12.AN a aldeídos e cetonas QUI02015 6 (1)

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16/09/14 
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339 
 
Prof. Dr. José Eduardo Damas Martins 
Oxidação de aldeídos e 
cetonas 
340 
 
Prof. Dr. José Eduardo Damas Martins 
Aldeídos são muito mais facilmente oxidados 
do que as cetonas 
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Prof. Dr. José Eduardo Damas Martins 
O Produto da oxidação de um aldeído é um 
ácido carboxílico. 
R C H
O
R C OH
O
[O]
Agente oxidante
Ácido carboxílicoAldeído
342 
 
Prof. Dr. José Eduardo Damas Martins 
Agentes oxidantes comuns como Na2Cr2O7, 
KMnO4 e Ag2O são suficientes para efetuar 
a oxidação. 
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343 
 
Prof. Dr. José Eduardo Damas Martins 
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Exemplo 1 
Aldeído Ácido 
carboxílico 
344 
 
Prof. Dr. José Eduardo Damas Martins 
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Exemplo 2 
Aldeído Ácido 
carboxílico 
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345 
 
Prof. Dr. José Eduardo Damas Martins 
Aldeídos podem ser oxidados a ácidos 
carboxílicos, inclusive, pelo oxigênio do ar. 
346 
 
Prof. Dr. José Eduardo Damas Martins 
H
O
OH
O
ar
Benzaldeído Ácido benzóico
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Prof. Dr. José Eduardo Damas Martins 
Oxidação de 
Baeyer-Villiger 
348 
 
Prof. Dr. José Eduardo Damas Martins 
É um método útil para converter aldeídos e 
cetonas em ésteres através da inserção de 
um átomo de oxigênio na molécula. 
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Prof. Dr. José Eduardo Damas Martins 
R1 R2
O
R1 O
R2
O
R CO3H
R CO3H = Ácido peroxi benzóico
R O
OH
O
350 
 
Prof. Dr. José Eduardo Damas Martins 
O
O
O
RCO3H
O
O
O
RCO3H
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351 
 
Prof. Dr. José Eduardo Damas Martins 
O Ácido meta cloro perbenzóico, m-CPBA, é 
um dos peróxidos mais utilizados em 
oxidações de Baeyer-Villiger. 
352 
 
Prof. Dr. José Eduardo Damas Martins 
O
H
+
O
O R
O O O O
R
O
H
O
H
O
O R
O
O
H
+ O
O R
O
Mecanismo 1 
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353 
 
Prof. Dr. José Eduardo Damas Martins 
O O O
R
O
H
O
O
+
O
R
O
H
Ác. carboxílicoÉster
Mecanismo 
concertado 
354 
 
Prof. Dr. José Eduardo Damas Martins 
O
H
O
O R
O
O
H
+ O
O R
O
O
H
+
O
O R
O O O O
R
O
H
Mecanismo 2 
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Prof. Dr. José Eduardo Damas Martins 
O O O
R
O
H
1
2
3
4
O
O
O
R
O
H
Ác. carboxílicoÉster
+
Mecanismo 
concertado 
356 
 
Prof. Dr. José Eduardo Damas Martins 
Capacidade migratória 
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357 
 
Prof. Dr. José Eduardo Damas Martins 
R
O
H
O
O CF3
O
R
O
H
+ O
O CF3
O
R
O O O
CF3
O
H
Intermediário
358 
 
Prof. Dr. José Eduardo Damas Martins 
Possibilidade 1 
R
O O O
R
O
H
1
2
3
4
R O
O
O
CF3
O
H
Ác. carboxílicoÉster
+
Mecanismo 
concertado 
Migração do 
grupo fenil 
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Prof. Dr. José Eduardo Damas Martins 
Possibilidade 2 
R
O O O
R
O
H
1
2
3
4
O
CF3
O
H
Ác. carboxílico
+
O
O
Éster
R
Mecanismo 
concertado 
Migração do 
grupo R 
360 
 
Prof. Dr. José Eduardo Damas Martins 
O grupo que melhor estabiliza um carbocátion tem maior 
probabilidade de migrar 
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361 
 
Prof. Dr. José Eduardo Damas Martins 
Ordem de migração 
t-Bu i-Pr Ph Et Me> > > >
M e s m a o r d e m d e 
e s t a b i l i z a ç ã o d e 
carbocátions 
362 
 
Prof. Dr. José Eduardo Damas Martins 
Esta tendência sugere que no estado de 
transição exista a formação de cargas 
positivas a serem estabilizadas. 
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363 
 
Prof. Dr. José Eduardo Damas Martins 
Me
O O O
R
O
H
(+)
(+) _( )
≠
Me
O O O
R
O
H
Me O
O
Me
O
Me O
O
RCOOH
Majoritário
Estado de transição 
364 
 
