Chapter 21Carboxylic Acid Derivatives

Organic Chemistry, 6th EditionL. G. Wade, Jr.

Chapter 21 2

Acid Derivatives

• All can be converted to the carboxylic acid by acidic or basic hydrolysis.

• Esters and amides common in nature.

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Chapter 21 3

Naming Esters

• Esters are named as alkyl carboxylates.

• Alkyl from the alcohol, carboxylate from the carboxylic acid precursor.

CH3CH2 OH HO C

O

CH3

H+

+ + H2OCH3CH2 O C

O

CH3

ethanol

ethyl alcohol

ethanoic acid

acetic acid

ethyl ethanoate

ethyl acetate

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Chapter 21 4

Name These

CH3CHCH2OCCH3

CH3 O

HCOCH2

O

isobutyl acetate2-methylpropyl ethanoate

benzyl formatebenzyl methanoate

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Chapter 21 5

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.

O

O

H3C

CH3

4-hydroxy-2-methylpentanoic acid lactone-methyl--valerolactone

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Chapter 21 6

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.

HC

O

N

H

HH

C

O

N

H

H

_

+

Bond angles around Nare close to 120. =>

Chapter 21 7

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).

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Chapter 21 8

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.

CH3CHC N

O

CH2CH3

CH3

CH3

N-ethyl-N,2-dimethylpropanamideN-ethyl-N-methylisobutyramide

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Chapter 21 9

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.

N

O

CH3

H4-aminopentanoic acid lactam

-valerolactam

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Chapter 21 10

Nitriles• -CN 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).

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Chapter 21 11

Naming Nitriles

• For IUPAC names, add -nitrile to the alkane name.

• Common names come from the carboxylic acid. Replace -ic acid with -onitrile.

CH3CHCH2CH2CH2CN

Br

5-bromohexanenitrile-bromocapronitrile

C N

Cyclohexanecarbonitrile =>

Chapter 21 12

Acid Halides

• More reactive than acids; the halogen withdraws e- density from carbonyl.

• Named by replacing -ic acid with -yl halide.

C

O

Cl CH3CHCH2C

Br O

Br

benzoyl chloride

3-bromobutanoyl bromide-bromobutyryl bromide

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Chapter 21 13

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.

R C

O

O H RC

O

OH R C

O

O C

O

R

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Chapter 21 14

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.

CH3 C

O

O C

O

CH3

ethanoic anhydrideacetic anhydride

O

O

O1,2-benzenedicarboxylic anhydride

phthalic anhydride =>

Chapter 21 15

Multifunctional Compounds

• The functional group with the highest priority determines the parent name.

• Acid > ester > amide > nitrile > aldehyde > ketone > alcohol > amine > alkene > alkyne.

C

CN

O

OCH2CH3 ethyl o-cyanobenzoate=>

Chapter 21 16

Boiling Points

Even 3 amides havestrong attractions.

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Chapter 21 17

Melting Points

• Amides have very high melting points.

• Melting points increase with increasing number of N-H bonds.

m.p. -61C m.p. 28C m.p. 79C

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Chapter 21 18

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 acetateDimethylformamide (DMF)Acetonitrile

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Chapter 21 19

Interconversion ofAcid Derivatives

• Nucleophile adds to the carbonyl to form a tetrahedral intermediate.

• Leaving group leaves and C=O regenerates.

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Chapter 21 20

ReactivityReactivity decreases as leaving group

becomes more basic.

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Chapter 21 21

Interconversion of Derivatives

More reactive derivatives can be converted to less reactive derivatives.

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Chapter 21 22

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. =>

+ HClC

O

R OC

O

R'

_

C

O

R Cl

OH C

OR'

C

O

R ClR' C

O

O H+

- H+

Chapter 21 23

Acid Chloride to Ester

• Alcohol attacks the C=O.

• Tetrahedral intermediate forms.

• Chloride ion leaves, C=O is restored, H+

is abstracted. =>

+ HClC

O

R OR'

_

C

O

R Cl

OH R'

C

O

R Cl+

- H+

R' O H

Chapter 21 24

Acid Chloride to Amide• Ammonia yields a 1 amide

• A 1 amine yields a 2 amide

• A 2 amine yields a 3 amide

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Chapter 21 25

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 26

Anhydride to Amide• Ammonia yields a 1 amide

• A 1 amine yields a 2 amide

• A 2 amine yields a 3 amide

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Chapter 21 27

Ester to Amide• Nucleophile must be NH3 or 1 amine.

• Prolonged heating required.

Surprise!

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Chapter 21 28

Leaving Groups

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

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Chapter 21 29

Transesterification

• One alkoxy group can be replaced by another with acid or base catalyst.

• Use large excess of preferred alcohol.