Reações de redução e oxidação de compostos carbonílicos

QFL0342 Reatividade de Compostos Orgânicos (2016)
Reações de redução e oxidação de
compostos carbonílicos
Reductive amination
O + NH3
O + RNH2
O + R2NH
H2, Ni
or NaBH3CN
H2, Ni
CH NH2
1o amine
CH NHR
2o amine
CH NR2
3o amine
or NaBH3CN
H2, Ni
or NaBH3CN
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.
Preparation of Amines—Reductive Amination
• The most effective reducing agent for this reaction is sodium cyanoborohydride
(NaBH3CN).
Compare to NaBH4
Preparation of Amines—Reductive Amination
Retrosynthetic analysis
Preparation of Amines—Reductive Amination
• 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?
Redução de Wolff-Kishner
8
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)
H
H-B-H
Li + H-Al-H
H
Boro-hidreto de
sódio
H
Hidreto de lítio
alumínio
Na
H
••
+
H
Íon hidreto
Reduction of aldehyde with LiAlH4
https://www.youtube.com/watch?v=odkFRsbWLF4
Reduction of carboxylic acid with LiAlH4
LiAlH4 reage violentamente com água, metanol e outros solventes
próticos. As reduções usando LiAlH4 são realizadas em éter
dietílico ou tetra-hidrofurano (THF) anidros.
LiAlH4 + 4 H2O → LiOH + Al(OH)3 + 4 H2
https://www.youtube.com/watch?v=odkFRsbWLF4
Redução com LiAlH4
O
Éter dietílico
4 RCR + LiAlH 4
ou THF
-
+
(R 2 CHO) 4 Al Li
tetralcoxi aluminato
H2 O
OH
4 RCHR + Sais de alumínio
Uso de LiAlH4 em reações de redução
reduzidos por NaBH4
R
O
O
O
O
C
C
C
C
X
haletos
de acila
R
O
R
anidridos
R
não são reduzidos por NaBH4
O
H
aldeídos
R
C
O
O
R'
cetonas
reduzidos por LiAlH4
R
C
OR
ésteres
R
C
O
NH2
amidas
R
C
OH
ácidos
carboxílicos
• 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
O
4 RCH + NaBH 4
metanol
+ H 2O
O)
B
Na
(RCH2 4
Um tetralcoxi borato
4 RCH 2 OH + Boratos
Redução com NaBH4
H
+
O
Na H-B-H + R-C-R'
H
O BH 3 Na
+
R-C-R'
H
from
hydride
A partirthe
do agente
redutor
reducing
agent
H2 O
OH
R-C-R'
H
Afrom
partir da
água
water
Quimiosseletividade nas reduções
O
RCH=CHCR'
1 . NaBH 4 4
2 . HH2O2 O
O
RCH=CHCR'
+
H2
Rh
OH
RCH=CHCHR'
O
RCH 2 CH 2 CR'
DIBAL-H (hidreto de diisobutilaluminio)
(Hidreto mais brando)
(i-Bu2AlH)2
• Treatment of a nitrile with a milder reducing agent such as DIBAL-H followed by water
forms an aldehyde.
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.
O
reduz
C
R
H
reduz lentamente
via
alcool
ou DIBAL
não reduz
R
C
H
iminas
O
O
NH
R
C
H
aldeídos
R
C
LiAlH4
o
O C
O
O
R'
cetonas
R
C
via
cloretos
de acila
OR
R
C
O
NH2
ésteres
amidas
R
R
R
C
OH
ácidos
carboxílicos
NaCNBH3
NaBH4
LiBH4
LiAlH4
BH3
OH
R
NHR
R
OH
R
R
OH
NR2
R
OH
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.
O
O
CH3(CH2)4
C
H
Jones
CH3(CH2)4
C
OH
• 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
Oxidation of Alcohols and aldehydes with
cromic acid
alcohol
aldehyde
Ester chromate
gem-diol
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
CrO3/H2SO4
N
H
CrO3Cl
H2CrO4
Pyridinium chlorochromate
(PCC)
Chromic Acid
(Jones Reagent)
• 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
General Oxidizing Agent Selection
• Just as in Reductions, Oxidation Products Depend on Reagent
• Generally Don’t Oxidize 3° Alcohols (No Texas Carbons)
MeOH
1° Alcohol
2° Alcohol
3° Alcohol
PCC
H2C=O
Aldehyde
Ketone
No
Reaction
Cr6+
H2SO4
HCO2H
Carboxylic
Acid
Ketone
No
Reaction
• PCC Good For Aldehydes From Primary Alchols
• Cr6+/H2SO4 Reagents, KMNO4 Primary  Carboxylic Acids
• Use What You Like For Most Ketones