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

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

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

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

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

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

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

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

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

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

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: Cr6+ Cr3+,  202 bottom – 203 top Jones’ reagent: CrO3 & H2SO4,  203 middle Collins’ reagent: CrO3 in pyridine,  203 bottom OCFC-Chap 9 Chapter 9

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

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

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

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

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

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

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

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

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