Difficulty: Intermediate to Advanced | Prerequisites: Reduction chemistry, radical mechanisms, carboxylic acid structure (Ch. 19 Part 1)
This section covers two key reactions of carboxylic acids: reduction (converting –COOH to –CH₂OH) and decarboxylation (removing the –COOH as CO₂ to leave R–Br). Both are transformations you will use in multi-step synthesis problems. The selectivity differences between LiAlH₄, NaBH₄, and BH₃ are a particular focus, as is the radical chain mechanism of the Hunsdiecker-type decarboxylation. You should be comfortable with the concept of reducing agents and with radical chain mechanisms (initiation, propagation, termination) before working through this material.
LiAlH₄ reduces carboxylic acids to primary alcohols (NaBH₄ does not). BH₃ can selectively reduce a –COOH in the presence of other carbonyls. Decarboxylation (Hunsdiecker reaction) converts RCO₂H to R–Br + CO₂ via a radical chain mechanism, using Hg(II) or Ag(I) or Pb(IV) salts with Br₂ or I₂.
LiAlH₄ (lithium aluminium hydride)
A powerful reducing agent that delivers H⁻ (hydride) to carbonyl groups. Reduces carboxylic acids, esters, aldehydes, and ketones to alcohols. Requires anhydrous conditions (THF as solvent) and aqueous workup. In simple terms, it is the "strong" hydride that reduces almost every carbonyl you throw at it, including the stubborn –COOH group.
NaBH₄ (sodium borohydride)
A milder reducing agent that reduces aldehydes and ketones to alcohols but does not reduce carboxylic acids. In simple terms, it is too gentle to tackle –COOH.
BH₃ (borane)
A reducing agent with an unusual selectivity: it reduces carboxylic acids faster than other carbonyl groups. This means BH₃ can convert –COOH to –CH₂OH while leaving an aldehyde or ketone in the same molecule untouched. Think of it as the opposite of what you might expect, since –COOH is normally the hardest carbonyl to reduce.
Decarboxylation
The loss of CO₂ from a carboxylic acid, replacing –COOH with another group (typically –Br or –I in the Hunsdiecker reaction). In simple terms, chopping the acid group off the molecule.
Hunsdiecker reaction (and variants)
A radical chain reaction that converts RCO₂H into R–Br (or R–I) plus CO₂. Uses heavy-metal salts (Ag(I), Hg(II), or Pb(IV)) with Br₂ or I₂. The metal salt generates the acyl hypohalite intermediate that kicks off the radical chain.
Conditions: 1) LiAlH₄, THF; 2) H₂O (may need heat)
Product: Primary alcohol (RCH₂OH)
LiAlH₄ is strong enough to reduce the carboxylic acid all the way down from –COOH to –CH₂OH. It also reduces any other carbonyl groups in the molecule (aldehydes, ketones, esters), so it is not selective.
This is a critical selectivity point. NaBH₄ reduces aldehydes and ketones but leaves –COOH untouched. If a molecule has both a ketone and a carboxylic acid, NaBH₄ reduces only the ketone.
Conditions: 1) BH₃, THF; 2) H₂O
BH₃ reduces carboxylic acids faster than it reduces other carbonyl groups. This is the key selectivity tool:
A molecule with both an aldehyde (–CHO) and a carboxylic acid (–COOH) treated with LiAlH₄ gives reduction of both groups (both become –CH₂OH).
The same molecule treated with BH₃ gives reduction of only the –COOH (to –CH₂OH), leaving the aldehyde intact.
This selectivity is counterintuitive, since carboxylic acids are normally the most resistant carbonyls to reduction. BH₃ is the exception, and it is worth memorising.
Selective reduction is essential in pharmaceutical synthesis where a molecule may contain multiple carbonyl groups and you need to modify only one of them.
Tags: LiAlH₄, NaBH₄, BH₃, borane, reduction of carboxylic acids, selective reduction, primary alcohol
RCO₂H + HgO, Br₂ / CCl₄ → R–Br + CO₂
The carboxyl group is removed as CO₂, and the R group picks up a bromine.
Initiation: The acyl hypohalite (RCO₂–Br, formed in situ from the acid and the metal salt/Br₂) undergoes homolytic cleavage of the O–Br bond, generating an acyloxy radical (RCO₂•) and a bromine radical (Br•).
Propagation (two steps):
The acyloxy radical (RCO₂•) loses CO₂ to give the carbon radical R•.
R• reacts with another molecule of acyl hypohalite (RCO₂–Br), abstracting Br to form R–Br and regenerating the acyloxy radical RCO₂•.
Termination: R• + Br• → R–Br (radical combination).
The source notes that you can use different metal salts and halogens:
Metal salts: Ag(I), Hg(II), or Pb(IV) salts all work to generate the acyl hypohalite.
Halogens: Br₂ or I₂ can be used, giving R–Br or R–I respectively.
