Aldehydes, Ketones & Carboxylic Acids

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Aldehydes, Ketones & Carboxylic Acids — Key Facts for Makerere University (Uganda) Core concept: Carbonyl compounds contain the C=O functional group. Aldehydes have it at the end of the chain, ketones in the middle. Carboxylic acids have the –COOH group and are the most oxidized form High-yield points: Nucleophilic addition to carbonyls; oxidation reactions (aldehydes oxidize to acids; ketones don’t); reduction back to alcohols; distinguishing tests; acylation reactions ⚡ Exam tip: Questions frequently test your ability to distinguish aldehydes from ketones using Tollens’ or Fehling’s test, and to predict products of Grignard addition

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Aldehydes, Ketones & Carboxylic Acids — Makerere University (Uganda) Study Guide

1. Carbonyl Group — Structure and Reactivity

Structure of C=O

• Geometry: Trigonal planar, sp² hybridized carbon
• Bond angle: ~120°
• Bond length: ~123 pm (shorter than C–O single bond, ~143 pm)
• Bond energy: ~745 kJ/mol (stronger than C=C, ~611 kJ/mol, but addition is easier due to polar nature)
• Polarity: C=O is strongly polar; carbon is δ+ (electrophilic), oxygen is δ− (nucleophilic)

Resonance Structures

    δ+        δ−              δ+         δ−
    R–C=====O   ↔   R–C+–O⁻
    (major)      (minor)

The carbonyl carbon has a partial positive charge, making it susceptible to nucleophilic attack.

2. Aldehydes (–CHO)

Nomenclature

Suffix: -al (position 1 is always the aldehyde carbon)

• HCHO: Methanal (formaldehyde) — gas, pungent odor, preservative
• CH₃CHO: Ethanal (acetaldehyde) — bp 20°C, apple-like odor
• CH₃CH₂CHO: Propanal (propionaldehyde)
• CH₃(CH₂)₂CHO: Butanal
• Aromatic: C₆H₅CHO: Benzaldehyde (almond oil)

Physical Properties

• First three members are water-soluble (can H-bond via carbonyl oxygen)
• Boiling points higher than alkanes but lower than alcohols of similar MW
• Lower MW aldehydes have sharp, pungent odors; higher ones are fruity
• Methanal is a gas; ethanal is a volatile liquid

3. Ketones (–CO–)

Nomenclature

Suffix: -one (with locant for carbonyl position)

• CH₃COCH₃: Propanone (acetone) — bp 56°C, important solvent
• CH₃COC₂H₅: Butanone (methyl ethyl ketone, MEK)
• CH₃COC₃H₇: Pentan-2-one
• CH₃CH₂COCH₂CH₃: Pentan-3-one
• Aromatic: C₆H₅COCH₃: Acetophenone (phenyl ethanone)
• C₆H₅COC₆H₅: Benzophenone

Physical Properties

• Water solubility decreases with increasing MW
• Boiling points slightly higher than aldehydes of similar MW (more polarizable)
• Acetone is fully miscible with water and is a widely used solvent
• Pleasant odors (acetophenone smells like orange blossom)

Comparison: Aldehydes vs Ketones

Property	Aldehydes	Ketones
Structure	–CHO at chain end	–CO– in chain
Formula suffix	-al	-one
Oxidation	Readily oxidized	Resistant to mild oxidation
Tollens’ test	Positive	Negative
Fehling’s test	Positive	Negative
Polarity	More polar (higher bp)	Less polar (lower bp)

4. Carboxylic Acids (–COOH)

Nomenclature

Suffix: -oic acid

• HCOOH: Methanoic acid (formic acid) — from ants, corrosive
• CH₃COOH: Ethanoic acid (acetic acid) — vinegar, bp 118°C
• CH₃CH₂COOH: Propanoic acid
• CH₃(CH₂)₂COOH: Butanoic acid (butyric acid) — rancid butter odor
• HOOC–COOH: Ethanedioic acid (oxalic acid)
• Aromatic: C₆H₅COOH: Benzoic acid

Physical Properties

• Strong H-bonding (dimer formation via two H-bonds) → high boiling points
• First four members are water-soluble (miscible with water)
• Distinctive sharp/vinegar odors (acetic acid)
• Higher MW acids are waxy solids (fatty acids)
• Can form dimers in the solid and liquid state

Acidic Nature

Carboxylic acids are weak acids (pKa ~ 4.76 for acetic acid, ~4.9 for benzoic acid).

