1

Chapter 14 Ethers, Epoxides,

and Sulfides

Chem 233Dr. Hoeger

Ethers Ethers 2

Introduction• Formula R-O-R′ where R and R′ are alkyl

or aryl.• Symmetrical or unsymmetrical• Examples:

O CH3

CH3 O CH3 O

2

Ethers Ethers 3

Structure and Polarity

• Bent molecular geometry• Oxygen is sp3 hybridized• Tetrahedral angle

=>

Ethers Ethers 4

Boiling PointsSimilar to alkanes of comparable molecular weight.

=>

3

Ethers Ethers 5

Hydrogen Bond Acceptor• Ethers cannot H-bond to each other.• In the presence of

-OH or -NH (donor), the lone pair ofelectrons from ether forms ahydrogen bond with the -OH or-NH.

=>

Ethers Ethers 6

Solvent Properties

• Nonpolar solutes dissolvebetter in ether than inalcohol.

• Ether has large dipolemoment, so polar solutesalso dissolve.

• Ethers solvate cations.• Ethers do not react with

strong bases. =>

4

Ethers Ethers 7

Ether Complexes

• Grignard reagents

• Electrophiles

• Crown ethers

O B

H

H

H

+_

BH3 THF

=>

Ethers Ethers 8

Common Names of Ethers• Alkyl alkyl ether• Current rule: alphabetical order• Old rule: order of increasing complexity• Symmetrical: use dialkyl, or just alkyl.• Examples:

CH3CH2 O CH2CH3

diethyl ether orethyl ether

CH3 O C

CH3

CH3

CH3

t-butyl methyl ether ormethyl t-butyl ether =>

5

Ethers Ethers 9

IUPAC Names• Alkoxy alkane• Examples:

CH3 O C

CH3

CH3

CH3

2-methyl-2-methoxypropane

O CH3

Methoxycyclohexane

=>

Ethers Ethers 10

Cyclic Ethers

• Heterocyclic: oxygen is in ring.

• Epoxides (oxiranes) H2C CH2

O

• OxetanesO

• Furans (Oxolanes )O O

• Pyrans (Oxanes )O O

•DioxanesO

O

=>

6

Ethers Ethers 11

Naming Epoxides

• Epoxy attachment to parent compound, 1,2-epoxy-cyclohexane

• Alkene oxide, from usual synthesis methodperoxybenzoic acid

O

H

H

cyclohexene oxide

• Oxirane as parent, oxygen number 1

trans-2-ethyl-3-methyloxiraneO

H

H

CH3

CH3CH2

=>

Ethers Ethers 12

Spectroscopy of Ethers

• IR: Compound contains oxygen, butO-H and C=O stretches are absent.

• MS: α-cleavage to form oxonium ion, or loss of either alkylgroup.

• NMR: 13C-O signal between δ65-δ90, 1H-C-O signal between δ3.5-δ4.

=>

7

Ethers Ethers 13

Williamson Synthesis

• Alkoxide ion + 1° alkyl bromide (or tosylate)• Example:

CH3 O H

CH3

CH3

+ K CH3 O

CH3

CH3

_K

+

CH3 O

CH3

CH3

_+ CH3CH2 C

H

H

Br CH3 O

CH3

CH3

CH2CH2CH3 + Br

_

=>

Ethers Ethers 14

Phenyl Ethers• Phenoxide ions are easily produced for use in the Williamson

synthesis.• Phenyl halides or tosylates cannot be used in this synthesis

method.

O H

+ NaOH

O_

Na+

+ HOH

=>

8

Ethers Ethers 15

Alkoxymercuration-DemercurationUse mercuric acetate with an alcohol to add RO-H to a double

bond and form the Markovnikov product.

=>

Ethers Ethers 16

Bimolecular Dehydrationof Alcohols

• Industrial method, not good lab synthesis.• If temperature is too high, alkene forms.

=>

H O CH2CH3CH3CH2 O H CH3CH2 O CH2CH3+

H2SO4

140°C

9

Ethers Ethers 17

Cleavage of Ethers

• Ethers are unreactive toward base, but protonated ethers canundergo substitution reactions with strong acids.

