Difficulty: Intermediate to Advanced | Prerequisites: Oxidation-reduction, Grignard reactions, SN2 mechanism, alkene chemistry
There are six main routes to carboxylic acids covered in Chapter 19: three oxidation methods, hydrolysis of nitriles, and the Grignard reaction with CO₂. Each method starts from a different functional group, so the choice depends on what starting material you have. This is the kind of material that appears in synthesis problems: "show how to convert X into a carboxylic acid." You will need familiarity with oxidation states, Grignard chemistry, and the SN2 mechanism to follow along.
Carboxylic acids can be made by oxidising benzylic groups, alkenes, alcohols, or aldehydes, by hydrolysing nitriles, or by treating a Grignard reagent with CO₂ followed by acid workup. Each method has specific limitations worth knowing for exams.
Jones' reagent (CrO₃, H₂SO₄, H₂O, acetone)
A chromium-based oxidising agent that converts primary alcohols and aldehydes to carboxylic acids. In simple terms, it is a strong oxidant that pushes a –CH₂OH or –CHO all the way to –COOH.
KMnO₄ (potassium permanganate)
A powerful oxidising agent used to cleave alkenes (with H₃O⁺) into carboxylic acid fragments, and to oxidise benzylic C–H bonds to –COOH. Think of it as one of the most aggressive oxidants in the organic chemistry toolkit.
Grignard reagent (RMgBr)
An organomagnesium halide that acts as a strong nucleophilic carbon. When it attacks CO₂, the product (after acid workup) is a carboxylic acid with one more carbon than the original halide. In simple terms, it is a way to build a new C–C bond and end up with –COOH at the new junction.
Nitrile hydrolysis
The acid-catalysed reaction of R–C≡N with water to produce a carboxylic acid (RCO₂H) and ammonia or an ammonium salt. Think of it as "unmasking" a hidden carboxyl group from a triple bond to nitrogen.
Benzylic position
A carbon directly attached to a benzene ring. KMnO₄ can oxidise a benzylic C–H to –COOH, but only if a benzylic hydrogen is present.
Tollens' reagent (Ag₂O, NH₄OH)
A mild oxidising agent selective for aldehydes. Converts RCHO to RCO₂H without affecting other functional groups. In simple terms, the "silver mirror" test reagent that also happens to make a carboxylic acid.
Reagent: KMnO₄ / H₂O
What it does: Oxidises a carbon attached to a benzene ring (the benzylic position) all the way to –COOH, regardless of the chain length at that position. For example, toluene (PhCH₃) becomes benzoic acid (PhCO₂H), and PhCH₂CH₂OH also becomes PhCO₂H.
The benzylic carbon must have at least one C–H bond. If the benzylic carbon has no hydrogen (e.g., Ph–C(CH₃)₃, a tert-butyl group on benzene), no reaction occurs.
Non-benzylic substrates are unaffected. Cyclohexane with a methyl group, for instance, does not react because there is no aromatic ring to create a benzylic position.
Tags: benzylic oxidation, KMnO₄, toluene to benzoic acid, benzylic C–H requirement
Reagent: KMnO₄ / H₃O⁺ (oxidative cleavage conditions)
What it does: Cleaves the C=C double bond completely. Each carbon of the former double bond becomes a carboxyl group (–COOH), provided that carbon had at least one hydrogen (a vinylic C–H). If both carbons of the double bond had hydrogens, you get two carboxylic acid fragments.
Cyclic alkenes give a single product: a dicarboxylic acid (a diacid). For example, cyclohexene treated with KMnO₄/H₃O⁺ yields a six-carbon diacid with –COOH at both ends.
A vinylic C–H bond is required on each side that you want to become –COOH. A fully substituted alkene carbon (no H) gives a ketone fragment instead.
Other oxidisable functional groups in the molecule may also react, so this is not always selective.
Tags: oxidative cleavage, KMnO₄/H₃O⁺, alkene to carboxylic acid, vinylic C–H, dicarboxylic acid from cyclic alkene
Reagent: Jones' reagent (CrO₃, H₂SO₄, H₂O, acetone)
Primary alcohols (RCH₂OH) are oxidised in two steps: first to the aldehyde (RCHO), then onward to the carboxylic acid (RCO₂H). Jones' reagent drives both steps in one pot.
Secondary alcohols give ketones with Jones' reagent (they stop at the ketone; there is no further oxidation to an acid).
Two reagent options:
Jones' reagent (CrO₃, H₂SO₄, H₂O, acetone): works for any aldehyde.
Tollens' reagent (Ag₂O, NH₄OH): a milder, selective option. Oxidises aldehydes to acids without touching other carbonyl groups (ketones, esters) in the molecule.
NaBH₄ is a reducing agent, not an oxidising agent, but students often confuse the direction. NaBH₄ does not oxidise alcohols to acids. (This detail matters more in the "Reactions" section but is mentioned here because the source flags it.)
Tags: Jones' reagent, CrO₃, Tollens' reagent, Ag₂O, primary alcohol oxidation, aldehyde oxidation, selective oxidation
Reagent: R–C≡N + H₃O⁺ (acid-catalysed hydrolysis)
What it does: Converts a nitrile (R–C≡N) into a carboxylic acid (RCO₂H). The carbon of the C≡N triple bond becomes the carboxyl carbon.
The standard route is an SN2 reaction: treat an alkyl halide (R–Br) with sodium cyanide (NaCN). The cyanide ion (CN⁻) is a good nucleophile and displaces the halide.
R–Br + NaCN → R–CN + NaBr
Then hydrolyse: R–CN + H₃O⁺ → RCO₂H
CN⁻ is a nucleophile, so this is an SN2 reaction. It works best with primary (1°) alkyl halides, is acceptable with secondary (2°), and fails with tertiary (3°) halides (elimination dominates).
