Process Analytical Technology (PAT) for enhanced development and control of continuous processes
JON GOODE1, DOMINIQUE HEBRAULT2*
*Corresponding author
1. METTLER TOLEDO, 64 Boston Road, Leicester LE4 1AW, United Kingdom
2. METTLER TOLEDO, 7075 Samuel Morse Drive, Columbia, MD 21046, USA
Abstract
In chemical development, the need for improvements in product quality, process safety and overall synthetic efficiency have become key factors in driving chemists and engineers to seek alternative technologies. Continuous flow reactor technologies provide the opportunity to significantly expand the scope of possible chemistries at laboratory scale, and allow for rapid testing, optimization, and scaling. However, a limiting factor relates to inline monitoring which is of great importance with respect to optimization and flow process understanding. One of the most convenient and nondestructive methods for real-time inline monitoring is mid-infrared (IR) spectroscopy, increasingly utilized to investigate chemistries challenging to analyze using standard offline techniques. Through several case studies, this article describes laboratory applications using instruments specifically designed for the in situ, real-time monitoring of flow chemistry.
INTRODUCTION
Technical breakthroughs in chemical development, process operations and modelling are necessary to meet today’s challenges posed to the chemical and pharmaceutical industries. Proper integration of process analytical technologies and process control result in information rich experiments that can expedite chemical process development and facilitate energy and material efficiencies downstream (1). Modern continuous flow reactor technologies provide the opportunity to significantly expand the range and scope of possible chemistries available to today’s synthetic chemist, and allow for rapid testing, optimization, and scaling of chemical sequences (2). This is reflected in the dramatic increase in the variety and depth of published chemistry over the last few years (3, 4). However, a limiting factor with these methods relates to inline monitoring as it facilitates and enhances optimization and synchronized control of single and multi-step reactions (5). Real-time in situ FTIR analysis has already become a standard tool increasingly utilized to investigate chemistries challenging to analyze using standard offline techniques (6). This powerfu ...
