Chapter 16 Ethers, Epoxides, and Sulfides Copyright © The McGraw-Hill Companies, Inc. Permission...

Chapter 16Ethers, Epoxides, and Sulfides

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

© 2013 Pearson Education, Inc. Chapter 14 2

Ethers

• Formula is R—O—Rwhere R and R are alkyl or aryl.

• Symmetrical or unsymmetrical

Nomenclature of Ethers, Epoxides, and Sulfides

name as alkoxy derivatives of alkanes

CH3OCH2 CH3

methoxyethane

CH3CH2OCH2 CH3

ethoxyethane

CH3CH2OCH2CH2CH2Cl

3-chloro-1-ethoxypropane

Substitutive IUPAC Names of Ethers

Name the groups attached to oxygen in alphabetical order as separate words; "ether" is last word.

CH3OCH2 CH3

ethyl methyl ether

CH3CH2OCH2 CH3

diethyl ether

CH3CH2OCH2CH2CH2Cl

3-chloropropyl ethyl ether

Functional Class IUPAC Names of Ethers

bent geometry at oxygen analogousbent geometry at oxygen analogous

to water and alcohols to water and alcohols

Structure and Bondingin

Ethers and Epoxides


Structure and Polarity

• Oxygen is sp3 hybridized.• Bent molecular geometry.• Tetrahedral C—O—C angle is 110°.• Polar C—O bonds.

H

OH

(CH3)3CO

C(CH3)3

112°

105° 108.5°

132°

HO

CH3

CH3

OCH3

Bond angles at oxygen are sensitiveto steric effects

Most stable conformation of diethyl ether

resembles that of pentane.

An oxygen atom affects geometry in much thesame way as a CH2 group

Most stable conformation of tetrahydropyran

resembles that of cyclohexane.

An oxygen atom affects geometry in much thesame way as a CH2 group

Physical Properties of Ethers

boiling point

36°C

35°C

117°C

Table 16.1 Ethers resemble alkanes more than alcohols

with respect to boiling point O

OH

Intermolecular hydrogenbonding possible in alcohols; not possible in alkanes or ethers.

solubility in water (g/100 mL)

very small

9

7.5

Table 16.1 Ethers resemble alcohols more than alkanes

with respect to solubility in water O

OH

Hydrogen bonding towater possible for ethersand alcohols; not possible for alkanes.


Hydrogen Bond Acceptor

• Ethers cannot hydrogen bond with other ether molecules, so they have a lower boiling point than alcohols.

• Ether molecules can hydrogen bond with water and alcohol molecules.

• They are hydrogen bond acceptors.


Ethers as Solvents • Ethers are widely used as solvents

because they can dissolve nonpolar and polar

substances. they are unreactive toward strong bases.

Ethers are relatively unreactive.

Their low level of reactivity is one reason why

ethers are often used as solvents in chemical

reactions.


Ether Complexes

• Grignard reagents: Complexation of an ether with a Grignard reagent stabilizes the reagent and helps keep it in solution.

• Electrophiles: The ether’s nonbonding electrons stabilize the borane (BH3).

O B

H

H

H

+ _

BH3 THF

Crown Ethers


structurecyclic polyethers derived from repeating

—OCH2CH2— units

propertiesform stable complexes with metal ions

applicationssynthetic reactions involving anions

Crown Ethers


Crown Ether Complexes

• Crown ethers can complex metal cations in the center of the ring.

• The size of the ether ring will determine which cation it can solvate better.

• Complexation by crown ethers often allows polar inorganic salts to dissolve in nonpolar organic solvents.

O

O O

O

O

O

18-Crown-6

forms stable Lewis acid/Lewis base complex with K+

K+

not soluble in benzene

Ion-Complexing and Solubility

K+F–


K+F–

add 18-crown-6

benzene

O

O O

O

O

O


18-crown-6 complex of K+ dissolves in benzene

benzene

F–

O

O O

O

O

O

O

O O

O

O

O

K+


+ F–F– carried into benzene to preserve electroneutrality

benzene

O

O O

O

O

O

O

O O

O

O

O

K+

Application to organic synthesis

Complexation of K+ by 18-crown-6 solubilizes potassium salts in benzene.

Anion of salt is in a relatively unsolvated state in benzene (sometimes referred to as a "naked anion").

