Biginelli Reaction And Biginelli-Like Reaction Catalyzed By Hydration Ferric Sulfate

3,4-Dihydropyrimidinone （DHPM） derivatives have attracted considerable interest in recent yearsbecause of their diverse types of pharmacological activity such as calcium channel modulation,α_1a-antagonists, mitotic kinesin Eg5inhibition, antiviral, anticancer, antibacterial and antifungal activity,melanin concentrating hormone receptor antagonists etc. Moreover, some alkaloids isolated from marinesources, which contain the dihydropyrimidine core unit, also show interesting biological properties. In1893,3,4-dihydropyrimidin-2（1H）-ones （DHPMs） were first reported by Pietro Biginelli, which was synthesizedby the three-component condensation of an benzaldehyde, β-ketoester and urea under a strongly acidiccondition. However, the major drawback of this so-called Biginelli reaction is the low yields which arefrequently encountered when using substituted aromatic or aliphatic aldehydes. Recently, in order toimprove the reaction yield or the scope of the Biginelli reaction, new catalysts to synthesize DHPMs viaBiginelli reaction continually received extensive attention. More than hundreds of improved procedures toform3,4-dihydropyrimidin-2（1H）-ones （DHPMs） have been reported recently. In these catalysts,3,4-dihydropyrimidin-2（1H）-ones have been gained at higher yields. However, these alternates suffer fromseveral drawbacks, such as the use of expensive or less easily available reagents, harsh reaction conditions,long reaction times, high temperatures, and difficulties in the isolation of products etc. Moreover, almost allof them are applicable to a limited substrates （aromatic aldehydes, β-keto esters, urea）, seldom beingapplicable to alphatic aldehydes, other dicarbonyl compounds than β-keto esters, and thiourea.This dissertation aims at the development of new approaches to3,4-dihydropyrimidin-2（1H）-ones/thiones and their derivatives with widely range of substrates. This research work includes a classicalBiginelli reaction and a Biginelli-like reaction catalyzed by Fe2（SO4）3·xH2O.In our efforts to develop clean methods for organic transformations, we found Fe₂（SO₄）₃·xH₂O was anefficient, reusable, operationally simple, and environmentally benign catalyst. Herein, we disclose animproved Biginelli reaction procedure using Fe₂（SO₄）₃·xH₂O as a catalyst which is applicable to a widerange of substrates for synthesizing a variety of3,4-DHPMs and thiones in high-to-excellent yields in shorttime. Using this method,34kinds of different3,4-dihydropyrimidin-2-ketone/thiones, which are identifiedby¹H NMR,¹³C NMR and high-resolution mass spectrometry, were prepared in yields of70-92%. This method is also applicable to Biginelli-like reaction of cyclopentanone or cyclohexanone, aldehydes, urea orthiourea.30Arylidene heterobicyclic compounds were prepared in better yields than those of knownmethods.This method we developed is applicable to a broad range of aldehyde substrates including aliphatic,aromatic, α,β-unsaturated, and heterocyclic aldehydes, and dicarbonyl compound substrates, includingβ-keto esters, β-keto amides, and1,3-diketones to give high to excellent yields in short reaction time. Thetolerance to acid sensitive reactant such as furyl carbaldehyde, applicability to a wide range of substrates,inexpensive and environmentally friendly nature of catalyst, ease of product isolation, short reaction times,high-to-excellent yields, and simple recyclability without significantly losing catalytic activity make this asvaluable addition to existing methods.