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(1<i>H</i>)-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 (<i>t</i>) followed exponential function, [radical] = <i>A<b>e</b></i>^{–<i>t</i>/<i>a</i>} + <i>B<b>e</b></i>^{–<i>t</i>/<i>b</i>} + <i>C</i>. Then, the differential style of this equation led to the relationship between the reaction rate (<i><b>r</b></i>) and the reaction time (<i>t</i>), –<i>d</i>[radical]/<i>dt</i> = (<i>A</i>/<i>a</i>)<i><b>e</b></i>^{–<i>t</i>/<i>a</i>} + (<i>B</i>/<i>b</i>)<i><b>e</b></i>^{–<i>t</i>/<i>b</i>}, which can be used to calculate the reaction rate at any time point. On the basis of the concept of the reaction rate, <i><b>r</b></i> = <i><b>k</b></i>[radical]­[antioxidant], the rate constant (<i><b>k</b></i>) can be calculated with the time point being <i>t</i> = 0. By the comparison of <i><b>k</b></i> of DHPMs, it can be concluded that phenolic <i>ortho</i>-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 <i>ortho</i>-dihydroxyl groups still played the key role in this case