Grignard Reagents: What They Make and What Destroys Them

What it is

An alkyl or aryl magnesium halide, made by reacting the halide with magnesium in dry ether. The carbon–magnesium bond is strongly polarised toward carbon, so the carbon behaves as a nucleophile — effectively a carbanion, which is the reverse of its usual electrophilic character in the parent halide.

That polarity reversal is the whole point. It lets a carbon atom attack another carbon, which is how new carbon skeletons get built.

The products, by what it attacks

The first three rows are the pattern most questions rely on: the class of alcohol produced tells you which carbonyl was used, and vice versa. Working backwards from a target alcohol to the required carbonyl and Grignard is a standard synthesis question.

What destroys a Grignard reagent

Being effectively a carbanion, it is a very strong base. Any acidic hydrogen protonates it instantly, converting it to the parent hydrocarbon and wasting the reagent.

That rules out water, alcohols, carboxylic acids, terminal alkynes, amines and thiols — anything with O–H, N–H or S–H. It is why the ether solvent must be scrupulously dry, and why apparatus is dried before use.

The consequence for synthesis questions

A substrate containing both a carbonyl and a hydroxyl cannot simply be treated with a Grignard reagent — the hydroxyl destroys it before it reaches the carbonyl. The correct answer protects the hydroxyl first, performs the addition, then deprotects. Spotting the incompatibility is usually worth more than the mechanism itself.

Why ether

Ether is not merely an inert solvent. Its oxygen lone pairs coordinate to magnesium, stabilising the reagent and keeping it in solution. Tetrahydrofuran works similarly and is often better for less reactive halides. A hydrocarbon solvent alone does not sustain the reagent, and explaining why is a good short question.

Limitations worth stating

• Aryl and vinyl halides form Grignards less readily than alkyl halides.
• Substrates with reducible or acidic groups elsewhere need protection.
• Sterically hindered ketones can give reduction or enolisation instead of addition.
• The reagent cannot be made in the presence of the carbonyl it is meant to attack, since it would react as it forms.

Frequently asked questions

Why must the apparatus be completely dry?

Water protonates the reagent immediately, giving the alkane and magnesium hydroxide halide. Even trace moisture destroys a proportional amount, which is why yields collapse with wet glassware.

How does a Grignard differ from an organolithium reagent?

Organolithiums are more reactive and more basic. That makes them useful where a Grignard is too sluggish, but also means they are less tolerant of other functional groups.

What happens with an epoxide?

The Grignard attacks the less hindered carbon, opening the ring to give an alcohol two carbons further along the chain. It is a reliable way to extend a chain by exactly two carbons.

Can a Grignard be used on a compound containing an alkyne?

Only if the alkyne is internal. A terminal alkyne has an acidic hydrogen that destroys the reagent, and this is a favourite trap in synthesis questions.