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Organic Chemistry II Alcohols, Phenols, Thiols 5/12/2017 Dr Seemal Jelani Chem-240 1 Chapter Objectives • Nomenclature • Properties • Preparation • Reaction 5/12/2017 Dr Seemal Jelani Chem-240 2 Alcohols and Phenols • Important solvents and intermediates • Phenols contain an OH group connected to a carbon in a benzene ring • Methanol, CH3OH, common name is methyl alcohol, a solvent, a fuel additive, produced in large quantities 5/12/2017 Dr Seemal Jelani Chem-240 3 • Ethanol, CH3CH2OH, common name is ethyl alcohol, a solvent, fuel, beverage, produced in large quantities 5/12/2017 Dr Seemal Jelani Chem-240 4 Alcohols, Phenols, Thiols, Ethers • Considered derivatives of water OH SH OH alcohol thiol phenol O thiophenol S ether 5/12/2017 SH sulfide Dr Seemal Jelani Chem-240 5 Nomenclature of Alcohols • Derivatives of alkane with –ol suffix • Name longest chain containing OH • Number the chain starting nearest the carbon bearing the OH group • Number substituents, name, and list alphabetically 5/12/2017 Dr Seemal Jelani Chem-240 6 Examples propanol OH OH trans-1,2-cyclopentanediol OH OH 3-ethylheptan-3-ol 5/12/2017 Dr Seemal Jelani Chem-240 7 Classification of Alcohols • Primary – OH is attached to a carbon bearing one carbon atom • Secondary – OH is attached to a carbon bearing two carbon atoms • Tertiary – OH is attached to a carbon bearing three carbon atoms 5/12/2017 Dr Seemal Jelani Chem-240 8 Examples OH primary alcohol secondary alcohol OH tertiary alcohol OH 5/12/2017 Dr Seemal Jelani Chem-240 9 Common Names OH OH OH benzyl alcohol OH allyl alcohol HO HO OH OH glycerol ethylene glycol t-butyl alcohol 5/12/2017 Dr Seemal Jelani Chem-240 10 Phenols • Common natural source – coal tar • Found in many plants OH OH CO2CH3 oil of wintergreen OH coal tar OH OH CO2H R willow bark bioactive ingredient poison ivy and oak 5/12/2017 Dr Seemal Jelani Chem-240 11 Phenols OH OH OMe OMe eugenol (oil of clove) isoeugenol (oil of nutmeg) OH OMe OH O O C5H11 tetrahydrocannabinol 5/12/2017 vanillin Dr Seemal Jelani Chem-240 12 Nomenclature of Phenols • Use “phene” (the French name for benzene) as • the parent hydrocarbon name, not benzene Name substituents on aromatic ring by their position from OH OH OH H3C p-methylphenol 5/12/2017 OH Cl o-chlorophenol Dr Seemal Jelani Chem-240 O2N NO2 2,4-dinitrophenol 13 Common Names • Many common names in use OH OH OH H3C CH3 CH3 o-cresol p-cresol m-cresol OH OH OH HO OH OH catechol 5/12/2017 hydroquinone resorcinol Dr Seemal Jelani Chem-240 14 Nomenclature of Thiols • Same naming system as alcohols • Suffix is –thiol • Sometimes named as mercaptans SH SH CH3 isopropyl thiol cis-2-methylcycloheptane thiol OH SH m-mercaptophenol 5/12/2017 Dr Seemal Jelani Chem-240 15 Biosynthesis of Ethanol (Fermentation) O OH H3C C6H12O6 O glucose pyruvate O OH H3C CH3CH2OH O pyruvate 5/12/2017 Dr Seemal Jelani Chem-240 16 Properties • Alcohols and phenols are similar to water form • • • • • strong H-bonds Giving higher boiling points than the corresponding hydrocarbon Thiols do not form H-bonds (EN of S is low) Alcohols and phenols are weakly basic Alcohols and