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N × 1,000 mL ≠ 600 gallons
EDITORIAL
N 1,000 mL 6¼ 600 gallons
hallowed halls of the academe. These topics include but are certainly not limited to:
Some time ago a relatively small chemical manufacturer asked that I look at the safety surrounding a reduction reaction using lithium–aluminum hydride combined with a lithium alkylborohydride compound in a flammable solvent. The reaction was straightforward – even understandable to this physical chemist who does not regularly push around electrons for a living. It was clear that reaction was exothermic, but it also had some interesting twists in it as well. Particularly interesting were two issues: the boroncontaining reactant is also pyrophoric and quenching the excess reagent was extremely exothermic. Their research chemist had recently achieved the desired results and yield for the compounded they wanted to manufacture so it was time for ‘‘scale up.’’ But instead of scaling up to, for instance, 20 L, he wanted to go directly to production with the company’s 600 gallon (roughly 2,300 L) reactor. While I admire the chemist’s enthusiasm, I didn’t admire his approach to scale-up. When asked how much of the pyrophoric material he was going to use in the final reaction, he replied, ‘‘About 340 L per batch.’’ I found the company president in his office and asked if we could sit down for a few minutes and discuss what his employees had planned and if he was aware of what was going in. A few minutes of conversation indicated to me that he was, shall we say, ‘‘uninformed.’’ Clearly this was a teachable moment for everyone, so we all gathered in the conference room for the chemist’s equivalent of a tailgate safety meeting. There are a number of very important safety considerations for scale-up reactions – topics that are just not taught to bench-scale chemists in the
WHAT AM I GOING TO DO WITH THE HEAT?
1871-5532/$32.00 doi:10.1016/j.jchas.2009.01.002
Heat generation is generally dependent on the volume of the reactants in the reactor, while heat removal is dependent on the surface area of the reactor. In math-speak that boils down to heat generation is a third-order (or cubic) function while heat removal is a second-order (squared) function. In a rough sense that means if one were to double the volume of reactants, the heat generated will be eight times the previous volume (23) while the capacity for removing that heat will only be four times the original volume (22). That can lead to a run-away scenario or an overpressure situation especially if the reaction is carried out under pressure or a reflux condenser becomes clogged.
MATERIAL HANDLING ISSUES
In this case, the bench chemist was handling milliliter quantities of the pyrophoric material in the laboratory. A spill, contained in a glovebox or even in a hood can be easily contained. In bulk, the pyrophoric liquid reactant was delivered in a cylinder under nitrogen pressure, approximately 20 psig, and was transported around the facility using a forklift. I asked if anyone had given any consideration as to what might occur if the truck driver punctured the cylinder with the fork. While this seemed like an implausible accident to the audience, missing pallets and skewering product containers is a common accident in industry. A more plausible scenario was the likelihood for spraying the material on the production floor. In order to
remove the material from the cylinder, nitrogen was applied to a valve at the top and the material was removed from a second valve at the top connected to a tube that reached to the bottom of the cylinder. Failure of a connection or of the flexible piping connecting the cylinder to the reactor seemed fairly plausible to them, probably because it had happened before.
PLANNING FOR THE EMERGENCY
My client had not considered how they would react to spilling the entire cylinder’s contents.
EXPOSURE CONTROL ISSUES
Controlling the vapor and preventing inhalation overexposure from a few milliliters of solvent used in a hood or glovebox is fundamentally different from controlling the vapors generated in a reactor room from a hundred gallons of the solvent. Since the material was pyrophoric, my client used a closed transfer process with nitrogen as the pressure source. During reaction, however, fugitive vapors from the solvent would be emitted into the reactor room and employee exposure would have to be controlled – probably via respirator use – meaning a respiratory protection program, medical clearance and fit testing – expenses that the client had not considered and was reluctant to incur. Simply put, scaling up a reaction requires more than a multiplication factor for your reactants if you want to do it safely.
H.J. Elston
ß Division of Chemical Health and Safety of the American Chemical Society Elsevier Inc. All rights reserved.
