Chapter 21 (part 1) - Reactions of carboxylic acid derivatives. This chapter predict the products and propose mechanisms for the reactions of carboxylic acid derivatives with reducing agents, alcohols, amines, and organometallic reagents; propose multistep syntheses using acid derivatives as starting materials and intermediates. | Chapter 21 Copyright © 2010 Pearson Education, Inc. Organic Chemistry, 7th Edition L. G. Wade, Jr. Part 2: Reactions of Carboxylic Acid Derivatives Chapter 21 Nucleophilic Acyl Substitution Interconversion of acid derivatives occur by nucleophilic acyl substitution. Nucleophile adds to the carbonyl forming a tetrahedral intermediate. Elimination of the leaving group regenerates the carbonyl. Nucleophilic acyl substitutions are also called acyl transfer reactions because they transfer the acyl group to the attacking nucleophile. Chapter 21 Mechanism of Acyl Substitution This is an addition–elimination mechanism. Chapter 21 Reactivity of Acid Derivatives Chapter 21 Interconversion of Derivatives More reactive derivatives can be converted to less reactive derivatives. Chapter 21 Acid Chloride to Anhydride The carboxylic acid attacks the acyl chloride, forming the tetrahedral intermediate. Chloride ion leaves, restoring the carbonyl. Deprotonation . | Chapter 21 Copyright © 2010 Pearson Education, Inc. Organic Chemistry, 7th Edition L. G. Wade, Jr. Part 2: Reactions of Carboxylic Acid Derivatives Chapter 21 Nucleophilic Acyl Substitution Interconversion of acid derivatives occur by nucleophilic acyl substitution. Nucleophile adds to the carbonyl forming a tetrahedral intermediate. Elimination of the leaving group regenerates the carbonyl. Nucleophilic acyl substitutions are also called acyl transfer reactions because they transfer the acyl group to the attacking nucleophile. Chapter 21 Mechanism of Acyl Substitution This is an addition–elimination mechanism. Chapter 21 Reactivity of Acid Derivatives Chapter 21 Interconversion of Derivatives More reactive derivatives can be converted to less reactive derivatives. Chapter 21 Acid Chloride to Anhydride The carboxylic acid attacks the acyl chloride, forming the tetrahedral intermediate. Chloride ion leaves, restoring the carbonyl. Deprotonation produces the anhydride. Chapter 21 Acid Chloride to Ester The alcohol attacks the acyl chloride, forming the tetrahedral intermediate. Chloride ion leaves, restoring the carbonyl. Deprotonation produces the ester. Chapter 21 Acid Chloride to Amide Ammonia yields a 1 amide. A 1 amine yields a 2 amide. A 2 amine yields a 3 amide. Chapter 21 Anhydride to Ester Alcohol attacks one of the carbonyl groups of the anhydride, forming the tetrahedral intermediate. The other acid unit is eliminated as the leaving group. Chapter 21 Anhydride to Amide Ammonia yields a 1 amide; a 1 amine yields a 2 amide; and a 2 amine yields a 3 amide. Chapter 21 Ester to Amide: Ammonolysis Nucleophile must be NH3 or 1 amine. Prolonged heating is required. Chapter 21 Leaving Groups in Nucleophilic Acyl Substitution A strong base, such as methoxide (-OCH3), is not usually a leaving group, except in an exothermic step. Chapter 21 Energy Diagram In the
