Oxidation of Alcohol to

Aldehyde and Ketone

Chromium-based reagent
Jones Reagent
Sarett and Collins reagent
(Cr03.2Py)

PDC (Piridium dichromate)

PCC (Pyridium chlorocromate)

ativated Dimethyl Sulfoxide

PfitznerMoffatt Oxidation
(Dicyclohexilcarbodiimide/ DCC) + DMSO
Albright Goldman Oxidation
(Acetic anhydride+DMSO)
Albright Onodera Oxidation (P205 + DMSO)
Parikh Doering Oxidation (SO3.Py)
Omura sharma swern Oxidation (TFFA +
DMSO)
Swern Oxidation (Oxalyl chloride)
Corey Kim Oxidation

Hypervalent Iodine
Compound
Iodine compound in a high valence
state behave as a strong oxidant.
(-): lack of solubility and poor
solubility in organic solvent.
Dess Martin Periodinane
IBX

Ruthenium-based
Oxidations
Ruthenium tetraoxide, (RuO4) -
milder oxidant (Ru +8, +7, atau +6)

TPAP (tetra-n-poluamonium
perruthenante)

Oxidations Mediated by TEMPO

and Related Stable Nitroxide
Radicals (Anelli Oxidation)
TEMPO (54)

Oxidations by Hydride Transfer from

a Metallic Alkoxide
Oppenauer Oxidation,

Mukaiyama Oxidation
ADD as oxidant with
magnesium alkoxide as catalyst

Oppenauer Oxidation
From Book. Strategic
Applications of Named
Reaction in Organic Synthesis
By. Barbara Czako and Laszlo
Kurti

 The oxidation of primary and secondary

alcohols with ketones in the presence of
metal alkoxides (e.g.,aluminum isopropoxide)
to the corresponding aldehydes and ketones
is known as the Oppenauer oxidation
In 1937, R.V. Oppenauer oxidized steroids
with secondary alcohol functionality to the
corresponding ketones using acetone in
benzene in the presence of catalytic amounts
of aluminum tert-butoxide.

 This oxidation proved to be high yielding and superior to other

existing oxidation methods due to its mildness.
Oppenauer's method came more than a decade after three
researchers independently described reduction of carbonyl
compounds with the use of aluminum alkoxides:
1) in 1925, H. Meerwein successfully reduced aldehydes with
ethanol in the presence of aluminum ethoxide
2) during the same year A. Verley reduced ketones with aluminum
ethoxide as well as aluminum isopropoxide but found that
sterically hindered ketones (e.g., camphor) reacted very slowly
and
3) in 1926, W. Ponndorf demonstrated that the reduction of
aldehydes and ketones was general for a variety of metal
alkoxides (e.g., alkali metal and aluminum alkoxides) derived from
secondary alcohols, and he found the process completely
reversible.

The general features of the

Oppenauer oxidation
1. The reaction is completely reversible and can be driven
to completion according to Le Chatelier's principle by
adding large excess of the ketone (e.g., acetone) to the
reaction mixture;
2. The reaction conditions are mild, since the substrates
are usually heated in acetone/benzene mixtures;
3. Most functional groups are tolerated (alkenes, alkynes,
esters, amides, etc.), but if the substrate contains basic
nitrogen atoms, the use of alkali metal alkoxides is
necessary in place of aluminum alkoxides;
4. in order to achieve reasonable reaction rates,
stoichiometric amounts of the aluminum alkoxide needs
to be used;

5. most commonly aluminum isopropoxide, t-butoxide,

and phenoxide are used;
6. a wide range of primary and secondary alcohols are
oxidized under the reaction conditions ( secondary
alcohols are oxidized much faster than primary
alcohols, so complete chemoselectivity can be
achieved (this feature makes the Oppenauer
oxidation unique compared to other oxidations);
7. overoxidation of aldehydes to carboxylic acids never
happens;
8. the oxidation of 1,4- and 1,5-diols usually yields
lactones.

