OXIDATION OF FUNCTIONAL GROUPS IN

ORGANIC SYNTHESIS

Purposes:
• to modify the electronic property of the molecules – resulting in
chemical, physical and biological characteristics.

H H O
R C OH R C O R C OH CO 2
R C H
H H H

• Transition metal derivatives : Cr, Mn, Se, Os

• Peroxides
• Ozone
• Oxygen molecule
• Other oxidants
CHROMIUM (VI) BASED
+
O
CrO 3 + H2O H HO Cr OH (H2CrO 4)
O
Reaction mechanism

O R O
R2CHOH + HO Cr OH R C O OH + H2O
O H O
(slow)
R O
C O + Cr OH (HCrO 3)
R O
 R2CH-OH + H2CrO4 R2C=O + HCrO3+ + H2O

R2CH-OH + H2CrO3 + 3 H+ R2C=O + Cr3+ + H2O

R2CH-OH + HCrO3 + 3 H+ R2C=O + HCrO3+ + 3 H2O

Variations in Cr Reagents

CrO3 + PYRIDINE = JONES REAGENT

CrO2Cl2 + PYRIDINE = COLLIN'S REAGENT

EXAMPLES:

H2CrO 4
CH 3CH 2CH 2OH CH 3CH 2CH=O
H2O

OH O
H2CrO 4
acetone

OH O
CrO3
C6H5C-CH 2CH 2CH 3 C H C-CH 2CH 2CH 3
CH 3COOH, H 2O 6 5
CH(CH 3)2
CH(CH 3)2
OH
O
H2CrO 4
ether

CH 3
CH 3

OH O
H2CrO 4
acetone

CrO 3-pyridine
OH O
CH 2Cl 2
 OH O
CH3
CrO3-pyridine
CH2Cl2

CH 3 CH 3
CH 3 CH 3

CrO3-pyridine
CH 3 CH 3
CH2Cl2
CH 3 OH CH 3 CH 3 O CH 3

CrO3-pyridine
CH 3(CH 2)8CH 2-OH CH 3(CH 2)8CH=O
CH2Cl2
CrO3-pyridine CH 3(CH 2)4CH=CHCH=O
CH 3(CH 2)4CH=CHCH 2-OH
CH2Cl2
 OH O

CrO3-pyridine
CH2Cl2

CrO3-pyridine
CH 2-OH CH2Cl2 CH=O

CrO3-pyridine
HO-CH 2CH=CHCH 2O CH2Cl2 O=HC-CH=CHCH 2O
MANGANESE (IV) AND MANGANESE (VII)

MANGANESE (IV) = MnO: MORE USEFUL, MORE SELECTIVE

MANGANESE (VII) = KMnO4

CH 3-CH-CO 2C2H5 KMnO4, CH 3-C-CO 2C2H5

NaH 2PO4,
OH O
MgSO4, H2O,
pet. ether
CH 2OH CH=O
MnO 2

MnO 2
C6H5CH=CHCH 2OH C6H5CH=CHCH=O

MnO 2
CH 2OH CH=O

OH O OO
MnO 2
CH 3CH 2CH-C-CH 2CH 3 CH 3CH 2C-C-CH 2CH 3
OH O
MnO 2
HC=C-C=CH-CH=CH-CH HC=C-C=CH-CH=CH-CCH 3

CH 3 CH 3 CH 3
 OH O
CHCH 2CH 2CH 2OH MnO 2
C-CH 2CH 2CH 2OH

HO
O
MnO 2
O
O
O
O
DIALKYLCARBODIIMIDE - DMSO
:O: H+
CH 3-S-CH 3 + R-N=C=N-R R-N=C-NH-R
O
(H 3C) 2S
R H O
R-N=C-NH-R + H-O-CH 2-R' O
O N-R R'
S CH 3 + R-NH-C-NH-R
O H3C S H H
(H 3C) 2S C H2C
R'CH 2O H2

