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Ethers and Epoxides

Chapter 18

Ethers and Their RelativesAn ether has two organic groups (alkyl, aryl, or vinyl) bonded to the same oxygen atom, R–O–R′Diethyl ether is used industrially as a solventTetrahydrofuran (THF) is a solvent that is a cyclic ether Epoxides contain a C-O-C unit which make-up a three membered ringThiols (R–S–H) and sulfides (R–S–R′) are sulfur (for oxygen) analogs of alcohols and ethers

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18.1 Naming Ethers

Ethers are named two ways:As alkoxy derivatives of alkanesDerived by listing the two alkyl groups in the general structure of ROR’ in alphabetical order as separate words and adding the word ether

When both alkyl groups are the same, the prefix di- precedes the name of the alkyl group(Ethers can be described as symmetrical or unsymmetrical)

Naming Ethers

CH3CH2 O CH2CH3

Diethyl etherEthoxyethane

CH3CH2 O CH3

Ethyl methyl etherMethoxyethane

CH3CH2 O CH2CH2CH2Cl3-Chloropropyl ethyl ether1-Chloro-3-ethoxypropane

Naming Ethers

Epoxides (oxiranes)“epoxy” always preceeds the name of the alkane

O

1,2-Epoxycyclohexane

O2-Methyl-2,3-epoxybutane

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Name the following according to IUPAC rules:

CH3CHOCHCH3

CH3 CH3

Br

OCH3OCH3

O

O

18.2 Structure, Properties, and Sources of Ethers

R–O–R ~ tetrahedral bond angle (112° in dimethyl ether)Oxygen is sp3-hybridized Oxygen atom gives ethers a slight dipole moment (diethyl ether 1.2 D)

Structure, Properties, and Sources of Ethers (comparative boiling points)

CH3CH2OCH2CH3Diethyl ether

bp =35oCsolubility in water: 7.5 g/100mL

CH3CH2CH2CH2CH3Pentanebp =36oC

solubility in water: insoluble

CH3CH2CH2CH2OH1-Butanolbp =117oC

solubility in water: 9 g/100mL

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Preparation of Ethers

Acid catalyzed synthesis of ethers:

H2SO4

Dibutyl ether130oC

OH2butanol

O

+ H2O

Limited to symmetrical ethers. WHY?

Preparation of Ethers

Williamson ether synthesis

Metal alkoxides react with primary alkyl halides by an SN2 pathway to yield ethers.

Williamson ether synthesis

Complete the reaction:

CH3CH2CH2CH2CH2OButoxide ion

+ CH3CH2IIodoethane

the alkoxide ion is produced by treating an alcohol with a strong base: NaH

An alternative is the use of silver oxide, AgO2:

CH3CH2CH2CH2CH2OHButanol

CH3CH2IAgO2

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Williamson ether synthesis

Secondary and tertiary substrates react following an E2 mechanism:

O + CH3CH2BrSN2 ?

BrCH3CH2OE1 ?+

Consider:

The treatment of cyclohexanol with NaH gives an alkoxide ion that reacts with iodoethane to yield an ether. Write the reaction showing all steps

How would you prepare the following compounds using a Williamson synthesis?

Methyl propyl etherAnisole (methyl phenyl ether)Benzyl isopropyl etherEthyl 2,2-dimethylpropyl ether

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Predict the product:

+Br

CH3CH2CHCH3

O

18.4 Alkoxymercuration of Alkenes

React alkene with an alcohol and mercuric acetate or trifluoroacetateDemercuration with NaBH4 yields an etherOverall Markovnikov addition of alcohol to alkene

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Predict the product:

CH31. Hg(O2CCF3)2, (CH3)2CHOH

2. NaBH4?

18.5 Reactions of Ethers: Acidic Cleavage

Ethers are generally unreactiveStrong acid will cleave an ether at elevated temperatureHI, HBr produce an alkyl halide from less hindered component by SN2 (tertiary ethers undergo SN1)

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Mechanism:

Note that the halide attacks the protonated ether at the less highly substituted site.