9. acetone is used most often as the oxidant, but aromatic and aliphatic
aldehydes are suitable as oxidants due to their low reduction potentials;
10.addition of protic acids dramatically increases the rate of oxidation; and
11.the oxidation can be conducted using heterogeneous catalysts
(e.g.,alumina, zeolites), which has one great advantage over the
traditional homogeneous variant: the catalyst can be easily separated
from the reaction mixture.
The most important side reactions are:
1) aldol condensation of aldehyde products, which have an -hydrogen
atom to form -hydroxy aldehydes and/or ,-unsaturated aldehydes, but
with ketones this side reaction is not common;
2) Tishchenko reaction of aldehyde products with no -hydrogen atom, but
this can be suppressed by the use of anhydrous solvents; and
3) the migration of the double bond during the oxidation of allylic and
homoallylic alcohol substrates.

Persamaan Reaksi dan

Mekanisme

 The mechanism of this Oppenauer

oxidation
reaction involves conversion of the
alcohol
(R2CHOH) to be oxidized into an
alkoxide species (R2CHO-) that
transfers a hydride ion
to acetone. As a result, acetone is
reduced and the alkoxide ion
becomes a carbonyl compound

Application
P. Kocovsky, Tetrahedron Letter. 1993, 34,
6139-6140

Tetrasiklik
diol
Oxidant : 1-metil, 4-piperidone
HN

enon
e

Sternbach, D.D. Ensinger, C.L. Synthesis of polyquinanes. J. Org. Chem.

1990, 55, 2725-2736

Intramoleculer Diels-Alder approach (in situ)

cyclopentadiene ring and , -unsaturated ketone

Shing, T.K.M, Lee., C,M, Lo, H.Y. Synthesis of the CD ring in taxol from (S)Carvone. Tetrahedron Lett. 2001, 42. 8361-8363.

(S)- Carvone
Bicyclic -hydroxy
ketone
Isomerized by an
intramolecular redox
reaction

Modification Oppenauer
Oxidation
Heathcock, C.H., Kleinman, E.F., Binkley, E.S. Total synthesis of licopodium
alcaloids. J. Am. Chem.Soc 1982, 104, 1054-1068

Primar
y
alcoh
ol

Aldol
condensati
on
N-dealkilated
Tricyclic
tricyclic amino
enone
ketone)

Side reaction

TERIMA KASIH

1
5

Ponndorf (Meerwein-Verley) reduction

Reduction of ketones/aldehydes to alcohols

The reverse reaction is known as the Oppenauer oxidation

 asasLe Chateliersebagai
berikut:Bila pada sistem
kesetimbangan diadakan aksi, maka
sistem akan mengadakan reaksi
sedemikian rupa sehingga pengaruh
aksi itu menjadi sekecil-kecilnya

 Nucleophilic addition to C=X and

activated C=C multiple bonds (e.g.,
Michael Reaction). These reactions
also work best when a reasonably
stabilized anion is being formed. The
reverse reaction (retro-Michael)
occurs readily if the nucleophile was
a stabilized anion.

 From reducing metals

Alkoxides can be produced by several routes starting from an alcohol.
Highly reducing metals react directly with alcohols to give the
corresponding metal alkoxide. The alcohol serves as an acid, and
hydrogen is produced as a by-product. A classic case is sodium
methoxide produced by the addition of sodium metal to methanol:
2CH3OH + 2Na 2CH3ONa + H2 Other alkali metals can be used in
place of sodium, and most alcohols can be used in place of methanol.
From electrophilic chlorides
The tetrachloride of titanium reacts with alcohols to give the
corresponding tetraalkoxides, concomitant with the evolution of
hydrogen chloride:
TiCl4 + 4 (CH3)2CHOH Ti(OCH(CH3)2)4 + 4 HCl The reaction can be
accelerated by the addition of a base, such as a tertiary amine. Many
other metal and main group halides can be used instead of titanium,
for example SiCl4, ZrCl4, and PCl3.

