Wednesday, March 13, 2013

Process Wednesday: too much surface area!

From the very interesting book "Organometallics in Process Chemistry" [1] comes this story of what happens when a group of Sandoz Pharmaceuticals chemists (circa 1982) were looking for a process-friendly Simmons-Smith cyclopropanation. After going from diethyl ether (!) to 1,2-dimethoxyethane to get some higher heat capacity, they faced another interesting problem -- their source of zinc and its surface area:
The high cost of utilizing zinc-copper amalgam led to the develop of a cheaper process employing various forms of metallic zinc (mossy, rods or foil.) The reaction was performed using ultrasonic irradiation, thus requiring no chemical activation of the zinc. This method also help to eliminate the delayed exotherm, and the reaction time and yield were more reproducible. Initially, the reaction was performed using zinc powder  which often led to excessive foaming. This was replaced with a solid piece of zinc, which not only reduced the foaming, but also dampened the exotherm due to a decrease in the reactive surface area. The zinc block could be removed at any time to slow the reaction. At the conclusion of the reaction  the zinc block was conveniently removed from the mixture before workup.  
Interestingly, on a 1 liter scale, zinc paddles attached to the glass stirrer shaft were tested. Even though they partially dissolved throughout the reaction, an excess of zinc was used in the design so that efficient stirring continued to the end of the reaction.  This curious design was later replaced with zinc cones, a shape that provided a practical surface area to weight ratio. 
I think this was a set of very interesting choices, and I think it was based on the understanding that the foaming and the exotherm were due to the surface area of the powder. (Where does one get a solid block of zinc, anyway?)

1. DelMonte, A.J.; Dowdy, E.D.; Watson, D.J. "Development of Transition Metal-Mediated Cyclopropanation Reactions." Topics in Organometallic Chemistry (2004) 6: 97-122. DOI: 10.1007/b94550

1 comment:

  1. In grad school, I was wracking my brain to figure out why I couldn't reproduce a lit result for Zn/Cu couple. Finally figured out that their 'mossy' zinc was reacting quite differently from my zinc powder.


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