Biginelli Condensation: Synthesis and Structure Diversification of 3,4-Dihydropyrimidin-2(1H)-one Derivatives

Oxidative Dehydrosulfurative Carbon–Oxygen Cross-Coupling of 3,4-Dihydropyrimidine-2-thiones with Aryl Alcohols

“…13 Due to the requirement for multistep synthesis of most of the pyrimidine partners, especially for densely substituted ones, these reaction protocols are limited with respect to rapid diversification. To Biginelli three-component reaction, 14 as a surrogate for the C2-(pseudo)halopyrimidine. DHPMs with diverse substituents at the C4−C6 positions were demonstrated to be suitable substrates for Pd-catalyzed/ Cu-mediated dehydrosulfurative C−C or C−N cross-coupling with concomitant oxidative dehydrogenation (aromatization) to yield C2-arylated (azolated), 15 -alkynylated, 16 and -aminated pyrimidines 17 in a single step.…”

A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines

“…the S-MITU formation is the first step followed by the Biginelli with the established protocol [28]. iodide which most researchers used earlier [3,16,22,24,29]. Thus, newly designed MCR also avoids the use of these toxic/expensive reagents, which are some added benefits of this novel approach.…”

“…A survey of recent literature revealed that modifications at the N1, C2, and N3 are particularly productive in offering drug-like candidates. Looking towards the libraries generated by the classical Biginelli reaction and the number of C2 modified DHPM derivatives showed tremendous scope for medicinal chemistry in the last decade [ 16 ]. In our earlier work on DHPMs [ 17 , 18 ], we noticed that working on DHPM areas deserve more effort.…”

Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions

“…As our final reaction for study, we turned to the Biginelli reaction (Scheme 4) [43–48]. This acid-catalyzed cyclocondensation of urea, β-ketoesters and aromatic aldehydes to yield dihydropyrimidines has received significant attention, these products having pharmacological activity including calcium channel modulation, mitotic kinesin Eg5 inhibition, and antiviral and antibacterial activity [49–50].…”