A cyclopentane carboxylic acid + HgO/Br₂ → bromocyclopentane + CO₂
A cyclopentene carboxylic acid + Pb(OAc)₄/I₂ → iodocyclopentene + CO₂
Tags: decarboxylation, Hunsdiecker reaction, radical chain, acyl hypohalite, CO₂ loss, R–Br formation, Ag(I), Hg(II), Pb(IV)
Students often assume NaBH₄ can reduce carboxylic acids. It cannot. Only LiAlH₄ and BH₃ reduce –COOH.
Students frequently forget the selectivity of BH₃: it reduces –COOH faster than other carbonyls. This is the opposite of the usual reactivity order (aldehydes > ketones > esters > acids), and exams love testing it.
Students sometimes draw the decarboxylation mechanism as an ionic process. The Hunsdiecker reaction proceeds through radicals (homolytic cleavage, radical chain), not through heterolytic steps.
Students mix up which metals and halogens can be used. Any of Ag(I), Hg(II), or Pb(IV) work, paired with Br₂ or I₂.
⚠️ "Which reducing agent reduces a carboxylic acid to an alcohol?" is a straightforward exam question. Know the answer is LiAlH₄ (or BH₃), never NaBH₄.
⚠️ The BH₃ selectivity question is a favourite: "A compound has both –CHO and –COOH. Show the product with BH₃ vs. LiAlH₄." With BH₃, only –COOH becomes –CH₂OH. With LiAlH₄, both are reduced.
⚠️ Be able to write out the three stages of the Hunsdiecker radical mechanism (initiation, propagation, termination). Mechanism questions on this reaction are common.
⚠️ In synthesis problems, decarboxylation is a way to shorten a carbon chain by one carbon. If the target has one fewer carbon than the available acid, think Hunsdiecker.
True or False: NaBH₄ reduces carboxylic acids to primary alcohols. (False, it does not react with –COOH.)
Fill in the blank: BH₃ reduces –COOH ______ than it reduces aldehydes or ketones. (faster)
True or False: The Hunsdiecker reaction proceeds through a cationic mechanism. (False, it is a radical chain mechanism.)
Fill in the blank: LiAlH₄ reduces a carboxylic acid to a primary ______. (alcohol)
True or False: Only Hg(II) salts can be used in the Hunsdiecker reaction. (False, Ag(I) and Pb(IV) also work.)
Q: A molecule contains both an aldehyde group and a carboxylic acid group. What product do you get with (a) LiAlH₄, then H₂O, and (b) BH₃, then H₂O?
A: (a) LiAlH₄ reduces both groups: the aldehyde becomes a primary alcohol (–CH₂OH) and the carboxylic acid also becomes a primary alcohol (–CH₂OH). The product is a diol. (b) BH₃ selectively reduces only the carboxylic acid to –CH₂OH, leaving the aldehyde (–CHO) intact.
Q: Write the initiation and propagation steps for the Hunsdiecker reaction of RCO₂H with HgO/Br₂.
A: Initiation: RCO₂–Br → RCO₂• + Br•. Propagation step 1: RCO₂• → R• + CO₂. Propagation step 2: R• + RCO₂–Br → R–Br + RCO₂•. The acyloxy radical is regenerated in step 2, sustaining the chain.
Q: Why does NaBH₄ fail to reduce carboxylic acids while LiAlH₄ succeeds?
A: LiAlH₄ is a much stronger hydride donor than NaBH₄. The carboxyl group is a poor electrophile compared to aldehydes and ketones (the lone pairs on –OH donate electron density into the carbonyl, making it less electrophilic). NaBH₄ is not reactive enough to overcome this, while LiAlH₄ is.
Q: How would you convert hexanoic acid (CH₃(CH₂)₄CO₂H) into 1-bromopentane?
A: Treat hexanoic acid with HgO and Br₂ in CCl₄ (Hunsdiecker reaction). This removes the carboxyl group as CO₂ and replaces it with Br, giving CH₃(CH₂)₃CH₂Br (1-bromopentane). The chain is shortened by one carbon.
The reduction chemistry here connects to reduction of other carbonyl derivatives (esters, amides, acid chlorides) in the next chapters. The selectivity hierarchy (which reducing agent works on which functional group) is tested across multiple chapters.
The radical mechanism of the Hunsdiecker reaction connects to radical halogenation from earlier chapters. The three-stage structure (initiation, propagation, termination) is identical in concept.
BH₃ selectivity also connects to hydroboration of alkenes, where BH₃ is used for a completely different purpose. Recognising when BH₃ is acting as a reducing agent vs. a hydroborating agent depends on the substrate.
Reduction of carboxylic acids, LiAlH₄, lithium aluminium hydride, NaBH₄, sodium borohydride, BH₃, borane, selective reduction, primary alcohol, decarboxylation, Hunsdiecker reaction, radical chain mechanism, acyl hypohalite, HgO, Ag₂O, Pb(OAc)₄, Br₂, I₂, CO₂ loss, carbon chain shortening, Chapter 19, organic chemistry