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18.6 Reactions of Ethers: Claisen Rearrangement

Specific to allyl aryl ethers, ArOCH2CH=CH2

Heating to 200–250°C leads to an o-allylphenolResult is alkylation of the phenol in an ortho position

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Claisen Rearrangement Mechanism

Concerted pericyclic 6-electron, 6-membered ring transition stateMechanism consistent with 14C labeling

18.7 Cyclic Ethers: Epoxides

Cyclic ethers behave like acyclic ethers, except if ring is 3-memberedDioxane and tetrahydrofuran are used as solvents

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Epoxides (Oxiranes)Three membered ring ether is called an oxirane (root “ir” from “tri” for 3-membered; prefix “ox” for oxygen; “ane” for saturated)Also called epoxidesEthylene oxide (oxirane; 1,2-epoxyethane) is industrially important as an intermediatePrepared by reaction of ethylene with oxygen at 300 °C and silver oxide catalyst

Preparation of Epoxides Using a Peroxyacid

Treat an alkene with a peroxyacid

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+H

H C6H5

C6H5

E-1,2-Diphenyletheneperoxyacetic

acid

CH3COOHO

+

H

H C6H5

C6H5

trans-2.3-DiphenyloxiraneO

acetic acid

CH3COHO

Epoxides from Halohydrins

Addition of HO-X to an alkene gives a halohydrinTreatment of a halohydrin with base gives an epoxideIntramolecular Williamson ether synthesis

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NaOH

H2O?

OHBr

18.8 Ring-Opening Reactions of Epoxides

Water adds to epoxides with dilute acid at room temperatureProduct is a 1,2-diol (on adjacent C’s: vicinal)Mechanism: acid protonates oxygen and water adds to opposite side (trans addition)

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Mechanism of acid catalyzed ring-openings:

Ethylene Glycol1,2-ethanediol from acid catalyzed hydration of ethyleneWidely used as automobile antifreeze (lowers freezing point of water solutions)

Halohydrins from EpoxidesAnhydrous HF, HBr, HCl, or HI combines with an epoxideGives trans product

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Regiochemistry of Acid-Catalyzed Opening of Epoxides

Nucleophile preferably adds to less hindered site if primary and secondary C’sAlso at tertiary because of carbocation character (See Figure 18.2)

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Base-Catalyzed Epoxide Opening

Strain of the three-membered ring is relieved on ring-openingHydroxide cleaves epoxides at elevated temperatures to give trans 1,2-diols

Complete the reaction and diagram the mechanism:

CH2

O

OH-

H2O, 100oC

Methylenecyclohexane oxide

Complete the reactions:

H3CH2CHC CH2

ONH2

NH3

H3CH2CHC CH2

OH3

18O+

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Other strong bases:

Addition of Grignards to Ethylene Oxide

Adds –CH2CH2OH to the Grignard reagent’s hydrocarbon chainAcyclic and other larger ring ethers do not react

18.9 Crown Ethers Large rings consisting repeating (-OCH2CH2-) or similar unitsNamed as x-crown-yx is the total number of atoms in the ringy is the number of oxygen atoms18-crown-6 ether: 18-membered ring containing 6 oxygens atoms

Central cavity is electronegative and attracts cations

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Uses of Crown EthersComplexes between crown ethers and ionic salts are soluble in nonpolar organic solventsCreates reagents that are free of water that have useful propertiesInorganic salts dissolve in organic solvents leaving the anion unassociated, enhancing reactivity

Other Cylic Ethers

OO

O

O

O

Oxetane Oxolane(Tetrahydrofuran)

Oxane(Tetrahydropyran)

1,4-Dioxane

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18.10 Thiols and Sulfides

Thiols (RSH), are sulfur analogs of alcoholsNamed with the suffix -thiolSH group is called “mercapto group” (“capturer of mercury”)

SulfidesSulfides (RSR′), are sulfur analogs of ethers

Named by rules used for ethers, with sulfide in place of ether for simple compounds and alkylthioin place of alkoxy

Thiols: Formation and ReactionFrom alkyl halides by displacement with a sulfur nucleophile such as −SH

The alkylthiol product can undergo further reaction with the alkyl halide to give a symmetrical sulfide, giving a poorer yield of the thiol

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SulfidesThiolates (RS−) are formed by the reaction of a thiol with a baseThiolates react with primary or secondary alkyl halide to give sulfides (RSR’)Thiolates are excellent nucleophiles and react with many electrophiles

18.11 Spectroscopy of Ethers Infrared: C–O single-bond stretching 1050 to 1150 cm−1 overlaps many other absorptions.Proton NMR: H on a C next to ether O are shifted downfield to δ 3.4 to δ 4.5

The 1H NMR spectrum of dipropyl ether shows the these signals at δ 3.4In epoxides, these H’s absorb at δ 2.5 to δ 3.5 d in their 1H NMR spectra

Carbon NMR: C’s in ethers exhibit a downfield shift to δ 50 to δ 80

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End fo Chapter 18