Transcript Miscellaneous Reactions

Hydrolysis of Acid Derivatives
Acid chlorides and anhydrides
O
O
HOH
RC Y
RC OH
Y = Cl or OCOR - room temperature
O
O
RC OCR
HOH
O
OCR
O
RC OH
USUALLY UNWANTED SIDE REACTIONS
Hydrolysis of Esters and Amides
Require acid or base catalyst and heat
ESTERS - REVIEW SAPONIFICATION
AMIDES - 6M HCl or 40% NaOH and prolonged heating
O
O
6M HCl
OH
NH2
O
NH2
NH
CH3
40% NaOH
heat
R
O
+
R
DEPROTECTION OF ACETANILDES
-O
CH3
Cyclic compounds
O
Y
HOH
O
Y = O, NH
O
HOH
NR Heat
H+
O
O
OH
Y
O
O
OH
NHR
O
RNH2
+
Phthalic acid
Reactions of Cyclic Anhydrides
with ROH
O
O
O
HOR
H+
O
OR
OH
O
Half Acid
Lactones with ROH & Amines
O
ROH
O
O
RNH2
O
O
OR
OH
O
NHR
OH
HO-(CH2)4COOR
HO-(CH2)4CONHR
Reduction Reactions
RCH2OH
RCO2R
LAH
Recall Reduction of amides to give amines
Acid chlorides to aldehydes
Look over carefully:
Summary of the Chemistry of Acid Chlorides
1) Synthesis - acid + SOCl2
2) Reactions
a. Conversion to all other acid derivatives: NO catalyst
b. Rx with organmetallics (p. 977)
RMgX or RLi ----> alcohols
LAH ---> primary alcohols
R2CuLi -------> ketones
Li(t-BuO)3H -------> aldehyde
Friedel-Acylation (AlCl3)
Acid Anhydrides
1. Preparation - from acid chlorides and carboxylic acids
2. Reactions
1. Conversion to less reactive acid derivatives No Catalyst
2. Friedel-Craft Acylations - catalyst required
O
O
O
+
R
O
R
AlCl3
O
R +
R
OH
NOTE above: One part of anhydride adds to ring: the other is
sacrificed
Mechanism of FC
THINK OF THE MECHANISM AS A TYPICAL ACID
CATALYZED ADDITION-ELIMINATION MECHANISM
OF NUCLEOPHILIC ACYL SUBSTITUTION
+
O
O
E
+
E+
Y
Y
ADDITION
Think of AlCl3 as big proton!!!!! IT IS E+
O
WHAT IS Y?
O
E
O
:NU
E
L
I
M
I
N
A
T
I
O
N
NU
Y
-E+
-Y
O
WHERE DOES E+ (AlCl3) ADD? The C=O oxygen
NU
WHICH IS NUKE? ELECTRON PAIR ON AROMATIC RING
ACTUAL MECHANISM
_
O
O
AlCl3
+ OAlCl
3
O
O
O
-
OAlCl3
_
+ OAlCl
3
O
O
O
+
O
-AlCl3
O
O
O
loss of
+
-H
H
+
-O
Please don’t do problem 31a, but
please do problem 32c
Chapter 22 Alpha Substitutions
and Condensations of Enols and
Enolate Ions
Actually this the chemistry of a-hydrogen atoms
O-
O
O
H
Base
C
Aldehydes, ketones and esters
C
C
enolate ion
IMPORTANT: enolate is a nuke; attacks via of its alpha carbon
Reactions of Enolates with
Electrophiles
O
X
X2
O-
O
RCH2X
C
R
O
R
O
OH
R
R
R
ALDOL REACTION - Borodin
C
EXAMPLES
O
O
H
CH2
+ H
CH2CH3
CH3
Dangle the group
attached to alpha carbon
O
OH
H
CH
CH
CH3
H
nuke portion
CH3
electrophilic portion
MECHANISM OF ALDOL
REACTION
O
+
CH2
H
O
O
H
OCH3
H
OH-
CH3
H
O
H
HOH
-OH-
CH3
O
H
OH
H
CH3