20.10 Ester Hydrolysis in Base: Saponification

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20.10Ester Hydrolysis in BaseSaponification
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Ester Hydrolysis in Aqueous Base

R'OH

• is called saponification
• is irreversible, because of strong stabilization
  of carboxylateion
• if carboxylic acid is desired product,
  saponification is followedby a separate
  acidification step (simply a pH adjustment)

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Example

NaOH
water-methanol, heat

(95-97)
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Example

CH3OH
(87)
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Soap-Making

• Basic hydrolysis of the glyceryl triesters (from
  fats and oils) gives salts of long-chain
  carboxylic acids.
• These salts are soaps.

K2CO3, H2O, heat
CH3(CH2)xCOK
CH3(CH2)yCOK
CH3(CH2)zCOK
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Which bond is broken when esters arehydrolyzed
in base?

• One possibility is an SN2 attack by hydroxide on
  the alkyl group of the ester. Carboxylate is the
  leaving group.

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Which bond is broken when esters arehydrolyzed
in base?

• A second possibility is nucleophilic acyl
  substitution.

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18O Labeling gives the answer

• 18O retained in alcohol, not carboxylate
  therefore nucleophilic acyl substitution.

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Stereochemistry gives the same answer

• alcohol has same configuration at chirality
  center as ester therefore, nucleophilic acyl
  substitution
• not SN2

KOH, H2O

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Does it proceed via a tetrahedral intermediate?

• Does nucleophilic acyl substitution proceed in a
  single step, or is a tetrahedral intermediate
  involved?

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18O Labeling Studies

H2O

• Ethyl benzoate, labeled with 18O at the carbonyl
  oxygen, was subjected to hydrolysis in base.
• Ethyl benzoate, recovered before the reaction had
  gone to completion, had lost its 18O label.
• This observation is consistent with a tetrahedral
  intermediate.

HO

H2O
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18O Labeling Studies

H2O
HO
HO

H2O
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Mechanism of Ester Hydrolysisin Base

• Involves two stages
• 1) formation of tetrahedral intermediate 2) diss
  ociation of tetrahedral intermediate

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First stage formation of tetrahedral
intermediate

• water adds to the carbonyl group of the ester
• this stage is analogous to the base-catalyzed
  addition of water to a ketone

HO
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Second stage cleavage of tetrahedralintermediat
e

R'OH
HO
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Mechanism of formationoftetrahedral intermediate
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Step 1
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Step 2
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Dissociation oftetrahedral intermediate
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Step 3
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Step 4
H2O
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Key Features of Mechanism

• Nucleophilic addition of hydroxide ion to
  carbonylgroup in first step
• Tetrahedral intermediate formed in first stage
• Hydroxide-induced dissociation of
  tetrahedralintermediate in second stage

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20.11Reactions of Esterswith Ammonia and Amines
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Reactions of Esters
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Reactions of Esters
Esters react with ammonia and aminesto give
amides


R'2NH
RCOR'
R'OH
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Example
H2O

CH3OH
(75)
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Example
heat
(61)
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20.12Amides
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Physical Properties of Amides
Amides are less reactive toward nucleophilic
acyl substitution than other acid derivatives.
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Physical Properties of Amides
Amides are capable of hydrogen bonding.
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Physical Properties of Amides
Amides are less acidic than carboxylic acids.
Nitrogen is less electronegative than oxygen.
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Preparation of Amides
Amides are prepared from amines by acylationwith

• acyl chlorides (Table 20.1)
• anhydrides (Table 20.2)
• esters (Table 20.5)

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Preparation of Amides
Amines do not react with carboxylic acids to
giveamides. The reaction that occurs is
proton-transfer(acid-base).




R'NH3
R'NH2

• If no heat-sensitive groups are present, the
  resulting ammonium carboxylate salts can be
  converted to amides by heating.

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Preparation of Amides
Amines do not react with carboxylic acids to
giveamides. The reaction that occurs is
proton-transfer(acid-base).




R'NH3
R'NH2
heat

H2O
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Example


225C

H2O
(80-84)