1. Chapter 9 Oxidation Reactions
Organic Chemistry of Fine Chemicals
Spring 2006
Chapter 9 Oxidation Reactions
general types of oxidation
dehydrogenation:  184 top
catalytic, hydride transfer, elimination:  184 (9.1~9.5)
substitution of H by Y group:  185 top (9.6 & 9.7)
one-electron abstraction:  185 middle (9.8)
addition of oxygen atoms:  185 bottom (9.9 & 9.10)
OCFC-Chap 9
Chapter 9

2. Oxidation of Hydrocarbons (I)
Organic Chemistry of Fine Chemicals
Spring 2006
Oxidation of Hydrocarbons (I)
alkanes: less selective & unreactive,  186 top
Barton reaction: mechanism;  186 middle
intramolecular reactions:  186 bottom & 187 top
low yield in acylic systems:  187 bottom
allylic oxidation: stabilized radical / cation
alcohols: Pb(OAc)4, SeO2, R-O-O-R’;  188 top
mechanisms:  188 middle
ketones: CrO3 (not KMnO4),  188 bottom & 189 top
OCFC-Chap 9
Chapter 9

3. Oxidation of Hydrocarbons (II)
Organic Chemistry of Fine Chemicals
Spring 2006
Oxidation of Hydrocarbons (II)
benzylic oxidation: stabilized radical / cation
oxidation of aromatics: CrO3 & KMnO4;  189 bottom
milder oxidation: no acids but ketones,  190 top
oxidation of naphthalenes: CrO3 & KMnO4;  190 middle
controlled oxidation: alcohols / aldehydes
free-radical halogenation:  190 bottom & 191 top
Étard reaction: CrO2Cl2 / CrO2(OAc)2,  191 middle
OCFC-Chap 9
Chapter 9

4. Oxidation of Hydrocarbons (III)
Organic Chemistry of Fine Chemicals
Spring 2006
Oxidation of Hydrocarbons (III)
other benzylic oxidations: (continued)
alcohols:Pb(OAc)4;  191 bottom
auto(o)xidation: O2,  11 top
condensation with nitrosoarene:  192 top
nitrosation:  192 middle
2-methylpyridine: 2-pyridinemethanol:  192 bot
OCFC-Chap 9
Chapter 9

5. Organic Chemistry of Fine Chemicals
Spring 2006
Dehydrogenation
catalytic dehydrogenation: aromaticity
Pd/C with no H2:  193 middle
hydride transfer / elimination
hydride acceptor: chloranil / DDQ,  194
substitution or addition / elimination
alkenes:  195 middle  alkynes:  195 bottom
OCFC-Chap 9
Chapter 9

6. Oxidative Addition of Alkenes (I)
Organic Chemistry of Fine Chemicals
Spring 2006
Oxidative Addition of Alkenes (I)
epoxidation (oxirane): per(oxy)acids or peroxides
isolated alkenes: concerted (retention),  196 top & bottom
RCO3H, RCO2H / H2O2 (SPB, SPC), mCPBA, dioxirane
a,b-unsaturated alkenes: basic H2O2;  197 top (9.17)
slow reaction with mCPBA & step-wise mechanism
OCFC-Chap 9
Chapter 9

7. Stable Peroxides SPC SPB (sodium percarbonate) (sodium perborate)
dimethyldioxirane
mCPBA
(m-chloroperbenzoic acid)
OCFC-Chap 9

8. Oxidative Addition of Alkenes (II)
Organic Chemistry of Fine Chemicals
Spring 2006
Oxidative Addition of Alkenes (II)
dihydroxylation: 1,2-diols
hydrolysis of epoxides: trans-diols,  197 middle & bottom
cis-diols: KMnO4 & OsO4,  198 top & bottom
Prévost reaction: trans-diols,  199 top (9.20a)
Woodward modification: cis-diols with H2O,  199 top (9.20b)
opposite selectivities:  200 top
CAN [Ce(NH4)2(NO3)6]: one-electron oxidation;  200 bot
OCFC-Chap 9
Chapter 9

9. Oxidative Cleavage of Alkenes
Organic Chemistry of Fine Chemicals
Spring 2006
Oxidative Cleavage of Alkenes
ozonolysis: 1,3-dipolar cycloaddition,  201 top
mechanism: formation of the primary / secondary ozonides
reductive work-up: aldehydes (ketones): Zn in AcOH, Me2S, R3P
alcohol: metal hydrides; LAH, NaBH4,  201 middle
oxidative work-up: carboxylic acids; RCO3H, H2O2 ,  201 bot
cleavage of syn diols after dihydroxylation of olefins
Pb(OAc)4, NaIO4: aldehydes (ketones);  210 bot – 211 top
KMnO4: dicarboxylic acids
OCFC-Chap 9
Chapter 9

10. Organic Chemistry of Fine Chemicals
Spring 2006
Oxidation of Alkynes
oxidative addition: less useful
1,2-diketones:  202 top
oxidative coupling:  51 bot & 52 top
OCFC-Chap 9
Chapter 9

11. Oxidation of Alcohols & Derivatives (I)
Organic Chemistry of Fine Chemicals
Spring 2006
Oxidation of Alcohols & Derivatives (I)
dehydrogenation: substitution followed by elimination
chromium oxidants: CrO3 (in acid), H2CrO4, K2Cr2O7
good for 2o alcohols:  202 bottom (9.22)
stoichiometry: Cr Cr3+,  202 bottom – 203 top
Jones’ reagent: CrO3 & H2SO4,  203 middle
Collins’ reagent: CrO3 in pyridine,  203 bottom
OCFC-Chap 9
Chapter 9

