CH3CH2CH2 Organic Chemistry, 5th Edition L. G. Wade, Jr. Br CH3CH2CH2 H C O H H H Br Types of Alcohol Reactions • • • • • • • Chapter 11 Reactions of Alcohols Jo Blackburn Richland College, Dallas, TX Dallas County Community College District © 2003, Prentice Hall Dehydration to alkene Oxidation to aldehyde, ketone Substitution to form alkyl halide Reduction to alkane Esterification Tosylation Williamson synthesis of ether H C O H H H => Chapter 11 CH3CH2CH2 Br Summary Table 2 CH3CH2CH2 H C O H H H Br Oxidation States H C O H H H • Easy for inorganic salts ¾CrO42- reduced to Cr2O3 ¾KMnO4 reduced to MnO2 • Oxidation: loss of H2, gain of O, O2, or X2 • Reduction: gain of H2 or H-, loss of O, O2, or X2 • Neither: gain or loss of H+, H2O, HX => Chapter 11 => 3 Chapter 11 CH3CH2CH2 1º, 2º, 3º Carbons Br CH3CH2CH2 H C O H H H Br Oxidation of 2° Alcohols • • • • OH Na2Cr2O7 / H2SO 4 O CH3CCH2CH3 => => 5 H C O H H H 2° alcohol becomes a ketone Reagent is Na2Cr2O7/H2SO4 Active reagent probably H2CrO4 Color change: orange to greenish-blue CH3CHCH2CH3 Chapter 11 4 Chapter 11 6 1 CH3CH2CH2 Oxidation of 1° Alcohols Br H C O H H H • 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. OH N H CrO3Cl CH3CH2CH2CH2 CH3CH2CH2 3° Alcohols Don’t Oxidize • Cannot lose 2 H’s • Basis for chromic acid test O => 7 CH3CH2CH2 Br Other Oxidation Reagents H C O H H H Collins reagent: Cr2O3 in pyridine Jones reagent: chromic acid in acetone KMnO4 (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 11 9 => Chapter 11 Biological Oxidation Br Alcohol as a Nucleophile H H C O H H H R X • ROH is weak nucleophile • RO- is strong nucleophile • New O-C bond forms, O-H bond breaks. => Chapter 11 11 CH3CH2CH2 Br H C O H H H => Chapter 11 10 CH3CH2CH2 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) O 8 • 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. CH3CH2CH2 C H C O H H H CH3CH2CH2CH Chapter 11 • • • • • • Br Br H C O H H H H ∂+ C O C-Nuc bond forms, C-O bond breaks => Chapter 11 12 2 CH3CH2CH2 Br Formation of Tosylate Ester CH3CH2CH2 H C O H H H Br SN2 Reactions of Tosylates H C O H H H H C O C C H O O Cl O S N O O CH3 S O O S CH3 O CH3 p-toluenesulfonyl chloride TsCl, “tosyl chloride” ROTs, a tosylate ester => Chapter 11 • • • • • • 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 LiAlH4 produces alkane => 13 Chapter 11 14 CH3CH2CH2 Summary of Tosylate Reactions Br H C O H H H CH3CH2CH2 Reduction of Alcohols OH H2SO4 alcohol OH => CH3CHCH3 alcohol Chapter 11 15 CH2 CHCH3 H2 Pt alkene TsCl CH3CH2CH3 alkane OTs CH3CHCH3 tosylate LiAlH4 Br H C O H H H -OH of alcohol is protonated -OH2+ is good leaving group 3° and 2° alcohols react with Br- via SN1 1° alcohols react via SN2 R O H H3O + H R O H - Br R Br => => CH3CH2CH3 alkane Chapter 11 CH3CH2CH2 • • • • H C O H H H • Dehydrate with conc. H2SO4, then add H2 • Tosylate, then reduce with LiAlH4 CH3CHCH3 Reaction with HBr Br 16 CH3CH2CH2 Reaction with HCl Br H C O H H H • Chloride is a weaker nucleophile than bromide. • Add ZnCl2, which bonds strongly with -OH, to promote the reaction. • The chloride product is insoluble. • Lucas test: ZnCl2 in conc. HCl ¾1° alcohols react slowly or not at all. ¾2° alcohols react in 1-5 minutes. ¾3° alcohols react in less than 1 minute. => Chapter 11 17 Chapter 11 18 3 CH3CH2CH2 Br Limitations of HX Reactions • • • • CH3CH2CH2 H C O H H H Reactions with Phosphorus Halides HI does not react Poor yields of 1° and 2° chlorides May get alkene instead of alkyl halide Carbocation intermediate may rearrange. • • • • Br H C O H H H Good yields with 1° and 2° alcohols PCl3 for alkyl chloride (but SOCl2 better) PBr3 for alkyl bromide P and I2 for alkyl iodide (PI3 not stable) => => Chapter 11 19 Chapter 11 CH3CH2CH2 Mechanism with PBr3 Br Reaction with Thionyl Chloride H C O H H H • • • • • P bonds to -OH as Br- leaves • Br- attacks backside (SN2) • HOPBr2 leaves => Chapter 11 20 Chapter 11 H C O H H H 22 => CH3CH2CH2 Dehydration Reactions Br 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 21 Br CH3CH2CH2 CH3CH2CH2 H C O H H H Br Dehydration Mechanisms H C O H H H H • • • • • • Conc. H2SO4 produces alkene Carbocation intermediate Saytzeff product Bimolecular dehydration produces ether Low temp, 140°C and below, favors ether High temp, 180°C and above, favors alkene => Chapter 11 23 OH CH3CHCH3 H2SO4 OH CH3CHCH3 CH3CHCH3 alcohol H2O CH3OH H3O CH2 CHCH3 + CH3 CH3 OH2 O CH3 H CH3OH H2O Chapter 11 CH3OCH3 => 24 4 CH3CH2CH2 Energy Diagram, E1 Br CH3CH2CH2 H C O H H H Br Unique Reactions of Diols H C O H H H • Pinacol rearrangement • Periodic acid cleavage => Chapter 11 25 => Chapter 11 26 CH3CH2CH2 Pinacol Rearrangement Br CH3CH2CH2 H C O H H H Periodic Cleavage of Glycols • Pinacol: 2,3-dimethyl-2,3-butanediol • Dehydration with sulfuric acid CH3 CH3 CH3 C CH3 OH OH H CH3 C C OH OH CH3 CH3 CH3 C C CH3 OH CH3 H CH3 CH3 C OH C CH3 CH3 CH3 CH3 C C OH CH3 CH3 CH3 CH3 C C CH3 OH CH3 C O Chapter 11 C H CH3 C C OH OH HIO4 CH3 CH3 CH3 C C H3C 27 pinacolone + O CH3 => CH3 Chapter 11 28 CH3CH2CH2 Br Esterification • • • • • C CH3 O3 (CH3)2S H => CH3 CH3 H C O OsO4 H2O2 CH3 CH3 H C O H H H Same products formed as from ozonolysis of the corresponding alkene. CH3 CH3 CH3 + C Br CH3CH2CH2 H C O H H H Br Fischer Esterification H C O H H H • Acid + Alcohol yields Ester + Water • Sulfuric acid is a catalyst. • Each step is reversible. Fischer: alcohol + carboxylic acid Tosylate esters Sulfate esters Nitrate esters Phosphate esters O CH3 C OH CH3 + H O CH2CH2CHCH3 + H O CH3 CH3C OCH2CH2CHCH3 + HOH => => Chapter 11 29 Chapter 11 30 5 CH3CH2CH2 Br Tosylate Esters CH3CH2CH2 H C O H H H Br Sulfate Esters • Alcohol + p-Toluenesulfonic acid, TsOH • Acid chloride is actually used, TsCl Alcohol + Sulfuric Acid O O CH3CH2 O H HO + HO S H C O H H H CH3 S O + OH H + H O CH2CH3 HO O S OCH2CH3 O O O O CH3CH2 O S CH3 => CH3CH2O H + HO S O + OCH2CH3 H CH3CH2O O O 31 Br Nitrate Esters O + + O H H O CH2CH3 32 O H CH2 O H CH2 O H 3 HO NO 2 + CH3CH2CH2 H C O H H H Br Phosphate Esters O N OCH2CH3 HO O CH2 O P OH CH3OH CH3O OH CH2 O NO2 CH2 O NO2 CH2 O NO2 P OH Chapter 11 CH3OH CH3O P OCH3 OCH3 => Chapter 11 34 CH3CH2CH2 H C O H H H Br Alkoxide Ions base O OCH3 CH3OH CH3CH2CH2 Phosphate Esters in DNA P OH O 33 Br H C O H H H O CH3O OH nitroglycerine => glycerine O CH2 => Chapter 11 CH3CH2CH2 N OH OCH2CH3 + HOH Chapter 11 O S O H C O H H H H H • ROH + Na (or NaH) yields sodium alkoxide • RO- + 1° alkyl halide yields ether (Williamson ether synthesis) H O O CH2 P O base O H O H H O O CH2 O H P O base O H H O O CH2 P O CH3 base O CH3CH2CHCH3 H O H Br O H O + CH3CH2 CH2CH2CH O CH2CH3 => O P O Chapter 11 O => 35 Chapter 11 36 6