Grignard Reaction

A Grignard reagent is an alkyl-magnesium halide complex that is extremely nucleophilic and basic. It is often used to make carbon-carbon bonds through addition or substitution reactions. They are also known as organomagnesium halides.



Structure of a Grignard:

Generic-Grignard-R-MgX

Generic Grignard R-MgX

The Grignard reagent’s structure is an alkyl anion with a magnesium halide complex. The two most common ways to draw it are shown above; the first way shows a bond between the alkyl group (shown as “R”) and the magnesium, and the second way shows two ions. Notice that in the ionic representation the positive charge is on the whole magnesium halide complex. The usual halide used is Br to create MgBr, but MgCl and MgI complexes are also used. 

Preparation:

Preparing a Grignard reagent is actually very simple! All that needs to be done is to add elemental magnesium to an alkyl halide in an aprotic solvent like diethyl ether or THF. Let’s prepare ethylmagnesium bromide real quick:

Preparation-of-GrignardPreparation of Grignard


Reactions:

Given that the Grignard has a negatively charged carbon, it can act as an extremely powerful nucleophile and base. Let’s explore some examples of reactions Grignards undergo using ethylmagensium bromide as our nucleophile. Keep in mind that these reactions usually take place in a dry ether solvent and are then “quenched” with water.

Acid-base:

Grignard-as-base

Grignard as base

Here we have the Grignard deprotonating water. It will primarily acts as a base over a nucleophile if given the opportunity. I’ve drawn both versions of the Grignard reagent, but they’re totally equivalent. 

Epoxides:

Grignard-and-epoxideGrignard and epoxide

When reacting with epoxides (aka oxiranes), Grignard reagents attack the less-substituted side. This is no different from any other anionic nucleophile; they tend to attack the side that isn’t as sterically hindered. This particular reaction created a secondary alcohol.

Nucleophilic addition:

Nucleophilic-additionNucleophilic addition

Grignard reagents will react with aldehydes and ketones at the electrophilic carbonyl carbon in a reaction called nucleophilic addition. Reactions with an aldehyde produce a secondary alcohol, and reactions with a ketone produce a tertiary alcohol.

Nucleophilic acyl substitution:

Grignards can also participate as nucleophiles in nucleophilic acyl substitution reactions. Let’s see how that works with a carboxylic acid:

How-to-ruin-your-GrignardHow to ruin your Grignard

Reacting a Grignard directly with a carboxylic acid will only result in a ruined Grignard! It’ll react with that acidic hydroxyl group instead of the carbonyl carbon. So, how can we get it to react at the carbonyl? We have to swap that hydroxyl group with an aprotic group like a chlorine or alkoxy group.

Nucleophilic-acyl-substitutionNucleophilic acyl substitution

Using thionyl chloride, we can convert the carboxylic acid into an acyl chloride (acid chloride). The Grignard can then react with the carbonyl carbon without an issue. Since the first substitution creates a ketone, the Grignard will attack again to produce a tertiary alcohol.

Carbonation:

Last one! Reacting a Grignard with carbon dioxide (CO2) is a great way to produce a carboxylate, which can then be protonated to form a carboxylic acid. Let’s check out the mechanism:


Carbonation-of-GrignardCarbonation of Grignard

So that’s it for reactions of Grignards! To see how the other organometallics (including organolithiums and Gilman reagents) react, check out my videos here. Good luck studying!