Skip to content

Air Sensitive Synthesis Essay

Overview

Source: Tamara M. Powers, Department of Chemistry, Texas A&M University 

Inorganic chemists often work with highly air- and water-sensitive compounds. The two most common and practical methods for air-free synthesis utilize either Schlenk lines or gloveboxes. This experiment will demonstrate how to perform simple manipulations on a Schlenk line with a focus on solvent preparation and transfer. Through the synthesis of a reactive Ti(III) metallocene complex, we will demonstrate a new, simple method to degas solvent as well as how to transfer solvent by cannula and by syringe on a Schlenk line.

The synthesis of a Ti(III) metallocene compound 3 is shown in Figure 1.1 Compound 3 is highly reactive with O2, (see oxidation of compound 3 to Ti(IV) metallocene 4 shown in Figure 1). Therefore, it is important to run the synthesis under anaerobic conditions. The synthesis of target compound 3 can be monitored visually and progresses through one additional color change before arriving at the desired product, which is blue in color. If during the experiment there is an observed color change from blue to yellow (or green = blue + yellow), this is an indication that O2 entered the flask and that undesired oxidation of compound 3 to the Ti(IV) analog (compound 4) has occurred.


Figure 1. Synthesis of Ti(III) metallocene compound 3 and it's reaction with O2.

Cite this Video

JoVE Science Education Database. Inorganic Chemistry. Synthesis Of A Ti(III) Metallocene Using Schlenk Line Technique. JoVE, Cambridge, MA, (2018).

Principles

Schlenk line technique uses positive pressure of inert gases to keep air out of a system when handling air- and water-sensitive reagents. An introduction to Schlenk line technique can be found in the "Schlenk Lines Transfer of Solvent" video in the Essentials of Organic Chemistry series. In this module, two experimental techniques using the Schlenk line will be explored: solvent degassing and air-free solvent transfer.

Anaerobic synthesis requires removal of air that is dissolved in reaction solvents (i.e., degassing the solvent). The solubility of a gas in a liquid is dependent on the identity of the gas and the solvent, as well as the temperature of the system and the partial pressure of the gas above the liquid. Henry's law states that at a given temperature, the amount of gas dissolved in a specific volume of liquid is directly proportional to the partial pressure of that gas in the system. To degas a solvent, the air above the liquid is removed or replaced with an inert gas, such as N2 or Ar. By reducing or removing the pressure of air above the liquid, the amount of air dissolved in that liquid decreases. The process of degassing ultimately results in the removal of all of the air dissolved in the solvent.

There are several methods that can be used to degas solvent, including freeze-pump-thaw and bubbling inert gas through the solvent (purging). While the freeze-pump-thaw method is the more rigorous of the two methods for removing dissolved O2 (see the "Degassing Liquids" video in the Essentials of Organic Chemistry series), purging is useful when using smaller volumes of liquid and when the reactants and/or products are not water sensitive. Here we demonstrate how to degas solvent by purging. It is important to remember that degassing solvent does not remove water.

The most common methods to add solvent to a reaction using a Schlenk line include transfer by syringe or by cannula (a long double pointed needle, Figure 2). Syringes are used when a specific volume of liquid needs to be added to the reaction (i.e., adding a liquid reagent). Cannula transfers can be used to transfer an exact volume into a dropping funnel, or an approximate volume if transferring solvent to the reaction. Cannula transfer relies on a pressure difference between two flasks to transfer solvent from one vessel (donor flask) to another (receiving flask) (Figure 3), and the pressure differential can be achieved by either application of vacuum or pressure. Vacuum-based cannula transfer is conducted by putting the receiving flask under static or dynamic vacuum, while the donor flask is connected to positive N2 pressure. In pressure-based cannula transfer, the receiving flask is vented while positive N2 pressure is fed into the donor flask. In both cases, the lower pressure in the receiving flask results in solvent flowing through the cannula from the donor flask to the receiving flask. Here we demonstrate how to use the pressure method for cannula transfer.


Figure 2. Cannula.


Figure 3. Basics of cannula transfer. Schlenk flask A (the receiving flask, left) contains the solid reactants and Schlenk flask B (the donor flask, right) contains the degassed acetonitrile.

Procedure

1. Setup of the Schlenk Line

For a more detailed procedure, please review the "Schlenk Lines Transfer of Solvent" video in the Essentials of Organic Chemistry series. Schlenk line safety should be reviewed prior to conducting this experiment. Glassware should be inspected for star cracks before use. Care should be taken to ensure that O2 is not condensed in the Schlenk line trap if using liquid N2. At liquid N2 temperature, O2 condenses and is explosive in the presence of organic solvents. If it is suspected that O2 has been condensed or a blue liquid is observed in the cold trap, leave the trap cold under dynamic vacuum. Do NOT remove the liquid N2 trap or turn off the vacuum pump. Over time the liquid O2 will sublime into the pump - it is only safe to remove the liquid N2 trap once all of the O2 has sublimed.

  1. Close the pressure release valve.
  2. Turn on the N2 gas and the vacuum pump.
  3. As the Schlenk line vacuum reaches its minimum pressure, prepare the cold trap with either liquid N2 or dry ice/acetone.
  4. Assemble the cold trap.

