Why anhydrous conditions

Gov't, Non-P. Research Support, U. Gov't, P. Molecular sieves should not be used for drying acetone, because they are basic and induce an aldol reaction in acetone. So one must be sure that it has fully evaporated before moving the beads to the high temperature oven. Note: in undergraduate laboratories solvents are sometimes dried using the drying agents listed in Table 2 in the section below.

This method is sufficient for reactions that are not very water sensitive but will not render sufficiently dry solvents to run sensitive reactions such as a Grignard reaction. Table 1. Reagents in a chemical reaction can be solid or liquid and in very rare cases gases.

Different methods are employed to dry solids than are used to dry liquids. Liquid reagents can generally be made anhydrous by similar methods as for solvents described above.

Reagents that are freshly purchased are often sufficiently anhydrous. Reagents need to be dried if they are not fresh or if they were synthesized as part of a multi-step synthesis. In a multi-step synthesis the product of one reaction step is the reagent for the next step. The product formation of many reactions requires a quenching step, which means contact with a large quantity of water. Afterward the product, whether it is solid or liquid, should be dried in order to ensure anhydrous conditions for the following step.

This is afforded first by extraction, a method by which the aqueous phase is separated from the organic phase thereby removing macroscopic amounts of water. After extraction the organic phase, which contains the product dissolved in an organic solvent, will still have microscopic traces of water present.

Following extraction the organic phase must be dried over a highly hygroscopic drying agent that is usually an inorganic salt. There are many different drying agents, and some of the most common ones are listed in Table 2. For drying purposes, the drying agent is added to the organic phase until freshly added drying agent no longer clumps together but rolls around freely and the solution is clear and not cloudy.

The organic phase should be covered and stored over the drying agent for a short period of time usually an hour to ensure drying. Afterward the drying agent is filtered off and the solvent is removed under reduced pressure in a rotary evaporator. For a product that is a liquid, further drying can be achieved by storing it over a drying agent and freshly distilling it before use. For a product that is solid, drying is achieved preferably by storage in a vacuum oven at a temperature below its melting point mp.

Water will still evaporate over time and applied vacuum will accelerate the process. Alternatively the solid may be dried by storage inside a vacuum desiccator over an appropriate drying agent typically P 2 O 5.

After drying, the anhydrous reagent should be stored in a bottle under inert atmosphere N 2 or Ar and the bottle's lid should be tightly sealed with Parafilm.

The bottle should be kept inside a desiccator until the reagent is needed. Note: some solid reagents, such as the magnesium metal for a Grignard reaction may be dried inside the apparatus during the flame-drying process. Liquid reagents can alternatively be dried by molecular sieves as described in the previous section for solvents.

This is indicated when large amounts of a reagent need to be dried. Typically reagents in small-scale syntheses are used in small amounts a few mL or less. Drying of such small amounts with molecular sieves is impractical and drying with the above methods should suffice. Table 2. The most commonly used drying agents in organic laboratories. Subscription Required. Please recommend JoVE to your librarian. 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. Chemical reactions that are moisture-sensitive must be carried out in an anhydrous, or water free, environment. Reagents and reactants can sometimes react with or absorb water from the atmosphere.

If this happens, the chemical or physical properties of the reagents can change, and the desired reaction will not take place or lead to a poor yield. To prevent undesired reactions with water from occurring sensitive reactions are carried out under an inert atmosphere, such as nitrogen or argon, using anhydrous reagents and equipment. Extremely water-sensitive reactions must be carried out inside a glovebox that can maintain an anhydrous environment.

This video will demonstrate how to properly dry glassware, solvents, and reagents in order to run an anhydrous reaction. The chemical makeup of glass causes a film of water to coat the surface that must be removed before preparing an anhydrous reaction.

