● CHAPTER 16 ETHERS, EPOXIDES, AND SULFIDES SOLUTIONS TO TEXT PROBLEMS 16.1 (b) Oxirane is the IUPAC name for ethylene oxide. A chloromethyl group(CICH,)is attached to position 2 of the ring in 2-(chloromethyl)oxirane CH,HC— CHCHO Oxirane 2-( Chloromethyl)oxiran This compound is more commonly known as epichlorohydrin (c) Epoxides may be named by adding the prefix epoxy to the IuPAC name of a parent compound, specifying by number both atoms to which the oxygen is attached CHa CHLCH=CH, H,C--CHCH=CH 1-Butene 3, 4-Epoxy-l-butene 16.2 1, 2-Epoxybutane and tetrahydrofuran both have the molecular formula C4HO--that is, they are constitutional isomers-and so it is appropriate to compare their heats of combustion directly. Angle strain from the three-membered ring of 1, 2-epoxybutane causes it to have more internal energy than tetrahydrofuran, and its combustion is more exothermic H,C一 CHCHCH 1, 2-Epoxybutane Tetrahydrofuran eat of combustion 2546 kJ/mol heat of combustion 2499 kJ/mol (609.1 kcal/mol (597.8 kcal/ 401 Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
401 CHAPTER 16 ETHERS, EPOXIDES, AND SULFIDES SOLUTIONS TO TEXT PROBLEMS 16.1 (b) Oxirane is the IUPAC name for ethylene oxide. A chloromethyl group (ClCH2@) is attached to position 2 of the ring in 2-(chloromethyl)oxirane. This compound is more commonly known as epichlorohydrin. (c) Epoxides may be named by adding the prefix epoxy to the IUPAC name of a parent compound, specifying by number both atoms to which the oxygen is attached. 16.2 1,2-Epoxybutane and tetrahydrofuran both have the molecular formula C4H8O—that is, they are constitutional isomers—and so it is appropriate to compare their heats of combustion directly. Angle strain from the three-membered ring of 1,2-epoxybutane causes it to have more internal energy than tetrahydrofuran, and its combustion is more exothermic. 1,2-Epoxybutane; heat of combustion 2546 kJ/mol (609.1 kcal/mol) H2C CHCH2CH3 Tetrahydrofuran; heat of combustion 2499 kJ/mol (597.8 kcal/mol) O O 1-Butene CH3CH2CH CH2 3,4-Epoxy-1-butene H2C CHCH CH2 O H2C CH2 Oxirane H2C CHCH2Cl 2-(Chloromethyl)oxirane O O 3 2 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
402 ETHERS, EPOXIDES, AND SULFIDES 16.3 An ether can function only as a proton acceptor in a hydrogen bond, but an alcohol can be either roton acceptor or a donor. The only hydrogen bond possible between an ether and an alcohol therefore the one shown Ether Alcohol 16.4 The compound is 1, 4-dioxane; it has a six-membered ring and two oxygens separated by CHy--Ch 1.4-dioxane (“6- crown-2”) 16.5 Protonation of the carbon-carbon double bond leads to the more stable carbocation (CH,),C=CH,+ H (CH3)2C—CH 2-Methylpropene tert-Butyl cation Methanol acts as a nucleophile to capture tert-butyl cation CH3 (CH3)2C-CH,+ (CH3)C Deprotonation of the alkyloxonium ion leads to formation of tert-butyl methyl ether. (CH3)3COCH3 H,OCH tert-Butyl methyl ether 16.6 Both alkyl groups in benzyl ethyl ether are primary, thus either may come from the alkyl halide in a williamson ether synthesis. The two routes to benzyl ethyl ether are CBH CH,ONa CH_ CH, Br C6HSCH2OCH, CH3 NaBr Sodium benzyloxide Bromoethane Benzyl ethyl ether Sodium C6H CH Br CHCH,ONa- CHS CH,OCH,CH3 NaBr Benzyl bromide Sodium ethoxide Benzyl ethyl ether 16.7(b) A primary carbon and a secondary carbon are attached to the ether oxygen. The secondary car- bon can only be derived from the alkoxide, because secondary alkyl halides cannot be used in the preparation of ethers by the williamson method. The only effective method uses an allyl (CH3)2CHONa t H,C=CHCH,Br- H,C=CHCH,OCH(CH3)2 NaBi Sodium isopropoxide Allyl bromide Allyl isopropyl ether Elimination will be the major reaction of an isopropyl halide with an alkoxide base Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
