Transcript Carboxylic Acid Derivatives Acid Chlorides Acid Anhydrides Esters Amides Nitriles Nucleophilic Acyl Substitution Reactivity of Acid Derivatives.

Carboxylic Acid Derivatives
Acid Chlorides
Acid Anhydrides
Esters
Amides
Nitriles
Nucleophilic Acyl Substitution
Reactivity of Acid Derivatives
Nucleophilic Acyl Substitution
I.U.P.A.C. Nomenclature
(uses carboxylic acid template)
O
O
Cl
drop "ic acid" add "yl chloride"
pentanoyl chloride
O
O
O
drop "acid" add "anhydride"
pentanoic anhydride
O
NH2
drop "oic acid" add "amide"
pentanamide
OCH3
"alkyl" _ drop "ic acid" add "ate"
methyl pentanoate
CN
drop "ic acid" add "e_nitrile"
pentanenitrile
Acid Chlorides
OCH3 O
Cl
CCl
O
o-methoxybenzoyl chloride
(E) 2-octenoyl chloride
O
CH3O
CH2CCl
(p-methoxyphenyl)acetyl chloride
Acid Anhydrides
O
O
O
butanoic anhydride
butyric anhydride
O
O
C
C
O
CH3
acetic benzoic anhydride
O
HO
O
succinnic acid
OH
O
O
O
succinnic anhydride
Esters
O
COCH2CH2CH3
O
O
propyl benzoate
(Z) cyclopentyl 2-butenoate
O
COCH2CH(CH3)2
isobutyl cyclohexanecarboxylate
O
CH2COCH2CH3
ethyl phenylacetate
O
Amides
CNH2
H2N
CH3
meta methylbenzamide
O
2-ethyl-3-methylpentanamide
-ethyl--methylvaleramide
O
CN(CH3)2
O
HCN
H
N-benzylformamide
N,N-dimethylcyclopentanecarboxamide
Lactones (cyclic esters)
O
O
O
HO
+ H2O
OH
-valerolactone
-hydroxyvaleric acid
O
O
O
OH
OH
-hydroxyenanthic acid
+
H2O
-enantholactone
Gamma Hydroxybutyrate
HO
CO2H
-hydroxybutyric acid
+
H3O
O
O + H2O
-butyrolactone
HO
CO2 Na
sodium 4-hydroxybutanoate
or sodium -hydroxybutyrate
(GHB)
CNS depressant
as of 2000, Schedule I
controlled substance
If mixed with ROH, the depressant
effects are enhanced
All Acid Derivatives can be
Hydrolyzed
O
O
(CH3)2CHO
OCH(CH3)2
diisopropyl pimelate
Hydrolysis
+
H3O or
in base
O
HO
O
OH
+ 2 (CH3)2CHOH
What are the 3 Hydrolysis
Products?
O
C N(CH2CH3)2
+
H3O
O
O
Two hydrolyzable groups
products are carboxylic acid(s)
+ conjugate acid of the LGs
O
CO2H
C N(CH2CH3)2
+
H3O
O
O
OH
+ HN(CH2CH3)2
+
HO
O
Draw the Hydrolysis Products
O
CH2CNH
+
H3O
S
N
O
penicillin G
CH3
CH3
- +
CO2 K
Hydrolysis of Penicillin
O
CH2CNH
+
H3O
S
N
O
penicillin G
CH3
CH3
- +
CO2 K
CH2CO2H
NH2
S
CO2H N
H
CO2H
Aspartame
O
O
O
HOCCH2CHCNHCHCOCH3
NH2
CH2
O
+
H3O
O
HOCCH2CHCOH
HOCH3
NH2 O
methanol
aspartic acid
H2NCHCOH
phenylalanine CH2
Hydrolysis of an Acid Chloride
Acid Chloride Preparation
O
O
COH
CCl
SOCl2
in
N
+ SO2
+ HCl
O
O
OH
CCl
SOCl2, pyridine
+ HCl
+ SO2
O
Cl
S
O
Cl
O
S
O
C OH
C
Cl
O
Cl
O
S Cl
O Cl
C OH
O
O
O
S
S
O
Cl
C OH
pyr:
C
Cl
O
Cl
Nucleophilic Acyl Substitution
O
O
LG
+ Nu
O
LG
Nu
O
LG = Cl , OCCH3 , OCH3 , NH2
best
worst
Nu
+ LG
With Acid Chlorides,
No Catalyst is Needed
Anhydride Prep.
