Cambridge, Massachusetts is a unique place due to having one of the largest (per capita) and most impressive populations of scientists and engineers in the world. Because of this, Cambridge is recognized as a global hub for biotechnology. This makes the Boston area an attractive venue to organize a chemical process development gathering. Continue reading
Last week, John Tedesco and I had the privilege to attend the 3rd International Symposium on Green Processing in the Pharmaceutical & Fine Chemical Industries in Boston, MA. Continue reading
During the fall, a number of events related to green chemistry, green engineering, and other sustainability topics for the pharmaceutical and chemical industries are planned. Some notable green events are:
Dominique Hebrault will present the online seminar New Developments in the Use of PAT and Laboratory Automation from the Pharmaceutical and Chemical Industries on September 15. Specific case studies that Dominique will discuss include: Continue reading
Recently, I saw a conversation on the LinkedIn Organic Process Research & Development (OPRD) Group that began with the subject: “Precaution during scale-up of a Grignard reaction?”. This discussion regarding the safety of Grignard reactions on scale made me realize how useful old chemical reactions can be, although not necessarily well-understood or controlled. Continue reading
During Part I of his two part The Role of Process Analytical Technology (PAT) in Green Chemistry and Green Engineering online seminar series, Dominique Hebrault discussed scale-up challenges faced today by chemists and engineers. Too often, offline sampling methods – mostly chromatographic methods such as High Performance Liquid Chromatography (HPLC) or Gas Chromatography (GC) – are used to monitor processes which fail to resolve common issues like reaction monitoring, poor mass balance, delayed initiation/reaction stalled, and loss of yield/by-products. From a reaction engineering standpoint, obtaining heat mass balance information and preliminary kinetic data can be difficult using traditional offline methods during process scale-up. Forming the final solid can be challenging using traditional offline methods, including filtration/drying a bottleneck, excessive washing, polymorph inconsistency, and batch to batch variability can be difficult.
When you run a chemical reaction, a process, an experiment… it is probably critical to you that you do it well – otherwise you wouldn’t waste your time, right?
It’s like buying a car, spending money on gas, taking the wheel and spending your time trying to get to somewhere you need to be. Now, monitoring the reaction in real time is like driving with your eyes opened: you want to know in real time what’s going on in order to be able to take preventive measures and corrective actions (turn, brake, speed up, stop…) and hopefully prevent a car crash that would waste your money, your time, and possibly hurt yourself and your family.
In the driving world, sampling for offline reaction analysis would be like driving with your eyes closed, opening them only once in a while… only to look at a picture of the road a few minutes before… (Yes, it typically takes time to run an analysis and get the results after you’ve taken a sample.)
Who would dare to drive like this? Why would you monitor a chemical process this way then – especially when the chemical process is no less dangerous, and there are options available to “see” exactly where you are and where you are headed? You take the risk of wasting your time, your money, and possibly hurting yourself and your co-workers.
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A few months ago, I came across two letters in Chemical & Engineering News that I would like to bring to your attention. Both letters relate to ensuring the safety of chemical processes.
The first, from Tom Vickery and colleagues at Merck, made the point that a recently published procedure (for preparation of 2-bromo-3-methylbutenal) presents a safety issue with dramatic consequences for scale-up:
I recently had a chance to meet with Danny Levin, President at Norac Pharma, during the 21st International Conference on Organic Process Research & Development (Scientific Update), January 2010, San Diego, CA.
After my presentation at the Organic Process Research & Development (OPRD) conference, Danny Levin described a paper he published a few years ago when he was head of research at NPIL Pharma Torcan (Org. Process Res. Dev., 2006, 10(6), pp 1296–1298). I had already used Danny Levin’s paper several times in my conference talks (figure 1) to illustrate the power of heat flow (Tr-Tj) at small scale, and Danny graciously provided some additional insight:
“I thought you might be interested in a publication of my own where I used METTLER TOLEDO MultiMax to good purpose in identifying and mitigating process scale up safety concerns during process development of a Horner Wadsworth Emmons reaction […]
The situation with the case study that I published was that we had been given a chemistry procedure that was believed by the originator to be safe and under control by virtue of slow addition of reagents. The MultiMax plot of (Tr-Tj) showed that this wasn’t the case – reagents were accumulating and the reaction and all the significant heat output occurred during warming for work-up!!!
It was the MultiMax data that quickly demonstrated the scale up hazard and allowed us to define a safely scaleable process. This critical aspect was not obvious from the presentation summary you kindly sent. You may wish to emphasize this point in future presentations to demonstrate the role of MultiMax in identifying and highlighting unsafe chemistry”.
As part of the on-going Recent Advances in Organic Chemistry by Academia Using Real-Time In Situ FTIR online seminar series, Dominique Hebrault will review recent advances in organic chemistry where real-time mid-infrared (mid-IR) analytics played a role in the advancement of organic chemistry research. This will take place on Wednesday, March 10.
Research topics include:
Advances in metal-catalyzed chemical transformations
Heterobimetallic for metal carbenoid chemistry as described by Huw M.L. Davies and colleagues at Emory University (United States)
Organolithium transformation from Vito Capriati, Saverio Florio, and colleagues from the University of Bari (Italy)
Palladium-catalyzed cross-coupling reactions as reported by Aiwen Lei and colleagues at Peking University (China)
Ruthenium-catalyzed dynamic kinetic resolution as described by Jan-E. Backvall and colleagues at Stockholm University (Sweden)
Highly selective polymerization reactions from Donald J. Darensbourg and colleagues at Texas A&M University (United States)
Chemical reactions in supercritical CO2 and system characterization from Paul A. Charpentier and colleagues at University of Western Ontario
Visit the Recent Advances in Organic Chemistry by Academia Using Real-Time In Situ FTIR online seminar page for more information.