Aldehydes, Ketones & Carboxylic Acids - Concept Based Problems - Reactivity order of compounds towards nucleophile

  • Aldehydes, ketones & carboxylic acids are important organic compounds.
  • They exhibit different reactivities towards nucleophiles.
  • The reactivity order of compounds towards nucleophile depends on the presence of electron-withdrawing or electron-donating groups.
  • Nucleophiles are electron-rich species that attack electron-deficient centers.
  • The nucleophile attacks the carbonyl carbon in aldehydes, ketones, and carboxylic acids.

Reactivity order of compounds towards nucleophile based on structure

  1. Aldehydes generally show higher reactivity compared to ketones.
  1. Aldehydes have a hydrogen atom attached to the carbonyl carbon, which makes them more electron-deficient.
  1. Ketones have two alkyl groups attached to the carbonyl carbon, which makes them less electron-deficient.

Reactivity order of compounds towards nucleophile based on substituents

  1. Electron-withdrawing groups (EWG) attached to the carbonyl carbon decrease the reactivity.
    • Examples: Nitro group (-NO2), halogens (-Cl, -Br, -I), cyano group (-CN), etc.
  1. Electron-donating groups (EDG) attached to the carbonyl carbon increase the reactivity.
    • Examples: Alkyl groups (-CH3, -C2H5), methoxy group (-OCH3), amino group (-NH2), etc.

Examples

  1. Reactivity towards nucleophile:
    • Aldehyde: Formaldehyde > Acetaldehyde > Benzaldehyde
    • Ketone: Acetone > Cyclohexanone > Benzophenone
    • Carboxylic Acid: Formic acid > Acetic acid > Benzoic acid
  1. Influence of substituents:
    • Aldehyde with nitro group: Less reactive
    • Aldehyde with alkyl group: More reactive
  1. Comparing ketones with different alkyl groups:
    • Methyl ethyl ketone (MEK) > Methyl isobutyl ketone (MIBK)

Reactivity order and nucleophilic addition

  • The reactivity order determines the ease of nucleophilic addition reactions.
  • Nucleophilic additions lead to the formation of alcohols or carboxylates, depending on the reaction conditions.

Mechanism of nucleophilic addition

  1. Nucleophile attacks the carbonyl carbon, forming a tetrahedral intermediate.
  1. Proton transfer occurs, leading to the formation of alcohol or carboxylate.
  1. The reaction depends on the strength and nucleophilicity of the attacking nucleophile.

Summary

  • Reactivity order towards nucleophile:
    1. Aldehydes > Ketones
    2. Electron-withdrawing groups decrease reactivity
    3. Electron-donating groups increase reactivity
  • Nucleophilic addition reactions:
    • Form tetrahedral intermediate
    • Proton transfer leads to the formation of alcohol or carboxylate

