Abstract
The hetero-Diels-Alder reactions of in situ-generated azoalkenes with thioketones were shown to offer a straightforward method for an efficient and regioselective synthesis of scarcely known N-substituted 1,3,4-thiadiazine derivatives. The scope of the method was fairly broad, allowing the use of a series of aryl-, ferrocenyl-, and alkyl-substituted thioketones. However, in the case of N-tosyl-substituted cycloadducts derived from 1-thioxo-2,2,4,4-tetramethylcyclobutan-3-one and the structurally analogous 1,3-dithione, a more complicated pathway was observed. By elimination of toluene sulfinic acid, the initially formed cycloadducts afforded 2H-1,3,4-thiadiazines as final products. Advanced DFT calculations revealed that the observed high regioselectivity was due to kinetic reaction control and that the (4 + 2)-cycloadditions of sterically less unhindered thiones occurred via highly unsymmetric transition states with shorter C..S-distances (2.27–2.58 Å) and longer N..C-distances (3.02–3.57 Å). In the extreme case of the sterically very hindered 2,2,4,4- tetramethylcyclobutan-1,3-dione-derived thioketones, a zwitterionic intermediate with a fully formed C-S bond was detected, which underwent ring closure to the 1,3,4-thiadiazine derivative in a second step. For the hypothetical formation of the regioisomeric 1,2,3-thiadiazine derivatives, the DFT calculations proposed more symmetric transition states with considerably higher energies.
Abstract
The hetero-Diels-Alder reactions of in situ-generated azoalkenes with thioketones were shown to offer a straightforward method for an efficient and regioselective synthesis of scarcely known N-substituted 1,3,4-thiadiazine derivatives. The scope of the method was fairly broad, allowing the use of a series of aryl-, ferrocenyl-, and alkyl-substituted thioketones. However, in the case of N-tosyl-substituted cycloadducts derived from 1-thioxo-2,2,4,4-tetramethylcyclobutan-3-one and the structurally analogous 1,3-dithione, a more complicated pathway was observed. By elimination of toluene sulfinic acid, the initially formed cycloadducts afforded 2H-1,3,4-thiadiazines as final products. Advanced DFT calculations revealed that the observed high regioselectivity was due to kinetic reaction control and that the (4 + 2)-cycloadditions of sterically less unhindered thiones occurred via highly unsymmetric transition states with shorter C..S-distances (2.27–2.58 Å) and longer N..C-distances (3.02–3.57 Å). In the extreme case of the sterically very hindered 2,2,4,4- tetramethylcyclobutan-1,3-dione-derived thioketones, a zwitterionic intermediate with a fully formed C-S bond was detected, which underwent ring closure to the 1,3,4-thiadiazine derivative in a second step. For the hypothetical formation of the regioisomeric 1,2,3-thiadiazine derivatives, the DFT calculations proposed more symmetric transition states with considerably higher energies.
Additional indexing
Item Type: | Journal Article, refereed, original work |
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Communities & Collections: | 07 Faculty of Science > Department of Chemistry |
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Dewey Decimal Classification: | 540 Chemistry |
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Language: | English |
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Date: | 27 April 2021 |
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Deposited On: | 28 Apr 2021 10:08 |
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Last Modified: | 27 Jan 2022 06:50 |
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Publisher: | MDPI Publishing |
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ISSN: | 1420-3049 |
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OA Status: | Gold |
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Free access at: | Publisher DOI. An embargo period may apply. |
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Publisher DOI: | https://doi.org/10.3390/molecules26092544 |
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Project Information: | - : FunderNational Science Center (Cracow)
- : Grant IDgrant #2016/23/G/ST5/04115/l
- : Project Title
- : FunderAlexander von Humboldt Foundation (Bonn)
- : Grant ID
- : Project Title
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