Nucleophilic Cleavage of O-H Bond

• In nucleophilic cleavage, a nucleophile attacks the carbonyl carbon of aldehydes/ketones
• This reaction results in the formation of two new compounds

Example:

R | R-C=O + Nu^(-) → (R-C)-O(-)Nu + R' | H

• Here, R and R’ denote alkyl or aryl groups, and Nu represents a nucleophile

Nucleophilic Cleavage of O-H Bond (contd.)

• Let’s explore some notable examples of nucleophilic cleavage reactions:

1. Reaction with Grignard reagents: R | R-C=O + R'-Mg-X → (R-C)-O(-)MgX + R' | H

2. Reaction with Sodium cyanide: R | R-C=O + NaCN → (R-C)-O(-)CN + Na^+ | H

3. Reaction with Hydrazine derivatives: R | R-C=O + NH_2-NH_2 → (R-C)-O(-)NH-NH_2 + H_2O | H

Acidic Cleavage of O-H Bond

• In acidic cleavage, water or other water molecules act as an acid and donate a proton
• This reaction results in the formation of an alcohol as one product

Example:

R | R-C=O + H_2O → R-C-(OH_2)^+ + OH^(-) | H

• Here, R represents an alkyl or aryl group

Acidic Cleavage of O-H Bond (contd.)

• Let’s look at some examples of acidic cleavage reactions:

1. Reaction with dilute mineral acids: R | R-C=O + H_2SO_4 → R-C-(OH_2)^+ + HSO_4^(-) | H

2. Reaction with dilute alkali: R | R-C=O + NaOH → R-C-(OH_2)^+ + Na^+ | H

3. Reaction with phenols: R | R-C=O + PhOH → R-C-(OH_2)^+ + PhO^(-) | H

Summary

• Cleavage of the O-H bond is a significant reaction in aldehydes, ketones, and carboxylic acids
• Nucleophilic cleavage results in the formation of two new compounds
• Acidic cleavage leads to the formation of an alcohol
• Various nucleophiles and acids can be used for this reaction
• Understanding these reactions can enable the synthesis of organic compounds Remember, practice is essential for mastering these reactions!

11. Nucleophilic Cleavage of O-H Bond (contd.)

• Reaction with Sodium borohydride: R | R-C=O + NaBH_4 → (R-C)-OH + NaBH_3=O | H
• Reaction with Lithium aluminum hydride: O / \\ R-C O + LiAlH_4 → R-CH_2OH + LiAl(OH)_3 | H
• These reactions are often used for the reduction of aldehydes and ketones to alcohols

12. Acidic Cleavage of O-H Bond (contd.)

• Reaction with hydroxylamine: R | R-C=O + NH_2OH → R-C=NHOH + H_2O | H
• Reaction with phenylhydrazine: R | R-C=O + C_6H_5NHNH_2 → R-C=N-NHC_6H_5 + H_2O | H
• These reactions are commonly used for the synthesis of oximes and hydrazones

13. Aldol Condensation - Overview

• Aldol condensation is a reaction between two molecules of aldehyde or ketone
• This reaction results in the formation of a β-hydroxyaldehyde or β-hydroxyketone
• The process involves the nucleophilic addition of an enolate ion to the carbonyl group of another molecule
• The resulting compound is often dehydrated to generate an α,β-unsaturated carbonyl compound

14. Aldol Condensation - Mechanism

• The aldol condensation reaction involves several steps, including:
  1. Formation of an enolate ion from the carbonyl compound
  2. Nucleophilic attack of enolate ion on another carbonyl compound
  3. Formation of a β-hydroxyaldehyde or β-hydroxyketone
  4. Dehydration to yield an α,β-unsaturated carbonyl compound
• The reaction is typically catalyzed by either an acid or a base

15. Aldol Condensation - Example

• Example 1: Cross aldol condensation O O //\\ //\\ CH_3-C-CH_3 + CH_3-C-CH_3 → CH_3-C-C-CH_3 + H_2O | | H H
• Example 2: Self-aldol condensation O O //\\ //\\ CH_3-C-CH_2 + CH_3-C-CH_2 → CH_3-C-C-CH_2 + H_2O | | H H

16. Cannizzaro Reaction - Overview

• The Cannizzaro reaction is a disproportionation reaction of an aldehyde
• This reaction involves the simultaneous oxidation and reduction of the same aldehyde molecule
• One molecule of the aldehyde is reduced to an alcohol, while another molecule of the aldehyde is oxidized to a carboxylic acid
• This reaction occurs in the presence of a strong base

17. Cannizzaro Reaction - Mechanism

• The Cannizzaro reaction proceeds through the following steps:
  1. Deprotonation of the aldehyde to form an anion
  2. Nucleophilic attack of the anion on another aldehyde molecule
  3. Simultaneous oxidation and reduction reactions take place, forming an alcohol and a carboxylic acid
• The reaction is usually carried out in an alcoholic or aqueous alkaline medium