The overall sequence (R–Br → R–CN → RCO₂H) adds one carbon to the chain. This is a key retrosynthetic insight: if the target acid has one more carbon than the available halide, think nitrile hydrolysis.
Tags: nitrile hydrolysis, R–CN, SN2, NaCN, chain extension, one-carbon homologation
Reagents: 1) R–MgBr + CO₂, then 2) H₃O⁺
What it does: The Grignard reagent (R–MgBr) attacks the electrophilic carbon of CO₂ (which is δ+ because it sits between two δ- oxygens). After acid workup, the product is a carboxylic acid (RCO₂H).
The nucleophilic carbon of R–MgBr attacks the electrophilic carbon of O=C=O.
This forms a carboxylate salt (RCO₂⁻ MgBr⁺).
Acid workup (H₃O⁺) protonates the carboxylate to give RCO₂H.
Grignard reagents can be made from 1°, 2°, 3° alkyl bromides, as well as vinyl and aryl bromides. This makes the Grignard + CO₂ route very versatile.
Like nitrile hydrolysis, this method adds one carbon (the CO₂ carbon becomes the –COOH). In retrosynthesis, disconnect the bond between the R group and the carboxyl carbon to reveal R–MgBr + CO₂.
Example from the source:
CH₃CH₂Br → (Mg, Et₂O) → CH₃CH₂MgBr → (1. CO₂, 2. H₃O⁺) → CH₃CH₂CO₂H (propanoic acid)
Tags: Grignard reagent, RMgBr, CO₂, carboxylation, one-carbon homologation, retrosynthesis
Students often think KMnO₄ oxidises any C–H bond on a benzene ring substituent. It only works at the benzylic position and only when a benzylic hydrogen exists. A tert-butyl group on benzene is inert.
Students sometimes forget that nitrile hydrolysis and the Grignard + CO₂ route both add one carbon. In retrosynthesis, the target acid has one more carbon than the starting halide.
Students confuse the two chromium-based reactions: Jones' reagent oxidises all the way to –COOH from a primary alcohol, while PCC (not covered here, but from earlier chapters) stops at the aldehyde.
Students occasionally try to use Tollens' reagent on ketones. Tollens' reagent is selective for aldehydes; ketones do not react.
⚠️ "Show how to convert compound X into a carboxylic acid" is a standard synthesis question. You need to pick the right method based on the starting material.
⚠️ The benzylic oxidation limitation (must have a benzylic C–H) is a common trick question. If they draw PhC(CH₃)₃ + KMnO₄, the answer is "no reaction."
⚠️ The Grignard + CO₂ sequence is a favourite for multi-step synthesis problems. Know how to form the Grignard (R–Br + Mg in Et₂O) and then add CO₂.
⚠️ Be ready to compare methods. If asked "which reagent converts an aldehyde to an acid without affecting a ketone in the same molecule," the answer is Tollens' reagent (Ag₂O / NH₄OH).
True or False: KMnO₄ can oxidise cyclohexane with a methyl group to a carboxylic acid. (False, there is no benzylic position.)
Fill in the blank: The Grignard + CO₂ reaction adds ______ carbon(s) to the chain. (one)
True or False: NaCN reacts with tertiary alkyl halides by SN2 to form nitriles. (False, SN2 fails with 3° halides.)
Fill in the blank: Jones' reagent is a combination of CrO₃, H₂SO₄, H₂O, and ______. (acetone)
True or False: Tollens' reagent oxidises both aldehydes and ketones to carboxylic acids. (False, only aldehydes.)
Q: Show how to convert bromobenzene into benzoic acid using a Grignard reaction.
A: Treat bromobenzene with Mg in Et₂O to form phenylmagnesium bromide (PhMgBr). Then add CO₂, followed by H₃O⁺ workup. The product is benzoic acid (PhCO₂H).
Q: What product(s) do you get when cyclohexene is treated with KMnO₄ / H₃O⁺?
A: Oxidative cleavage of the ring gives a linear six-carbon diacid: hexanedioic acid (adipic acid), with a –COOH at each end of the chain.
Q: Propose a two-step synthesis of phenylacetic acid (PhCH₂CO₂H) from benzyl bromide (PhCH₂Br).
A: Step 1: PhCH₂Br + NaCN → PhCH₂CN (SN2). Step 2: PhCH₂CN + H₃O⁺ → PhCH₂CO₂H (nitrile hydrolysis). This adds one carbon to the chain.
Q: A molecule contains both an aldehyde and a ketone. Which reagent selectively oxidises only the aldehyde to a carboxylic acid?
A: Tollens' reagent (Ag₂O / NH₄OH). It is mild enough to oxidise the aldehyde and leave the ketone untouched.
The Grignard reaction here connects back to Grignard additions to aldehydes and ketones from earlier chapters. The same R–MgBr nucleophile is used, just with a different electrophile (CO₂ instead of a carbonyl compound).
Nitrile hydrolysis connects forward to amide chemistry: under milder conditions, a nitrile can be partially hydrolysed to an amide rather than going all the way to the acid.
Oxidation of benzylic positions will reappear in aromatic synthesis problems when you need to install a –COOH on a ring.
Preparation of carboxylic acids, synthesis of RCOOH, KMnO₄ oxidation, benzylic oxidation, oxidative cleavage of alkenes, Jones' reagent, CrO₃, Tollens' reagent, Ag₂O, aldehyde oxidation, nitrile hydrolysis, SN2 with cyanide, Grignard reaction, RMgBr + CO₂, one-carbon homologation, chain extension, retrosynthesis, Chapter 19, organic chemistry