Conclusion

  • Understanding the reactivity order of aldehydes, ketones, and carboxylic acids towards nucleophiles helps in predicting the outcome of nucleophilic addition reactions.
  • The presence of electron-withdrawing or electron-donating groups further influences the reactivity order.
  1. Reactive groups:
    • Electron-withdrawing groups:
      • Nitro group (-NO2)
      • Halogens (-Cl, -Br, -I)
      • Cyano group (-CN)
      • Ester group (-COO-R)
    • Electron-donating groups:
      • Alkyl groups (-CH3, -C2H5)
      • Methoxy group (-OCH3)
      • Amino group (-NH2)
  1. Examples of reactive groups:
    • Aldehyde with nitro group: Benzaldehyde with -NO2 group
    • Ketone with halogen group: Acetophenone with -Cl group
    • Aldehyde with alkyl group: Butanal with -CH3 group
  1. Reactivity of aldehydes and ketones with carbon nucleophiles:
    • Carbon nucleophiles: Grignard reagents, organolithium compounds
    • Easily add to the carbonyl carbon of aldehydes and ketones
    • Form alcohols as products
    • Example equation: Benzaldehyde + CH3MgBr → Benzyl alcohol + MgBr2
  1. Reactivity of aldehydes and ketones with nitrogen nucleophiles:
    • Nitrogen nucleophiles: Primary and secondary amines
    • Add to the carbonyl carbon of aldehydes and ketones
    • Form imines (aldimines/ketimines) as products
    • Example equation: Penta-2,4-dienal + Ethylamine → Penta-2,4-dienimine + Ethanol
  1. Reactivity of aldehydes and ketones with oxygen nucleophiles:
    • Oxygen nucleophiles: Water, alcohol
    • Add to the carbonyl carbon of aldehydes and ketones
    • Form hydrates as products (in the presence of acid)
    • Example equation: Ethanal + Methanol → Methoxyethanol
  1. Reactivity of carboxylic acids with ammonia:
    • Carboxylic acids react with ammonia (NH3)
    • Form primary amides as products
    • Example equation: Ethanoic acid + Ammonia → Ethyl amide + Water
  1. Reactivity of carboxylic acids with alcohols:
    • Carboxylic acids react with alcohols
    • Form esters as products (in the presence of acid catalyst)
    • Example equation: Acetic acid + Methanol → Methyl acetate + Water
  1. Reactivity of carboxylic acids with bases:
    • Carboxylic acids react with strong bases (e.g., sodium hydroxide)
    • Form carboxylate salts as products
    • Example equation: Benzoic acid + NaOH → Sodium benzoate + Water
  1. Reactivity of carboxylic acids with acyl chlorides:
    • Carboxylic acids react with acyl chlorides
    • Form acid anhydrides as products
    • Example equation: Ethanoyl chloride + Ethanoic acid → Ethanoic anhydride + HCl
  1. Summary:
    • Aldehydes and ketones have different reactivities towards nucleophiles.
    • Reactive groups can enhance or decrease the reactivity.
    • Aldehydes and ketones can undergo addition reactions with carbon, nitrogen, and oxygen nucleophiles.
    • Carboxylic acids can react with ammonia, alcohols, bases, and acyl chlorides.

Slide 21: Nucleophilic addition reactions of aldehydes and ketones

  • Nucleophilic addition reactions involve the addition of nucleophiles to the carbonyl carbon of aldehydes and ketones.
  • These reactions form new carbon-nucleophile bonds and result in the formation of alcohol or imine products.
  • Nucleophiles that can undergo addition reactions include:
    • Carbon nucleophiles (Grignard reagents, organolithium compounds),
    • Nitrogen nucleophiles (primary and secondary amines), and
    • Oxygen nucleophiles (water and alcohols).
  • Example equations:
    • Aldehyde + CH3MgBr → Alcohol + MgBr2
    • Ketone + RLi → Alcohol + RL

Slide 22: Nucleophilic addition reactions of carboxylic acids

  • Carboxylic acids can also undergo nucleophilic addition reactions.
  • The reactions involve the addition of nucleophiles to the carbonyl carbon of carboxylic acids.
  • The resulting products can be amides, esters, carboxylate salts, or acid anhydrides, depending on the specific nucleophile used.
  • Example equations:
    • Carboxylic acid + NH3 → Amide + Water
    • Carboxylic acid + alcohol → Ester + Water
    • Carboxylic acid + base → Carboxylate salt + Water
    • Carboxylic acid + acyl chloride → Acid anhydride + HCl

Slide 23: Reduction of carbonyl compounds

  • Reduction reactions involve the addition of hydrogen (H2) or hydride (H^-) to the carbonyl carbon, resulting in the formation of alcohols.
  • Reducing agents commonly used are lithium aluminum hydride (LiAlH4) and sodium borohydride (NaBH4).
  • LiAlH4 is a strong reducing agent and can reduce both aldehydes and ketones.
  • NaBH4 is a milder reducing agent and primarily reduces aldehydes and some ketones.
  • Example equation: Aldehyde/Ketone + NaBH4 → Alcohol