2. Preparation of the Solid Reactants

  1. Weigh 100 mg (0.40 mmol) of solid dicyclopentadienyltitanium(IV) dichloride (compound 1, Figure 1) and 78 mg (1.2 mmol) zinc dust into a Schlenk flask (Schlenk flask A).
  2. Fit Schlenk flask A with a greased glass stopper and attach the Schlenk flask side arm to the Schlenk line with Tygon tubing.
  3. Open the stopcock of the Schlenk line tube attached to Schlenk flask A to vacuum. Slowly open the stopcock on Schlenk flask A. Evacuate Schlenk flask A for 5 min.
  4. Repressurize Schlenk flask A with N2 by first closing the stopcock on the Schlenk flask. Slowly repressurize the Schlenk line tubing with N2 by turning the Schlenk line stopcock to N2. Make several (at least 5) quick 180 ° turns on the Schlenk flask stopcock, making sure the stopcock is closed after each turn. Slowly open the stopcock to finish filling Schlenk flask A with N2.
  5. Close the Schlenk flask A stopcock.
  6. Repeat steps 2.3-2.5 two more times. On the last cycle, leave the stopcock to the Schlenk flask A open.

3. Preparation of the Solvent

NOTE: Since the reaction is not water sensitive, glassware and solvents do not need to be dried. However, if the preparation is for use in the glovebox, all glassware and solvents should be appropriately dried.

  1. Measure 15 mL of acetonitrile and transfer the solvent to a new Schlenk flask (Schlenk flask B). Fit Schlenk flask B with a septum.
  2. Connect Schlenk flask B to the Schlenk line using Tygon tubing. Evacuate the tubing for 5 min and refill the tubing with N2 (the stopcock to the Schlenk flask should remain closed). Repeat the evacuation/refill cycles two more times. Leave the tubing under N2.
  3. Purge one of the unused Tygon tubes on the Schlenk line with N2, fitted with a long needle.
  4. Insert the needle into the septum of Schlenk flask B and lower the needle into the acetonitrile.
  5. Insert a second needle (not attached to the Schlenk line) into the septum of Schlenk flask B. This is the vent needle. Upon insertion of the vent needle, N2 should start bubbling through the acetonitrile.
  6. Allow the acetonitrile to degas for 15 min.
  7. Open the stopcock to Schlenk flask B.
  8. Remove the vent needle, followed by the needle connected to the Schlenk line. Close the stopcock on the Schlenk line that is connected to the long needle.

4. Addition of Solvent via Cannula (Figure 3)

  1. Make sure that the stopcocks to both of the Schlenk flasks (A & B) are open to N2.
  2. Replace the glass stopper on Schlenk flask A with a rubber septum.
  3. Insert one end of the cannula through the septum on Schlenk flask B (the donor flask). Do NOT put the needle into the acetonitrile.
  4. Ensure N2 is flowing through the cannula by putting the opposite end of the cannula close to the skin of the arm.
  5. Insert the other end of the cannula into Schlenk flask A (the receiving flask).
  6. Close the stopcock to Schlenk flask A.
  7. Lower the cannula in Schlenk flask B so that the tip reaches the bottom of the acetonitrile.
  8. Insert a vent needle in the septum of Schlenk flask A. Solvent should begin to flow. If no solvent is flowing, try increasing the N2 flow or raising the solvent flask above the height of the receiving flask.
  9. Transfer all 15 mL of the acetonitrile from Schlenk flask B to A. If only a portion of the solvent is desired, simply remove the cannula tip from the solvent in Schlenk flask B to stop the flow of liquid.
  10. Remove the vent needle from the septum and open the stopcock to Schlenk flask A.
  11. Remove the cannula from Schlenk flask A.
  12. Remove the cannula from Schlenk flask B.

5. Synthesis of Ti(III) Metallocene (Compound 3)

  1. Vigorously stir the solution for 15 min (or until the reaction mixture turns blue).
  2. If a green color persists, add more zinc dust (1-2 additional equivalents). To add more zinc dust to the system without introducing O2, make sure that the Schlenk flask stopcock is open to positive N2 pressure. Remove the rubber septum and add the solid to the flask. Re-attach the rubber septum. If the addition of excess zinc dust does not effect the desired color change to blue, O2 was likely introduced into the system.

6. Addition of Solvent via Syringe

  1. Degas 10 mL of acetonitrile as described in step 3 in Schlenk flask B.
  2. Make sure that both Schlenk flask A & B stopcocks are open to N2 and are fitted with rubber septa.
  3. Insert the syringe needle into either flask and pull N2 gas into the syringe.
  4. Remove the needle and eject the N2 into the hood.
  5. Repeat steps 6.3-6.4 two more times.
  6. Insert the syringe needle fitted to a 10 mL syringe into Schlenk flask B and pull up the desired volume of solvent (5 mL).
  7. Remove the needle from the solvent but leave the needle in the Schlenk flask. Bend the needle so that the syringe is pointing up (the needle should form an arch) and pull ~1 mL of N2 gas into the needle. There should be a gas "bubble" at the top of the syringe.
  8. While keeping the needle arched, remove the needle from Schlenk flask B. The syringe should still be pointed up with the bubble of N2 at the tip of the syringe where the needle is attached. The N2 bubble will prevent acetonitrile from leaking out of the syringe.
  9. With the needle still arched and the syringe pointing up, insert the needle into the septum of Schlenk flask A.
  10. Slowly add acetonitrile to Schlenk flask A. At this point, the position of the syringe is irrelevant.
  11. When solvent addition is complete, remove the syringe needle from Schlenk flask A.

