1. Chapter 11 Alcohols and Ethers

2. Nomenclature Nomenclature of Alcohols (Sec. 4.3F)
Nomenclature of Ethers
Common Names
The groups attached to the oxygen are listed in alphabetical order
IUPAC
Ethers are named as having an alkoxyl substituent on the main chain
Chapter 11

3. Chapter 11 Cyclic ethers can be named using the prefix oxa-
Three-membered ring ethers can be called oxiranes; Four-membered ring ethers can be called oxetanes
Chapter 11

4. 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

5. Synthesis of Alcohols from Alkenes
Acid-Catalyzed Hydration of Alkenes
This is a reversible reaction with Markovnikov regioselectivity
Oxymercuration-demercuration
This is a Markovnikov addition which occurs without rearrangement
Chapter 11

6. Hydroboration-Oxidation
This addition reaction occurs with anti-Markovnikov regiochemistry and syn stereochemistry
Chapter 11

7. Alcohols as Acids Alcohols have acidities similar to water
Sterically hindered alcohols such as tert-butyl alcohol are less acidic (have higher pKa values)
Why?: The conjugate base is not well solvated and so is not as stable
Alcohols are stronger acids than terminal alkynes and primary or secondary amines
An alkoxide can be prepared by the reaction of an alcohol with sodium or potassium metal
Chapter 11

8. Conversion of Alcohols into Alkyl Halides
Hydroxyl groups are poor leaving groups, and as such, are often converted to alkyl halides when a good leaving group is needed
Three general methods exist for conversion of alcohols to alkyl halides, depending on the classification of the alcohol and the halogen desired
Reaction can occur with phosphorus tribromide, thionyl chloride or hydrogen halides
Chapter 11

9. Alkyl Halides from the Reaction of Alcohols with Hydrogen Halides
The order of reactivity is as follows
Hydrogen 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
These reactions are prone to carbocation rearrangements
In step 1 the hydroxyl is converted to a good leaving group
In step 2 the leaving group departs as a water molecule, leaving behind a carbocation
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10. Primary and methyl alcohols undergo substitution by an SN2 mechanism
In step 3 the halide, a good nucleophile, reacts with the carbocation
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
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11. Alkyl Halides from the Reaction of Alcohols with PBr3 and SOCl2
These reagents only react with 1o and 2o alcohols in SN2 reactions
In each case the reagent converts the hydroxyl to an excellent leaving group
No rearrangements are seen
Reaction of phosphorous tribromide to give alkyl bromides
Chapter 11

12. Reaction of thionyl chloride to give alkyl chlorides
Often an amine is added to react with HCl formed in the reaction
Chapter 11

13. 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

14. 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
Triflate anion is such a good leaving group that even vinyl triflates can undergo SN1 reaction
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
The mechanism is an SN2 reaction
Chapter 11

16. 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

17. Synthesis of Ethers by Alkoxymercuration-Demercuration
An alcohol is the nucleophile (instead of the water nucleophile used in the analogous reaction to form alcohols from alkenes)
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

18. Silyl Ether Protecting Groups
Silyl 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

19. Reactions of Ethers
Acyclic ethers are generally unreactive, except for cleavage by very strong acids to form the corresponding alkyl halides
Dialkyl ethers undergo SN2 reaction to form 2 equivalents of the alkyl bromide
Chapter 11

20. Epoxides Epoxides 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

21. Epoxidation is stereospecfic
Magnesium monoperoxyphthalate (MMPP) is a common and safe peroxy acid for epoxidation
Epoxidation is stereospecfic
Epoxidation of cis-2-butene gives the meso cis oxirane
Epoxidation of trans-2-butene gives the racemic trans oxirane
Chapter 11

22. Reaction of Epoxides
Epoxides 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 reactive
Acid-catalyzed hydrolysis of an epoxide leads to a 1,2-diol
Chapter 11

23. In unsymmetrical epoxides, the nucleophile attacks primarily at the most substituted carbon of the epoxide
Chapter 11

24. Base-catalyzed reaction with strong nucleophiles (e. g
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

25. Anti 1,2-Dihydroxylation of Alkenes via Epoxides
Opening of the following epoxide with water under acid catalyzed conditions gives the trans diol
Chapter 11

26. Epoxide ring-opening is a stereospecific process
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27. Chapter 11