Chapter 11 Carboxylic Acid Derivatives

Acid Derivatives All acid derivatives can be converted to the carboxylic acid by acidic or basic hydrolysis. Esters and amides are common in nature. Chapter 11

Naming Esters IUPAC Nomenclature Common Nomenclature As usual the long chain will contain the carbonyl carbon. Drop the “e” then add oate suffix. The remaining carbon chain is named as substituent and used as a prefix. Common Nomenclature Esters are named from the common name of the acid used to form them. Drop the “oic acid” from the common acid name and att the suffix “ate”. The other carbon group is named as a substituent. ethanol ethyl alcohol ethanoic acid acetic acid Chapter 11

Naming Esters IUPAC Nomenclature Common Nomenclature As usual the long chain will contain the carbonyl carbon. Drop the “e” then add oate suffix. The remaining carbon chain is named as substituent and used as a prefix. Common Nomenclature Esters are named from the common name of the acid used to form them. Drop the “oic acid” from the common acid name and att the suffix “ate”. The other carbon group is named as a substituent. ethanol ethyl alcohol ethanoic acid acetic acid ethyl ethanoate ethyl acetate Chapter 11

Name These Chapter 11

Name These (Common) Chapter 11

isobutyl acetate (Common) Name These isobutyl acetate (Common) Chapter 11

Name These isobutyl acetate (Common) benzyl formate (common) Chapter 11

Name These isobutyl acetate (Common) benzyl formate (common) 2-methylpropyl ethanoate (IUPAC) benzyl formate (common) Chapter 11

Name These isobutyl acetate (Common) benzyl formate (common) 2-methylpropyl ethanoate (IUPAC) benzyl formate (common) benzyl methanoate (IUPAC) Chapter 11

4-hydroxy-2-methylpentanoic acid lactone 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 Chapter 11

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 11

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 11

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 11

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 11

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 11

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

4-aminopentanoic acid lactam 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. 4-aminopentanoic acid lactam -valerolactam 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 11

Naming Nitriles For IUPAC names, add -nitrile to the alkane name. Common names come from the carboxylic acid. Replace -ic acid with -onitrile. Chapter 11

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 11

Acid Halides More reactive than acids; the halogen withdraws e- density from carbonyl. Named by replacing -ic acid with -yl halide. Chapter 11

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 11

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 11

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. => Chapter 11

1,2-benzenedicarboxylic 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 1,2-benzenedicarboxylic anhydride phthalic anhydride => Chapter 11

Multifunctional Compounds The functional group with the highest priority determines the parent name. Acid > ester > amide > nitrile > aldehyde > ketone > alcohol > amine > alkene > alkyne. Chapter 11

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 11

Boiling Points Even 3 amides have strong attractions. Chapter 11

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 m.p. 79C Chapter 11

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 11

Interconversion ofAcid Derivatives Nucleophile adds to the carbonyl to form a tetrahedral intermediate. Leaving group leaves and C=O regenerates. Chapter 11

Reactivity Reactivity decreases as leaving group becomes more basic. Chapter 11

Interconversion of Derivatives More reactive derivatives can be converted to less reactive derivatives. Chapter 11

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 11

Acid Chloride to Ester Alcohol attacks the C=O. Tetrahedral intermediate forms. Chloride ion leaves, C=O is restored, H+ is abstracted. Chapter 11

Acid Chloride to Amide Ammonia yields a 1 amide A 1 amine yields a 2 amide A 2 amine yields a 3 amide Chapter 11

Anhydride to Ester Alcohol attacks one C=O of anhydride. Tetrahedral intermediate forms. Carboxylate ion leaves, C=O is restored, H+ is abstracted. Chapter 11

Anhydride to Amide Ammonia yields a 1 amide A 1 amine yields a 2 amide A 2 amine yields a 3 amide Chapter 11

Ester to Amide Nucleophile must be NH3 or 1 amine. Prolonged heating required. Surprise! Chapter 11

Leaving Groups A strong base is not usually a leaving group unless it’s in an exothermic step. Chapter 11

Transesterification One alkoxy group can be replaced by another with acid or base catalyst. Use large excess of preferred alcohol. Chapter 11

TRANSESTERIFICATION OF COCAINE

Hydrolysis of Acid Chlorides and Anhydrides Hydrolysis occurs quickly, even in moist air with no acid or base catalyst. Reagents must be protected from moisture. => Chapter 11

Acid Hydrolysis of Esters Reverse of Fischer esterification. Reaches equilibrium. Use a large excess of water. => Chapter 11

