Synthesis of 1,5-Disubstituted Tetrazoles from Nitrones by Using Bis(p-nitrophenyl) Phosphorazidate in the Presence of 4-(Dimethylamino)pyridine
Kotaro Ishihara, Takayuki Shioiri, Masato Matsugi*
*Department of Applied Biological Chemistry, Faculty of
Agriculture, Meijo University, 1-501 Shiogamaguchi, Tempaku-ku, Nagoya 468-8502,
Japan, Email: matsugi
meijo-u.ac.jp
K. Ishihara, T. Shioiri, M. Matsugi, Synlett, 2022, 33, 781-784.
DOI: 10.1055/a-1800-2011
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Abstract
The reaction of various nitrones with bis(p-nitrophenyl) phosphorazidate provides 1,5-disubstituted tetrazoles in the presence of 4-(dimethylamino)pyridine without the need for toxic or explosive reagents.
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Details
The document describes a novel method for synthesizing 1,5-disubstituted tetrazoles from nitrones using bis(p-nitrophenyl) phosphorazidate (p-NO2DPPA) in the presence of 4-(dimethylamino)pyridine (DMAP). This method avoids the use of toxic or explosive azide sources, making it safer and more efficient. The optimal conditions for the reaction were determined to be using DMAP as the base and THF as the solvent under reflux, achieving yields up to 90%. The method was tested on various nitrones, showing good yields for substrates with different substituents, although bulky groups near the reaction site reduced the yield. The proposed mechanism involves DMAP activating p-NO2DPPA, leading to the formation of a nitrilium ion, which then undergoes nucleophilic addition and cyclization to form the tetrazole. This method is advantageous due to its operational simplicity and the avoidance of hazardous reagents. The research was supported by several foundations and the authors declared no conflict of interest. Detailed analytical data and supporting information are available online.
Synthesis of 5-Substituted 1H-Tetrazoles from Aldoximes Using Diphenyl Phosphorazidate
K. Ishihara, M. Kawashima, T. Shioiri, M. Matsugi, Synlett, 2016, 27, 2225-2228.
K. Ishihara, M. Kawashima, T. Matsumoto, T. Shiori, M. Matsugi, Synthesis, 2018, 50, 1141-1151.
Key Words
nitrones, bisnitrophenyl phosphorazidate, azides, tetrazoles, cycloaddition
ID: J72-Y2022