3
N 1,000 mL 6¼ 600 gallons
hallowed halls of the academe. These topics include but are certainly not limited to:
Some time ago a relatively small chemical manufacturer asked that I look at the safety surrounding a reduction reaction using lithium–aluminum hydride combined with a lithium alkylborohydride compound in a flammable solvent. The reaction was straightforward – even understandable to this physical chemist who does not regularly push around electrons for a living. It was clear that reaction was exothermic, but it also had some interesting twists in it as well. Particularly interesting were two issues: the boroncontaining reactant is also pyrophoric and quenching the excess reagent was extremely exothermic. Their research chemist had recently achieved the desired results and yield for the compounded they wanted to manufacture so it was time for ‘‘scale up.’’ But instead of scaling up to, for instance, 20 L, he wanted to go directly to production with the company’s 600 gallon (roughly 2,300 L) reactor. While I admire the chemist’s enthusiasm, I didn’t admire his approach to scale-up. When asked how much of the pyrophoric material he was going to use in the final reaction, he replied, ‘‘About 340 L per batch.’’ I found the company president in his office and asked if we could sit down for a few minutes and discuss what his employees had planned and if he was aware of what was going in. A few minutes of conversation indicated to me that he was, shall we say, ‘‘uninformed.’’ Clearly this was a teachable moment for everyone, so we all gathered in the conference room for the chemist’s equivalent of a tailgate safety meeting. There are a number of very important safety considerations for scale-up reactions – topics that are just not taught to bench-scale chemists in the
WHAT AM I GOING TO DO WITH THE HEAT?
1871-5532/$32.00 doi:10.1016/j.jchas.2009.01.002
Heat generation is generally dependent on the volume of the reactants in the reactor, while heat removal is dependent on the surface area of the reactor. In math-speak that boils down to heat generation is a third-order (or cubic) function while heat removal is a second-order (squared) function. In a rough sense that means if one were to double the volume of reactants, the heat generated will be eight times the previous volume (23) while the capacity for removing that heat will only be four times the original volume (22). That can lead to a run-away scenario or an overpressure situation especially if the reaction is carried out under pressure or a reflux condenser becomes clogged.
MATERIAL HANDLING ISSUES
In this case, the bench chemist was handling milliliter quantities of the pyrophoric material in the laboratory. A spill, contained in a glovebox or even in a hood can be easily contained. In bulk, the pyrophoric liquid reactant was delivered in a cylinder under nitrogen pressure, approximately 20 psig, and was transported around the facility using a forklift. I asked if anyone had given any consideration as to what might occur if the truck driver punctured the cylinder with the fork. While this seemed like an implausible accident to the audience, missing pallets and skewering product containers is a common accident in industry. A more plausible scenario was the likelihood for spraying the material on the production floor. In order to
remove the material from the cylinder, nitrogen was applied to a valve at the top and the material was removed from a second valve at the top connected to a tube that reached to the bottom of the cylinder. Failure of a connection or of the flexible piping connecting the cylinder to the reactor seemed fairly plausible to them, probably because it had happened before.
PLANNING FOR THE EMERGENCY
My client had not considered how they would react to spilling the entire cylinder’s contents.
EXPOSURE CONTROL ISSUES
Controlling the vapor and preventing inhalation overexposure from a few milliliters of solvent used in a hood or glovebox is fundamentally different from controlling the vapors generated in a reactor room from a hundred gallons of the solvent. Since the material was pyrophoric, my client used a closed transfer process with nitrogen as the pressure source. During reaction, however, fugitive vapors from the solvent would be emitted into the reactor room and employee exposure would have to be controlled – probably via respirator use – meaning a respiratory protection program, medical clearance and fit testing – expenses that the client had not considered and was reluctant to incur. Simply put, scaling up a reaction requires more than a multiplication factor for your reactants if you want to do it safely.
H.J. Elston
ß Division of Chemical Health and Safety of the American Chemical Society Elsevier Inc. All rights reserved.
3