CHEM 2122 / Organic Synthesis 2 - Grignard Reaction

• Why do conditions need to be carefully selected when using a Grignard reagent?

• What happens when a Grignard reagent comes into contact with water?

• How do we prevent quenching in organometallic reactions?

• The nucleophilic and basic nature of the Grignard reagent makes it very reactive, so conditions need to be selectively chosen to not hinder its reactivity.

• Many organometallic reactions are moisture sensitive, meaning the presence of water will destroy the organometallic reagent, a process known as quenching.

• When performing organometallic reactions, we typically use dry solvents and reagents.

How are dry solvents and reagents prepared for organometallic reactions?

Dry solvents and reagents are subjected to various chemicals and procedures to ensure all traces of water are removed.

• Why can some reactions be hazardous when exposed to water?

• How do we ensure glassware is dry for moisture-sensitive reactions?

• Some reactions are extremely exothermic if exposed to water and therefore can be a severe hazard.

• In handling moisture sensitive reactions, we will also need to ensure the glassware used is also free from water, which typically involves storing the glassware in the oven.

How do you perform the synthesis part of this experiment to kick the reaction off?

• From the drying oven, collect a 50mL distillation flask, condenser tube, drying tube, Claisen head, and dropping funnel and allow the glassware to cool.

• Collect a mortar and pestle from the front of the lab. Crush 0.5g of Mg turnings and then add into a 50mL distillation flask charged with a dry magnetic stir bar.

• Assemble the Claisen head, condenser tube, drying tube, and separatory funnel.

• Ensure that the water in the condenser is running (water in from the bottom and out from the top). Carefully check that there’s no water leaking out of the tubing because even a very minor leak, over an hour, will be detrimental to the reaction.

• When collecting the anhydrous (anh) diethyl ether, minimize exposure to air since it’ll absorb moisture from the environment. On that note, stopper the liquid you’re transporting. Keep and work with the ether in the fume hood. When the dispenser is not in use, turn the nozzle off.

• Add 5mL anh diethyl ether to the magnesium turnings through the separatory funnel. keep the stopcock closed following the addition.

• Add 3.0mL bromobenzene using a graduated pipette, and add 5mL anh diethyl ether into the closed separatory funnel. Ensure solution is mixed.

• Add about 0.5mL of bromobenzene (5 drops-ish) to the Mg turnings. Watch to see if reaction occurring.

if the reaction doesn’t occur, what do you do?

• Warm the mixture gently.

• Add some additional freshly crushed Mg turnings.

• Add a pinch of iodine.

How do you perform the synthesis part of this experiment once the reaction begins?

• Once the reaction commences, gently reflux the reaction mixture by heating it to the boiling point of the solvent for a sustained period. The purpose of the condenser is to condense the solvent vapours so that after a period of heating there is a minimal amount of solvent lost.

• Add the remaining bromobenzene-diethyl ether solution dropwise to the stirred reaction mixture while reflux is maintained.

• The Grignard reaction is exothermic so if the boiling becomes too vigorous, stop the halide addition and/or remove the reaction flask from the heat source. Upon full addition of the bromobenzene solution, continue to reflux for an additional 20 minutes.

• The reaction is complete when all the magnesium has been consumed. When the reaction is complete, allow the reaction mixture to cool to room temperature.

• Weigh about 10g of dry ice into a 125mL or 250mL Erlenmeyer. Do not let the dry ice sit in open air for any length of time since water will start to condense on its surface and quench the Grignard reagent.

• Slowly pour the Grignard reagent solution on the dry ice while vigorously swirling. Do not get any remaining Mg turnings into Erlenmeyer. Rinse the distillation flask with 2mL diethyl ether and add the rinsing to the Erlenmeyer flask.

How do you perform the workup and recrystallization?

• Add a certain amount of HCl and an additional 10% to Erlenmeyer.

• Heat the resulting solution to boiling on the hotplate in the fume hood. The diethyl ether will also boil off during this step.

• The newly formed benzoic acid should be fully soluble in hot water.

• Cool to room temp and then in an ice bath. Isolate the crystals by vacuum filtration and place in a sample vial and save for next week.

• Wash glassware and return distillation flask, condenser tube, drying tube, Claisen head, and dropping funnel (remove stopcock) to the drying oven. Clean the mortar and pestle with soap and water and a final rinse with acetone before returning to the front of the room.

• Any remaining bromobenzene should be disposed of in halogenated waste.