Chemists frequently encounter air-sensitive chemical reagents and reactions, and thus have to apply special techniques when working with them.

The slightest trace of air in a chemical reaction would likely result in unwanted side products. To avoid this, first traces of oxygen are removed by purging equipment and reagents.

Then, in order to maintain an oxygen-free atmosphere, reagents are handled in a glovebox, or transferred from one closed system to another by cannulation using a Schlenk line.

This video will illustrate a procedure for purging oxygen from a reaction mixture and maintaining an air-free atmosphere in the synthesis of a Ti(III) metallocene. This will be followed by a few examples demonstrating the application of this technique.

Inorganic chemical reactions, such as the conversion of titanocene dichloride to its dimeric form and the final Ti(III) metallocene, are highly sensitive to oxygen, and therefore must be carried out in air-free conditions.

To start, in a fume hood equipped with a Schlenk line, also known as a double manifold, weigh Cp2(Ti4+)Cl2 and zinc dust into a 200 mL Schlenk flask equipped with a stir bar, labeled as "A". Seal the flask with a greased glass stopper and secure with a rubber band. Attach Tygon tubing from the Schlenk line to flask sidearm.

Open the stopcock to vacuum and evacuate for 5 min, then close the stopcock to the flask, switch to N2, and make at least five rapid 180 ° turns before slowly opening to fill the flask with N2.

In a separate Schlenk flask labeled "B", measure 15 mL of acetonitrile and seal with a rubber septum. Attach Tygon tubing from the Schlenk line to the flask sidearm, then evacuate the tubing for 5 min. Refill the tubing with N2.

Attach a long needle to a second Tygon tube on the Schlenk line, and purge with N2 for several minutes. Insert the purged needle into the Schlenk flask containing acetonitrile, followed by the venting needle. Bubble N2 into the solvent for 15 min, then open the flask stopcock to N2 and remove the needles.

With Schlenk flask A under N2, remove the glass stopper and replace it with a rubber septum. With the two Schlenk flasks open to N2, insert one end of the cannula into the donor flask, above the level of the solvent, and determine whether N2 is flowing through the other end. Then insert the other end of the cannula into the receiving flask containing the reagents, close the receiving flask's stopcock, and attach a venting needle.

Lower the cannula into the solvent, and allow all of the acetonitrile to drip or slowly flow along the sides of the receiving flask. Once the addition is complete, reopen the receiving flask stopcock to N2, and remove the cannula and venting needle.

After the solvent is added, vigorously stir the reaction mixture of acetonitrile, zinc dust, and Cp2(Ti4+)Cl2 until it turns blue, indicating formation of Ti(III) metallocene complex.

If the reaction mixture remains green after 15 min, keep the stopcock open to positive N2 pressure, remove the septum and add 1-2 equivalents of zinc dust. If the mixture is still green or has turned yellow, it is likely that oxygen has entered the system, which results in further oxidation to the Ti(IV) metallocene complex.

Now you know how to use a cannula transfer, but in case this is not possible, the solvent can be added via a syringe. First, make sure both the receiving and donor flasks are open to N2.

Insert the needle fitted to a 12 mL syringe into either flask and pull only N2 into it. Remove the needle and eject the N2 into the hood.

Once the needle and syringe are purged, insert the needle into the donor flask and pull up the desired volume of solvent. Then, raise the needle slightly, bend it to an arch and pull up 1 mL of N2. Keep the needle arched and syringe pointing up and remove it from the donor flask.

Insert the arched needle into the receiving flask. Slowly add the solvent, and remove the syringe needle from receiving flask when finished.

Now that we have discussed a procedure for an air-free synthesis, let's look at a few applications.

Cadmium selenide quantum dots are semiconductor nanocrystals composed of a cadmium selenide core and a ligand shell. These multicomponent structures are capable of manipulating electrons at the nanoscale.

The synthesis of these nanocrystals requires precise reaction conditions, especially an oxygen-free atmosphere.

Titanocene dichloride, the reagent used in this video, is an organotitanium compound commonly used in organic and organometallic synthesis. The compound itself is synthesized by reacting 2 equivalents of sodium cyclopentadiene (NaCp) with TiCl4 in anhydrous, oxygen-free THF. Titanocene dichloride is also used for the production of the Petasis reagent, which is a useful reagent applied in the conversion of esters to vinyl ethers.

Another titanocene dichloride reagent, called the Tebbe reagent, is applied to convert various carbonyl functional groups to alkenes, or also known as methylenation.

