Novel Biginelli-like three-component cyclocondensation reaction: efficient synthesis of 5-unsubstituted 3,4-dihydropyrimidin-2(1H)-ones

Iron (III) catalyzed the three-component Biginelli-like cyclocondensation reaction efficiently in acetonitrile to afford the corresponding 5-unsubstituted 3,4-dihydropyrimidin-2-(1H)-ones in high yields. The first Biginelli-like reactions of urea, aldehydes and ketones were furnished important new 3,4-dihydropyrimidin-2-(1H)-ones derivatives suitable for further study.     

Biginelli reaction starting directly from alcohols

An efficient of one-pot oxidative access to 3,4-dihydropyrimidin-2-(1H)-ones directly from aromatic alcohols under mild conditions is reported. The protocol involves 1-methylimidazolium hydrogen sulphate [Hmim]HSO₄ catalyzed oxidation of aromatic alcohols to aromatic aldehydes with NaNO₃ followed by their cyclocondensation with 1,3-dicarbonyl compounds and urea in the same reaction vessel at 80 °C within 2-4 h to afford 3,4-dihydropyrimidin-2-(1H)-ones in 55-97% overall yields. Thus, the present work utilizing alcohols instead of aldehyde in Biginelli reaction is a valid and green alternative to the classical synthesis of 3,4-dihydropyrimidin-2-(1H)-ones.     

A novel method for the synthesis of highly functionalized 3,4-dihydropyrimidin-2(1H)-ones through the 1,4-addition on pyrimidin-2(1H)-ones

A novel method for synthesizing hitherto unreported 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) through 1,4-addition of nucleophiles on pyrimidin-2(1H)-ones is disclosed herein.     

Synthesis and Suzuki-Miyaura reactions of 5-halo-3,4-dihydropyrimidin-2(1H)-ones

A novel synthesis of 6-methyl-4-phenyl-5-substituted-3,4-dihydropyrimidin-2(1H)-ones from 6-methyl-4-phenyl-5-halo-3,4-dihydropyrimidin-2(1H)-ones via the Suzuki-Miyaura reaction is reported. These previously unknown heterocyclic halides are easily prepared using the Biginelli multicomponent reaction followed by halodecarboxylation. The effect of varied substitution at the C-4 position on the cross-coupling reaction is also examined.     

ZrCl4 or ZrOCl2 under neat conditions: optimized green alternatives for the Biginelli reaction

Biginelli reactions were performed using either ZrCl₄ or ZrOCl₂·8H₂O as catalysts under neat conditions. Shorter reaction time than most of the classical methods was required when ZrCl₄ was used. In general, 3,4-dihydropyrimidin-2(1H)-ones and thioxo-3,4-dihydropyrimidin-2(1H)-ones were obtained under neat conditions in moderate to good yields and good purity without using harmful solvents in the work up.     

Magnesium/methanol: an effective reducing agent for chemoselective reduction of pyrimidine-2(1H)-ones

Magnesium in methanol is an effective reagent for the chemoselective reduction of pyrimidine-2(1H)-ones. Other reducible functionalities such as ester and alkene of enamine ester and uriedo carbonyl remain unaffected. This constitutes the first example of the formation of Biginelli 3,4-dihydropyrimidin-2(1H)ones through the reduction of pyrimidine-2(1H)-ones.     

p-Sulfonic acid calixarenes as efficient and reusable organocatalysts for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones/-thiones

A new and efficient methodology is proposed for obtaining 3,4-dihydropyrimidin-2(1H)-ones/-thiones through Biginelli reactions. It is based on the use of less than the stoichiometric amount of p-sulfonic acid calixarenes as organocatalysts. A number of aromatic aldehydes as well as urea or thiourea can be employed for successfully synthesizing the corresponding Biginelli adducts. The described methodology is devoid of metal-containing catalysts, which in turn is very attractive for safely producing 3,4-dihydropyrimidin-2-(1H)-ones/-thiones of pharmacological interest. In addition, the catalyst efficiency is not compromised after its successive use in reactions. This is the first report about the application of calixarenes as catalysts in the multicomponent Biginelli reaction.     