402 ETHERS, EPOXIDES, AND SULFIDES 16.3 An ether can function only as a proton acceptor in a hydrogen bond, but an alcohol can be either a proton acceptor or a donor. The only hydrogen bond possible between an ether and an alcohol is therefore the one shown: 16.4 The compound is 1,4-dioxane; it has a six-membered ring and two oxygens separated by CH2—CH2 units. 16.5 Protonation of the carbon–carbon double bond leads to the more stable carbocation. Methanol acts as a nucleophile to capture tert-butyl cation. Deprotonation of the alkyloxonium ion leads to formation of tert-butyl methyl ether. 16.6 Both alkyl groups in benzyl ethyl ether are primary, thus either may come from the alkyl halide in a Williamson ether synthesis. The two routes to benzyl ethyl ether are 16.7 (b) A primary carbon and a secondary carbon are attached to the ether oxygen. The secondary carbon can only be derived from the alkoxide, because secondary alkyl halides cannot be used in the preparation of ethers by the Williamson method. The only effective method uses an allyl halide and sodium isopropoxide. Elimination will be the major reaction of an isopropyl halide with an alkoxide base. (CH3)2CHONa Sodium isopropoxide Allyl bromide H2C CHCH2Br CHCH2OCH(CH3)2 NaBr Allyl isopropyl ether Sodium bromide H2C C6H5CH2Br CH 3CH2ONa Benzyl bromide Sodium ethoxide C6H5CH2OCH2CH3 NaBr Benzyl ethyl ether Sodium bromide C6H5CH2ONa CH 3CH2Br Sodium benzyloxide Bromoethane C6H5CH2OCH2CH3 NaBr Benzyl ethyl ether Sodium bromide (CH3)3C OCH3 H O H CH3 H2OCH3 (CH3)3COCH3 tert-Butyl methyl ether (CH3)2C CH3 (CH3)3C OCH3 H O H CH3 H (CH3)2C CH2 2-Methylpropene (CH3)2C CH3 tert-Butyl cation O O 1,4-dioxane (‘‘6-crown-2”) O R R Ether H O R Alcohol Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
ETHERS, EPOXIDES, AND SULFIDES 403 (c) Here the ether is a mixed primary-tertiary one. The best combination is the one that uses the primary alkyl halide CH3)COK CH CH, Br -(CH3),COCH, C6Hs t KBi Benzyl bromide Benzyl tert-butyl ether Potassium rt-butoxide The reaction between( CH3)3CBr and C6HS CH,O is elimination, not substitution. 16.8 CH,,OCH,CH3 60, Diethyl ether Oxygen Carbon Water 16.9(b) If benzyl bromide is the only organic product from reaction of a dialkyl ether with hydrogen bromide, then both alkyl groups attached to oxygen must be benzyl C6HSCH,OCH, C6H 2C6H5 CH,Br H,o Benzyl bromide Water (c) Since I mole of a dihalide, rather than 2 moles of a monohalide, is produced per mole of ether, the ether must be cyclic. 2HB, BrCH,CH, CH,CH, CH, Br H,O Tetrahydropyran 16.10 As outlined in text Figure 16.4, the first step is protonation of the ether oxygen to give a dialkylox onium ion Tetrahydrofuran Hydrogen Dialkyloxonium lodide In the second step, nucleophilic attack of the halide ion on carbon of the oxonium ion gives +C3-H Dialkyloxonium 4-lodo-l-butanol The remaining two steps of the mechanism correspond to those in which an alcohol is converted to an alkyl halide, as discussed in Chapter 4 OH, H+ +h,o: 4.Iodobutane Water Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
