Chapter 11 Alcohols & Ethers Ch. 11 - 1 1. Structure & Nomenclature Alcohols have a hydroxyl (–OH) group bonded to a saturated carbon atom (sp3 hybridized) OH OH OH 1o 2o 3o Ethanol 2-Propanol 2-Methyl- (isopropyl 2-propanol alcohol) (tert-butyl alcohol) Ch. 11 - 2 OH OH 2-Propenol 2-Propynol (allyl alcohol) (propargyl alcohol) OH Benzyl alcohol Ch. 11 - 3 Phenols ● Compounds that have a hydroxyl group attached directly to a benzene ring OH OH Cl OH H3C Phenol 4-Methylphenol 2-Chlorophenol Ch. 11 - 4 Ethers ● The oxygen atom of an ether is bonded to two carbon atoms O CH O 3 Diethyl ether tert-Butyl methyl ether O O Divinyl ether Ethyl phenyl ether Ch. 11 - 5 1A. Nomenclature of Alcohols Rules of naming alcohols ● Identify the longest carbon chain that includes the carbon to which the –OH group is attached ● Use the lowest number for the carbon to which the –OH group is attached ● Alcohol as parent (suffix) ending with “ol” Ch. 11 - 6 Examples OH OH OH OH 2-Propanol 1,2,3-Butanetriol (isopropyl alcohol) Ch. 11 - 7 Example OH 3-Propyl-2-heptanol 8 7 wrong or 6 1 5 7 3 1 2 3 4 6 5 4 2 OH OH Ch. 11 - 8 1B. Nomenclature of Ethers Rules of naming ethers ● Similar to those with alkyl halides CH3O– Methoxy CH3CH2O– Ethoxy Example O Ethoxyethane (diethyl ether) Ch. 11 - 9 Cyclic ethers O O Oxacyclopropane Oxacyclobutane or oxirane or oxetane (ethylene oxide) O O O Oxacyclopentane 1,4-Dioxacyclohexane (tetrahydrofuran or THF) (1,4-dioxane) Ch. 11 - 10 2. Physical Properties of Alcohols and Ethers Ethers have boiling points that are roughly comparable with those of hydrocarbons of the same molecular weight (MW) Alcohols have much higher boiling points than comparable ethers or hydrocarbons Ch. 11 - 11 For example O OH Diethyl ether Pentane 1-Butanol (MW = 74) (MW = 72) (MW = 74) b.p. = 34.6oC b.p. = 36oC b.p. = 117.7oC Alcohol molecules can associate with each other through hydrogen bonding, whereas those of ethers and hydrocarbons cannot Ch. 11 - 12 Water solubility of ethers and alcohols ● Both ethers and alcohols are able to form hydrogen bonds with water ● Ethers have solubilities in water that are similar to those of alcohols of the same molecular weight and that are very different from those of hydrocarbons ● The solubility of alcohols in water gradually decreases as the hydrocarbon portion of the molecule lengthens; long- chain alcohols are more “alkane-like” and are, therefore, less like water Ch. 11 - 13 Physical Properties of Ethers Name Formula mp bp (oC) (oC) (1 atm) Dimethyl ether CH3OCH3 -138 -24.9 Diethyl ether CH3CH2OCH2CH3 -116 34.6 Diisopropyl ether (CH3)2CHOCH(CH3)2 -86 68 1,2-Dimethoxyethane CH3OCH2CH2OCH3 -68 83 (DME) O Oxirane -112 12 Tetrahydrofuran (THF) -108 65.4 O Ch. 11 - 14 Physical Properties of Alcohols Name Formula mp bp (oC) * (oC) (1 atm) Methanol CH3OH -97 64.7 inf. Ethanol CH3CH2OH -117 78.3 inf. Isopropyl alcohol CH3CH(OH)CH3 -88 82.3 inf. tert-Butyl alcohol (CH3)3COH 25 82.5 inf. Hexyl alcohol CH3(CH2)4CH2OH -52 156.5 0.6 Cyclohexanol OH 24 161.5 3.6 OH Ethylene glycol HO -12.6 197 inf. * Water solubility (g/100 mL H2O) Ch. 11 - 15 4. Synthesis of Alcohols from Alkenes Acid-catalyzed Hydration of Alkenes H C C C C H O ⊕ 2 H H OH H2O C C C C H H2O H O H H Ch. 11 - 16 Acid-Catalyzed Hydration of Alkenes ● Markovnikov regioselectivity ● Free carbocation intermediate ● Rearrangement of carbocation possible Ch. 11 - 17 Oxymercuration–Demercuration OH OH Hg(OAc)2 NaBH4 C C C C C C H2O, THF NaOH HgOAc H ● Markovnikov regioselectivity ● Anti stereoselectivity ● Generally takes place without the complication of rearrangements ● Mechanism Discussed in Section 8.6 Ch. 11 - 18 Hydroboration–Oxidation OH 1. BH3 THF H 2. H2O2, OH ● Anti-Markovnikov regioselectivity ● Syn-stereoselectivity ● Mechanism Discussed in Section 8.7 Ch. 11 - 19 Markovnikov regioselectivity OH + H , H2O or R 1. Hg(OAc)2, H2O, THF 2. NaBH , NaOH 4 H R 1. BH3 • THF H 2. H2O2, NaOH OH R Anti-Markovnikov regioselectivity Ch. 11 - 20 Example Synthesis? (1) OH OH Synthesis? (2) Ch. 11 - 21 Synthesis (1) H OH ● Need anti-Markovnikov addition of H–OH ● Use hydroboration-oxidation H OH 1. BH3 • THF 2. H2O2, NaOH Ch. 11 - 22 Synthesis (2) OH H ● Need Markovnikov addition of H–OH ● Use either acid-catalyzed hydration or oxymercuration-demercuration ● Acid-catalyzed hydration is NOT