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.
What is Grignard Reagent?
A grignard reagent is an extremely strong nucleophile and can behave like carbonyl compounds with electrophiles.
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.
A grignard reagent is an extremely powerful nucleophile and can react with electrophiles like carbonyl compounds. To determine the products made in a grignard reaction, the magnesium halide portion of the reagent and the grignard reagent act as a carbanion.
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.
In a rate controlling step, the grignard reagent coordinates with the ketone on the simultaneous displacement of an ether molecule of solvation. This is followed by a rapid reaction with a second monomeric Grignard reagent to form alcohol via a six membered transition state. It has been proposed that the reaction can proceed with RMgX, RMg or both of these organometallic compounds.
Important Reactions of Grignard Reagents
Grignard reagents have many applications in organic and organometallic chemistry. Some 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.
To conclude, the reaction of magnesium with alkyl or aryl halides gives the Grignard reagent as a product, which is quite useful in the synthesis of alcohols, aldehydes or ketones. The Grignard reaction can also facilitate the formation of carbon-carbon bonds.
Frequently Asked Questions – FAQs
Are Grignard reactions reversible?
The Grignard addition reaction is considered to be a reversible method with allylic reagents but the reversibility with other alkyl magnesium halides has not been demonstrated so far. It has been developed, by using crossover experiments, that the benzyl addition reaction is also a reversible transformation.
Why is mg used in Grignard reagent?
The reaction to forming Grignard reagents typically involves the use of the magnesium ribbon. All magnesium is coated with a passivating magnesium oxide layer, which inhibits the organic halide reactions. Addition of Grignard preformed reagent is often used as initiator.
Why are Grignard reagents so reactive?
Grignard reagents are commonly prepared in a nitrogen atmosphere by reaction of an organohalogen with magnesium, because the reagent is highly reactive to oxygen and moisture. Organohalogens differ significantly in their magnesium reaction levels. Grignard reagents are solid bases and powerful nucleophiles.
What is a Grignard reagent given its general formula?
A Grignard reagent has an RMgX formula, where X is a halogen, and R is a group of alkyl or aryl (based on a benzene ring). We will take R for the alkyl group for the purposes of this article.
Can Grignard reagents react with alcohol?
When there are alcohols on a carbon chain, the Grignard reagent will react to the alcohol with the hydrogen before it reacts with the carbonyl carbon. The same occurs when adding water to the reaction before the Grignard reagent has reacted with the aldehyde / ketone.
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