Carey - Organic Chemistry - sgchapt16

Carey - Organic Chemistry - sgchapt16

(Parte 1 de 2)

CHAPTER 16 ETHERS, EPOXIDES, AND SULFIDES

This compound is more commonly known as epichlorohydrin. (c)Epoxides may be named by adding the prefix epoxyto the IUPAC name of a parent compound, specifying by number both atoms to which the oxygen is attached.

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)

Tetrahydrofuran; heat of combustion 2499 kJ/mol (597.8 kcal/mol)

1-Butene

CH2CH3CH2CH

3,4-Epoxy-1-butene

CHCH CH2H2C O

2-(Chloromethyl)oxirane O O

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402ETHERS, EPOXIDES, AND SULFIDES

16.3An 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:

16.5Protonation 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.

16.6Both 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)Aprimary 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 isopropoxideAllyl bromide

Allyl isopropyl etherSodium bromide

Benzyl ethyl etherSodium bromide

Benzyl ethyl etherSodium bromide tert-Butyl methyl ether

CH3

R Ether

Alcohol

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(c)Here the ether is a mixed primary–tertiary one. The best combination is the one that uses the primary alkyl halide.

(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.

16.10As 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

1,4-Diiodobutane

Hydrogen iodide

H 4-Iodo-1-butanol

Iodideion

Dialkyloxonium ion

4-Iodo-1-butanol I OH

Tetrahydrofuran I Iodide ion

Hydrogeniodide

Dialkyloxonium ion

Tetrahydropyran BrCH2CH2CH2CH2CH2Br1,5-Dibromopentane

H2O Water

Dibenzyl ether

Benzyl bromideWater HBrheat H2O

Carbon dioxide

4CO2

Water 5H2O

Benzyl tert-butyl etherPotassium bromide

Potassium tert-butoxide

ETHERS, EPOXIDES, AND SULFIDES403

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16.11The 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.

16.13 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

3-Hexyn-1-ol (48%)

Ethylene oxide

HOCH2CH2OHEthylene glycol

NaOH H2O

Ethylene oxide

Ethylene oxide N3CH2CH2OH 2-Azidoethanol

CH3H3CHH O cis-2,3-Epoxybutane

(Plane of symmetry passes through oxygen and midpoint of carbon–carbon bond.)

O HH3CHC H3 O

Nonsuperposable mirror-image (enantiomeric) forms of trans-2,3-epoxybutane

Plane of symmetry

404ETHERS, EPOXIDES, AND SULFIDES

BackForwardMain MenuTOCStudy Guide TOCStudent OLCMHHE Website substitution with retention of configuration, which is not the normal mode of epoxide ring opening.

16.14Acid-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 lesshindered carbon of the epoxide ring, whereas attack by methanol under acid-catalyzed conditions occurs at the moresubstituted carbon.

16.15Begin 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.

16.16Reaction 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 cis-2-Butene via meso-2,3-Butanediol

CH3

O Os trans-2-Butene

C H3CH H

CH3 trans-2,3-Epoxybutane meso-2,3-Butanediol

CH3

C H3C H

CH3

CH3COOH O meso-2,3-Butanediol

CH3HOO CH3

Protonated form of 1-methyl-1,2- epoxycyclopentane

Compound A

OCH3H CH3 CH3HO

ETHERS, EPOXIDES, AND SULFIDES405

BackForwardMain MenuTOCStudy Guide TOCStudent OLCMHHE Website of the tosylate with a nucleophile proceeds by inversion of configuration in an SN2 process. The product has the Sconfiguration.

16.17Phenyl vinyl sulfoxide lacks a plane of symmetry and is chiral. Phenyl vinyl sulfone is achiral; aplane of symmetry passes through the phenyl and vinyl groups and the central sulfur atom.

16.18As 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.

