CH 18: Ethers and Epoxides

Renee Y. Becker

Valencia Community College

CHM 2211

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Ethers and Their Relatives

• An 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 solvent

• Tetrahydrofuran (THF) is a solvent that is a cyclic ether

• Epoxides contain a C-O-C unit which make-up a three membered ring

• Thiols (R–S–H) and sulfides (R–S–R) are sulfur (for oxygen) analogs of alcohols and ethers

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Naming Ethers

• Ethers are named two ways:

– As alkoxy derivatives of alkanes

– Derived 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)

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Naming Ethers

CH3CH2 O CH2CH3

Diethyl etherEthoxyethane

CH3CH2 O CH3

Ethyl methyl etherMethoxyethane

CH3CH2 O CH2CH2CH2Cl

3-Chloropropyl ethyl ether1-Chloro-3-ethoxypropane

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Naming Ethers

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

O

1,2-Epoxycyclohexane

O

2-Methyl-2,3-epoxybutane

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Example 1: Name

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1

2

3

4

5

6

7

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O

O

O

Br

O

BrCl

Br OCH3

OCH3

O

O

1

2

3

4

5

6

7

8

O

O

O

Br

O

BrCl

Br OCH3

OCH3

O

O

Example 2: Draw

1. Isopropyl methyl ether

2. 4-t-butoxy-1-cyclohexene

3. Phenyl propyl ether

4. O- nitro anisole

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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)

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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 ether

130oCOH2

butanolO

+ H2O

Limited to symmetrical ethers. WHY?

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Mechanism 1: Acid catalyzed synthesis of ethers

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2130 C

H---Cl

H3O+

Cl-

H3O+ Cl-OH O

OH O+

H

H OH

O+

H

OHH

O

HCl

+

+

+

+2130 C

H---Cl

H3O+

Cl-

H3O+ Cl-OH O

OH O+

H

H OH

O+

H

OHH

O

HCl

+

+

+

+

Preparation of Ethers

• Williamson ether synthesis

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

•Secondary and tertiary substrates react following an E2 mechanism

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Mechanism 2: Williamson Ether Synthesis

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NaH

THFCH3CH2----I

THF

H2

Na+ H-

NaI

H2

CH3CH2----I

NaI

THF

Na+

Na+

OH O– O

O–O

H

O

+

+

+

+

+

+

N a H

T H F

C H

3CH2----ITHF

H2

Na+ H-

NaI

H2

CH3CH2----I

NaI

THF

Na+

Na+

OH O– O

O–O

H

O

+

+

+

+

+

+

Example 3: Williamson ether synthesis

O + CH3CH2BrSN2

?

BrCH3CH2OE2 ?+

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Example 4

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

• Methyl propyl ether

• Anisole (methyl phenyl ether)

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Example 5: Predict the product:

+

Br

CH3CH2CHCH3

O

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Alkoxymercuration of Alkenes

• React alkene with an alcohol and mercuric acetate or trifluoroacetate

• Demercuration with NaBH4 yields an ether

• Overall Markovnikov addition of alcohol to alkene

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Reactions of Ethers: Acidic Cleavage

• Ethers are generally unreactive

• Strong acid will cleave an ether at elevated temperature

• HI, HBr produce an alkyl halide from less hindered component by SN2 (tertiary ethers undergo SN1)

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Mechanism 3: Acidic Cleavage

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

Example 6

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Reactions of Ethers: Claisen Rearrangement

• Specific to allyl aryl ethers, ArOCH2CH=CH2

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

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Mechanism 4: Claisen Rearrangement

• Concerted pericyclic 6-electron, 6-membered ring transition state

• Mechanism consistent with 14C labeling

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Example 7

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Cyclic Ethers: Epoxides

• Cyclic ethers behave like acyclic ethers, except if ring is 3-membered

• Dioxane 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 epoxides

• Ethylene oxide (oxirane; 1,2-epoxyethane) is industrially important as an intermediate

• Prepared by reaction of ethylene with oxygen at 300 °C and silver oxide catalyst

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Preparation of Epoxides Using a Peroxyacid

• Treat an alkene with a peroxyacid

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Mechanism 5: Preparation of Epoxides Using a Peroxyacid

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(E)-1,2-diphenylethene

peroxyacetic acid

trans-1,2-diphenyloxirane acetic acid

CH3

OH

OO

O

HO

CH3

H

HC6H5

H5C6

O

H

H C6H5

H5C6

+ +

( E ) - 1 , 2 - d i p h e n y l e t h e n e

p e r o x y a c e t i c a c i d

t r a n s - 1 , 2 - d i p h e n y l o x i r a n ea c e t i c a c i d

CH3

OH

OO

O

HO

CH3

H

HC6H5

H5C6

O

H

H C6H5

H5C6

+ +

Epoxides from Halohydrins

• Addition of HO-X to an alkene gives a halohydrin• Treatment of a halohydrin with base gives an epoxide• Intramolecular Williamson ether synthesis

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Ring-Opening Reactions of Epoxides

• Water adds to epoxides with dilute acid at room temperature

• Product is a 1,2-diol (on adjacent C’s: vicinal)

• Mechanism: acid protonates oxygen and water adds to opposite side (anti-addition)

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Mechanism 6: Acid catalyzed ring-openings

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Ethylene Glycol

• 1,2-ethanediol from acid catalyzed hydration of ethylene

• Widely used as automobile antifreeze (lowers freezing point of water solutions)

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Halohydrins from Epoxides

• Anhydrous HF, HBr, HCl, or HI combines with an epoxide

• Gives trans product

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Base-Catalyzed Epoxide Opening

• Strain of the three-membered ring is relieved on ring-opening

• Hydroxide cleaves epoxides at elevated temperatures to give trans 1,2-diols– Complete the reaction

CH2

O

OH-

H2O, 100oC

Methylenecyclohexane oxide 41

Mechanism 7: Base-Catalyzed Epoxide Opening

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-OH

100 C

-OHCH2

O O–

CH2OH

OHH OH

CH2OH+

-OH

100 C

-OHCH2

O O–

CH2OH

OHH OH

CH2OH+

Mechanism 7: Base-Catalyzed Epoxide Opening

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Addition of Grignards to Ethylene Oxide

• Adds –CH2CH2OH to the Grignard reagent’s hydrocarbon chain

• Acyclic and other larger ring ethers do not react

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Thiols

• Thiols (RSH), are sulfur analogs of alcohols– Named with the suffix -thiol

– SH group is called “mercapto group”

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Example 8: Name

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1

2

3

SH

SH

SH

Br

1

2

3

SH

SH

SH

Br

Example 9: Draw

1. Cyclopentanethiol

2. 3-methyl-4-heptanethiol

3. 4-ethyl-4-isopropyl-2-methyl-3-hexanethiol

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Sulfides

• Sulfides (RSR), are sulfur analogs of ethers– Named by rules used for ethers, with sulfide in

place of ether for simple compounds and alkylthio in place of alkoxy

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Example 10: Name or Draw

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1

2

3

4

ethyl phenyl sulfide

sec-butyl isopropyl sulfide

S

S1

2

3

4

e t h y l p h e n y l s u l f i d e

s e c - b u t y l i s o p r o p y l s u l f i d e

S

S

Thiols: Formation and Reaction

• From 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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Sulfides

• Thiolates (RS) are formed by the reaction of a thiol with a base

• Thiolates react with primary or secondary alkyl halide to give sulfides (RSR’)

• Thiolates are excellent nucleophiles and react with many electrophiles

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