(c) Here the ether is a mixed primary–tertiary one. The best combination is the one that uses the primary alkyl halide. The reaction between (CH3)3CBr and C6H5CH2O is elimination, not substitution. 16.8 16.9 (b) If benzyl bromide is the only organic product from reaction of a dialkyl ether with hydrogen bromide, then both alkyl groups attached to oxygen must be benzyl. (c) Since 1 mole of a dihalide, rather than 2 moles of a monohalide, is produced per mole of ether, the ether must be cyclic. 16.10 As outlined in text Figure 16.4, the first step is protonation of the ether oxygen to give a dialkyloxonium ion. In the second step, nucleophilic attack of the halide ion on carbon of the oxonium ion gives 4-iodo-1-butanol. The remaining two steps of the mechanism correspond to those in which an alcohol is converted to an alkyl halide, as discussed in Chapter 4. Water I H2O I OH2 1,4-Diiodobutane I I I Hydrogen iodide H I 4-Iodo-1-butanol I OH OH2 I I Iodide ion Dialkyloxonium ion O H 4-Iodo-1-butanol I OH O Tetrahydrofuran I Iodide ion H I Hydrogen iodide Dialkyloxonium ion O H 2HBr heat O Tetrahydropyran BrCH2CH2CH2CH2CH2Br 1,5-Dibromopentane H2O Water Dibenzyl ether C6H5CH2OCH2C6H5 2C6H5CH2Br Benzyl bromide Water HBr heat H2O Diethyl ether CH3CH2OCH2CH3 Oxygen 6O2 Carbon dioxide 4CO2 Water 5H2O (CH KBr 3)3COCH2C6H5 Benzyl tert-butyl ether Potassium bromide (CH3)3COK Potassium tert-butoxide C6H5CH2Br Benzyl bromide ETHERS, EPOXIDES, AND SULFIDES 403 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
404 ETHERS, EPOXIDES, AND SULFIDES 16.11 The cis epoxide is achiral. It is a meso form containing a plane of symmetry. The trans isomer is hiral; its two mirror-image representations are not superposable Plane of symmetry H3C f影 cis-2,3-Epoxybutane Plane of symmetry passes Irans.2.3)_nc)forms ofage Neither the cis nor the trans epoxide is optically active when formed from the alkene. The cis epox ide is achiral; it cannot be optically active. The trans epoxide is capable of optical activity but is formed as a racemic mixture because achiral starting materials are used 16.12 (b) Azide ion [: N=N=N:] is a good nucleophile, reacting readily with ethylene oxide to yield 2-azidoethanol HC—CH NaN N, CHCH.OH Ethylene oxide (c) Ethylene oxide is hydrolyzed to ethylene glycol in the presence of aqueous base HC—CH HOCH,CH,OH (a) Phenyllithium reacts with ethylene oxide in a manner similar to that of a Grignard reagent. H,CCH2 1.CH, Li, diethylether C6H-CH, CH,OH Ethylene oxide 2-Phenylethanol (e) The nucleophilic species here is the acetylenic anion CH,CH,C=C:, which attacks a carbon atom of ethylene oxide to give 3-hexyn-l-ol HC—CH2 CH2CH2C≡CCH2CH2OH 16.13 Nucleophilic attack at C-2 of the starting epoxide will be faster than attack at C-1, because C-1 is ding to attack at c-1. is likely pound B Compound B not only arises by methoxide ion attack at C-2 but also satisfies the stereo- chemical requirement that epoxide ring opening take place with inversion of configuration at the site of substitution Compound B is correct. Compound C, although it is formed by methoxide substitution at the less crowded carbon of the epoxide, is wrong stereochemically. It requires Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
16.11 The cis epoxide is achiral. It is a meso form containing a plane of symmetry. The trans isomer is chiral; its two mirror-image representations are not superposable. Neither the cis nor the trans epoxide is optically active when formed from the alkene. The cis epoxide is achiral; it cannot be optically active. The trans epoxide is capable of optical activity but is formed as a racemic mixture because achiral starting materials are used. 16.12 (b) Azide ion is a good nucleophile, reacting readily with ethylene oxide to yield 2-azidoethanol. (c) Ethylene oxide is hydrolyzed to ethylene glycol in the presence of aqueous base. (d) Phenyllithium reacts with ethylene oxide in a manner similar to that of a Grignard reagent. (e) The nucleophilic species here is the acetylenic anion CH3CH2C>C: , which attacks a carbon atom of ethylene oxide to give 3-hexyn-1-ol. 16.13 Nucleophilic attack at C-2 of the starting epoxide will be