Saponification Base-catalyzed hydrolysis of ester. “Saponification” means “soap-making.” Soaps are made by heating NaOH with a fat (triester of glycerol) to produce the sodium salt of a fatty acid - a soap. One example of a soap is sodium stearate, Na+ -OOC(CH2)16CH3. Chapter 11

Hydrolysis of Amides Prolonged heating in 6 M HCl or 40% aqueous NaOH is required. Chapter 11

Hydrolysis of Nitriles Under mild conditions, nitriles hydrolyze to an amide. Heating with aqueous acid or base will hydrolyze a nitrile to an acid. Chapter 11

Reduction to Alcohols Lithium aluminum hydride reduces acids, acid chlorides, and esters to primary alcohols. Chapter 11

Acid Chloride Synthesis Use thionyl chloride, SOCl2, or oxalyl chloride, (COCl)2. Other products are gases. Chapter 11

Acid Chloride Reactions (1) ester amide acid anhydride Chapter 11

Lab Synthesis of Anhydrides React acid chloride with carboxylic acid or carboxylate ion. Heat dicarboxylic acids to form cyclic anhydrides. Chapter 11

Anhydride Reactions acid ester amide acylbenzene AlCl3 Chapter 11

Anhydride vs. Acid Chloride Acetic anhydride is cheaper, gives a better yield than acetyl chloride. Use acetic formic anhydride to produce formate esters and formamides. Use cyclic anhydrides to produce a difunctional molecule. Chapter 11

Synthesis of Esters acid acid chloride acid anhydride methyl ester Chapter 11

Synthesis of Amides acid acid chloride acid anhydride ester nitrile Chapter 11

Reactions of Amides acid and amine amine 1° amine nitrile Chapter 11

CHAPTER 11 REVIEW Chapter 11

Name a. Ethyl ethanoate b. Propyl propanoate c. Ethyl propanoate d. Propyl ethanoate e. Propyl butanoate

Answer a. Ethyl ethanoate b. Propyl propanoate c. Ethyl propanoate d. Propyl ethanoate e. Propyl butanoate The longest chain is three carbons. Propyl is the alkoxy group.

Name a. 3-Hydroxybutanoic acid lactone b. 4-Hydroxybutanoic acid lactone c. 4-Hydroxypentanoic acid lactone d. 5-Hydroxypentanoic acid lactone

Answer a. 3-Hydroxybutanoic acid lactone b. 4-Hydroxybutanoic acid lactone c. 4-Hydroxypentanoic acid lactone d. 5-Hydroxypentanoic acid lactone A lactone is a cyclic ester. The hydroxy is on the fifth carbon.

Name a. Pentanamide b. Butanamide c. N-Ethylethanamide d. N-Ethylpropanamide e. N-Methylethanamide

Answer a. Pentanamide b. Butanamide c. N-Ethylethanamide d. N-Ethylpropanamide e. N-Methylethanamide Ethyl is attached to the nitrogen. The longest chain is three carbons.

21.4 Name a. 3-Aminobutanoic acid lactam b. 4-Aminobutanoic acid lactam c. 4-Aminopentanoic acid lactam d. 5-Aminopentanoic acid lactam

Answer a. 3-Aminobutanoic acid lactam b. 4-Aminobutanoic acid lactam c. 4-Aminopentanoic acid lactam d. 5-Aminopentanoic acid lactam A lactam is a cyclic amide. The amino group is on the fifth carbon.

Name a. Pentanenitrile b. Butanenitrile c. Propanenitrile d. 2-Methylbutanenitrile e. 3-Methylbutanenitrile

Answer a. Pentanenitrile b. Butanenitrile c. Propanenitrile d. 2-Methylbutanenitrile e. 3-Methylbutanenitrile The longest chain has four carbons. The methyl is on the third carbon.

Name a. 1-Chloroethanoyl chloride b. 2-Chloroethanoyl chloride c. 1-Chloropropanoyl chloride d. 2-Chloropropanoyl chloride

Answer a. 1-Chloroethanoyl chloride b. 2-Chloroethanoyl chloride c. 1-Chloropropanoyl chloride d. 2-Chloropropanoyl chloride The longest chain has three carbons. Chlorines are on the second carbon and the carbonyl carbon.

