9。零 CHAPTER 16 ETHERS EPOXIDES, AND SULFIDES n contrast to alcohols with their rich chemical reactivity, ethers(compounds contain- ng a C-o-C unit)undergo relatively few chemical reactions. As you saw when we discussed Grignard reagents in Chapter 14 and lithium aluminum hydride reduc- tions in Chapter 15, this lack of reactivity of ethers makes them valuable as solvents in a number of synthetically important transformations. In the present chapter you will learn of the conditions in which an ether linkage acts as a functional group, as well as the methods by which ethers are prepared Unlike most ethers, epoxides(compounds in which the C-O-C unit forms a three-membered ring) are very reactive substances. The principles of nucleophilic substi- tution are important in understanding the preparation and properties of epoxides Sulfides(rsr)are the sulfur analogs of ethers. Just as in the preceding chapter where we saw that the properties of thiols(RSH)are different from those of alcohols, we will explore differences between sulfides and ethers in this chapter. 16.1 NOMENCLATURE OF ETHERS, EPOXIDES, AND SULFIDES Ethers are named, in substitutive IUPAC nomenclature as alkoxy derivatives of alkanes Functional class IUPAC names of ethers are derived by listing the two alkyl groups in the general structure ROR'in alphabetical order as separate words, and then adding the word"ether"at the end. When both alkyl groups are the same, the prefix di- precedes the name of the alkyl group CH3CH,OCH,CH: CH3 CH,OCH3 CH3CH,OCH, CH, CH,CI Substitutive IuPac name: Ethoxyethane I-Chloro-3-ethoxypropane Functional class IUPAC name Diethyl ether 3-Chloropropyl ethyl ether 619 Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
619 CHAPTER 16 ETHERS, EPOXIDES, AND SULFIDES I n contrast to alcohols with their rich chemical reactivity, ethers (compounds containing a C±O±C unit) undergo relatively few chemical reactions. As you saw when we discussed Grignard reagents in Chapter 14 and lithium aluminum hydride reductions in Chapter 15, this lack of reactivity of ethers makes them valuable as solvents in a number of synthetically important transformations. In the present chapter you will learn of the conditions in which an ether linkage acts as a functional group, as well as the methods by which ethers are prepared. Unlike most ethers, epoxides (compounds in which the C±O±C unit forms a three-membered ring) are very reactive substances. The principles of nucleophilic substitution are important in understanding the preparation and properties of epoxides. Sulfides (RSR) are the sulfur analogs of ethers. Just as in the preceding chapter, where we saw that the properties of thiols (RSH) are different from those of alcohols, we will explore differences between sulfides and ethers in this chapter. 16.1 NOMENCLATURE OF ETHERS, EPOXIDES, AND SULFIDES Ethers are named, in substitutive IUPAC nomenclature, as alkoxy derivatives of alkanes. Functional class IUPAC names of ethers are derived by listing the two alkyl groups in the general structure ROR in alphabetical order as separate words, and then adding the word “ether” at the end. When both alkyl groups are the same, the prefix di- precedes the name of the alkyl group. CH3CH2OCH2CH3 Ethoxyethane Diethyl ether Substitutive IUPAC name: Functional class IUPAC name: CH3CH2OCH3 Methoxyethane Ethyl methyl ether CH3CH2OCH2CH2CH2Cl 1-Chloro-3-ethoxypropane 3-Chloropropyl ethyl ether Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER SIXTEEN Ethers, Epoxides, and Sulfides Ethers are described as symmetrical or unsymmetrical depending on whether the two groups bonded to oxygen are the same or different Unsymmetrical ethers are also called mixed ethers. Diethyl ether is a symmetrical ether; ethyl methyl ether is an unsymmet rical ether Cyclic ethers have their oxygen as part of a ring-they are heterocyclic compounds (Section 3. 