• Alcohol leaving group is replaced by a halide.• Reactivity: HI > HBr >> HCl

=>

Ethers Ethers 18

Mechanism for Cleavage

CH3 O CH3 H Br CH3 O CH3

H_

Br_

++

Br_ +

CH3 O CH3

H

Br CH3 + H O CH3

• Ether is protonated.

• Alcohol leaves as halide attacks.

• Alcohol is protonated, halide attacks, andanother molecule of alkyl bromide is formed.=>

10

Ethers Ethers 19

Phenyl Ether Cleavage• Phenol cannot react further to become halide.• Example:

O CH2CH3

HBr

OH

+ CH3CH2 Br

=>

Ethers Ethers 20

Autoxidation of Ethers

• In the presence of atmospheric oxygen, ethers slowlyoxidize to hydroperoxides and dialkyl peroxides.

• Both are highly explosive.• Precautions:

Do not distill to dryness.Store in full bottles with tight caps.

=>

11

Ethers Ethers 21

Sulfides (Thioethers)• R-S-R′, analog of ether.• Name sulfides like ethers, replacing “sulfide” for “ether” in

common name, or “alkylthio” for “alkoxy” in IUPAC system.• Example:

S CH3 methyl phenyl sulfide ormethylthiobenzene =>

Ethers Ethers 22

Thiols and Thiolates

• R-SH about same acidity as phenols.

CH3CH2 SH + NaOH Na++ HOHCH3CH2 S

_

• Thiolates are better nucleophiles, weaker bases, than alkoxides.

CH3 C CH3

H

Br

CH3OH

CH3S_

CH3 C CH3

H

SCH3

2° halide Substitution product =>

12

Ethers Ethers 23

Sulfide Reactions

• Sulfides are easily oxidized to sulfoxides and sulfones.

• Sulfides react with unhindered alkyl halides to give sulfoniumsalts.

+CH3 S CH3 CH3 I CH3 S CH3

CH3

+I

_

=>

CH3 S CH3

H2O2

CH3COOHCH3 S CH3

O

CH3COOH

H2O2CH3 S CH3

O

O

Ethers Ethers 24

Synthesis of Epoxides

• Peroxyacid epoxidation

• Cyclization of Halohydrin

HH

H2O, Cl2

ClH

HO H OH_

ClH

O H_

H H

O

=>

13

Ethers Ethers 25

Ring Opening in Acid• Trans diol formed in water solvent.

• Alkoxy alcohol formed in alcohol solvent.

• 1,2-Dihalide formed with HI or HBr.

H

O

H

H+, H2O

H

HO H

OH

H

O

H

H+, CH3OH

H

HO H

OCH3

Ethers Ethers 26

Biosynthesis of Steroids

=>

14

Ethers Ethers 27

Ring Opening in BaseEpoxide’s high ring strain makes it susceptible to nucleophilic

attack.

=>

Ethers Ethers 28

Epoxide Opening in Base• With aqueous hydroxide, a trans 1,2-diol is formed.• With alkoxide in alcohol, a trans 1,2-alkoxy alcohol is

formed.• These are the same products that were formed in acid.• Different products are formed in acid and base if epoxide is

unsymmetrical. =>

15

Ethers Ethers 29

Orientation of Epoxide Opening

• Base attacks the least hindered carbon.

• In acid, the nucleophile attacks the protonated epoxide at themost substituted carbon.

CH3CH2OHHC CH2

CH3

OH

OCH2CH3

_

HC CH2

CH3

O

OCH2CH3OCH2CH3

HC CH2

CH3

O

=>

HC CH2

OHH3C

OCH2CH3+

HC CH2

OHH3C

OCH2CH3H

CH3CH2OH

+

HC CH2

CH3

O

H

Ethers Ethers 30

Reaction with Grignard and R-Li• Strong base opens the epoxide ring by attacking the less

hindered carbon.• Example:

H2C CHCH3

O

+

MgBr1) ether

2) H3O+

CH2 CHCH3

OH

=>

16

Ethers Ethers 31

Epoxy Resins

Polymer of bisphenol A and epichlorohydrin

HO C

CH3

CH3

OH

bisphenol A

H2C CHCH2Cl

O

epichlorohydrin

=>

Ethers Ethers 32

End of Chapter 14Homework: 33, 35, 37, 39, 40, 42, 45-47