20'4 Nucleophilic Substitution in Acyl Chlorides

1
20.4Nucleophilic Substitutionin Acyl Chlorides
2
Preparation of Acyl Chlorides
from carboxylic acids and thionyl
chloride(Section 12.7)
SOCl2


SO2
HCl
heat
(90)
3
Reactions of Acyl Chlorides
4
Reactions of Acyl Chlorides
Acyl chlorides react with carboxylic acids to
giveacid anhydrides


HCl
5
Example

pyridine
(78-83)
6
Reactions of Acyl Chlorides
Acyl chlorides react with alcohols to give esters


R'OH
HCl
7
Example
pyridine

(CH3)3COH
(80)
8
Reactions of Acyl Chlorides
Acyl chlorides react with ammonia and aminesto
give amides


R'2NH
H2O
HO

Cl
9
Example
NaOH

H2O
(87-91)
10
Reactions of Acyl Chlorides
Acyl chlorides react with water to
givecarboxylic acids (carboxylate ion in base)


H2O
HCl


2HO
Cl

H2O
11
Reactions of Acyl Chlorides
Acyl chlorides react with water to
givecarboxylic acids (carboxylate ion in base)


H2O
HCl
via
12
Example


H2O
HCl
13
Reactivity

• Acyl chlorides undergo nucleophilic substitution
  much faster than alkyl chlorides.

C6H5CH2Cl
Relative rates ofhydrolysis (25C)
1,000
1
14
20.5Nucleophilic Acyl Substitution in
Carboxylic Acid Anhydrides

• Anhydrides can be prepared from acyl chlorides as
  described in Table 20.1

15
Some anhydrides are industrial chemicals
Aceticanhydride
Phthalicanhydride
Maleicanhydride
16
From dicarboxylic acids

• Cyclic anhydrides with 5- and 6-membered rings
  can be prepared by dehydration of dicarboxylic
  acids

H2O
(89)
17
Reactions of Anhydrides
18
Reactions of Acid Anhydrides
Carboxylic acid anhydrides react with alcoholsto
give esters


R'OH

• normally, symmetrical anhydrides are used(both R
  groups the same)
• reaction can be carried out in presence of
  pyridine (a base) or it can be catalyzed by acids

19
Reactions of Acid Anhydrides
Carboxylic acid anhydrides react with alcoholsto
give esters


R'OH
via
20
Example
H2SO4
(60)
21
Reactions of Acid Anhydrides
Acid anhydrides react with ammonia and aminesto
give amides


2R'2NH
22
Example

(98)
23
Reactions of Acid Anhydrides
Acid anhydrides react with water to
givecarboxylic acids (carboxylate ion in base)

H2O
2RCOH


2HO
2RCO
H2O
24
Reactions of Acid Anhydrides
Acid anhydrides react with water to
givecarboxylic acids (carboxylate ion in base)

H2O
2RCOH
25
Example

H2O
26
20.6Sources of Esters
27
Esters are very common natural products
3-methylbutyl acetate

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

28
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

29
Esters of Glycerol
Tristearin found in many animal and vegetable
fats
30
Cyclic Esters (Lactones)
(Z)-5-Tetradecen-4-olide(sex pheromone of female
Japanese beetle)
31
Preparation of Esters

• Fischer esterification (Sections 15.8 and 19.14)
• from acyl chlorides (Sections 15.8 and 20.4)
• from carboxylic acid anhydrides (Sections
  15.8and 20.6)
• Baeyer-Villiger oxidation of ketones (Section
  17.16)

32
20.7Physical Properties of Esters
33
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
34
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
35
20.8Reactions of EstersA Review and a Preview
36
Reactions of Esters

• with Grignard reagents (Section 14.10)
• reduction with LiAlH4 (Section 15.3)
• with ammonia and amines (Sections 20.12)
• hydrolysis (Sections 20.10 and 20.11)

37
20.9Acid-Catalyzed Ester Hydrolysis
38
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

39
Example
(80-82)
40
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)

41
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
42
Second stage cleavage of tetrahedralintermediat
e

R'OH
H
43
Mechanism of formationoftetrahedral intermediate
44
Step 1

O

RC
O
R'


45
Step 1

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

46
Step 2
47
Step 3
48
Cleavage of tetrahedralintermediate
49
Step 4
50
Step 5
51
Step 5
52
Step 6
53
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

54
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
55
18O Labeling Studies

H2O
H