CH3CH2OCH2CH2CH3 and CH3CH2OCH(CH3)2 Ethyl propyl etherEthyl isopropyl ether

CH3OCH2CH2CH2CH3Butyl methyl ether

CH3OCHCH2CH3

CH3 sec-Butyl methyl ether m/z 87

Dimethylsulfide

Dodecyl iodide Dodecyldimethylsulfonium iodide

Phenyl vinyl sulfoxide (chiral)

Phenyl vinyl sulfone (achiral)

Sodium benzenethiolate

(S)-1-Methylheptyl phenyl sulfide(R)-1-Methylheptyl tosylate

O SC H3 O

C HH3C

OHC HH3C

Cl CH3O S p-Toluenesulfonyl chloride

OC HH3C

CH3O S

O (R)-1-Methylheptyl tosylate

406ETHERS, EPOXIDES, AND SULFIDES

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These ethers could also have been named as “alkoxyalkanes.” Thus, sec-butyl methyl ether would become 2-methoxybutane.

16.21Isoflurane and enflurane are both halogenated derivatives of ethyl methyl ether.

Isoflurane:

Enflurane:

16.2 (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

(d)Eight carbon atoms are continuously linked and bridged by an oxygen. We name the compound as an epoxy derivative of cyclooctane.

1,5-Epoxycyclooctane

6 1,4-Epoxycyclohexane

O Epoxycyclopropane

Cl C FH F

F C O CHF2

2-Chloro-1,1,2-trifluoroethyl difluoromethyl ether

FC F Cl

F CH O CHF2

1-Chloro-2,2,2-trifluoroethyl difluoromethyl ether

ETHERS, EPOXIDES, AND SULFIDES407

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(c)Disulfides possess two adjacent sulfur atoms. 1,2-Dithiane is a disulfide.

16.24Intramolecular hydrogen bonding between the hydroxyl group and the ring oxygens is possible when the hydroxyl group is axial but not when it is equatorial.

16.25The 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 CH3CH2CH2ONaSodium propoxide

CH3OCH2CH2CH3 Methyl propyl ether

CH3ONa

Sodium methoxide CH3CH2CH2Br1-Bromopropane

CH3OCH2CH2CH3 Methyl propyl ether andCH3OCH2CH2CH3Methyl propyl ether CH3OCH(CH3)2Isopropyl methyl ether

CH3CH2OCH2CH3 Diethyl ether

Less stable conformation; no intramolecular hydrogen bonding

More stable conformation; stabilized by hydrogen bonding

S S 1,2-Dithiane

1,3,5-Trithiane

2-Methylthiane (chiral)

3-Methylthiane (chiral)

CH3

4-Methylthiane (achiral)

408ETHERS, EPOXIDES, AND SULFIDES

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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:

(R)-2-Ethoxybutane

CH3CH2CHCH3

Sodium 2-butanolate Br Bromocyclohexane

CH3CH2CHCH3

2-Butanol Cyclohexene NaBr Sodium bromide

Sodium ethoxideEthyl bromide

CH3CH2OCH2CH3 Diethyl ether NaBr Sodium bromide

CH3CH2OHEthanol

CH3CH2Br Ethyl bromide

PBr3 (or HBr)

CH3CH2OHEthanol

CH3CH2ONa Sodium ethoxide

CH3BrMethyl bromide (CH3)2CHONaSodium isopropoxide

CH3OCH(CH3)2 Isopropyl methyl ether

CH3CH2CH2OH1-Propanol

CH3CH2CH2ONa Sodium propoxide

CH3OHMethanol

CH3Br

Methyl bromide

PBr3 (or HBr)

CH3CH2CH2OH1-Propanol

CH3CH2CH2Br 1-Bromopropane

PBr3 (or HBr)

CH3OHMethanol

CH3ONa

Sodium methoxide

ETHERS, EPOXIDES, AND SULFIDES409

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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.

