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 CH3CH2 O CH3

Diethyl ether Ethyl methyl ether
Ethoxyethane Methoxyethane

CH3CH2 O CH2CH2CH2Cl
3-Chloropropyl ethyl ether
1-Chloro-3-ethoxypropane

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 Naming Ethers

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

O
O
1,2-Epoxycyclohexane 2-Methyl-2,3-epoxybutane

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 Example 1: Name

OCH3
1 O 6

O
2
O
7
3
O
Br

4 O
8 O
Cl Br

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Br OCH3

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 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)

CH3CH2OCH2CH3
Diethyl ether
bp =35oC
solubility in water: 7.5 g/100mL

CH3CH2CH2CH2CH3
Pentane
bp =36oC
solubility in water: insoluble

CH3CH2CH2CH2OH
1-Butanol
bp =117oC
solubility in water: 9 g/100mL
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 Preparation of Ethers

• Acid catalyzed synthesis of ethers:

H2SO4
2 OH O
130oC
butanol
Dibutyl ether
+ H2O

Limited to symmetrical ethers. WHY?

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 Mechanism 1: Acid catalyzed synthesis of ethers

HCl
OH O +
2 H3 O+ + Cl-
130 C

O
H H
H H O
OH H---Cl O+
H H
O+
+ Cl -

H3O+ + O

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 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

OH NaH O – Na+ O
THF
+ CH3CH2----I + NaI
THF
+ H2

O THF O– Na+
H
+ Na+ H-
CH3CH2----I

+ H2

NaI +

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 Example 3: Williamson ether synthesis

SN2
O + CH3CH2Br ?

+ E2 ?
CH3CH2O Br

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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 O
+ CH3CH2CHCH3

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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

Note that the halide attacks the protonated ether at

the less highly substituted site.
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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

peroxyacetic acid

C6H5 H
H
O O
H C6H5
OH
+ O CH3 O +
O CH3
H5C6 H H5C6 H

(E)-1,2-diphenylethene trans-1,2-diphenyloxirane acetic acid

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 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

O
CH2
OH-
H2O, 100oC
Methylenecyclohexane
oxide 41
 Mechanism 7: Base-Catalyzed Epoxide Opening

O OH
O -
O– H H
OH CH 2OH
CH2 -
CH 2OH + OH
100 C

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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

1 SH

2
SH

Br

SH

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 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
1 S

2
S

3 ethyl phenyl sulfide

4 sec-butyl isopropyl sulfide

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 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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