R'-CH=O + CH 3-SCH 3
DMSO-SO3

H3C O H3C O
S O + S S O S O-
O O
H3C H3C O

H3C O H
-
R2CH-OH + S O S O: R O S CH 3 + SO 4
pyridine
H3C O R CH 3

R
C O + CH 3-SCH 3 + H+
R
DMSO-Ac2O

H3C O H3C O
S O + H3CC OCOCH 3 S O C CH 3 + CH3CO2
H3C (Ac 2O) H3C

H3C O H
R2CH-OH + S O C CH 3 R O S CH 3 + CH3COOH
H3C pyridine R CH 3

R
+
C O + CH 3-SCH 3 + H
R
N-CHLOROSUCCINIMIDE-MIMETHYL SULFIDE

O
H3C
N Cl + CH3-S-CH3 S Cl
H3C
O
(NCS)
H3C H
R2CH-OH + S Cl R O S CH 3 + HCl
H3C pyridine
R CH 3
O
R
C O + CH 3-SCH 3 + N H
R
O
EXAMPLES:

H3C H3C
CH 3 CH 3
CH 2OH CH=O
CH 3 DMSO, CH 3
dicyclohexyl-
carbodiimide

CH 3 CH 3
CH 3 CH 3
DMSO,
SO3
OH CH 3 OH CH 3
OH O

CH 3 DMSO, CH 3
N C-CH 2OH Ac2O N C-CH=O
CH 3 CH 3

CH 3(CH 2)6CH 2-OH DMSO, CH 3(CH 2)6CH=O

NCS
OXIDATION OF DOUBLE BONDS
R R' OH OH R R'
R O R'
R R' O O
R R' R R' R R' R R'

R R'
O O
PERACIDS OR PEROXYACIDS R R'

O O O O O O
H H R H R R
alkyl peroxide dialkyl peroxide
(H 2O2)
(R = ALKYL; ACYL)
O O O
R C OOH H3C C OOH C6H5 C OOH
peroxyacid peroxyacetic acid perbenzoic acid
(peracetic acid)
MECHANISM O HO
H C R'' C R''
O O O
R R'
C C R O R'
R R'
R R'
REACTIVITY OF ALKNES

CH 2=CH2 < CH3-CH=CH 2 < CH3-CH=CH-CH 3

REACTIVITY OF PERACIDS
O O O O
CF 3COOH CHF 2COOH CH 2FCOOH CH 3COOH

O O
COOH COOH

Cl
m-chloroperbenzoic acid perbenzoic acid
(m-MCPBA)
NUCLEOPHILICITY

H2O2 + OH- H2O + HOO-

O O
O OH O
- H H O R'
HOO + R-CH=CH-C-R' RCH C C R' C C
R H

R-C N + H2O2

NH NH
O
R COOH + + R COOH
EXAMPLES:

O H
m-MCPBA + H
H
96%H 4% O
O H3C
CH 2 H3C O
H3C + 3C
H
H3C m-MCPBA H3C
H3C H3C
H3C
OH 69% 31%
OH H
m-MCPBA O
H
 CH=CH 2 O
C6H5CO 3H

H O
C6H5CO 3H H
H
H
H3C O CO 2CH 3
CH 3CH=CHCO 2CH 3 CF 3CO 3H
H H
CH 3 CH 3
m-CPBA
CH2Cl2 O
CH 3 CH 3
O O

H2O2, OH-
O
CH 3 CH 3
O NO 2
C6H5 NO 2 -C6H5
H2O2, OH
H CH 3
H CH 3
NATURES OF REACTIONS

H
O O OH OH2 OH OH
H+ H2O - H+

O OH- O OH OH OH
H2O
+ OH-

HYDROLYSIS
OH
H2O2,
HCO 2H
OH

H2O2, OH
HCO 2H

CH 3 CH 3
1) H2O2, HCO 2H

CO 2H 2) NaOH
CO 2H
OH
OH
 O OH
H H H2SO4 H3CHC CHCH 3
H3C CH 3 CH 3OH OCH 3

H C6H5 OH C6H5
O C6H5 HBr H
H C6H5
H Br
O OH Cl
H C6H5 HCl
C6H6 H C6H5
C6H5 H C6H5 H
O OH
HClO4 CH 2OH
H2O
N O N O
NUCLEOPHILIC REAGENTS

