20.6 Sources of Esters

1
20.6Sources of Esters
2
Esters are very common natural products
3-methylbutyl acetate

• also called "isopentyl acetate" and "isoamyl
  acetate"
• contributes to characteristic odor of bananas

3
Esters of Glycerol

• R, R', and R" can be the same or different
• called "triacylglycerols," "glyceryl triesters,"
  or "triglycerides"
• fats and oils are mixtures of glyceryl triesters

4
Esters of Glycerol
Tristearin found in many animal and vegetable
fats
5
Cyclic Esters (Lactones)
(Z)-5-Tetradecen-4-olide(sex pheromone of female
Japanese beetle)
6
Preparation of Esters

• Fischer esterification (Sections 15.8 and 19.14)
• from acyl chlorides (Sections 15.8 and 20.3)
• from carboxylic acid anhydrides (Sections
  15.8and 20.5)
• Baeyer-Villiger oxidation of ketones (Section
  17.16)

7
20.7Physical Properties of Esters
8
Boiling Points

• Esters have higher boiling points than alkanes
  because they are more polar.
• Esters cannot form hydrogen bonds to other ester
  molecules, so have lower boiling points than
  alcohols.

boilingpoint
28C
O
57C
CH3COCH3
99C
9
Solubility in Water

• Esters can form hydrogen bonds to water, so low
  molecular weight esters have significant
  solubility in water.
• Solubility decreases with increasing number of
  carbons.

Solubility(g/100 g)
0
O
33
CH3COCH3
12.5
10
20.8Reactions of EstersA Review and a Preview
11
Reactions of Esters

• with Grignard reagents (Section 14.10)
• reduction with LiAlH4 (Section 15.3)
• with ammonia and amines (Sections 20.13)
• hydrolysis (Sections 20.9 and 20.10)

12
20.9Acid-Catalyzed Ester Hydrolysis
13
Acid-Catalyzed Ester Hydrolysis
is the reverse of Fischer esterification

R'OH

• maximize conversion to ester by removing water
• maximize ester hydrolysis by having large excess
  of water
• equilibrium is closely balanced because carbonyl
  group ofester and of carboxylic acid are
  comparably stabilized

14
Example
(80-82)
15
Mechanism of Acid-CatalyzedEster Hydrolysis

• Is the reverse of the mechanism for
  acid-catalyzed esterification.
• Like the mechanism of esterification, it involves
  two stages
• 1) formation of tetrahedral intermediate (3
  steps)
• 2) dissociation of tetrahedral intermediate
  (3 steps)

16
First stage formation of tetrahedral
intermediate

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

H
17
Second stage cleavage of tetrahedralintermediat
e

R'OH
H
18
Mechanism of formationoftetrahedral intermediate
19
Step 1
20
Step 1

O

RC
O
R'




O
H
RC


21
Step 1

• carbonyl oxygen is protonated because cation
  produced is stabilized by electron delocalization
  (resonance)

22
Step 2

23
Step 2

24
Step 3
25
Step 3
26
Cleavage of tetrahedralintermediate
27
Step 4
28
Step 4
29
Step 5
30
Step 5

31
Step 5
32
Step 6
33
Key Features of Mechanism

• Activation of carbonyl group by protonation of
  carbonyl oxygen
• Nucleophilic addition of water to carbonyl
  groupforms tetrahedral intermediate
• Elimination of alcohol from tetrahedral
  intermediate restores carbonyl group

34
18O Labeling Studies

H2O

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

H

H2O
35
18O Labeling Studies

H2O
H
H

H2O
36
20.10Ester Hydrolysis in BaseSaponification
37
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)

38
Ester Hydrolysis in Aqueous Base

R'OH
H
39
Example

NaOH
water-methanol, heat

(95-97)
40
Example

CH3OH
(87)
41
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
42
Which bond is broken when esters arehydrolyzed
in base?

• One possibility is an SN2 attack by hydroxide on
  the alkyl group of the ester (alkyl-oxygen
  cleavage). Carboxylate is the leaving group.

43
Which bond is broken when esters arehydrolyzed
in base?

• A second possibility is nucleophilic acyl
  substitution (acyl-oxygen cleavage).

44
18O Labeling gives the answer

• 18O retained in alcohol, not carboxylate
  therefore nucleophilic acyl substitution
  (acyl-oxygen cleavage).

45
Stereochemistry gives the same answer

• alcohol has same configuration at stereogenic
  center as ester therefore, nucleophilic acyl
  substitution (acyl-oxygen cleavage)
• not SN2

KOH, H2O

46
Does it proceed via a tetrahedral intermediate?

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

47
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
48
18O Labeling Studies

H2O
HO
HO

H2O
49
Mechanism of Ester Hydrolysisin Base

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

50
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
51
Second stage cleavage of tetrahedralintermediat
e

R'OH
HO
52
Mechanism of formationoftetrahedral intermediate
53
Step 1

O

RC
OR'


54
Step 1
55
Step 2
56
Step 2
57
Dissociation oftetrahedral intermediate
58
Step 3
59
Step 3
60
Step 4
HO
H2O
61
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

62
20.11Reactions of Esterswith Ammonia and Amines
63
Reactions of Esters
64
Reactions of Esters
Esters react with ammonia and aminesto give
amides


R'2NH
RCOR'
R'OH
65
Reactions of Esters
Esters react with ammonia and aminesto give
amides


R'2NH
RCOR'
R'OH
via
66
Example
H2O

CH3OH
(75)
67
Example
heat
(61)
68
20.12Thioesters
69
Thioesters
Thioesters are compounds of the type

• Thioesters are intermediate in reactivity between
  anhydrides and esters.
• Thioester carbonyl group is less stabilized than
  oxygen analog because CS bond is longer than CO
  bond which reduces overlap of lone pair orbital
  and CO p orbital

70
Thioesters
Many biological nucleophilic acyl
substitutionsinvolve thioesters.


R'S
H
via