You've just watched JoVE's introduction to Synthesis of a Ti(III) metallocene using the Schlenk Line Technique. You should now understand how to perform degassing as well as cannula transfer, and some of its applications. Thanks for watching!

Results

Upon addition of the acetonitrile in step 4, the solution should change color from orange, to green, to blue (Figure 4). Failure to obtain the blue color indicates a leak in the system. Addition of acetonitrile by syringe in step 6 should result in no color change if anaerobic conditions are maintained. If oxygen is present, the solution will turn from blue, to green, to orange.




Figure 4. Three color stages during the synthesis of Ti(III) metallocene compound 3.

Applications and Summary

Here, we demonstrated standard Schlenk line technique to synthesize an air-sensitive Ti(III) metallocene complex. The solvent was degassed by bubbling N2 through the liquid in a Schlenk flask. We also demonstrated how to set up a reaction under anaerobic conditions on the Schlenk line and transfer solvent anaerobically by cannula transfer as well as by syringe.

Inorganic chemists use Schlenk line technique in the synthesis of air- and water-sensitive compounds. The solvent used in the synthesis of highly-reactive materials can be prepared using the Schlenk line. Air-sensitive reactions can also be set up and worked up using a Schlenk line. The Schlenk line technique is a powerful method for air-free manipulations used in synthesis, purification (i.e.,distillation, sublimation, and crystallization), catalysis, and gas reactions. In the next module, we will demonstrate how to use a glovebox for air-free synthesis. While some air-free manipulations are easier to perform in a glovebox, there are certain situations when one cannot use a glovebox and must rely on Schlenk line technique (such as heating a reaction). Some metallocene complexes (metal compounds featuring typically two cyclopentadienyl anions(Cp, C5H5-)) exhibit catalytic properties. For example, titanocene is a catalyst used in olefin metathesis.

The Ti(III) metallocene synthesized herein can be used on the Schlenk line or in the glove box as an atmospheric test. Oxidation of the Ti(III) metallocene by O2 on the Schlenk line or in the glove box would result in a color change and would provide a visual indication that the atmosphere contains O2.

References

  1. Burgmayer, S. N. Use of a Titanium Metallocene as a Colorimetric Indicator for Learning Inert Atmosphere Techniques. J Chem Educ. 75, 460 (1998).

1. Setup of the Schlenk Line

For a more detailed procedure, please review the "Schlenk Lines Transfer of Solvent" video in the Essentials of Organic Chemistry series. Schlenk line safety should be reviewed prior to conducting this experiment. Glassware should be inspected for star cracks before use. Care should be taken to ensure that O2 is not condensed in the Schlenk line trap if using liquid N2. At liquid N2 temperature, O2 condenses and is explosive in the presence of organic solvents. If it is suspected that O2 has been condensed or a blue liquid is observed in the cold trap, leave the trap cold under dynamic vacuum. Do NOT remove the liquid N2 trap or turn off the vacuum pump. Over time the liquid O2 will sublime into the pump - it is only safe to remove the liquid N2 trap once all of the O2 has sublimed.

  1. Close the pressure release valve.
  2. Turn on the N2 gas and the vacuum pump.
  3. As the Schlenk line vacuum reaches its minimum pressure, prepare the cold trap with either liquid N2 or dry ice/acetone.
  4. Assemble the cold trap.

2. Preparation of the Solid Reactants

  1. Weigh 100 mg (0.40 mmol) of solid dicyclopentadienyltitanium(IV) dichloride (compound 1, Figure 1) and 78 mg (1.2 mmol) zinc dust into a Schlenk flask (Schlenk flask A).
  2. Fit Schlenk flask A with a greased glass stopper and attach the Schlenk flask side arm to the Schlenk line with Tygon tubing.
  3. Open the stopcock of the Schlenk line tube attached to Schlenk flask A to vacuum. Slowly open the stopcock on Schlenk flask A. Evacuate Schlenk flask A for 5 min.
  4. Repressurize Schlenk flask A with N2 by first closing the stopcock on the Schlenk flask. Slowly repressurize the Schlenk line tubing with N2 by turning the Schlenk line stopcock to N2. Make several (at least 5) quick 180 ° turns on the Schlenk flask stopcock, making sure the stopcock is closed after each turn. Slowly open the stopcock to finish filling Schlenk flask A with N2.
  5. Close the Schlenk flask A stopcock.
  6. Repeat steps 2.3-2.5 two more times. On the last cycle, leave the stopcock to the Schlenk flask A open.

3. Preparation of the Solvent

NOTE: Since the reaction is not water sensitive, glassware and solvents do not need to be dried. However, if the preparation is for use in the glovebox, all glassware and solvents should be appropriately dried.

