Sulfated Zirconia-Catalyzed Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones (DHPMs) Under Solventless Conditions: Competitive Multicomponent Biginelli vs. Hantzsch Reactions

Abstract

Abstract:The catalytic ability of ZrO 2 /SO 4 2-to promote solventless three-component condensation reactions of a diversity of aromatic aldehydes, urea or thoiurea and ethyl acetoacetate was studied. Products resulting from Hantzsch and/or Biginelli multicomponent reactions are obtained in the presence of solid acid catalysts using the same reactants but different temperature conditions. The sulfated zirconia catalyst can be recovered and recycled in subsequent reactions with a gradual decrease of activity.

Comparative Study of Regioselective Synthesis of β-Aminoalcohols under Solventless Conditions Catalyzed by Sulfated Zirconia and SZ/MCM-41

“…The classical approach for the synthesis of β-aminoalcohols, involving nucleophilic opening of epoxides by amines requires heat treatment and requires an excess of amine. Several catalysts have been utilized in these reactions: montmorillonite [16], Ti(o-i-Pr) 4 [17], SmI 2 , [18] basic metal amides, [19] SmCl 3 [20], metal triflates such as Sn(OTf) 2 , Cu(OTf) 2 , LiOTf and Yb(OTf) 3 [21], ammonium decatungstocerate (IV) [22], RuCl 3 [23], zirconium (IV) chloride [24], cyclodextrins [25] and also CeCl 3 [26], silica-gel [27], alumina [28], ionic liquids [29], water [30] We have successfully used sulfated zirconia for Biginelli condensation reactions, [35] for the Paal Knorr reaction in the synthesis of tetrahydroindolone derivatives [36] and for the acylal protection and deprotection reactions [37]. In this paper we have synthesized, characterized and evaluated sulfated zirconia and SZ/MCM-41 in the oxirane opening with amines to obtain β-aminoalcohols under mild, solventless conditions.…”

Study of the Synthesis of Some Biginelli-type Products Catalyzed by Nano-ZrO2

“…The results presented in Table 2 indicate that various aldehydes can be converted to their corresponding 3,4-dihydropyrimidin-2(1H)-ones by using nano-ZrO 2 as catalyst in good to excellent yields, comparable with the SO 4 2− /ZrO 2 catalyst [13]. Furthermore, the other advantages of this method are the mild reaction conditions, short reaction time, and low cost.…”

“…More detailed conclusions may be drawn by comparing the performance of the present work with some other recent reports available in the literature [13].…”

“…They prepared sulfated zirconia (SO 4 2− /ZrO 2 ) by a multistep procedure and applied it as an acid catalyst replacement for common acid substances in the Biginelli reaction [13]. In this method a mixture of catalyst (50 mg, 0.26 mmol vis.…”

Similarity and Competition between Biginelli and Hantzsch Reactions: an Opportunity for Modern Medicinal Chemistry

“…There are several examples in the literature which demonstrate that the increase of reaction temperatures to over 100°C is responsible for both the release of the water absorbed on the solid surface, thus activating the catalytic hydrolysis of urea, and the switch to the Hantzsch reaction (entries 3-5, Table 2). Moreover, the morphology of the solid catalyst, as well as its acidity, play a role in the competition, [98][99][100] in particular for a solid support with a higher surface area and lower acidity. Indeed, low acidity means low catalytic efficiency toward both MCRs.…”