Chapter 18: Enols,

Enolates, Enals, and

Enones

-Hydrogens/ hydrogen- pd
senyawa karbonil bersifat asam

Deprotonasi senyawa karbonil

Enolates: Oxaallyls

(CH3)2CHCHO pKa ~ 16

Dominant form

CH3COCH3 pKa ~ 20
Compare: ethene (44) or ethyne (25)

Basa u/ deprotonasi
stoikiometri: KH, LDA

Acetone enolate

Reactivity: Ambident, attack on either O or C:

Tautomerization

Alkilasi

(Thermodynamic)

Protonasi
(Kinetic)

Keto-Enol Equilibria
Kita sering tdk membutuhkan pembentukan enolat stoichiometric:
Asam atau basa mbtk enol/enolat pd konsentrasi equilibrium, cukup
u/ transformasi rx berikutnya.

H+ or OH cat.

Keto form

Enol form

K <<1 usually

H+ or OH cat.

Worse, because CH3

stabilizes keto form

Mechanisms of enol to keto tautomerization

(and the reverse):

Base-catalyzed

Acid-catalyzed

Bgm enolisasi terdeteksi ? NMR:

pertukaran H-D dg D2O, D+, or D2O,
OD (-H signal mengilang).

Konsekuensi lain dr enolisasi: Loss of

stereochemistry

Cis

Trans
More stable

Halogenasi: katalitik H+ atau HOAcid-catalyzed:

Cl

HCl

+ Cl2

+ HCl
Stops here!

Base-catalyzed:
O

+ Cl2

NaOH

Cl
Cl

Cl
Cl
Perchlorination

+NaCl

Mechanisms: Acid-catalyzed

Ethenol is
e-rich

Like a Markovnikov alkene bromination

substituent Br mengurangi kebasaan oksigen:

memperlambat halogenasi berikutnya

Base-catalyzed

Like an SN2 reaction

Br substituen Br meningkatkan
keasaman -Hs: mempercepat
halogenasi berikutnya.

Alkilasi

Alkilasi enolat dpt sulit dikontrol

1.

Ion Enolat adl basa kuat: E2 problems

Alkilasi paling baik bila guna halomethan, haloalkana primer,
halida alilik
2. Aldehid diserag o/ enolat pd karbon karbonil
Aldol condensation (later)
baik digunakan keton yg kurang reaktif (at carbonyl)
3. Ketone punya masalah sendiri
produk akan kehilangan hydrogen yg lain dan teralkilasi utk
kedua kalinya
keton asimetris memicu 2 produk regioisomerik

BBoys
LipAlkn

Only one H
Good alkylating
agent

Solusi masalah ini:

Enamina
Rute alternative alkilasi aldehid dan keton.
Enamina bersifat neutral dan ik. Rangkap
karbon-karbon kaya elektron.
-carbon bersifat nucleophilic karena resonansi.

Ethenamine

Prosedur:
1. Pembentukan Enamina memakai amin pembantu,
e.g. azacyclopentane;
2. Alkilasi
3. Larutan asam work-up (hydrolysis)

Example:

Berfungsi jg utk aldehid:

Penting, enolat aldehid bereaksi dg precursor

aldehidnya pd kondensasi aldol.

Kondensasi Aldol
(Aldehyde alcohol)

Catalytic

New bond

Dpt dilakukan scr

stoikiometri preformed
enolat.

Stereochemistry
depends on sterics

Examples of a catalytic aldol condensations:

Stepwise:

50-60%
Isolable,
if wanted
One pot:

(Sterically
controled)

Mechanism of Aldol Formation:

Monr
Lipsh

Aldol Dehydration:

Animn

The crossed aldol reaction is nonselective...