Name a. Ethanoic methanoic anhydride b. Methanoic propanoic anhydride c. Ethanoic anhydride d. Ethanoic propanoic anhydride e. Propanoic anhydride

Answer a. Ethanoic methanoic anhydride b. Methanoic propanoic anhydride c. Ethanoic anhydride d. Ethanoic propanoic anhydride e. Propanoic anhydride The three-carbon chain is on the left. A two-carbon chain is on the right.

a. Ethanoic methanoic anhydride b. Methanoic propanoic anhydride c. Ethanoic anhydride d. Ethanoic propanoic anhydride

Answer a. Ethanoic methanoic anhydride b. Methanoic propanoic anhydride c. Ethanoic anhydride d. Ethanoic propanoic anhydride An acid halide reacts with a carboxylic acid to form an anhydride.

a. Methyl ethanoate b. Methyl propanoate c. Ethyl ethanoate d. Ethyl propanoate

Answer a. Methyl ethanoate b. Methyl propanoate c. Ethyl ethanoate d. Ethyl propanoate An acid halide reacts with an alcohol to form an ester.

a. N-Methylethanamide b. N-Methylpropanamide c. N,N-Dimethylethanamide d. N,N-Dimethylpropanamide

Answer a. N-Methylethanamide b. N-Methylpropanamide c. N,N-Dimethylethanamide d. N,N-Dimethylpropanamide An acid halide reacts with an amine to form an amide.

a. Ethanoic acid + ethanol b. Propanoic acid + methyl ethanoate c. Ethanoic acid + ethyl ethanoate d. Propanoic acid + methyl propanoate e. Ethanoic acid + ethyl propanoate

Answer a. Ethanoic acid + ethanol b. Propanoic acid + methyl ethanoate c. Ethanoic acid + ethyl ethanoate d. Propanoic acid + methyl propanoate e. Ethanoic acid + ethyl propanoate An anhydride reacts with an alcohol to give a carboxylic acid and an ester.

a. N,N-Diethylpropanamide + propanoic acid b. N-Ethylpropanamide + propanoic acid c. N-Ethylethanamide + ethanoic acid d. N,N-Diethylethanamide + ethanoic acid

Answer a. N,N-Diethylpropanamide + propanoic acid b. N-Ethylpropanamide + propanoic acid c. N-Ethylethanamide + ethanoic acid d. N,N-Diethylethanamide + ethanoic acid An anhydride reacts with an amide to form an amide and a carboxylic acid.

a. N-Propyl propanamide + methanol b. N-Propyl ethanamide + ethanol c. N-Ethyl propanamide + methanol d. N-Ethyl ethanamide + ethanol e. N-Ethyl ethanamide + propanol

Answer a. N-Propyl propanamide + methanol b. N-Propyl ethanamide + ethanol c. N-Ethyl propanamide + methanol d. N-Ethyl ethanamide + ethanol e. N-Ethyl ethanamide + propanol An ester reacts with an amine to produce an amide and an alcohol.

a. Propanal + ammonia b. Ethanoic acid + ammonia c. Propanoic acid + methylamine d. Ethanoic acid + methylamine

Answer a. Propanal + ammonia b. Ethanoic acid + ammonia c. Propanoic acid + methylamine d. Ethanoic acid + methylamine An amide is hydrolyzed under acidic conditions to form a carboxylic acid and an amine.

a. Propylamine b. Propanamide c. Propanoic acid d. Butanoic acid e. No reaction

Answer a. Propylamine b. Propanamide c. Propanoic acid d. Butanoic acid e. No reaction A nitrile is hydrolyzed to a carboxylic acid in the presence of acid and heat.

a. Methanol + ethanol b. Methanol + propanol c. Ethanol + propanol d. Ethanol

Answer a. Methanol + ethanol b. Methanol + propanol c. Ethanol + propanol d. Ethanol An ester is reduced to two alcohols.

a. Ethyl methyl amine b. Ethyl propyl amine c. Methyl propyl amine d. Methyl amine + propanoic acid e. Ethyl amine + propanoic acid

Answer a. Ethyl methyl amine b. Ethyl propyl amine c. Methyl propyl amine d. Methyl amine + propanoic acid e. Ethyl amine + propanoic acid An amide is reduced to an amine with lithium aluminum hydride.

a. 2-Methyl-2-butanol b. 3-Methyl-3-pentanol c. 1-Butanol d. 3-Methyl-2-butanol e. 3-Ethyl-3-pentanol

Answer a. 2-Methyl-2-butanol b. 3-Methyl-3-pentanol c. 1-Butanol d. 3-Methyl-2-butanol e. 3-Ethyl-3-pentanol Two methyl groups add to the carbon of the carbonyl. Hydrolysis yields the tertiary alcohol.

a. 2-Methyl-2-butanol + ethanol b. 2-Methyl-2-butanol + methanol c. 2-Butanone + ethanol d. 2-Methyl-2-butanol + ethanol

Answer a. 2-Methyl-2-butanol + ethanol b. 2-Methyl-2-butanol + methanol c. 2-Butanone + ethanol d. 2-Methyl-2-butanol + ethanol The reaction of an ester with a Grignard reagent forms a tertiary alcohol and an alcohol.

End of Chapter 11 Chapter 11