O OCH 3
H3C H + CH O- (H 3C) 2C CHCH 3
3
H3C CH 3 OH
C2H5
O
H3C H + HN (H 3C) 2C CH N
H3C C2H5 OH

O OH
CHCH 2N(CH 3)2 + HS- HSCH 2CHCH 2(CH 3)2

O N3
H3CHC CHCH 3 + NaN3 H3CHC CHCH 3
OH
RING OPENNING HYDRIDE TRANSFER AND ORGANOMTALLIC REAGENTS
H3C H3C OH
O
LiAlH 4

LiAlH 4 OH
O
CH 3

O
CH 3CH 2CH 2-C CH 2 LiBH(C 2H5)3 CH 3CH 2CH 2C(CH 3)2
CH 3 OH

H
H3C H3C
LiAlH4 H3C
H3C O AlCl3 OH
H3C H3C
H H
 S S
H3C Li H3C
CHCH 2CH 2 CHCH 2CH 2
H3C O H3C O
H3C O H3C OH
S
H2C
O OH S
(CH 3)2CuLi
CH 3CHCH 2CH 3
H3C
O OH
(CH 3)2CuLi
CH 3CH-CH-COC 2H5
H3C CO 2C2H5
OH
O
DMF O
BrH2CH 2C + Na+ -CH(CO2C2H5)2
CH-CH 2CH 2-CH(CO 2C2H5)2

NaOCH 3, CH3OH

HO
CO 2C2H5
CO 2C2H5
 REACTIONS WITH STRONG BASES

O
H R-CH=CHCH 2OH
R-CH
OH
O LDA
CH 3CH 2CH 2CH CHCH 2CH 2CH 3 CH 3CH 2CH 2CH-CH=CHCH 2CH 3

O CH 2
LDA OH

O LDA OH
CHCH 2CH 3 CHCH 2CH 3

OH OH
O CH 3
KOt-Bu CH2=CH-C(CH3)2 + CH3-CH-C=CH2
H3CHC
CH 3 DMSO CH 3
REARRANGEMENT:
H O O
+
H3C O CH 3 H
H3C C CH 3 H3C C C(CH 3)
H3C CH 3
CH 3 CH 3
Cl
ZnCl 2 O
O
Cl
O
OC-CH 3 O
ZnCl 2
O O
OC-CH 3
ALKENES TO GLYCOL
H H
R H O O-
R H2O, R OH
+ MnO4- Mn
R O O OH- R OH
R H
H H

H H
R H O O
R R OH
+ OsO4- Os
R O O R OH
R H
H H
H H KMnO4, OH OH
NaOH, H 2O H H
CH 3(CH 2)7CH 2 CH 2(CH 2)6COOH CH 3(CH 2)7CH 2 CH 2(CH 2)6COOH

KMnO4, OH
NaOH, OH
H2O,
t-BuOH
 KMnO4, OH
NaOH, OH
H2O,
t-BuOH
OH
CH 3
OsO4, CH 3
pyridine, OH
CH 3 acetone CH 3
O O OH
OsO4

OH
OAc OAc
OsO4 HSO3- HO

CO 2CH 3 HO CO 2CH 3
OAc OAc
CLEAVAGE OF DOUBLE BONDS

H H
R H
IO 4- R O O-
R OH
+ MnO4- R'
I
R OH O O
R H H
H

R-CH=O + R'-CH=O
 PERIODATE (ION)
IO4-
(periodate ion)

KMnO4, KIO4, H2O

CH 3(CH 2)7CH=CH(CH 2)7COOH CH 3(CH 2)7COOH + HOOC-(CH 2)7-COOH
K2CO 3, H2O H+
CH 3 O O
OH KIO 4
CH 3-C-(CH 2)3-C-CH 3
CH 3
OH

OsO4 O=CH(CH2)4CH=O
NaIO4
COOH
H2CrO 4
COOH
 R'
R' O
+ R'-CO2R'
OZONOLYSIS R O
R' R' R
O dioxetane
R' R' R' O
R'
+ O3 O O O R O
R
R R R
R

R'
R' O R dissociation R' O
O O O
R O
R' R
R
recombi- R-CH=O 1,2,3-troxolane
nation
R' O R R' O R''
R' R R' H
O O O O
final ozonide 1,3,4-troxolane
INVOLVEMENT OF ALDEHYDE/KETONE