O
HO
Cl
O
addition
O H
O
Cl
elimination
O
O H
O
Cl
O
deprotonation
O
O
O
+ HCl
Ester Preparation
from an acid chloride
Amide Preparation
from an Acid Chloride
Amide from Anhydride
Fischer Esterification
Fischer Esterification Shows
Oxygen “Scrambling”
a methanolysis
O
O
C
C
OH
+ CH3OH
+
H (cat.)
&
OCH3
+ HOH
O
C
OCH3
+ HOH
most basic
oxygen
C
O
H
O
C
OH + CH OH
3
+
H (cat.)
OCH3
+ HOH
H
O
C
H
OH
intermolecular
proton
C
OH transfer
OCH3
OH
H
OH
C
OH
OCH3
H
OH
C
O
OCH3
H2O
or CH3OH
H
Diazomethane Preparation of
Methyl Esters
Diazomethane has a Basic Carbon
O
O
COH
H
H
C
H
COCH3
CH2N2, ether
N
C
N
H
N
N
Mechanism
O
Flavors and FragrancesO
apple
O
O
peach
O
O
COCH3
pear
O
grape
O
banana
NH2
O
OH
O
"juicy fruit"
O
O
O
COCH3
wintergreen
O
rum
O
O
O
orange
O
honey
Intramolecular Fischer
Esterification - GHB
O
O
HO
+
H3O
OH
O + HO
2
O
O
H 3O
HO
+
O + HO
2
OH
O
HO
H
O
HO
HO
OH
OH
H
OH
O H
+
H trans.
HO
OH
O
H
H 2O
H
O
O
Lactam (cyclic amide) Formation
-Lactams as Antibiotics
Acid Catalyzed “Olysis”
Reactions
O
COH
+
H3O
hydrolysis
O
O
+
OCH2C6H5
NH3, H (pH 4)
CNH2
+ C6H5CH2OH
aminolysis
O
CH3OH, H
+
methanolysis
COCH3
Transesterification
a Methanolysis
O
O
OCH2C6H5
CH3OH, H
+
OCH3
+ C6H5CH2OH
O
H
+
OCH2C6H5
O
CH3OH, H
+
OCH3
+ C6H5CH2OH
O
H
CH3OH
O H
OCH3
OCH2C6H5
HOCH3
OH
OH
+
OCH2C6H5
OCH3
H
H trans.
H
OCH2C6H5
OCH3
Aspirin Synthesis
CO2H
O O
OH
CH3COCCH3
H2SO4 (aq)
CO2H
O
OCCH3
+ CH3CO2H
H
O O
CH3COCCH3
CO 2H
O O
OH
H
+
CO 2H
O
OCCH3
CH3COCCH3
+ CH3CO2H
H2SO4 (aq)
CO 2H
O
H
OH2
OCCH3
+ CH3CO2H
CO 2H
OH
H
O
OCOCCH3
H CH3
CO 2H
+
H transf.
O
OC
O
OCCH3
CH3 H
Basic Hydrolysis
Saponification
Basic Hydrolysis of an Amide
Mechanism
O
O
CN(CH2CH3)2
C
NaOH, H2O
OH
O Na
+
H carb.
acid
+ HN(CH2CH3)2
O
O
C
OH
N(CH2CH3)2
C
OH
+ N(CH2CH3)2
O
LiAlH4 Reductions
CCl
CH2OH
+ HCl
O O
CH2OH
COCCH3
+ CH3CH2OH
CO2H
1) LiAlH 4
O
2) H3O
COCH3
CH2OH
+ H2O
+
CH2OH
+ CH3OH
O
CNH2
CH2NH2
Reduction of Esters with
LiAlH4
DIBAH
Diisobutyl Aluminum Hydride
Reduction of an Ester to an Aldehyde
O
O
COCH2CH3
1) DIBAH
in toluene
+
2) H3O
CH
+ CH3CH2OH
H
DIBAH
(CH3)2CHCH2
Al
CH2CH(CH3)2