Carey - Organic Chemistry - chapt16

Carey - Organic Chemistry - chapt16

(Parte 1 de 4)

CHAPTER 16 ETHERS, EPOXIDES, AND SULFIDES

In 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.

16.1NOMENCLATURE OF ETHERS, EPOXIDES, AND SULFIDES

Ethers are named, in substitutive IUPAC nomenclature, as alkoxyderivatives 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

EthoxyethaneDiethyl etherSubstitutive IUPAC name: Functional class IUPAC name:

CH3CH2OCH3

Methoxyethane Ethyl methyl ether

CH3CH2OCH2CH2CH2Cl

1-Chloro-3-ethoxypropane 3-Chloropropyl ethyl ether

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Ethers are described as symmetricalor unsymmetricaldepending 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.Tetrahydrofuranand tetrahydropyranare acceptable synonyms for oxolane and oxane, respectively.

PROBLEM 16.1Each 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

Many substances have more than one ether linkage. Two such compounds, often used as solvents, are the diethers1,2-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 alkylthiogroups. 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

CH3OCH2CH2OCH31,2-Dimethoxyethane OO1,4-Dioxane

CH3OCH2CH2OCH2CH2OCH3

Diethylene glycol dimethyl ether (diglyme)

Oxirane

(Ethylene oxide)

OOxetane O Oxolane

(Tetrahydrofuran)

Oxane (Tetrahydropyran)

620CHAPTER SIXTEENEthers, Epoxides, and Sulfides

Recall from Section 6.18 that epoxides may be named as -epoxyderivatives of alkanes in substitutive IUPAC nomenclature.

Sulfides are sometimes informally referred to as thioethers,but this term is not part of systematic IUPAC nomenclature.

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16.2STRUCTURE 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 CH2unit 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 16.2The 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.

147 pm

144 pm

C O C C C O angle 61.5° angle 59.2°

Anti conformation of diethyl etherChair conformation of tetrahydropyran

Methanol

Dimethyl ether

Di-tert-butyl ether

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.

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16.3PHYSICAL 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 16.3Ethers tend to dissolve in alcohols and vice versa. Represent the hydrogen-bonding interaction between an alcohol molecule and an ether molecule.

16.4CROWN 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.

Ether (Lewis base)

Metal ion (Lewis acid)

R2O M

Ether–metal ion complex

CH3CH2OCH2CH3 Diethyl ether

35°C7.5 g/100 mLBoiling point: Solubility in water:

CH3CH2CH2CH2CH3

CH3CH2CH2CH2OH

622CHAPTER SIXTEENEthers, 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.

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The strength of this bonding depends on the kind of ether. Simple ethers form relatively weak complexes with metal ions. Amajor advance in the area came in 1967 when Charles J. Pedersen of Du Pont described the preparation and properties of a class of polyethersthat 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 repeat- ing ±OCH2CH2±units; they are polyethers based on ethylene glycol (HOCH2CH2OH) as the parent alcohol.

PROBLEM 16.4What 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 hydrocarbon-

like exterior associated with the CH2groups. 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

12-Crown-4

18-Crown-6

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 spacefilling 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.

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624CHAPTER SIXTEENEthers, Epoxides, and Sulfides POLYETHER ANTIBIOTICS

One way in which pharmaceutical companies search for new drugs is by growing colonies of microorganisms in nutrient broths and assaying the substances produced for their biological activity. This method has yielded thousands of antibiotic substances, of which hundreds have been developed into effective drugs. Antibiotics are, by definition, toxic (anti “against”; bios “life”), and the goal is to find substances that are more toxic to infectious organisms than to their human hosts.

Since 1950, a number of polyether antibiotics have been discovered using fermentation technology. They are characterized by the presence of several cyclic ether structural units, as illustrated for the case of monensinin Figure 16.3a.Monensin and other naturally occurring polyethers are similar to crown ethers in their ability to form stable complexes with metal ions. The structure of the monensin– sodium bromide complex is depicted in Figure 16.3b, where it can be seen that four ether oxygens and two hydroxyl groups surround a sodium ion. The alkyl groups are oriented toward the outside of the complex, and the polar oxygens and the metal ion are on the inside. The hydrocarbon-like surface of the complex permits it to carry its sodium ion through the hydrocarbon-like interior of a cell membrane. This disrupts the normal balance of sodium ions within the cell and interferes with important processes of cellular respiration. Small amounts of monensin are added to poultry feed in order to kill parasites that live in the intestines of chickens. Compounds such as monensin and the crown ethers that affect metal ion transport are referred to as ionophores (“ion carriers”).

HOCH2

CH3

CH3

OCH3 CH3

CH3

CH3

CH3

CH3 H O

H3C O

HO CH3

CH3

CH3

FIGURE 16.3 (a) The structure of monensin; (b) the structure of the monensin–sodium bromide complex showing coordination of sodium ion by oxygen atoms of monensin.

BackForwardMain MenuTOCStudy Guide TOCStudent OLCMHHE Website this complex (Figure 16.2b), K , with an ionic radius of 266 pm, fits comfortably within the 260–320 pm internal cavity of 18-crown-6. Nonpolar CH2groups dominate the outer surface of the complex, mask its polar interior, and permit the complex to dissolve in nonpolar solvents. Every K that is carried into benzene brings a fluoride ion with it, resulting in a solution containing strongly complexed potassium ions and relatively unsolvated fluoride ions.

In media such as water and alcohols, fluoride ion is strongly solvated by hydrogen bonding and is neither very basic nor very nucleophilic. On the other hand, the poorly solvated, or “naked,” fluoride ions that are present when potassium fluoride dissolves in benzene in the presence of a crown ether are better able to express their anionic reactivity. Thus, alkyl halides react with potassium fluoride in benzene containing 18- crown-6, thereby providing a method for the preparation of otherwise difficultly accessible alkyl fluorides.

No reaction is observed when the process is carried out under comparable conditions but with the crown ether omitted.

Catalysis by crown ethers has been used to advantage to increase the rate of many organic reactions that involve anions as reactants. Just as important, though, is the increased understanding that studies of crown ether catalysis have brought to our knowledge of biological processes in which metal ions, including Na and K , are transported through the nonpolar interiors of cell membranes.

16.5PREPARATION OF ETHERS

Because they are widely used as solvents, many simple dialkyl ethers are commercially available. Diethyl ether and dibutyl ether, for example, are prepared by acid-catalyzed condensation of the corresponding alcohols, as described earlier in Section 15.7.

In general, this method is limited to the preparation of symmetrical ethers in which both alkyl groups are primary. Isopropyl alcohol, however, is readily available at low cost and

(Parte 1 de 4)

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