A Brief Review on the Synthesis of the <i>N</i>-CF<sub>3</sub> Motif in Heterocycles
The trifluoromethyl group is widely recognized for its significant role in the fields of medicinal chemistry and material science due to its unique electronic and steric properties that can alter various physiochemical properties of the parent molecule, such as lipophilicity, acidity, and hydrogen b...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/7/3012 |
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| author | Zizhen Lei Wenxu Chang Hong Guo Jiyao Feng Zhenhua Zhang |
| author_facet | Zizhen Lei Wenxu Chang Hong Guo Jiyao Feng Zhenhua Zhang |
| author_sort | Zizhen Lei |
| collection | DOAJ |
| description | The trifluoromethyl group is widely recognized for its significant role in the fields of medicinal chemistry and material science due to its unique electronic and steric properties that can alter various physiochemical properties of the parent molecule, such as lipophilicity, acidity, and hydrogen bonding capabilities. Compared to the well-established C-trifluoromethylation, <i>N</i>-trifluoromethylation has received lesser attention. Considering the extensive contribution of nitrogen to drug molecules, it is predicted that constructing <i>N</i>-trifluoromethyl (<i>N</i>-CF<sub>3</sub>) motifs will be of great significance in pharmaceutical and agrochemical industries. This review is mainly concerned with the synthesis of heterocycles containing this motif. In three-membered heterocycles containing the <i>N</i>-CF<sub>3</sub> motif, the existing literature mostly demonstrated the synthetic strategy, as it does for four- and larger-membered heterocycles. Certain structures, such as oxaziridines, could serve as an oxidant or building blocks in organic synthesis. In five-membered heterocycles, it has been reported that <i>N</i>-CF<sub>3</sub> azoles showed a higher lipophilicity and a latent increased metabolic stability and Caco-2-permeability compared with their N-CH<sub>3</sub> counterparts, illustrating the potential of the <i>N</i>-CF<sub>3</sub> motif. Various <i>N</i>-CF<sub>3</sub> analogues of drugs or bioactive molecules, such as sildenafil analogue, have been obtained. In general, the <i>N</i>-CF<sub>3</sub> motif is developing and has great potential in bioactive molecules or materials. Give the recent development in this motif, it is foreseeable that its synthesis methods and applications will become more and more extensive. In this paper, we present an overview of the synthesis of <i>N</i>-CF<sub>3</sub> heterocycles, categorized on the basis of the number of rings (three-, four-, five-, six- and larger-membered heterocycles), and focus on the five-membered heterocycles containing the <i>N</i>-CF<sub>3</sub> group. |
| first_indexed | 2024-03-11T05:30:04Z |
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| id | doaj.art-c6b33952d479484da9d6337f8f4150e7 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T05:30:04Z |
| publishDate | 2023-03-01 |
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| series | Molecules |
| spelling | doaj.art-c6b33952d479484da9d6337f8f4150e72023-11-17T17:12:15ZengMDPI AGMolecules1420-30492023-03-01287301210.3390/molecules28073012A Brief Review on the Synthesis of the <i>N</i>-CF<sub>3</sub> Motif in HeterocyclesZizhen Lei0Wenxu Chang1Hong Guo2Jiyao Feng3Zhenhua Zhang4College of Science, China Agricultural University, Beijing 100193, ChinaCollege of Science, China Agricultural University, Beijing 100193, ChinaCollege of Science, China Agricultural University, Beijing 100193, ChinaCollege of Science, China Agricultural University, Beijing 100193, ChinaCollege of Science, China Agricultural University, Beijing 100193, ChinaThe trifluoromethyl group is widely recognized for its significant role in the fields of medicinal chemistry and material science due to its unique electronic and steric properties that can alter various physiochemical properties of the parent molecule, such as lipophilicity, acidity, and hydrogen bonding capabilities. Compared to the well-established C-trifluoromethylation, <i>N</i>-trifluoromethylation has received lesser attention. Considering the extensive contribution of nitrogen to drug molecules, it is predicted that constructing <i>N</i>-trifluoromethyl (<i>N</i>-CF<sub>3</sub>) motifs will be of great significance in pharmaceutical and agrochemical industries. This review is mainly concerned with the synthesis of heterocycles containing this motif. In three-membered heterocycles containing the <i>N</i>-CF<sub>3</sub> motif, the existing literature mostly demonstrated the synthetic strategy, as it does for four- and larger-membered heterocycles. Certain structures, such as oxaziridines, could serve as an oxidant or building blocks in organic synthesis. In five-membered heterocycles, it has been reported that <i>N</i>-CF<sub>3</sub> azoles showed a higher lipophilicity and a latent increased metabolic stability and Caco-2-permeability compared with their N-CH<sub>3</sub> counterparts, illustrating the potential of the <i>N</i>-CF<sub>3</sub> motif. Various <i>N</i>-CF<sub>3</sub> analogues of drugs or bioactive molecules, such as sildenafil analogue, have been obtained. In general, the <i>N</i>-CF<sub>3</sub> motif is developing and has great potential in bioactive molecules or materials. Give the recent development in this motif, it is foreseeable that its synthesis methods and applications will become more and more extensive. In this paper, we present an overview of the synthesis of <i>N</i>-CF<sub>3</sub> heterocycles, categorized on the basis of the number of rings (three-, four-, five-, six- and larger-membered heterocycles), and focus on the five-membered heterocycles containing the <i>N</i>-CF<sub>3</sub> group.https://www.mdpi.com/1420-3049/28/7/3012<i>N</i>-trifluoromethyl groupheterocycles |
| spellingShingle | Zizhen Lei Wenxu Chang Hong Guo Jiyao Feng Zhenhua Zhang A Brief Review on the Synthesis of the <i>N</i>-CF<sub>3</sub> Motif in Heterocycles Molecules <i>N</i>-trifluoromethyl group heterocycles |
| title | A Brief Review on the Synthesis of the <i>N</i>-CF<sub>3</sub> Motif in Heterocycles |
| title_full | A Brief Review on the Synthesis of the <i>N</i>-CF<sub>3</sub> Motif in Heterocycles |
| title_fullStr | A Brief Review on the Synthesis of the <i>N</i>-CF<sub>3</sub> Motif in Heterocycles |
| title_full_unstemmed | A Brief Review on the Synthesis of the <i>N</i>-CF<sub>3</sub> Motif in Heterocycles |
| title_short | A Brief Review on the Synthesis of the <i>N</i>-CF<sub>3</sub> Motif in Heterocycles |
| title_sort | brief review on the synthesis of the i n i cf sub 3 sub motif in heterocycles |
| topic | <i>N</i>-trifluoromethyl group heterocycles |
| url | https://www.mdpi.com/1420-3049/28/7/3012 |
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