Aldehydes, Ketones and Carboxylic Acids

The carbonyl group, C=O, is the defining feature of aldehydes and ketones. The carbonyl carbon is sp² hybridised and lies at the centre of a trigonal planar arrangement, with bond angles close to 120°. In an aldehyde the carbonyl carbon is bonded to at least one hydrogen atom (the –CHO group), while in a ketone it is bonded to two carbon-containing groups (–CO–). Because oxygen is more electronegative than carbon, the C=O bond is strongly polarised, leaving the carbonyl carbon electrophilic (δ+) and the oxygen nucleophilic (δ−). This polarisation is the reason for almost all of the chemistry in this chapter.

In the IUPAC system, aldehydes are named by replacing the -e of the parent alkane with -al, and ketones by replacing it with -one. The longest chain containing the carbonyl carbon is the parent chain; for aldehydes the carbonyl carbon is always C1, while for ketones it is given the lowest possible locant. For example, CH₃–CH(CH₃)–CH₂–CH₂–CHO is numbered from the CHO carbon outward, giving 4-methylpentanal; CH₃–CH₂–CO–CH₂–CH₃ is pentan-3-one. Many common names (formaldehyde, acetaldehyde, acetone, benzaldehyde) remain in everyday use.

Several standard routes are used to prepare aldehydes and ketones:

• Controlled oxidation of alcohols: primary alcohols give aldehydes and secondary alcohols give ketones. Strong oxidants (KMnO₄, acidic K₂Cr₂O₇) tend to over-oxidise primary alcohols to carboxylic acids, so a milder, selective reagent such as PCC (pyridinium chlorochromate) is used to stop cleanly at the aldehyde.
• Rosenmund reduction: an acid chloride is hydrogenated over palladium on barium sulphate poisoned with sulphur/quinoline, which stops the reduction at the aldehyde stage instead of going on to the alcohol.
• Stephen reaction: a nitrile is reduced with SnCl₂/HCl to an imine salt, which is hydrolysed to the aldehyde.
• Ozonolysis of alkenes: the C=C bond is cleaved by ozone followed by reductive work-up (Zn/H₂O) to give two carbonyl fragments — useful both for synthesis and for structure determination.
• Ketones from nitriles or acid chlorides: reaction of a nitrile with a Grignard reagent (followed by hydrolysis) or an acid chloride with a milder organometallic reagent gives a ketone; Friedel–Crafts acylation of an arene with an acid chloride/anhydride (AlCl₃) is the standard route to aryl ketones.

Worked example: Predict the products of ozonolysis of 2-methylbut-2-ene, (CH₃)₂C=CH–CH₃, followed by Zn/H₂O work-up. The C=C bond is cleaved; each carbon of the former double bond becomes a carbonyl carbon. The more substituted carbon, (CH₃)₂C=, bears two methyl groups and becomes a ketone, (CH₃)₂C=O (acetone); the less substituted carbon, =CH–CH₃, bears one hydrogen and becomes an aldehyde, CH₃CHO (ethanal). So ozonolysis of 2-methylbut-2-ene gives a mixture of acetone and acetaldehyde.

Because the carbonyl group is polar but cannot hydrogen-bond with itself (there is no O–H or N–H), aldehydes and ketones have boiling points higher than hydrocarbons and ethers of comparable molar mass, but lower than alcohols of similar size. For example, propan-1-ol (molar mass 60, b.p. 97 °C) boils well above propanal (molar mass 58, b.p. 49 °C) or acetone (molar mass 58, b.p. 56 °C), even though the three have almost identical molar mass — only the alcohol can form intermolecular hydrogen bonds. The lower aldehydes and ketones (up to about 4 carbons) are miscible with water because the carbonyl oxygen can hydrogen-bond with water molecules; water solubility falls as the hydrocarbon part of the molecule grows.