15). Several have specific IUPAC names. Oxirane Oxolane Oxane (Ethylene oxide) (Tetrahydrofuran) (Tetrahydropyran) Recall from Section 6.18 that In each case the ring is numbered starting at the oxygen. The IUPAC rules also permit epoxides oxirane(without substituents)to be called ethylene oxide. Tetrahydrofuran and tetrahy -epoxy derivatives of alkanes dropyran are acceptable synonyms for oxolane and oxane, respectivel n substitutive IUPAC nomen. clature PROBLEM 16.1 Each of the following ethers has been shown to be or is sus- pected to be a mutagen, which means it can induce mutations in test cells. Write he structure of each of these ethers (a) Chloromethyl methyl ether (b)2-(Chloromethyl)oxirane(also known as epichlorohydrin) SAMPLE SOLUTION (a)Chloromethyl methyl ether has a chloromethyl group (CICH2-)and a methyl group (CH3)attached to oxygen. Its structure is Many substances have more than one ether linkage. Two such compounds, often used as solvents, are the diethers 1, 2-dimethoxyethane and 1, 4-dioxane. Diglyme, also CH3OCH2CH2OCH3 CH3OCH2CH2OCH2CH2OCH3 Molecules that contain several ether functions are referred to as polyethers. Polyethers have received much recent attention, and some examples of them will appear in Section 16.4 Sulfides are so The sulfur analogs(rs-)of alkoxy groups are called alkylthio groups. The first two of the following examples illustrate the use of alkylthio prefixes in substitutive thioethers, but this term is nomenclature of sulfides. functional class iupac names of sulfides are derived not part ot systematic iUPAc exactly the same way as those of ethers but end in the word"sulfide. Sulfur heterocy les have names analogous to their oxygen relatives, except that ox-is replaced by thi. Thus the sulfur heterocycles containing three-, four-, five, and six-membered rings are named thiirane, thietane, thiolane, and thane, respectively CH3CH2SCH, CH3 Ethylthioethane (Methylthio Thiirane Diethyl sulfide Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Ethers are described as symmetrical or unsymmetrical depending on whether the two groups bonded to oxygen are the same or different. Unsymmetrical ethers are also called mixed ethers. Diethyl ether is a symmetrical ether; ethyl methyl ether is an unsymmetrical ether. Cyclic ethers have their oxygen as part of a ring—they are heterocyclic compounds (Section 3.15). Several have specific IUPAC names. In each case the ring is numbered starting at the oxygen. The IUPAC rules also permit oxirane (without substituents) to be called ethylene oxide. Tetrahydrofuran and tetrahydropyran are acceptable synonyms for oxolane and oxane, respectively. PROBLEM 16.1 Each of the following ethers has been shown to be or is suspected to be a mutagen, which means it can induce mutations in test cells. Write the structure of each of these ethers. (a) Chloromethyl methyl ether (b) 2-(Chloromethyl)oxirane (also known as epichlorohydrin) (c) 3,4-Epoxy-1-butene (2-vinyloxirane) SAMPLE SOLUTION (a) Chloromethyl methyl ether has a chloromethyl group (ClCH2±) and a methyl group (CH3±) attached to oxygen. Its structure is ClCH2OCH3. Many substances have more than one ether linkage. Two such compounds, often used as solvents, are the diethers 1,2-dimethoxyethane and 1,4-dioxane. Diglyme, also a commonly used solvent, is a triether. Molecules that contain several ether functions are referred to as polyethers. Polyethers have received much recent attention, and some examples of them will appear in Section 16.4. The sulfur analogs (RS±) of alkoxy groups are called alkylthio groups. The first two of the following examples illustrate the use of alkylthio prefixes in substitutive nomenclature of sulfides. Functional class IUPAC names of sulfides are derived in exactly the same way as those of ethers but end in the word “sulfide.” Sulfur heterocycles have names analogous to their oxygen relatives, except that ox- is replaced by thi-. Thus the sulfur heterocycles containing three-, four-, five-, and six-membered rings are named thiirane, thietane, thiolane, and thiane, respectively. CH3CH2SCH2CH3 Ethylthioethane Diethyl sulfide SCH3 (Methylthio)cyclopentane Cyclopentyl methyl sulfide S Thiirane CH3OCH2CH2OCH3 1,2-Dimethoxyethane O O 1,4-Dioxane CH3OCH2CH2OCH2CH2OCH3 Diethylene glycol dimethyl ether (diglyme) 1 O 2 3 Oxirane (Ethylene oxide) O Oxetane O Oxolane (Tetrahydrofuran) O Oxane (Tetrahydropyran) 620 CHAPTER SIXTEEN Ethers, Epoxides, and Sulfides Recall from Section 6.18 that epoxides may be named as -epoxy derivatives of alkanes in substitutive IUPAC nomenclature. Sulfides are sometimes informally referred to as thioethers, but this term is not part of systematic IUPAC nomenclature. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
