Air Free Reaction Setup

Materials

• Schlenk line (vacuum + inert gas manifold) or a N₂/Ar tank with bubbler + balloon
• Oven dried Schlenk flask/tube (or septum capped round bottom), stir bar
• Rubber septa, needles (various gauges), gas tight syringes
• Liquid N₂ (or dry ice/acetone) bath for freeze pump thaw
• Glovebox, if your catalyst is extremely O₂ sensitive (e.g. some Cu(I) complexes)

Step by step

1. Dry the glassware. Oven dry the flask overnight at 120 to 150 °C, or flame/heat gun dry under vacuum on the Schlenk line, then cool under inert gas. Any residual water will hydrolyze catalysts or terminate chains.
2. Purge the empty vessel. Cap with a septum, then do 3 evacuate/backfill cycles on the Schlenk line (vacuum until it holds, then backfill with N₂ or Ar). This renders the flask's headspace inert before anything goes in.
3. Add solids under counter flow. With inert gas flowing out through the septum (needle vent, or briefly removing the septum under positive pressure), quickly add air stable solids: initiator, ligand, monomer if solid, then reseal immediately. Anything pyrophoric or very O₂ sensitive (e.g. neat CuBr) goes in inside a glovebox instead.
4. Add solvent and monomer via syringe.
5. Degas: freeze pump thaw (FPT), the gold standard. See the dedicated Freeze Pump Thaw Method section below for the full procedure. Repeat 3 to 4 cycles total; backfill with inert gas after the last one.

   Simpler alternative: sparge with N₂/Ar through a long needle to the bottom of the flask (with a second needle as vent) for 20 to 30+ min. Less rigorous than FPT and can strip volatile monomer, but adequate for RAFT/FRP or ARGET type ATRP.

6. Add the catalyst last, under inert atmosphere. For ATRP, the Cu(I)/ligand complex is usually the most O₂ sensitive component. Prepare it as a degassed stock solution and add it by syringe (or cannula) right before heating, since this is effectively what starts the clock. Same idea for ROMP: add the Grubbs/Hoveyda catalyst as a stock solution last.
7. Heat with positive pressure maintained. Submerge in a preheated oil bath or heating block; keep a slight positive N₂/Ar flow (bubbler or balloon) throughout so air can't diffuse back in through the septum.
8. Sampling (if tracking conversion). Withdraw aliquots by syringe/needle quickly, ideally with gas still flowing out of a second needle to prevent air being drawn in. Use an internal standard added to the bulk reaction mixture up front so the conversion you calculate from each aliquot is trustworthy regardless of aliquot size.
9. Quench. Open to air (this terminates ATRP by oxidizing Cu(I)→Cu(II)) or add a radical inhibitor/scavenger, then cool and work up (precipitation, dialysis, etc.).

Freeze Pump Thaw Method

Freeze pump thaw (FPT) removes dissolved gas (mostly O₂ and N₂) from a liquid by alternately freezing it solid, pulling vacuum on the headspace, and letting it thaw. Each cycle releases gas that was trapped in the liquid. It's the most thorough degassing method and the standard for ATRP.

What you need

• Schlenk flask/tube with a sidearm stopcock (or a septum plus a needle to a Schlenk line), rated for vacuum
• Vacuum source with a cold trap in line (liquid N₂ or dry ice/acetone) to protect the pump from condensing solvent/monomer vapor
• Liquid N₂ in a wide mouth Dewar, deep enough to submerge the flask's contents
• Insulated gloves, cryogenic rated face/eye protection

Procedure (one cycle)

1. Freeze. Lower the flask into the liquid N₂ bath (stopcock still open to the inert gas line, not to vacuum yet) and swirl briefly until the contents are fully frozen solid. A partially frozen liquid can still splash or bump when vacuum is applied.
2. Evacuate. With the contents frozen (so nothing can boil over into the vacuum line), open the flask to vacuum. Evacuate until the vacuum gauge reads close to the line's static base pressure and holds steady. This pulls the headspace gas out through the solid.
3. Isolate. Close the stopcock to seal the flask under vacuum, then remove it from the liquid N₂ bath.
4. Thaw. Let the flask warm to room temperature undisturbed (a room temperature water bath speeds this up). As it melts, dissolved gas that migrated to the surface during freezing bubbles out into the now evacuated headspace. Let it fully liquefy and sit a minute so the gas has time to escape.
5. Repeat. Refreeze and repeat the evacuate → isolate → thaw sequence 3 to 4 times total. Each cycle should show visibly less bubbling on thaw than the last; once you barely see bubbles on the final thaw, degassing is essentially complete.
6. Backfill. On the last cycle, instead of opening to vacuum, backfill the flask with inert gas (N₂/Ar) while still cold, then let it warm under a positive inert atmosphere.

Technique specific notes

• ATRP: most O₂ sensitive. Do the full 3 to 4x FPT. ARGET/ICAR/SARA variants continuously regenerate Cu(I) and tolerate trace O₂ better, so sparging alone is sometimes acceptable there.
• RAFT: no O₂ sensitive metal, but O₂ scavenges initial radicals and causes an induction period. FPT (3x) or thorough sparging both work; less rigor needed than ATRP.
• ROMP: Grubbs type catalysts are fairly bench stable as solids but degrade in solution with O₂/moisture. Degas the monomer solution and add catalyst last as a fresh stock solution.
• FRP: most O₂ tolerant, but degassing still shortens the induction period and improves reproducibility.