Solvent-Free and Catalyst-Free Biginelli Reaction To Synthesize Ferrocenoyl Dihydropyrimidine and Kinetic Method To Express Radical-Scavenging Ability

Abstract

Benzoyl and ferrocenoyl 3,4-dihydropyrimidin-2(1H)-ones (-thiones) (DHPMs) were synthesized in modest yields via catalyst-free and solvent-free Biginelli condensation of 1-phenylbutane-1,3-dione or 1-ferrocenylbutane-1,3-dione, hydroxyl benzaldehyde, and urea or thiourea. This synthetic protocol revealed that catalysts may not be necessary for the self-assembling Biginelli reaction. The radical-scavenging abilities of the obtained 11 DHPMs were carried out by reacting with 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(+•)), galvinoxyl radical, and 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH), respectively. The variation of the concentration of these radicals with the reaction time (t) followed exponential function, [radical] = Ae(-t/a) + Be(-t/b) + C. Then, the differential style of this equation led to the relationship between the reaction rate (r) and the reaction time (t), -d[radical]/dt = (A/a)e(-t/a) + (B/b)e(-t/b), which can be used to calculate the reaction rate at any time point. On the basis of the concept of the reaction rate, r = k[radical][antioxidant], the rate constant (k) can be calculated with the time point being t = 0. By the comparison of k of DHPMs, it can be concluded that phenolic ortho-dihydroxyl groups markedly enhanced the abilities of DHPMs to quench ABTS(+•), but the introduction of ferrocenoyl group made DHPMs efficient ABTS(+•) scavengers even in the absence of phenolic hydroxyl group. This phenomenon was also found in DHPM-scavenging galvinoxyl radical. In contrast, the ferrocenoyl group cannot enhance the abilities of DHPMs to scavenge DPPH, and phenolic ortho-dihydroxyl groups still played the key role in this case.