16.2 Structure and Bonding in Ethers and Epoxide 16.2 STRUCTURE AND BONDING IN ETHERS AND EPOXIDES Bonding in ethers is readily understood by comparing ethers with water and alcohols Van der Waals strain involving alkyl groups causes the bond angle at oxygen to be larger in ethers than alcohols, and larger in alcohols than in water. An extreme example is di tert-butyl ether, where steric hindrance between the tert-butyl groups is responsible for a dramatic increase in the C-o-c bond angle cH是cH,c1c是cc参a models of water ater Methanol Dimethyl ether Di-ferl-butyl ether ol, dimethyl ether, and (e typical carbon-oxygen bond distances in ethers are similar to those of alcohols their geometries, and examine pm)and are shorter than carbon-carbon bond distances in alkanes(153 pm). bond angle. Compare the C-o An ether oxygen affects the conformation of a molecule in much the same way bond distances in dimethyl ether that a CH2 unit does. The most stable conformation of diethyl ether is the all-staggered and di-tert-butyl ether. anti conformation. Tetrahydropyran is most stable in the chair conformation-a fact that has an important bearing on the structures of many carbohydrates Chair conformation of tetrahydropyraN Incorporating an oxygen atom into a three-membered ring requires its bond angle to be seriously distorted from the normal tetrahedral value In ethylene oxide, for exam- ple, the bond angle at oxygen is 61.5 H2C、CH2C-0- C angle615° C-C-O angle 59.20 Thus epoxides, like cyclopropanes, are strained. They tend to undergo reactions that open the three-membered ring by cleaving one of the carbon-oxygen bond PROBLEM 16.2 The heats of combustion of 1, 2-epoxybutane (2-ethyloxirane) and tetrahydrofuran have been measured: one is 2499 kJ/mol(597. 8 kcal/mol); the other is 2546 kJ/mol(609 1 kcal/mol). Match the heats of combustion with the respective compounds Ethers, like water and alcohols, are polar. Diethyl ether, for example, has a dipe moment of 1. 2 D Cyclic ethers have larger dipole moments; ethylene oxide and tetra drofuran have dipole moments in the 1.7-to 1. 8-D range--about the same as that of Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
16.2 STRUCTURE AND BONDING IN ETHERS AND EPOXIDES Bonding in ethers is readily understood by comparing ethers with water and alcohols. Van der Waals strain involving alkyl groups causes the bond angle at oxygen to be larger in ethers than alcohols, and larger in alcohols than in water. An extreme example is ditert-butyl ether, where steric hindrance between the tert-butyl groups is responsible for a dramatic increase in the C±O±C bond angle. Typical carbon–oxygen bond distances in ethers are similar to those of alcohols (142 pm) and are shorter than carbon–carbon bond distances in alkanes (153 pm). An ether oxygen affects the conformation of a molecule in much the same way that a CH2 unit does. The most stable conformation of diethyl ether is the all-staggered anti conformation. Tetrahydropyran is most stable in the chair conformation—a fact that has an important bearing on the structures of many carbohydrates. Incorporating an oxygen atom into a three-membered ring requires its bond angle to be seriously distorted from the normal tetrahedral value. In ethylene oxide, for example, the bond angle at oxygen is 61.5°. Thus epoxides, like cyclopropanes, are strained. They tend to undergo reactions that open the three-membered ring by cleaving one of the carbon–oxygen bonds. PROBLEM 16.2 The heats of combustion of 1,2-epoxybutane (2-ethyloxirane) and tetrahydrofuran have been measured: one is 2499 kJ/mol (597.8 kcal/mol); the other is 2546 kJ/mol (609.1 kcal/mol). Match the heats of combustion with the respective compounds. Ethers, like water and alcohols, are polar. Diethyl ether, for example, has a dipole moment of 1.2 D. Cyclic ethers have larger dipole moments; ethylene oxide and tetrahydrofuran have dipole moments in the 1.7- to 1.8-D range—about the same as that of water. H2C O CH2 147 pm 144 pm C O C C C O angle 61.5° angle 59.2° Anti conformation of diethyl ether Chair conformation of tetrahydropyran H H O 105° Water H CH 108.5° 3 O Methanol CH3 112° CH3 O Dimethyl ether 132° O C(CH3)3 (CH3)3C Di-tert-butyl ether 16.2 Structure and Bonding in Ethers and Epoxides 621 Use Learning By Modeling to make models of water, methanol, dimethyl ether, and di-tert-butyl ether. Minimize their geometries, and examine what happens to the C±O±C bond angle. Compare the C±O bond distances in dimethyl ether and di-tert-butyl ether. