Developing a fast and catalyst-free protocol to form C=N double bond with high functional group tolerance
The carbon–nitrogen double bond (C=N) is a fundamentally important functional group in organic chemistry. This is largely due to the fact that C=N acts as electrophilic synthon to give nitrogen-containing compounds. Here, we report the condensation of primary amine or hydrazine with very electron-de...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
The Royal Society
2023-10-01
|
| Series: | Royal Society Open Science |
| Subjects: | |
| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsos.231263 |
| _version_ | 1797666853457231872 |
|---|---|
| author | Bin Zhong Feng Chen Yushu Ge Dan Liu |
| author_facet | Bin Zhong Feng Chen Yushu Ge Dan Liu |
| author_sort | Bin Zhong |
| collection | DOAJ |
| description | The carbon–nitrogen double bond (C=N) is a fundamentally important functional group in organic chemistry. This is largely due to the fact that C=N acts as electrophilic synthon to give nitrogen-containing compounds. Here, we report the condensation of primary amine or hydrazine with very electron-deficient aldehyde to form C=N bond in the absence of any catalysts (metals and acids). The protocol performs at room temperature and applies water as co-solvent. Two hundred examples are presented here. With its intrinsic advantages of wide substrate scopes, excellent efficiency (high yields and short reaction time), operational simplicity, mild condition (room temperature as reaction temperature, no catalysts, no additions, water as co-solvent and opening to air) and available starting materials, the protocol can be compatible with various drugs, prodrugs, dyes and pharmacophores containing primary amino group. In addition, we also successfully apply this protocol to rapidly synthesize the core scaffolds of bioactive molecules. |
| first_indexed | 2024-03-11T20:04:35Z |
| format | Article |
| id | doaj.art-8682a8b04c7d491ba6260eed299604ca |
| institution | Directory Open Access Journal |
| issn | 2054-5703 |
| language | English |
| last_indexed | 2024-03-11T20:04:35Z |
| publishDate | 2023-10-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Royal Society Open Science |
| spelling | doaj.art-8682a8b04c7d491ba6260eed299604ca2023-10-04T07:05:28ZengThe Royal SocietyRoyal Society Open Science2054-57032023-10-01101010.1098/rsos.231263Developing a fast and catalyst-free protocol to form C=N double bond with high functional group toleranceBin Zhong0Feng Chen1Yushu Ge2Dan Liu3Heifei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, People's Republic of ChinaHeifei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, People's Republic of ChinaHeifei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, People's Republic of ChinaHeifei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, People's Republic of ChinaThe carbon–nitrogen double bond (C=N) is a fundamentally important functional group in organic chemistry. This is largely due to the fact that C=N acts as electrophilic synthon to give nitrogen-containing compounds. Here, we report the condensation of primary amine or hydrazine with very electron-deficient aldehyde to form C=N bond in the absence of any catalysts (metals and acids). The protocol performs at room temperature and applies water as co-solvent. Two hundred examples are presented here. With its intrinsic advantages of wide substrate scopes, excellent efficiency (high yields and short reaction time), operational simplicity, mild condition (room temperature as reaction temperature, no catalysts, no additions, water as co-solvent and opening to air) and available starting materials, the protocol can be compatible with various drugs, prodrugs, dyes and pharmacophores containing primary amino group. In addition, we also successfully apply this protocol to rapidly synthesize the core scaffolds of bioactive molecules.https://royalsocietypublishing.org/doi/10.1098/rsos.231263no catalystmild conditionC=N forminghigh functional group toleranceno addition |
| spellingShingle | Bin Zhong Feng Chen Yushu Ge Dan Liu Developing a fast and catalyst-free protocol to form C=N double bond with high functional group tolerance Royal Society Open Science no catalyst mild condition C=N forming high functional group tolerance no addition |
| title | Developing a fast and catalyst-free protocol to form C=N double bond with high functional group tolerance |
| title_full | Developing a fast and catalyst-free protocol to form C=N double bond with high functional group tolerance |
| title_fullStr | Developing a fast and catalyst-free protocol to form C=N double bond with high functional group tolerance |
| title_full_unstemmed | Developing a fast and catalyst-free protocol to form C=N double bond with high functional group tolerance |
| title_short | Developing a fast and catalyst-free protocol to form C=N double bond with high functional group tolerance |
| title_sort | developing a fast and catalyst free protocol to form c n double bond with high functional group tolerance |
| topic | no catalyst mild condition C=N forming high functional group tolerance no addition |
| url | https://royalsocietypublishing.org/doi/10.1098/rsos.231263 |
| work_keys_str_mv | AT binzhong developingafastandcatalystfreeprotocoltoformcndoublebondwithhighfunctionalgrouptolerance AT fengchen developingafastandcatalystfreeprotocoltoformcndoublebondwithhighfunctionalgrouptolerance AT yushuge developingafastandcatalystfreeprotocoltoformcndoublebondwithhighfunctionalgrouptolerance AT danliu developingafastandcatalystfreeprotocoltoformcndoublebondwithhighfunctionalgrouptolerance |