- Air-free technique
Air-free techniques refer to a range of manipulations in the chemistry
laboratoryfor the handling of compounds that are air-sensitive. These techniques prevent the compounds from reacting with components of air, usually waterand oxygen; less commonly carbon dioxideand nitrogen. A common theme among these techniques is the use of a high vacuumto 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
gloveboxand a Schlenk line. In both methods, glassware (often Schlenk tubes) 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 or the vacuum is applied for an extend period of time. One of the differences between the use of a glovebox and a Schlenk line is where the "purge-and-refill" cycle is applied. When using a glovebox the "purge-and-refill" is applied to an airlockattached to the glovebox, commonly called the "port" or "ante-chamber". In contrast when using a Schlenk line the "purge-and-refill" is applied directly to the reaction vessel through a hose or ground glass joint that is connected to the manifold. [Duward F. Shriver and M. A. Drezdzon "The Manipulation of Air-Sensitive Compounds" 1986, J. Wiley and Sons: New York. ISBN 0-471-86773-X.]
The most straightforward type of air-free technique is the use of a
glovebox. A glove baguses the same idea, but is usually a poorer substitute because it is more difficult to purge, and less well sealed. 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.
In the glovebox, conventional laboratory equipment can often be set up and manipulated, despite the need to handle the apparatus with the gloves. By providing a sealed but recirculating atmosphere of the inert gas, the glove box necessitates few other precautions. Cross contamination of samples due to poor technique is also problematic, especially where a glovebox is shared between workers using differing reagents; volatile ones in particular.
Two styles have evolved in the use of gloveboxes for
synthetic chemistry. In a more conservative mode, they are used solely to store, weigh, and transfer air-sensitive reagents. Reactions are thereafter carried out using Schlenk techniques. The gloveboxes are thus only used for the most air-sensitive stages in an experiment. In their more liberal use, gloveboxes are used for the entire synthetic operations including reactions in solvents, work-up, and preparation of samples for spectroscopy.
Not all reagents and solvents are acceptable for use in the glovebox, although again, different laboratories adopt different cultures. The "box atmosphere" is usually continuously deoxygenated over a copper catalyst. Certain volatile chemicals such as halogenated compounds and especially strongly coordinating species such as
phosphinesand thiols can be problematic because they irreversibly poison the copper catalyst. Because of this problem, many experimentalists choose to handle such compounds using Schlenk techniques. In the more liberal use of gloveboxes, it is accepted that the copper catalyst will require more frequent replacement but this cost is considered to be an acceptable trade-off for the efficiency of conducting an entire synthesis within a protected environment
The other main technique for the preparation and handing of air-sensitive compounds are associated with the use of a
Schlenk line. The main techniques include:
* counterflow additions, where air-stable
reagents are added to the reaction vessel against a flow of inert gas.
* the use of syringes and rubber
septato transfer liquids and solutions
* "cannula transfer", where liquids or solutions of air-sensitive reagents are transferred between different vessels stoppered with septa using
Glassware are usually connected via tightly-fitting and greased
ground glass joints. Round bends of glass tubingwith ground glass joints may be used to adjust the orientation of various vessels.
Filtration under inert conditions poses a special challenge that 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(see gallery below), swivel frit
air-free sublimation- see gallery below for a drawing scheme for an example
air-free solid addition- e.g. see solid addition tube, swivel frit
air-free liquid addition- e.g. see cannulation, syringing, dropping funnel, vacuum transfer
air-free NMR tube preparation
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 additional purification can be accomplished by piping the inert gas line through a heated column of copper
catalyst, which converts the oxygen to copper oxide. Water is removed by piping the gas through a column of desiccant such as phosphorus pentoxideor molecular sieves.
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. More typically, solvent is dispensed directly from a still or solvent purification column.
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. [cite web | title = Freeze-Pump-Thaw Degassing of Liquids | author = Mark Lonergan | publisher = University of Oregon| url = http://www.uoregon.edu/~lnrgn/Assets/FPT.pdf]
The second procedure is to simply subject the solvent to a vacuum. Stirring or mechanical agitation using a
ultrasonicatoris 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.
Solvent are traditionally purified by
distillationover an appropriate desiccantunder an inert atmosphere. The main problem with the use of sodium as a desiccant (below its melting point) is associated with the slow rate of reaction between a solid and a solution. When however, the desiccant is soluble, the speed of drying is much higher. Benzophenone is often used to generate such a soluble drying agent. An advantage to this application is the intense blue color of the ketyl radical anion. Thus, sodium/benzophenone can be used as an indicator of air-free and moisture-free conditions in the purification of solvents by distillation. [cite web | author = Nathan L. Bauld | publisher = University of Texas| year = 2001 | title = Unit 6: Anion Radicals | url = http://research.cm.utexas.edu/nbauld/unit6_anrad.htm] [cite book | author = W. L. F. Armarego and C. Chai | title = Purification of laboratory chemicals | year = 2003 | publisher = Butterworth-Heinemann | city = Oxford | isbn = 0750675713]
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 with activated
alumina. [cite journal | author = Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K. and Timmers, F. J. | title = Safe and Convenient Procedure for Solvent Purification | journal = Organometallics| year = 1996 | volume = 15 | issue = 5 | pages = 1518–20 | doi = 10.1021/om9503712]
Drying of solids can be brought about by storing the solid over a drying agent such as chem|P|2|O|5 or silica, storing in a drying oven/vacuum-drying oven, heating under a high vacuum or in a
drying pistol, or to remove trace amounts of water, simply storing the solid in a glove box that has a dry atmosphere.
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 tubefilled with calcium chlorideto the reflux condenserto prevent moisture contamination.
desiccants such as molecular sieves, or the removal of water by azeotropic distillationcan also be used.
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