Grignard Reaction Mechanism

Grignard reaction mechanism explains the addition of alkyl/vinyl/aryl magnesium halides to any carbonyl group in an aldehyde/ketone. The reaction is considered an important tool to form carbon-carbon bonds. These alkyl, vinyl or aryl magnesium halides are referred to as Grignard reagents. The Grignard reactions and reagents are named after their discoverer - French scientist Francois Auguste Victor Grignard, who was awarded the Nobel Prize in Chemistry in 1912 for this discovery.

Grignard reagents are strong nucleophiles and can form carbon-carbon bonds, making them somewhat similar to organolithium reagents. When an amido group substituent is used instead of the alkyl substituent (amido magnesium halides are called Hauser Bases), the nucleophilicity of the reagent further increases.

Preparation of Grignard Reagents

Magnesium can be reacted with alkyl halides or aryl halides to form Grignard reagents. The organic halide is added to a magnesium suspension in an ether solvent. It is important to note that the Reagent can be made with alkyl chlorides, bromides, and iodides but not with fluorides. Magnesium has 2 electrons in the valence shell, therefore only one equivalent of magnesium is enough to balance the equation as shown below.

The solvent used here is called diethyl ether. Tetrahydrofuran is another popular choice of solvent for the synthesis of Grignard reagents.

Reaction Contributors

It can be noted that the reactions between metallic magnesium and organic halides are NOT Grignard reactions. However, they yield Grignard reagents. The various factors that affect these reactions are listed below.

  • The synthesis of the Grignard reagent occurs on the surface of the magnesium metal. Therefore, breaking up the magnesium into smaller chunks can increase the effective surface area and accelerate the speed of the reaction.

  • The formation of magnesium oxide on the surface of the magnesium metal can also hinder the reaction as it is quite unreactive with alkyl halides. The breaking up of the magnesium metal also exposes fresh, unoxidized magnesium to the reaction.

  • The complete dryness of the solvent and apparatus will also help the reaction as water is quite harmful to Grignard reagents.

Grignard Reaction Mechanism

The synthesized Grignard reagent is highly nucleophilic as discussed earlier. This reagent attacks the electrophilic carbon in the polar bond of the carbonyl group. The mechanism of this Grignard reaction proceeds through a six-membered ring transition state, as shown below:

Other reactions of Grignard reagents may proceed through a single electron transfer process. Some of these processes involve the formation of a carbon-phosphorus bond, carbon-silicon bond, and carbon-boron bond.

Important Reactions of Grignard Reagents

Grignard reagents have many applications in organic and organometallic chemistry. Some of the important reactions of these reagents are listed below.

  • Epoxides (compounds containing a three-membered ring consisting of two carbon atoms and one oxygen atom) can react with Grignard reagents, resulting in the formation of a new carbon-carbon bond. The nucleophilic attack takes place at the least substituted carbon of the epoxide.

  • The carbonyl carbons of aldehydes and ketones are electrophilic in nature. In their Grignard reactions, the carbon-oxygen pi bond is cleaved and a new C-C bond is formed, resulting in the formation of an alkoxide. These alkoxides can be subjected to an acidic workup to yield alcohols.

  • The reaction between a Grignard reagent and an ester proceeds in a manner similar to the Grignard reactions of aldehydes or ketones. The carbon-oxygen double bond is broken and a new carbon-carbon bond is formed. Alcohols are formed from the acidic workup of the resulting alkoxides.