  1. Measure 15 mL of acetonitrile and transfer the solvent to a new Schlenk flask (Schlenk flask B). Fit Schlenk flask B with a septum.
  2. Connect Schlenk flask B to the Schlenk line using Tygon tubing. Evacuate the tubing for 5 min and refill the tubing with N2 (the stopcock to the Schlenk flask should remain closed). Repeat the evacuation/refill cycles two more times. Leave the tubing under N2.
  3. Purge one of the unused Tygon tubes on the Schlenk line with N2, fitted with a long needle.
  4. Insert the needle into the septum of Schlenk flask B and lower the needle into the acetonitrile.
  5. Insert a second needle (not attached to the Schlenk line) into the septum of Schlenk flask B. This is the vent needle. Upon insertion of the vent needle, N2 should start bubbling through the acetonitrile.
  6. Allow the acetonitrile to degas for 15 min.
  7. Open the stopcock to Schlenk flask B.
  8. Remove the vent needle, followed by the needle connected to the Schlenk line. Close the stopcock on the Schlenk line that is connected to the long needle.

4. Addition of Solvent via Cannula (Figure 3)

  1. Make sure that the stopcocks to both of the Schlenk flasks (A & B) are open to N2.
  2. Replace the glass stopper on Schlenk flask A with a rubber septum.
  3. Insert one end of the cannula through the septum on Schlenk flask B (the donor flask). Do NOT put the needle into the acetonitrile.
  4. Ensure N2 is flowing through the cannula by putting the opposite end of the cannula close to the skin of the arm.
  5. Insert the other end of the cannula into Schlenk flask A (the receiving flask).
  6. Close the stopcock to Schlenk flask A.
  7. Lower the cannula in Schlenk flask B so that the tip reaches the bottom of the acetonitrile.
  8. Insert a vent needle in the septum of Schlenk flask A. Solvent should begin to flow. If no solvent is flowing, try increasing the N2 flow or raising the solvent flask above the height of the receiving flask.
  9. Transfer all 15 mL of the acetonitrile from Schlenk flask B to A. If only a portion of the solvent is desired, simply remove the cannula tip from the solvent in Schlenk flask B to stop the flow of liquid.
  10. Remove the vent needle from the septum and open the stopcock to Schlenk flask A.
  11. Remove the cannula from Schlenk flask A.
  12. Remove the cannula from Schlenk flask B.

5. Synthesis of Ti(III) Metallocene (Compound 3)

  1. Vigorously stir the solution for 15 min (or until the reaction mixture turns blue).
  2. If a green color persists, add more zinc dust (1-2 additional equivalents). To add more zinc dust to the system without introducing O2, make sure that the Schlenk flask stopcock is open to positive N2 pressure. Remove the rubber septum and add the solid to the flask. Re-attach the rubber septum. If the addition of excess zinc dust does not effect the desired color change to blue, O2 was likely introduced into the system.

6. Addition of Solvent via Syringe

  1. Degas 10 mL of acetonitrile as described in step 3 in Schlenk flask B.
  2. Make sure that both Schlenk flask A & B stopcocks are open to N2 and are fitted with rubber septa.
  3. Insert the syringe needle into either flask and pull N2 gas into the syringe.
  4. Remove the needle and eject the N2 into the hood.
  5. Repeat steps 6.3-6.4 two more times.
  6. Insert the syringe needle fitted to a 10 mL syringe into Schlenk flask B and pull up the desired volume of solvent (5 mL).
  7. Remove the needle from the solvent but leave the needle in the Schlenk flask. Bend the needle so that the syringe is pointing up (the needle should form an arch) and pull ~1 mL of N2 gas into the needle. There should be a gas "bubble" at the top of the syringe.
  8. While keeping the needle arched, remove the needle from Schlenk flask B. The syringe should still be pointed up with the bubble of N2 at the tip of the syringe where the needle is attached. The N2 bubble will prevent acetonitrile from leaking out of the syringe.
  9. With the needle still arched and the syringe pointing up, insert the needle into the septum of Schlenk flask A.
  10. Slowly add acetonitrile to Schlenk flask A. At this point, the position of the syringe is irrelevant.
  11. When solvent addition is complete, remove the syringe needle from Schlenk flask A.

Chemists frequently encounter air-sensitive chemical reagents and reactions, and thus have to apply special techniques when working with them.

The slightest trace of air in a chemical reaction would likely result in unwanted side products. To avoid this, first traces of oxygen are removed by purging equipment and reagents.

Then, in order to maintain an oxygen-free atmosphere, reagents are handled in a glovebox, or transferred from one closed system to another by cannulation using a Schlenk line.

This video will illustrate a procedure for purging oxygen from a reaction mixture and maintaining an air-free atmosphere in the synthesis of a Ti(III) metallocene. This will be followed by a few examples demonstrating the application of this technique.

Many of the compounds encountered in organometallic chemistry are sensitive toward moisture and/or oxygen. Likewise, some organic syntheses or preparations require volatile or pyrophoric reactants. A compound is classed as air-sensitive if it reacts with O2, water, N2, or CO2. Air-sensitive compounds must be isolated from the atmosphere and handled in a controlled environment. Typically, an atmosphere of nitrogen or argon is used. This comes in a suitably pure form from a cylinder fitted with an appropriately sized regulator. As argon is more expensive than nitrogen, nitrogen is usually the preferred gas unless the compound(s) under study react with nitrogen.


Table 1. Examples of compounds that oxidize, decompose, or explode under the influence of oxygen or moisture.