phenols are weakly acidic Phenols and Thiols are more acidic than water 5/12/2017 Dr Seemal Jelani Chem-240 17 Acidity Constants OH CH3CH2OH H2O pKa = 18 pKa = 16 pKa = 15.7 CH3OH pKa = 15.5 pKa = 10.3 CH3SH OH pKa = 10.2 H3C OH pKa = 9.9 OH pKa = 7.2 decreasing acidity O2N 5/12/2017 Dr Seemal Jelani Chem-240 18 Acidity of Alcohols • Do not react with amines or NaHCO3 • Limited reactivity with NaOH • React with alkali metals Na, K • React with strong bases like NaH or NaNH2 or RLi and RMgBr • Forms the alkoxide (RO-1) 5/12/2017 Dr Seemal Jelani Chem-240 19 Reactions with Bases ROH + NH3 No Reaction ROH + NaHCO3 5/12/2017 No Reaction ROH + NaOH RO- + H2O ROH + NaH RO- + H2 ROH + Na RO- + H2 ROH + RLi RO- + RH ROH + RMgX RO- + RH Dr Seemal Jelani Chem-240 20 Acidity of Phenols • • • • • ArOH is more acidic than ROH Soluble in dilute NaOH Anion is resonance stabilized EWG make phenols more acidic than phenol EDG make phenols less acidic than phenol O O OH - NaOH 5/12/2017 Dr Seemal Jelani Chem-240 21 Alcohols an Overview • Alcohols are derived from many types of • • • • compounds Alkenes, alkyl halides, ketones, esters, aldehydes, and carboxylic acids can provide the alcohol Alcohols are among most common natural materials The alcohol hydroxyl can be converted to many other functional groups This makes alcohols useful in synthetic planning 5/12/2017 Dr Seemal Jelani Chem-240 22 Preparation 5/12/2017 Dr Seemal Jelani Chem-240 23 Preparation of Alcohols • Hydration of Alkenes • BH3/THF followed by H2O2 in NaOH • Hg(OAc)2 followed by NaBH4 • OsO4 followed by NaHSO3 (cis1,2-diols) • RCO3H followed by aqueous acid (trans-1,2-diols) 5/12/2017 Dr Seemal Jelani Chem-240 24 • From Aldehydes and Ketones • Reduction with NaBH4 – Reduces alpha beta unsaturated carbonyls as well Reduction with LiAlH4 – Doesn’t touch alpha beta unsaturated carbonyls • From Esters – Reduction with LiAlH4 (LAH) – No reaction with NaBH4 5/12/2017 Dr Seemal Jelani Chem-240 25 Reduction of Ketones OH OH NaBH4 O + OH LAH 5/12/2017 Dr Seemal Jelani Chem-240 26 Preparation of Alcohols • From carboxylic acids – Reduction with LiAlH4 is slow – Reduction with NaBH4 doesn’t occur – Reduction with BH3 is preferred method LiAlH4 RCO2H RCH2OH slow NaBH4 No Reaction RCO2H BH3 RCO2H 5/12/2017 RCH2OH Dr Seemal Jelani Chem-240 27 From Alkyl halides • RX + Mg provides the Grignard reagent • Grignard reagents react with carbonyls to provide the alcohols CH3Br + Mg 5/12/2017 CH3-Mg-Br Dr Seemal Jelani Chem-240 28 Grignard Reactions • With aldehydes or O OH 1. CH3MgBr ketones 2. H3O+ O CH3 OH 1. CH3MgBr H H • With esters 2. H3O+ 1. CH3MgBr O CH3 OH CH3 OMe 5/12/2017 Dr Seemal Jelani 2. H3O+ Chem-240 CH3 29 Grignard Reactions • With carboxylic acids • Grignard's are strong bases • React with the acidic proton O 1. CH3MgBr OH 5/12/2017 O 2. OH H3O+ Dr Seemal Jelani Chem-240 + CH4 30 Reactions 5/12/2017 Dr Seemal Jelani Chem-240 31 Reactions of Alcohols • Alcohols react at – the O-H bond – the C-O bond 5/12/2017 Dr Seemal Jelani Chem-240 32 Alcohols to Alkyl Halides tertiary alcohols HCl Cl OH HBr Br OH primary or secondary alcohols SOCl2 OH OH 5/12/2017 Cl PBr3 Dr Seemal Jelani