Download Chapter 9 Oxidation

Chapter 9 Oxidation
The opposite of reduction
Dehydrogenation
Substitution of hydrogen by a functional group
One-electron abstraction from a nucleophilic centre
Additon of oxygen-containing reagents to multiple bonds
and heteroatoms
1
2
a)
Catalytic dehydrogenation
b) Dehydrogenation by successive hydride and proton transfers
c)
Dehydrogenation by substitution-elimination and additionelimination process
3
Three general categories
 Transition metal oxidants (Cr, Mn, Ti, Hg etc.)
Cr (VI) ---> Cr(III)
Mn (+7) ---> Mn (+2)
i.e. 2 CrO3 + 3 R2CHOH + 6 H+ ---> 3 R2C=O + 2 Cr+3 + 6 H2O
2 MnO4- + 5 R2CHOH + 6 H+ ---> 5 R2C=O + 2 Mn+2 + 8 H2O
Note: in each case, acid is consumed and H2O produced.
 Oxygenators (O2, O3, RCO2OH)
 Others (DMSO, Pb(OAc)4, NCS, Al(O-iPr)3 etc.)
4
 Transition metal oxidants : Cr (Oxidation of alcohols)
 CrO3 (Chromium trioxide)
 dissolves in H2O
 Chromate ion (sodium chromate) dimerizes:
5
Mechanism of 2o Alcohol Oxidation
Note!
• First forming a
chromate ester
• Then E2 elimination
Cr(+4) + Cr(+6) ----> 2 Cr(+5)
Cr(+5) + R2CHOH ----> R2C=O + Cr(+3) + 2 H+
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Jones’ reagent
• Aqueous solution of chrominium (VI) oxide and sulfuric acid.
• Alcohols containing double or triple bonds may be selective
oxidized.
• Usage:
– Add reagent to ice cold solution of ROH in acetone.
– Watch color change: Orange-red ----> green.
– Destroy excess reagent with i-PrOH. (----> acetone)
JonesÊÔ¼Á
O
HO
H3C
H
C
C
OH O
CH3
JonesÊÔ
¼Á
H3C
CH3
C
C
O
7¼×
O£¨ ²» Ñõ»¯ÜÐ
»ù£©
Chrominium(VI) oxide in pyridine
(Collins reagent and Sarett reagent)
O
O
Cr
O
O
O
+HCl
O
Cr
OH
N
Cl
O
Cr
OH
N
Cl
• CrO3 is added to pyridine, not reverse.
• Used as solution in CH2Cl2; Milder Oxidant.
• Be used for oxidations of alcohols having acid sensitive group.
•
Good for Primary ROH ----> aldehydes.
• Also good for allylic alcohols and benzylic alcohols.
8
C C CH2OH CrO3/Py
H H
HO
CH2OH
C
H
HO
C
H
CHO
CHO
CrO3/Py
9
PCC (pyridinium chlorochromate, CrO3ClH-pyridine)
PDC (pyridinium dichromate, [(C5H5NH+)2Cr2O72-])
Good for Primary ROH ----> aldehydes.
Also good for allylic alcohols and benzylic alcohols.
10
Transition metal oxidants : Cr (Oxidation of C-H Bonds)
Occurs with Cr(VI) under more forcing conditions
11
Etard reagent (chromyl chloride, CrO2Cl2, in an inert
solvent (CCl4, CS2))
CrO3+HCl
Cl
O
H2SO4
£¼10¡æ
O
Cr
bp117¡æ
Cl
• Controlled benzylic oxidation to aldehyde.
CH3
CHO
Etard
CH3
CH3
CHO
CH3
+2CrO2Cl2
R
R=H
90%
2-CH3
65%
CS2
2-NO2
50%
R
3-CH3
70%
(Á¢Ìå ЧӦʹÁÚ
λ ÊÕ
ÂÊµÍ )
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Transition metal oxidants: Manganese
KMnO4 - Potassium permanganate - less selective - tends toward
over-oxidation
MnO2 - Manganese dioxide - more selective
H+
MnO4-+8H++5e
Mn2++4H2O
OH-
MnO4-+2H2O+3e
MnO2¡ý+4OH-(KOH)
Reactivity of KMnO4 : acidic > basic > neutral
Heating makes stronger reactivity
Freshly prepared MnO2, used in the benzylic and allylic alcohols
13
OCH3
OCH3
H2
C C CH2
H
KMnO4/H2O
NaHCO3
H3CO
H H
C C
KMnO4Crown ether
PhH
CH2OH
active MnO2
CH2COOH
H3CO
2
COOH
(100%)
CHO
CH2Cl2 r.t
CH2OH
HO
CH2OH
OH
HO
OH
active MnO2
HO
O
14
H
C
N KMnO4
OH
without H at ¦Á-position
H2 OHH2
OH
R C C C R' KMnO
4
H
Having H at ¦Á-position
OH
CH CH3
CH CH3
OH
C
N
O
OHH
2
R C C C R'
H
O
KMnO4
C
Mg(NO3)2
C
CH3
66%
CH3
O
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OsO4 osmium tetroxide:
reacts similar to KMnO4, but: more specific (milder), more
expensive, more toxic.