Vacuum/inert gas manifold systems, commonly called Schlenk lines, are ideal for isolating and handling air-sensitive material. Their design is simple and they are straightforward to use. Combine this with specially adapted glassware with standardized Quick-Fit joints, and you have a highly modular and flexible system that enables a variety of experimental set-ups. For these reasons, Schlenk lines are routinely used for the handling and manipulation of air-sensitive compounds.


While Schlenk lines are conceptually simple, at first glance the mass of tubing and exotic glassware can be daunting for the first-time user. Here we present the basics of Schlenk line technique and in follow-up articles we will look at the various types of reaction set-up that are possible as well as the isolation and analysis of your air-sensitive product.



Basic Design and Glassware

The design of Schlenk lines varies from line to line, from lab to lab. There are, however, several key features that a Schlenk line will include (Figs. 1 and 2):

  • Dual manifold
  • Inert gas inlet
  • Inert gas outlet via a bubbler
  • Vacuum pump
  • One or more cold traps for solvents
  • Taps to switch between gas and vacuum
  • Tubing to connect apparatus to line


The dual manifold is the main body of the Schlenk line (Fig. 1). It has two parallel glass tubes; one connected to the inert gas supply and the other to the vacuum. Taps allow switching between the gas and the vacuum lines and a Schlenk line will generally have 4–6 taps to allow multiple reactions to be performed simultaneously.

Figure 1. Basic vacuum/inert gas manifold.


High Vacuum Line or Schlenk Line?

Schlenk lines are generally used for reactions performed in solution as they lend themselves well to cannula and counterflow techniques. Manipulations involving the measurement or condensation of gases are usually performed on a high vacuum line.

Schlenk lines differ from high vacuum lines by several small features. High vacuum lines, as the name implies, have better vacuum than Schlenk lines. This arises from use of a diffusion pump instead of or in addition to the mechanical pump generally used with a Schlenk line. Schlenk lines employ flexible rubber or plastic tubing to connect the apparatus to the line, while apparatus is connected to a high vacuum line via joints that provide a better seal and vacuum.


The Inert Gas Line

The gas manifold is attached to an inert gas supply and to the gas outlet by flexible rubber or plastic tubing (Fig. 2, A). The inert gas, usually nitrogen or argon, is fed directly to the manifold, or can be passed through a drying or deoxygenation column first. The supply comes from either cylinders of compressed gas, or in the case of N2, from the run off from the main in-house liquid nitrogen tank. As argon is more expensive than N2, nitrogen is usually the preferred gas unless the compound(s) under study react with nitrogen.

The gas exits the manifold through a mercury or oil bubbler (Fig. 2). The bubbler provides a pressure release system for the line and a visible means of monitoring the general flow of gas. The bubbler should vent to the back of the fumehood or close to wherever the fumehood exhaust is, especially if it is a mercury bubbler. Mercury bubblers give a slightly higher pressure of gas in the line due to the relative higher weight of mercury compared to oil. This can be useful when it comes to filling a vessel on the line with inert gas (see part 2) as it reduces the chances of contaminating the line with air. However, due to the toxic effects of mercury, these bubblers are becoming less common.

Figure 2. Complete Schlenk line set-up.



Vacuum Line and Cold Trap

The vacuum manifold is closed at one end (usually with a stopper) and attached to a pump at the other. Use of a removable stopper rather than a permanently sealed end allows access to inside of the line to facilitate its cleaning. In between the manifold and the pump there should be a cold trap (Fig 2). The trap prevents volatile or corrosive solvent vapors entering the pump and degrading the pump oil. This degradation can be harmful to pumps and shorten their lifespan, reduce their efficiency, or cause them to seize. Depending on the design of the line, the cold trap can be isolated from the vacuum line by a tap (Fig. 2, F) and opened to the external atmosphere by a tap between the trap and the pump (Fig. 2, G). This tap also allows the line to be repressurized to atmosphere once you are finished with the line.

The trap is submerged in a Dewar flask containing liquid nitrogen. The liquid nitrogen cools the trap and forces vapors and gases from the Schlenk line to condense. An alternative to liquid nitrogen is to use an acetone/dry ice combination in the trap. One trap is considered the minimum for standard Schlenk line operation. If you are intending to use the Schlenk line to evaporate solvent, two traps are recommended. Some lines have space for a second trap in series with the first, however, if the line you are using does not, a second trap can be included on the flexible tubing between the Schlenk flask and the Schlenk line. After use, the traps can be removed and the solvent allowed to thaw. The solvent can then be disposed of and the trap cleaned (see below for correct procedure for turning a Schlenk line off!).


Switching From Gas to Vacuum

On some dual manifold lines there are two taps per port or “workstation” to open the workstation to gas or vacuum. This allows individual control over the gas supply and vacuum for each line. These taps consist of a Young’s tap-type or Teflon tap that forms a seal.

Other Schlenk lines have ground-glass, two-way taps that control access to the gas and vacuum (Fig 2, B–E and Fig. 3). These taps prevent you from having both gas and vacuum lines open at the same time and feeding the inert gas straight into the vacuum pump. Ground-glass taps must be greased to ensure an air-tight seal and to make them easier to turn (see below).

Figure 3. Side view of vacuum/inert gas manifold and positions of two-way taps for a) vacuum; b) inert gas; c) off.


