Aldehydes, Ketones and Carboxylic Acids
Easy Overview
Aldehydes and ketones are the turning point in organic chemistry. Up to now, we have dealt mostly with alkanes, alkenes, alkyl halides, and alcohols — compounds that either donate electrons or are fairly neutral. Aldehydes and ketones contain the carbonyl group (C=O), which is highly polarized (Cδ⁺ = Oδ⁻) and acts as an electrophile. This opens up a universe of nucleophilic addition reactions, which are arguably the most important class of reactions in organic synthesis. The carbonyl carbon is sp² hybridized, making the C=O group planar with bond angles of about 120°. The C=O bond length (~122 pm) is shorter than a C-O single bond (~143 pm) and the bond energy is very high (about 745 kJ/mol — indeed the CO bond strength makes carbon monoxide so stable). The key to carbonyl chemistry: the electronegative oxygen pulls electron density away from carbon, making the carbon strongly electrophilic. Nucleophiles (like CN⁻, H⁻, RMgX, NH₃ derivatives) attack this carbon. The electrons move to the oxygen, forming a tetrahedral alkoxide intermediate — and that intermediate can go on to form many products. Aldehydes (R-CHO) have at least one H attached to the carbonyl group. Ketones (R-CO-R') have two alkyl/aryl groups. This difference is crucial for reactivity: aldehydes are generally more reactive than ketones because of steric (less crowded) and electronic (alkyl groups are electron-donating, making the ketone carbonyl less δ⁺) reasons. Aldehydes can also be oxidized to carboxylic acids (a key distinguishing feature) while ketones resist oxidation unless under harsh conditions that break C-C bonds. Both form hydrates (gem-diols) in water, but only small aldehydes exist significantly as hydrates. Formaldehyde in water exists mostly as H₂C(OH)₂. This chapter teaches you the addition-elimination pattern that carries through to carboxylic acids and their derivatives, amines, and many biomolecules.
Structure, nomenclature, and physical properties
The carbonyl group (C=O) is sp² hybridized — trigonal planar, with a π-bond perpendicular to the σ-framework. The C=O is polar (dipole moment ~2.5-2.8 D). Nomenclature: Aldehydes — replace -e of alkane with -al (methanal, ethanal, propanal). The aldehyde group is always at position 1 of the chain, so no number needed. Common names: formaldehyde (HCHO), acetaldehyde (CH₃CHO), benzaldehyde (C₆H₅CHO). Ketones — IUPAC: -e → -one, number the position of C=O (propanone, butan-2-one). Common: dimethyl ketone (acetone), diethyl ketone, ethyl methyl ketone. Physical properties: Carbonyl compounds have higher boiling points than alkanes (dipole-dipole interactions) but lower than alcohols (no O-H···O hydrogen bonding). Lower aldehydes/ketones are water-soluble. Formaldehyde (bp -19°C) is a gas at room temperature (formalin = 40% aqueous solution). Acetone is miscible with water. All have characteristic smells — aldehydes often have fruity/pleasant odours (except formaldehyde).
Preparation of aldehydes and ketones
From alcohols: 1° alcohol [O] → aldehyde (use PCC for aldehyde, CrO₃/H₂SO₄ for acid). 2° alcohol [O] → ketone (any oxidizing agent works). From alkenes: (1) Ozonolysis — alkene + O₃ → ozonide → reductive work-up (Zn/H₂O) → aldehydes and/or ketones depending on substitution. (2) Oxymercuration-demercuration with alkynes (for methyl ketones). From alkyl halides: Friedel-Crafts acylation — benzene + RCOCl (AlCl₃) → aromatic ketone (acetophenone, benzophenone). Gattermann-Koch formylation — benzene + CO + HCl (AlCl₃, CuCl) → benzaldehyde (special case — introduces CHO directly). From acid chlorides: Rosenmund reduction — RCOCl + H₂ (Pd/BaSO₄, poisoned with quinoline-S) → RCHO. From esters: reduction with DIBAL-H (diisobutylaluminium hydride) at -78°C → aldehyde (stops at aldehyde; LiAlH₄ goes to alcohol). In industry: Ethanal — Wacker process (ethene + O₂, PdCl₂/CuCl₂ catalyst). Acetone — cumene hydroperoxide route (from phenol synthesis).
