Experiment 8. The Grignard Reaction. Preparation of Benzoic Acid

References: Ege, Chapter 13

Background

Grignard reagents are prepared (eq. 1) from alkyl halides by treatment with magnesium metal in the form of turnings in the presence of dry ether. The reaction proceeds satisfactorily only if the reagent and the apparatus are scrupulously dry.

The alkyl magnesium halide is soluble in the ether solution and is used in this medium. The solubility results from the solvation of the organometallic compound by the ether. Hydrocarbon solvents are not useful in the preparation of Grignard agents because they cannot solvate the product.

If the solvent is "wet" (i.e. contains traces of water), the Grignard reagent is destroyed as fast as it is formed.

Besides reacting with H₂O, Grignard reagents also react with (and are decomposed by) carboxylic acids, alcohols, amines, ammonium salts and other compounds which are slightly acidic. Grignard reagents will also react with O₂ and CO₂ and if a very high yield of product is desired it is preferable to carry out the reaction in a nitrogen atmosphere. In the present experiment, the oxygen-free atmosphere is obtained by keeping the ether solution warm during the preparation of the reagent. Ether is sufficiently volatile that a blanket of ether vapour above the solution keeps the reagent reasonably well insulated from contact with air. Organometals such as Grignard reagents and the organolithiums are very widely used reagents in organic synthesis. This experiment illustrates the method used to prepare a Grignard reagent as well as its reaction with carbon dioxide to form a carboxylic acid.

Preparation of Benzoic Acid

In this experiment the Grignard reaction will be illustrated through the preparation of benzoic acid formed in reaction of phenyl magnesium bromide with carbon dioxide (eq. 2). Carbon dioxide, in the form of solid CO₂, will be provided but the phenyl magnesium bromide will be prepared from bromobenzene according to eq. 1, (R = C₆H₅), and then quenching with CO₂ and isolation of the benzoic acid from the acidified reaction mixture (as shown in equations (2) and (3) below).

Procedure

CAUTION: Ether is very flammable. Do NOT use ether if there is a flame in the laboratory.

1. Preparation of Phenyl Magnesium Bromide

Set up a reflux apparatus using a 100 mL flask and a condenser fitted with a calcium chloride drying tube. Make sure that the flask and condenser are DRY before you assemble your apparatus. Add your 1" magnetic stir bar, and then 0.25 g Mg turnings to the flask, reassemble the apparatus. Without cooling water in the condenser, heat the flask in a heating mantle by rotating it gently. When the flask cools, dry air will be sucked into the apparatus through the drying tube while the heating should have removed any film of moisture on the surface of the magnesium or the flask. Before proceeding with the next step, attach your condenser to the cooling water.

Note: make sure the cold water inlet to your condenser is tight and that no droplets of water get into the round bottom flask joint. Avoid turning the water flow rate on too high!

Prepare a communal ice bath for the bench-row in case any of the reactions to be carried out become too vigorous. Remove the flask from the condenser, add 5 mL of absolute dry ether to the flask (there are two types of ether on the bench, one is a specially prepared dry or "absolute" ether, the other is ordinary ether to be used for extraction), and 1.35 mL (2.0 g) of bromobenzene, swirl the flask to mix the ether and bromobenzene and reassemble the apparatus and set the magnetic stirrer operating. If you have followed directions carefully (i.e., everything was clean and dry) the reaction should begin immediately or after slight warming with your hands placed against the bottom of the flask (the stirring action of the magnetic stirrer also helps). You will recognize that the reaction has begun by the appearance of a cloudiness in the ether and eventual boiling of the ether.

If the reaction does not start, the following steps should be carried out:

1. Using a dry stirring rod, crush a piece if magnesium firmly against the bottom of the flask (take care not to break the flask!). The reaction should begin, if not try 2.
2. Warm the flask gently on a heating mantle, with swirling. Remove the heat and see if boiling continues. If not try 1 again. If still no reaction, go to 3.
3. Add a very small crystal of iodine. If still no reaction, warm gently or add a couple of drops of 1,2-dibromoethane. If there is still no action, go to 4.
4. Tough Luck: try again but this time dry everything. [If you use a water, acetone sequence to dry your flask, make sure you do a final rinse with 5 - 10 mL of ether to remove the last traces of acetone. Acetone undergoes a pinacol reduction with Mg and this appears to inactivate the Mg surface to organometallic formation.]

As soon as you are sure that the reaction is proceeding satisfactorily, add an additional 6 mL of absolute ether through the top of the condenser. The reaction mixture should continue to boil but if it should become sluggish apply gentle heat with a heating mantle until all but the tiniest flakes of the magnesium has disappeared (periodically stop the stirrer to check how much Mg remains; this may take up to 30 min.). If at any point during the process you appear to be losing ether from your reaction mixture, add a few more mL of ether through the top of the condenser via a dropping pipette, to keep the volume about 10-12 mL. You have now prepared a solution of phenyl magnesium bromide in ether and it should be used immediately in the next step.

2. Reaction of Phenyl Magnesium Bromide ("phenyl Grignard") with Carbon Dioxide

Just before you are ready to use it, place finely divided (crushed) solid carbon dioxide (7 g) in a beaker. With vigorous stirring, slowly add the prepared solution of the Grignard reagent. Stir until the mixture bcomes thick and sticky. When the solid carbon dioxide has all gone, slowly add a mixture of water (15 mL), ice (15 g) and concentrated hydrochloric acid (2.0 mL). Mix thoroughly. Add the mixture to a separating funnel. Extract the aqueous phase  with two portions of ether (15 mL each). Combine the ether layers and extract them with three portions (7-8 mL each) of 1.0 M or 5% NaOH (whichever is available). Combine the NaOH extracts and acidify with concentrated hydrochloric acid to pH 2 (Congo Red paper). Make sure the reaction mixture is reasonably cool as benzoic acid has appreciable solubility in warm water.

[IF NO precipitate forms, then likely some ether is present on the surface of your benzoic acid solution. Gently blow off the ether on the acidified solution until crystals appear. Continue to cool in ice bath until precipitation is complete.]

Collect the precipitate by vacuum filtration. Dry the product as thoroughly as possible, weigh it, and recrystallize it from hot water. (The ether layer contains neutral non-polar compounds such as unreacted bromobenzene and biphenyl. It should be discarded into the ORGANIC WASTE bottle.) Calculate the yield of benzoic acid. Take a sample of the recrystallized material and determine its melting point. (Place the remainder of your benzoic acid in the jar provided.)

[Note: at the end of the day, discard the CaCl₂ in your drying tube into the "Inorganic Solid Waste". If you don't, after a few days you will be left with a "brick-like" mass of CaCl₂.2H₂O which is very tedious to remove.]

Questions to answer before coming to the lab

1. Write a mechanism for the reaction of phenylmagnesium bromide with carbon dioxide.

2. Why must the solid carbon dioxide be prepared just before you add the solution of the Grignard reagent?

3. What is the molar ratio of CO₂ to Grignard reagent used in this experiment?  Why do you use an excess of CO₂?

28nov97; wjl