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%)

2-(o-Bromophenyl)-2-methyloxirane 1-Amino-2-(o-bromophenyl)- 2-propanol

C H3C OH

CH2NH2 Br

H3C BrO

NH3 methanol

1,2-Epoxycyclohexane trans-2- Azidocyclohexanol (61%)

NaN3 dioxane–water

Benzoic acid(Z)-1-Phenylpropene

CH3 cis-2-Methyl-3- phenyloxirane

OHH CH3

Peroxybenzoic acid

CH3CH2CHCH2BrOH CH3CH2CH CH2NaOH BrO

CH3CH2CH CH2

1-Bromo-2-butanol 1,2-Epoxybutane O

410ETHERS, EPOXIDES, AND SULFIDES

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(h)Under acidic conditions, substitution is favored at the carbon that can better support a positive charge. Aryl substituents stabilize carbocations, making the benzylic position the one that is attacked in an aryl substituted epoxide.

16.27Oxidation of 4-tert-butylthiane yields two sulfoxides that are diastereomers of each other.

Oxidation of both stereoisomeric sulfoxides yields the same sulfone.

16.28Protonation of oxygen to form an alkyloxonium ion is followed by loss of water. The resulting carbocation has a plane of symmetry and is achiral. Capture of the carbocation by methanol yields both enantiomers of 2-methoxy-2-phenylbutane. The product is racemic.

(Achiral carbocation)

CH3CH2 CH3 OH

2-Methoxy-2-phenylbutane (racemic)

CH3CH2 CH3

CH3CH2CH3

Cl H

Octadecyl tosylate

CH3CH2CH2CH2SNa

Sodium butanethiolate CH3CH2CH2CH2SCH2(CH2)16CH3 Butyl octadecyl sulfide

CH CH2 HCl CHCl3

2-Phenyloxirane 2-Chloro-2-phenylethanol (71%)

CHCH2OH Cl

ETHERS, EPOXIDES, AND SULFIDES411

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16.29 The proper approach to this problem is to first write the equations in full stereochemical detail. (a)

It now becomes clear that the arrangement of groups around the stereogenic center remains unchanged in going from starting materials to products. Therefore, choose conditions such that the nu- cleophile attacks the CH2 group of the epoxide rather than the stereogenic center. Base-catalyzed hydrolysis is required; aqueous sodium hydroxide is appropriate.

Inversion of configuration at the stereogenic center is required. The nucleophile must therefore attack the stereogenic center, and acid-catalyzed hydrolysis should be chosen. Dilute sulfuric acid would be satisfactory.

The nucleophile (a water molecule) attacks that carbon atom of the ring that can better support a positive charge. Carbocation character develops at the transition state and is better supported by the carbon atom that is more highly substituted.

16.30The key intermediate in the preparation of bis(2-chloroethyl) ether from ethylene is 2-chloroethanol, formed from ethylene by reaction with chlorine in water. Heating 2-chloroethanol in acid gives the desired ether.

16.31(a)There is a temptation to try to do this transformation in a single step by using a reducing agent to convert the carbonyl to a methylene group. No reagent is available that reduces esters in this way! The Clemmensen and Wolff–Kishner reduction methods are suitable only for aldehydes and ketones. The best way to approach this problem is by reasoning backward. The desired

Ethylene 2-Chloroethanol

OH2 OH

CH3C O

H2O NaOHH2C

HOCH2

HOCH2 OH

HC CH3

412ETHERS, EPOXIDES, AND SULFIDES

BackForwardMain MenuTOCStudy Guide TOCStudent OLCMHHE Website product is an ether. Ethers can be prepared by the Williamson ether synthesis involving an alkyl halide and an alkoxide ion.

Both the alkyl halide and the alkoxide ion are prepared from alcohols. The problem then becomes one of preparing the appropriate alcohol (or alcohols) from the starting ester. This is readily done using lithium aluminum hydride.

Then and

The following sequence is also appropriate once methanol and benzyl alcohol are obtained by reduction of methyl benzoate:

(Parte 1 de 2)

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