Why are carboxylic acids acidic? The carboxylate anion (R–COO⁻) is resonance-stabilized:

    O
    ‖
R–C–O⁻   ↔   R–C=O←O⁻
   (both canonical forms equivalent)

The negative charge is delocalized over two oxygen atoms, making the conjugate base stable.

Reaction with bases: R–COOH + NaOH → R–COONa + H₂O R–COOH + NaHCO₃ → R–COONa + CO₂ + H₂O (effervescence! — distinguishes from phenols) R–COOH + Na₂CO₃ → R–COONa + NaHCO₃ (or CO₂ if excess acid)

⚠️ Note: Carboxylic acids react with NaHCO₃ (producing CO₂) but phenols do not (phenol is too weak an acid, pKa ~10).

5. Reactions of Aldehydes and Ketones

Nucleophilic Addition Reactions

The carbonyl carbon (δ+) is attacked by nucleophiles. After attack, the tetrahedral alkoxide intermediate is protonated.

General mechanism:

    δ+     δ−         Nu⁻ attacks    Tetrahedral intermediate
    R–C=O    →     R–C–O⁻    →    (after protonation) R–C–OH
       |
    (no H at R end
     for ketone)

5.1 Addition of Hydrogen Cyanide (HCN)

R–CHO + HCN → R–CH(OH)–CN (cyanohydrin)

Conditions: Usually generated in situ from NaCN + acid, or KCN + acid Mechanism: CN⁻ attacks carbonyl carbon → alkoxide → protonation → cyanohydrin

⚠️ Toxicity: HCN and cyanides are extremely toxic — handle with care.

Example: Propanone + HCN → 2-hydroxy-2-methylpropanenitrile (acetone cyanohydrin) Used in: Synthesis of hydroxy acids, lactones, as intermediate in有机合成.

5.2 Addition of Sodium Hydrogensulfite (NaHSO₃)

R–CHO + NaHSO₃ → R–CH(OH)–SO₃Na (bisulfite addition compound) Conditions: Saturated aqueous NaHSO₃ (large excess) Note: Methyl ketones (R–CO–CH₃) also react, but not ketones with larger R groups. Uses: Purification of aldehydes and methyl ketones (bisulfite adduct can be regenerated).

5.3 Addition of Alcohols — Acetal and Ketal Formation

Aldehyde + 2ROH → R–CH(OR’)₂ + H₂O (acetal) Ketone + 2ROH → R–C(OR’)₂–R” + H₂O (ketal)

Conditions: Acid catalysis (HCl or p-toluenesulfonic acid), removal of water Mechanism:

1. Aldehyde + ROH → hemiacetal (R–CH(OH)–OR)
2. Hemiacetal + ROH → acetal (R–CH(OR)₂) + H₂O

Acetals and ketals are protecting groups — protect aldehydes/ketones from oxidation or reduction.

Example: Acetaldehyde + ethanol: CH₃CHO + 2C₂H₅OH → CH₃CH(OC₂H₅)₂ (diethyl acetal) + H₂O

5.4 Addition of Grignard Reagents

R–CHO + R’MgX → R–CH(OMgX)–R’ → (H₃O⁺) → R–CH(OH)–R’

Formaldehyde → 1° alcohol Aldehyde → 2° alcohol Ketone → 3° alcohol

Example: Acetone (CH₃COCH₃) + CH₃MgI → after workup → (CH₃)₂C(OH)–CH₃ (2-methylpropan-2-ol, a tertiary alcohol)

5.5 Addition of Amines

R–CHO + H₂N–R’ → R–CH=N–R’ + H₂O (imine/schiff base) R–CHO + H₂N–OH → R–CH=N–OH + H₂O (oxime) R–CHO + H₂N–NH–R’ → R–CH=N–NHR’ + H₂O (hydrazone) R–CHO + H₂N–NHCONH₂ → R–CH=N–NHCONH₂ (semicarbazone)

Conditions: Acid catalysis (often using molecular sieves to remove water) Note: Ketones also form these derivatives but more slowly.