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER SIXTEEN Ethers, Epoxides, and Sulfides 16.3 PHYSICAL PROPERTIES OF ETHERS It is instructive to compare the physical properties of ethers with alkanes and With respect to boiling point, ethers resemble alkanes more than alcohols. With to solubility in water the reverse is true: ethers resemble alcohols more than CH3, CH3 CH3 CH, CH,CH2 CH3 CH3 CH,CH2CH,OH g point: 117°C ability in water: 7.5 g/100 mL Insoluble 9g/100mL In general, the boiling points of alcohols are unusually high because of hydrogen bonding(Section 4.5). Attractive forces in the liquid phases of ethers and alkanes, which ack -OH groups and cannot form intermolecular hydrogen bonds, are much weaker, and their boiling points lower. As shown in Figure 16.1, however, the presence of an oxygen atom permits ethers to participate in hydrogen bonds to water molecules. These attractive forces cause ethers to dissolve in water to approximately the same extent as comparably constituted alco- hols. Alkanes cannot engage in hydrogen bonding to water. PROBLEM 16. 3 Ethers tend to dissolve in alcohols and vice versa. Represent the hydrogen-bonding interaction between an alcohol molecule and an ether molecule 16. 4 CROWN ETHERS Ro:+M- R,O-M Ether Metal Ether-metal ion FIGURE 16.1 Hydro- gen bonding between di- and water. th attractive force betw een the neaa ed of diethyl ether and one of drogens of water. The ele trostatic potential surfaces illustrate the complementary interaction between the electron-rich (red) region o diethyl ether and the elec tron-poor (blue) region of Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
16.3 PHYSICAL PROPERTIES OF ETHERS It is instructive to compare the physical properties of ethers with alkanes and alcohols. With respect to boiling point, ethers resemble alkanes more than alcohols. With respect to solubility in water the reverse is true; ethers resemble alcohols more than alkanes. Why? In general, the boiling points of alcohols are unusually high because of hydrogen bonding (Section 4.5). Attractive forces in the liquid phases of ethers and alkanes, which lack ±OH groups and cannot form intermolecular hydrogen bonds, are much weaker, and their boiling points lower. As shown in Figure 16.1, however, the presence of an oxygen atom permits ethers to participate in hydrogen bonds to water molecules. These attractive forces cause ethers to dissolve in water to approximately the same extent as comparably constituted alcohols. Alkanes cannot engage in hydrogen bonding to water. PROBLEM 16.3 Ethers tend to dissolve in alcohols and vice versa. Represent the hydrogen-bonding interaction between an alcohol molecule and an ether molecule. 16.4 CROWN ETHERS Their polar carbon–oxygen bonds and the presence of unshared electron pairs at oxygen contribute to the ability of ethers to form Lewis acid-Lewis base complexes with metal ions. R2O Ether (Lewis base) M Metal ion (Lewis acid) R2O M Ether–metal ion complex CH3CH2OCH2CH3 Diethyl ether 35°C 7.5 g/100 mL Boiling point: Solubility in water: CH3CH2CH2CH2CH3 Pentane 36°C Insoluble CH3CH2CH2CH2OH 1-Butanol 117°C 9 g/100 mL 622 CHAPTER SIXTEEN Ethers, Epoxides, and Sulfides FIGURE 16.1 Hydrogen bonding between diethyl ether and water. The dashed line represents the attractive force between the negatively polarized oxygen of diethyl ether and one of the positively polarized hydrogens of water. The electrostatic potential surfaces illustrate the complementary interaction between the electron-rich (red) region of diethyl ether and the electron-poor (blue) region of water. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