...kecuali aldehid nonenolizable ada:

O

O
H

NaOH,

Keton bisa bekerja mll kondensasi aldol:

Endothermic

Equilibrium

Exothermic

Intramolecular Aldol

Strain

X X

Four-membered
ring and cannot
dehydrate

Thermodynamically
and kinetically
favored

X
X

Strained
bridge

Good

OH,

-H2O
Six-membered
ring

90%

,- Aldehid dan Keton

tak jenuh

Acidic

HH
O

Acidic
pKa ~ 16-20

H
H H

Basic

Persiapan
1. Eliminasi -Halogenasi
2. Oksidasi alkohol alilik dg MnO2
RCH=CHCH2OH

MnO2

3. Kondensasi aldol

O
R

4. Reaksi Wittig Stabilized

Ylides
O
ClCH2CH
NaOH

P(C6H5)3

(C6H5)3P

O
Cl-

(C6H5)3PCH2CH
H

CH CH
O

H
C_

(C6H5)3P
Stabilized by
resonance:
Can be isolated,
reacts only with
(C6H5)3P C
aldehydes, not
H
ketones

H
O

CH
O

81%

CH
O

Trans

Karakter karbonil ,-tak

jenuh
Stabilized by resonance

akibatnya:
,-sistem tak jenu tersusun kembali
mjd isomer ,-enone.

Acid- or base-catalyzed

Mechanism:
Acid-catalyzed
Reprotonation
to the more
stable cation

Base-catalyzed

Reaktivitas Karbonil ,tak jenuh

-Undergo many reactions characteristic of
alkenes and ketones/aldehydes

Examples:
O

H2, Pd/C

H
CH3Li

OH

Pd adisi, reaktivitas baru utk seluruh

sistem (as in conjugated dienes)
1,4-Addition (conjugate addition)

1. Adisi konjugasi Hidrogen Cyanide

Not cyanohydrin
formation (1,2addition reversible)

Mechanism:

2. O and N Nucleophiles
a. H2O or ROH: Conjugate Hydration
or Ether Formation

Mechanism:

Ether Formation: Strychnine

Synthesis by Woodward

N
O

H N

H N

H
HO

Base

N
O

H
H

Strychnine

b. Adisi Amina, RNHR: Aminasi

Intramolecular

O
OH

HN

Product mainly
cis due to ring
fusion

3. Organometalik
RLi reagents attack mainly at C=O

Cuprates, R2CuLi, add 1,4-

Example of 1,4-addition with cuprate:

Mekanisme yg kompleks, melibatkan inisial transfer e(radical intermediates). Disebut -adisi nukleofilik.
Catatan: Cuprat adl organometalik dan moisture
sensitive. Rx pd media aprotik, shg menghasilkan ion
enolat sebagai produk. Protonation occurs on work-up.

The initial enolate product of cuprate 1,4addition can be trapped with RX: Double
alkylation of the C=C double bond!

O
1.

(C6H5)2CuLi

CH3

2. CH3I
84%

C6 H 5

Mostly trans
due to sterics

4. Enolate Ions As Nucleophiles

Enolat menyerang ,-ketones tak jenuh and
aldehydes pd1,4-sense:
Michael Addition (adisi aldol konjugate).
Bekerja dg
aldehid dan keton sederhana.
Forms the thermodynamic enolate

Mechanism:

1,5-Dicarbonyl compounds

Anulasi Robinson
Kombinasi Adisi Michael dan
Kondensation Aldol intermolekuler

Example:
Forms the thermodynamic enolate

Anim

More acidic:
Benzylic (like
allylic)

Application to steroid synthesis:

Acidic -H

Conjugated
Aldehydes and
Vision

Vertebrates have two kind of

photoreceptor cells:
Cones and Rods
Cones
Function in bright light
Color vision
Rods
Function in dim light
No color

 Human retina has 3 million cones and

100 million rods
A single h of light can excite a rod
cell!
How?
Rods covered with photoreceptors
h Atomic motion Nerve
impulse

Formation of rhodopsin from the protein

opsin and 11-cis-retinal:

Remember retinol = vitamin A, derived from carotene.

Deficiency causes night blindness, then blindness

The process of vision is

for a photon to impinge on
rhodopsin and effect cistrans isomerization. The
resulting geometrical
change causes a nerve
impulse perceived as light.

h cis,trans
in picoseconds
(10-12 sec)