Transcript 19_03_05rw

19.3
General Mechanism
for
Nucleophilic Acyl Substitution
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Nucleophilic Acyl Substitution
••
••
O ••
R
C
O ••
+
X
HNu
R
C
+
Nu
Reaction is feasible when a less stabilized
carbonyl is converted to a more stabilized
one (more reactive to less reactive).
HX
General Mechanism for Nucleophilic Acyl Substitution
Involves formation and dissociation
of a tetrahedral intermediate
••
R
C
••
OH
O ••
HNu
O ••
-HX
R
C
X
Nu
R
C
Nu
X
Both stages can involve several elementary steps.
General Mechanism for Nucleophilic Acyl Substitution
First stage of mechanism (formation of tetrahedral
intermediate) is analogous to nucleophilic addition
to C=O of aldehydes and ketones.
••
OH
O ••
R
C
HNu
R
C
X
X
Nu
General Mechanism for Nucleophilic Acyl Substitution
Second stage is restoration of C=O by elimination.
Complicating features of each stage involve
acid-base chemistry.
••
R
C
••
OH
O ••
HNu
O ••
-HX
R
C
X
X
Nu
R
C
Nu
General Mechanism for Nucleophilic Acyl Substitution
Acid-base chemistry in first stage is familiar in that
it has to do with acid/base catalysis of nucleophilic
addition to C=O.
••
R
C
••
OH
O ••
HNu
O ••
-HX
R
C
X
X
Nu
R
C
Nu
General Mechanism for Nucleophilic Acyl Substitution
Acid-base chemistry in second stage concerns
form in which the tetrahedral intermediate exists
under the reaction conditions and how it dissociates
under those conditions.
••
R
C
••
OH
O ••
HNu
O ••
-HX
R
C
X
X
Nu
R
C
Nu
The Tetrahedral Intermediate
Tetrahedral Intermediate (TI)
••
H O ••
R
H
R
O ••
•X
•
C
H
C
••
Nu ••
X+
Conjugate acid of tetrahedral
intermediate (TI+)
Nu ••
R
– ••
• O ••
•
C
Nu ••
•• X
Conjugate base of tetrahedral
intermediate (TI–)
Dissociation of TI—H+
B ••
H
R
••
O ••
C
X
+
H
•• Nu
••
+B—H
O ••
+
R
C
+
Nu ••
•X
•
H
Dissociation of TI
B ••
H
R
••
O ••
C
X••
•• Nu
••
+B—H
O ••
+
R
C
+
Nu ••
• X •–
• •
Dissociation of TI–
•• –
•• O
••
R
X••
C
•• Nu
••
O ••
R
C
+
Nu ••
• X •–
• •
19.4
Nucleophilic Acyl Substitution
in Acyl Chlorides
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 Derivatives
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
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
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
O
RCCl + R'2NH + HO–
RCNR'2 + H2O
H
+ Cl–
O
via:
R
C
Cl
NR'2
Example
O
O
C6H5CCl + HN
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
19.5
Nucleophilic Acyl Substitution in
Acid Anhydrides
Anhydrides can be prepared from acyl
chlorides as described in Table 19.1.
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
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
RCNR'2 + RCO–
RCOCR + 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
2RCOH
O
+ 2HO–
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