16.4 Crown Ethers The strength of this bonding depends on the kind of ether. Simple ethers form relatively weak complexes with metal ions. A major advance in the area came in 1967 when Charles J. Pedersen of Du Pont described the preparation and properties of a class of Pedersen was a corecipient polyethers that form much more stable complexes with metal ions than do simple ethers. of the 1987 Nobel Prize in Pedersen prepared a series of macrocyclic polyethers, cyclic compounds contain- chemistry ing four or more oxygens in a ring of 12 or more atoms. He called these compounds crown ethers, because their molecular models resemble crowns. Systematic nomencla ture of crown ethers is somewhat cumbersome. and so pedersen devised a shorthand description whereby the word"crown"is preceded by the total number of atoms in the ring and is followed by the number of oxygen ator 12-Crown-4 18-Crown-6 he parent i 12-Crc and 18-crown-6 are a cyclic tetramer and hexamer, respectively, of repeat CH2- units; they are polyethers based on ethylene glycol(HOCH2CHrOH) Acohol PROBLEM 16.4 What organic compound mentioned earlier in this chapter is a yclic dimer of -OCH2CH2--units The metal-ion complexing properties of crown ethers are clearly evident in their effects on the solubility and reactivity of ionic compounds in nonpolar media. Potassium fluoride(Kf)is ionic and practically insoluble in benzene alone, but dissolves in it when 18-crown-6 is present. The reason for this has to do with the electron distribution of 18- crown-6 as shown in Figure 16.2a. The electrostatic potential surface consists of essen- tially two regions: an electron-rich interior associated with the oxygens and a hydrocarbon- FIGURE 16.2 like exterior associated with the CH2 groups. When KF is added to a solution of 18- electrostatic potential map crown-6 in benzene, potassium ion(K )interacts with the oxygens of the crown ether of 18-crown-6. The region of to form a Lewis acid-Lewis base complex. As can be seen in the space-filling model of highest electron density and their lone pairs. The outer periphery of the crown ether(blue)is relatively non polar(hydrocarbon-like)and soluble in nonpolar solvent fom o benzene.(b)Aspace crown ether where it is bound Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
The strength of this bonding depends on the kind of ether. Simple ethers form relatively weak complexes with metal ions. A major advance in the area came in 1967 when Charles J. Pedersen of Du Pont described the preparation and properties of a class of polyethers that form much more stable complexes with metal ions than do simple ethers. Pedersen prepared a series of macrocyclic polyethers, cyclic compounds containing four or more oxygens in a ring of 12 or more atoms. He called these compounds crown ethers, because their molecular models resemble crowns. Systematic nomenclature of crown ethers is somewhat cumbersome, and so Pedersen devised a shorthand description whereby the word “crown” is preceded by the total number of atoms in the ring and is followed by the number of oxygen atoms. 12-Crown-4 and 18-crown-6 are a cyclic tetramer and hexamer, respectively, of repeating ±OCH2CH2± units; they are polyethers based on ethylene glycol (HOCH2CH2OH) as the parent alcohol. PROBLEM 16.4 What organic compound mentioned earlier in this chapter is a cyclic dimer of ±OCH2CH2± units? The metal–ion complexing properties of crown ethers are clearly evident in their effects on the solubility and reactivity of ionic compounds in nonpolar media. Potassium fluoride (KF) is ionic and practically insoluble in benzene alone, but dissolves in it when 18-crown-6 is present. The reason for this has to do with the electron distribution of 18- crown-6 as shown in Figure 16.2a. The electrostatic potential surface consists of essentially two regions: an electron-rich interior associated with the oxygens and a hydrocarbonlike exterior associated with the CH2 groups. When KF is added to a solution of 18- crown-6 in benzene, potassium ion (K) interacts with the oxygens of the crown ether to form a Lewis acid-Lewis base complex. As can be seen in the space-filling model of O O O O 12-Crown-4 O O O O O O 18-Crown-6 16.4 Crown Ethers 623 Pedersen was a corecipient of the 1987 Nobel Prize in chemistry. (a) (b) FIGURE 16.2 (a) An electrostatic potential map of 18-crown-6. The region of highest electron density (red ) is associated with the negatively polarized oxygens and their lone pairs. The outer periphery of the crown ether (blue) is relatively nonpolar (hydrocarbon-like) and causes the molecule to be soluble in nonpolar solvents such as benzene. (b) A space- filling model of the complex formed between 18-crown-6 and potassium ion (K). K fits into the cavity of the crown ether where it is bound by Lewis acid-Lewis base interaction with the oxygens. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website