Heat or acetone is often used to remove this layer from clean glassware before use. Many solvents also absorb water from the environment and must be dried before use. Solvent stills or desiccants are often used to remove water prior to setting up a reaction. Solvent stills use alkali metals such as sodium to react with water and leave a residual water content of around 10 parts per million. Desiccants are highly hygroscopic solids, meaning they readily absorb water. Certain desiccants, like sodium sulfate, are used to remove water from small amounts of an organic solvent and must be filtered out before further use.

Molecular sieves are the most commonly used desiccant and are used to dry larger volumes of solvents. They are made from a microporous material composed of sodium and calcium aluminosilicates.

Molecular sieves work by trapping water inside the beads effectively removing it from the solvent. Once used they can be regenerated in an oven. Finally, there are multiple ways to dry solid reagents. The heat drives water from the reagent leaving behind a dry compound. If the solid can't be heated or has too low of a melting point it can be dried in a vacuum desiccator. Once dry, the anhydrous reagent can be stored in a bottle under an inert atmosphere inside the desiccator.

Now that you've seen the concepts behind drying the equipment and reagents for anhydrous reactions, let's take a closer look and see how it's done in the laboratory. To dry glassware in an oven, first gather all the required components for the reaction apparatus.

Remove all pieces not made of glass such as the stopcock of a Schlenk flask. After 24 h, put on heat protection gloves and remove the glassware from the oven. Assemble the apparatus while the glassware is still hot.

When the glassware is fully assembled and cool, flush the apparatus with an inert gas such as nitrogen. Finally, add back any pieces that were removed prior to drying. The glassware is now ready for the anhydrous reaction. A faster option than oven drying glassware is to use a Bunsen burner. Certain glassware shouldn't be flame dried, so make sure the setup is safe to flame dry before starting.

To begin, set up the full apparatus and remove all components that are not made of glass. Put on heat resistant gloves, then light the Bunsen burner. Begin flame drying the glassware by heating the bottom of the apparatus.

Drive the water out of the setup by moving the flame upward. Continue this process until fogging and steaming stops. After drying, the molecular sieves may be stored for weeks before use. When they are needed, remove the beads from the drying oven or desiccator. Work fast and cover the container from this point onward to minimize contact of the beads with atmospheric water. Weigh out the necessary amount of active beads on a scale.

Add the beads to the solvent. For a volatile solvent, such as dichloromethane, leave the lid on top of the bottle but wait a few minutes before fully screwing the lid on to avoid pressure build-up. Seal the area around the lid by wrapping it with Parafilm to keep moisture out. Store the solvent with the beads for at least 24 h. Afterward, the anhydrous solvent can be used in a reaction. Solid reagents are often dissolved in organic solvents.

Before removing the liquid and recovering the solid reagent excess water must be removed from the solution. Obtain a dry container and add the solution. Next, add a drying agent to the container using a spatula. The drying agent will initially clump together, but continue adding until freshly added drying agent no longer clumps and moves freely. Cover the container with a stopper or aluminum foil and allow the solution to sit for at least 1 h.

Avoid transferring the drying agent, as the filter may clog. When most of the liquid has been transferred onto the funnel and drained into the flask below, add the remainder with the drying agent and allow it to sit for a few minutes.

Turn off the vacuum and transfer the filtered solution into a dry round bottom flask. Connect the round-bottom flask to a rotary evaporator and remove all solvent under reduced pressure. The solid or liquid that remains should now be dry.

To dry an already solid reagent place the compound in an open container and determine its weight. Then place it into a drying oven set to a temperature below the melting point of the solid. Allow the reagent to dry for several hours inside the oven. Remove the container from the oven and place it into a desiccator.

Then, allow the sample to cool to room temperature. Reweigh and ensure that the mass is less than before oven drying. Repeat the drying steps until the weight no longer changes. When this happens the reagent is sufficiently dry. Enzyme activity and dynamics in near-anhydrous conditions. Nat Prec Download citation. Received : 21 October Accepted : 28 October Published : 28 October Anyone you share the following link with will be able to read this content:.

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