Transcript Reactions of Acyl Chlorides

20.3
Nucleophilic Substitution
in Acyl Chlorides
General Mechanism for Nucleophilic Acyl Substitution
involves formation and dissociation
of a tetrahedral intermediate
••
R
C
••
OH
O ••
HY
O ••
-HX
R
C
X
X
Y
R
C
Y
Preparation of Acyl Chlorides
from carboxylic acids and thionyl chloride
(Section 12.7)
O
(CH3)2CHCOH
O
SOCl2
heat
(CH3)2CHCCl + SO2 + HCl
(90%)
Reactions of Acyl Chlorides
O
RCCl
O O
RCOCR'
O
RCOR'
O
RCNR'2
O
RCO–
Reactions of Acyl Chlorides
Acyl chlorides react with carboxylic acids to give
acid anhydrides:
O
O
RCCl + R'COH
O O
RCOCR'
+
HCl
Reactions of Acyl Chlorides
Acyl chlorides react with carboxylic acids to give
acid anhydrides:
O
O O
O
RCCl + R'COH
RCOCR'
H
via:
R
O
O
C
OCR'
Cl
+
HCl
Example
O
O
CH3(CH2)5CCl +
CH3(CH2)5COH
pyridine
O O
CH3(CH2)5COC(CH2)5CH3
(78-83%)
Reactions of Acyl Chlorides
Acyl chlorides react with alcohols to give esters:
O
RCCl + R'OH
O
RCOR'
+
HCl
Reactions of Acyl Chlorides
Acyl chlorides react with alcohols to give esters:
O
O
RCCl + R'OH
RCOR'
H
O
via:
R
C
Cl
OR'
+
HCl
Example
O
O
C6H5CCl + (CH3)3COH
pyridine
C6H5COC(CH3)3
(80%)
Reactions of Acyl Chlorides
Acyl chlorides react with ammonia and amines
to give amides:
O
RCCl + R'2NH + HO–
O
RCNR'2 + H2O
+ Cl–
Reactions of Acyl Chlorides
Acyl chlorides react with ammonia and amines
to give amides:
O
O
RCCl + R'2NH + HO–
RCNR'2 + H2O
H
+ Cl–
O
via:
R
C
Cl
NR'2
Example
O
O
C6H5CCl + H
N
NaOH
H2O
C6H5CN
(87-91%)
Reactions of Acyl Chlorides
Acyl chlorides react with water to give
carboxylic acids (carboxylate ion in base):
O
RCCl + H2O
O
RCCl + 2HO–
O
RCOH
+
HCl
+
Cl–
O
RCO–
+ H2O
Reactions of Acyl Chlorides
Acyl chlorides react with water to give
carboxylic acids (carboxylate ion in base):
O
O
RCCl + H2O
RCOH
H
O
via:
R
C
Cl
OH
+
HCl
Example
O
C6H5CH2CCl + H2O
O
C6H5CH2COH + HCl
Reactivity
Acyl chlorides undergo nucleophilic
substitution much faster than alkyl chlorides.
O
C6H5CCl
Relative rates of
hydrolysis (25°C)
1,000
C6H5CH2Cl
1
20.4
Preparation of
Carboxylic Acid Anhydrides
Anhydrides can be prepared from acyl
chlorides as described in Table 20.2
Some anhydrides are industrial chemicals
O O
O
O
CH3COCCH3
O
Acetic
anhydride
Phthalic
anhydride
O
O
O
Maleic
anhydride
From dicarboxylic acids
Cyclic anhydrides with 5- and 6-membered
rings can be prepared by dehydration of
dicarboxylic acids
O
H
COH
C
H
C
H
tetrachloroethane
O
130°C
COH
O
O
H
O
(89%)
+ H2 O
20.5
Reactions of
Carboxylic Acid Anhydrides
Table 20.3
Reactions of Anhydrides
O O
RCOCR'
O
RCOR'
O
RCNR'2
O
RCO–
Reactions of Acid Anhydrides
Carboxylic acid anhydrides react with alcohols
to give esters:
O O
RCOCR + R'OH
O
RCOR'
O
+ RCOH
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
Reactions of Acid Anhydrides
Carboxylic acid anhydrides react with alcohols
to give esters:
O
O O
RCOCR + R'OH
RCOR'
H
O
via:
R
OR'
C
OCR
O
O
+ RCOH
Example
O O
CH3COCCH3
+ CH3CHCH2CH3
OH
H2SO4
O
CH3COCHCH2CH3
CH3
(60%)
Reactions of Acid Anhydrides
Acid anhydrides react with ammonia and amines
to give amides:
O
O O
RCOCR
+ 2R'2NH
O
RCNR'2 + RCO–
+
R'2NH2
Reactions of Acid Anhydrides
Acid anhydrides react with ammonia and amines
to give amides:
O
O O
RCOCR
RCNR'2 + RCO–
+ 2R'2NH
H
+
R'2NH2
O
via:
O
R
NR'2
C
OCR
O
Example
O O
CH3COCCH3
+ H2N
CH(CH3)2
O
CH3CNH
CH(CH3)2
(98%)
Reactions of Acid Anhydrides
Acid anhydrides react with water to give
carboxylic acids (carboxylate ion in base):
O O
RCOCR
O
+ H2O
O O
RCOCR + 2HO–
2RCOH
O
2RCO–
+
H2O
Reactions of Acid Anhydrides
Acid anhydrides react with water to give
carboxylic acids (carboxylate ion in base):
O O
RCOCR
O
+ H2O
2RCOH
H
O
R
OH
C
OCR
O
Example
O
O
COH
O + H2O
COH
O
O