Syn-addition
R
H
H
:O
C
+
C
R
:O
O
Py
Os
R
C
R
H
R C OH
R C OH
H
O
Os
O
H
Ph
C
Py
+
O
O
Py
O
H
O
HO
Os
HO
O
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CH3
CH3
HO
CH3
OsO4/Py
Et2O
OH
Á½¸öOHÔÚλ×èСµÄµØ·½Éú³É
OH
CH3
OsO4/Py
Et2O
HO
OH OH
OsO4/Py
Et2O
OH
OH
17
Sharpless dihydroxylation
18
Mechanism:
19
Mechanism:
From: M. H. Junttila, O. E. O. Hormi, J. Org. Chem., 2004, 69, 4816-4820.
20
Example:
M. H. Junttila, O. E. O. Hormi, J. Org. Chem., 2004, 69, 4816-4820.
L. C. Branco, C. A. M. Afonso, J. Org. Chem., 2004, 69, 4381-4389
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Sharpless epoxidation (transition metal Ti)
Putative transtition state
22
Oxygenators (O2, O3, RCO2OH)
RCOOH + H2O2
RCOOOH + H2O
Common Peracids:
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Properties:
• PKa Peracids are weaker acids than corresponding
carboxylic acids
formic acid
3.6
performic
7.1
acetic acid
4.8
peracetic
8.2
• Hence do not react with inorganic buffers.
more volatile (lower bp)
dissolve in nonpolar organic solvents
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Peracids for epoxidation of C=C Double Bonds
Mechanism - Electrophilic attack
CH3
CH3
RCO3 H
O
CH3
CH3
CH3CO3H
O
H3C CH2
CH2 7 COOH
7
C
C
PhCOOOH
R
R
C
H
C
O
H25
Ph
H2C
C
H
C
H
CH2
Ph
H
C
O
CF3CO3H
COOEt
H2C
H
C
CH2
COOEt
O
Payne oxidation
Mechanism:
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Baeyer-Villager Reaction
(Peracids for oxidation of Carbonyl compounds)
O
O
Mechanism:
R
C
R
R' + R''COOOH
C
O
R'
O
O C
O
-R''COO
R
C
R'
R'
R''
O
C
OR
O
O
R
C
OR'
Migratory Aptitudes:
t-alkyl > cyclohexyl - sec-alkyl > benzyl - phenyl > primary alkyl > cyclopropyl > methyl
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O
C
CF3CO3H
C
O2N
O
O
NO2
RCO3H
O
O
O
O
H3CO
COCH3
CH3CO3H
H3CO
OCCH3
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Oxygenators (O2, O3, RCO2OH)
•Ozone typically generated by electric discharge on 3 O2 to give
about 3-5% O3 / O2 mixture.
•Ozone has pungent smell, blue color, very corrosive
(used to purify H2O)
•The mechanism has been subject of much discussion
Mechanism:
Typical Reduction Conditions: Me2S, Ph3P, Zn/HOAc, H2, Pd/C
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HC C CH3
H
CHO
¢ÙO3
OCH3
OCH3
+ CH3CHO
¢ÚH2O
OCH3
OCH3
¢ÙO3
CHO
¢ÚZn/HOAc
H3C
C
C
CH3
O3
CH3COCCH3
CH2CH2CHO
H2O
2CH3COOH
O O
acid anhydride
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 Others (DMSO, Pb(OAc)4, NCS, Al(O-iPr)3 etc.)
Dimethylsulfoxide (DMSO), in conjunction with a variety of other
electrophiles (e.g., DCC, Ac2O, TFA, SO3) can act as an oxygen transfer agent.
i.e, Pfitzner-Moffat Oxidation:
Good mild oxidant: Primary ROH ----> aldehydes and Allylic ROH ----> enones
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HO
COCH3
COCH3
DMSO
H3C
DCC
¦Á
¦Â
O
O
¦Á:99% ¦Â:6.5%
CH3
CH3
DMSO-Ac2O
47%
r.t
OH
CH3 OH
CH3 O
O
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 Others (DMSO, Pb(OAc)4, NCS, Al(O-iPr)3 etc.)
Oppenauer oxidation
R
O
H
C
Al(O-iPr) 3
R ' + CH3CCH3
R
R' +
C
H3C
O
O
CH3
OH
O
HO
H
C
O
CH3CCH3
Al(O-ipr)3
60%
O
O
HO
Al(O-ipr)3
H
C
83%
Ȯ
Ìå ͪ
H
C
CH2
HO
CH2
O
CH
H3CO
N
Ph2CO
N
¿üÄþ
H3CO
C
N
Al(O-ipr) 3
N
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