Direct synthesis of paracetamol via site-selective electrochemical ritter-type C–H amination of phenol Irshad Taily, Debarshi Saha, Prabal Banerje Indian Institute Of Technology, Ropar, India N -Acetyl-para-aminophenol (APAP), commonly known as paracetamol or acetaminophen, is a century-old analgesic that epitomizes the N -arylamide class of molecules. It is an active pharmaceutical ingredient (API) in hundreds of other over the-counter (OTC) and prescription drugs and holds a place in the World Health Organization’s List of Essential Medicines.Despite having relative structural simplicity, only a few protocols for the preparation of APAP have been demonstrated to date, and all the routesthat have gained industrial acceptance still rely on multistep protocols involving the utilization of a stoichiometric amount of oxidizing/reducing or other corrosive agents. With the aim to develop an environmentally benign synthetic protocol, herein we revisited, redesigned, and reported a regioselective electrochemical Ritter-type reaction at the C(sp2)–H of unprotected phenol toward the environmentally benign and direct synthesis of paracetamol (API of high commercial importance). 1 This strategy is eco-friendly, operationally simple, and robust, avoids the use of exogenous stoichiometric chemical oxidants, and furnishes the acetaminophen in just one step from phenol.The protocol is scalable, can be deployed to a variety of phenols, and tolerates a variety of sensitive functional groups.Moreover, the methodology can be easily applied to reconsider the conventional routes of synthetically rlevant drugs like practolol (β-adrenergic blocker, used for the treatment of cardiac arrhythmias).
References 1. Taily, I. M.; Saha, D.; Banerjee, P. Org. Lett. 2022 , 24 , 2310-2314.
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© The Author(s), 2022
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