PCH 314/302 Oxidation-Reduction Reactions PDF

PCH 314/ PCH 302 OXIDATION-REDUCTION REACTIONS  OXIDATION-REDUCTION In organic chemistry, oxidation is seen as – addition of oxygen and/or removal of hydrogen. Reduction is viewed as – addition hydrogen and/or removal of oxygen RCH2OH [O] RCHO...

PCH 314/ PCH 302 OXIDATION-REDUCTION REACTIONS  OXIDATION-REDUCTION In organic chemistry, oxidation is seen as – addition of oxygen and/or removal of hydrogen. Reduction is viewed as – addition hydrogen and/or removal of oxygen RCH2OH [O] RCHO R2C=O [H] R2CHOH Oxidizing agents bring about oxidation while reducing agents effect reduction. However in organic chemistry, substrate is the focus 2  OXIDATION REACTIONS Alcohols: RCH2OH [O] RCHO [O] RCOOH R2CH-OH [O] R2C=O R3C-OH [O] Difficult to oxidize Oxidizing agent is usually alkaline KMnO4 or chromic acid - H2CrO4 (generated in situ by K2Cr2O7/ H2SO4 or CrO3/ H2SO4). H2CrO4 is especially useful for 2ry alcohols with α,β-unsaturation. RCH2OH + KMnO4 KOH (aq) RCOO-K+ + MnO2 H+ RCOOH 3R2CHOH + 2 H2CrO4 + 6H+ → 3R2C=O + 2Cr3+ + 8H2O For 1ry alcohols it is difficult to stop the reaction at aldehyde stage, except if the aldehyde is removed as soon as it is formed, usually by distillation (since aldehydes often have lower b.p. than acids) Benedict’s & Fehling’s reagents give +ve test with aldehydes and α- hydroxyketones (i.e. aldoses and ketoses). The reagents, which contain Cu2+ (citrate in Benedict’s; tartrate in Fehling’s), is reduced to Cu2O – seen as a brick-red precipitate 3  Also, Tollens’ reagent (AgNO3/aq. NH3) generates [Ag(NH3)2]+ which, tho’ a weak oxidizing agent, oxidizes aldehydes and α-hydroxyket- ones. In the process Ag metal is deposited on the test tube wall, appearing like a mirror (silver mirror test). Ketones do not react RCHO + [Ag(NH3)2]+ → RCOO- + Ag R-CO-CH(OH)R' + [Ag(NH3)2]+ → R-CO-CO-R' + Ag Oppenauer oxidation: process by which 2ry alcohols are oxidized to ketones using Al alkoxide (usually t-butoxide) in the presence of a large excess of acetone (to drive the equilibrium in the forward direction). The process involves an initial alkoxy exchange followed by hydride ion transfer. The reverse reaction (i.e. reduction of ketone to 2ry alcohol) is known as Meerwein-Ponndorf-Verley (MPV) reduction. 3R2CHOH + (Me3C-O-)3Al (R2CH-O-)3Al + Me3C-OH (R2CH-O-)3Al + Me2C=O 3R2C=O + (Me2CH-O-)3Al 4  Side chain oxidation of alkylbenzenes Alkylbenzenes can be oxidized to benzoic acid using: hot, dil.HNO3; hot chromic acid; OR hot, alkaline KMnO4 (best). Oxidation always occurs at the benzylic carbon CH3 COOH 1. KMnO4/ OH-, heat 2. H+ CH2CH2CH3 COOH 1. KMnO4/ OH-, heat 2. H+ 5  Oxidative cleavage of alkenes Hot KMnO4: yields carboxylic acids. If terminal alkene is involved, CO2 is formed. Rxn used to locate double bond position in alkenes RCH=CHR' hot KMnO4 RCOO-K+ + R'COOH H+ RCOOH RCH=CH2 hot KMnO4 RCOOH + CO2 + H2O Ozonolysis: addition of ozone, 1st yields molozonide, then ozonide. Because ozonide is unstable and may explode it is not usually isolated but reduced to carbonyl. This reaction can also be used to locate position of double bonds in alkenes. R R'' R O R'' R R'' C C + O3 R' C C R''' R' C C R''' R''' R' O O O O ozone O Alkene molozonide ozonide Zn/ H2O R R'' C O + O C + Zn(OH)2 R' R''' 6  Oxidative coupling Alkynes: undergo oxidative coupling and dimerize to form diynes R-CΞCH Cu2Cl2/NH3/O2 R-CΞC-CΞC-R Phenols: oxidative coupling of phenols is very important in biosynthesis of alkaloids. Loss of a proton and an electron results in radical which may couple ortho-ortho, ortho-para, or para-para 7  Oxidative coupling contd. O. O O O OH.. [O] -e- , -H+. O O O O OH OH H H.. enolization O O OH H.. O O OH H H O.. O O O HO OH H 8  Baeyer-Villiger oxidation Oxidative cleavage of C-C bond adjacent to carbonyl, converting ketone to ester (cyclic ketone to lactone). It is carried out by peracids (RCOOOH) or hydrogen peroxide in the presence of a Lewis acid O O H2O2 BF 3 O O P hC O3H O C H2C l2 O O O P hC O3H BF3 O 9  Migratory ability of the substituents attached to carbonyl is such that groups that better stabilize +ve charges migrate more readily (R3C- > cyclohexyl > R2CH- > Ph- > RCH2- > CH3-) Mechanism: - -B F +O BF3 O O 3 +BF3 R R' R R' R + R' -BF BF 3 3 O O O O O O + - O R + R' R R' O R '' O- R OR ' R '' O R '' O 10  Epoxidation (Prilezhaev Reaction) Conversion of an alkene to oxirane (epoxide) by peracids such as MCPBA (meta-chloro perbenzoic acid) or peracetic acid R R' C H3C OOOH O R R' H R '' Mechanism: H R '' O R O R O + O H O O H 11  Cannizzaro Reaction Redox disproportionation (autoxidation) of non-enolizable aldehydes (i.e aldehydes with no α-H). The aldehyde acts as both oxidising and reducing agents. Rxn takes place in conc base 2PhCHO + KOH →PhCH2OH + PhCOO-K+ → PhCOOH α-Keto aldehydes give intramolecular (concerted) disproportionation products O O - HO O OH R H R OH 12  REDUCTION Alkenes: RR'C=CR''R''' + H2 Ni, Pd, or Pt RR'CH-CHR''R''' Aldehydes RCHO [H] RCH2OH; Ketones: RR'C=O [H] RR'CHOH Acids: RCOOH [H] RCH2OH ; Esters: RCOOR' [H] RCH2OH + R'OH Amides: RCONHR' [H] RCH2NHR' Nitriles: R-CΞN [H] RCH2NH2 Reagents used H2/catalyst: catalysts include Ni, Pd, Pt Metal/Acid: Examples include: Zn-Hg/HCl (Clemmensen reduction); Fe/HCl; Fe/glacial AcOH; Sn/HCl Na/alcohol (Hydrogenolysis): High pressure hydrogenation. Usually an industrial process employed in reduction of esters RCOOR' [Na/EtOH] RCH2OH + R'OH Metal hydrides: Most widely used are LiAlH4 & NaBH4 - LiAlH4 is powerful and unselective (reduces virtually all groups) - NaBH4 is mild and selective (reduces only aldehydes and ketones) 13 - LiAlH4 must be used in anhydrous condition because it reacts violently with water (water is added cautiously after the reaction to break down the Al complex). NaBH4 is used in aqueous medium - Mechanism: Always involves hydride ion transfer to the carbonyl carbon. The process is repeated until all the hydride from the reducing agent has been transferred. The complex formed is then decomposed by water. Using NaBH4 the process is shown below R R H H H 3 C O H C O B Na+ R C OBH3 Na+ R' R C O B-Na+ R' H H R' R' 4 H H 3 H2O R C O B-Na+ 4 R C OH + NaH2BO3 R' 4 R' 14  Other Reduction Reactions Nitro reduction: Nitro groups are usually reduced by metal/acid or H2/catalyst. However selective nitro reduction can be achieved by using H2S in aqueous alcoholic ammonia NO2 NH2 Fe / HCl NO2 NH2 H2S NO2 NH3 / EtOH NH2 Wolff-Kishner reduction: Used when Clemmensen reduction fails or when strongly acidic conditions cannot be used because acid-labile groups are present. It involves heating the hydrazone or semicarbazone formed from a carbonyl with KOH or NaOEt Ph(R)C=O H2NNH2 Ph(R)C=N-NH2 KOH PhCH2R + N2 Hydrazine Hydrazone 15  Huang-Minlon modification (of Wolff-Kishner reduction): The hydrazone is formed in situ by refluxing the carbonyl in diethylene glycol with hydrazine and KOH. Advantages of this method are: - No need to isolate the hydrazine - Reaction time is reduced - Reaction can be carried out at atmospheric pressure, & large scale - Good yield obtained Meerwein-Ponndorff-Verley (MPV) reduction: is the reverse of Oppenauer oxidation. The alkoxide commonly used is Al isopropoxide. In order to favour the formation of alcohol, acetone formed is removed by distillation (drives equilibrium to the right). MPV reduction is also very selective for carbonyls (i.e. groups such as conjugated double bond, nitro or halogen are unaffected). 3 R(R')C=O + (Me2CH-O-)3Al (RR'CH-O-)3Al + Me2C=O 16  Reductive amination: process by which aldehydes and ketones are converted to 1ry amines thro’ catalytic or chemical reduction in the presence of ammonia. An imine is formed as intermediate. R R H - H2O H2/Ni C O + NH3 C NH R C NH2 R' R' R' Birch Reduction: Benzene is reduced to 1,4-cyclohexadiene by treating it with an alkali metal (Na, K or Li) in a mixture of liquid NH3 & an alcohol Na NH3 / EtOH Note that when benzene is hydrogenated under pressure using H2/ metal catalyst, cyclohexane is the final product. The intermediates – 1,3- and 1,4-cyclohexadiene, & cyclohexene cannot be isolated since they undergo hydrogenation faster than benzene H2 / Ni H2 / Ni H2 / Ni + 17  Rosenmund Reduction Catalytic hydrogenation of acid chlorides to produce aldehydes O O H2, P d / BaS O4 + HC l R Cl R H The Pd catalyst must be poisoned (e.g with BaSO4) cos the untreated catalyst is too reactive and will cause the rxn to go further to give other products (such as RCH2OH and RCH3) Some of the side products can be avoided by carrying out the rxn in strictly anhydrous solvents 18