Slide 24: Oxidation of alcohols to carbonyl compounds

  • Oxidation of alcohols involves the removal of hydrogen from the alcohol, resulting in the formation of carbonyl compounds.
  • Oxidizing agents commonly used are potassium permanganate (KMnO4) and chromium trioxide (CrO3).
  • Primary alcohols can be oxidized to aldehydes and further to carboxylic acids.
  • Secondary alcohols can be oxidized to ketones.
  • Tertiary alcohols cannot be oxidized.
  • Example equations:
    • Primary alcohol → Aldehyde → Carboxylic acid
    • Secondary alcohol → Ketone

Slide 25: Reaction of aldehydes with Tollen’s reagent

  • Aldehydes react with Tollen’s reagent (ammoniacal silver nitrate) to form a silver mirror.
  • This reaction is used as a test for aldehydes.
  • In the presence of an aldehyde, Tollen’s reagent is reduced to metallic silver, which forms a mirror-like deposit on the test tube or container.
  • Ketones do not react with Tollen’s reagent and therefore do not produce a silver mirror.
  • Example equation: Aldehyde + Tollen’s reagent → Silver mirror

Slide 26: Reaction of aldehydes with Fehling’s solution

  • Aldehydes react with Fehling’s solution (copper(II) ions complexed with tartrate ions) to form a brick-red precipitate of copper(I) oxide.
  • This reaction is also used as a test for aldehydes.
  • Ketones do not react with Fehling’s solution and therefore do not produce a precipitate.
  • Example equation: Aldehyde + Fehling’s solution → Brick-red precipitate

Slide 27: Reaction of aldehydes and ketones with 2,4-DNP

  • Aldehydes and ketones react with 2,4-dinitrophenylhydrazine (2,4-DNP) to form yellow/red/orange precipitates known as 2,4-DNP derivatives.
  • This reaction is used as a test to identify aldehydes and ketones.
  • The specific colored precipitate formed can be used to identify the specific aldehyde or ketone.
  • Example equation: Aldehyde/Ketone + 2,4-DNP → 2,4-DNP derivative

Slide 28: Aldol condensation reaction

  • Aldol condensation is a reaction between two molecules of aldehyde or ketone to form a β-hydroxyaldehyde or β-hydroxyketone, respectively.
  • The reaction involves the addition of the α-carbon of one molecule to the carbonyl group of the other molecule, followed by dehydration to eliminate water.
  • This reaction is highly useful in organic synthesis for the formation of larger molecules.
  • Example equation: Aldehyde/Ketone + Aldehyde/Ketone → Aldol + Water

Slide 29: Claisen condensation reaction

  • Claisen condensation is a reaction between two molecules of ester or ketone to form a β-ketoester or β-diketone, respectively.
  • The reaction involves the addition of the α-carbon of one molecule to the carbonyl group of the other molecule, followed by dehydration to eliminate alcohol.
  • This reaction is important in organic synthesis for the formation of carbon-carbon bonds.
  • Example equation: Ester/Ketone + Ester/Ketone → β-ketoester/β-diketone + Alcohol

Slide 30: Summary and Key Takeaways

  • Nucleophilic addition reactions of aldehydes and ketones form alcohol or imine products.
  • Carboxylic acids can undergo nucleophilic addition to form amides, esters, carboxylate salts, or acid anhydrides.
  • Reduction reactions convert carbonyl compounds to alcohols using LiAlH4 or NaBH4.
  • Oxidation reactions convert alcohols to carbonyl compounds using KMnO4 or CrO3.
  • Aldehydes show characteristic reactions with Tollen’s reagent and Fehling’s solution.
  • Aldehydes and ketones form 2,4-DNP derivatives.
  • Aldol condensation and Claisen condensation are important carbon-carbon forming reactions.