Cl Chem-240 33 Alcohols to Alkenes • • • • Dehydration Acid catalyzed reaction Excellent reaction for tertiary alcohols (E1) Provides the Zaitsev product 5/12/2017 Dr Seemal Jelani Chem-240 34 • When the substrate is asymmetric, regioselectivity is determined by Zaitsev’s rule • The one -step mechanisms is E2 reaction and two step reaction mechanism is called E1 reaction, respectively. Dr Seemal Jelani 5/12/2017 35 What is regioselectivity •It is the preference of one direction of chemical bond making or breaking over all other possible directions Dr Seemal Jelani 5/12/2017 36 What is Zaitsev’s rule • In chemistry, Zaitsev's rule, Saytzeff's rule or Saytsev's rule is a rule that states “that if more than one alkene can be formed during dehalogenation by an elimination reaction the more stable alkene is the major product” Dr Seemal Jelani 5/12/2017 37 Who is then stable • In general, the compound that has a more highly substituted C=C double bond is more stable. Dr Seemal Jelani 5/12/2017 38 Dr Seemal Jelani 5/12/2017 39 Alcohol to Alkene • Milder reaction developed • E2 process 5/12/2017 Dr Seemal Jelani Chem-240 40 Alcohols to Esters • • • • Alcohols react with carboxylic acids Reaction is acid catalyzed Alcohols react with acid chlorides Reaction is base catalyzed O R ROH/H+ OH H3O+ O R OR SOCl2 O 5/12/2017 R O ROH/pyridine Cl R Dr Seemal Jelani Chem-240 OR 41 Alcohols to Tosylate Esters • Reaction with p-toluenesulfonyl chloride (tosyl • • chloride, p-TosCl) in pyridine yields alkyl tosylates, ROTos Formation of the tosylate does not involve the C–O bond so configuration at a chirality center is maintained Alkyl tosylates react like alkyl halides 5/12/2017 Dr Seemal Jelani Chem-240 42 Oxidation of Alcohols • Can be accomplished by inorganic reagents, such as KMnO4, CrO3, and Na2Cr2O7 or by more selective, expensive reagents 5/12/2017 Dr Seemal Jelani Chem-240 43 Oxidation of Primary Alcohols • To aldehyde: pyridinium chlorochromate (PCC = C5H6NCrO3Cl) in dichloromethane • Other reagents produce carboxylic acids 5/12/2017 Dr Seemal Jelani Chem-240 44 Oxidation of Secondary Alcohols • Effective with inexpensive reagents such as • Na2Cr2O7 in acetic acid PCC is used for sensitive alcohols at lower temperatures 5/12/2017 Dr Seemal Jelani Chem-240 45 Preparation and Uses of Phenols • Industrial process from readily available cumene • Forms cumene hydroperoxide with oxygen at • high temperature Converted into phenol and acetone by acid 5/12/2017 Dr Seemal Jelani Chem-240 46 Industrial Preparation of Phenol Cl 5/12/2017 NaOH/heat Dr Seemal Jelani Chem-240 OH 47 Laboratory Preparation of Phenols • From aromatic sulfonic acids by melting with • NaOH at high temperature Limited to the preparation of alkyl-substituted phenols 5/12/2017 Dr Seemal Jelani Chem-240 48 Reactions of Phenols • The hydroxyl group is a strongly activating, • • making phenols substrates for electrophilic halogenation, nitration, sulfonation, and Friedel– Crafts reactions Reaction of a phenol with strong oxidizing agents yields a quinone Fremy's salt [(KSO3)2NO] works under mild conditions through a radical mechanism 5/12/2017 Dr Seemal Jelani Chem-240 49