Chapter 21 Carboxylic Acid Derivatives Organic Chemistry, 6 th Edition L. G. Wade, Jr.

Chapter 212 Acid Derivatives All can be converted to the carboxylic acid by acidic or basic hydrolysis. Esters and amides common in nature. =>

Chapter 213 Naming Esters Esters are named as alkyl carboxylates. Alkyl from the alcohol, carboxylate from the carboxylic acid precursor. ethanol ethyl alcohol ethanoic acid acetic acid ethyl ethanoate ethyl acetate =>

Chapter 214 Name These isobutyl acetate 2-methylpropyl ethanoate benzyl formate benzyl methanoate =>

Chapter 215 Cyclic Esters Reaction of -OH and -COOH on same molecule produces a cyclic ester, lactone. To name, add word lactone to the IUPAC acid name or replace the -ic acid of common name with -olactone. 4-hydroxy-2-methylpentanoic acid lactone  -methyl-  -valerolactone =>

Chapter 216 Amides Product of the reaction of a carboxylic acid and ammonia or an amine. Not basic because the lone pair on nitrogen is delocalized by resonance. Bond angles around N are close to 120 . =>

Chapter 217 Classes of Amides 1  amide has one C-N bond (two N-H). 2  amide or N-substituted amide has two C-N bonds (one N-H). 3  amide or N,N-disubstituted amide has three C-N bonds (no N-H). =>

Chapter 218 Naming Amides For 1  amide, drop -ic or -oic acid from the carboxylic acid name, add -amide. For 2  and 3  amides, the alkyl groups bonded to nitrogen are named with N- to indicate their position. N-ethyl-N,2-dimethylpropanamide N-ethyl-N-methylisobutyramide =>

Chapter 219 Cyclic Amides Reaction of -NH 2 and -COOH on same molecule produces a cyclic amide, lactam. To name, add word lactam to the IUPAC acid name or replace the -ic acid of common name with -olactam. 4-aminopentanoic acid lactam  -valerolactam =>

Chapter 2110 Nitriles -C  N can be hydrolyzed to carboxylic acid, so nitriles are acid derivatives. Nitrogen is sp hybridized, lone pair tightly held, so not very basic (pK b about 24). =>

Chapter 2111 Naming Nitriles For IUPAC names, add -nitrile to the alkane name. Common names come from the carboxylic acid. Replace -ic acid with -onitrile. 5-bromohexanenitrile  -bromocapronitrile Cyclohexanecarbonitrile =>

Chapter 2112 Acid Halides More reactive than acids; the halogen withdraws e - density from carbonyl. Named by replacing -ic acid with -yl halide. benzoyl chloride 3-bromobutanoyl bromide  -bromobutyryl bromide =>

Chapter 2113 Acid Anhydrides Two molecules of acid combine with the loss of water to form the anhydride. Anhydrides are more reactive than acids, but less reactive than acid chlorides. A carboxylate ion is the leaving group in nucleophilic acyl substitution reactions. =>

Chapter 2114 Naming Anhydrides The word acid is replaced with anhydride. For a mixed anhydride, name both acids. Diacids may form anhydrides if a 5- or 6- membered ring is the product. ethanoic anhydride acetic anhydride 1,2-benzenedicarboxylic anhydride phthalic anhydride =>

Chapter 2115 Multifunctional Compounds The functional group with the highest priority determines the parent name. Acid > ester > amide > nitrile > aldehyde > ketone > alcohol > amine > alkene > alkyne. ethyl o-cyanobenzoate =>

Chapter 2116 Boiling Points Even 3  amides have strong attractions. =>

Chapter 2117 Melting Points Amides have very high melting points. Melting points increase with increasing number of N-H bonds. m.p. -61  Cm.p. 28  Cm.p. 79  C =>

Chapter 2118 Solubility Acid chlorides and anhydrides are too reactive to be used with water or alcohol. Esters, 3  amides, and nitriles are good polar aprotic solvents. Solvents commonly used in organic reactions:  Ethyl acetate  Dimethylformamide (DMF)  Acetonitrile =>

Chapter 2119 Interconversion of Acid Derivatives Nucleophile adds to the carbonyl to form a tetrahedral intermediate. Leaving group leaves and C=O regenerates. =>

Chapter 2120 Reactivity Reactivity decreases as leaving group becomes more basic. =>

Chapter 2121 Interconversion of Derivatives More reactive derivatives can be converted to less reactive derivatives. =>

Chapter 2122 Acid Chloride to Anhydride Acid or carboxylate ion attacks the C=O. Tetrahedral intermediate forms. Chloride ion leaves, C=O is restored, H + is abstracted. =>

Chapter 2123 Acid Chloride to Ester Alcohol attacks the C=O. Tetrahedral intermediate forms. Chloride ion leaves, C=O is restored, H + is abstracted. =>

Chapter 2124 Acid Chloride to Amide Ammonia yields a 1  amide A 1  amine yields a 2  amide A 2  amine yields a 3  amide =>

Chapter 2125 Anhydride to Ester Alcohol attacks one C=O of anhydride. Tetrahedral intermediate forms. Carboxylate ion leaves, C=O is restored, H + is abstracted. =>

Chapter 2126 Anhydride to Amide Ammonia yields a 1  amide A 1  amine yields a 2  amide A 2  amine yields a 3  amide =>

Chapter 2127 Ester to Amide Nucleophile must be NH 3 or 1  amine. Prolonged heating required. Surprise! =>

Chapter 2128 Leaving Groups A strong base is not usually a leaving group unless it’s in an exothermic step. =>

Chapter 2129 Transesterification One alkoxy group can be replaced by another with acid or base catalyst. Use large excess of preferred alcohol.