O3 CH=O 18 O18
H H
C C CH CH
O O

O O O
O O
CH3 + H3C CH
+ O3
CH 3
O

O O O O
O O O
+
O
CH 3
CH 3
QUENCHING OF INTERMEDIATES

O O O
O3 C6H5-CH + C6H5-CH=O + CH 2 + CH2=O
C6H5-CH=CH2 CH 3OH
27% 26%

O OH O OH
C6H5 CH CH 2
OCH 3 OCH 3
31% 23%

O3
R-CH=CH-R CH 3OH R-CH-OCH3 + R-CH=O

O OH
(CH 3)2S

R-CH=O
 1) O3 R-CH2OH + R'-CH2OH
R-CH=CH-R' 2) NaBH4

C(CH 3)2 O
CH 3 CH 3
O3 (CH3)S
CH 3CO 2CH 3 CH 3CO 2CH 3
H3C H3C CH 3
CH 3
O3 Na 2SO3

H3C CH=CH 2 H3C CH=O

CH 2CH=CHCH 2Cl CH 2CH=O

O3 NaI
NO 2 NO 2
 CH 3 CH=O
O3 (C 6H5)3P

H3C H3C CH=O

O O
O3, H2O2 COOH
O HCO 2H O
COOH
O O
O O
O3 HCO 2H,
C6H5-P-(CH 2CH=CH 2)2
H2O2
OXIDATION WITH SINGLET OXYGEN

CH 3 CH 3 CH 3
CH 3
hv (fluorescence lamp) LiAlH 4 +
O2, hematoporphine
OH OH
-700 C CH 2 CH 3 CH 2
CH 3
CH 3 CH 2 CH 3
HO HO
hv (fluorescence lamp) LiAlH 4 +
O2, hematoporphine
-700 C H H

C6H5 C6H5
hv, O2 H2C COC 6H5
+
O2, methylene blue OOH H2C COC 6H5
C6H5 -700 C C6H5
oxidative cleavage through functional groups other than double bonds
H H
R OH Pb(OAc)4 R O OAc
Pb + 2 HOAc
R' OH R' O OAc
H H

R-CH=O + R'-CH=O + Pb(OAc)2

KIO 4, CH 3(CH 2)7-CH=O + O=HC-(CH 2)7COOH

CH 3(CH 2)7CH CH(CH 2)7COOH
H2SO4
OH OH H2O
KIO 4, 2 CH3COOH
CH 3-CO-COCH 3
HOAc, H2O
COOH
CH 3 CH 3 CH=O
OH
CH 3 CH 3
NaIO4,
HO HOAc
HO
acetone, H 2O
H H H H
 CO 2C2H5
OH Pb(OAc)4
2 O=HC-CO2C2H5
C6H6
OH
CO 2C2H5

CH 2=CH(CH 2)8-CHCH 2-OH Pb(OAc)4

CH 2=CH(CH 2)8-CH=O + CH 2=O
C6H6
OH

OH
H Pb(OAc)4 O=HC-(CH 2)3-CH=O
OH HOAc
H
OH O
Pb(OAc)4

O O
OH O
OXIDATIVE DECARBOXYLATION
COOH
CHCl3
hv, Pb(OAc)4

R-CH 2-CH 2-COO-Pb(OAc) 3 R-CH 2-CH 2 + CO2 + Pb(OAc)3

- e- (Cu2+)
H
RCH CH 2 R-CH=CH 2

AcO-

R-CH 2-CH 2OAc

R-COOH + Pb(OAc) 4 R-COOPb(OAc)3 + HOAc
R-COOPb(OAc) 3 R + CO2 + Pb(OAc)3

ligand
Pb(OAc)4-n + (n X) PbXn(OAc)4-n + n OAc-
exchange
R + PbXn(OAc)4-n R-X + PbXn-1(OAc)4-n