Unsolvated anion is very reactive.

Only catalytic quantities of 18-crown-6 are needed.

Example

CH3(CH2)6CH2BrKF

18-crown-6benzene

CH3(CH2)6CH2F

(92%)

Preparation of EthersPreparation of Ethers

Acid-Catalyzed Condensation of Alcohols*

2 CH3CH2CH2CH2OH

H2SO4, 130°C

CH3CH2CH2CH2OCH2CH2CH2CH3

(60%)

Method is good for primary alcohols. Diethyl ether is made on Method is good for primary alcohols. Diethyl ether is made on

industrial scale using this method. Ethylene will form at higher industrial scale using this method. Ethylene will form at higher

temperatures. Secondary and tertiary alcohols give alkenes as temperatures. Secondary and tertiary alcohols give alkenes as

main product. main product.

H+

(CH3)2C=CH2 + CH3OH (CH3)3COCH3

tert-Butyl methyl ether

tert-Butyl methyl ether (MTBE) was produced on a

scale exceeding 15 billion pounds per year in the U.S.

during the 1990s. It is an effective octane booster in

gasoline, but contaminates ground water if allowed to

leak from storage tanks. Further use of MTBE is unlikely.

Addition of Alcohols to Alkenes

The Williamson Ether SynthesisThe Williamson Ether Synthesis


Williamson Ether Synthesis

• This method involves an SN2 attack of the alkoxide on an unhindered primary halide or tosylate.

• The alkoxide is commonly made by adding Na, K, or NaH to the alcohol

(71%)

CH3CH2CH2CH2ONa + CH3CH2I

CH3CH2CH2CH2OCH2CH3 + NaI

Example

Another Example

+ CH3CHCH3

ONa

CH2Cl

(84%)CH2OCHCH3

CH3

Alkyl halide must be

primary or methyl

Alkoxide ion can be derived

from methyl, primary,

secondary, or tertiary alcohol.

CH3CHCH3

OH

Na

CH2OH

HCl

CH2OCHCH3

CH3

CH2Cl + CH3CHCH3

ONa

(84%)

Origin of Reactants

What happens if the alkyl halide is not primary?

CH2ONa + CH3CHCH3

Br

CH2OH + H2C CHCH3

Elimination by the E2 mechanism becomes

the major reaction pathway.

Reactions of Ethers:Reactions of Ethers:

Acid-Catalyzed Cleavage of Ethers

Ethers can be cleaved by heating with concentrated HBr and HI.

Reactivity: HI > HBr

HBrCH3CHCH2CH3

OCH3

CH3Br+

(81%)

CH3CHCH2CH3

Brheat

Example


Mechanism of Ether Cleavage • Step 1: Protonation of the oxygen.

• Step 2: The halide will attack the carbon and displace the alcohol (SN2).


Mechanism of Ether Cleavage

•This does not occur with aromatic alcohols (phenols).

Step 3: The alcohol reacts further with the acid Step 3: The alcohol reacts further with the acid to produce another mole of alkyl halide.to produce another mole of alkyl halide.

HI

150°CICH2CH2CH2CH2I

(65%)

O

Cleavage of Cyclic Ethers

O••

••

HI

H

O••

+

••

••

••I ••–

ICH2CH2CH2CH2I

HI H

O

••

••

••I ••••

Mechanism


Autoxidation of Ethers

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

• Both are highly explosive.

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


Autoxidation of Ethers


Preparation of Epoxides:Preparation of Epoxides:

A Review and a PreviewA Review and a Preview



Epoxides are prepared by two major methods.Both begin with alkenes.

Reaction of alkenes with peroxy acids(Section 6.19)

Conversion of alkenes to vicinalhalohydrins, followed by treatmentwith base (Section 16.10, this chapter)

Preparation of Epoxides


Synthesis of Epoxides

• Peroxyacids are used to convert alkenes to epoxides.• Most commonly used peroxyacid is meta-

chloroperoxybenzoic acid (MCPBA).• The reaction is carried out in an aprotic acid to

prevent the opening of the epoxide.


Halohydrin Cyclization

• If an alkoxide and a halogen are located in the same molecule, the alkoxide may displace a halide ion and form a ring.

• Treatment of a halohydrin with a base leads to an epoxide through this internal SN2 attack.


