Experimental and theoretical study on a one-pot, three-component route to 3,4-dihydropyrimidin-2(1H)-ones/thiones TiCl3OTf-[bmim]Cl

Farhadi, Asadollah; Noei, Jalil; Aliyari, Rasoul Haji; Maryam, Albakhtiyari; Takassi, Mohammad Ali

doi:10.1007/s11164-015-2092-4

Cited by 17 publications

(4 citation statements)

References 14 publications

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“…16 Deve-se notar que o uso deste tipo de β-cetoéster ainda não havia sido relatado na literatura, que trazia (até então) apenas relatos de utilização de βcetoésteres alifáticos e aromáticos. 57 Sua motivação era eliminar do processo o uso de solventes, principalmente os tóxicos, conseguindo excelentes resultados. Cálculos realizados em nível B3LYP/6-311G, em fase gasosa, indicam que quando usadas estas condições reacionais o mecanismo seguido nesta reação é a via de Knoevenagel, sem, no entanto, haver uma abordagem experimental para sua comprovação.…”

Section: Figura 11 Mecanismo Proposto Por Sweets E Fissekis Em 1973 51unclassified

Theory Behind Biginelli Reaction Revisited

Tejero

Kümmerle²,

Bauerfeldt³

2019

Rev. Virtual Quim.

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Multicomponent reactions (MCRs) have received great attention in organic and chemical synthesis, since they allow planning of new molecules and pharmaceuticals, in particular, with great structural complexity and in excellent yields. One of the most remarkable MCRs is the Biginelli reaction, which forms the dihydropyrimidinones / thiones product through the reaction of aldehyde, β-ketoester and urea or thiourea. In the mechanism of this reaction three pathways can be expected: the Knoevenagel pathway, the iminium ion pathway and the enamine pathway, as this reaction occurs through bimolecular combinations of the reactants. After several experimental and theoretical studies, it was possible to observe that the mechanism of this reaction occurs preferentially through the formation of iminium ion, but may lead to other initiation pathways, depending on the experimental conditions. The goal of this work is to present the changes in the initiation of the reaction mechanism, in view of the different experimental arrangements, observed through studies conducted for this type of reaction over the years, as well as to discuss the results of theoretical studies that support these experimental observations.

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Section: Figura 11 Mecanismo Proposto Por Sweets E Fissekis Em 1973 51unclassified

Theory Behind Biginelli Reaction Revisited

Tejero

Kümmerle²,

Bauerfeldt³

2019

Rev. Virtual Quim.

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“…In this sense, three possible pathways proposed for the reaction of aromatic aldehyde, urea, and methyl acetoacetate: Iminium route, enamine-intermediate, and Knoevanagel pathway ( Figure 2) [13]. Some works have reported theoretical calculations that supplied sharp pieces of evidence that the iminium route is likely to occur when urea used as reagent [17,18,29,30]. However, no theoretical calculations had reported when thiourea was used.…”

Section: Transition State and Mechanismmentioning

confidence: 99%

Understanding the Lack of Reactivity of 2,4-Dihydroxybenzaldehyde Towards the Biginelli Adduct Using Density Functional Theory Molecular Modeling

et al. 2019

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The Biginelli reaction is a multicomponent reaction for obtaining dihydropyrimidinthiones quickly, with multiple substitution patterns. The reaction mechanism remains unclear. Three possible pathways proposed for the reaction are the iminium route, an enamine intermediate, and the Knoevenagel pathway. However, when thiourea was used, no theoretical calculations were reported. Thus, based on the literature, the iminium pathway was used to obtain evidence explaining the lack of reactivity of 2,4-dihydroxybenzaldehyde towards the Biginelli adduct, compared with 4-hydroxybenzaldehyde. This computational study, carried out using the B3LYP/6-31++G(d,p) level of theory, showed an increment of 150 kJ/mol in the activation energy of the slowest pathway, due to the presence of a hydroxyl group in position 2 (ortho) of the aromatic aldehyde, decreasing its reactivity. Natural bond orbital (NBO) calculations suggest that the determinant steps are simultaneous, i.e., the polarization of the carbonyl group and its corresponding protonation by the hydrogen of the SH fragment of the thiourea tautomer. The activation enthalpy values suggest that the nucleophile attack takes place later on the compound 2,4-dihydroxybenzaldehyde compared to 4-hydroxybenzaldehyde-TS, confirming that the OH group in position 2 hinders the condensation reaction.

