Aldehydes, Ketones and Carboxylic Acids · Lesson 10 of 15
Preparing Carboxylic Acids
“Choose oxidation, hydrolysis and carbon-chain extension routes with correct functional-group compatibility.”
• Prepare acids by oxidation and hydrolysis. • Track the extra carbon in nitrile and Grignard routes. • Explain benzylic hydrogen requirements for side-chain oxidation. • Plan compatible routes for multifunctional substrates.
Oxidation reaches the acid stage
Primary alcohols can be oxidised through aldehydes to carboxylic acids. Suitable conditions include aqueous permanganate or acidified dichromate; CrO₃/H₂SO₄ in aqueous medium is commonly described as Jones oxidation. The general formal balance is RCH₂OH + 2[O] → RCOOH + H₂O. If oxidation occurs in alkaline medium, the immediate product is carboxylate, and acidification is required to isolate RCOOH. A primary alcohol retains its carbon count; a secondary alcohol normally gives a ketone before any vigorous cleavage chemistry.
Aldehydes oxidise more readily, including with mild silver-based reagents. RCHO + [O] → RCOOH is a formal overall equation, while the actual Tollens’ product is RCOO⁻ before acidification. Selective aldehyde oxidation can preserve an alkene in a substrate where strong hot permanganate would also attack C=C. Reagent choice determines which structural features survive.
Side-chain oxidation needs a benzylic C–H bond
Hot permanganate or another strong suitable oxidant converts many alkylbenzene side chains with at least one benzylic H into a ring-attached COOH group. Toluene and ethylbenzene therefore both give benzoic acid after work-up. Excess side-chain carbons are oxidised away rather than appearing as a longer acid chain. An isopropyl side chain also has a benzylic H and can react. A tert-butyl side chain has none at its ring-attached carbon and resists this ordinary transformation.
This is different from phenylacetic acid synthesis: PhCH₂COOH requires retaining a methylene spacer between ring and acid, so simply oxidising an alkylbenzene side chain vigorously is not the desired route. With more than one oxidisable side chain, more than one COOH group can form. Vigorous oxidation of 4-methylacetophenone can give benzene-1,4-dicarboxylic acid, because both the methyl side chain and the acetyl side chain can be converted under the stated strong conditions.
Strong oxidative cleavage of alkenes can also yield acids. Ring cleavage of cyclohexene gives HOOC(CH₂)₄COOH, hexanedioic acid, after suitable hot oxidation and work-up. Styrene, PhCH=CH₂, can give benzoic acid while the terminal carbon is oxidised further. The products depend on substitution and work-up; do not describe every alkene carbon as becoming a retained acid carbon without checking attached hydrogens.
Nitrile hydrolysis keeps its carbon
Nitriles hydrolyse through amides. Acidic hydrolysis with water and heat ultimately gives acid and ammonium; alkaline hydrolysis gives carboxylate and ammonia. For a nitrile RCN, the CN carbon becomes the acid carbon. An amide RCONH₂ hydrolyses similarly. Mild conditions may stop a nitrile at the amide, but complete acid formation normally requires sufficiently extensive hydrolysis.
A primary alkyl halide can undergo substitution with CN⁻ to give a nitrile, followed by hydrolysis. Since cyanide contributes a carbon, RX → RCN → RCOOH lengthens the carbon chain by one relative to RX. Benzyl alcohol can first become benzyl bromide with HBr, then PhCH₂CN with KCN, then phenylacetic acid on acidic hydrolysis. Ordinary aryl halides do not undergo the same easy primary-alkyl SN2 reaction; do not use one set of conditions indiscriminately for both.
Problem
Convert benzyl alcohol to phenylacetic acid.
- 1.PhCH₂OH → PhCH₂Br with HBr replaces OH by Br without changing carbon count.
- 2.PhCH₂Br + CN⁻ → PhCH₂CN + Br⁻ adds the cyanide carbon at the benzylic site.
- 3.Hydrolyse with aqueous acid and heat to PhCH₂COOH. There are eight product carbons, one more than benzyl alcohol; direct oxidation of the alcohol would instead give seven-carbon benzoic acid.
Carbon dioxide supplies an acid carbon to a Grignard reagent
RMgX reacts with dry CO₂ in an anhydrous ethereal medium to form a magnesium carboxylate. Subsequent acid work-up gives RCOOH. A carbon nucleophile bonds to the electrophilic carbon of CO₂, so the product contains one additional carbon relative to R. Bromobenzene can form PhMgBr, then react with CO₂ and acid to give benzoic acid. Acid must be added after carboxylation, because it otherwise consumes the Grignard reagent.
