A few years ago I was trying to make a series of small, cationic amphiphiles. The synthesis was a simple series of peptide coupling reactions, and was my first experience with solid phase. Almost giddy with excitement, I ran nine reactions on the same substrate over about four days, then purified them with a poor a poor man’s HPLC (turn out that you can buy C18 flash silica). This gave me with about 30mg of compound, dissolved in slightly over 200mL of water/methanol mixture.
And trouble set in. Charged amphiphiles? Great foaming agents. When the pressure on the rotovap dropped below about 10 Torr my RBF lit up like a science fair volcano, coating half the apparatus in a thin layer of compound-rich foam. Adding n-pentanol as a deflocculant did little to help, and our lab doesn’t have access to something fancy like a lyophilizer. So, I started searching the “literature.” The best piece of advice I could find came from Org Prep Daily’s milkshake, who recommended silanizing the glassware to reduce seeding sites for the foam. Unfortunately, our lab didn’t have any of the silanizing reagent in stock, and after being so productive earlier in the week I was a little impatient.
Thankfully, our old lab space had been running since the mid-sixties, with each research group acquiring their own personalized glassware along the way. The old equipment was never thrown out, and so we’d built up a rather eclectic mix of glassware. A little searching and I turned up this gem.
This was probably intended to be part of a vacuum line, and it works wonderfully in reverse. Attaching the side arm to house vacuum causes a steady stream of air to flow through the system, slow enough that solvent is doesn’t bubble or spray. This occurred in January, and during winter our lab is about as humid as the Sahara desert. Because I knew my material wasn’t oxidation sensitive, I left the RBF under a gentle stream of air and went home for the night. Coming back the next morning both the water and methanol was gone, leaving behind a nice, thick oil on the bottom of the flask. It was dry enough that I could put it on our high-vacuum line to fully dry without issue, and then proceed to NMR and all the rest.
Since then I’ve used this trick on at least forty different compounds (related structures), and not once have I had to worry about foaming. Concentrating after NMR is done in trusty 4mL vials following the same principle, though in those cases I use a smurf septa and two needles instead of the large glass adapter (one needle for the air inlet, the other for the vacuum line).
This technique works in the summer as well, but can take as much as twice as long because of the increased humidity. If you have an ocean view I’d advise that you add some drying agent to the line, or set things up over the weekend. A safer alternative would be to use nitrogen gas instead, something you would have to do anyway for oxidation sensitive compounds. Just feed the gas in through the top port.