Reactions

Letters to the editor

Continuous processing

The article on continuous processing (C&EN, April 29, page 28) recalls my first experience with the concept. It was in 1988, shortly after I joined DuPont. We had a Grignard reagent to be reacted with an α-chloroketone to make a chlorohydrin intermediate to DuP 860, an antifungal drug candidate. The addition generated so much heat, on scale it couldn’t be kept at the temperature range required for stability over a reasonable reaction period. Instead we fried our first attempt and had to work day and night in the lab running 12 L reactors to make the amount required. My engineer, Mark Lauritsen, considered our resources at our pilot plant at Chambers Works in New Jersey and asked me for a 4 L jacketed glass reactor. We set up a continuous process in the midst of a bay with two large feed tanks (Grignard reagent and α-chloroketone) leading into the glass reactor and an overflow line leading out to a 100 gal (378.5 L) quench tank. The tiny glass reactor, dwarfed by the other fixed vessels in the bay, seemed so out of place. But once it started up, the continuous process worked perfectly and we made our delivery! Such a logical and simple solution, and my first experience with continuous processing.

Jaan Pesti
Yardley, Pennsylvania

Congratulations on a very important cover story on continuous processing for the drug industry. Transformational change such as this takes decades, and there are always trade-offs, which you articulate well, with one exception: safety. There are no trade-offs with safety. Continuous manufacturing is an inherently safer technology (IST) that also can be kinder to the environment because it often generates less waste and consumes less energy.

It is unfortunate that almost once a month, a chemical facility somewhere in the world experiences a tragedy related to the numerous highly energetic reactions that occur while making the world’s drugs and other products, such as the nitrate ester reaction that Peter Pöchlauer describes in the article. At Corning, we have clearly seen the tipping point for use of this technology in the production of molecules both inside and outside the pharma industry, and much of it is driven by safety concerns. We also see that economic value has been created by doing precisely what Ian Shott points out. Specifically, it is all about the process and not the gear.

We at Corning have teams of engineers around the world who do process development for factories on our flow equipment. We never want to drop our equipment into factories or process development labs and hope for the best. Our teams have developed and gathered more than a decade’s worth of knowledge and data on mixing, heat transfer, and kinetics for hundreds of reactions, and we use this as a starting point to optimize production so that the value is clear and compelling. Traditional “dump and run” batch processing will be around forever because it is fine for many types of reactions, but for important chemical transformations, the train has left the station and is accelerating to full speed.

Gary S. Calabrese
Corning, New York

Editor’s note: Calabrese is senior vice president and director of Corning Global Research.

From the web

Teacher appreciation

To celebrate National Teacher Day, we asked Twitter users to share stories of chemistry teachers; here are some of our favorites.

My AP chem teacher Mr. Ewing truly made me love science. Married my HS sweetheart and invited Mr. Ewing to the wedding to bring a chemicals for a reaction. He is retired and going to cover my maternity leave this fall because I became a HS chemistry teacher.

@chembeauregard

Shoutout to my honors chem teacher from the @LGBTSTEM community. She made the subject so much fun, ex. we had to make our own periodic element super hero and I was able to flex my creativity and make it into a trading card. Also we made silly putty & everyone did well in class.

@StemCorps

My most influential chemistry teacher was my mother. As a young child she taught me informally through fun experiments at home. As a teenager I was lucky to have her as a teacher for my first ever formal chemistry course.

Sadly, she passed shortly after that experience. To this day I often have moments in my career (PhD ChemE) where I use a concept that was first introduced to me by her, and I use those times to remember her joy and impact in the classroom.

@CarolineSzcz

I’m thinking of Juliana Boerio-Goates.

She was the first and only woman I’ve had as a chemistry professor.

When I thought about dropping out of grad school I reached out to her. She was incredibly supportive and encouraged me to finish my degree. Honestly, I’m so glad I did.

@heydebigale