faster than attack at C-1, because C-1 is more sterically hindered. Compound A, corresponding to attack at C-1, is not as likely as compound B. Compound B not only arises by methoxide ion attack at C-2 but also satisfies the stereochemical requirement that epoxide ring opening take place with inversion of configuration at the site of substitution. Compound B is correct. Compound C, although it is formed by methoxide substitution at the less crowded carbon of the epoxide, is wrong stereochemically. It requires Ethylene oxide H2C CH2 NH3 NaC CCH2CH3 3-Hexyn-1-ol (48%) CH3CH2C CCH2CH2OH O C6H5CH2CH2OH 2-Phenylethanol 1. C6H5 Li, diethyl ether 2. H3O Ethylene oxide H2C CH2 O HOCH2CH2OH Ethylene glycol NaOH H2O Ethylene oxide H2C CH2 O Ethylene oxide N3CH2CH2OH 2-Azidoethanol NaN3 ethanol–water H2C CH2 O N N ] [ N H3CH HCH3 O cis-2,3-Epoxybutane (Plane of symmetry passes through oxygen and midpoint of carbon–carbon bond.) CH3 H H3C H O H H 3CH CH3 O Nonsuperposable mirror-image (enantiomeric) forms of trans-2,3-epoxybutane Plane of symmetry 404 ETHERS, EPOXIDES, AND SULFIDES Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
ETHERS, EPOXIDES, AND SULFIDES 405 substitution with retention of configuration, which is not the normal mode of epoxide ring 16.14 Acid-catalyzed nucleophilic ring opening proceeds by attack of methanol at the more substituted carbon of the protonated epoxide. Inversion of configuration is observed at the site of attack. The correct product is compound A. H CHO 0 HO: CH Protonated Compound A form of 1-methyl-1. 2. epoxycyclopentane The nucleophilic ring openings in both this problem and Problem 16 13 occur by inversion of configuration. Attack under basic conditions by methoxide ion, however, occurs at the less hindered carbon of the epoxide ring, whereas attack by methanol under acid-catalyzed conditions occurs at the more substituted carbon 16.15 Begin by drawing meso-2, 3-butanediol, recalling that a meso form is achiral. The eclipsed confor- mation has a plane of symmetry Ho meso-23-Butanediol Epoxidation followed by acid-catalyzed hydrolysis results in anti addition of hydroxyl groups to the double bond. trans-2-Butene is the required starting material CH Ho H3C CH, COOH H,O+ H3C H > CH3 trans-2-Butene trans-2,3-Epoxybutane meso-23-Butanediol Osmium tetraoxide hydroxylation is a method of achieving syn hydroxylation. The necessary start ing material is cis-2-butene HO COOH. OsO, CH,COH. HO cis-2-Butene meso-23-Butanediol 16.16 Reaction of (R)-2-octanol with p-toluenesulfonyl chloride yields a p-toluenesulfonate ester (tosylate) having the same configuration; the stereogenic center is not involved in this step Reaction Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
substitution with retention of configuration, which is not the normal mode of epoxide ring opening. 16.14 Acid-catalyzed nucleophilic ring opening proceeds by attack of methanol at the more substituted carbon of the protonated epoxide. Inversion of configuration is observed at the site of attack. The correct product is compound A. The nucleophilic ring openings in both this problem and Problem 16.13 occur by inversion of configuration. Attack under basic conditions by methoxide ion, however, occurs at the less hindered carbon of the epoxide ring, whereas attack by methanol under acid-catalyzed conditions occurs at the more substituted carbon. 16.15 Begin by drawing meso-2,3-butanediol, recalling that a meso form is achiral. The eclipsed conformation has a plane of symmetry. Epoxidation followed by acid-catalyzed hydrolysis results in anti addition of hydroxyl groups to the double bond. trans-2-Butene is the required starting material. Osmium tetraoxide hydroxylation is a method of achieving syn hydroxylation. The necessary starting material is cis-2-butene. 