3-1 Topic 3 Alcohols and Ethers 11.1 3-2 Alcohols and Ethers alcohol Examples: ' ether 3C C3 ( )-Menthol Vanillin Anethole (from peppermint) (from vanilla beans) (from fennel) n Poly(phenyl ether) (PPE) CEM 2312 all 2017 n Polyethylene glycol (PEG)
11.1 3-3 omenclature: Alcohols 3 C 3 C methanol ethanol propanol alkane => alkanol or methyl alcohol ethyl alcohol propionaldehdye alkyl alcohol Alcohols are classified as 1 (primary), 2 (secondary), or 3 (tertiary), depending on the number of carbons bonded to the alcohol carbon: propanol 2-propanol 2-methyl-2-propanol (propyl alcohol) (isopropyl alcohol) (tert-buty alcohol) Compounds with a hydroxyl group attached directly to a benzene ring are called phenols: phenol 3 C p-methyl phenol (p-cresol) 11.1 3-4 omenclature: Ethers 3 C C 3 C 3 3 C dimethyl ether ethyl methyl ether allyl ethyl ether ' alkane => alkyl alkyl ether or more complicated structures, the IUPAC substitutive name for ethers should be used where the group is named an alkoxy group: C 3 3 C 3 C C 3 2-methoxypentane 1-ethoxy-4-methylbenzene 1,2-dimethoxyethane (DME) Cyclic ethers can be named based on replacement nomenclature using the prefix oxa. A cyclic 3-membered ether is named oxirane, a 4-membered ether is called oxetane: oxacyclopropane oxacyclobutane oxacyclopentane 1,4-dioxacyclohexane oxirane oxetane (tetrahydrofurane) (1,4-dioxane) CEM 2312 all 2017
3-5 Problem: Give IUPAC names for the following compounds. 11.2 3-6 Physical Properties diethyl ether pentane 1-butanol MW 72 MW 72 MW 74 b.p. 34.6 C b.p. 36 C b.p. 117.7 C Ethers have boiling points that are comparable with those of hydrocarbons of the same molecular weight (MW) Alcohols have much higher boiling points than comparable ethers or hydrocarbons Water solubility: Both ethers and alcohols are able to form hydrogen bonds with water Ethers have solubilitiesthat are similar to those of alcohols of the same molecular weight (but are very different from those of hydrocarbons) gradually decreases as the hydrocarbon portion of the molecule increases CEM 2312 all 2017
11.2 3-7 Physical Properties: Alcohols 3-8 Problem: The antifreeze compound 1,2-ethanediol (ethylene glycol) has a higher boiling point than either propyl or isopropyl alcohol (see Table on slide 2-7), even though all compounds have roughly the same molecular weight. Propose an explanation. CEM 2312 all 2017
11.2 3-9 Physical Properties: Ethers 11.3 3-10 Ethanol Can be made by the fermentation of sugars, and it is the alcohol of all alcoholic beverages. ote: Ethanol content limited to 12-15% as yeast enzymes are deactivated at higher concentrations Industrial ethanol is produced by acid-catalyzed hydration of ethene: CEM 2312 all 2017
11.3 3-11 Diethyl Ether Low boiling, highly flammable liquid eacts slowly with oxygen by a radical process called autoxidation to form hydroperoxides and peroxides 11.4 3-12 1. Acid-catalyzed hydration: Synthesis of Alcohols from Alkenes cat. 2 S 4 2 Mechanism: CEM 2312 all 2017
11.4 3-13 2. xymercuration-demercuration: g(ac) 2, 2 ab 4, xymercuration: g Ac g mercurinium ion g 11.4 3-14 3. ydroboration-xidation: B 3, T 2 2, Mechanism: B B alkyl borane Ph B Ph Ph trialkyl borane Ph Ph Ph Ph B B B 2 CEM 2312 all 2017
3-15 Problem: Predict the major product(s) for each of the following reactions: cat. 2 S 4 2 1. B 3 -T 2. 2 2, a 1. g(ac) 2, 2 2. ab 4, a 11.5 3-16 eactivity of Alcohols The oxygen of an alcohol polarizes the both the C bond and the bond of an alcohol: Alcohols as bases: Alcohols as acids: CEM 2312 all 2017
11.6 3-17 Problem: Write equations for the acid-base reaction that would occur if ethanol were added to each of the following compounds: a a 2 a 11.7 3-18 Conversion of Alcohols into Alkyl alides conc. Cl 25 C conc. Br reflux PBr 3 10 to 0 C 3 C SCl 2 pyridine CEM 2312 all 2017
11.8 Alkyl alides from the eaction of Alcohols with ydrogen alides 3-19 + X X + 2 eactivity: 3 > 2 > 1 alcohols; I > Br > Cl ( is generally unreactive) Mechanism: + fast slow + Cl fast 11.8 3-20 otes: Primary alcohols are converted to alkyl halides under acidic conditions by an S 2 mechanism: Acid is required: The carbocation intermediate can undergo a rearrangement reaction: Br Br Br CEM 2312 all 2017
