Organic Chemistry Chapter 18 ETHERS AND EPOXIDES THIOLS AND SULFIDES Chapter Contents 18 1 Names and Properties of Ethers 18 2 Preparing Ethers 18 3 Reactions of Ethers Acidic Cleavage 18 4 Cyclic Ethers Epoxides 18 5 Reactions of Epoxides Ring Opening 18 6 Crown Ethers 18 7 Thiols and Sulfides 18 8 Spectroscopy of Ethers Preview of Carbonyl Chemistry Ethers Diethyl Ether Anisole and Tetrahydrofuran Naming Ethers No Other Functional Groups Naming Ethers Other Functional Groups Ether Geometry Preparing Ethers Industrially with H2SO4 and catalyst Preparing Ethers Williamson Ether Synthesis part 1 Alternative to Williamson is with the use of Ag2O direct reaction no salt as intermediate Preparing Ethers Williamson Ether Synthesis part 3 Tertiary halides compete with E2 Because the Williamson synthesis is an SN2 reaction it is subject to all the usual constraints Primary halides and tosylates work best because competitive E2 elimination can occur with more hindered substrates Previous chapter Alcohol Preparation part 1 Addition to a double bond Preparing Ethers Alkoxymercuration of Alkenes by electrophilic addition of Hg2 to the alkene Mercuric trifluoroacetate Worked Example 18 1 Synthesizing an Ether How would you prepare ethyl phenyl ether Use whichever method you think is more appropriate Williamson synthesis or the alkoxymercuration reaction Worked Example 18 1 Strategy Draw the target ether identify the two groups attached to oxygen and recall the limitations of the two methods for preparing ethers Williamson synthesis uses an SN2 reaction and requires that one of the two groups attached to oxygen be either secondary or preferably primary The alkoxymercuration reaction requires that one of the two groups come from an alkene precursor Ethyl phenyl ether could be made by either method Worked Example 18 1 Solution Reactions of Ethers Acidic Cleavage part 1 Reactions of Ethers Acidic Cleavage part 2 Reactions of Ethers Acidic Cleavage part 3 Worked Example 18 2 Predicting the Product of an Ether Cleavage Reaction Predict the products of the following reaction Worked Example 18 2 Strategy Identify the substitution pattern of the two groups attached to oxygen in this case a tertiary alkyl group and a primary alkyl group Then recall the guidelines for ether cleavages An ether with only primary and secondary alkyl groups usually undergoes cleavage by SN2 attack of a nucleophile on the less hindered alkyl group but an ether with a tertiary alkyl group usually undergoes cleavage by an SN1 mechanism In this case an SN1 cleavage of the tertiary C O bond will occur giving 1 propanol and a tertiary alkyl bromide In addition a competitive E1 reaction leading to alkene might occur Worked Example 18 2 Solution Cyclic Ethers Epoxides part 1 Cyclic Ethers Epoxides part 2 intermediate in the manufacture of both ethylene glycol used for automobile antifreeze and polyester polymers Cyclic Ethers Epoxides part 3 Cyclic Ethers Epoxides part 4 Acid Catalyzed Epoxide Opening part 1 Acid Catalyzed Epoxide Opening part 2 Acid Catalyzed Epoxide Opening part 3 When both epoxide carbon atoms are either primary or secondary attack of the nucleophile occurs primarily at the less highly substituted site an SN2 like result When one of the epoxide carbon atoms is tertiary however nucleophilic attack occurs primarily at the more highly substituted site an SN1 like result Figure 18 2 No racemic thus SN2 character of the TS Ring opening of 1 2 epoxy 1 methylcyclohexane with HBr There is a high degree of SN1 like carbocation character in the transition state which leads to backside attack of the nucleophile at the tertiary center and to formation of a product isomer that has Br and OH groups trans Worked Example 18 3 Predicting the Product of Epoxide Ring Opening Predict the major product of the following reaction Worked Example 18 3 Strategy Identify the substitution pattern of the two epoxide carbon atoms In this case one carbon is secondary and one is primary Then recall the guidelines for epoxide cleavages An epoxide with only primary and secondary carbons usually undergoes cleavage by SN2 like attack of a nucleophile on the less hindered carbon but an epoxide with a tertiary carbon atom usually undergoes cleavage by backside attack on the more hindered carbon In this case an SN2 cleavage of the primary C O epoxide bond will occur Worked Example 18 3 Solution Base Catalyzed Epoxide Opening part 1 Unlike other ethers epoxide rings can be cleaved by bases and nucleophiles as well as by acid Although an ether oxygen is normally a poor leaving group in an SN2 reaction the strain of the three membered ring causes epoxides to react with hydroxide ion at elevated temperatures Base Catalyzed Epoxide Opening part 2 Base Catalyzed Epoxide Opening part 3 Base Catalyzed Epoxide Opening part 4 Crown Ethers 18 Crown 6 Ether The importance of crown ethers stems from their ability to sequester specific metal cations in the center of the polyether cavity 18 Crown 6 ether Ex Potassium permanganate KMnO4 dissolves in toluene in the presence of 18 crown 6 for instance and the resulting solution is a valuable reagent for oxidizing alkenes Crown Ethers Valinomycin antibiotic Thiols part 1 Thiols also called mercaptans are sulfur analogs of alcohols Thiols part 2 The reaction often works poorly unless an excess of the nucleophile is used because the product thiol can undergo a second SN2 reaction with alkyl halide to give a sulfide R S R as by product To circumvent this problem thiourea NH2 2C S Thiols part 4 This thiol disulfide interconversion is a key part of numerous biological processes Ex Sulfides part 1 Sulfides are the sulfur analogs of ethers just as thiols are the sulfur analogs of alcohols Sulfides part 2 Ex Sulfides Sulfides part 5 Figure 18 3 The infrared spectrum of diethyl ether CH3CH2OCH2CH3 Figure 18 4 The infrared spectrum of anisole Figure 18 5 The 1H NMR spectrum of dipropyl ether Protons on carbon next to oxygen are shifted downfield to 3 4 Figure 18 6 The 1H NMR spectrum of 1 2 epoxypropane