16.16 Reaction of (R)-2-octanol with p-toluenesulfonyl chloride yields a p-toluenesulfonate ester (tosylate) having the same configuration; the stereogenic center is not involved in this step. Reaction O O C H3C CH3 H H C cis-2-Butene via meso-2,3-Butanediol (CH3)3COOH, OsO4(cat) (CH3)3COH, HO C H HO OH CH3 H CH3 H CH3 C H CH3 O C C O Os trans-2-Butene C C H3C H H CH3 trans-2,3-Epoxybutane O C C meso-2,3-Butanediol H3O C H CH3 CH3 H C H3C H OH H HO CH3 CH3COOH O meso-2,3-Butanediol C H HO OH CH3 H CH3 C CH3OH H O H O HO CH3 CH3 H H H Protonated form of 1-methyl-1,2- epoxycyclopentane Compound A H OCH3 CH3 HO CH3 ETHERS, EPOXIDES, AND SULFIDES 405 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
406 ETHERS, EPOXIDES, AND SULFIDES of the tosylate with a nucleophile proceeds by inversion of configuration in an Sy2 process. The product has the S configuration H,C H H-C CH3(CH)CH CH3(CH2)CH (R)-2-0ctanol (R)-l-Methy heptyl tosylate chloride HC yo}cm;+cAsx一 CHS (R)-1-Methy heptyl tosylate (S)1-Methylheptyl phenyl sulfide benzenethiolate 16.17 Phenyl vinyl sulfoxide lacks a plane of symmetry and is chiral. Phenyl vinyl sulfone is achiral a plane of symmetry passes through the phenyl and vinyl groups and the central sulfur atom. CSHE CH H,C=CH O H,C=CH Phenyl vinyl sulfoxide (chiral) 16.18 As shown in the text, dodecyldimethylsulfonium iodide may be prepared by reaction of dodecyl methyl sulfide with methyl iodide. An alternative method is the reaction of dodecyl iodide with dimethyl sulfide (CH3)2S+ CH, (CH))loCH,I CH3(CH)1oCHrS(CH3)2I Dimethyl The reaction of a sulfide with an alkyl halide is an Sn2 process. The faster reaction will be the one that uses the less sterically hindered alkyl halide. The method presented in the text will procee faster 16.19 The molecular ion from sec-butyl ethyl ether can also fragment by cleavage of a carbor bond in its ethyl group to give an oxygen-stabilized cation of m/z87 -CHCH,CHa CH3 CH2= CH3 m/87 16.20 All the constitutionally isomeric ethers of molecular formula CsHno belong to one of two general groups: CH,OCAHo and CH,CH,OC3H, Thus, we have CH_OCH, CH CH, CH3 CHyOCHCH, CH CH, OCH,CH(O CH,OC(CH,) Isobutyl methyl ether tert-Butyl methyl ether CHaCH2OCH, CH,, and CH, CH,OCH(CH3) Ethyl propyl ether Ethyl isopropyl ether Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
of the tosylate with a nucleophile proceeds by inversion of configuration in an SN2 process. The product has the S configuration. 16.17 Phenyl vinyl sulfoxide lacks a plane of symmetry and is chiral. Phenyl vinyl sulfone is achiral; a plane of symmetry passes through the phenyl and vinyl groups and the central sulfur atom. 16.18 As shown in the text, dodecyldimethylsulfonium iodide may be prepared by reaction of dodecyl methyl sulfide with methyl iodide. An alternative method is the reaction of dodecyl iodide with dimethyl sulfide. The reaction of a sulfide with an alkyl halide is an SN2 process. The faster reaction will be the one that uses the less sterically hindered alkyl halide. The method presented in the text will proceed faster. 16.19 The molecular ion from sec-butyl ethyl ether can also fragment by cleavage of a carbon–carbon bond in its ethyl group to give an oxygen-stabilized cation of mz 87. 