Highly Efficient Synthesis of Substituted 3,4-Dihydropyrimidin-2-(1H)-ones (DHPMs) Catalyzed by Hf(OTf)4: Mechanistic Insights into Reaction Pathways under Metal Lewis Acid Catalysis and Solvent-Free Conditions
| Autor: | Shan-Shan Gong, Xiao-Chong Peng, Shuai-Bo Han, Zhen-Biao Xie, Rui Kong, Jing-Ying Wei, Qi Sun |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Biginelli reaction
Pharmaceutical Science mechanism Chemistry Techniques Synthetic Pyrimidinones 010402 general chemistry 01 natural sciences solvent-free Article Catalysis Analytical Chemistry Enamine Adduct Reaction rate lcsh:QD241-441 chemistry.chemical_compound lcsh:Organic chemistry Drug Discovery Lewis acids and bases Physical and Theoretical Chemistry 3 4-dihydropyrimidin-2-(1H)-ones Lewis Acids Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry Combinatorial chemistry hafnium triflate 0104 chemical sciences Lewis acid catalysis Chemistry (miscellaneous) Metals Solvents Molecular Medicine Knoevenagel condensation Hafnium |
| Zdroj: | Molecules Volume 24 Issue 2 Molecules, Vol 24, Iss 2, p 364 (2019) |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules24020364 |
| Popis: | In our studies on the catalytic activity of Group IVB transition metal Lewis acids, Hf(OTf)4 was identified as a highly potent catalyst for &rdquo one-pot, three-component&rdquo Biginelli reaction. More importantly, it was found that solvent-free conditions, in contrast to solvent-based conditions, could dramatically promote the Hf(OTf)4-catalyzed formation of 3,4-dihydro-pyrimidin-2-(1H)-ones. To provide a mechanistic explanation, we closely examined the catalytic effects of Hf(OTf)4 on all three potential reaction pathways in both &ldquo sequential bimolecular condensations&rdquo and &ldquo manners. The experimental results showed that the synergistic effects of solvent-free conditions and Hf(OTf)4 catalysis not only drastically accelerate Biginelli reaction by enhancing the imine route and activating the enamine route but also avoid the formation of Knoevenagel adduct, which may lead to an undesired byproduct. In addition, 1H-MMR tracing of the H-D exchange reaction of methyl acetoacetate in MeOH-d4 indicated that Hf(IV) cation may significantly accelerate ketone-enol tautomerization and activate the &beta ketone moiety, thereby contributing to the overall reaction rate. |
| Databáze: | OpenAIRE |
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