Fluorinated and Non-Fluorinated 1,4-Diarylpyrazoles via MnO<sub>2</sub>-Mediated Mechanochemical Deacylative Oxidation of 5-Acylpyrazolines
A solvent-free two-step synthesis of polyfunctionalized pyrazoles under ball-milling mechanochemical conditions was developed. The protocol comprises (3 + 2)-cycloaddition of in situ generated nitrile imines and chalcones, followed by oxidation of the initially formed 5-acylpyrazolines with activate...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/23/8446 |
| _version_ | 1797462594286518272 |
|---|---|
| author | Greta Utecht-Jarzyńska Anna Kowalczyk Marcin Jasiński |
| author_facet | Greta Utecht-Jarzyńska Anna Kowalczyk Marcin Jasiński |
| author_sort | Greta Utecht-Jarzyńska |
| collection | DOAJ |
| description | A solvent-free two-step synthesis of polyfunctionalized pyrazoles under ball-milling mechanochemical conditions was developed. The protocol comprises (3 + 2)-cycloaddition of in situ generated nitrile imines and chalcones, followed by oxidation of the initially formed 5-acylpyrazolines with activated MnO<sub>2</sub>. The second step proceeds via an exclusive deacylative pathway, to give a series of 1,4-diarylpyrazoles functionalized with a fluorinated (CF<sub>3</sub>) or non-fluorinated (Ph, COOEt, Ac) substituent at C(3) of the heterocyclic ring. In contrast, MnO<sub>2</sub>-mediated oxidation of a model isomeric 4-acylpyrazoline proceeded with low chemoselectivity, leading to fully substituted pyrazole as a major product formed via dehydrogenative aromatization. The presented approach extends the scope of the known methods carried out in organic solvents and enables the preparation of polyfunctionalized pyrazoles, which are of general interest in medicine and material sciences. |
| first_indexed | 2024-03-09T17:39:48Z |
| format | Article |
| id | doaj.art-8ae070dd42a74a02be99c94d982e0b10 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T17:39:48Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8ae070dd42a74a02be99c94d982e0b102023-11-24T11:42:26ZengMDPI AGMolecules1420-30492022-12-012723844610.3390/molecules27238446Fluorinated and Non-Fluorinated 1,4-Diarylpyrazoles via MnO<sub>2</sub>-Mediated Mechanochemical Deacylative Oxidation of 5-AcylpyrazolinesGreta Utecht-Jarzyńska0Anna Kowalczyk1Marcin Jasiński2Department of Organic and Applied Chemistry, Faculty of Chemistry, University of Lodz, Tamka 12, 91403 Lodz, PolandDepartment of Organic and Applied Chemistry, Faculty of Chemistry, University of Lodz, Tamka 12, 91403 Lodz, PolandDepartment of Organic and Applied Chemistry, Faculty of Chemistry, University of Lodz, Tamka 12, 91403 Lodz, PolandA solvent-free two-step synthesis of polyfunctionalized pyrazoles under ball-milling mechanochemical conditions was developed. The protocol comprises (3 + 2)-cycloaddition of in situ generated nitrile imines and chalcones, followed by oxidation of the initially formed 5-acylpyrazolines with activated MnO<sub>2</sub>. The second step proceeds via an exclusive deacylative pathway, to give a series of 1,4-diarylpyrazoles functionalized with a fluorinated (CF<sub>3</sub>) or non-fluorinated (Ph, COOEt, Ac) substituent at C(3) of the heterocyclic ring. In contrast, MnO<sub>2</sub>-mediated oxidation of a model isomeric 4-acylpyrazoline proceeded with low chemoselectivity, leading to fully substituted pyrazole as a major product formed via dehydrogenative aromatization. The presented approach extends the scope of the known methods carried out in organic solvents and enables the preparation of polyfunctionalized pyrazoles, which are of general interest in medicine and material sciences.https://www.mdpi.com/1420-3049/27/23/8446pyrazolenitrile iminemechanochemistry(3 + 2)-cycloadditiondeacylationoxidation |
| spellingShingle | Greta Utecht-Jarzyńska Anna Kowalczyk Marcin Jasiński Fluorinated and Non-Fluorinated 1,4-Diarylpyrazoles via MnO<sub>2</sub>-Mediated Mechanochemical Deacylative Oxidation of 5-Acylpyrazolines Molecules pyrazole nitrile imine mechanochemistry (3 + 2)-cycloaddition deacylation oxidation |
| title | Fluorinated and Non-Fluorinated 1,4-Diarylpyrazoles via MnO<sub>2</sub>-Mediated Mechanochemical Deacylative Oxidation of 5-Acylpyrazolines |
| title_full | Fluorinated and Non-Fluorinated 1,4-Diarylpyrazoles via MnO<sub>2</sub>-Mediated Mechanochemical Deacylative Oxidation of 5-Acylpyrazolines |
| title_fullStr | Fluorinated and Non-Fluorinated 1,4-Diarylpyrazoles via MnO<sub>2</sub>-Mediated Mechanochemical Deacylative Oxidation of 5-Acylpyrazolines |
| title_full_unstemmed | Fluorinated and Non-Fluorinated 1,4-Diarylpyrazoles via MnO<sub>2</sub>-Mediated Mechanochemical Deacylative Oxidation of 5-Acylpyrazolines |
| title_short | Fluorinated and Non-Fluorinated 1,4-Diarylpyrazoles via MnO<sub>2</sub>-Mediated Mechanochemical Deacylative Oxidation of 5-Acylpyrazolines |
| title_sort | fluorinated and non fluorinated 1 4 diarylpyrazoles via mno sub 2 sub mediated mechanochemical deacylative oxidation of 5 acylpyrazolines |
| topic | pyrazole nitrile imine mechanochemistry (3 + 2)-cycloaddition deacylation oxidation |
| url | https://www.mdpi.com/1420-3049/27/23/8446 |
| work_keys_str_mv | AT gretautechtjarzynska fluorinatedandnonfluorinated14diarylpyrazolesviamnosub2submediatedmechanochemicaldeacylativeoxidationof5acylpyrazolines AT annakowalczyk fluorinatedandnonfluorinated14diarylpyrazolesviamnosub2submediatedmechanochemicaldeacylativeoxidationof5acylpyrazolines AT marcinjasinski fluorinatedandnonfluorinated14diarylpyrazolesviamnosub2submediatedmechanochemicaldeacylativeoxidationof5acylpyrazolines |