The dominant reaction type of the carbonyl group is nucleophilic addition. A nucleophile attacks the electrophilic carbonyl carbon from a direction roughly perpendicular to the C=O plane; the π electrons move fully onto oxygen, generating a tetrahedral alkoxide intermediate, which is then protonated (by solvent or on aqueous work-up) to give the neutral addition product. Because this depends on how open and how electron-poor the carbonyl carbon is, reactivity decreases as alkyl substitution increases — both a steric effect (bulkier groups hinder the nucleophile's approach) and an electronic effect (alkyl groups are electron-donating and reduce the positive charge on carbon): HCHO > other aldehydes > ketones.

Typical nucleophilic addition reactions include:

• Addition of HCN to give a cyanohydrin, R₂C(OH)CN — adds one carbon and a nitrile that can later be hydrolysed to –COOH.
• Addition of NaHSO₃ to give a crystalline bisulphite addition compound, used to purify aldehydes and methyl ketones.
• Addition of Grignard reagents (R′MgX) followed by acidic work-up, giving secondary or tertiary alcohols — one of the most important carbon–carbon bond-forming reactions in organic synthesis.
• Addition of alcohols under acid catalysis to give a hemiacetal, then a second equivalent of alcohol gives the acetal (or ketal); this is reversible and acetals are used as protecting groups for carbonyls.
• Addition of ammonia derivatives — hydroxylamine, hydrazine, phenylhydrazine, 2,4-dinitrophenylhydrazine — which add and then lose water to give an oxime, hydrazone or 2,4-DNP derivative; these are crystalline solids with sharp melting points, classically used to identify carbonyl compounds.

Worked example: Write the mechanism for base-catalysed addition of HCN to acetone. Step 1: CN⁻ attacks the electrophilic carbonyl carbon of (CH₃)₂C=O; the C=O π electrons shift onto oxygen. Step 2: this gives a tetrahedral alkoxide intermediate, (CH₃)₂C(O⁻)(CN). Step 3: the alkoxide is protonated by HCN (regenerating CN⁻) or by aqueous work-up, giving the cyanohydrin (CH₃)₂C(OH)CN, 2-hydroxy-2-methylpropanenitrile.

Aldehydes and ketones can be reduced in two distinct ways depending on the product needed. Reduction to the corresponding alcohol is achieved with hydride donors such as NaBH₄ or LiAlH₄ (or by catalytic hydrogenation, H₂/Ni). Complete removal of the oxygen, reducing the carbonyl carbon all the way to a –CH₂– group, is done by either the Clemmensen reduction (Zn–Hg amalgam with concentrated HCl; chosen for substrates that would be attacked by strong base) or the Wolff–Kishner reduction (hydrazine, NH₂NH₂, followed by strong base such as KOH in ethylene glycol, heat; chosen for substrates that would be damaged by strong acid).

Oxidation highlights a key chemical difference between aldehydes and ketones. Aldehydes have a hydrogen atom directly attached to the carbonyl carbon, so they are easily oxidised to carboxylic acids even by mild oxidants; this is the basis of two classic identification tests — Tollens' reagent (ammoniacal AgNO₃), which deposits a bright silver mirror, and Fehling's solution (alkaline Cu²⁺ tartrate complex), which gives a brick-red precipitate of Cu₂O. Ketones have no such hydrogen and resist mild oxidation, giving a negative result with both tests; only powerful oxidants under harsh conditions cleave a C–C bond of a ketone into a mixture of smaller carboxylic acids.

When an aldehyde or ketone has at least one alpha-hydrogen (a hydrogen on the carbon next to the carbonyl), dilute base can remove it to form a resonance-stabilised enolate, which attacks a second carbonyl molecule — the aldol reaction. The initial product is a beta-hydroxy aldehyde/ketone (an "aldol"); on warming, this readily loses water to give an alpha,beta-unsaturated carbonyl compound — the combined two-step sequence is aldol condensation. When one partner has no alpha-hydrogen (e.g. an aromatic aldehyde such as benzaldehyde) and is used with a ketone under base, the reaction is often called a Claisen–Schmidt condensation.

Carbonyl compounds with no alpha-hydrogen (e.g. HCHO, benzaldehyde, (CH₃)₃C–CHO) cannot undergo aldol condensation. Instead, with concentrated alkali they undergo the Cannizzaro reaction: two molecules of the aldehyde disproportionate, one being oxidised to a carboxylate salt and the other reduced to the alcohol.

