Ch. 13 - Alcohols and Carbonyl CompoundsWorksheetSee all chapters
All Chapters
Ch. 1 - A Review of General Chemistry
Ch. 2 - Molecular Representations
Ch. 3 - Acids and Bases
Ch. 4 - Alkanes and Cycloalkanes
Ch. 5 - Chirality
Ch. 6 - Thermodynamics and Kinetics
Ch. 7 - Substitution Reactions
Ch. 8 - Elimination Reactions
Ch. 9 - Alkenes and Alkynes
Ch. 10 - Addition Reactions
Ch. 11 - Radical Reactions
Ch. 12 - Alcohols, Ethers, Epoxides and Thiols
Ch. 13 - Alcohols and Carbonyl Compounds
Ch. 14 - Synthetic Techniques
Ch. 15 - Analytical Techniques: IR, NMR, Mass Spect
Ch. 16 - Conjugated Systems
Ch. 17 - Aromaticity
Ch. 18 - Reactions of Aromatics: EAS and Beyond
Ch. 19 - Aldehydes and Ketones: Nucleophilic Addition
Ch. 20 - Carboxylic Acid Derivatives: NAS
Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon
Ch. 22 - Condensation Chemistry
Ch. 23 - Amines
Ch. 24 - Carbohydrates
Ch. 25 - Phenols
Ch. 26 - Amino Acids, Peptides, and Proteins
Johnny Betancourt

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.

1. Acid-base:

Grignard as baseGrignard as base

Here we have the Grignard deprotonating water. It will primarily acts as a base over a nucleophile if given the opportunity. This is why we can't use water or other protic solvents for Grignard reactions! I’ve drawn both versions of the Grignard reagent, but they’re totally equivalent. 

2. 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.

3. 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.

4. 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.

5. 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!



Johnny Betancourt

Johnny got his start tutoring Organic in 2006 when he was a Teaching Assistant. He graduated in Chemistry from FIU and finished up his UF Doctor of Pharmacy last year. He now enjoys helping thousands of students crush mechanisms, while moonlighting as a clinical pharmacist on weekends.