 By metathesis reactions
Many alkoxides are prepared by salt-forming reactions from a metal
chloride and sodium alkoxide:
n NaOR + MCln M(OR)n + n NaCl Such reactions are favored by the
lattice energy of the NaCl, and purification of the product alkoxide is
simplified by the fact that NaCl is insoluble in common organic solvents.
By electrochemical processes
Many alkoxides can be prepared by anodic dissolution of the
corresponding metals in water-free alcohols in the presence of
electroconductive additive. The metals may be Co, Ga, Ge, Hf, Fe, Ni,
Nb, Mo, La, Re, Sc, Si, Ti, Ta, W, Y, Zr, etc. The conductive additive may
be lithium chloride, quaternary ammonium halide, or other. Some
examples of metal alkoxides obtained by this technique: Ti(OC 3H7-iso)4,
Nb2(OCH3)10, Ta2(OCH3)10, [MoO(OCH3)4]2, Re2O3(OCH3)6, Re4O6(OCH3)12,
and Re4O6(OC3H7-iso).

 Metal alkoxides hydrolyse with water according to the following equation:[3]

2 LnMOR + H2O [LnM]2O + 2 ROH where R is an organic substituent and L is an unspecified ligand
(often an alkoxide) A well-studied case is the irreversible hydrolysis of titanium ethoxide:
1/n [Ti(OCH2CH3)4]n + 2 H2O TiO2 + 4 HOCH2CH3 By controlling the stoichiometry and steric properties
of the alkoxide, such reactions can be arrested leading to metal-oxy-alkoxides, which usually are
oligonuclear complexes. Other alcohols can be employed in place of water. In this way one alkoxide can
be converted to another, and the process is properly referred to as alcoholysis (unfortunately, there is
an issue of terminology confusion with transesterification, a different process - see below). The position
of the equilibrium can be controlled by the acidity of the alcohol; for example phenols typically react
with alkoxides to release alcohols, giving the corresponding phenoxide. More simply, the alcoholysis can
be controlled by selectively evaporating the more volatile component. In this way, ethoxides can be
converted to butoxides, since ethanol (b.p.78C) is more volatile than butanol (b.p.118C).
In the transesterification process, metal alkoxides react with esters to bring about an exchange of alkyl
groups between metal alkoxide and ester. With the metal alkoxide complex in focus, the result is the
same as for alcoholysis, namely the replacement of alkoxide ligands, but at the same time the alkyl
groups of the ester are changed, which can also be the primary goal of the reaction. Sodium methoxide,
for example, is commonly used for this purpose, a reaction that is relevant to the production of "
bio-diesel."
Formation of oxo-alkoxides
Many metal alkoxide compounds also feature oxo-ligands. Oxo-ligands typically arise via the hydrolysis,
often accidentally, and via ether elimination:
2 LnMOR [LnM]2O + R2O Additionally, low valent metal alkoxides are susceptible to oxidation by air .

 name molecular formula comment

Titanium isopropoxide Ti(O-i-Pr)4 monomeric because of
steric bulk, used in organic synthesis Titanium ethoxide
Ti4(OEt)16 for sol-gel processing of Ti oxides
Zirconium ethoxide Zr4(OEt)16 for sol-gel processing of Zr
oxides Tetraethyl orthosilicate Si(OEt)4 for sol-gel
processing of Si oxides; Si(OMe)4 is avoided for safety
reasons Aluminium isopropoxide Al4(O-i-Pr)12 reagent for
MeerweinPonndorfVerley reduction Niobium ethoxide
Nb2(OEt)10 for sol-gel processing of Nb oxides
Tantalum ethoxide Ta2(OEt)10 for sol-gel processing of Ta
oxides Potassium tert-butoxide, K4(O-t-Bu)4 basic
reagent for organic elimination reactions