6. Reduction Reactions

Reduction to Alcohols

NaBH₄ (mild) or LiAlH₄ (strong) or H₂/Ni:

• Aldehyde → 1° alcohol
• Ketone → 2° alcohol

Example: Butanal + NaBH₄ → butan-1-ol Example: Butanone + NaBH₄ → butan-2-ol

Reduction to Methylene (C=O → CH₂)

Wolff-Kishner Reduction (hydrazine + KOH, high temperature): R₂C=O → R₂CH₂ (alkane) Huang-Minlon Modification: R₂C=O + N₂H₄ + KOH → R₂CH₂ (works at lower temperature)

Clemmensen Reduction (Zn(Hg)/conc. HCl): R₂C=O → R₂CH₂ (alkane)

Both methods reduce C=O to CH₂ without affecting C=C double bonds (Wolff-Kishner is compatible with unsaturation).

7. Oxidation Reactions

Aldehydes — Readily Oxidized

Acidified K₂Cr₂O₇ or KMnO₄: R–CHO → R–COOH (carboxylic acid)

Tollens’ Reagent (Ag(NH₃)₂⁺): R–CHO + 2Ag(NH₃)₂⁺ + H₂O → R–COO⁻NH₄⁺ + 2Ag⁰ + 3NH₃ (Silver mirror test — a positive result confirms aldehyde)

Fehling’s Solution (Cu²⁺/tartrate): R–CHO + 2Cu²⁺ + 2H₂O → R–COO⁻ + Cu₂O (brick-red) + 4H⁺

Ketones — Resistant to Oxidation

Ketones do NOT oxidize under mild conditions. Exception: ω-oxidation of methyl ketones (e.g., CH₃–CO–R) can give carboxylic acids under vigorous conditions (hot KMnO₄ or hot CrO₃), cleaving the bond adjacent to the carbonyl.

Haloform Reaction (Methyl Ketones Only)

CH₃–CO–R + 3I₂ + 4NaOH → CHI₃ (yellow precipitate of iodoform) + R–COONa + 3NaI + 3H₂O

Positive iodoform test = methyl ketone (or ethanol which oxidizes to acetaldehyde → methyl ketone)

Example: Acetone gives CHI₃ (iodoform) with I₂/NaOH.

8. Reactions of Carboxylic Acids

8.1 Salt Formation

R–COOH + NaOH → R–COONa + H₂O R–COOH + Na₂CO₃ → R–COONa + NaHCO₃ (or CO₂ + H₂O with excess acid) R–COOH + NaHCO₃ → R–COONa + CO₂↑ + H₂O (effervescence!)

8.2 Esterification (Fischer Esterification)

R–COOH + R’–OH ⇌ R–COOR’ + H₂O Conditions: Acid catalyst (conc. H₂SO₄), heating Mechanism: Nucleophilic acyl substitution (via tetrahedral intermediate) Note: The reaction is reversible; excess alcohol or removal of water drives forward (Le Chatelier).

Examples:

• Acetic acid + ethanol → ethyl acetate (fruity odor)
• Benzoic acid + methanol → methyl benzoate

8.3 Reduction

LiAlH₄: R–COOH → R–CH₂OH (primary alcohol) NaBH₄ does NOT reduce carboxylic acids.

Example: Acetic acid + LiAlH₄ → ethanol

8.4 Decarboxylation

R–COOH → (soda lime, NaOH+CaO, heat) → R–H + CO₂

Mechanism: Heating with soda lime causes loss of CO₂ from the carboxyl group. Example: Sodium acetate + NaOH/CaO → methane CH₃COONa + NaOH → CH₄ + Na₂CO₃

8.5 Acyl Chloride Formation (SOCl₂ or PCl₅)

R–COOH + SOCl₂ → R–COCl + SO₂ + HCl Acid chlorides are very reactive derivatives used in further synthesis.