desired due to rearrangement of carbocation Ch. 11 - 23 Acid-catalyzed hydration HO H⊕ H2O H Rearrangement of carbocation (2o cation) Ch. 11 - 24 Oxymercuration-demercuration OH H Hg(OAc)2 OH NaBH4 H2O, THF NaOH HgOAc Ch. 11 - 25 5. Reactions of Alcohols The reactions of alcohols have mainly to do with the following ● The oxygen atom of the –OH group is nucleophilic and weakly basic ● The hydrogen atom of the –OH group is weakly acidic ● The –OH group can be converted to a leaving group so as to allow substitution or elimination reactions Ch. 11 - 26 δ− δ+ O C–O & O–H bonds of an H + δ alcohol are polarized Protonation of the alcohol converts a poor leaving group (OH⊖) into a good one (H2O) H C O H + H A C O H + A alcohol strong protonated acid alcohol Ch. 11 - 27 Once the alcohol is protonated substitution reactions become possible H H SN2 Nu + C O H Nu C + O H protonated alcohol The protonated –OH group is a good leaving group (H2O) Ch. 11 - 28 6. Alcohols as Acids Alcohols have acidities similar to that of water pK a Values for Some Weak Acids Acid pKa CH3OH 15.5 H2O 15.74 CH3CH2OH 15.9 (CH3)3COH 18.0 Ch. 11 - 29 Relative Acidity H2O & alcohols are the strongest acids in this series H2O > ROH > RC CH > H2 > NH3 > RH Increasing acidity Relative Basicity OH⊖ is the weakest acid in this series R > NH2 > H > RC C > RO > HO Increasing basicity Ch. 11 - 30 7. Conversion of Alcohols into Alkyl Halides R OH R X ● HX (X = Cl, Br, I) ● PBr3 ● SOCl2 Ch. 11 - 31 Examples OH conc. HCl Cl + HOH 25oC (94%) OH PBr3 Br (63%) Ch. 11 - 32 8. Alkyl Halides from the Reaction of Alcohols with Hydrogen Halides R OH + HX R X + H2O The order of reactivity of alcohols ● 3o > 2o > 1o < methyl The order of reactivity of the hydrogen halides ● HI > HBr > HCl (HF is generally unreactive) Ch. 11 - 33 R OH + NaX No Reaction! OH⊖ is a poor leaving group H R OH + NaX R X X R O H ⊕ H3O is a good H leaving group Ch. 11 - 34 8A. Mechanisms of the Reactions of Alcohols with HX Secondary, tertiary, allylic, and benzylic alcohols appear to react by a mechanism that involves the formation of a carbocation Step 1 H + H O H H + O H O O H fast H H Ch. 11 - 35 Step 2 H + O H O slow H H Step 3 + Cl fast Cl Ch. 11 - 36 Primary alcohols and methanol react to form alkyl halides under acidic conditions by an SN2 mechanism H H H H X + R C O H X C R + O H H H (a good protonated 1o alcohol leaving group) or methanol Ch. 11 - 37 9. Alkyl Halides from the Reaction of Alcohols with PBr3 or SOCl2 Reaction of alcohols with PBr3 3 R OH + PBr3 R Br + H3PO3 (1o or 2o) ● The reaction does not involve the formation of a carbocation and usually occurs without rearrangement of the carbon skeleton (especially if the temperature is kept below 0°C) Ch. 11 - 38 Reaction of alcohols with PBr3 ● Phosphorus tribromide is often preferred as a reagent for the transformation of an alcohol to the corresponding alkyl bromide Ch. 11 - 39 Mechanism Br PBr2 R OH + P R O + Br Br Br H protonated alkyl dibromophosphite PBr2 Br + R O R Br + HOPBr2 H a good leaving group Ch. 11 - 40 Reaction of alcohols with SOCl2 o o ● SOCl2 converts 1 and 2 alcohols to alkyl chlorides ● As with PBr3, the reaction does not involve the formation of a carbocation and usually occurs without rearrangement of the carbon skeleton (especially if the temperature is kept below 0°C) ● Pyridine (C5H5N) is often included to promote the reaction Ch. 11 - 41 Mechanism O H O Cl R O H + Cl S Cl R O S Cl N − Cl (C5H5N) O H O N + R O S Cl R O S Cl Ch. 11 - 42 Mechanism O O − Cl N + R O S Cl R O S N Cl⊖ O + O O + N S R Cl O S N Ch. 11 - 43 10. Tosylates, Mesylates, & Triflates: Leaving Group Derivatives of Alcohols O OTs = O S CH3 (Tosylate) O O OMs = O S CH3 (Mesylate) O Ch. 11 - 44 Direct displacement of the –OH group with a nucleophile via an SN2 reaction is not possible since OH⊖ is a very poor leaving group OH + Nu No Reaction! Thus we need to convert the OH⊖ to a better leaving group first Ch. 11 - 45 Mesylates (OMs) and Tosylates (OTs) are good leaving groups and they can be prepared easily from an alcohol (methane sulfonyl chloride) O pyridine OH + CH3 S Cl O O O S CH + + Cl 3 N O same as H OMs (a mesylate) Ch. 11 - 46 Preparation of Tosylates (OTs) from an alcohol (p-toluene sulfonyl chloride) O pyridine OH + H3C S Cl O O O S CH + + Cl 3 N O same as H OTs (a tosylate) Ch.