Chemistry 2412LGrignard Reaction Pre-lab lecture

The Grignard Reaction

• The Grignard reaction is a very important reaction in organic synthesis used to make carbon-carbon bonds.

• It involves the reaction of an appropriate organic molecule with a organomagnesium halide, called the Grignard reagent.

The Grignard Reagent• Grignard reagents (RMgX) are formed from the reaction of an alkyl

halide and magnesium• The solvent is typically diethyl ether (“ether”, Et2O) or

tetrahydrofuran (THF)

• The reaction occurs on the metal surface, and is often difficult to start. You can help the reaction start by gently heating the flask, grinding the Mg against the inside of the flask with a glass stir rod.

• The reaction has started when the mixture becomes cloudy and generates enough heat to boil the solvent without additional heat being added.

R XMg

Et2OR Mg X

The Grignard Reagent• The Grignard reaction will not take place in the

presence of water. Water “kills” the Grignard reagent by reacting with the reagent:

• It is very important that the reaction apparatus, reagents, and solvents must all be kept dry. You will be using glassware from your organic lab kits for this experiment. It is a good idea to dry your glassware in the oven before starting the reaction. Also make sure to keep the reagent bottles capped.

R HR Mg X HO Mg XH2O

+

The Grignard Reaction

• Grignard reagents react with carbonyl compounds to form alcohols. The type of alcohol produced depends on the type of carbonyl reacted.

• In this experiment you will generate a tertiary alcohol from the reaction of a Grignard reagent with an ester. This process consists of two reactions:1. Formation of Grignard Reagent

2. Reaction of Grignard Reagent to form the alcohol

1. Formation of Grignard Reagent

• Bromobenzene reacts with Mg metal in ether to form phenylmagnesium bromide:

Br

Mg

Et2O

MgBr

2. Reaction of Grignard Reagent

• Methyl benzoate reacts with phenylmagnesium bromide (step 1), followed by aqueous acid work-up (step2), to form triphenylmethanol:

C1. 2

2. H3O+

MgBr

O

O

CH3

C OH

Procedure Notes• Pictures of the apparatus and reaction in progress

can be found at this site. It will be very helpful for you to look at these pictures before you begin this experiment.

• Week 1: – Preparation of Grignard reagent (reaction 1) and first

step of reaction 2– Once reaction 1 has started it should keep going on its

own. If the reaction slows you may need to add a little heat to continue the reflux.

– Be careful not to overheat the reaction. Remember ether boils at 35°C. Do not confuse the reaction starting with the ether boiling. You will see a cloudiness and change in color when the reaction has started.

– Use your time wisely. While one partner monitors reaction 1 the other should prepare the ester for reaction 2.

– Most of the Mg will dissolve during the reaction. Any remaining Mg will dissolve in the work-up (week 2).

– At the end of this week’s procedure, stopper and label the round-bottom flask and put in in the Rotovap hood.

Procedure Notes

• Week 2:– Finish reaction and isolate product– Make sure you keep all layers during the

extractions until you are certain you have recovered your product

– Petroleum ether is not the same thing as diethyl ether. Be careful you are using the correct solvent. Pet ether is used to remove a common by-product of this reaction: biphenyl. Think about how biphenyl was formed in this reaction.

– Analysis of product (yield, mp, IR)

Safety Notes

• Ether is highly flammable. There should be no flames in the laboratory during this experiment.

• Dispose of all waste as directed by your instructor. Do not pour anything down the drain.