HOH

BrH

NaOH

H2O

(81%)

H

H

O

Another look

O Br

HH

••

••••

•• ••••–

via:


anti

additioninversion

Epoxidation via Vicinal Halohydrins

Br2

H2O

OH

Corresponds to overall syn addition ofoxygen to the double bond.

Br NaOH

O

Reactions of Epoxides:Reactions of Epoxides:A Review and a PreviewA Review and a Preview

Reactions of epoxides involve attack by anucleophile and proceed with ring-opening.For ethylene oxide:

Nu—H +

Nu—CH2CH2O—H

H2C CH2

O

In General...

NaOCH2CH3

CH3CH2OH

(50%)

Example

H2C

O

CH2

CH3CH2O CH2CH2OH

••••O

H2C CH2

CH3CH2 O••

•• ••–

••

•

•CH3CH2 O

••CH2CH2 O

••H ••

•

••

•

O CH2CH3

–

Mechanism

–

••

•• •

•CH3CH2 O ••CH2CH2 O

••

O CH2CH3

•••

•

H

Example

O

H2C CH2

KSCH2CH2CH2CH3

ethanol-water, 0°C

(99%)

CH2CH2OHCH3CH2CH2CH2S

For epoxides where the two carbons of thering are differently substituted:

In General...

CH2

O

C

R

H

Nucleophiles attack herewhen the reaction iscatalyzed by acids:

Anionic nucleophilesattack here:

Anionic Nucleophile Attacks Less-crowded Carbon

1. diethyl ether2. H3O+

MgBr

+

O

H2C CHCH3

CH2CHCH3

OH

(60%)

Hydride attacksless-crowded

carbon.

Lithium Aluminum Hydride Reduces Epoxides

O

H2C CH(CH2)7CH3

1. LiAlH4, diethyl ether2. H2O

(90%)OH

H3C CH(CH2)7CH3

Acid-Catalyzed Ring-OpeningReactions of Epoxides

Example

O

H2C CH2 CH3CH2OCH2CH2OH

(87-92%)

CH3CH2OCH2CH2OCH2CH3 formed only on heating and/or longer reaction times.

CH3CH2OH

H2SO4, 25°C

Example

O

H2C CH2 HBr

10°CBrCH2CH2OH

(87-92%)

BrCH2CH2Br formed only on heating and/or longer reaction times.

Mechanism Br••

••••

–••

••

•

•O••

Br

CH2CH2 H

••••

••O

H2C CH2

••HBr

••••

••

••O

H2C CH2+

H

Acid-Catalyzed Hydrolysis of Ethylene Oxide

••O

H2C CH2

••

O••

H

H

H+

••O

H2C CH2+

HO••

H

H

••

Step 1

••O

H2C CH2+

H

O

••••

H

H

Step 2

+ ••

•

•O

O

CH2CH2

H

H

H

•

•


•

•

Step 3

+ ••

•

•O

O

CH2CH2

H

H

H

O••

••

H

H •

•

O••

H

H+

H

••

•

•O

O

CH2CH2

H

H

••


Acid-Catalyzed Ring Opening of Epoxides

Nucleophile attacks more substituted carbon of protonated epoxide.

Inversion of configuration at site of nucleophilic attack.

Characteristics:

CH3OH

CC

H

H3C CH3

CH3O

Nucleophile Attacks More-substituted Carbon

H2SO4

CH3CH CCH3

CH3OH

OCH3

(76%)

Stereochemistry

Inversion of configuration at carbon being attacked by nucleophile

(73%)

H

H

O HBr

HOH

BrH

O

R

R

(57%)

R

S

Stereochemistry

H3C CH3

H3C CH3

H

HH

H OHCH3O

Inversion of configuration at carbon being attacked by nucleophile

CH3OH

H2SO4

R O

R

S

R

Stereochemistry

H3C CH3

H3C CH3

H

HH

H OHCH3OCH3OH

H2SO4

+ +CH3O O

H3CH

H3CH

H+

H

anti-Hydroxylation of Alkenes H

H

CH3COOH

O

H

H

O

H2O

HClO4

(80%)

HOH

OHH

+ enantiomer

Chapter 16 Ethers, Epoxides, and Sulfides Copyright © The McGraw-Hill Companies, Inc. Permission...

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