11.9 3-21 Alkyl alides from the eaction of Alcohols with PBr 3 3 + PBr 3 Br + 3 P 3 1 or 2 does not involve carbocation intermediate => occurs without rearrangement preferred reagent for the conversion of alcohols to alkyl bromides Mechanism: 11.9 Alkyl alides from the eaction of Alcohols with Thionylchloride + SCl 2 Cl + S 2 + Cl 1 or 2 3-22 Mechanism: CEM 2312 all 2017
11.10 3-23 Leaving Group Derivatives of Alcohols ucleophilic substitution with tosylates, mesylates, and triflates: 11.10 3-24 ote: Substitution at the sulfur atom of sulfonyl chloride follows an S 2 mechanism: S Cl S 2 S S CEM 2312 all 2017
11.11 3-25 Synthesis of Ethers 1. Intermolecular Dehydration of Alcohols: + 2. Williamson Ether Synthesis: A 2 a + ' X ' + ax 3. Alkoxymercuration-Demercuration: 1. g(c 3 C 2 ) 2 t-bu 2. ab 4, 4. tert-butyl Ethers by Alkylation of of Alcohols: + 2 S 4 11.11A 3-26 Intermolecular Dehydration of Alcohols Competition between acid-catalyzed dehydration and nucleophilic substitution: Mechanism: CEM 2312 all 2017
11.11B 3-27 Williamson Ether Synthesis a + ' X ' + ax ucleophilic substitution (S 2) Electrophilic substrate must be unhindered (1 or 2 alkyl halides or sufonates) and bear a good leaving group Example: a a + 2 I 11.11C 3-28 Problem: Propose a multistep synthesis for the following conversion: CEM 2312 all 2017
11.11E 3-29 Using Ethers as a Protecting Groups Challenge: Br + a tert-butyl Protecting Group Br + 2 S 4 Br 11.11 3-30 Silyl Ether Protecting Group + Me Me Cl Si t-bu imidazole DM Me Me Si t-bu imidazole Cleavage: Me Me Si t-bu Bu 4 + T + Me Me Si t-bu CEM 2312 all 2017
11.11 3-31 Problem: Supply the missing reagents and intermediates A-E. (TBS = tert-butyldimethylsilyl) A C 4 9 Br B TBS Br C TBS D Bu 4 + DM E 11.12 3-32 Cleavage of Ethers eating dialkyl ethers with strong acids (I, Br, and 2 S 4 ) results in cleavage + 2 Br Br + 2 Mechanism: Br + Br + Br + Br Br Br + 2 CEM 2312 all 2017
11.11 3-33 Problem: Propose a mechanism for the following reaction: Cl C 3 Cl 11.13 3-34 Epoxides an epoxide IUPAC: oxirane ethylene oxide Synthesis: 1. Epoxidation with meta-chloroperbenzoic acid + + Cl mcpba 81% Cl 2. Synthesis from bromohydrines: BS 2 Br a 60 C a bromohydrin 85% CEM 2312 all 2017
11.13 3-35 Epoxidation with mcpba occurs through a concerted transition state Mechanism: mcpba Cl Stereochemistry: concerted transition state mcpba + trans product (racemate) mcpba cis product 11.14 3-36 ing-pening of Epoxides Acid-Catalyzed ing-pening 3 + 2 1,2-diol ote: nucleophilic attack occurs at the more substituted carbon Base-Catalyzed ing-pening a ote: nucleophilic attack occurs at the less substituted carbon CEM 2312 all 2017
11.11 3-37 Problem: Propose a mechanism for the following reaction: Ph Mea Me Me Ph 3-38 Phenols omenclature: phenol Cl m-chlorophenol 1-naphthol 2-naphthol C 3 C 3 C 3 p-cresol m-cresol o-cresol hydroquinone resorcinol catechol CEM 2312 all 2017
3-39 Phenols: Acidity + 2 + 3 pk a = 9.89 phenol phenolate anion 2 2 2 C 3 Cl 2 2 2 pk a = 18 10.17 8.11 7.15 3.96 0.38 3-40 free energy transition state ΔG, A + 2 ΔG G = T ln K a K a = [ 3 + ][A ] [A][ 2 ] A + 3 + reaction coordinate Electron withdrawing substituents stabilize the negatively charged phenolate anion Electron donating substituents destabilize the negatively charged phenolate anion CEM 2312 all 2017
3-41 The degree of resonance stabilization depends on the substituent position: pk a = 7.15 pk a = 8.28 3-42 Problem: rder the following compounds with increasing pk a : CEM 2312 all 2017
3-43 Phenols: Synthesis 1. ydrolysis of aryldiazonium salts (slide 2-45) 2 a 2 Cu 2, Cu 2+ Cl 2 2. Industrial syntheses: Cl 2 Cl a a + e 350 C high pressure 2 2 S 4 3 P 4 250 C 95-135 C 50-90 C 3-44 Phenols: eactions 1. Phenol oxygen as nucleophile: Cl pyridine pyridine 1. a, 2 conc. Br 2. Br CEM 2312 all 2017
3-45 2. Aromatic -system as nucleophile: excess Br 2 3 2 S 4 conc. 2 S 4 3-46 Kolbe eaction: 1. a 2. C 2 3. 3 + Mechanism: CEM 2312 all 2017
3-47 Problem: Starting from phenol, suggest a synthesis for Aspirin Aspirin 3-48 Problem: Starting from phenol, suggest a synthesis for acetaminophen (Tylenol) Acetaminophen CEM 2312 all 2017
3-49 Epoxy Glues Two-component expoxy adhesives: + Cl a bisphenol A epichlorohydrin n 2 TETA (hardener) 2 = n cured epoxy resin CEM 2312 all 2017