Solvent-Free and Catalyst-Free
Biginelli Reaction
To Synthesize Ferrocenoyl Dihydropyrimidine and Kinetic Method To
Express Radical-Scavenging Ability
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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<sup>+•</sup>), 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><sup>–<i>t</i>/<i>a</i></sup> + <i>B<b>e</b></i><sup>–<i>t</i>/<i>b</i></sup> + <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><sup>–<i>t</i>/<i>a</i></sup> + (<i>B</i>/<i>b</i>)<i><b>e</b></i><sup>–<i>t</i>/<i>b</i></sup>, 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<sup>+•</sup>, but the introduction of ferrocenoyl group
made DHPMs efficient ABTS<sup>+•</sup> 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