Three component condensations catalyzed by iodine-alumina for the synthesis of substituted 3,4-dihydropyrimidin-2(1H)-ones under microwave irradiation and solvent-free conditions

Condensation of an aldehyde, ethyl acetoacetate and urea or thiourea under microwave irradiation in the presence of 10% iodine adsorbed on neutral alumina gives substituted 3,4-dihydropyrimidin-2(1H)-ones in excellent yields.     

An efficient bakers’ yeast catalyzed synthesis of 3,4-dihydropyrimidin-2-(1H)-ones

Bakers’ yeast (Saccharomyces cerevisiae) efficiently catalyzes the three-component Biginelli reaction of aldehydes, β-keto esters, and urea/thiourea to form 3,4-dihydropyrimidin-2-(1H)-ones in good to excellent yields.     

Reaction of (S)-(+)-4-amino-4-aryl-5,5,5-trifluoropentan-2-ones with α-chlorobenzyl isocyanates. Synthesis of (S)-(+)-4-aryl-6-(2-arylethenyl)-4-trifluoromethyl-3,4-dihydro-pyrimidin-2(1H)-ones

(S)-(+)-4-Amino-4-aryl-5,5,5-trifluoropentan-2-ones reacted with 6h-chlorobenzyl isocyanates with formation of (S)-(+)-4-aryl-6-(2-arylethenyl)-4-trifluoromethyl-3,4-dihydropyrimidin-2(1H)-ones.     

Optically active 4-amino-4-aryl-5,5,5-trifluoropentan-2-ones: Versatile reagents for synthesis of chiral 4-trifluoromethyl-3,4-dihydroazin-2-ones

A cyclocondensation of disubstituted (thio)ureas and isocyanates derived from enantiomerically enriched 4-amino-4-aryl-5,5,5-trifluoropentan-2-ones affords a novel synthetic access to chiral 4-trifluoromethyl-substituted 3,4-dihydropyrimidin-2(1H)-(thi)ones and 3,4-dihydro-1,3-oxazin-2-ones, respectively.     

BiVO<Subscript>4</Subscript>-NPs: an efficient nano-catalyst for the synthesis of biscoumarins,bis(indolyl)methanes and 3,4-dihydropyrimidin-2(1<Emphasis Type="Italic">H</Emphasis>)-ones (thiones) derivatives

BiVO₄-NPs can be used as an efficient and reusable nano-catalyst for the promotion of the synthesis of biscoumarins, bis(indolyl)methanes and 3,4-dihydropyrimidin-2(1H)-ones (thiones) derivatives. The structures of the products were characterized by IR, ¹H NMR and ¹³C NMR spectroscopy and comparison with the authentic samples. Easy work-up procedure, excellent yields, short reaction times and reusability of the catalyst are some advantages of this work. In addition, in this article and for the first time, the preparation of 3,4-dihydropyrimidin-2(1H)-ones and -thiones from the protected derivatives of aldehydes including oximes, semicarbazones and 1,1-diacetates is reported.     

Applying density functional theory on tautomerism in 3,4-dihydropyrimidin-2(1H)-ones

In the present study, the density functional theory (DFT) and Gibbs free energy calculations were performed to investigate the stability and tautomerism of C4-substituted-3,4-dihydropyrimidin-2(1H)-ones. Three different forms are possible for the ethyl 3,4-dihydropyrimidinones (ethyl 4-aryl-6-methyl-3,4-dihydropyrimidin-2(1H)-one-5-carboxylates, ethyl 4-aryl-2-hydroxy-6-methyl-1,4-dihydropyrimidine-5-carboxylates and ethyl 4-aryl-2-hydroxy-6-methyl-3,4-dihydropyrimidine-5-carboxylates) forms that the most stable form is ethyl 4-aryl-6-methyl-3,4-dihydropyrimidin-2 (1H)-one-5-carboxylates (keto-form). The obtained data showed that the substitution on the C4-substitut position can be effective on the equilibrium constant (K _eq).     