9. Derivatives of Carboxylic Acids

Acid Chlorides (R–COCl)

• Very reactive — hydrolyze easily to carboxylic acid
• Formed from R–COOH + SOCl₂ or PCl₅
• Used in Friedel-Crafts acylation of arenes

Acid Anhydrides (R–CO–O–CO–R)

• Formed from acid chlorides + carboxylate salts, or by dehydration of acids
• Acetic anhydride: (CH₃CO)₂O — important acetylating agent
• Propanoic anhydride from propanoic acid (P₂O₅)

Esters (R–COOR’)

• Formed from acid + alcohol (Fischer esterification)
• Can be hydrolyzed: acid-catalyzed (reversible) or base-catalyzed (irreversible — saponification)

Amides (R–CONH₂, R–CONHR’, R–CONR₂)

• Formed from acid chlorides + amines
• Least reactive of the carboxylic acid derivatives
• Can be hydrolyzed back to carboxylic acids

Reactivity Order of Acid Derivatives

Acid chloride > Acid anhydride > Ester > Amide > Carboxylate anion

(From most electrophilic/least stabilized to least electrophilic/most stabilized)

10. Distinguishing Tests

Test	Aldehyde	Ketone	Carboxylic Acid	Alcohol
NaHCO₃	No effervescence	No effervescence	Effervescence (CO₂)	No effervescence
Tollens’	Silver mirror	No reaction	No reaction	No reaction
Fehling’s	Red precipitate	No reaction	No reaction	No reaction
K₂Cr₂O₇/H⁺	Oxidizes to acid	No reaction	No reaction	Oxidizes
2,4-DNP	Orange/red crystals	Orange/red crystals	No reaction	No reaction
I₂/NaOH	Iodoform if methyl ketone	Iodoform if methyl ketone	No reaction	Iodoform if ethanol

11. Exam-Style Questions & Tips

Common exam question patterns at Makerere:

1. “Write the structure of [aldehyde/ketone/carboxylic acid] and state two of its characteristic reactions”
2. “How would you distinguish between [compound A] and [compound B] using chemical tests?”
3. “Describe the mechanism of nucleophilic addition to a carbonyl group”
4. “Explain why carboxylic acids are acidic despite being weak acids”
5. “Predict the product(s) when [compound] reacts with [reagent]”
6. “State and explain the difference in reactivity between aldehydes and ketones”

⚡ Exam tips:

• Aldehydes are more reactive than ketones toward nucleophilic addition (less substituted carbonyl = more electrophilic carbon; less steric hindrance)
• Carboxylic acids do NOT give positive Tollens’ or Fehling’s tests (they oxidize with difficulty)
• The iodoform test works for methyl ketones AND ethanol (which oxidizes to acetaldehyde → methyl ketone)
• Remember: NaBH₄ reduces aldehydes and ketones but NOT esters; LiAlH₄ is needed for ester reduction

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12. Reaction Mechanisms — Detailed

Nucleophilic Addition — Detailed Mechanism

Step 1: Nucleophile (Nu:) attacks carbonyl carbon (C=O)
        The π bond electrons move toward oxygen
        O becomes negatively charged (alkoxide intermediate)

Step 2: Protonation of alkoxide oxygen
        By solvent or acid (if acid-catalyzed)
        Final alcohol product forms

Acid-catalyzed version: Carbonyl oxygen is protonated first, making the carbon even more electrophilic, then nucleophile attacks.

Fischer Esterification Mechanism

Step 1: Acid protonates carbonyl oxygen
Step 2: Alcohol attacks carbonyl carbon (nucleophilic acyl substitution)
Step 3: Proton transfers
Step 4: Loss of water (elimination) — leaving group is H₂O
Step 5: Deprotonation gives ester

Key point: The –OH of the acid (not the alcohol) is lost as water. This can be proven by isotopic labeling (¹⁸O experiments).

Decarboxylation Mechanism

For beta-keto acids (β-keto acids), decarboxylation occurs readily because:

1. A cyclic six-membered transition state allows the carboxyl group to leave as CO₂
2. The resulting enolate is resonance-stabilized

Example: Acetoacetic ester synthesis: CH₃–CO–CH₂–COOEt → (heat or acid) → CH₃–CO–CH₃ + CO₂

13. Important Named Reactions

Aldol Condensation

Aldehydes with α-hydrogens undergo self-condensation in base: 2CH₃CHO → CH₃–CH(OH)–CH₂–CHO (aldol) → (heat, base) → CH₃–CH=CH–CHO (crotonaldehyde) + H₂O

Uses: Formation of C–C bonds; synthesis of longer-chain carbonyl compounds.

Cannizzaro Reaction

Aldehydes WITHOUT α-hydrogens undergo disproportionation in concentrated base: 2HCHO + OH⁻ → CH₃OH + HCOO⁻ (formaldehyde + base → methanol + formate) 2C₆H₅CHO + OH⁻ → C₆H₅CH₂OH + C₆H₅COO⁻ (benzaldehyde → benzyl alcohol + benzoate)

Required: Aldehyde must lack α-hydrogen (formaldehyde, benzaldehyde, p-methoxybenzaldehyde).

