1 Chapter 16: Carbonyl Compounds I Learning Objectives: 1. Recognize the general structures of carboxylic acids, acyl halides, acid anhydrides, esters, amides, and nitriles, and be able to assign names to simple members of these compound families. 2. Identify and be able to write the general mechanism for nucleophilic acyl substitution, and be able to judge the relative reactivities of carbonyl compounds in this reaction. 3. Identify and be able to write the mechanisms for nucleophilic substitutions of acyl halides, and esters. 4. Identify and be able to write the mechanism for the acid-catalyzed hydrolysis of an ester and of a nitrile. 5. Identify and be able to write the mechanism for the hydroxide-promoted hydrolysis of an ester. 6. Identify and be able to write the mechanisms for the acid-catalyzed and the hydroxide-promoted hydrolysis of amides. 7. Identify and be able to write the mechanism for the Fischer esterification of a carboxylic acid 8. Be able to describe the structures of fats, oils, and soaps, and be able to explain how detergents and surfactants work. 9. Be able to describe how to use chemical reagents for the desired transformation among acid derivatives. Sections: 16.1 Nomenclature of Carboxylic Acids and Carboxylic Acid Derivatives 16.2 Structures of Carboxylic Acids and Carboxylic Acid Derivatives 16.3 Physical Properties of Carbonyl Compounds 16.4 Naturally Occurring Carboxylic Acids and Carboxylic Acids Derivatives# 16.5 How Class I Carbonyl Compounds React* 16.6 Relative Reactivities of Carboxylic Acids and Carboxylic Acid Derivatives* 16.7 General Mechanism for Nucleophilic Acyl Substitution Reactions* 16.8 Reactions of Acyl Halides 16.9 Reactions of Acid Anhydrides 16.10 Reactions of Esters 16.11 Acid-Catalyzed Ester Hydrolysis and Transesterification* 16.12 Hydroxide –Ion Promoted Ester Hydrolysis* 16.13 Soaps, Detergents, and Micelles 16.14 Reactions of Carboxylic Acids 16.15 Reactions of Amides 16.16 Acid-Catalyzed Hydrolysis of Amides* 16.17 Hydrolysis of Amides Is Catalyzed by Acids 16.18 Hydrolysis of an Imide: A Way to Synthesize Primary Amines 16.19 Hydrolysis of Nitrile* 16.20 Designing a Synthesis V: The Synthesis of Cyclic Compounds 16.21 How Chemists Activate Carboxylic Acids* 16.22 How Cell Activate Carboxylic Acids# 16.23 Dicarboxylic Acids and Their Derivatives * Sections that will be focused2 # Sections that will be skipped Recommended additional problems 16.45 – 16.87 Class Note 16.1 Nomenclature of Carboxylic Acids and Carboxylic Acid Derivatives ROArOAr: aryl groupR: alkyl groupacyl groupOcarbonyl group OOHOOHOOHOOH OOOClOClOCO2HCO2H3 OOCH3OOOOOOBrNa NHONH2ONHONO Lactone Lactam R C NN4 16.2 Structures of Carboxylic Acids and Carboxylic Acid Derivatives 16.3 Physical Properties of Carbonyl Compounds5 16.5 How Class I Carbonyl Compounds React*, 16.6 Relative Reactivities of Carboxylic Acids and Carboxylic Acid Derivatives* and 16.7 General Mechanism for Nucleophilic Acyl Substitution Reactions* A. General mechanism (i) Nucleophile (nucleophilicity) and leaving group (ii) Nucleophilicity, basicity, and pKa6 (iii) Nucleophilic acyl substitution reaction (an addition-elimination reaction) R LG (Y)OR LGO NuNu ( Z)tetrahedral intermediateR Nu (Z)OLG ( Y)7 (iv) Molecular orbital view of nucleophilic acyl substitution reaction B. Relative reactivities of carboxylic acid derivatives R ClOacyl chlorideR OOROacid anhydrideR OR'OesterR OHOcarboxylic acidR NHR'Oamide (i) Inductive effect vs. resonance effect (ii) Nucleophilicity, basicity, and pKa8 16.8 Reactions of Acyl Halides A. Reactions9 B. Why two equivalents of amine are needed for the formation of amide?10 16.9 Reactions of Acid Anhydrides11 16.10 Reactions of Esters12 16.11 Acid-Catalyzed Ester Hydrolysis and Transesterification*13 16.12 Hydroxide –Ion Promoted Ester Hydrolysis* A. Comparison of hydrolysis of ester in acidic and basic conditions14 B. Mechanistic studies using isotope15 16.13 Soaps, Detergents, and Micelles16 16.14 Reactions of Carboxylic Acids A. Fisher esterification B. Other reactions17 16.15 Reactions of Amides, 16.16 Acid-Catalyzed Hydrolysis of Amides* and 16.17 Hydrolysis of Amides Is Catalyzed by Acids18 16.18 Hydrolysis of an Imide: A Way to Synthesize Primary Amines A. Gabriel synthesis19 16.19 Hydrolysis of Nitrile*20 16.20 Designing a Synthesis V: The Synthesis of Cyclic Compounds21 16.21 How Chemists Activate Carboxylic Acids* A. Use of SOCl2, PCl3, PBr3 B. Use of P2O522 16.23 Dicarboxylic Acids and Their