Acidity oft Hydrogen Atoms -

Strong Bases can abstract the weakly addict proton to forman -

enolate anion

( :-)
Base :O
µ ÷ . ,

Keto Enol Isomerization

-

Aldehydes and ketones exlstlheaulllbrium

A- Carbonyl compound withal proton
rapidly
-

equilibrates w/ Its enol

0 OH
more stable less stable
weaker acid ! acid !
H
stronger

Keto tautomer enol tautomer

Isomerization can be base or acid

catalyzed
µ+
•
Basic conditions T

( ÷8 :]
° :O OH
riots , . .

enolate anion enol

•
ACIDIC CONDITIONS
OH
" "

t.it
] eno .

Stabilized Ends
thots are stabilized by conjugation and intramolecular hydrogen bonding
stabilization Increases the amount of enol present in the equilibrium
O O
-
- H
.

O
.

O
O o
9 f
0 OH
5% 95%
Carbonyl A- Substitution Reactions
* Remember : Basewillformenolateanaaadwlllformenol

Iii;
°
O O
CHSOH

+;r¥n ,
'"'
c'III ,

enolate
O o

Ctb
ar :
Inversion
of Stereo Chem
CH3 H

A- Halogenatlon
ACIDIC Or basic conditions
O
O
Br
CH3C00H
,
+ By ,

ACIDIC →
mono substitution

Basic
poly substitution
→

SNZ substitution preferred WI primary halides

O CH3 O
f 25°C " 11

( CH 3) as
,

Br -

CH2 C Ph
-
-

acetone 1h20 Hsc S CHIC- -

-

Ph
-
EL elimination is preferred when a weak base ( pyridine ) or
strong
base ( Kot Bulls used .

Basich Halogenate on ( polynalogenatlon )

-

O O
HO fast
-

R >
R
Halogenate on is the

Rt Brz Base R Step

H H Br Br
A- Halogenatlon of carboxylic Acids
The Hell Volhard Zelinsky ( HV 2) Reaction
-
-

X
x OH por Pxz OH
,
t Xz A- Cl Br
R R
.

O 0

OH
OH

Br H2O >
O
X OH 171383 OH
>

O
Br2
O
NHS NHZ
OH

When the d- Carbons actuality center ,

the product is a racemic mixture

Ctb
B. OH
pporz
too!?BVOH
>
Bra tent .

O O

A- Alkylation
Reaction of an enolate anion Wlan alkyl halide

O °

( )
°
LDA RX
> >
+, ...
e

° °

( )
°
LDA
> £
.
CHSCHZBY -
cHzCH3

€ )
C"
LDA .
CH3I o
>
>
o
 CHS
"

[ c=N)CH3
LDA E
-

CEN
>
CEN

Aldol condensation
I

0 0 OH
09 Base B
hydroxy
-

& B
Fun carbonyl compound
enolate
carbonyl An Aldol

0 OH °
f Basye Analdolcan dehydrate in base

An Aldol

If aldol has no A- hydrogens ,

Itcannot dehydrate !
CH3cH3
CH3fCH3
CH3
NaOH µ
2~Ht WH non -
HK
HK ethanol
O
2 +130 µzC
0
OH O
target missile

Aldehydes are more reactive

blctheyare Unhindered Eaull . .

favors Aldol
ketones are less reactive b/c are hindered Eau favors reactants
they .
.

*
Highly substituted ketones do not react .

NaOH
NO Reaction
Intramolecular Aldol condensation
O
O O

CH3 NaOH H2O

✓ >
o
>

Ethanol
CH3 CH 's
a) OH
CH3

crossed Aldol Reactions

the carbonyl compound w/ non -

H cannot form enolate anion

O
( O OH O

H NaOH "

↳÷H H2O
H
> dehydrate
Ethanol
missile
non H -

target
Ada
slowly

synthesis of complex Alcohols

OH O O
GO 0
NaOH
yV H2O
M
>
~
+
H H
.
H Ethanol
a

target missile pd
H2 '

zenana
yemoresdb
°

reduces 2nCHg )
# < n H
carbonyl aa HCl
-

Claisen condensation
reaction
of two esters
having and H -

with one equiv .

of base to yield
a B keto
-

ester
O O
0 leave O
NaOH Clegane )
Z M ?

\O
+
O ai
O ethanol B
✓
.

H3Ot x

youneedaudtodnvetherxnto completion .
 determine the SM

Ott
Ott
} 2
>
o

O O

Intramolecular Claisen condensation

rxnworksbestifborll membered
rings are formed
O leaves O
O
m
Nott tea NAOHIETOH ✓
[ >
Ott
or. O H3Ot
\ "
C
Ott

crossed Claisen condensation

when two
diff esters are used one ester has not
hydrogens
-

.
.

