Chap. 6

Alcohols and Ethers

Solomons: Chapter 11

Chapter 11 2

Physical Properties of Alcohols and Ethers Ether boiling points are roughly comparable to hydrocarbons of

the same molecular weight Molecules of ethers cannot hydrogen bond to each other

Alcohols have considerably higher boiling points Molecules of alcohols hydrogen bond to each other

Both alcohols and ethers can hydrogen bond to water and have similar solubilities in water

Diethyl ether and 1-butanol have solubilites of about 8 g per 100 mL in water

Chapter 11 3

アルコール類の合成法

１． Alcohols from Alkenes （酸触媒存在下での水和）

２． Hydroboration-Oxidation 　 of Akenes　（水素ホウ素化）

Chapter 11 4

Synthesis of Alcohols from Alkenes

Acid-Catalyzed Hydration of AlkenesThis is a reversible reaction with Markovnikov regioselectivity

Chapter 11 5

Hydroboration-Oxidation

This addition reaction occurs with anti-Markovnikov regiochemistry and syn stereochemistry

Chapter 11 6

アルコール類の反応

1． Conversion of Alcohols into Alkyl Halides

2． Sulfonate誘導体を経る変換反応 (SN2反応）

Chapter 11 7

Conversion of Alcohols into Alkyl HalidesHydroxyl groups are poor leaving groups, and as such, are

often converted to alkyl halides when a good leaving group is needed

Three general methods

Chapter 11 8

Alkyl Halides from the Reaction of Alcohols with Hydrogen Halides

The order of reactivity is as followsHydrogen halide HI > HBr > HCl > HF Type of alcohol 3o > 2o > 1o < methyl

Mechanism of the Reaction of Alcohols with HX SN1 mechanism for 3o, 2o, allylic and benzylic alcohols

Chapter 11 9

Primary and methyl alcohols undergo substitution by an SN2 mechanism

Primary and secondary chlorides can only be made with the assistance of a Lewis acid such as zinc chloride

Chapter 11 10

Alkyl Halides from the Reaction of Alcohols with PBr3 and SOCl2

These reagents only react with 1o and 2o alcohols in SN2 reactions

Reaction of phosphorous tribromide to give alkyl bromides

Chapter 11 11

Reaction of thionyl chloride to give alkyl chloridesOften an amine is added to react with HCl formed in the

reaction

Chapter 11 12

Tosylates, Mesylates, and Triflates:

　　 Leaving Group Derivatives of Alcohols The hydroxyl group of an alcohol can be converted to a good leaving group

by conversion to a sulfonate ester

Sulfonyl chlorides are used to convert alcohols to sulfonate esters Base is added to react with the HCl generated

Chapter 11 13

A sulfonate ion (a weak base) is an excellent leaving group

If the alcohol hydroxyl group is at a stereogenic center then the overall reaction with the nucleophile proceeds with inversion of configuration The reaction to form a sulfonate ester proceeds with retention

of configuration

Chapter 11 14

Ethers

Chapter 11 15

Synthesis of Ethers Ethers by Intermolecular Dehydration of Alcohol

Primary alcohols can dehydrate to ethers This reaction occurs at lower temperature than the

competing dehydration to an alkene This method generally does not work with secondary or

tertiary alcohols because elimination competes strongly

Chapter 11 16

The mechanism is an SN2 reaction

Chapter 11 17

Williamson Ether Synthesis This is a good route for synthesis of unsymmetrical ethers

The alkyl halide (or alkyl sulfonate) should be primary

to avoid E2 reaction

Substitution is favored over elimination at lower temperatures

Chapter 11 18

tert-Butyl Ethers by Alkylation of Alcohols: Protecting Groups

This method is used to protect primary alcohols The protecting group is removed using dilute acid

Chapter 11 19

Silyl Ether Protecting GroupsSilyl ethers are widely used protecting groups for alcohols

The tert-butyl dimethysilyl (TBDMS) ether is common The protecting group is introduced by reaction of the alcohol with

the chlorosilane in the presence of an aromatic amine base such as imidazole or pyridine

The silyl ether protecting group is removed by treatment with fluoride ion (e.g. from tetrabutyl ammonium fluoride)

Chapter 11 20

Reactions of EthersAcyclic ethers are generally unreactive, except for cleavage by very

strong acids to form the corresponding alkyl halidesDialkyl ethers undergo SN2 reaction to form 2 equivalents of the

alkyl bromide

Chapter 11 21

EpoxidesEpoxides are three-membered ring cyclic ethers

These groups are also called oxiranes

Epoxides are usually formed by reaction of alkenes

with peroxy acids This process is called epoxidation and involves syn addition of

oxygen

Chapter 11 22

Magnesium monoperoxyphthalate (MMPP) is a common and safe peroxy acid for epoxidation

Chapter 11 23

Reaction of EpoxidesEpoxides are considerably more reactive than regular ethers

The three-membered ring is highly strained and therefore very reactive

Acid-catalyzed opening of an epoxide occurs by initial protonation of the epoxide oxygen, making the epoxide even more reactiveAcid-catalyzed hydrolysis of an epoxide leads to a 1,2-diol

Chapter 11 24

In unsymmetrical epoxides, the nucleophile attacks primarily at the most substituted carbon of the epoxide

Chapter 11 25

Base-catalyzed reaction with strong nucleophiles (e.g. an alkoxide or hydroxide) occurs by an SN2 mechanism

The nucleophile attacks at the least sterically hindered carbon of the epoxide

Chapter 11 26

Anti 1,2-Dihydroxylation of Alkenes via Epoxides Opening of the following epoxide with water under acid catalyzed

conditions gives the trans diol