Guide to Safely Transfer Anhydrous Reagents from a Sealed Container for Air Sensitive Reactions

Many reactions in the chemistry lab are air or moisture sensitive, often causing potentially catastrophic accidents if mishandled. Common reagents such as lithium aluminum hydride, Grignard reagents, and alkali metals fall under this category. In late 2008, Sheharbano Sangji, a research assistant working at the University of California in Los Angeles, was involved in a tragic accident involving pyrophoric tert-butyllithium. As the chemical made contact with the air, it ignited. The victim suffered second and third-degree burns, followed by organ failure, and eventually passed away under extensive care. This guideline serves to introduce safe and efficient air-sensitive reaction setup techniques.


Checklist of appropriate gear/glassware

  • Fume hood/glovebox
    A lot of water sensitive chemicals release H2 gas upon reaction with water. Make sure these reactions are performed in fume hoods or glove boxes with fire retardant or extinguishers nearby in case of accidents.
  • Flame resistant lab coat
  • Gloves
    Preferably Kevlar or leather for fire protection
  • Safety goggles
  • Air sensitive solvents stored in dry and cool places
  • Appropriate dried glassware
    Glassware surfaces can absorb a thin layer of water moisture over time. Before use, dry them in a 120°C oven to remove the water moisture, followed by storage in a desiccator (if not used immediately after drying). This is even more important for microscale reactions, due to the large surface area to reactant amount ratio. Note that containers for analytical/volumetric purposes such as cuvettes, volumetric flasks and NMR tubes should not be placed in the oven for longer than ~10 minutes at high oven temperatures, or the containers will deform.

Safety Tip 1 - If the Schlenk line or extreme heat/cold is involved in the solvent transfer, be sure to check for star cracks on the glassware to avoid possible implosion of glassware. 


After you have oven-dried and dessicated the glassware, add any air insensitive reagents and seal the reaction container using rubber septums. Grease any joints to make sure it is air-tight. Too little grease is detrimental as the connections may not be vacuum sealed, but too much grease will result in contamination of your samples. Use enough so that the joints clear up, but not to the point where the grease overflows beyond the connections between glassware.

Safety Tip 2 - Compressed gas tanks can be a projectile hazard if mishandled. Get the proper safety training before handling compressed gas. 

With Schlenk Line

To set up a reaction with inert atmosphere, a Schlenk line with preset adaptors connected to gas lines could conveniently supply inert gas to clear the empty flask of any non-inert gasses.

To purge a reaction solvent, the freeze-pump-thaw method could be performed using the Schlenk line’s vac and back cycle. It is an effective albeit time-consuming way to remove any dissolved oxygen or carbon dioxide from a reaction solvent.

Without Schlenk Line

Without a Schlenk line, air purging* with an inert gas source is necessary. In this technique, a needle would be flushed with inert gas for 5 min, before it is inserted to the reaction flask through the rubber septum. The needle tip should be immersed near the bottom of the solvent and a pressure releasing exhaust needle is inserted to release built up pressure and any non-inert gases.

* Purging the solvent with inert gas (N2 or Ar) for 20 minutes to 1 hour depending on the volume of solvent will remove the majority of atmospheric gases. For more stringent reactions, the freeze-pump-thaw method is more suitable. 


J&K Seal (Figure 1) containers are often used when containing air sensitive solvents. This seal keeps air or moisture from entering as the elastomer seal has excellent resealing properties. When using J&K Seal, it is imperative that the container is given positive pressure in the form of an inert gas before taking any solvent out for transfer. This prevents a partial vacuum from forming inside the J&K Seal container, thus inhibiting potential air/moisture from entering the container during solvent withdrawal. To do so, the following steps should be followed:

  1. Clean and dry glass syringes and needles that will be used in the transfer in an oven and desiccate before use.
  2. Prepare a dry reaction flask with inert gas being pumped into it, sealed with fitting rubber septum and an exhaust needle releasing pressure and any non inert gas.
  3. Flush (draw and expel out into the fumehood) the syringe with inert gas at least 3 times.
  4. Insert a needle that is connected to a nitrogen/argon source into the J&K seal cap, and introduce a positive pressure of inert gas into the container.
  5. Insert a clean long needle with a cleaned syringe (see step 3) and draw out the solvent as it is pushed out by the inert gas. Expel any bubbles by pushing them back into the solvent container.
  6. Transfer the solvent into the dry reaction flask (Step 2) by pushing the needle into the septum of the reaction flask and expelling the contents slowly. Ensure that the inert gas is still being pushed into the reaction flask, and an exhaust is present so that no atmospheric gas enter the reaction mixture.
Figure 1. J&K Seal components. 


  1. Should I use argon or nitrogen for the inert gas?
    Nitrogen is cheaper but is more reactive than argon. Also, argon due to its heavier density compared to atmospheric air, can “blanket” a reaction and would not escape from the reaction flask as easily as nitrogen would. However, nitrogen leaves a smaller carbon footprint. Use whichever necessary, but usually nitrogen would suffice.
  2. My reaction didn’t work, and my air sensitive reagent/solvent came into contact with air.
    Make sure everything is sealed and purged/freeze-pump-thawed before use. During purging, make sure the solution is bubbling. Otherwise, the solution is only being kept under positive pressure, and no gas is being expelled. The time period of purging is also dependent on the amount of solvent and rate of purging.  In the case of freeze-pump-thaw, make sure the oil bubbler of the Schlenk line is bubbling when vacuuming solvent.
  3. I lost some/all my solvent during freeze-pump-thaw.
    Don’t turn on the vacuum when liquid solvent is exposed. It will then work as a rotary evaporator. The solvent must be frozen before entering the vacuum pump phase.
  4. There are solvents reaching the Schlenk line’s vacuum pump.
    There must be a cold trap set up on the Schlenk line, cooled down with a Dewar that contains liquid nitrogen. 



  1. A young lab worker, a professor and a deadly accident. The star. (accessed November 11, 2019)
  2. Anhydrous Reaction Conditions. In Techniques in Organic Chemisry, third ed. J.R. Mohring, C.N. Hammond, and P.F. Schatz. P61-62 W.H. Freeman and Company, New York.
  3. Transfer of Reagents Using Syringe Techniques. In Techniques in Organic Chemisry, third ed. J.R. Mohring, C.N. Hammond, and P.F. Schatz. P216-218 W.H. Freeman and Company, New York.
By Qinling Li


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