16.20 All the constitutionally isomeric ethers of molecular formula C5H12O belong to one of two general groups: CH3OC4H9 and CH3CH2OC3H7. Thus, we have CH3CH2OCH2CH2CH3 and CH3CH2OCH(CH3)2 Ethyl propyl ether Ethyl isopropyl ether CH3OCH2CH(CH3)2 Isobutyl methyl ether CH3OC(CH3)3 tert-Butyl methyl ether CH3OCH2CH2CH2CH3 Butyl methyl ether CH3OCHCH2CH3 CH3 sec-Butyl methyl ether CH3 CH2 CHCH2CH3 CH3 O CH3 CH2 CHCH2CH3 CH3 O m/z 87 Dimethyl sulfide Dodecyl iodide Dodecyldimethylsulfonium iodide (CH3)2S CH3(CH2)10CH2 I CH3(CH2)10CH2S(CH3)2 I Phenyl vinyl sulfoxide (chiral) S C6H5 O H2C CH Phenyl vinyl sulfone (achiral) S C6H5 O O H2C CH 2 C6H5S Na Sodium benzenethiolate C6H5S C (R)-1-Methylheptyl tosylate (S)-1-Methylheptyl phenyl sulfide O S CH3 O O H CH3 C H H3C CH3(CH2)4CH2 CH2(CH2)4CH3 C OH H H3C CH3(CH2)4CH2 (R)-2-Octanol Cl CH3 O S O p-Toluenesulfonyl chloride C O H H3C CH3(CH2)4CH2 CH3 O S O (R)-1-Methylheptyl tosylate 406 ETHERS, EPOXIDES, AND SULFIDES Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
ETHERS, EPOXIDES, AND SULFIDES 407 These ethers could also have been named as"alkoxyalkane. Thus sec-butyl methyl ether would become 2-methoxybutane 16.21 Isoflurane and enflurane are both halogenated derivatives of ethyl methyl ether F-C-CH-O—CHF2 1-Chloro-2, 2, 2-trifluoroethyl Enflurane ClC-C-0—CHF 2-Chloro-1, 1, 2-trifluoroethyl difluoromethyl ether 16.22 (a) The parent compound is cyclopropane. It has a three-membered epoxide function, and thus a reasonable name is epoxycyclopropane. Numbers locating positions of attachment(as in 1, 2-epoxycyclopropane")are not necessary, because no other structures (1, 3 or 2, 3)are pos sible here (b) The longest continuous carbon chain has seven carbons, and so the compound is named as a derivative of heptane. The epoxy function bridges C-2 and C-4. Therefore H H H,CH3 (c) The oxygen atom bridges the C-1 and C-4 atoms of a cyclohexane ring 1, 4-Epoxycyclohexane (d) Eight carbon atoms are continuously linked and bridged by an oxygen. We name the com Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
These ethers could also have been named as “alkoxyalkanes.” Thus, sec-butyl methyl ether would become 2-methoxybutane. 16.21 Isoflurane and enflurane are both halogenated derivatives of ethyl methyl ether. Isoflurane: Enflurane: 16.22 (a) The parent compound is cyclopropane. It has a three-membered epoxide function, and thus a reasonable name is epoxycyclopropane. Numbers locating positions of attachment (as in “1,2-epoxycyclopropane”) are not necessary, because no other structures (1,3 or 2,3) are possible here. (b) The longest continuous carbon chain has seven carbons, and so the compound is named as a derivative of heptane. The epoxy function bridges C-2 and C-4. Therefore is 2-methyl-2,4-epoxyheptane. (c) The oxygen atom bridges the C-1 and C-4 atoms of a cyclohexane ring. (d) Eight carbon atoms are continuously linked and bridged by an oxygen. We name the compound as an epoxy derivative of cyclooctane. 1 5 2 3 4 6 7 8 O 1,5-Epoxycyclooctane O 1 2 3 5 4 6 1,4-Epoxycyclohexane CH2CH2CH3 H3C H3C 1 2 3 4 567 O O Epoxycyclopropane Cl C F H F F C O CHF2 2-Chloro-1,1,2-trifluoroethyl difluoromethyl ether F C F Cl F CH O CHF2 1-Chloro-2,2,2-trifluoroethyl difluoromethyl ether ETHERS, EPOXIDES, AND SULFIDES 407 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
408 ETHERS, EPOXIDES, AND SULFIDES 6.23 (a) There are three methyl-substituted thanes two of which are chiral (b) The locants in the name indicate the positions of the sulfur atoms in 1, 4-dithiane and 1,3,5- 1. 4-Dithiane 13.5-Trithiane (c) Disulfides possess two adjacent sulfur atoms. 1, 2-Dithiane is a disulfide. 1. 2-Dithiane (d) Two chair conformations of the sulfoxide derived from thane are possible; the oxygen atom may be either equatorial or axial 16.24 Intramolecular hydrogen bonding between the hydroxyl group and the ring oxygens is possible when the hydroxyl group is axial but not when it is equatorial HO Less stable conformation: More stable conformation: no intramolecular hydrogen bonding hydrogen bonding 16.25 The ethers that are to be prepared are CHaOCH, CH,CH3 CH,OCH(CH3)2 CH CH,OCH, Methyl propyl ether Isopropyl methyl ether Diethyl ether First examine the preparation of each ether by the williamson method. Methyl propyl ether can be prepared in two ways: CH, ONa CH, CHCH,Br CH,OCH,CH,CH 1-Bromopropane Methyl propyl ether CH3 Br CH3 CH, CH,ONa CH,OCH, CH, CH Sodium propoxide Methyl propyl ether Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