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“…4,9 Due to the problems associated with the classical Biginelli reaction such as harsh reaction conditions, low yields, and long reaction times and also regarding to the significance of DHPMs, hence the numerous reaction conditions using various Lewis and Brønsted acid catalysts have been developed so far. 5 To date, a plenty of homogeneous and heterogeneous catalysts such as nano BF 3 •SiO 2 , 10 Bi(III) supported on silica-coated Fe 3 O 4 nanoparticles, 11 TiCl 3 OTf-[bmim]Cl, 12 [TEAPS]H 2 PMo 12 O 40 , 13 CuCl 2 /HCl, 14 sulfated silica tungstic acid, 15 ErCl 3 •6H 2 O, 16 SnCl 2 /nano SiO 2 , 17 L-proline nitrate, 18 D-xylonic acid, 19 Fe(OTs) 3 •6H 2 O, 20 NiCl 2 •6H 2 O/ HCl, 21 Co@imine-Na + -montmorillonite, 22 dendrimer-attached phosphotungstic acid nanoparticles immobilized on nanosilica, 23 Ce(LS) 3 , 24 bentonite/PS-SO 3 H, 25 silica sulfuric acid, 26 HClO 4 •SiO 2 , 27 and the exchanged cations in an Algerian montmorillonite 28 under conventional heating, ultrasound and microwave irradiations as well as solvent-free conditions have been reported to achieve DH-PMs synthesis. 5 Although these protocols are accompa-nied with several advantages; however, they suffer from several defects such as the use of metal-based, corrosive, toxic, expensive, non-reusable, and moisture sensitive catalysts, tedious work-up and purification processes, environmental contaminations, the use of harmful organic solvents, inadequate yields, and also long reaction times.…”

Section: Introductionmentioning

confidence: 99%

Chitosan-silica Sulfate Nano Hybrid: An Efficient Biopolymer Based-heterogeneous Nano Catalyst for Solvent-free Synthesis of 3,4-Dihydropyrimidine-2(1H)-one/thiones

Behrouz

Abi

Piltan

2021

ACSi

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A green and highly efficient approach for the synthesis of 3,4-dihydropyrimidine-2(1H)-one/thione derivatives is described. In this approach, the three-component Biginelli reaction between (thio)urea, methyl acetoacetate and aldehydes under solvent-free condition in the presence of chitosan-silica sulfate nano hybrid (CSSNH) as a green and heterogeneous nano catalyst affords the corresponding products in good to excellent yields and in short reaction times. CSSNH is a cheap, eco-friendly, and non-toxic nano catalyst that could be easily prepared, handled, and reused for many reaction runs without significant loss of its activity.

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Experimental and theoretical study on a one-pot, three-component route to 3,4-dihydropyrimidin-2(1H)-ones/thiones TiCl3OTf-[bmim]Cl

Cited by 17 publications

References 14 publications

Theory Behind Biginelli Reaction Revisited

Theory Behind Biginelli Reaction Revisited

Understanding the Lack of Reactivity of 2,4-Dihydroxybenzaldehyde Towards the Biginelli Adduct Using Density Functional Theory Molecular Modeling

Chitosan-silica Sulfate Nano Hybrid: An Efficient Biopolymer Based-heterogeneous Nano Catalyst for Solvent-free Synthesis of 3,4-Dihydropyrimidine-2(1H)-one/thiones

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