Preparing Anhydrous Reagents and Equipment

Drying of Glassware

1. Oven-Drying

1. Remove all pieces that are not made of glass, such as the stopcock of an addition funnel.
2. Place all glassware that are part of the apparatus in a drying-oven set to about 125 °C for at least 24 h before use.
3. Put on heat protection gloves and remove glassware from the oven. Be very careful when handling hot glass while assembling the apparatus.
4. For best results flush the apparatus with an inert gas such as N₂ while assembling the apparatus.

2. Flame-Drying

1. Set up the full apparatus but remove all components that are not made of glass (such as stopcocks of dropping funnels or rubber sleeves etc.). Do not attach any tubing to the apparatus at this point.
2. Put on heat-protection gloves.
3. Set up a Bunsen burner and carefully flame-dry the apparatus. Start from the bottom and move the flame upward, "accompanying" the water on its way out. Steam will develop and fog up the glassware. Continue flame-drying until fogging stops.
4. Wait for the apparatus to cool down to about 60 °C. This takes a couple of minutes and the glass will still be warm to the touch but won't cause burns if contact is short.
5. Carefully add the rest of the apparatus that is not made of glass, such as tubing and stopcocks. Do not remove heat-protection gloves when handling the apparatus to avoid burns.
6. After everything is properly assembled, flush the apparatus with an inert gas such as N₂to accelerate cooling of the glassware to a point where the reagents may be added.

Note: During the flame-drying process never have any solvent or the magnetic stir-bar inside the flask nor any of the reagents unless specifically demanded by the procedure. (However, when performing the Grignard reaction it is okay to leave the magnesium shavings in the flask during flame-drying).

3. Drying with Acetone

1. Rinse glassware with acetone.
2. Collect the acetone rinsings in a designated solvent waste container.
3. Flush the glassware with N₂ gas or dry compressed air to accelerate drying.

Drying of Solvents

1. Drying with Active Sodium Metal

1. Carefully cut sodium metal under petroleum ether to minimize the risk of ignition as the metal reacts with air. The metal surface oxidizes quickly giving a white residue. Cut the metal into thin slices exposing as much metallic surface area as possible.
2. Under N₂ gas add the metal shavings to a distillation flask containing solvent.
3. Next add benzophenone, an indicator that is used to monitor the reaction. In the presence of water the solution is clear or yellow, but when the solvent is dry the solution is blue or purple.
4. Reflux the solution using a heating mantle until a change of coloration to blue/purple is observed.
5. Distill the solvent, collect it in a dry flask, and use in a reaction immediately after cooling down.
   Waste Disposal: After the drying process it is important to safely dispose of any remaining sodium in the distillation flask.
6. For this, carefully add ethanol to the sodium until hydrogen evolution has ceased.
7. Stir the solution carefully, but well, and make sure that no sodium lumps remain that might have active sodium metal trapped inside.
8. Carefully add methanol to the mixture and leave the mixture in the back of the hood for several hours to make sure the sodium is completely consumed.
9. Finally, add the mixture very carefully to a large excess of water and dispose of the mixture in an appropriate waste disposal container.

2. Drying over Molecular Sieves

1. Open a bottle containing molecular sieves and fill them into a thermo-stable glass beaker. Dry more than needed for the current experiment for future use.
2. For activation place the beaker with the beads in a high temperature oven and store for 3–3.5 h at a temperature of 300–350 °C. Alternatively, if available, store for in a vacuum oven at 200 °C for the same amount of time.
3. Using high heat-resistant gloves remove the beaker with the beads and place it in a conventional drying oven at temperatures above 120 °C. Alternatively store the beaker with the beads inside of a desiccator. The beads may be stored for weeks before use.
4. Remove the beaker with the beads from the drying oven or the desiccator. Work fast from this point onward to minimize contact of the beads with atmospheric water.
5. If removing the beads from an oven allow them to cool down to about room temperature. Cover the beaker with a dry towel to minimize air exposure during this cooling time.
6. To test whether the beads are still active, put on disposable gloves and place a small amount of beads in your hand. Add about 2 volume equivalents of water. If the beads become very hot then it means they are activated.
7. Weigh off the needed amount of active beads on a scale. For example, to achieve a 10% m/v of beads in a 500-mL bottle of solvent, 50 g of beads are required.
8. Add the room-temperature beads to a freshly opened bottle of solvent. Be certain that the beads are cooled, especially if the solvent is volatile. Never add the beads to a solvent directly after removing them from the oven.
9. For a volatile solvent, such as DCM, leave the lid on top of the bottle but wait a few minutes before fully screwing the lid on the bottle to avoid pressure build-up.
10. Seal the area around the lid by wrapping it with Parafilm to keep moisture out.
11. Store the solvent over the beads for the appropriate amount of time, for example 24 h.

