Phenolate‐Induced N−O Bond Formation versus Tiemann‐Type Rearrangement for the Synthesis of 3‐Aminobenzisoxazoles and 2‐Aminobenzoxazoles
Abstract A novel oxadiazolone‐based method for the synthesis of 3‐aminobenzisoxazoles by N−O bond formation and of 2‐aminobenzoxazoles through a Tiemann‐type rearrangement has been developed. The synthesis of these two pharmaceutically relevant heterocycles was realized by an unexplored retrosynthet...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley-VCH
2022-12-01
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| Series: | ChemistryOpen |
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| Online Access: | https://doi.org/10.1002/open.202200252 |
| _version_ | 1797954143604703232 |
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| author | Benedikt Hufnagel W. Felix Zhu Hanna M. Franz Prof. Dr. Ewgenij Proschak Dr. Victor Hernandez‐Olmos |
| author_facet | Benedikt Hufnagel W. Felix Zhu Hanna M. Franz Prof. Dr. Ewgenij Proschak Dr. Victor Hernandez‐Olmos |
| author_sort | Benedikt Hufnagel |
| collection | DOAJ |
| description | Abstract A novel oxadiazolone‐based method for the synthesis of 3‐aminobenzisoxazoles by N−O bond formation and of 2‐aminobenzoxazoles through a Tiemann‐type rearrangement has been developed. The synthesis of these two pharmaceutically relevant heterocycles was realized by an unexplored retrosynthetic disconnection using a cyclic nitrenoid precursor‐based strategy. The selective formation of the two isomers was significantly influenced by steric and electronic effects of substituents. However, tetrabutylammonium chloride (TBACl) efficiently promoted the Tiemann‐type rearrangement over N−O bond formation. Control experiments indicate that deprotonation of the phenol induces both rearrangements. |
| first_indexed | 2024-04-10T23:14:02Z |
| format | Article |
| id | doaj.art-09566d7cd906458f86beca5c3e4ee655 |
| institution | Directory Open Access Journal |
| issn | 2191-1363 |
| language | English |
| last_indexed | 2024-04-10T23:14:02Z |
| publishDate | 2022-12-01 |
| publisher | Wiley-VCH |
| record_format | Article |
| series | ChemistryOpen |
| spelling | doaj.art-09566d7cd906458f86beca5c3e4ee6552023-01-13T01:50:53ZengWiley-VCHChemistryOpen2191-13632022-12-011112n/an/a10.1002/open.202200252Phenolate‐Induced N−O Bond Formation versus Tiemann‐Type Rearrangement for the Synthesis of 3‐Aminobenzisoxazoles and 2‐AminobenzoxazolesBenedikt Hufnagel0W. Felix Zhu1Hanna M. Franz2Prof. Dr. Ewgenij Proschak3Dr. Victor Hernandez‐Olmos4Institute of Pharmaceutical Chemistry Goethe University Frankfurt Max-von-Laue-Str. 9 60438 Frankfurt am Main GermanyInstitute of Pharmaceutical Chemistry Goethe University Frankfurt Max-von-Laue-Str. 9 60438 Frankfurt am Main GermanyInstitute of Pharmaceutical Chemistry Goethe University Frankfurt Max-von-Laue-Str. 9 60438 Frankfurt am Main GermanyFraunhofer Institute for Translational Medicine and Pharmacology ITMP Theodor-Stern-Kai 7 60596 Frankfurt am Main GermanyFraunhofer Institute for Translational Medicine and Pharmacology ITMP Theodor-Stern-Kai 7 60596 Frankfurt am Main GermanyAbstract A novel oxadiazolone‐based method for the synthesis of 3‐aminobenzisoxazoles by N−O bond formation and of 2‐aminobenzoxazoles through a Tiemann‐type rearrangement has been developed. The synthesis of these two pharmaceutically relevant heterocycles was realized by an unexplored retrosynthetic disconnection using a cyclic nitrenoid precursor‐based strategy. The selective formation of the two isomers was significantly influenced by steric and electronic effects of substituents. However, tetrabutylammonium chloride (TBACl) efficiently promoted the Tiemann‐type rearrangement over N−O bond formation. Control experiments indicate that deprotonation of the phenol induces both rearrangements.https://doi.org/10.1002/open.2022002523-aminobenzisoxazoles2-aminobenzoxazolesnitrenoid precursorsoxadiazoloneTiemann rearrangement |
| spellingShingle | Benedikt Hufnagel W. Felix Zhu Hanna M. Franz Prof. Dr. Ewgenij Proschak Dr. Victor Hernandez‐Olmos Phenolate‐Induced N−O Bond Formation versus Tiemann‐Type Rearrangement for the Synthesis of 3‐Aminobenzisoxazoles and 2‐Aminobenzoxazoles ChemistryOpen 3-aminobenzisoxazoles 2-aminobenzoxazoles nitrenoid precursors oxadiazolone Tiemann rearrangement |
| title | Phenolate‐Induced N−O Bond Formation versus Tiemann‐Type Rearrangement for the Synthesis of 3‐Aminobenzisoxazoles and 2‐Aminobenzoxazoles |
| title_full | Phenolate‐Induced N−O Bond Formation versus Tiemann‐Type Rearrangement for the Synthesis of 3‐Aminobenzisoxazoles and 2‐Aminobenzoxazoles |
| title_fullStr | Phenolate‐Induced N−O Bond Formation versus Tiemann‐Type Rearrangement for the Synthesis of 3‐Aminobenzisoxazoles and 2‐Aminobenzoxazoles |
| title_full_unstemmed | Phenolate‐Induced N−O Bond Formation versus Tiemann‐Type Rearrangement for the Synthesis of 3‐Aminobenzisoxazoles and 2‐Aminobenzoxazoles |
| title_short | Phenolate‐Induced N−O Bond Formation versus Tiemann‐Type Rearrangement for the Synthesis of 3‐Aminobenzisoxazoles and 2‐Aminobenzoxazoles |
| title_sort | phenolate induced n o bond formation versus tiemann type rearrangement for the synthesis of 3 aminobenzisoxazoles and 2 aminobenzoxazoles |
| topic | 3-aminobenzisoxazoles 2-aminobenzoxazoles nitrenoid precursors oxadiazolone Tiemann rearrangement |
| url | https://doi.org/10.1002/open.202200252 |
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