Nucleophilic addition reactions — mechanism
The carbonyl carbon (δ⁺) is attacked by nucleophiles (δ⁻). General mechanism: Nu⁻ attacks C=O → tetrahedral alkoxide intermediate → addition product (after protonation). The intermediate is negatively charged on oxygen. The reaction is reversible for many nucleophiles. Reactivity: Aldehydes > ketones. Why? (1) Steric — ketones have two alkyl groups that hinder approach of the nucleophile. (2) Electronic — alkyl groups are electron-donating (+I effect), making the carbonyl carbon less δ⁺ in ketones. Conjugated aldehydes/ketones (like benzaldehyde, CH₂=CH-CHO) are less reactive because the C=O is in conjugation with the C=C or aromatic ring, delocalizing the positive charge. Crowded carbonyls (like di-tert-butyl ketone) barely react at all — this is called steric hindrance to nucleophilic addition.
Reactions with HCN — cyanohydrins
Aldehydes and ketones react with HCN to form cyanohydrins (α-hydroxy nitriles). The reaction requires a base catalyst (CN⁻ is the actual nucleophile, HCN alone is slow). Mechanism: CN⁻ attacks C=O → tetrahedral intermediate → H⁺ from HCN → cyanohydrin + CN⁻ regenerated. RCHO + HCN ⇌ RCH(OH)CN. Acetone gives (CH₃)₂C(OH)CN. Cyanohydrins are important synthetic intermediates — the -CN group can be hydrolyzed to -COOH (→ α-hydroxy acids) or reduced to -CH₂NH₂ (→ β-amino alcohols). The reaction is reversible, and equilibrium favors cyanohydrin for aldehydes but less for ketones. In benzoin condensation (a special reaction of aromatic aldehydes with CN⁻ catalyst): 2 C₆H₅CHO → benzoin (C₆H₅CO-CHOH-C₆H₅), a coupling of two aldehyde molecules.
Reactions with Grignard reagents — alcohol synthesis
Grignard reagents (RMgX) are powerful carbon nucleophiles. They attack the carbonyl carbon, and the tetrahedral intermediate (magnesium alkoxide) is hydrolyzed to an alcohol. This is the most general method for synthesizing alcohols from carbonyls: Formaldehyde → primary alcohol. Other aldehydes → secondary alcohol. Ketones → tertiary alcohol. HCHO + RMgX → RCH₂OMgX → (H₃O⁺) RCH₂OH. CH₃CHO + RMgX → RCHOHCH₃. R'₂CO + RMgX → R'₂RCOH. Limitations: acidic H atoms (OH, NH, SH) destroy Grignard reagents — these groups must be protected or absent. The reaction has great synthetic value because you can build carbon skeletons by choosing the right combination of carbonyl compound and Grignard reagent.
Reactions with ammonia derivatives — imines and oximes
Ammonia and its derivatives (primary amines, hydroxylamine, hydrazine, semicarbazide) add to C=O via addition-elimination: nucleophilic addition forms a tetrahedral intermediate, which then loses H₂O to form a C=N bond (imine or related compound). Products: RCHO + NH₃ → imine (RCH=NH, unstable). RCHO + R'NH₂ → substituted imine (Schiff base). RCHO + NH₂-OH (hydroxylamine) → oxime (RCH=N-OH). RCHO + NH₂-NH₂ (hydrazine) → hydrazone (RCH=N-NH₂). RCHO + NH₂NHCONH₂ (semicarbazide) → semicarbazone (RCH=N-NHCONH₂). These reactions are catalyzed by mild acid (pH ~3-5) — too much acid ties up the amine, too little does not activate the carbonyl. Oximes, hydrazones, and semicarbazones are usually crystalline solids with sharp melting points — they are used to identify and characterize aldehydes and ketones (derivative formation). The 2,4-dinitrophenylhydrazine (DNP/DNPH) derivative gives yellow/orange/red crystals — the Brady's test. Imines are intermediates in many biological processes (transamination reactions in amino acid metabolism).
