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Introduction
The carboxyl group (-CO2H) is the parent group of a
family of compounds called acyl compounds or
carboxylic acid derivatives
Esters and amides common in nature.
Recall that aldehydes and ketones undergo nucleophilic
addition to the carbon-oxygen double bond
The carbonyl group of carboxylic acids and their derivatives
undergo nucleophilic addition-elimination
_
O
O O
- H+
C
R' O H R Cl R C Cl C R' + HCl
+O R O
H R'
_
O
O O
R'2 N H C
R Cl R C Cl C R'2
+N R N
+
H R'2 + -
R'2NH2 Cl
R'2 N H
_
O
O O O O
- H+
C
R' C O H R Cl R C Cl C C + HCl
+O R O R'
H C R'
O
Most anhydrides are named by dropping the word acid
from the carboxylic acid name and adding the word
anhydride
React acid chloride with carboxylic acid or
carboxylate ion.
O O O
C Cl O C O C CH
_ 3
+ CH3 C O
O heat
(EtO)3P O H
CH3 C OH C C O
H
O O O
H
C C O + CH3 C OH CH3 C O C CH3
H
O
H2O
R C OH + RCOOH acid
+
O
R'OH, H
O O R C OR' + RCOOH ester
R C O C R O
R'NH2
R C NHR' + RCOOH amide
O
Z
C R acylbenzene
AlCl3 Z
The names of esters are derived from the names of the
corresponding carboxylic acid and alcohol from which the ester
would be made
The alcohol portion is named first and has the ending yl The
carboxylic acid portion follows and its name ends with -ate or
-oate
Synthesis of Esters
From Carboxylic Acids
with ROH via mineral acid catalysis
via the use of diazomethane
From Acid Chlorides
From Acid Anhydrides
Esterification
O O
C OCH CH C OCH
2 3 + - 3
H or OCH3
+ CH3OH + CH3CH2OH
O
H2O
R C OH + R'OH acid
O
R''OH,
+ - R C OR'' + R'OH ester
H or OR''
O O
R''NH2
R C OR' R C NHR'' + R'OH amide
(1) LiAlH4
R CH2OH 1 alcohol
(2) H2O
OH
(1) 2 R''MgX
R C R''
(2) H2O 3 alcohol
R''
Formation favored for five- and six-membered rings.
+ O
OH H
+ H2O
COOH O
+ O
OH H
+ H2O
COOH
O
g- or d-Hydroxyacids undergo acid catalyzed reaction to give
cyclic esters known as g- or d-lactones, respectively
Lactones can be hydrolyzed with aqueous base
Acidification of the carboxylate product can lead back to
the original lactone if too much acid is added
Amides with no substituents on nitrogen are named by replacing -
ic acid in the name with amide
Amides with one or two hydrogens on nitrogen form very strong
hydrogen bonds and have high melting and boiling points
Hydrogen bonding between amides in proteins and peptides is an
important factor in determining their 3-dimensional shape
Amides From Acyl Chlorides
O
H2O
R C OH + R'NH2
H+ or -OH
acid and amine
(1) LiAlH4
(2) H2O
R CH2NHR' amine
O
Br-, OH-
R C NHR' R NH2 + CO2 1 amine
POCl3
R C N nitrile
(or P2O5)
Hydrolysis of Amides : heating an amide in concentrated
aqueous acid or base causes hydrolysis
Five- and six-membered rings can be formed by heating
g- and d-amino acids.
NH2 heat NH
COOH + H2O
O
Smaller or larger rings do not form readily.
-Lactams : found in antibiotics isolated from fungi.
Urea is the diamide of carbonic acid.
Urethanes are esters of a monoamide of carbonic acid.
O O
Cl C Cl + 2 NH3 H2N C NH2
urea
O O
N C O NH C OH NH C OR
H2O ROH