O leaves
O O
M O
O tea NAOHIETOH

①
> /
£ . O Hzot O

non H - enolate

Add Slowly

Modified Claisen condensations Rxnblw Esters .

'
-

ketones
Esterhasnot H cannot form enolate -

O O
O
H3C O H3C
leave
£
.
lea NaOH , ETOH H
M

¥9
+ >
HE Ott H3Ot HE

enolate non H -

Add Slowly
Modified Claisen -01N Esters and Aldehydes O
0 OH
C O
tea NaOH ,EtOH
H Ott

↳
>

Ott H3Ot
.

Add Slowly
Intramolecular Claisen ester and ketone in the same molecule

O 3
2

3
5 NaOH 4 I
4 I >
OEE
2
in
H3Ot O O
5
O leaves
CH3

Malone Ester synthesis preparation of substituted acetic acids

CH2CCOzEt)z
R X
-
> R CHZCOOH
-

Malone Ester

Br
COLET CO2 Et
NAOET Nao Et
+ > 7
ETOH H COLET CH3I coz Et
CHZCCOZEE)z cuz
N O EE

decapitate
use this to n
t
replace Br OH
CH3

Malonlcesterls the

only thing that works for this

 Aceto acetic Ester Synthesis preparation of methyl ketones

O O O O O O
NaOH >
>

#
Eto Ctb Eto Eto CH's
p
Aceto acetic Ester
to make enolate

O o
Br
+
Nao Et N CH3 H3Ot A CH3
> >
O ETOH
O Ll
coset
decarboxylase
ETO .
e CHS
-
replace Br

B keto esters can be used

-

in place of Aceto acetic Ester

O O O
O
H
(Hzph CHZPN
Ott Naoet ETOH
By . H3Ot
>
COLET >

PNCHZBR a

acyclic B keto ester

-

O O

a
NAO Eti OH
13 cuz CHS
CH3I CH3
COLET
COLEY decarboxylase
>
Conjugated Aldehydes ' ketones
-

conjugated more stable

-

Reactions :

carbonyl Addition (Adding to C- O ) Less stable

0 OH 1,2 Addition

t strong NUC . Kinetic

Nut, >

R p fast R R

gyougkeefffa.IE
NU
Aaaltloncaadstots)
conjugate
O Nu 0 More stable
Weaknuc .

1,4 Addition

HswaRyhermo
r

Strong NUC .
→
Brit ,N=_CiH5 .RS

R-COZH.R-O.H20.CHSOH.ETOH.EE
Weak NUC .
→

Title?¥ninem"Hirer:*.si:p

- - - - - - -
-

SM kinetic
thermo

Strongly BASIC Nucleophiles →

Direct Addition ( carbonyl )
° H O HO CH 's
OH

hIAlH4 CH3M9Br
> 7
H3Ot H3Ot

Nucleophiles
that add toC=O→RMgX.hlAlH4
Weakly Basic Nucleophile →
Conjugate Addition ( B position)
-

O O
Nucleophiles that
* 1. NACNIDMSO add to conjugate B→
-
2. H3Ot ROH NACN Rzcuhi
B
, ,

CN

O
O

+ CH3SH >

SCH 's

Michael Addition cat .

>
requires
O ✓ O O
H a NAOET ,
ETOH
+ B
Hzot
>
/
O
COZET COLET

Robinson Annulation canfuseasixmemberedcyclonexanoneohto

an existing
O
ring O
p Naottccat )
x

✓ CH 's EEOH
Hzot
>
dilute

O O Michael Add .
Jr O NAOET
VETO Hib
O O

-
H2O -

A
O O
OHL
dehydrate
 the initial reactants Ann Product
Identify Ofa Robinson .

CH3O O

CH 's

CH3 >
CH }
t

O O
o
CH3
Ctb
Ctb CH3

O
B
O
O
0-2 o
O

> 7 5

.it/4 516
23
'

34
Z
4
7
23
l
1
.
y
Remember : 1.5
✓

After Michael ,
do HO H -

dicarbonylis the

intramolecular aldol
o typical product of
O
O amkhaelrxn
O
( Z
t Ht
O
Z
'
> 3
y
L
U 4 .
; 4
p y

s
3
56 O
-

9
✓ O
CH3
CH3
OH

CH3
o

t >

O O
O

Michael Rxnwl Esters

x CHS
( H2 (COLET)z t B NAOEtccatfETOHCC02Etb.CH cuz
V
Malone ester
o
1430+0
and Decarboxylation
subsequent reactions Hydrolysis
-

O O O O

f +
NAOETIETOH
> Hzot
H3Ot
"
COOEE O V O
COOEE