Grignard Reagents

A representative example — structures drawn live.

How Grignards are made and why they are nucleophilic

A Grignard reagent forms when an alkyl or aryl halide (R–X) is stirred with magnesium metal in anhydrous ether (diethyl ether or THF). The magnesium inserts into the carbon–halogen bond to give R–Mg–X.

The key is the polarity of the C–Mg bond. Carbon is much more electronegative than magnesium, so the bonding electrons sit on carbon, giving it a partial negative charge (δ^–). This inverts carbon's usual role: the carbon is now electron-rich and behaves like a carbanion — strongly nucleophilic and strongly basic. It seeks out electron-poor carbons, above all the carbonyl carbon.

Adding to carbonyls: the core reaction

The Grignard carbon attacks the electrophilic carbon of a C=O group. The π electrons shift onto oxygen to form an alkoxide, which is then protonated in a separate acidic workup (dilute H₃O⁺) to reveal the alcohol. The class of alcohol you get is fixed by the carbonyl you start from:

• Formaldehyde (H₂C=O) → primary alcohol. The Grignard adds one R group to a carbon that keeps its two hydrogens.
• Any other aldehyde → secondary alcohol. The product carbon bears the new R, an H, and the aldehyde's R group.
• Ketone → tertiary alcohol. The carbinol carbon ends up with three carbon substituents.
• Carbon dioxide (CO₂) → carboxylic acid. The Grignard adds to CO₂ to give a carboxylate, protonated on workup. This adds exactly one carbon to your chain.

Esters add twice

Esters are a special case. When a Grignard attacks an ester, the first addition expels the alkoxy leaving group to give a ketone — but that ketone is even more reactive than the ester, so a second equivalent of Grignard adds immediately. You cannot stop at the ketone. The result after workup is a tertiary alcohol bearing two identical R groups from the Grignard. Acid chlorides behave similarly, also adding twice to give tertiary alcohols.

The fatal weakness: any protic hydrogen destroys it

Because the Grignard carbon is such a strong base, it grabs a proton from anything even weakly acidic far faster than it does useful chemistry. A single molecule of water quenches it, converting R–MgX into R–H (the alkane) and doing nothing productive. The same fate awaits it around:

• –OH groups (alcohols, carboxylic acids, water)
• –NH groups (amines, amides)
• terminal alkynes (the ≡C–H is acidic enough)

This is why the glassware, solvent, and reagents must be scrupulously dry and often air-free, and why the acidic workup is always the last step, never mixed in early. If your substrate contains an OH, NH, or terminal alkyne, you must protect it first or the Grignard will simply deprotonate it.

Putting it to work

Grignards are among the most important C–C bond-forming tools in the sophomore toolbox. To make a specific alcohol, work backwards: pick a carbonyl and an R group whose union gives your target. Need 2-phenyl-2-butanol (a 3° alcohol)? Combine a methyl or ethyl Grignard with the matching ketone. Need to lengthen a chain by one carbon and cap it with an acid? Run the Grignard into CO₂. Master the carbonyl-to-alcohol map above and Grignard problems become bookkeeping.