16.23 (a) There are three methyl-substituted thianes, two of which are chiral. (b) The locants in the name indicate the positions of the sulfur atoms in 1,4-dithiane and 1,3,5- trithiane. (c) Disulfides possess two adjacent sulfur atoms. 1,2-Dithiane is a disulfide. (d) Two chair conformations of the sulfoxide derived from thiane are possible; the oxygen atom may be either equatorial or axial. 16.24 Intramolecular hydrogen bonding between the hydroxyl group and the ring oxygens is possible when the hydroxyl group is axial but not when it is equatorial. 16.25 The ethers that are to be prepared are First examine the preparation of each ether by the Williamson method. Methyl propyl ether can be prepared in two ways: CH3Br Methyl bromide CH3CH2CH2ONa Sodium propoxide CH3OCH2CH2CH3 Methyl propyl ether CH3ONa Sodium methoxide CH3CH2CH2Br 1-Bromopropane CH3OCH2CH2CH3 Methyl propyl ether CH3OCH2CH2CH3 and Methyl propyl ether CH3OCH(CH3)2 Isopropyl methyl ether CH3CH2OCH2CH3 Diethyl ether O HO O Less stable conformation; no intramolecular hydrogen bonding O O O H More stable conformation; stabilized by hydrogen bonding S O S O S S 1,2-Dithiane S S 1,4-Dithiane S S S 1,3,5-Trithiane S CH3 2-Methylthiane (chiral) S CH3 3-Methylthiane (chiral) S CH3 4-Methylthiane (achiral) 408 ETHERS, EPOXIDES, AND SULFIDES Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
ETHERS, EPOXIDES, AND SULFIDES 409 Either combination is satisfactory. The necessary reagents are prepa shown CHOH CH ONa Methanol Sodium CHCH..OH (or HBr) CH,CH - Bromopropane CHB Meth Meth CHCH, CH,OH CHaCH,CHLONa Isopropyl methyl ether is best prepared by the reaction CHa Br +(CH3)2CHONa CH3OCH(CH3) Methyl bromide Sodium isopropoxide The reaction of sodium methoxide with isopropyl bromide will proceed mainly by elimination Methyl bromide is prepared as shown previously; sodium isopropoxide can be prepared by adding sodium to isopropyl alcohol. Diethyl ether may be prepared as outlined CHaCHLOH CHCHONa Sodium ethoxide CHa CH2OHfor HBr) CH3CH2Br Ethyl bromide CHaCHLONa CH3 CH, Br CHa CH,OCH- CH3 NaBr Sodium ethoxide Ethyl bromide Diethyl ether bromide 16.26 (a) Secondary alkyl halides react with alkoxide bases by E2 elimination as the major pathway The Williamson ether synthesis is not a useful reaction with secondary alkyl hali CH3CH CHCH3 CH; CH,CHCH,+ NaBr Sodium 2-butanolate Bromocyclohexane yclohexene Sodium (b) Sodium alkoxide acts as a nucleophile toward iodoethane to yield an alkyl ethyl ether. CH,CH, CH3 CHCH CH3 O Na CHaCH, -OCH,CH (R)-2-Ethoxybutane Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
Either combination is satisfactory. The necessary reagents are prepared as shown. Isopropyl methyl ether is best prepared by the reaction The reaction of sodium methoxide with isopropyl bromide will proceed mainly by elimination. Methyl bromide is prepared as shown previously; sodium isopropoxide can be prepared by adding sodium to isopropyl alcohol. Diethyl ether may be prepared as outlined: 16.26 (a) Secondary alkyl halides react with alkoxide bases by E2 elimination as the major pathway. The Williamson ether synthesis is not a useful reaction with secondary alkyl