Reacoes de reducao e oxidacao de compostos carbonílicos

Prévia do material em texto

QFL0342 Reatividade de Compostos Orgânicos (2016)
Reações de redução e oxidação de 
compostos carbonílicos
Reductive amination
O
H2, Ni
or NaBH3CN
CH NH2+ NH3
O
H2, Ni
or NaBH3CN
CH NHR+ RNH2
O
H2, Ni
or NaBH3CN
CH NR2+ R2NH
1o amine
3o amine
2o amine
Preparation of Amines—Reductive Amination
[1] Nucleophilic attack of NH3 on the carbonyl group forms an imine.
[2] Reduction of the imine forms an amine.
• The most effective reducing agent for this reaction is sodium cyanoborohydride
(NaBH3CN).
Preparation of Amines—Reductive Amination
Compare to NaBH4
Preparation of Amines—Reductive Amination
Retrosynthetic analysis
• How to prepare 2o and 3o amines? Which starting material would you use 
for it? 
Preparation of Amines—Reductive Amination
• How would you prepare methamphetamine?
Preparation of Amines—Reductive Amination
8
Redução de Wolff-Kishner
Reações de aldeídos ou cetonas com diversos 
hidretos
Redução com hidretos metálicos
• Os reagentes mais comuns usados em laboratório 
para a redução de aldeídos e cetonas são NaBH4; 
LiAlH4 NaH (fontes de íon hidreto H:-, um poderoso 
nucleófilo)
Íon hidretoHidreto de lítio
alumínio
Boro-hidreto de 
sódio
••
H
H H
H
H-B-H H-Al-HLi +Na
+
H
Reduction of carboxylic acid with LiAlH4
Reduction of aldehyde with LiAlH4
https://www.youtube.com/watch?v=odkFRsbWLF4
LiAlH4 + 4 H2O → LiOH + Al(OH)3 + 4 H2
LiAlH4 reage violentamente com água, metanol e outros solventes 
próticos. As reduções usando LiAlH4 são realizadas em éter 
dietílico ou tetra-hidrofurano (THF) anidros. 
https://www.youtube.com/watch?v=odkFRsbWLF4
Redução com LiAlH4
+
+ Sais de alumínio 
Éter dietílico
ou THF
O
OH
4 RCR LiAlH 4
4 RCHR
tetralcoxi aluminato
(R2CHO)4 Al
-
Li
+ H2 O
Uso de LiAlH4 em reações de redução
R
C
OH
O
R
C
OR
O
R
C
X
O
R
C
NH2
O
R
C
O
O
C
O
R
haletos 
de acila
ácidos
carboxílicos
ésteresanidridos amidas
R
C
R'
O
R
C
H
O
aldeídos cetonas
reduzidos por LiAlH4
reduzidos por NaBH4 não são reduzidos por NaBH4
• Reduções com NaBH4 podem ser realizadas em metanol 
aquoso, em metanol puro, ou em etanol
• Um mol de NaBH4 reduz quatro mols de aldeído e cetona
Um tetralcoxi borato
Boratos+
+
metanol
O
4 RCH NaBH 4
(RCH2O)4B
-Na+ 4 RCH 2 OH
H2O
Redução com NaBH4 
from 
water
from the hydride 
reducing agent
+
H
H O O BH3
OH
H
H
H-B-HNa
+
R-C-R' R-C-R'
Na
+
H2 O
R-C-R'
A partir da 
água
A partir do agente 
redutor
Quimiosseletividade nas reduções
O OH
RCH=CHCR' RCH=CHCHR'
1 . NaBH 4
2 . H 2 O
+
Rh
O O
RCH=CHCR' RCH 2 CH2 CR'H2
4
H2O
• Treatment of a nitrile with a milder reducing agent such as DIBAL-H followed by water
forms an aldehyde.
(i-Bu2AlH)2
DIBAL-H (hidreto de diisobutilaluminio) 
(Hidreto mais brando)
Redução de ésteres com DIBALH
• O hidreto de di-isobutilalumínio (DIBALH) a -78°C reduz 
seletivamente ésteres a aldeídos
– a -78°C, o intermediário somente é liberado após a 
hidrólise ácida.
• With DIBAL-H, nucleophilic addition of one equivalent of hydride forms an anion which is
protonated with water to generate an imine. The imine is then hydrolyzed in water to
form an aldehyde.
R
C
OH
O
R
C
OR
O
R
C
NH2
O
ácidos
carboxílicos
ésteres amidas
R
C
R'
O
R
C
H
O
aldeídos cetonas
LiBH4
NaBH4
NaCNBH3
LiAlH4
BH3
R
C
H
NH
iminas
R
C
H
O
LiAlH4
O
o
C
via
alcool
ou DIBAL
via 
cloretos
de acila
R NHR R OH R R
OH
R OH R NR2 R OH
reduz
não reduz
reduz lentamente
Equivalentes biológicos de hidretos metálicos
NADH
(hidreto biológico)
NAD+
nicotinamida adenina
dinucleotídeo
(forma oxidada)
NADH
nicotinamida adenina
dinucleotídeo reduzida
NAD+ NAD+
NAD+
Reduções quimiosseletivas por enzimas
Oxidation of Aldehydes and Ketones
• Aldehydes are readily oxidized to carboxylic acid but ketones are unreactive 
(except under the most vigorous conditions). 
• Aldehydes are more easily oxidized because they posses a hydrogen atom 
bonded to the carbonyl carbon. This hydrogen atom can be removed as a proton 
with the final result being the oxidation (loss of hydrogen) from the original 
aldehyde. Ketones have no expendable carbonyl-hydrogen bond.
Oxidation of Aldehydes and Ketones
• Many oxidizing agents will convert aldehydes to carboxylic 
acids. Some of these are Jones reagent, hot nitric acid and 
KMnO4.
• One drawback to the Jones reagent is that it is acidic. Many 
sensitive aldehydes would undergo acid - catalyzed 
decomposition before oxidation if Jones reagent was used 
CCH3(CH2)4
O
H CCH3(CH2)4
O
OH
Jones
Oxidation of Alcohols and aldehydes with 
cromic acid
Ester chromate 
aldehyde gem-diol
alcohol
Carboxylic acid
A Milder Oxidizing Agent
• For acid sensitive molecules a milder oxidizing agent such as the 
silver ion (Ag+) may be used. A dilute ammonia solution of silver 
oxide, Ag2O, (Tollens reagent) oxidizes aldehydes in high yield without 
harming carbon-carbon double bonds or other functional groups.
Oxidizing Agents in Organic Chemistry
• PCC Generally a Mild Oxidant (1° Alcohol  Aldehyde)
• Jones Reagent Harsher Oxidant (1° Alcohol  Carboxylic Acid)
• Alcohol Often Dissolved in Acetone While Jones Reagent Added
N H CrO3Cl
Pyridinium chlorochromate
(PCC)
H2CrO4
Chromic Acid
(Jones Reagent)
CrO3/H2SO4
General Oxidizing Agent Selection
MeOH 1° Alcohol 2° Alcohol 3° Alcohol
PCC H2C=O Aldehyde Ketone
No 
Reaction
Cr6+ 
H2SO4
HCO2H
Carboxylic 
Acid
Ketone
No 
Reaction
• Just as in Reductions, Oxidation Products Depend on Reagent
• Generally Don’t Oxidize 3° Alcohols (No Texas Carbons)
• PCC Good For Aldehydes From Primary Alchols
• Cr6+/H2SO4 Reagents, KMNO4 Primary  Carboxylic Acids
• Use What You Like For Most Ketones