Chapter 18 Ethers and Epoxides; Thiols and Sulfides Ethers • Ethers (R–O–R’): – Organic derivatives of water, having two organic groups bonded to the same oxygen atom © 2016 Cengage Learning 2 NAMES AND PROPERTIES OF ETHERS 3 Nomenclature: Common Names • Simple ethers are named by identifying two organic substituents and adding the word ether – Name the groups in alphabetical order – Symmetrical: Use dialkyl or just alkyl © 2016 Cengage Learning 4 Nomenclature: IUPAC Names • The more complex alkyl group is the parent name • The group with the oxygen becomes an alkoxy group © 2016 Cengage Learning 5 Nomenclature: Cyclic Ethers (Heterocycles) • Heterocyclic: Oxygen is part of the ring. O • Epoxides (oxiranes) H2C CH2 O • Oxetanes • Furans (Oxolanes) O O • Pyrans (Oxanes) O O O • Dioxanes O © 2013 Pearson Education, Inc. 6 Epoxide Nomenclature • Name the starting alkene and add “oxide” © 2013 Pearson Education, Inc. 7 Epoxide Nomenclature • The oxygen can be treated as a substituent (epoxy) on the compound • Use numbers to specify position • Oxygen is 1, the carbons are 2 and 3 • Substituents are named in alphabetical order © 2013 Pearson Education, Inc. 8 Properties of Ethers • Possess nearly the same geometry as water – Oxygen atom is sp3-hybridized – Bond angles of R–O–R bonds are approximately tetrahedral • Polar C—O bonds © 2013 Pearson Education, Inc. 9 Properties of Ethers: Hydrogen Bond • Hydrogen bond is a attractive interaction between an electronegative atom and a hydrogen atom bonded to another electronegative atom • Ethers cannot hydrogen bond with other ether molecules, so they have a lower boiling point than alcohols • Ether molecules can hydrogen bond with water and alcohol molecules • They are hydrogen bond acceptors © 2013 Pearson Education, Inc. 10 Properties of Ethers • Very useful as solvents in the laboratory – They can dissolve nonpolar and polar substances – They are unreactive toward strong bases • Ionic substance are moderately soluble in ethers – Lithium iodide • The small lithium cation is strongly solvated by the ether’s lone pairs of electrons • Ether cannot serve as hydrogen bond donors – Does not solvate small anions well © 2013 Pearson Education, Inc. 11 Worked Example • Name the following ethers: a) b) • Solution: – a) Di-isopropyl ether – b) Allyl vinyl ether 12 ETHER PREPARATION 13 Synthesis of Ethers • Simple symmetrical ethers are prepared industrially by sulfuric acid (H2SO4) catalyzed reaction of alcohols – Bimolecular condensation of alcohols – Limited to use with primary alcohols • 2o and 3o alcohols dehydrate by to form alkenes – If temperature is too high, alkene forms © 2016 Cengage Learning 14 Williamson Ether Synthesis • Best method for the preparation of ethers • This method involves an SN2 attack of the alkoxide on an unhindered primary halide or tosylate – The alkoxide is commonly made by adding a strong base (i.e. NaH) to the alcohol © 2016 Cengage Learning 15 Silver Oxide-Catalyzed Ether Formation • Reaction of alcohols with Ag2O directly with alkyl halide forms ether in one step Glucose reacts with excess iodomethane in the presence of Ag2O to generate a pentaether in 85% yield © 2016 Cengage Learning 16 Worked Example • How are the following ethers prepared using a Williamson synthesis? a) Methyl propyl ether b) Anisole (methyl phenyl ether) • Solution: a) b) 17 To convert two alcohols to an ether, convert the more hindered alcohol to its alkoxide. Convert the less hindered alcohol to its tosylate (or an alkyl halide). Make sure the tosylate (or halide) is a good SN2 substrate. 18 Alkoxymercuration of Alkenes • Alkene is treated with an alcohol in the presence of mercuric acetate or mercuric trifluoroacetate – Demercuration with NaBH4 yields an ether – Markovnikov addition of alcohol to alkene • Primary, secondary and tertiary alcohols will react with this synthesis – Ditertiary ethers can not be prepared due to steric hindrance © 2016 Cengage Learning 19 Worked Example • Rank the following halides in order of their reactivity in Williamson synthesis: a) Bromoethane, 2-bromopropane, bromobenzene b) Chloroethane, bromoethane, 1-iodopropene • Solution: Most reactive Least reactive a) b) 20 REACTIONS OF ETHERS 21 Cleavage of Ethers • Ethers are unreactive, which makes them ideal solvents for a lot of different reactions • They can be cleaved by heating with concentrated HBr and HI • Reactivity: HI > HBr © 2016 Cengage Learning 22 Mechanism of Ether Cleavage • Step 1: Protonation of the oxygen. • Step 2: The halide will attack the carbon and displace the alcohol (SN2). © 2013 Pearson Education, Inc. 23 Mechanism of Ether Cleavage • Step 3: The alcohol reacts further with the acid to produce another mole of alkyl halide – This does not occur with aromatic alcohols (phenols) © 2013 Pearson Education, Inc. 24 Phenyl Ether Cleavage • Phenol cannot react further to become a halide because an SN2 reaction cannot occur on an sp2 carbon © 2013 Pearson Education, Inc. 25 HBr and HI convert both alkyl groups (but not aromatic groups) of an ether to alkyl halides. Phenolic products are unreactive, however. 