Chapter 21 Carboxylic Acid Derivatives

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

=> Acid Derivatives • All can be converted to the carboxylic acid by acidic or basic hydrolysis. • Esters and amides common in nature. Chapter 21

ethyl ethanoate ethyl acetate ethanol ethyl alcohol ethanoic acid acetic acid => Naming Esters • Esters are named as alkyl carboxylates. • Alkyl from the alcohol, carboxylate from the carboxylic acid precursor. Chapter 21

benzyl formate benzyl methanoate => Name These isobutyl acetate 2-methylpropyl ethanoate Chapter 21

4-hydroxy-2-methylpentanoic acid lactone -methyl--valerolactone => 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. Chapter 21

Bond angles around N are close to 120. => 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. Chapter 21

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 21

N-ethyl-N,2-dimethylpropanamide N-ethyl-N-methylisobutyramide => 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. Chapter 21

4-aminopentanoic acid lactam -valerolactam => Cyclic Amides • Reaction of -NH2 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. Chapter 21

=> 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 (pKb about 24). Chapter 21

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 21

Acid Halides • More reactive than acids; the halogen withdraws e- density from carbonyl. • Named by replacing -ic acid with -yl halide. 3-bromobutanoyl bromide -bromobutyryl bromide => benzoyl chloride Chapter 21

=> 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 21

1,2-benzenedicarboxylic anhydride phthalic anhydride => 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 Chapter 21

ethyl o-cyanobenzoate => Multifunctional Compounds • The functional group with the highest priority determines the parent name. • Acid > ester > amide > nitrile > aldehyde > ketone > alcohol > amine > alkene > alkyne. Chapter 21

=> Boiling Points Even 3 amides have strong attractions. Chapter 21

m.p. 79C => Melting Points • Amides have very high melting points. • Melting points increase with increasing number of N-H bonds. m.p. -61C m.p. 28C Chapter 21

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 21

=> Interconversion ofAcid Derivatives • Nucleophile adds to the carbonyl to form a tetrahedral intermediate. • Leaving group leaves and C=O regenerates. Chapter 21

Reactivity Reactivity decreases as leaving group becomes more basic. => Chapter 21

Interconversion of Derivatives More reactive derivatives can be converted to less reactive derivatives. => Chapter 21

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 21

Acid Chloride to Ester • Alcohol attacks the C=O. • Tetrahedral intermediate forms. • Chloride ion leaves, C=O is restored, H+ is abstracted. => 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 C=O of anhydride. • Tetrahedral intermediate forms. • Carboxylate ion leaves, C=O is restored, H+ is abstracted. => Chapter 21

=> Anhydride to Amide • Ammonia yields a 1 amide • A 1 amine yields a 2 amide • A 2 amine yields a 3 amide Chapter 21

Surprise! => Ester to Amide • Nucleophile must be NH3 or 1 amine. • Prolonged heating required. Chapter 21

Leaving Groups A strong base is not usually a leaving group unless it’s in an exothermic step. => Chapter 21

Transesterification • One alkoxy group can be replaced by another with acid or base catalyst. • Use large excess of preferred alcohol. Chapter 21

Chapter 21 Carboxylic Acid Derivatives