Prof. Dr. José Eduardo Damas Martins 
Oxidação de Baeyer-Villiger 
em cetonas cíclicas 
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Prof. Dr. José Eduardo Damas Martins 
A reação com cetonas cíclicas forma 
lactonas. 
The overall consequence of the Favorskii rearrangement is that an alkyl group is transferred from
one side of a carbonyl group to the other.
This means that it can be used to build up heavily branched esters and carboxylic acids—the sort
that are hard to make by alkylation because of the problems of hindered enolates and unreactive sec-
ondary alkyl halides. Heavily substituted acids, where CO2H
is attached to a tertiary carbon atom,
would be hard to make by any other method. And the Favorskii rearrangement is a key step in this
synthesis of the powerful painkiller Pethidine.
Try writing a mechanism for this last reaction and you run into a problem—there are no acidic
protons so the ketone cannot be enolized! Yet the Favorskii rearrangement still works. Despite our
warnings against confusing the mechanisms of the Favorskii and benzilic acid rearrangements, the
Favorskii rearrangement may, in fact, follow a benzilic (or ‘semibenzilic’, by analogy with the semi-
pinacol) rearrangement mechanism, if there are no acidic hydrogens available.
Migration to oxygen: the Baeyer–Villiger reaction
In 1899, the Germans, A. Baeyer and V. Villiger, found that treating a ketone with a peroxy-acid
(RCO3H) can produce an ester. An oxygen atom is ‘inserted’ next to the carbonyl group.
Now, you saw a similar ‘insertion’ reaction
earlier in the chapter, and the mechanism
here is not dissimilar. Both peracids and dia-
zomethane contain a nucleophilic centre that
carries a good leaving group, and addition of
peracid to the carbonyl group gives a struc-
ture that should remind you of a semipinacol
intermediate with one of the carbon atoms
replaced by oxygen.
Carboxylates are not such good leaving groups as nitrogen, but the oxygen–oxygen single bond is
very weak and monovalent oxygen cannot bear to carry a positive charge so that, once the peracid
992 37 . Rearrangements
R1
X
O
R2
R3O
R1
O
R2
Favorskii
one 
C=O
MeN
Cl
Ph
O
MeN
OH
O
PhNaOH
Pethidine
!
The Favorskii mechanism will help
you understand the
Ramberg–Bäcklund reaction in
Chapter 46—the two reactions
have quite similar mechanisms.
MeN
Cl
Ph
O
OH
MeN
Cl
Ph
O
OH
MeN
O
Ph
OH
MeN
O
Ph
O
‘semibenzilic’ Favorskii rearrangement of nonenolisable ketones
no protons 
α to C=O
NaOH
O
Ph
Ph
O
OH
compare the migration step with 
this benzylic acid rearrangement
O O
O
O O
CH2
R
O
OHO
NH2C N
RCO3H
oxygen "inserted" here
CH2N2
CH2 "inserted" here
nucleophilic 
atom
carrying good 
leaving group
peracid
diazomethane
O
O
O R
HO
O
O
O
R
HO
 ±H
R migrates 
from one 
side of C=O
to the other
O
Cl KOH
HO2C
Lactona 
366 
 
Prof. Dr. José Eduardo Damas Martins 
Mecanismo 
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367 
 
Prof. Dr. José Eduardo Damas Martins 
RCOOH
O
O
O
+ R OH
O
Cetona em 
anel de cinco 
membros 
lactona em 
anel de seis 
membros 
Mecanismo ? 
368 
 
Prof. Dr. José Eduardo Damas Martins 
m-CPBA
O
O
O
O
O
+
Majoritário Cetona em 
anel de seis 
membros 
Mecanismo ? 
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369 
 
Prof. Dr. José Eduardo Damas Martins 
m-CPBA
O
O
O
Único 
produto 
Mecanismo ? 
370 
 
Prof. Dr. José Eduardo Damas Martins 
Limitações 
Cetonas insaturadas podem 
sofrer epoxidação mais 
rapidamente do que baeyer-
Villiger 
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371 
 
Prof. Dr. José Eduardo Damas Martins 
m-CPBA
O
Mistura de produtos
The most commonly used peroxy-acid is known as m-CPBA, or meta-ChloroPeroxyBenzoic
Acid. m-CPBA is a safely crystalline solid. Here it is, reacting with cyclohexene, to give the epoxide in
95% yield.
As you will expect, the alkene attacks the peroxy-acid from the centre of the HOMO, its π orbital.
First, here is the orbital involved.
And now the curly arrow mechanism. The essence of the mechanism is electrophilic attack
by the weak, polarized O–O bond on the π orbital of the alkene, which we can represent most
simply as shown in the margin. But, in the real reaction, a proton (shown in brown in this
mechanism) has transferred from the epoxide oxygen to the carboxylic acid by-product. You can
represent this all in one step if you draw the arrows carefully. Start with the nucleophilic π bond:
send the electrons on to oxygen, breaking O–O and forming a new carbonyl bond. Use those
electrons to pick up the proton, and use the old O–H bond’s electrons to make the second new
C–O bond. Dont’ be put off by the spaghetti effect—each arrow is quite logical when you think the
mechanism through. The transition state for the reaction makes the bond-forming and -breaking
processes clearer.
504 20 . Electrophilic addition to alkenes
RO
O
O
RO
O
OH
H
Nu
Nu +
electrophilic 
oxygen
carboxylate: good 
leaving group
Peroxy-acids are prepared from the corresponding acid
anhydride and high-strength hydrogen peroxide. In
general, the stronger the parent acid, the more powerful
the oxidant (because the carboxylate is a better leaving
group): one of the most powerfully oxidizing peroxy-acids
is peroxy-trifluoroacetic acid. Hydrogen peroxide, at very
high concentrations (> 80%), is explosive and difficult to
transport.
Making peroxy-acids
F3C O
O
CF3
O
F3C O
O
OH
F3C OH
O
trifluoroacetic anhydride
H2O2
peroxy-trifluoroacetic acid trifluoroacetic acid
+
O
O
O
OH
HO
O
Cl
Cl
(= m-CPBA) +
95% yield
OOO
HR
HR
H
O
Ar R H
HR O
O
Ar
H
HOMO = 
filled π 
orbital
LUMO = empty σ* orbital
bonding interaction
epoxide
electrophilic attack by a peroxy-acid on an alkene
OO
HR
HR
H
O
Ar
O
R H
HR O
O
Ar
H
R
O
O
O
R
R H
H H
+ R
O
O
O
R
R H
H H
‡
transition state for epoxidation
Epóxido