Electrooxidative Hofmann Rearrangement of Phthalimides to Access Anthranilate Derivatives

Abstract

A simple and efficient electrooxidative Hofmann rearrangement reaction of phthalimides was developed. Anthranilate derivatives were synthesized in moderate to good yields under green and mild conditions using phthalimides as a rearrangement precursor. This approach not only provides a strategy for synthesizing anthranilates and deuterated anthranilate derivatives with high deuteration efficiency but also realizes efficient conversion at the gram scale. A possible reaction mechanism is proposed.

Multigram Electrochemical Hofmann Rearrangement Using a Spinning Three-Dimensional Anode

“…Matsumura and Xu and Zhang have reported that the electrochemical oxidation of catalytic amounts of a bromide salt in the presence of a primary amide can generate active bromine species (“Br + ”), initiating the Hofmann rearrangement, and thus avoiding the use of stoichiometric amounts of oxidants (Figure ). More recently, additional contributions have been made by Jubault and Liu . Moreover, recent advancements showing the scale-up of electrochemical methods and the fact that it can be operated at room temperature have significantly contributed to the recent resurgence of this technology in organic synthesis .…”

“…More recently, additional contributions have been made by Jubault 10 and Liu. 11 Moreover, recent advancements showing the scale-up of electrochemical methods and the fact that it can be operated at room temperature have significantly contributed to the recent resurgence of this technology in organic synthesis. 12 Ideally, the electrochemical Hofmann rearrangement can be performed by employing the simplest and most inexpensive bromide salts, such as NaBr.…”