_  +  Chapter 11 Reactions of Alcohols Organic Chemistry, 6 th Edition L. G. Wade, Jr.

_  +  Chapter 112 Types of Alcohol Reactions Dehydration to alkene Oxidation to aldehyde, ketone Substitution to form alkyl halide Reduction to alkane Esterification Tosylation Williamson synthesis of ether =>

_  +  Chapter 113 Summary Table =>

_  +  Chapter 114 Oxidation States Easy for inorganic salts  CrO 4 2- reduced to Cr 2 O 3  KMnO 4 reduced to MnO 2 Oxidation: loss of H 2, gain of O, O 2, or X 2 Reduction: gain of H 2 or H -, loss of O, O 2, or X 2 Neither: gain or loss of H +, H 2 O, HX =>

_  +  Chapter 115 1º, 2º, 3º Carbons =>

_  +  Chapter 116 Oxidation of 2° Alcohols 2° alcohol becomes a ketone Reagent is Na 2 Cr 2 O 7 /H 2 SO 4 Active reagent probably H 2 CrO 4 Color change: orange to greenish-blue =>

_  +  Chapter 117 Oxidation of 1° Alcohols 1° alcohol to aldehyde to carboxylic acid Difficult to stop at aldehyde Use pyridinium chlorochromate (PCC) to limit the oxidation. PCC can also be used to oxidize 2° alcohols to ketones. =>

_  +  Chapter 118 3° Alcohols Don’t Oxidize Cannot lose 2 H’s Basis for chromic acid test =>

_  +  Chapter 119 Other Oxidation Reagents Collins reagent: Cr 2 O 3 in pyridine Jones reagent: chromic acid in acetone KMnO 4 (strong oxidizer) Nitric acid (strong oxidizer) CuO, 300°C (industrial dehydrogenation) Swern oxidation: dimethylsulfoxide, with oxalyl chloride and hindered base, oxidizes 2  alcohols to ketones and 1  alcohols to aldehydes. =>

_  +  Chapter 1110 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 1111 Alcohol as a Nucleophile ROH is weak nucleophile RO - is strong nucleophile New O-C bond forms, O-H bond breaks. =>

_  +  Chapter 1112 Alcohol as an Electrophile OH - is not a good leaving group unless it is protonated, but most nucleophiles are strong bases which would remove H +. Convert to tosylate (good leaving group) to react with strong nucleophile (base). =>  + + C-Nuc bond forms, C-O bond breaks

_  +  Chapter 1113 Formation of Tosylate Ester p-toluenesulfonyl chloride TsCl, “tosyl chloride” ROTs, a tosylate ester =>

_  +  Chapter 1114 S N 2 Reactions of Tosylates With hydroxide produces alcohol With cyanide produces nitrile With halide ion produces alkyl halide With alkoxide ion produces ether With ammonia produces amine salt With LiAlH 4 produces alkane =>

_  +  Chapter 1115 Summary of Tosylate Reactions =>

_  +  Chapter 1116 Reaction with HBr -OH of alcohol is protonated -OH 2 + is good leaving group 3° and 2° alcohols react with Br - via S N 1 1° alcohols react via S N 2 =>

_  +  Chapter 1117 Reaction with HCl Chloride is a weaker nucleophile than bromide. Add ZnCl 2, which bonds strongly with -OH, to promote the reaction. The chloride product is insoluble. Lucas test: ZnCl 2 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 1118 Limitations of HX Reactions HI does not react Poor yields of 1° and 2° chlorides May get alkene instead of alkyl halide Carbocation intermediate may rearrange. =>

_  +  Chapter 1119 Reactions with Phosphorus Halides Good yields with 1° and 2° alcohols PCl 3 for alkyl chloride (but SOCl 2 better) PBr 3 for alkyl bromide P and I 2 for alkyl iodide (PI 3 not stable) =>

_  +  Chapter 1120 Mechanism with PBr 3 P bonds to -OH as Br - leaves Br - attacks backside (S N 2) HOPBr 2 leaves =>

_  +  Chapter 1121 Reaction with Thionyl Chloride Produces alkyl chloride, SO 2, HCl S bonds to -OH, Cl - leaves Cl - abstracts H + from OH C-O bond breaks as Cl - transferred to C =>

_  +  Chapter 1122 Dehydration Reactions Conc. H 2 SO 4 produces alkene Carbocation intermediate Zaitsev product Bimolecular dehydration produces ether Low temp, 140°C and below, favors ether High temp, 180°C and above, favors alkene =>

_  +  Chapter 1123 Dehydration Mechanisms =>

_  +  Chapter 1124 Energy Diagram, E1 =>

_  +  Chapter 1125 Alkoxide Ions ROH + Na (or NaH) yields sodium alkoxide RO - + 1° alkyl halide yields ether (Williamson ether synthesis) =>

_  +  Chapter 1126 End of Chapter 11