Organic Chemistry: Alcohols and Ethers - Naming, Properties, and Synthesis

1. Chapter 6Alcohols and Ethers

2. Nomenclature • Nomenclature of Alcohols • Examples • Common Names of simple alcohols are still often used and are approved by IUPAC Chapter 4

3. Nomenclature • 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 6

4. 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 6

5. 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 6

6. 1- Synthesis of Alcohols from Alkenes • Acid-Catalyzed Hydration of Alkenes • This is a reversible reaction with Markovnikovregioselectivity Chapter 6

7. Reactions of Carbonyl Compounds with Nucleophiles • Carbonyl groups can undergo nucleophilic addition • The nucleophile adds to the d+ carbon • The p electrons shift to the oxygen • The carbon becomes sp3 hybridized and therefore tetrahedral • Hydride ions and carbanions are two examples of nucleophiles that react with the carbonyl carbon Chapter 12

8. 2- Synthesis of Alcohols by Reduction of Carbonyl Compounds • A variety of carbonyl compounds can be reduced to alcohols • Carboxylic acids can be reduced to primary alcohols • These are difficult reductions and require the use of powerful reducing agents such as lithium aluminum hydride (LiAlH4 also abbreviated LAH) Chapter 12

9. Esters are also reduced to primary alcohols • LAH or high pressure hydrogenation can accomplish this transformation • Aldehydes and ketones are reduced to 1o and 2o alcohols respectively • Aldehydes and ketones are reduced relatively easily; the mild reducing agent sodium borohydride (NaBH4) is typically used • LAH and hydrogenation with a metal catalyst can also be used Chapter 12

10. Carboxylic acids and esters are considerably less reactive to reduction than aldehydes and ketones and require the use of LAH • Lithium aluminium hydride is very reactive with water and must be used in an anhydrous solvent such as ether • Sodium borohydride is considerably less reactive and can be used in solvents such as water or an alcohol Chapter 12

11. 3- Synthesis of Alcohols from Grignard Reagents Organometallic Compounds • Carbon-metal bonds vary widely in character from mostly covalent to mostly ionic depending on the metal • The greater the ionic character of the bond, the more reactive the compound • Organopotassium compounds react explosively with water and burst into flame when exposed to air Chapter 12

12. Grignard Reagents • Grignard reagents are prepared by the reaction of organic halides with magnesium turnings • An ether solvent is used because it forms a complex with the Grignard reagent which stabilizes it Chapter 12

13. 3- Synthesis of Alcohols from Grignard Reagents • Aldehydes and ketones react with Grignard reagents to yield different classes of alcohols depending on the starting carbonyl compound Chapter 12

14. Chapter 12

15. 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 6

16. Reactions of alcohols • Carbonyl groups and alcohols can be interconverted by oxidation and reduction reactions • Alcohols can be oxidized to aldehydes; aldehydes can be reduced to alcohols Chapter 6

17. 1- Oxidation of Alcohols • Oxidation of Primary Alcohols to Aldehydes • A primary alcohol can be oxidized to an aldehyde or a carboxylic acid • The oxidation is difficult to stop at the aldehyde stage and usually proceeds to the carboxylic acid • A reagent which stops the oxidation at the aldehyde stage is pyridiniumchlorochromate (PCC) • PCC is made from chromium trioxide under acidic conditions • It is used in organic solvents such as methylene chloride (CH2Cl2) Chapter 12

18. Oxidation of Primary Alcohols to Carboxylic Acids • Potassium permanganate (KMnO4) is a typical reagent used for oxidation of a primary alcohol to a carboxylic acid • The reaction is generally carried out in aqueous solution; a brown precipitate of MnO2 indicates that oxidation has taken place • Oxidation of Secondary Alcohols to Ketones • Oxidation of a secondary alcohol stops at the ketone • Many oxidizing agents can be used, including chromic acid (H2CrO4) and Jones reagent (CrO3 in acetone) Chapter 12

19. A Chemical Test for Primary and Secondary Alcohols • Chromium oxide in acid has a clear orange color which changes to greenish opaque if an oxidizable alcohol is present Chapter 12

20. 2- 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 6

21. Oxidation-Reduction Reactions in Organic Chemistry • Reduction: increasing the hydrogen content or decreasing the oxygen content of an organic molecule • A general symbol for reduction is [H] • Oxidation: increasing the oxygen content or decreasing the hydrogen content of an organic molecule • A general symbol for oxidation is [O] • Oxidation can also be defined as a reaction that increases the content of any element more electronegative than carbon Chapter 12

22. 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 6

23. 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 6

24. 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 • Reaction of thionyl chloride to give alkyl chlorides • Often an amine is added to react with HCl formed in the reaction Chapter 6

25. 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 6

26. 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 6

27. 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 6