halides. (b) Sodium alkoxide acts as a nucleophile toward iodoethane to yield an alkyl ethyl ether. (R)-2-Ethoxybutane O Na CH3CH2 C I C OCH2CH3 CH CH3 3CH2 H CH CH3 3CH2 H CH3CH2CHCH3 ONa Sodium 2-butanolate Br Bromocyclohexane CH3CH2CHCH3 OH 2-Butanol Cyclohexene NaBr Sodium bromide CH3CH2ONa CH3CH2Br Sodium ethoxide Ethyl bromide CH3CH2OCH2CH3 Diethyl ether NaBr Sodium bromide CH3CH2OH Ethanol CH3CH2Br Ethyl bromide PBr3 (or HBr) CH3CH2OH Ethanol CH3CH2ONa Sodium ethoxide Na CH3Br Methyl bromide (CH3)2CHONa Sodium isopropoxide CH3OCH(CH3)2 Isopropyl methyl ether CH3CH2CH2OH 1-Propanol CH3CH2CH2ONa Sodium propoxide Na CH3OH Methanol CH3Br Methyl bromide PBr3 (or HBr) CH3CH2CH2OH 1-Propanol CH3CH2CH2Br 1-Bromopropane PBr3 (or HBr) CH3OH Methanol CH3ONa Sodium methoxide Na ETHERS, EPOXIDES, AND SULFIDES 409 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
410 ETHERS, EPOXIDES, AND SULFIDES The ether product has the same absolute configuration as the starting alkoxide because no bonds to the stereogenic center are made or broken in the reaction (c) Vicinal halohydrins are converted to epoxides on being treated with base CH CH,CHCH, Br CH2CHCH—CH2Br CHCH, CH-CH 1-Bromo2-butanol 1. 2-Epoxybutane (d) The reactants, an alkene plus a peroxy acid, are customary ones for epoxide preparation. The reaction is a stereospecific syn addition of oxygen to the double bone CH3 CH COOH COH (Z)-1-Phenylpropene Peroxybenzoic acid cis-2-Methyl-3- Benzoic acid (e) Azide ion is a good nucleophile and attacks the epoxide function Substitution occurs at carbon with inversion of configuration. The product is trans-2-azidocyclohexanol H 1. 2-Epoxycyclohexane trans-2. (f) Ammonia is a nucleophile capable of reacting with epoxides. It attacks the less hindered car- bon of the epoxide function Br Br CH,NH HC H,C Aryl halides do not react with nucleophiles under these conditions, and so the bromine sub- tituent on the ring is unaffected (g) Methoxide ion attacks the less substituted carbon of the epoxide ring with inversion of configuration CHC 6H5 CHCH5 epoxycyclohexane methoxycyclohexanol (98%6) Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
The ether product has the same absolute configuration as the starting alkoxide because no bonds to the stereogenic center are made or broken in the reaction. (c) Vicinal halohydrins are converted to epoxides on being treated with base. (d) The reactants, an alkene plus a peroxy acid, are customary ones for epoxide preparation. The reaction is a stereospecific syn addition of oxygen to the double bond. (e) Azide ion is a good nucleophile and attacks the epoxide function. Substitution occurs at carbon with inversion of configuration. The product is trans-2-azidocyclohexanol. ( f ) Ammonia is a nucleophile capable of reacting with epoxides. It attacks the less hindered carbon of the epoxide function. Aryl halides do not react with nucleophiles under these conditions, and so the bromine substituent on the ring is unaffected. (g) Methoxide ion attacks the less substituted carbon of the epoxide ring with inversion of configuration. 1-Benzyl-1,2- epoxycyclohexane 1-Benzyl-trans-2- methoxycyclohexanol (98%) CH2C6H5 O OCH3 OCH3 CH2C6H5 OH 2-(o-Bromophenyl)-2- methyloxirane 1-Amino-2-(o-bromophenyl)- 2-propanol C H3C OH CH2NH2 Br H3C Br O NH3 methanol 1,2-Epoxycyclohexane trans-2- Azidocyclohexanol (61%) H H O OH H N3 H NaN3 dioxane–water COH O (Z)-1-Phenylpropene Benzoic acid C C H H CH3 cis-2-Methyl-3- phenyloxirane H H O CH3 Peroxybenzoic acid COOH O CH3CH2CHCH2Br OH CH3CH2CH CH2 NaOH Br O CH3CH2CH CH2 1-Bromo-2-butanol 1,2-Epoxybutane O 410 ETHERS, EPOXIDES, AND SULFIDES Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website