Green Synthesis of 2-Mercapto 5,6-Dihydro-4<i>H</i>-1,3-Thiazines via Sequential C–S Couplings
The six-membered N,S-heterocyclic 1,3-thiazines and their derivatives are widely acknowledged as pharmaceutical molecules with a wide range of biological activities. In this study, we developed a unique thiol-involved cascade reaction that enables the efficient construction of the 5,6-dihydro-4<i...
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MDPI AG
2024-11-01
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| Online Access: | https://www.mdpi.com/1420-3049/29/22/5255 |
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| author | Wenjie Liu Shuo Wang Li Pan Xiaojing Bi Enxue Shi |
| author_facet | Wenjie Liu Shuo Wang Li Pan Xiaojing Bi Enxue Shi |
| author_sort | Wenjie Liu |
| collection | DOAJ |
| description | The six-membered N,S-heterocyclic 1,3-thiazines and their derivatives are widely acknowledged as pharmaceutical molecules with a wide range of biological activities. In this study, we developed a unique thiol-involved cascade reaction that enables the efficient construction of the 5,6-dihydro-4<i>H</i>-1,3-thiazine scaffold through consecutive intermolecular thiol-isothiocyanate and intramolecular thiol-halogen click reactions. Structurally diverse 2-mercapto dihydrothiazines including three antitumour candidates of <i>bis</i>-dihydrothiazines were readily obtained in high yields from the readily available thiols and 3-chloroisothiocyanate in the green solvent EtOH/H<sub>2</sub>O (1:1) using K<sub>2</sub>CO<sub>3</sub> (0.6 equiv.) as the base. Between the two synthesis procedures investigated, the microwave-assisted reaction generally behaved more efficiently than that under routine heating conditions. Furthermore, DFT calculation confirmed the sequential addition–substitution mechanism. This cascade C–S coupling reaction methodology offers several advantages, including rapid completion, high reliability, easy purification, and benign conditions. |
| format | Article |
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| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2024-11-01 |
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| series | Molecules |
| spelling | doaj-art-e3b5c957fad842968cf26a7c2c05ac4f2025-08-20T01:54:08ZengMDPI AGMolecules1420-30492024-11-012922525510.3390/molecules29225255Green Synthesis of 2-Mercapto 5,6-Dihydro-4<i>H</i>-1,3-Thiazines via Sequential C–S CouplingsWenjie Liu0Shuo Wang1Li Pan2Xiaojing Bi3Enxue Shi4State Key Laboratory of NBC Protection for Civilian, Beijing 102205, ChinaState Key Laboratory of NBC Protection for Civilian, Beijing 102205, ChinaState Key Laboratory of NBC Protection for Civilian, Beijing 102205, ChinaState Key Laboratory of NBC Protection for Civilian, Beijing 102205, ChinaState Key Laboratory of NBC Protection for Civilian, Beijing 102205, ChinaThe six-membered N,S-heterocyclic 1,3-thiazines and their derivatives are widely acknowledged as pharmaceutical molecules with a wide range of biological activities. In this study, we developed a unique thiol-involved cascade reaction that enables the efficient construction of the 5,6-dihydro-4<i>H</i>-1,3-thiazine scaffold through consecutive intermolecular thiol-isothiocyanate and intramolecular thiol-halogen click reactions. Structurally diverse 2-mercapto dihydrothiazines including three antitumour candidates of <i>bis</i>-dihydrothiazines were readily obtained in high yields from the readily available thiols and 3-chloroisothiocyanate in the green solvent EtOH/H<sub>2</sub>O (1:1) using K<sub>2</sub>CO<sub>3</sub> (0.6 equiv.) as the base. Between the two synthesis procedures investigated, the microwave-assisted reaction generally behaved more efficiently than that under routine heating conditions. Furthermore, DFT calculation confirmed the sequential addition–substitution mechanism. This cascade C–S coupling reaction methodology offers several advantages, including rapid completion, high reliability, easy purification, and benign conditions.https://www.mdpi.com/1420-3049/29/22/52555,6-dihydro-4<i>H</i>-1,3-thiazinesthiol click reactioncascade C–S couplingmicrowave-assistedgreen synthesisDFT calculation |
| spellingShingle | Wenjie Liu Shuo Wang Li Pan Xiaojing Bi Enxue Shi Green Synthesis of 2-Mercapto 5,6-Dihydro-4<i>H</i>-1,3-Thiazines via Sequential C–S Couplings Molecules 5,6-dihydro-4<i>H</i>-1,3-thiazines thiol click reaction cascade C–S coupling microwave-assisted green synthesis DFT calculation |
| title | Green Synthesis of 2-Mercapto 5,6-Dihydro-4<i>H</i>-1,3-Thiazines via Sequential C–S Couplings |
| title_full | Green Synthesis of 2-Mercapto 5,6-Dihydro-4<i>H</i>-1,3-Thiazines via Sequential C–S Couplings |
| title_fullStr | Green Synthesis of 2-Mercapto 5,6-Dihydro-4<i>H</i>-1,3-Thiazines via Sequential C–S Couplings |
| title_full_unstemmed | Green Synthesis of 2-Mercapto 5,6-Dihydro-4<i>H</i>-1,3-Thiazines via Sequential C–S Couplings |
| title_short | Green Synthesis of 2-Mercapto 5,6-Dihydro-4<i>H</i>-1,3-Thiazines via Sequential C–S Couplings |
| title_sort | green synthesis of 2 mercapto 5 6 dihydro 4 i h i 1 3 thiazines via sequential c s couplings |
| topic | 5,6-dihydro-4<i>H</i>-1,3-thiazines thiol click reaction cascade C–S coupling microwave-assisted green synthesis DFT calculation |
| url | https://www.mdpi.com/1420-3049/29/22/5255 |
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