf) 3 , BiCl 3 , MnA C H T U N G T R E N N U N G (OAc) 3 , CuA C H T U N G T R E N N U N G (OTf) 2 , FeCl 3 , ZrCl 4 , or SnCl 2 [13][14][15][16][17] are now being increasingly used. The use of ionic liquids, [18][19][20] microwave irradiation, [7,[21][22][23][24][25][26][27][28][29][30][31] solid-phase reagents, [12,32,33] and polymer-supported catalysts have also been reported. [34,35] Two asymmetric versions of Biginelli reactions using CeCl 3 /InCl 3 or YbA C H T U N G T R E N N U N G (OTF) 3 in the presence of chiral ligands have also been recently reported.…”

Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues

“…Moreover, the most active compounds exhibited a cytotoxicity against A-549 cell line close to these of cisplatin, IC50 = 1.89 µM and are more potent than this reference drug against the MDA-MB-231 cell line. MW-assisted solvent-free synthesis has been widely employed for the preparation of pyrimidine derivatives [163][164][165][166][167]. Thus, Burgula et al [166] have reported a green procedure for the single-step preparation of series of uracil and cytosine nucleobases 174 and 175.…”

“…For these syntheses, using BF 3¨E t 2 O as Lewis acid significantly enhanced the reaction yields as well as the conversion rates. MW-assisted solvent-free conditions have been also used for a Biginelli multicomponent reaction as illustrated by the synthesis of a new series of 5-unsubstituted-3,4-dihydropyrimidin-2(1H)-ones 179 [167]. The procedure involved a three-component, one-pot condensation of an aromatic aldehyde 176, acetophenone (177) and urea (178), using ZnI2 as catalyst (Scheme 37).…”

“…The procedure involved a three-component, one-pot condensation of an aromatic aldehyde 176, acetophenone (177) and urea (178), using ZnI2 as catalyst (Scheme 37). This procedure not only provides improved yields related to the conventional Biginelli conditions, but also expands the scope MW-assisted solvent-free conditions have been also used for a Biginelli multicomponent reaction as illustrated by the synthesis of a new series of 5-unsubstituted-3,4-dihydropyrimidin-2(1H)-ones 179 [167]. The procedure involved a three-component, one-pot condensation of an aromatic aldehyde 176, acetophenone (177) and urea (178), using ZnI 2 as catalyst (Scheme 37).…”

“…Other pyridopyrimidine derivatives have also been reported for their potential use as anticardiovascular [171], anti-inflammatory [172,173], antibacterial [174,175], and anti-Parkinson agents [176]. MW-assisted solvent-free conditions have been also used for a Biginelli multicomponent reaction as illustrated by the synthesis of a new series of 5-unsubstituted-3,4-dihydropyrimidin-2(1H)-ones 179 [167]. The procedure involved a three-component, one-pot condensation of an aromatic aldehyde 176, acetophenone (177) and urea (178), using ZnI2 as catalyst (Scheme 37).…”