Chapter 11 Alcohols and Ethers

1. Chapter 11Alcohols 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. 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 Chapter 11

10. 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 Chapter 11

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. 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. 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 Chapter 11

27. Chapter 11