Air-free technique

Air-free techniques refer to a range of manipulations in the chemistry laboratory for the handling of compounds that are air-sensitive. These techniques prevent the compounds from reacting with components of air, usually water and oxygen; less commonly carbon dioxide and nitrogen. A common theme among these techniques is the use of a high vacuum to remove air, and the use of an inert gas: preferably argon, but often nitrogen.

The two most common types of air-free technique involve the use of a glovebox and a Schlenk line. In both methods, glassware are pre-dried in ovens prior to use. They may be flame-dried to remove adsorbed water. Prior to coming into an inert atmosphere, vessels are further dried by purge-and-refill — the vessel is subjected to a vacuum to remove gases and water, and then refilled with inert gas. This cycle is usually repeated three times. The difference between the use of a glovebox and a Schlenk line, is that the purge-and-refill refers to the airlock of the glovebox, and the interior of the reaction vessel connected to the Schlenk line.^[1]

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Glovebox

  The most straightforward type of air-free technique is the use of a glovebox. A glove bag uses the same idea, but is usually a poorer substitute because it is more difficult to purge, and less well sealed.

Normal laboratory equipment can be set up and manipulated through the use of the gloves. By providing a sealed but recirculating atmosphere of the inert gas, few other precautions are necessary. Inventive ways of accessing items beyond the reach of the gloves exist, such as the use of tongs and strings. The main drawbacks to using a glovebox are the cost of the glovebox itself, and limited dexterity wearing the gloves. Cross contamination of samples due to poor technique is also acute, especially where a glovebox is shared.

Because gloveboxes are expensive and have limited space, it is common for gloveboxes to be used to store, weigh, and transfer air-sensitive chemicals. Reactions are thereafter carried out using Schlenk technique. The gloveboxes are thus only used for the most air-sensitive reactions.

Schlenk line

  The other main types of techniques are associated with the use of a Schlenk line. The main methods here are:

• counterflow additions, where air-stable reagents are added to the reaction vessel against a flow of inert gas.
• the use of rubber septa with syringes to transfer liquids and solutions
• cannula transfer, where liquids or solutions of air-sensitive reagents are transferred between different vessels stoppered with septa using cannulae. Liquid flow is achieved via vacuum or inert gas pressure.^[2]

Glassware are usually connected via tightly-fitting and greased ground glass joints. Round bends of glass tubing with ground glass joints may be used to adjust the orientation of various vessels.

Filtration under inert conditions poses a special challenge which is usually tackled with specialized glassware. A Schlenk filter, consists of sintered glass funnel fitted with joints and stopcocks. By fitting the pre-dried funnel and receiving flask to the reaction flask against a flow of nitrogen, carefully inverting the set-up, and turning on the vacuum appropriately, the filtration may be accomplished with minimal exposure to air.

Other air-free methods

• air-free distillation - e.g. see reflux still, Perkin triangle
• air-free filtration - e.g. see filter stick
• air-free sublimation
• air-free solid addition - e.g. see solid addition tube
• air-free liquid addition - e.g. see cannulation, syringing, dropping funnel
• air-free NMR tube preparation

Associated preparations

Commercially available purified inert gas (argon or nitrogen) is adequate for most purposes. However, for certain applications, it is necessary to further remove water and oxygen. This can be accomplished by piping the inert gas line through a heated column of copper catalyst, which converts the oxygen to water. Residual water from the gas cylinder, and water generated from deoxygenation reaction are removed by passing through a column of desiccant such as phosphorus pentoxide.

Air- and water-free solvents are also necessary. If high-purity solvents are available in nitrogen-purged Winchesters, they can be brought directly into the glovebox. For use with Schlenk technique, they can be quickly poured into Schlenk flasks charged with molecular sieves, and degassed.

Degassing

See also: degasification

Two procedures for degassing are common. The first is known as freeze-pump-thaw — the solvent is frozen under liquid nitrogen, and a vacuum is applied. Thereafter, the stopcock is closed and the solvent is thawed in warm water, allowing trapped bubbles of gas escape.^[3]

The second procedure is to simply subject the solvent to a vacuum. Stirring or mechanical agitation using a ultrasonicator is useful. Dissolved gases evolve first; once the solvent starts to evaporate, noted by condensation outside the flask walls, the flask is refilled with inert gas. Both procedures are repeated three times.

Drying

  Solvent are traditionally purified by distillation over an appropriate desiccant under an inert atmosphere. The use of sodium and benzophenone affords oxygen-free solvents; the use of other desiccants may require further degassing.

However, distillation stills are fire hazards and are increasingly being replaced by alternative solvent-drying systems. Particularly popular is the filtration of deoxygenated solvents through columns filled of activated alumina.^[4]

Alternatives

Both these techniques require rather expensive equipment. Where air-free requirements are not as stringent, other techniques exist. For example, for preparing Grignard reagents which hydrolyze on exposure to water, it is usually sufficient to connect a guard tube filled with calcium chloride to the reflux condenser to prevent moisture contamination.

In situ desiccants such as molecular sieves, or the removal of water by azeotropic distillation can also be used.

References

1. ^ The Manipulation of Air-Sensitive Compounds, by Duward F. Shriver and M. A. Drezdzon 1986, J. Wiley and Sons: New York. ISBN 0-471-86773-X.
2. ^ Brown, H. C. “Organic Syntheses via Boranes” John Wiley & Sons, Inc. New York: 1975. ISBN 0-471-11280-1.
3. ^ Mark Lonergan. Freeze-Pump-Thaw Degassing of Liquids. University of Oregon.
4. ^ Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K. and Timmers, F. J. (1996). "Safe and Convenient Procedure for Solvent Purification". Organometallics 15 (5): 1518-20. doi:10.1021/om9503712.