18. Cannizzaro Reaction - Example

• Example: Formaldehyde undergoes the Cannizzaro reaction H H OH OH | | | | H-C-C-H + KOH → H-C-C-K + H-C-C-OH | | | | H H H OH

19. Decarboxylation - Overview

• Decarboxylation is a process that involves the loss of a carboxyl group (-COOH) from a compound
• This reaction is commonly observed in carboxylic acids
• Decarboxylation usually requires high temperatures or the use of catalysts
• It is an important reaction in the synthesis of various compounds, including hydrocarbons and organic acids

20. Decarboxylation - Example

• Example: Ethanoic acid undergoing decarboxylation CH_3-COOH → CH_4 + CO_2 | H Remember to practice these reactions and their mechanisms for a better understanding. Sure! Here are slides 21 to 30:

21. Esterification - Overview

• Esterification is a reaction that involves the formation of an ester from a carboxylic acid and an alcohol
• This is a condensation reaction that releases water as a byproduct
• The reaction is catalyzed by an acid, such as sulfuric acid or hydrochloric acid
• Esterification is widely used in the synthesis of fragrances, flavors, and plasticizers

22. Esterification - Mechanism

• Esterification proceeds through the following steps:
  1. Protonation of the carbonyl group of the carboxylic acid
  2. Nucleophilic attack of the alcohol on the carboxylic acid
  3. Formation of an intermediate compound
  4. Deprotonation and loss of water to yield the ester
• The reaction is typically reversible, meaning the ester can be hydrolyzed back into the carboxylic acid and alcohol under appropriate conditions

23. Esterification - Example

• Example: Esterification of acetic acid with ethanol to form ethyl acetate O O //\\ //\\ CH_3-C-C-OH + CH_3-CH_2-OH → CH_3-C-C-O-CH_2-CH_3 + H_2O | | H H

24. Hydrolysis of Esters - Overview

• Hydrolysis of esters is a reaction that involves the cleavage of an ester bond using water
• This reaction can occur under acidic, basic, or enzymatic conditions
• Acidic hydrolysis forms the carboxylic acid and alcohol, while basic hydrolysis forms the carboxylate ion and alcohol
• Enzymatic hydrolysis is a biologically important process that occurs in the presence of specific enzymes

25. Hydrolysis of Esters - Mechanism

• Hydrolysis of esters proceeds through the following steps:
  1. Protonation of the ester carbonyl group (acidic hydrolysis) or formation of the ester carboxylate ion (basic hydrolysis)
  2. Nucleophilic attack of water on the carbonyl carbon
  3. Cleavage of the ester bond, resulting in the formation of carboxylic acid (acidic hydrolysis) or carboxylate ion (basic hydrolysis) and alcohol

26. Hydrolysis of Esters - Example

• Example: Acidic hydrolysis of ethyl acetate O O //\\ //\\ CH_3-C-C-O-CH_2-CH_3 + H_2O → CH_3-C-C-OH + CH_3-CH_2-OH | | H H

27. Reduction of Carboxylic Acid - Overview

• Reduction of carboxylic acids involves the addition of hydrogen or hydride ions to the carbonyl group
• This reaction leads to the formation of primary alcohols or aldehydes
• Different reducing agents, such as lithium aluminum hydride (LiAlH4) or sodium borohydride (NaBH4), can be used for this reaction
• The reaction conditions and the choice of reducing agent determine the product obtained

28. Reduction of Carboxylic Acid - Example

• Example 1: Reduction of ethanoic acid to ethanol using lithium aluminum hydride O H OH H // | | | H-C-C-OH + H_2 → H-C-C-OH + H_2 | | | | H H H H
• Example 2: Reduction of ethanoic acid to ethanal using lithium aluminum hydride O H H // | | H-C-C-OH + H_2 → H-C-C-H + H_2O | | | H H OH

29. Oxidation of Aldehydes - Overview

• Oxidation of aldehydes is a reaction that involves the conversion of an aldehyde into a carboxylic acid
• This reaction usually occurs in the presence of an oxidizing agent, such as potassium permanganate (KMnO4) or chromic acid (H2CrO4)
• The carbonyl group of the aldehyde is oxidized to a carboxyl group, resulting in the formation of a carboxylic acid

30. Oxidation of Aldehydes - Example

• Example: Oxidation of ethanol to ethanoic acid using acidified potassium dichromate (K2Cr2O7) H H O H | | | | H-C-C-H + [O] → H-C-C-OH + H_2O | | | | H H O OH Make sure to understand the mechanisms and conditions for these reactions to score well in your exams!