Aldehydes, Ketones & Carboxylic Acids

1. Nucleophilic Addition to Carbonyl (C=O)

The carbonyl group is polarized (C $\delta$+ and O $\delta$-) due to the electronegativity difference. Nucleophiles attack the electrophilic carbon.

Mechanism: Nu:- attacks C=O carbon → tetrahedral alkoxide intermediate → protonation or elimination depending on the nucleophile.

Reactivity order (decreasing): HCHO > CH₃CHO > C₂H₅CHO > (CH₃)₂CO > C₆H₅COCH₃ > C₆H₅COC₆H₅

• Steric factor: Less steric hindrance at carbonyl C → more reactive. HCHO (no R groups) is most reactive.
• Electronic factor: Electron-donating groups (+I of alkyl) reduce electrophilicity. Electron-withdrawing groups (-I) increase it.

Key carbonyl compounds:

Acetaldehyde (CH₃CHO)

Acetone (CH₃COCH₃)

Benzaldehyde (C₆H₅CHO)

Acetophenone (C₆H₅COCH₃)

Key Nucleophilic Addition Reactions:

• HCN → Cyanohydrin: RCH=O + HCN → RCH(OH)CN (useful for chain elongation, C-C bond formation)
• NaHSO₃ → Bisulfite addition: RCHO + NaHSO₃ → RCH(OH)SO₃Na (crystalline, used for purification; works with aldehydes and methyl ketones only)
• RMgX (Grignard): HCHO → 1° alcohol; RCHO → 2° alcohol; R₂CO → 3° alcohol; R'COOR" → 3° alcohol (2 eq RMgX)
• RLi (Organolithium): Similar to Grignard but more reactive
• Ylide (Wittig): R₂CO + Ph₃P=CHR' → R₂C=CHR' + Ph₃P=O (alkene synthesis)

2. Nucleophilic Addition-Elimination (Condensation with N-nucleophiles)

When the nucleophile has an -NH₂ group, the initial addition product loses water.

3. Alpha-Hydrogen Reactions

The $\alpha$-C-H (adjacent to C=O) is acidic (pKa ~20 for ketones) due to enolate anion resonance stabilization.

Aldol Condensation: 2 RCHO → RCH(OH)-CH(R)-CHO ($\beta$-hydroxy aldehyde) → heat → $\alpha$,$\beta$-unsaturated aldehyde (aldol product loses water).

• Requires at least one $\alpha$-H
• Base-catalyzed: NaOH abstracts $\alpha$-H → enolate → nucleophilic attack on another carbonyl
• Crossed aldol: Two different carbonyl compounds, one with $\alpha$-H and one without (like HCHO or ArCHO)

Cannizzaro Reaction: Aldehydes WITHOUT $\alpha$-H undergo simultaneous oxidation and reduction in concentrated NaOH.

• 2HCHO + conc. NaOH → HCOONa + CH₃OH (one molecule oxidized, one reduced)
• Crossed Cannizzaro: HCHO + RCHO → RCH₂OH + HCOONa (HCHO always gets oxidized)

Haloform Reaction: Methyl ketones (RCOCH₃) + X₂/NaOH → RCOO-Na+ + CHX₃

• Iodoform test: RCOCH₃ + I₂/NaOH → yellow CHI₃ precipitate
• Also positive for: CH₃CHO, ethanol, isopropanol (oxidized to methyl ketones in situ)

4. Oxidation and Reduction

Oxidation:

• Aldehydes → Carboxylic acids: Tollens' (Ag+/NH₃ → Ag mirror), Fehling's (Cu₂+ → Cu₂O red ppt), KMnO₄, K₂Cr₂O₇
• Ketones resist mild oxidation; strong oxidants cleave C-C bond adjacent to C=O

Reduction:

• NaBH₄: Reduces aldehydes and ketones → alcohols (selective — doesn't reduce C=C, ester, amide)
• LiAlH₄: Reduces almost everything (C=O, COOH, COOR, CONR₂, C≡N) → alcohols/amines
• Clemmensen (Zn-Hg/HCl): C=O → CH₂ (acidic conditions)
• Wolff-Kishner (NH₂NH₂/KOH): C=O → CH₂ (basic conditions)
• Meerwein-Ponndorf-Verley: Al(OiPr)₃ reduces ketone via hydride transfer from isopropoxide

5. Carboxylic Acids

Acidity: RCOOH ⇌ RCOO- + H+ (pKa ~4-5). Stabilized by equivalent resonance of carboxylate anion (charge delocalized over 2 oxygens).

Effect of substituents on acidity:

• -I groups increase acidity: Cl₃CCOOH > Cl₂CHCOOH > ClCH₂COOH > CH₃COOH
• +I groups decrease acidity: (CH₃)₃CCOOH < (CH₃)₂CHCOOH < CH₃CH₂COOH < CH₃COOH < HCOOH

Acetic acid:

Benzoic acid:

Key Reactions of Carboxylic Acids:

• Esterification (Fischer): RCOOH + R'OH ⇌ RCOOR' + H₂O (H+ catalyst, reversible)
• Acid chloride formation: RCOOH + SOCl₂ → RCOCl + SO₂ + HCl (or PCl₅, PCl₃)
• Decarboxylation: RCOONa + NaOH/CaO → RH + Na₂CO₃ (soda-lime)
• HVZ reaction: RCOOH + Br₂/P → $\alpha$-bromo acid (Hell-Volhard-Zelinsky — via acid halide enolization)
• Reduction: RCOOH + LiAlH₄ → RCH₂OH; NaBH₄ does NOT reduce -COOH
• Kolbe electrolysis: 2RCOO- → R-R + 2CO₂ + 2e-
• Arndt-Eistert synthesis: RCOOH → RCOCl → RCOCHN₂ → RCH₂COOH (homologation by one CH₂)

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