pH Control in Aqueous Processes: N-4-Methylsulfonylphenylguanidine

Abstract

The kinetics and mechanism of the synthesis of the sulfonylguanidine 2 by reaction of the corresponding aniline, 1, with cyanamide have been investigated in aqueous acid solution. The reaction is acid-catalysed, but at low pH, where substantial protonation of 1 occurs, the dominant reaction occurring is a competing hydrolysis of cyanamide to urea. It is shown that reactions run under pH control in the region of pH 2 achieve close to maximum selectivity with respect to the desired guanidine formation, whilst still occurring at a practical rate.

Synthesis of Rovafovir Etalafenamide (Part II): Dynamic Control for Successful Scale-Up of an Oxygen-Releasing Elimination Reaction Mediated by Oxone

“…Control of pH can be especially challenging at scale and, considering the added difficulties associated with generation of oxygen, prompted us to consider the use of a feedback loop. Although widely utilized in bioprocessing, feedback pH control has been considered inconvenient in small-molecule synthesis, and yet real-time analysis and process automation are cornerstones of process analytical technology (PAT) and Green Chemistry, and have recently received significant attention from the pharmaceutical industry. , Herein, we describe our development activities to overcome these challenges and successfully demonstrate this process at manufacturing scale. The reaction performance and its context within the synthesis of 1 are covered in the previous manuscript in this series …”