A novel combination of (diacetoxyiodo)benzene and tert-butylhydroperoxide for the facile oxidative dehydrogenation of 3,4-dihydropyrimidin-2(1H)-ones

A clean and efficient oxidative dehydrogenation of 3,4-dihydropyrimidin-2(1H)-ones to 1,2-dihydropyrimidines has been achieved through a novel combination of (diacetoxyiodo)benzene and tert-butylhydroperoxide in CH₂Cl₂.     

Ammonium chloride-catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2-(1H)-ones under solvent-free conditions

Ammonium chloride as a very inexpensive and readily available reagent, and efficiently catalyzes one-pot, three component, Biginelli condensation reactions of aldehydes, 1,3-dicarbonyl compounds and urea or thiourea under solvent-free conditions to afford the corresponding 3,4-dihydropyrimidin-2-(1H)-ones in high yields at 100°C.     

An efficient, high yield protocol for the one-pot synthesis of dihydropyrimidin-2(1H)-ones catalyzed by iodine

The use of iodine, as a catalyst for the one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones is reported.     

A simple approach to the synthesis of 2-(2-amino-4-arylthiazol-5-yl)pyrimidines

The synthesis of 2-(2-amino-4-arylthiazol-5-yl)pyrimidin-4(3H)-ones from the available 2-(2-oxo-2-arylethylidene)-2,3-dihydropyrimidin-4(1H)-ones was developed.     

Photo-oxidation of 5-acetyl-3,4-dihydropyrimidin-2(1H)-ones

A variety of Biginelli 5-acetyl-3,4-dihydropyrimidin-2(1H)-ones are efficiently oxidized to their corresponding pyrimidin-2(1H)-one derivatives upon UV irradiation under argon atmosphere in chloroform solution. The nature of the additional substituent on the phenyl ring located on C-4 of the heterocyclic ring influences the rate of reaction. An electron-transfer induced photoreaction is proposed based on the formation of HCl and CH₂Cl₂.     

1,3-Dibromo-5,5-dimethylhydantoin as a useful reagent for efficient synthesis of 3,4-dihydropyrimidin-2-(1<Emphasis Type="Italic">H</Emphasis>)-ones under solvent-free conditions

Efficient syntheses of 3,4-dihydropyrimidin-2-(1H)-ones and the corresponding thioxo derivatives using 1,3-dibromo-5,5-dimethylhydantoin (DBH) catalysis of a one-pot three-component Biginelli reaction of aldehydes, ethyl acetoacetate, and urea or thiourea under microwave irradiation are described. The advantages of this method are its short reaction times, high yields of the products, inexpensive and commercially available catalyst, and solvent-free conditions. Typical isolated yields exceed 70 % for arylaldehydes (9 examples) and aliphatic aldehydes (2 examples).     

Synthesis of 5-nitro-3,4-dihydropyrimidin-2(1<Emphasis Type="Italic">H</Emphasis>)-ones catalyzed by metal salts. Retro-Henry reaction with formation of <Emphasis Type="Italic">N,N′</Emphasis>-disubstituted ureas

Three-component condensation of α-nitroacetophenone with aromatic aldehydes and urea in the presence of iron(III), cobalt(II), nickel(II), and copper(II) salts as catalyst led to the formation of 4,6-diaryl-5-nitro-3,4-dihydropyrimidin-2(1H)-ones and N-benzoyl-N′-(1-aryl-2-nitroethyl)ureas. The latter were formed as a result of retro-nitroaldol (retro-Henry) reaction of intermediate 4,6-diaryl-6-hydroxy-5-nitro-3,4,5,6-tetra-hydropyrimidin-2(1H)-ones.