Worked example (Cannizzaro stoichiometry): 60 g of formaldehyde, HCHO (molar mass 30 g/mol), is treated with excess concentrated NaOH. Moles of HCHO = 60/30 = 2 mol. The reaction is 2HCHO + NaOH → CH₃OH + HCOONa, so 2 mol HCHO gives 1 mol CH₃OH (molar mass 32) and 1 mol HCOONa (molar mass 68). Mass of methanol formed = 1 × 32 = 32 g; mass of sodium formate formed = 1 × 68 = 68 g. Check: 60 g HCHO + 40 g NaOH = 100 g reactants = 32 g + 68 g products, so mass is conserved.

Finally, methyl ketones (and any compound oxidisable to one, such as ethanol or propan-2-ol) give a positive iodoform test: I₂/NaOH converts the CH₃CO– group into a pale-yellow precipitate of triiodomethane (CHI₃), leaving the rest of the molecule as the sodium salt of a carboxylic acid. This is both a qualitative test and a synthetic method for shortening a chain by one carbon.

The functional group of a carboxylic acid is –COOH (the carboxyl group), formally a combination of a carbonyl (C=O) and a hydroxyl (–OH) on the same carbon. Saturated, straight-chain monocarboxylic acids have the general formula C_nH_2nO₂. The carboxyl carbon is sp² hybridised and planar. In the carboxylate ion (formed after loss of the acidic proton), both carbon–oxygen bonds are of equal, intermediate length — explained by resonance delocalisation of the negative charge equally over both oxygens. This delocalisation is the structural reason carboxylic acids are much more acidic than alcohols or phenols (covered in the next section).

In the IUPAC system, carboxylic acids are named by replacing the terminal -e of the corresponding alkane with -oic acid; the carboxyl carbon is always C1. For example, CH₃–CH₂–COOH is propanoic acid, and (CH₃)₂CH–CH₂–COOH is 3-methylbutanoic acid. Common names — formic acid (HCOOH), acetic acid (CH₃COOH), benzoic acid (C₆H₅COOH) — remain in wide use and are accepted by IUPAC.

Standard methods of preparation include:

• Oxidation of primary alcohols or aldehydes with strong oxidants such as acidified KMnO₄ or K₂Cr₂O₇ — unlike the controlled oxidation used to stop at an aldehyde, here oxidation is taken to completion.
• Oxidation of alkylbenzenes: hot alkaline KMnO₄ oxidises a benzylic side chain, regardless of its length, all the way to –COOH, so toluene gives benzoic acid; this requires at least one benzylic hydrogen on the side chain.
• Hydrolysis of nitriles, esters or amides under acidic or basic conditions regenerates the carboxylic acid (or its salt, which is then acidified).
• Grignard reagent + CO₂: a Grignard reagent adds to carbon dioxide to give a magnesium carboxylate, which on acidic work-up gives the carboxylic acid — this route adds exactly one carbon.

Worked example: 46 g of toluene (C₆H₅CH₃, molar mass 92 g/mol) is refluxed with excess alkaline KMnO₄ and then acidified, giving 80% of the theoretical yield of benzoic acid. Moles of toluene = 46/92 = 0.5 mol. The reaction C₆H₅CH₃ + 3[O] → C₆H₅COOH + H₂O is 1:1, so theoretical moles of benzoic acid (molar mass 122 g/mol) = 0.5 mol, i.e. theoretical mass = 0.5 × 122 = 61 g. At 80% yield, actual mass = 0.80 × 61 = 48.8 g.

Carboxylic acids are markedly acidic compared with alcohols and even phenols, because the carboxylate ion formed on loss of H⁺ is stabilised by resonance delocalisation of the negative charge over two equivalent oxygen atoms, whereas an alkoxide ion has no such delocalisation and a phenoxide ion delocalises charge less effectively (onto carbon, which is less electronegative than oxygen). Acid strength is expressed by the dissociation constant, K_a, or more conveniently by pK_a = −log₁₀K_a: a larger K_a (smaller pK_a) means a stronger acid.

