Chapter_11.ppt

Chapter 11 Reactions of Alcohols Organic Chemistry, 5th Edition L. G. Wade, Jr. Chapter 11 * Reaction Summary Table Chapter 11 Chapter 11 * Oxidation Reactions Chapter 11 Chapter 11 * Chapter 11 * Oxidation of 2° Alcohols 2° alcohol becomes a ketone Common reagent is Na2Cr2O7 in H2SO4 Active reagent probably H2CrO4 (Chromic Acid) Color change: orange to greenish-blue CrO3 (chromium trioxide) in H2SO4 same result Chapter 11 Chapter 11 * Chapter 11 * Oxidation of 1° Alcohols 1° alcohol to aldehyde then carboxylic acid Difficult to stop the reaction at aldehyde Common reagent to synthesize aldehyde is PCC Pyridinium ChloroChromate Mixture of pyridine, HCl and Na2Cr207 (or CrO3) Weak oxidant limits the oxidation Common reagent to synthesize CA is chromic acid Chapter 11 Chapter 11 * Chapter 11 * 3° Alcohols Don?t Oxidize Oxidation reagents cannot break C-C bonds Basis for chromic acid test Color change from orange to green indicates 1o/2o alcohol Chapter 11 Chapter 11 * Oxidation of Glycol/ Periodic Cleavage Same products as from ozonolysis of alkene. Chapter 11 * Summary of Oxidation Weak Oxidants Strong oxidants 1o alcohol ? aldehyde 2o alcohol ? ketone PCC ____________ Collins ____________ Swern ____________ Di-ol? Carbonyl HIO4 Thiol? Disulfide (R-SH? R-S-S-R) Br2 1o alcohol ? carboxylic acid 2o alcohol ? ketone Chromic Acid _______________ Jones ____________________ Nitric Acid _______________ Permanganate _______________ Sodium Hypochlorite___________ Copper Oxide _______________ Thiol? Sulfonic Acid R-SH? RSO3H Nitric Acid, Permanganate, Hypochlorite Chapter 11 * Chapter 11 * Biological Oxidation Catalyzed by ADH, alcohol dehydrogenase. Oxidizing agent is NAD+, nicotinamide adenine dinucleotide. Ethanol oxidizes to acetaldehyde, then acetic acid, a normal metabolite. Methanol oxidizes to formaldehyde, then formic acid, more toxic than methanol. Ethylene glycol oxidizes to oxalic acid, toxic. Treatment for poisoning is excess ethanol. Chapter 11 Chapter 11 * Chapter 11 Chapter 11 * Alcohol as a Nucleophile ROH is weak nucleophile RO- is strong nucleophile New O-C bond forms, O-H bond breaks. Chapter 11 Chapter 11 * Alcohol as an Electrophile -OH is not a good leaving group Trick - Convert the -OH into a good leaving group (a tosylate) then react with strong nucleophile ? + C-Nuc bond forms, C-O bond breaks Chapter 11 Chapter 11 * Chapter 11 * Formation of Tosylate Ester p-toluenesulfonyl chloride TsCl, ?tosyl chloride? ROTs, a tosylate ester C H 3 S O O O C C O H C H 3 S C l O O Chapter 11 Chapter 11 * SN2 Reactions of Tosylates With hydroxide (-OH) produces alcohol. With cyanide (-C?N) produces nitrile. With halide ion (-X) produces alkyl halide. With alkoxide ion (-OR) produces ether. With ammonia (NH3) produces amine salt. With LiAlH4 (-H) produces alkane. Chapter 11 Chapter 11 * Reduction of Alcohols Dehydrate with conc. H2SO4, then add H2 OR Tosylate, then reduce with LiAlH4 Chapter 11 Chapter 11 * Reaction with HBr/NaBr -OH of alcohol is protonated HOH is good leaving group 3° and 2° alcohols react with Br- via SN1 Racemic product of both R and S enantiomers Potential for rearrangement (hydride or methyl shift) 1° alcohols react via SN2 Poor reaction Only a single enantiomeric product Same reaction with safer NaBr reagent Chapter 11 Chapter 11 * Reaction with HCl Chloride is a weaker nucleophile than bromide. Add ZnCl2, which bonds strongly with -OH, to make it a better leaving group than HOH. The chloride by-product is insoluble. Lucas test: ZnCl2 in conc. HCl 1° alcohols react slowly or not at all. 2? alcohols react in 1-5 minutes. 3? alcohols react in less than 1 minute. Chapter 11 Chapter 11 * Limitations of HX Reactions HI does not react Poor yields of 1° and 2° halides May get alkene instead of alkyl halide Carbocation intermediate may rearrange. Chapter 11 Chapter 11 * Reactions with Phosphorus Halides (PX3) Good yields with 1° and 2° alcohols PCl3/PCl5 for alkyl chloride but SOCl2 better PBr3 for alkyl bromide P and I2 for alkyl iodide (PI3 not stable) Chapter 11 Chapter 11 * Mechanism with PBr3/PI3/PCl3 P bonds to -OH as Br- leaves Br- attacks backside (SN2) if?. HOPBr2 leaves Chapter 11 Chapter 11 * Reaction with Thionyl Chloride Produces alkyl chloride, SO2, HCl S bonds to -OH, Cl- leaves Cl- abstracts H+ from OH C-O bond breaks as Cl- transferred to C Chapter 11 Chapter 11 * Dehydration Reactions Conc. H2SO4 produces alkene Carbocation intermediate (E1) Saytzeff product Dehydration reaction is favored when reaction is at high temp (180°C and above) However Low temp, 140°C and below, favors ether formation (bimolecular dehydration) IF the alcohol is a primary alcohol. Chapter 11 Chapter 11 * Bimolecular dehydration Mechanism Dehydration Mechanism Chapter 11 Chapter 11 * Pinacol Rearrangement Pinacol: 2,3-dimethyl-2,3-butanediol Dehydration with sulfuric acid Chapter 11 Chapter 11 * Energy Diagram, E1 Chapter 11 Chapter 11 * Esterification Fischer: alcohol + carboxylic acid Tosylate esters Sulfate esters Nitrate esters Phosphate esters Chapter 11 Chapter 11 * Fischer Esterification Acid + Alcohol yields Ester + Water Sulfuric acid is a catalyst. Each step is reversible. Chapter 11 Chapter 11 * Tosylate Esters Alcohol + p-Toluenesulfonic acid, TsOH Acid chloride is actually used, TsCl Chapter 11 Chapter 11 * Sulfate Esters Alcohol + Sulfuric Acid Chapter 11 Chapter 11 * Nitrate Esters Chapter 11 Chapter 11 * Phosphate Esters Chapter 11 Chapter 11 * Phosphate Esters in DNA Chapter 11 Chapter 11 * Anion Chemistry ROH + Na (or NaH) yields sodium alkoxide RO- + 1° alkyl halide yields ether (Williamson ether synthesis) Can conduct same chemistry with the more reactive RSH thiol to form a sulfide Chapter 11