Oxidation reactions — distinguishing aldehydes from ketones
Aldehydes are easily oxidized to carboxylic acids — this is a key difference from ketones. The aldehyde C-H bond is weak and the hydrate (RCH(OH)₂, gem-diol) is easily formed. Oxidizing agents: KMnO₄/H⁺, K₂Cr₂O₇/H⁺, Tollens' reagent, Fehling's reagent, Benedict's reagent. Tollens' test: aldehyde + [Ag(NH₃)₂]⁺ (Tollens' reagent) → silver mirror on the test tube + carboxylic acid (as ammonium salt). CH₃CHO + 2[Ag(NH₃)₂]⁺ + 2OH⁻ → CH₃COO⁻NH₄⁺ + 2Ag↓ + 3NH₃ + H₂O. Tollens' reagent is made by adding NaOH to AgNO₃ (brown precipitate of Ag₂O) then dissolving in NH₃. Fehling's test: aldehyde + Fehling's reagent (Cu²⁺ in alkaline tartrate) → Cu₂O brick-red precipitate (aldehyde → acid). Only aliphatic aldehydes give Fehling's test (aromatic aldehydes like benzaldehyde do not). Benedict's test is similar. Ketones do NOT give these tests (except α-hydroxy ketones like fructose). These reactions are the basis for detecting glucose in urine (Benedict's test for diabetes).
Reduction reactions — alcohols and hydrocarbons
Aldehydes reduce to primary alcohols, ketones to secondary alcohols. Reagents: (1) NaBH₄ (sodium borohydride) — mild, reduces only C=O, not C=C, works in water/alcohol. (2) LiAlH₄ (lithium aluminium hydride) — powerful, reduces C=O, C=C, COOH, esters, nitriles; must be in dry ether. (3) Catalytic hydrogenation (H₂, Ni/Pt/Pd) — reduces C=O and also any C=C present. Clemmensen reduction (Zn(Hg), conc. HCl) — converts C=O to CH₂ (→ hydrocarbon). Works for both aldehydes and ketones. Especially useful for aromatic compounds (benzaldehyde → toluene). Wolff-Kishner reduction — C=O + NH₂NH₂ (hydrazine) + KOH/ethylene glycol (heat) → CH₂ + N₂. The hydrazone intermediate loses N₂ in base. These two reactions (Clemmensen and Wolff-Kishner) are the classic methods for complete deoxygenation of carbonyl compounds to alkanes. Aldehydes are more easily reduced (by all methods) than ketones.
Aldol condensation — carbon-carbon bond formation
Aldol condensation is one of the most important methods for forming C-C bonds. An aldehyde or ketone with α-hydrogens reacts with itself (or another carbonyl) in the presence of dilute base (or acid) to form a β-hydroxy carbonyl compound (aldol = aldehyde + alcohol). Mechanism: (1) Base abstracts an α-hydrogen, forming an enolate ion (resonance-stabilized: C=C-O⁻ ↔ ⁻C-C=O). (2) The enolate acts as a carbon nucleophile and attacks the carbonyl carbon of another molecule. (3) The alkoxide is protonated to give the aldol product. For acetaldehyde: CH₃CHO + CH₃CHO (dil. NaOH) → CH₃CH(OH)CH₂CHO (3-hydroxybutanal) — an aldol. On heating, the aldol dehydrates (loses H₂O) to form an α,β-unsaturated aldehyde (crotonaldehyde, CH₃CH=CHCHO). This dehydration step gives conjugated enones, which are important synthetic intermediates. For ketones (acetone): (CH₃)₂CO (dil. NaOH) → (CH₃)₂C(OH)CH₂COCH₃ (diacetone alcohol). Crossed aldol: between two different aldehydes/ketones → gives mixtures unless one has no α-hydrogen (like benzaldehyde + acetaldehyde → only one product). Cannizzaro reaction: aldehydes without α-hydrogen (HCHO, C₆H₅CHO) undergo disproportionation in conc. base: 2 RCHO → RCH₂OH + RCOOH.
