Highly Efficient Synthesis of Substituted 3,4-Dihydropyrimidin-2-(1<i>H</i>)-ones (DHPMs) Catalyzed by Hf(OTf)<sub>4</sub>: Mechanistic Insights into Reaction Pathways under Metal Lewis Acid Catalysis and Solvent-Free Conditions
In our studies on the catalytic activity of Group IVB transition metal Lewis acids, Hf(OTf)<sub>4</sub> was identified as a highly potent catalyst for „one-pot, three-component„ Biginelli reaction. More importantly, it was found that solvent-free conditions, in contra...
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MDPI AG
2019-01-01
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| Online Access: | https://www.mdpi.com/1420-3049/24/2/364 |
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| author | Rui Kong Shuai-Bo Han Jing-Ying Wei Xiao-Chong Peng Zhen-Biao Xie Shan-Shan Gong Qi Sun |
| author_facet | Rui Kong Shuai-Bo Han Jing-Ying Wei Xiao-Chong Peng Zhen-Biao Xie Shan-Shan Gong Qi Sun |
| author_sort | Rui Kong |
| collection | DOAJ |
| description | In our studies on the catalytic activity of Group IVB transition metal Lewis acids, Hf(OTf)<sub>4</sub> was identified as a highly potent catalyst for „one-pot, three-component„ Biginelli reaction. More importantly, it was found that solvent-free conditions, in contrast to solvent-based conditions, could dramatically promote the Hf(OTf)<sub>4</sub>-catalyzed formation of 3,4-dihydro-pyrimidin-2-(1<i>H</i>)-ones. To provide a mechanistic explanation, we closely examined the catalytic effects of Hf(OTf)<sub>4</sub> on all three potential reaction pathways in both “sequential bimolecular condensations„ and “one-pot, three-component„ manners. The experimental results showed that the synergistic effects of solvent-free conditions and Hf(OTf)<sub>4</sub> 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, <sup>1</sup>H-MMR tracing of the H-D exchange reaction of methyl acetoacetate in MeOH-<i>d</i><sub>4</sub> indicated that Hf(IV) cation may significantly accelerate ketone-enol tautomerization and activate the β-ketone moiety, thereby contributing to the overall reaction rate. |
| first_indexed | 2024-12-11T01:05:16Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-11T01:05:16Z |
| publishDate | 2019-01-01 |
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| series | Molecules |
| spelling | doaj.art-d79dd93d0ced43a1b70561942715a0362022-12-22T01:26:13ZengMDPI AGMolecules1420-30492019-01-0124236410.3390/molecules24020364molecules24020364Highly Efficient Synthesis of Substituted 3,4-Dihydropyrimidin-2-(1<i>H</i>)-ones (DHPMs) Catalyzed by Hf(OTf)<sub>4</sub>: Mechanistic Insights into Reaction Pathways under Metal Lewis Acid Catalysis and Solvent-Free ConditionsRui Kong0Shuai-Bo Han1Jing-Ying Wei2Xiao-Chong Peng3Zhen-Biao Xie4Shan-Shan Gong5Qi Sun6Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, 605 Fenglin Avenue, Nanchang 330013, Jiangxi, ChinaJiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, 605 Fenglin Avenue, Nanchang 330013, Jiangxi, ChinaJiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, 605 Fenglin Avenue, Nanchang 330013, Jiangxi, ChinaJiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, 605 Fenglin Avenue, Nanchang 330013, Jiangxi, ChinaJiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, 605 Fenglin Avenue, Nanchang 330013, Jiangxi, ChinaJiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, 605 Fenglin Avenue, Nanchang 