12. Oxidation of Alcohols & Derivatives (II)
Organic Chemistry of Fine Chemicals
Spring 2006
Oxidation of Alcohols & Derivatives (II)
chromium oxidants (continued)
PCC: in organic solvents,  204 top
PDC & others: for acid-labile FG,  204 middle
oxidation to aldehydes
dichromate: controlled conditions,  204 bottom
CrO3 with pyr:  204 bottommost
PCC / PDC: in CH2Cl2,  205 top
OCFC-Chap 9
Chapter 9

13. Oxidation of Alcohols & Derivatives (III)
Organic Chemistry of Fine Chemicals
Spring 2006
Oxidation of Alcohols & Derivatives (III)
dimethyl sulfoxide oxidants:  205 middle (9.23)
selective oxidation to aldehydes
halides / DMSO or R3N+-O-:  205 bottom – 206 top
Moffatt oxidation: DCC with DMSO,  207 top
Swern oxidation: (COCl)2 with DMSO:  206 bottom (9.25)
SO3 / Ac2O with DMSO:  207 top
TPAP: Pr4N+RuO4- (cat) & oxidant;  207 bottom
CAN: selective for benzylic & 2o alcohols;  208 top
OCFC-Chap 9
Chapter 9

14. Oxidation of Alcohols & Derivatives (IV)
Organic Chemistry of Fine Chemicals
Spring 2006
Oxidation of Alcohols & Derivatives (IV)
hydride-shift oxidation: hydride acceptor
Oppenauer oxidation: selective,  208 middle & bottom
cf, Meerwein-Ponndorf-Verley reduction:  167 top
Sommelet reaction: CH2=N+H2,  209 top & middle
MnO2 oxidation:  209 bottom – 210 top
selective for allylic & benzylic alcohols
OCFC-Chap 9
Chapter 9

15. Oxidation of Aromatics
Organic Chemistry of Fine Chemicals
Spring 2006
Oxidation of Aromatics
arenes to phenol: SPB & triflic acid;  211 middle
Elbs reaction: hydroquinone,  212 top (9.30)
electrophilic substitution with peroxysulfate
oxidation of phenols to quinones
phenoxy free radical with Frémy’s salt:  212 bottom (9.31)
oxidation of hydroquinone to (benzo)quinone:  213 top
oxidative coupling: dimerization,  213 bot & 214 top
OCFC-Chap 9
Chapter 9

16. Oxidation of Aldehydes & Ketones (I)
Organic Chemistry of Fine Chemicals
Spring 2006
Oxidation of Aldehydes & Ketones (I)
to carboxylic acids
Ag2O: mild & selective for aldehydes,  214 bottom
KMnO4 / HNO3: ketones,  215 top (9.33) & middle
haloform reactions: -COCH3 / -CH(OH)CH3,  215 bottom (9.34)
to 1,2-dicarbonyls from an active methylene group
SeO2 oxidation:  216 top
a-halogenation & DMSO oxidation:  216 middle
a-nitrosation & hydrolysis:  216 bottom
OCFC-Chap 9
Chapter 9

17. Oxidation of Aldehydes & Ketones (II)
Organic Chemistry of Fine Chemicals
Spring 2006
Oxidation of Aldehydes & Ketones (II)
to esters
Baeyer-Villager oxidation: ketones,  217 top (9.35)
migratory aptitude: more e--rich,  217 middle & bottom
Dakin reaction: aryl ketones / aldehydes,  217 top (9.36)
arene diols:  217 bottom – 218 top
oxidation with peroxides:  218 middle
OCFC-Chap 9
Chapter 9

18. Oxidation of Nitrogen Atoms (I)
Organic Chemistry of Fine Chemicals
Spring 2006
Oxidation of Nitrogen Atoms (I)
amines
3o amines: N-oxides,  218 bottom
2o amines: hydroxylamines,  218 bottommost
1o amines: nitroso or oximes,  219 top & middle
nitro with CF3CO3H / dry peroxyacids:  219 bottom
exception: amide formation;  219 bottommost
OCFC-Chap 9
Chapter 9

19. Oxidation of Nitrogen Atoms (II)
Organic Chemistry of Fine Chemicals
Spring 2006
Oxidation of Nitrogen Atoms (II)
imines
hydrazone to diazoalkanes with HgO,  220 top (9.36)
oxime/hydrazone: nitrile oxide/nitrile imine,  220 top (9.37)
nitroalkanes: Nef reaction
hydrolysis to carbonyls:  220 middle
SPC or CAN oxidation:  220 middle
OCFC-Chap 9
Chapter 9

20. Oxidation of Sulfur Atoms
Organic Chemistry of Fine Chemicals
Spring 2006
Oxidation of Sulfur Atoms
thiols (RSH)
disulfides (RS-SR):  220 bottom – 221 top
sulfonic acids (RSO3H):  221 middle
sulfides (R-S-R): sulfones via sulfoxides
sulfoxides (R2S=O):  221 middle
CAN with NaBrO3/O2: no over-oxidation to sulfones
sulfones (R2SO2):  221 bottom – 222 top
OCFC-Chap 9
Chapter 9