Drying of Reagents

1. Drying of the Organic Phase after Extraction

1. Upon separation of the phases in a separatory funnel, transfer the organic phase into a dry glass container, such as a beaker or Erlenmeyer flask (or a test tube for small scales).
2. Add a drying agent from Table 2 (usually NaSO₄or MgSO₄) to the organic phase using a spatula. Initially the drying agent clumps together.
3. Continue the addition until freshly added drying agent does not clump together and rolls about freely. Moreover, the solution should be clear and not cloudy.
4. If available, cover the glass container with a stopper, otherwise with some aluminum foil.
5. Allow the solution to stand for about 1 h over the drying agent. It is okay to allow it to stand for longer periods of time, for example over-night.
6. Assemble a vacuum-filtration apparatus with Büchner funnel and side-arm flask.
7. Add a filter paper to the Büchner funnel and turn on the vacuum.
8. Slowly decant off the organic phase into the Büchner funnel. Initially, try not to transfer any of the drying agent or the filter will clog.
9. When most of the liquid has been transferred onto the funnel and drained into the flask below, add the remainder of the organic phase together with the drying agent and allow to stand for a few minutes.
10. Turn off the vacuum and transfer the organic phase into a dry round bottom flask.
11. Connect the round-bottom flask to a rotary evaporator and remove all solvent under reduced pressure.
12. If the product is a liquid, store it over a drying agent and freshly distill it before use.

2. Drying of Solid Reagents

1. Place the solid reagent inside an open glass container and determine the combined weight.
2. Place the container with the reagent into a drying oven set to a temperature below the melting point of the solid. When available, use a vacuum oven. Use heat protection gloves if necessary.
3. Allow the reagent to dry for several hours inside the oven.
4. Remove the container with the reagent from the oven.
5. Allow the sample to cool to room temperature, ideally inside of a desiccator.
6. Determine the weight and ensure that it is lower than before drying. If necessary repeat steps 2.2 – 2.5.
7. Once the reagent is cooled to room temperature it is ready for use.
8. If the reagent does not need to be used immediately, flush the container with an inert gas, such as N₂ and seal it tightly with a lid and place Parafilm around the lid.
9. Place the container inside a desiccator and store it there until the reagent is needed.

3. Drying of Heat-Sensitive Solid Reagents

1. Prepare a desiccator by placing fresh anhydrous drying agent in the lower compartment (typically P₂O₅).
2. Place the solid reagent inside an open glass container and determine its weight.
3. Place the container with the reagent it inside a desiccator.
4. Close the lid of the desiccator, sliding it on horizontally from the side to ensure proper sealing.
5. Apply a vacuum to the desiccator using the stopcock connection.
6. After a few minutes close the stopcock and turn off the vacuum.
7. Allow the reagent to dry inside the desiccator for at least a few hours.
8. Open the stopcock on the desiccator and allow air to flow in.
9. Carefully slide off the lid of the desiccator horizontally. Do not attempt to pull the lid off vertically.
10. Remove the reagent from the desiccator and weigh it. It should have a lower weight than before it was dried.
11. If necessary repeat steps 3.3 – 3.10 until the weight remains stable and the reagent is fully dry.
12. If the reagent does not need to be used immediately, flush the container with an inert gas such as N₂ and seal it tightly with a lid and place Parafilm around the lid.
13. Place the container inside a desiccator and store it there until the reagent is needed.