Connecting Glassware to the Schlenk Line

Glassware for use in air-sensitive chemistry is similar to standard glassware, but has an additional side arm with tap with which to connect it to the Schlenk line. Two- or three-necked round bottomed flasks can be attached via an adapter. Schlenk flasks have an integrated side arm and are available in a range of sizes.

Some of the common types of glassware used are shown in Fig. 4.

Figure 4. Common types of glassware employed in air-sensitive chemistry. The valve, tube, and ground-glass joint sizes may vary, allowing for multiple possible combinations.


The glassware is attached via flexible rubber or plastic tubing, commonly Tygon or Portex PVC tubing. The tubing needs walls at least 3 mm thick to prevent it from collapsing under vacuum. The tubes should be long enough to reach the bench or floor of the fumehood and have 3–4 cm left over. Any longer and the tubes become unwieldy and can knock pieces of glassware off the bench. If the tubing does not reach the bench or floor of the fumehood, it can be awkward to work with and may require glassware to be positioned in unusual or precarious positions in order to make the tubing reach.

The extra 3–4 cm can be useful if the line is used a lot: After a while, the constant attaching and removal of glassware to the tube will loosen the end of it and you will no longer get a good seal around the side arm. When this happens, you can cut 1–2 cm off the end without having to replace the entire length of tubing.


To connect the tubing to the glassware, gentle pressure should be applied to ease the tubing onto the connector. A wiggling or rocking motion should be used rather than a twisting motion. Wiggling the tubing provides sufficient, but not excessive force, while a twisting motion puts unnecessary force on the joint connecting the side-arm to the body of the flask. This can cause the glassware to break as you are attempting to attach the tubing which often results in you stabbing yourself in the hand with broken glassware. To help ease the tubing onto the connecting side-arm, the tubing can be heated gently with a heat gun to soften it. Alternatively, a small amount of silicon grease can be applied to the glass. Another method is to dip the end of the tubing in acetone for approximately 10 s. This will soften the tubing and allow it to stretch slightly as it is eased onto the connecting side-arm.

To remove the tubing from the glassware, it should be eased off by applying pressure with the thumb of the hand holding the glassware while the other hand rocks the tubing from side to side. Again, twisting the tubing risks broken glassware and injury so should be avoided. If the tubing is particularly stubborn and will not come off, use a sharp knife to slit the end of the tubing attached to the glassware or cut the tubing to free the glassware.


Greasing Joints and Taps

One difference between using air-sensitive techniques and air-stable chemistry is that all the ground-glass joints must be greased to ensure an air-tight seal and prevent contamination by O2, for example. In organic chemistry labs, it is often recommended to avoid greasing joints as the grease can enter the reaction mixture and contaminate the reaction and spectra. For similar reasons, joints should not be over-greased when doing air-sensitive chemistry. A fine layer of grease applied evenly is better than a thick layer that seeps out of the top and bottom of the joint. To get a thin layer, apply two stripes of grease, on opposite sides of the male joint of any glassware, insert into the neck or female joint and rotate the two parts gently to evenly distribute the grease (Fig. 5). There should be a clear, continuous film between the surfaces of the joint. Use the end of a spatula or wooden splint if you don’t want to get covered in grease.

Figure 5. How to apply an even layer of grease to a joint. 



Safety Considerations

Used correctly, Schlenk lines enable the use of otherwise dangerous reactants, but as with all chemistry, the use of Schlenk lines can pose some serious risks. The main risks are those of condensed gases, particularly liquid oxygen, explosion, and implosion.


Liquid Oxygen and Other Condensed Gases:

  • Liquid oxygen – If a constant stream of air is pulled through the vacuum line while the cold trap is in place, oxygen will condense in the cold trap. Liquid oxygen is very dangerous and reactions violently with organic substances including vacuum grease, Teflon tape, and any organic solvents that may be in the trap. Liquid oxygen also generates a lot of pressure as it vaporizes. In the confined space of a Schlenk line, this can cause an explosion.
    To avoid condensing liquid oxygen, never open the vacuum line to the air when the cold trap is in place. As a matter of good practice, air should not be sucked into the line at any point, but particularly when the cold trap is in place.

What to do if you condense liquid oxygen

Liquid oxygen is light blue in color. If you find a light blue liquid in your trap, remove the liquid nitrogen Dewar and vent the trap (for example, open tap G in Fig. 2). Close the fumehood door and leave the room. Inform your colleagues of what is happening and make sure they do not approach your fumehood. Wait 20–30 min then cautiously check to see if the liquid oxygen has evaporated. If it hasn't, leave the area, checking back periodically until all the liquid oxygen has evaporated and it is safe to resume work.  

  • Other condensed gases – Some gases, such as carbon monoxide and ethylene, are easily condensed in a liquid nitrogen-based cold trap. Once the liquid nitrogen is removed, either by choice or through evaporation, the condensed liquid will convert back to a gas with an accompanying increase in pressure. Without suitable pressure release, this build up can cause an explosion. 
    Ensure a suitable pressure release system, such as an oil or mercury bubbler is attached to the line and the trap is vented as soon as the liquid nitrogen Dewar is removed.
  • Liquid nitrogen – When handling liquid nitrogen for the cold trap, or the cold glassware of the cold trap, appropriate heat resistant gloves should be worn. Cold burns can hurt just as much as regular burns.