Clemmensen Reduction

Zn(Hg) + conc. HCl reduces C=O to CH₂: R–CO–R’ → R–CH₂–R’ Does not reduce C=C double bonds. Used in: Structure determination of ketones (deuterium labeling can identify which carbon is the carbonyl carbon).

Wolff-Kishner Reduction

N₂H₄ + KOH (high temp) or Huang-Minlon modification (lower temp): R–CO–R’ → R–CH₂–R’ Compatible with reducible groups (C=C can survive).

14. Unsaturated Carbonyl Compounds

α,β-Unsaturated Carbonyls

Structure: –C=C–C=O (conjugated system)

Reactions:

• Nucleophiles can attack at two positions:
  1. Direct (1,2-) addition: Attack at carbonyl carbon (as normal)
  2. Conjugate (1,4-) addition: Attack at the β-carbon (C=C carbon)

Michael addition: Conjugate addition of nucleophiles (e.g., enolates, amines) to α,β-unsaturated carbonyls: R–CH=CH–CO–R’ + Nu: → R–CH(Nu)–CH₂–CO–R’

15. Industrially Important Compounds

Formaldehyde (Methanal)

• Produced by oxidation of methanol: CH₃OH + ½O₂ → HCHO + H₂O (Ag catalyst, high temp)
• Uses: Formaldehyde resins (Bakelite), plastics, preservation, synthesis of methanol

Acetaldehyde (Ethanal)

• From oxidation of ethanol or hydration of acetylene
• Intermediate in metabolism (alcohol dehydrogenase converts ethanol → acetaldehyde)

Acetone (Propanone)

• From cumene hydroperoxide process: cumene → phenol + acetone
• Important solvent; precursor to bisphenol A (plastic)
• Used in: nail polish remover, resin synthesis

Acetic Acid (Ethanoic Acid)

• Produced by methanol carbonylation (Monsanto process): CH₃OH + CO → CH₃COOH (Rh/I₂ catalyst)
• Also from oxidation of acetaldehyde or ethanol
• Uses: Vinegar, acetate fibers, aspirin synthesis

Benzoic Acid

• From oxidation of toluene: C₆H₅CH₃ + 3/2O₂ → C₆H₅COOH + H₂O
• Sodium benzoate used as food preservative (inhibits mold and bacteria in acidic foods)

Practice Problems

Q1: Write equations for the reactions of: (a) Propanal with Tollens’ reagent (b) Acetone with I₂/NaOH (c) Acetic acid with Na₂CO₃ (d) Ethyl acetate with NaOH (heat) (e) Acetone with CH₃MgBr followed by acidic workup

Q2: How would you distinguish between: (a) Propanal and propanone (b) Acetic acid and phenol (c) Ethanol and ethanoic acid (d) Methyl acetate and acetic acid

Q3: Describe the mechanism of Fischer esterification between ethanoic acid and ethanol.

Q4: Explain why ketones are less reactive than aldehydes toward nucleophilic addition.

Q5: A compound with formula C₄H₈O₂ has a pleasant fruity odor. It dissolves in NaOH solution with heating and acidification regenerates an acid with the same carbon skeleton. What is the structure?

Q6: Write the structure of the cyanohydrin formed from the reaction of propanone with HCN.

Common Mistakes to Avoid

1. Forgetting that aldehydes oxidize but ketones don’t (under mild conditions): This is key to distinguishing them.
2. Confusing the products of Grignard addition: Formaldehyde → 1° alcohol, aldehyde → 2° alcohol, ketone → 3° alcohol.
3. Thinking carboxylic acids are STRONG acids: They’re weak acids (pKa ~4-5), weaker than HCl or H₂SO₄. They DO react with carbonates though.
4. Forgetting the iodoform test: It works on methyl ketones AND ethanol (which oxidizes to acetaldehyde, itself a methyl ketone).
5. Confusing acetal and ketal formation: Both involve aldehyde/ketone + 2 alcohol equivalents; acetal from aldehydes, ketal from ketones.
6. Thinking all esters are water-soluble: Higher MW esters are not water-soluble despite being polar.

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