Substituents change acid strength mainly through the inductive effect. Electron-withdrawing groups (halogens, –NO₂, –CN, –OR) pull electron density away from the carboxylate oxygens through the sigma-bond framework, further stabilising the negative charge and so increasing K_a (decreasing pK_a). Electron-donating alkyl groups push electron density towards the carboxylate, destabilising the negative charge and so decreasing acid strength. The inductive effect falls off quickly with distance, so a halogen closer to –COOH increases acidity more than the same halogen farther away, and multiple electron-withdrawing groups have a cumulative (though diminishing) effect. For example, CH₃COOH < ClCH₂COOH < Cl₂CHCOOH < Cl₃CCOOH in acid strength (pK_a approximately 4.76, 2.86, 1.29 and 0.66 respectively) shows both effects clearly.

Worked example: Calculate the pH of a 0.01 M solution of acetic acid (K_a = 1.8 × 10⁻⁵). Let [H₃O⁺] = x at equilibrium. Then K_a = x²/(0.01 − x) ≈ x²/0.01 (assuming x is small compared with 0.01). So x² = 1.8 × 10⁻⁵ × 0.01 = 1.8 × 10⁻⁷, giving x = 4.24 × 10⁻⁴ mol/L. Checking: x/0.01 ≈ 4.2%, close to the usual 5% cut-off for the approximation; solving the exact quadratic gives x = 4.15 × 10⁻⁴ mol/L, essentially the same answer. So pH = −log(4.2 × 10⁻⁴) ≈ 3.38 — far more acidic than pure water (pH 7), but, as expected for a weak acid, well short of a strong acid at the same concentration (pH 2.00).

The –COOH group undergoes several characteristic transformations. In esterification (Fischer esterification), a carboxylic acid reacts reversibly with an alcohol in the presence of a strong acid catalyst (conc. H₂SO₄ or dry HCl gas) and heat to give an ester and water: R–COOH + R′OH ⇌ R–COOR′ + H₂O. Because this is an equilibrium, ester yield can be improved by using an excess of one reactant or by removing water as it forms. Carboxylic acids can also be converted to more reactive derivatives: acid chlorides with SOCl₂ or PCl₅, and anhydrides by dehydration or reaction with an acid chloride; both are far more electrophilic than the parent acid and are used as convenient acylating agents.

Worked example (equilibrium yield): 1 mol acetic acid is mixed with 1 mol ethanol and allowed to reach esterification equilibrium, for which K_eq = 4. Let x mol of ester form at equilibrium. Then K_eq = [ester][water] / [acid][alcohol] = x² / (1−x)² = 4. Taking the square root of both sides, x/(1−x) = 2, so x = 2(1−x) = 2 − 2x, giving 3x = 2 and x = 2/3 ≈ 0.667 mol of ethyl acetate at equilibrium — about 67% conversion, even though the reaction never goes to completion because it is a true equilibrium.

The alpha-carbon of a carboxylic acid can be halogenated by the Hell–Volhard–Zelinsky (HVZ) reaction: treatment with Cl₂ or Br₂ in the presence of a catalytic amount of red phosphorus converts the acid, via its acid halide (which is more enolisable than the acid itself), into the alpha-halo acid: R–CH₂–COOH + X₂ →(red P) R–CHX–COOH + HX (X = Cl, Br). Carboxylic acid salts undergo decarboxylation on heating with soda lime (NaOH/CaO), losing carbon as carbonate to give an alkane with one fewer carbon than the original acid — a classical method of shortening a carbon chain. Aromatic carboxylic acids undergo electrophilic aromatic substitution at the ring; because –COOH is electron-withdrawing, it deactivates the ring and directs incoming electrophiles to the meta position. Finally, –COOH is reduced all the way to –CH₂OH by the strong hydride donor LiAlH₄ (NaBH₄ is not strong enough for this reduction).

Practically, low-molecular-weight carboxylic acids and their salts are used as food preservatives (e.g. acetic acid in vinegar, sodium benzoate), and esters of carboxylic acids are responsible for many natural fruit fragrances and are used as synthetic flavouring and fragrance agents.