26 Worked Example • Predict the product(s) of the following reaction: • Solution: – A primary alkyl group and a tertiary alkyl group is bonded to the ether oxygen – When one group is tertiary, cleavage occurs by an SN1 or E1 route to give either an alkene or a tertiary halide and a primary alcohol © 2016 Cengage Learning 27 REACTIONS OF ETHERS 28 Reactions of Ethers: Claisen Rearrangement • Claisen rearrangement occurs with – Allyl aryl ethers – Allyl vinyl ethers • Caused by heating ally aryl ether to 200-250°C © 2016 Cengage Learning 29 Reactions of Ethers: Claisen Rearrangement • Takes place in a single step through a pericyclic mechanism – Reorganization of bonding electrons of a six- membered, cyclic transition state © 2016 Cengage Learning 30 Worked Example • What products are expected from Claisen rearrangement of 2- butenyl phenyl ether? • Solution: – Six bonds will either be broken or formed in the product - Represented by dashed lines in the transition state – Redrawing bonds to arrive at the intermediate enone – Rearranges to the more stable phenol © 2016 Cengage Learning 31 CYCLIC ETHERS 32 Cyclic Ethers • Behave like acyclic ethers with the exception of three-membered ring called epoxides – Strain of the three-membered ring gives epoxides a unique chemical reactivity 33 Preparation of Epoxides • Ethylene oxide is industrially important as an intermediate – Prepared by reaction of ethylene with oxygen at 300 °C over a silver oxide catalyst – -ene ending used because it is made from ethylene © 2016 Cengage Learning 34 Preparation of Epoxides • Epoxides are prepared in a laboratory – By treating alkenes with a peroxyacid (RCO3H) © 2016 Cengage Learning 35 Preparation of Epoxides • Epoxides are prepared in a laboratory – From halohydrins • Addition of HO–X to an alkene gives a halohydrin • Treatment of a halohydrin with base gives an epoxide – Intramolecular Williamson ether synthesis © 2016 Cengage Learning 36 Worked Example • Explain why reaction of cis-2-butene with m- chloroperoxybenzoic acid yields an epoxide different from that obtained by reaction of the trans isomer • Solution: – Epoxidation, in this case, is a syn addition of oxygen to a double bond – Original bond stereochemistry is retained; product is a meso compound 37 Worked Example – Reaction of trans-2-butene with m- chloroperoxybenzoic acid yields trans-2,3 epoxybutane 38 REACTIONS OF EPOXIDES: 39 Reactions of Epoxides: Ring-Opening • Water adds to epoxides with dilute acid at room temperature – Product is a 1,2-diol • Epoxides can be opened by reaction with acids + other than H3O © 2016 Cengage Learning 40 Reactions of Epoxides: Ring-Opening • Remember the bromination of alkenes • Anhydrous HF, HBr, HCl, or HI combine with an epoxide © 2016 Cengage Learning 41 Reactions of Epoxides: Ring-Opening • Regiochemistry of acid- catalyzed ring-opening depends on the epoxide’s structure • Nucleophilic attack occurs primarily at the more highly substituted site, when one epoxide carbon atoms is tertiary © 2016 Cengage Learning 42 Reactions of Epoxides: Ring-Opening • Regiochemistry of acid- catalyzed ring-opening depends on the epoxide’s structure • Nucleophilic attack occurs primarily at the more highly substituted site, when one epoxide carbon atoms is tertiary Ring-Opening of 1,2-epoxy-1- methylcyclohexane with HBr © 2016 Cengage Learning 43 Worked Example • Predict the major product of the following reaction: • Solution: © 2016 Cengage Learning 44 Base-Catalyzed Epoxide Opening • Epoxide rings can be cleaved by bases, nucleophiles, and acids – Strain of the three-membered ring is relieved on ring-opening • Hydroxide cleaves epoxides at elevated temperatures © 2016 Cengage Learning 45 Base-Catalyzed Epoxide Opening • Amines can be used for epoxide opening • Grignard reagents can be used for epoxide opening – Converts a Grignard reagent into a primary alcohol © 2016 Cengage Learning 46 Worked Example • Predict the major product of the following reaction: • Solution: – Addition of a Grignard reagent takes place at the less substituted epoxide carbon © 2016 Cengage Learning 47 CROWN ETHERS 48 Crown Ethers • Crown Ethers are – Large-ring polyethers – Named as x-crown-y • x is total number of atoms in the ring • y is the number of oxygen atoms • Central cavity is electronegative and attracts cations © 2016 Cengage Learning 49 Crown Ether Complexes • Crown ethers can complex metal cations in the center of the ring •