PbO2, Br2
R-COOH R-Br
 O

O Pb(OAc) 4 O
O

O O

O O O
O H
H
R O-H
R + HOAc
O R O Pb(OAc) 3
R
H
H O O

R CH
+ 2 CO2 + Pb(OAc)2 + HOAc
R CH
 OH O-H
R CH C OH + Pb(OAc)4 R CH C O Pb(OAc) 3
O O

R-CH=O + 2 CO2 + Pb(OAc)2 + HOAc

HYDROGEN PEROXIDE
O O- O O
R C COOH + H2O2 + HO- R C C-O - R C-OH + CO2 + HO-
O-OH
ALDEHYDES AND KETONES
O
COOH CH=O
Cr(VI) COOH + CH=O
or
Mn(VIII)
O O-CrO 3H O O
OH O
+ H2O H2CrO 4

H2CrO 4
COOH
COOH
 OAc
O OH O Pb OAc

R-CH 2-C-R' R-CH=C-R'

Pb(OAc) 4
H3C C O O

R R

OH O H2O OAc O
R CH C-R R CH C-R
O OLi O
OH
LDA MnO2, pyridine
(base) HMPA

O-H
H2CrO 4
R-CH=O R C O CrO 3H R-COOH + HCrO3- + H+
H
CH=O COOH
1) Ag2O, NaOH
HO 2) HCl HO
OCH 3 OCH 3
BAEYER-VILLIGER REACTION
O O O- O
R C R' + R'' C OOH R C R' R C O-R' + R''-COH
O O-COR''

FOR ASYMMETRICAL KETONES:

MIGRATORY APTITUDE: TERT-ALKYL > SEC-ALKYL > BENZYL,

PHENYL > PRIMARY ALKYL > CYCLOPROPYL > METHYL.

O- O O
R C R' R C O-R' or RO C R'
O O-COR''
EXAMPLES:
O
O H2SO5
O

O CH 3CO 3H O

CF 3CO 3H O
COCH 3 OCOCH 3

O CO 3H O
(CH 3)CHCH 2-C-CH 3 CO 2H (CH 3)CHCH 2O-C-CH 3
CH2Cl 2
O O
O CF 3CO 3H,
CH 3CO 2C2H5

O O
C C6H5 CF 3CO 3H, C OC6H5
NaHPO 4,
CH 2Cl 2
SELENIUM DIOXIDE
O
O R O H
R C CH 2R' + HO-Se-OH C CH-R' R C C R'
O O O SeOH
Se
OH
O O
O O R C C R'
SeO2

COCH 3 CO-CH=O
SeO2

BROMOFORM
O O
Br2, NaOH + CHBr3
C6H5 C CH 3 C6H5 C OH
ALLYLIC OXIDATION
O
CrO3-pyr
or

CH 3 CH 3

CrO3-pyr

CH 3 CH 3 CH 3 CH 3

O
 SELENIUM DIOXIDE

H
SeO2 H
R-CH2CH=CH-R' R-CH C CHR' R-CH=CH-CHR'
Se O
OSeOH
OH H2O
R C C R'
R-CH=CH-CHR'
H H
OH
H2O
R-CH-CH=CHR'
OH
 SeO2 OH

CH 3 CH 3 CH 3 CH 3
O OH OH
SeO2 + +

CH 3 CH 3 CH 3 CH 3

H3C CH 2CH 3 H3C CH 2CH 3

C C SeO 2 C C
H3C H O=HC H

PHENYLSELENIUM BROMIDE

1) PhSeBr
CH 3CH 2CH 2CH=CHCH 2CH 2CH 3 CH 3CH 2CH 2CH=CHCHCH 2CH 3
2) CH3CO2H OH
3) H2O2
REACTIONS ON NON-FUNCTIONALIZED CARBONS
CH 2-R CH-R CH-R
Cr( IV)
or Mn(VIII)

COOH CH-R

CH 3 COOH
KMnO4

Cl Cl
CH 2CH 2CH 3 COOH
KMnO4

CH 3 COOH
Na 2Cr 2O7
CH 3 COOH
 KMnO4

N CH 3 N COOH

KMnO4 H+
H HO

LEAD TETRACETATE

RCH2(CH 2)2CH 2OH + Pb(OAc)4 RCH2(CH 2)2CH 2O Pb(OAc) 3

(AcO)3Pb O HO O
CH 2 Pb(OAc)4 CH 2 H CH 2
H H CH 2
R C CH 2 R C CH 2 R CH
C C C
H2 H2 H2

+ H+
O
R