Carboxylic Acid Reduction Lialh4

Carboxylic Acids → Primary Alcohols with LiAlH₄

Carboxylic Acids → Primary Alcohols with LiAlH₄ (then H₃O⁺)

Lithium aluminum hydride (LiAlH₄, “LAH”) converts carboxylic acids (RCO₂H) into primary alcohols (RCH₂OH). The hydride reagent first acts as a base (acid–base step with H₂ evolution), then delivers two nucleophilic hydrides through an aluminum-carboxylate complex. Aqueous/acidic workup liberates the neutral alcohol. The aldehyde stage is never isolated; it exists only while coordinated to aluminum.

Quick Summary

Reagents / conditions	LiAlH₄ (1.5–3.0 eq) in dry Et₂O/THF, 0 °C → reflux under inert gas; staged quench (H₂O → dilute H₃O⁺).
Outcome	RCO₂H → RCH₂OH with H₂ evolution during the reaction and aluminum salts removed during workup.
Mechanism	(1) Acid–base → (2) Hydride acyl substitution → (3) Collapse to the bound aldehyde → (4) Second hydride → (5) Proton transfer with H₃O⁺ → (6) Workup liberates the alcohol.
Why it works	Al(III) coordination activates the acyl carbon and keeps the nascent aldehyde bound long enough for the second hydride.
Stereochemistry	The acyl carbon simply goes from sp² to sp³; no rearrangements or new chiral centers.
Contrasts & pitfalls	NaBH₄ is too weak for acids; LiAlH₄ also reduces esters, amides, nitriles, and epoxides, so chemoselectivity and careful quench technique are essential.

Mechanism — Six RDKit Frames

Step 1 LiAlH4 deprotonates the acid, forming an aluminum carboxylate and H₂. — Step 1 — Acid–base: LiAlH₄ deprotonates RCO₂H to give an Al-carboxylate and H₂(g).

Step 2 Hydride acyl substitution sends the π bond up and collapses to an Al-bound aldehyde. — Step 2 — Hydride acyl substitution gives an aluminum-bound “aldehyde stage” after collapse of the tetrahedral intermediate.

Step 3 — Collapse: electrons from O⁻ reform C=O while the Al–O fragment departs, revealing a bound aldehyde.

Step 4 A second hydride reduces the aldehyde to the aluminum alkoxide. — Step 4 — Second hydride converts the aldehyde equivalent into the aluminum alkoxide (RCH₂O–Al).

Step 5 Proton transfer from H₃O⁺ to the alkoxide. — Step 5 — Proton transfer: the alkoxide oxygen donates into an H₃O⁺ O–H bond while hydronium releases water.

Step 6 Final protonation releases the neutral primary alcohol. — Step 6 — Final workup protonates the alkoxide and releases the primary alcohol; aluminum salts stay in the aqueous layer.

Each SVG comes directly from the RDKit Mechanism Solver, so the curved arrows and overlays match the interactive experience.

Mechanistic Checklist (Exam Focus)

Show the acid–base kickoff: hydride grabs the acidic proton → H₂ bubbles off.
Depict an Al-carboxylate before hydride delivery (coordination activates the acyl carbon).
Two hydrides hit the same carbon: first gives an Al-bound aldehyde, the second yields an alkoxide.
Emphasize that the aldehyde never escapes—LiAlH₄ immediately pushes it to the alcohol.
Include a careful H₃O⁺ workup arrow; quenching incorrectly is a safety risk.
Contrast vs NaBH₄ (inactive toward acids) and BH₃·THF (acid-selective, gentler).

Worked Examples

Scope & Limitations

Broadly reduces: aliphatic/aromatic acids, diacids (→ diols), and polyfunctional acids (if no other reducible groups).
Too reactive for selectivity: LiAlH₄ will also reduce esters, acid chlorides, amides, nitriles, epoxides, nitro groups, and some halides. Protect or sequence wisely.
Aldehyde capture: cannot stop at an aldehyde; use LiAl(OR)₃H on acid chlorides or DIBAL-H on esters if you need RCHO.
Protic handles: free –OH or –NH groups will quench the reagent—protect or deprotonate beforehand.
Safety: reagent is pyrophoric when dry; every addition/quench must be ice cold and vented because H₂ evolves.

Practical Tips

Dry everything. Oven-dry glassware, dry ether/THF, and an inert atmosphere before LiAlH₄ is exposed.
Addition order: Slowly add the acid (or its solution) to a stirred suspension of LiAlH₄ at 0 °C. This keeps H₂ evolution manageable.
Quench sequence: Classic Fieser-style quench—EtOAc (consumes excess hydride) → H₂O → dilute NaOH → H₃O⁺/NH₄Cl—prevents runaway exotherms.
Solid workup: Expect aluminum salts; filter through Celite before concentrating.
Plan hydride equivalents: One equivalent is lost to acid–base, so plan ≥2 equiv per carboxyl group (1.5–3.0 eq in practice).

Exam-Style Summary

Net reaction: RCO₂H —(LiAlH₄, dry ether/THF)→ RCH₂O⁻·Al —(H₃O⁺)→ RCH₂OH
Takeaways: hydride first acts as base (H₂), then delivers twice to the carbonyl. Aldehyde never leaves the coordination sphere, and a careful aqueous workup protonates the alkoxide. NaBH₄ is inert toward carboxylic acids.

FAQ

Can I isolate the aldehyde?
Not from a carboxylic acid with LiAlH₄—the aldehyde forms only as an aluminum complex and is immediately reduced. To stop at RCHO, transform the acid to an acid chloride and use LiAl(OR)₃H or apply DIBAL-H to an ester at −78 °C.

Why does NaBH₄ fail here?
Carboxylic acids are too weakly electrophilic and too acidic; NaBH₄ is rapidly quenched without delivering hydride. LiAlH₄ is both basic and a much stronger hydride donor.

What is the safe way to quench LiAlH₄ reductions?
Cool to 0 °C, add a proton source in stages (e.g., EtOAc → H₂O → dilute acid) behind a blast shield. Never dump water all at once—H₂ evolution plus exotherm can be violent.

Interactive Toolbox

Mechanism Solver — Replay all six RDKit frames with overlays matching the article figures.
Reaction Solver — Compare LiAlH₄ vs NaBH₄ vs LiAl(OR)₃H on carboxylic acids, esters, and acid chlorides.
IUPAC Namer — Confirm the names for the resulting primary alcohols (benzyl alcohol, 1-hexanol, isobutanol, etc.).

Study Tools