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Published in

American Association for the Advancement of Science, Science, 6694(384), p. 446-452, 2024

DOI: 10.1126/science.adn7006

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Nitrate reduction enables safer aryldiazonium chemistry

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

Aryldiazonium salts remain a staple in organic synthesis and are still prepared largely in accord with the protocol developed in the 19th century. Because of the favorable reactivity that often cannot be achieved with other aryl(pseudo)halides, diazonium chemistry continues to grow. Facile extrusion of dinitrogen contributes to the desired reactivity but is also reason for safety concerns. Explosions have occurred since the discovery of these reagents and still result in accidents. In this study, we report a diazonium chemistry paradigm shift based on nitrate reduction using thiosulfate or dihalocuprates as electron donors that avoids diazonium accumulation. Because nitrate reduction is rate-limiting, aryldiazoniums are produced as fleeting intermediates, which results in a safer and often more efficient deaminative halogenation in a single step from anilines.