A nitro group is not compatible with the ordinary unprotected Grignard route. Therefore converting 3-nitrobromobenzene directly into a nitroarylmagnesium reagent with Mg/ether is not a sound routine preparation of 3-nitrobenzoic acid. A compatible alternative is suitable copper-mediated cyanation to the nitrobenzonitrile, followed by nitrile hydrolysis. This uses an aryl cyanation method rather than pretending an aryl bromide undergoes ordinary benzyl SN2. Exact preparative conditions must be chosen for that substrate; the conceptual route alone is not a laboratory protocol.
Hydrolyse an acid derivative
| Starting derivative | Hydrolysis outcome | Work-up distinction |
|---|---|---|
| RCOCl | RCOOH + HCl with water | Base gives RCOO⁻; acidification releases acid |
| (RCO)₂O | 2RCOOH with water | Mixed anhydrides give the two corresponding acids |
| RCOOR′ under H⁺ | RCOOH + R′OH | Reversible; sufficient water favours hydrolysis |
| RCOOR′ under OH⁻ | RCOO⁻ + R′OH | Carboxylate formation drives saponification |
| RCONH₂ under acid | RCOOH + NH₄⁺ | Heat is commonly needed |
An acyl chloride is highly reactive toward water; an ordinary amide requires more forcing hydrolysis because nitrogen donates strongly into C=O and is a poor leaving group unless appropriately activated. Hydrolysis changes the group attached to the acyl carbon but preserves that carbon in the acid. Ester hydrolysis splits the acyl and alkoxy portions into acid/carboxylate and alcohol; not every carbon of an ester belongs to the acid product.
Problem
Compare ethylbenzene, acetophenone, bromobenzene and styrene as precursors.
- 1.Ethylbenzene: hot side-chain oxidation, then acidification. Acetophenone: haloform cleavage gives benzoate, followed by acidification, or use a suitable vigorous oxidation.
- 2.Bromobenzene: Mg/dry ether, then CO₂, then acid. Styrene: sufficiently vigorous oxidative cleavage, followed by work-up.
- 3.These routes converge on PhCOOH, but carbon removal and addition differ. Check atom destinations instead of treating all preparations as an identical oxidation.
Quick Quiz
Quiz
What acid follows CH₃CH₂Br → nitrile → hydrolysis?
Explanation: CN contributes one carbon to the two-carbon ethyl group.
Which alkylbenzene lacks the benzylic H needed for ordinary side-chain oxidation?
Explanation: Its ring-attached carbon has three carbon substituents and no H.
What supplies the new acid carbon in Grignard carboxylation?
Explanation: The carbon nucleophile bonds to the carbon of carbon dioxide.
What is obtained immediately in basic ester hydrolysis?
Explanation: The basic medium deprotonates the acid product.
Why is an unprotected nitroaryl Grignard route unsuitable here?
Explanation: Functional-group compatibility prevents a simple Mg/ether assumption.
Practice Problems
- Convert butan-1-ol and butanal to butanoic acid.
- Prepare propanoic acid from bromoethane by two chain-extension routes.
- Explain why tert-butylbenzene resists the usual oxidation while isopropylbenzene does not.
- Hydrolyse ethyl benzoate under acidic and basic conditions.
- Give a compatible conceptual route from 3-nitrobromobenzene to 3-nitrobenzoic acid.
- What acid results from oxidative cleavage of cyclohexene, and why?
For butan-1-ol use a suitable aqueous oxidation such as acidified dichromate/Jones conditions or permanganate with appropriate work-up. For butanal use a mild aldehyde oxidation, with acidification if the oxidation mixture is alkaline. Both retain four carbons; the alcohol needs a greater overall oxidation change.
Key Takeaways
• Primary alcohol and aldehyde oxidation can retain the carbon skeleton. • Benzylic side-chain oxidation requires an appropriate benzylic H. • Nitrile carbon becomes the acid carbon on hydrolysis. • Cyanide substitution and CO₂ carboxylation can extend a chain by one carbon. • Acid work-up is required after carboxylate-forming basic reactions. • Aryl and primary-alkyl cyanation cannot be treated as identical SN2 reactions. • Check all functional groups before choosing a Grignard route.