Nucleophilic addition of water and alcohols
Water adds reversibly to the C=O group to form gem-diols (hydrates): R₂C=O + H₂O ⇌ R₂C(OH)₂. Equilibrium favors the hydrate for small aldehydes (formaldehyde exists mostly as H₂C(OH)₂ in water), less for ketones (acetone is only ~0.1% hydrated). Electron-withdrawing groups on the carbonyl stabilize the hydrate by reducing negative charge build-up on oxygen — chloral (Cl₃CCHO) is almost completely hydrated (chloral hydrate was historically used as a sedative). Alcohols add similarly to form hemiacetals (R₂C(OH)(OR)). This is catalyzed by acid or base. Hemiacetals are unstable and react further with another alcohol molecule to form acetals (R₂C(OR)₂) — a reversible reaction. Acetal formation is important for protecting carbonyl groups during multi-step synthesis. To form an acetal: aldehyde + 2 ROH (dry HCl) → acetal + H₂O. Acetals are stable to base and mild acid; they are hydrolyzed back to the aldehyde by aqueous acid. Cyclic acetals (using ethylene glycol, HOCH₂CH₂OH) are especially useful protecting groups.
Key Points
- •Carbonyl (C=O): sp² hybridized, planar, polar; C is δ⁺ (electrophilic)
- •Aldehydes (RCHO) are more reactive than ketones (RCOR') — steric and electronic reasons
- •Nucleophilic addition to C=O: Nu⁻ attacks Cδ⁺ → tetrahedral intermediate → product
- •Cyanohydrin: RCHO + HCN → RCH(OH)CN; useful for α-hydroxy acids and β-amino alcohols
- •Grignard: RMgX + HCHO → 1° alcohol; + R'CHO → 2° alcohol; + ketone → 3° alcohol
- •Imines/oximes/hydrazones: addition-elimination (C=O → C=N); Brady's test (DNP derivative)
- •Tollens' test (Ag mirror), Fehling's test (Cu₂O red ppt) — aldehyde only, not ketone
- •Reduction: NaBH₄ (mild, C=O only), LiAlH₄ (powerful), Clemmensen (C=O → CH₂), Wolff-Kishner (C=O → CH₂)
- •Aldol condensation: enolate attacks another C=O → β-hydroxy carbonyl → α,β-unsaturated (on heating)
- •Cannizzaro: aldehydes without α-H in conc. base → alcohol + acid (disproportionation)
- •Acetals: RCHO + 2 ROH (dry HCl) → RCH(OR)₂ — carbonyl protecting group
- •Distinction: aldehydes oxidize to acids; ketones do not (unless harsh conditions)
Practice Questions
- Explain the mechanism of nucleophilic addition to the carbonyl group. Why are aldehydes more reactive than ketones?
- What is aldol condensation? Write the mechanism for the aldol condensation of acetaldehyde.
- Distinguish between aldehydes and ketones using (a) Tollens' test (b) Fehling's test (c) Iodoform test.
- How are the following obtained from carbonyl compounds? (a) Cyanohydrin (b) Acetal (c) Oxime (d) Schiff base.
- Explain Clemmensen and Wolff-Kishner reductions. Give one example of each.
- What happens when acetaldehyde reacts with (a) HCN (b) NaBH₄ (c) RMgX (d) NH₂OH?
- Write a note on the Cannizzaro reaction. Why does it occur only with aldehydes having no α-hydrogen?
- Using Grignard reaction, how would you prepare: (a) 2-methyl-2-butanol (b) 1-phenylethanol (c) benzyl alcohol?