Common Causes of Explosion:

  • Use of pressurized gases – Explosion can occur if the inert gas pressure builds up in a closed system. Make sure there is a source of pressure relief in the form of a bubbler and that there is not a closed system when the gas line is open. An electronic pressure gauge or manometer can also be added to the line to monitor the pressure and provide extra peace of mind. 
  • Out of control reaction – A violent reaction can evolve a large volume of gas quickly. Again, ensure there is adequate pressure relief in the system, i.e., a bubbler, and that the reaction vessel is open to the line.
  • Heating a closed system – Increasing the temperature of a closed system (constant volume) increases the pressure. Make sure any vessel you heat is open to the line and there is pressure relief in the form of a bubbler attached to the line.

Common Cause of Implosion:

  • Cracks in glassware – Any weakness in the glassware, such as a star crack, can cause it to fail under vacuum. If you notice a crack in a vessel, do not use it. Many cracks can be repaired by a glassblower, so do not throw cracked glassware away without discussing it with your glassblower first. 



Getting Started

To avoid the potential dangers discussed above, Schlenk lines need to be started up and shut down in a specific order.


Turning a Schlenk Line On

It can take about 30 min to start and purge a Schlenk line before its first use, so make sure you allow yourself enough time. The following steps assume there is no gas flow through the system. If the gas is already on, skip steps 3–5.

Figure 6. Schlenk line before it is turned on.

  1. Check all taps are greased. If a tap feels dry or hard to turn, remove it and apply a light coat of suitable high vacuum grease to the tap, avoiding the holes which can become blocked with grease. Replace the tap and turn it several times to evenly distribute the grease. There should be a clear, continuous film between the surfaces.
  2. Check tap A is open and taps B–E and G are closed (Fig. 6).
  3. Open the gas supply. If you are using cylinders of compressed gas, check the cylinder has sufficient N2 or Ar before you begin and use standard cylinder safety and operating procedures.
  4. Adjust gas supply so that the exhaust bubbler has a flow rate of about one bubble per second. If there is no gas flow through the bubbler, turn off the gas supply, vent the manifold by opening tap G or one of taps B–E, and repeat steps 1–4.
  5. Purge the gas line for 20 min or more. Purge time can be reduced with a faster flow rate, but be careful not to increase the gas flow rate so that oil is blown out of the bubbler. Don’t forget to turn the flow rate down once the line is purged!
  6. While the gas line is purging, check the cold trap. Trap should be empty, clean, dry, and the connecting joint should be well greased.
    If it is not, empty the trap into the correct waste solvent container and rinse with acetone or other suitable cleaning solvent. Leave it to dry for several minutes or blow a stream of nitrogen or air into the trap to encourage solvent to evaporate. When it is dry, grease the joint at the top with suitable high vacuum grease. Re-attach the trap and rotate it once or twice to evenly distribute the grease across the joint and provide an air-tight seal. There should be a clear, continuous film between the surfaces. Clip trap in place – Do not rely on the vacuum to hold the trap in place.
  7. Place an empty Dewar flask under the trap so that the top of the flask is 1–2 cm below the bottom of the trap’s joint (Fig. 7).
  8. Check tap F is open and close tap G (Fig. 6).
  9. Turn on pump and allow it to warm up for 3–5 min.
  10. Fill the Dewar flask with liquid nitrogen.
  11. Cover the top of the flask with a towel, piece of cloth, or polystyrene block shaped to fit.
  12. You are now ready to begin work.

Figure 7. A) Correct position of Dewar flask and liquid nitrogen fill level for cold traps. B) Dewar flask and liquid nitrogen too high, which risks freezing the grease in the joint, breaking the seal and making the trap hard to remove. C) Dewar flask and liquid nitrogen too low, leading to incomplete condensation of gases and potential damage to pump.


Turning Off a Schlenk Line

  1. Make sure all vessels attached to the line are under nitrogen.
  2. Switch off pump and immediately remove the Dewar of liquid nitrogen.
  3. Vent the vacuum line by opening tap G (Fig. 6).
  4. Switch off gas. If someone else is going to use the Schlenk line after you, or if you are leaving a vessel open to nitrogen, only reduce the gas flow rate rather than turning it off completely.
  5. Remove cold trap carefully – Cold glassware can burn or get stuck to your skin.
  6. Allow the collected solvent to thaw. This can be done overnight if it is the end of the day. Dispose of the liquid solvent and clean the trap ready for next time.



Summary

Air-sensitive techniques and equipment can look daunting, but the usefulness of the Schlenk line cannot be denied. The two interconnected lines of the manifold provide a simple way to evacuate a flask and refill it with an inert atmosphere if the safety considerations are taken into account by performing the steps in the correct order.





Do you have any tip or tricks for handling air-sensitive compounds?Share them in the comments section ...


DOI: 10.1002/chemv.201300002

Article Views: 101041