Efficient One-Pot Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones via a Three-Component Biginelli Reaction

Abstract

Multicomponent reactions are considered to be of increasing importance as time progresses due to the economic and environmental advantages such strategies entail. The three-component Biginelli reaction involves the combination of an aldehyde, a β-ketoester and urea to produce 3,4-dihydropyrimidin-2(1H)-ones, also known as DHPMs. The synthesis of these products is highly important due to their myriad of medicinal properties, amongst them acting as calcium channel blockers and antihypertensive and anti-inflammatory agents. In this study, silicotungstic acid supported on Ambelyst-15 was used as a heterogeneous catalyst for the Biginelli reaction under solventless conditions. Electron-poor aromatic aldehydes gave the best results. Sterically hindered β-ketoesters resulted in lower reaction yields. The reaction was carried out under heterogeneous catalysis to allow easy recovery of the product from the reaction mixture and recycling of the catalyst. The heterogeneity of the reaction was confirmed by carrying out a hot filtration test.

Iron–Organic Framework Nanoparticle-Supported Tungstosilicic Acid as a Catalyst for the Biginelli Reaction

“…Compared with the electron-donating groups, such as −CH 3 and −OCH 3 (Scheme , 4f and 4i ), aromatic aldehydes with electron-withdrawing substituents (−Br, −Cl, −NO 2 (Scheme , 4b–4e, 4g and 4j) ) were obtained in higher yields. It can be explained by the fact that the more electrophilic the aldehyde group becomes, the more susceptible it is to urea nucleophilic attacks . In addition, for thiourea rather than urea, the Biginelli reaction acquired a good product yield with a longer reaction time (Scheme , 4k–4m ).…”

“…Subsequently, the TSA/MIL-88B nanoparticle was compared with other literature − (Table S1). The prepared catalyst in this study shows more mild conditions, high product yield, and outstanding TON value.…”

“…It can be explained by the fact that the more electrophilic the aldehyde group becomes, the more susceptible it is to urea nucleophilic attacks. 47 In addition, for thiourea rather than urea, the Biginelli reaction acquired a good product yield with a longer reaction time (Scheme 2, 4k−4m). In case various substituted aldehydes, methyl acetoacetate, and urea were used as substrates, the desired products were isolated with excellent yields (Scheme 2, 4n− 4p).…”

Visible-Light-Induced Radical Condensation Cyclization to Synthesize 3,4-Dihydropyrimidin-2-(1H)-ones/thiones Using Photoexcited Na2 Eosin Y as a Direct Hydrogen Atom Transfer (HAT) Catalyst

“…Numerous strategies are available. − Numerous instances occurred from these treatments. However, certain synthesis routes have drawbacks, such as limitations on the use of metal catalysts, severe reaction conditions, costly reagents, repetitive workup, low yield, prolonged reaction time, and environmental hazards.…”

Biginelli Reaction Mediated Synthesis of Antimicrobial Pyrimidine Derivatives and Their Therapeutic Properties

“…Further methods include using various catalysts, such as Bronsted acids, including H 3 BO 3 [ 15 ], HCOOH [ 21 ], p-TsOH-H 2 O [ 23 , 24 ], imidazole-1–yl-acetic acid [ 25 ], and L-(+)-tartaric acid-dimethylurea [ 26 ]; or Lewis acids, including LiClO 4 , Lal 3 , InCl 3 , BiCl 3 , Bi(OTf) 3 , Mn(OAc) 3 , Cu(OTf) 2 , CuCl 2 , FeCl 3 , ZrCl 4 , SnCl 2 , [ 27 , 28 , 29 , 30 , 31 , 32 ], Sr(OTf) 2 [ 33 ], VCl 3 [ 34 ], TaBr 5 [ 35 ], Ce(NO 3 ) 3 ·6H 2 O [ 36 ], ZrO 2 /SO 4 2− [ 37 ], silica-chloride (SiO 2 -Cl) [ 38 ], Sm(ClO 4 ) 3 [ 39 ], Y(NO 3 ) 3 ·6H 2 O [ 40 ], CeCl 3· 7H 2 O [ 41 ], Ce(NH 4 ) 2 (NO 3 ) 6 (CAN) [ 42 ], Fe(OTs) 3· 6H 2 O [ 43 ], Ca(HSO 4 ) 2 , Zn(HSO 4 ) 2 [ 44 ], SnCl 2 /nano SiO 2 [ 45 ], Cu(OAc) 2 [ 46 ], copper zirconium phosphate Cu(OH) 2 Zr(HPO 4 ) 2 [ 47 ], Sc(OTf) 3 , Yb(OTf) 3 , and Zn(OTf) 2 [ 48 ]. Other catalysts of the Biginelli reaction reported in the literature include co-phthalocyanines [ 49 ], NaHSO 4 [ 50 ], zeolites [ 51 , 52 ], clays [ 53 , 54 , 55 ], organic polymers [ 56 …”