Organometallic — carboxylic acid synthesis
Grignard carboxylation with CO₂
How the Grignard carboxylation with CO₂ works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.
In short. A 3-step mechanism. Typical reagents: R–MgBr, CO₂ (dry ice or gas); then H₃O⁺. Conditions: Et₂O or THF, –78 to 0 °C; acid workup. Bonds formed: C–C; carboxylate then COOH; bonds broken: C=O π (one); C–Mg. Stereochemistry: None for achiral R; one-carbon homologation of RX. Rate and selectivity: Fast; excess CO₂ prevents ketone by-products.
At a glance
Step 1: Carbanion-like carbon attacks CO₂
A Grignard reagent's polarized, carbanion-like carbon attacks CO₂'s electrophilic carbon directly — the same nucleophilic addition pattern as Grignard addition to any carbonyl, just with carbon dioxide standing in for an aldehyde or ketone.
Step 2: Carboxylate resists a second attack
This forms a magnesium carboxylate salt in a single addition step, with no possibility of over-addition since the resulting carboxylate is far too poor an electrophile for a second equivalent of Grignard to attack.
Step 3: Acid workup gives the carboxylic acid
Acidic aqueous workup protonates the carboxylate, giving a carboxylic acid with one more carbon than the original alkyl halide the Grignard was made from — a simple, reliable way to convert an alkyl halide into a carboxylic acid without needing a pre-existing carbonyl.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- THF
- Tetrahydrofuran. Cyclic ether solvent; its oxygen lone pairs solvate Li⁺/Mg²⁺ so organometallics stay dissolved and reactive.
- Et2O
- Diethyl ether. Low-boiling ether solvent, classic for Grignard reagents.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
How it compares with related reactions
| Grignard carboxylation with CO₂ | Bouveault aldehyde synthesis | Grignard addition to acetaldehyde | |
|---|---|---|---|
| Reagents | R–MgBr, CO₂ (dry ice or gas); then H₃O⁺ | n-BuLi or R–MgX (1 equiv.), DMF; then H₃O⁺ | CH₃MgBr in Et₂O or THF; then H₃O⁺ |
| Conditions | Et₂O or THF, –78 to 0 °C; acid workup | THF or Et₂O, –78 to 0 °C; aqueous acid workup | Dry ether, 0 °C → 25 °C; strictly anhydrous |
| Stereochemistry | None for achiral R; one-carbon homologation of RX | None (aldehyde product) | Planar C=O: both faces attacked (racemic if new stereocentre) |
| Rate / selectivity | Fast; excess CO₂ prevents ketone by-products | Addition fast at low temperature; intermediate stable until workup | Fast with aldehydes; RMgX is also a strong base — incompatible with acidic H |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Grignard carboxylation with CO₂?
R–MgBr, CO₂ (dry ice or gas); then H₃O⁺. Conditions: Et₂O or THF, –78 to 0 °C; acid workup.
Which bonds are formed and which are broken?
Formed: C–C; carboxylate then COOH. Broken: C=O π (one); C–Mg.
What is the stereochemical outcome?
None for achiral R; one-carbon homologation of RX
What controls the rate or the selectivity?
Fast; excess CO₂ prevents ketone by-products
Study guides that help with this reaction
- How to learn reaction mechanisms (without memorising everything)
- How to answer mechanism questions in an exam