330013, Jiangxi, ChinaJiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, 605 Fenglin Avenue, Nanchang 330013, Jiangxi, ChinaIn our studies on the catalytic activity of Group IVB transition metal Lewis acids, Hf(OTf)<sub>4</sub> was identified as a highly potent catalyst for „one-pot, three-component„ Biginelli reaction. More importantly, it was found that solvent-free conditions, in contrast to solvent-based conditions, could dramatically promote the Hf(OTf)<sub>4</sub>-catalyzed formation of 3,4-dihydro-pyrimidin-2-(1<i>H</i>)-ones. To provide a mechanistic explanation, we closely examined the catalytic effects of Hf(OTf)<sub>4</sub> on all three potential reaction pathways in both “sequential bimolecular condensations„ and “one-pot, three-component„ manners. The experimental results showed that the synergistic effects of solvent-free conditions and Hf(OTf)<sub>4</sub> 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, <sup>1</sup>H-MMR tracing of the H-D exchange reaction of methyl acetoacetate in MeOH-<i>d</i><sub>4</sub> indicated that Hf(IV) cation may significantly accelerate ketone-enol tautomerization and activate the β-ketone moiety, thereby contributing to the overall reaction rate.https://www.mdpi.com/1420-3049/24/2/364hafnium triflate3,4-dihydropyrimidin-2-(1<i>H</i>)-onessolvent-freeBiginelli reactionmechanism |
| spellingShingle | Rui Kong Shuai-Bo Han Jing-Ying Wei Xiao-Chong Peng Zhen-Biao Xie Shan-Shan Gong Qi Sun Highly Efficient Synthesis of Substituted 3,4-Dihydropyrimidin-2-(1<i>H</i>)-ones (DHPMs) Catalyzed by Hf(OTf)<sub>4</sub>: Mechanistic Insights into Reaction Pathways under Metal Lewis Acid Catalysis and Solvent-Free Conditions Molecules hafnium triflate 3,4-dihydropyrimidin-2-(1<i>H</i>)-ones solvent-free Biginelli reaction mechanism |
| title | Highly Efficient Synthesis of Substituted 3,4-Dihydropyrimidin-2-(1<i>H</i>)-ones (DHPMs) Catalyzed by Hf(OTf)<sub>4</sub>: Mechanistic Insights into Reaction Pathways under Metal Lewis Acid Catalysis and Solvent-Free Conditions |
| title_full | Highly Efficient Synthesis of Substituted 3,4-Dihydropyrimidin-2-(1<i>H</i>)-ones (DHPMs) Catalyzed by Hf(OTf)<sub>4</sub>: Mechanistic Insights into Reaction Pathways under Metal Lewis Acid Catalysis and Solvent-Free Conditions |
| title_fullStr | Highly Efficient Synthesis of Substituted 3,4-Dihydropyrimidin-2-(1<i>H</i>)-ones (DHPMs) Catalyzed by Hf(OTf)<sub>4</sub>: Mechanistic Insights into Reaction Pathways under Metal Lewis Acid Catalysis and Solvent-Free Conditions |
| title_full_unstemmed | Highly Efficient Synthesis of Substituted 3,4-Dihydropyrimidin-2-(1<i>H</i>)-ones (DHPMs) Catalyzed by Hf(OTf)<sub>4</sub>: Mechanistic Insights into Reaction Pathways under Metal Lewis Acid Catalysis and Solvent-Free Conditions |
| title_short | Highly Efficient Synthesis of Substituted 3,4-Dihydropyrimidin-2-(1<i>H</i>)-ones (DHPMs) Catalyzed by Hf(OTf)<sub>4</sub>: Mechanistic Insights into Reaction Pathways under Metal Lewis Acid Catalysis and Solvent-Free Conditions |
| title_sort | highly efficient synthesis of substituted 3 4 dihydropyrimidin 2 1 i h i ones dhpms catalyzed by hf otf sub 4 sub mechanistic insights into reaction pathways under metal lewis acid catalysis and solvent free conditions |
| topic | hafnium triflate 3,4-dihydropyrimidin-2-(1<i>H</i>)-ones solvent-free Biginelli reaction mechanism |
| url | https://www.mdpi.com/1420-3049/24/2/364 |
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