Organic Chemistry II Alcohols, Phenols, Thiols , Ethers, and Sulfides

1. Organic Chemistry IIAlcohols, Phenols, Thiols, Ethers, and Sulfides Dr. Ralph C. Gatrone Department of Chemistry and Physics Virginia State University

2. Chapter Objectives • Nomenclature • Properties • Preparation • Reactions • Spectroscopy

3. Alcohols and Phenols • Important solvents and intermediates • Phenols contain an OH group connected to a carbon in a benzene ring • Methanol, CH3OH, common name is methyl alcohol, a solvent, a fuel additive, produced in large quantities • Ethanol, CH3CH2OH, common name is ethyl alcohol, a solvent, fuel, beverage, produced in large quantities

4. Alcohols, Phenols, Thiols, Ethers • Considered derivatives of water

5. Nomenclature of Alcohols • Derivatives of alkane with –ol suffix • Name longest chain containing OH • Number the chain starting nearest the carbon bearing the OH group • Number substituents, name, and list alphabetically

6. Examples

7. Classification of Alcohols • Primary – OH is attached to a carbon bearing one carbon atom • Secondary – OH is attached to a carbon bearing two carbon atoms • Tertiary – OH is attached to a carbon bearing three carbon atoms

8. Examples

9. Common Names

10. Phenols • Common natural source – coal tar • Found in many plants

11. Phenols

12. Nomenclature of Phenols • Use “phene” (the French name for benzene) as the parent hydrocarbon name, not benzene • Name substituents on aromatic ring by their position from OH

13. Common Names • Many common names in use

14. Nomenclature of Thiols • Same naming system as alcohols • Suffix is –thiol • Sometimes named as mercaptans

15. Biosynthesis of Ethanol(Fermentation)

16. Properties • Alcohols and phenols are similar to water • Form strong H-bonds • Giving higher boiling points than the corresponding hydrocarbon • Thiols do not form H-bonds (EN of S is low) • Alcohols and phenols are weakly basic • Alcohols and phenols are weakly acidic • Phenols and thiols are more acidic than water

17. Acidity Constants

18. Acidity of Alcohols • Do not react with amines or NaHCO3 • Limited reactivity with NaOH • React with alkali metals • Na, K • React with strong bases like • NaH or NaNH2 or RLi and RMgBr • Forms the alkoxide (RO-1)

19. Reactions with Bases

20. Acidity of Phenols • ArOH is more acidic than ROH • Soluble in dilute NaOH • Anion is resonance stabilized • EWG make phenols more acidic than phenol • EDG make phenols less acidic than phenol

21. Alcohols an Overview • Alcohols are derived from many types of compounds • Alkenes, alkyl halides, ketones, esters, aldehydes, and carboxylic acids can provide the alcohol • Alcohols are among most common natural materials • The alcohol hydroxyl can be converted to many other functional groups • This makes alcohols useful in synthetic planning

22. Preparation of Alcohols • Hydration of Alkenes • BH3/THF followed by H2O2 in NaOH • Hg(OAc)2 followed by NaBH4 • OsO4 followed by NaHSO3 (cis-1,2-diols) • RCO3H followed by aqueous acid (trans-1,2-diols) • From Aldehydes and Ketones • Reduction with NaBH4 • Reduces alpha beta unsaturated carbonyls as well • Reduction with LiAlH4 • Doesn’t touch alpha beta unsaturated carbonyls • From Esters • Reduction with LiAlH4 (LAH) • No reaction with NaBH4

23. Reduction of Ketones

24. Preparation of Alcohols • From carboxylic acids • Reduction with LiAlH4 is slow • Reduction with NaBH4 doesn’t occur • Reduction with BH3 is preferred method

25. Preparation of Alcohols • From Alkyl Halides • RX + Mg provides the Grignard reagent • Grignard reagents react with carbonyls to provide the alcohols

26. Grignard Reactions • with aldehydes or ketones • with esters

27. Grignard Reactions • with carboxylic acids • Grignards are strong bases • React with the acidic proton

28. Reactions of Alcohols • Alcohols react at • the O-H bond • the C-O bond

29. Alcohols to Alkyl Halides

30. Alcohols to Alkenes • Dehydration • Acid catalyzed reaction • Excellent reaction for tertiary alcohols (E1) • Provides the Zaitsev product

31. Alcohol to Alkene • Milder reaction developed • E2 process

32. Alcohols to Esters • Alcohols react with carboxylic acids • Reaction is acid catalyzed • Alcohols react with acid chlorides • Reaction is base catalyzed

33. Alcohols to Tosylate Esters • Reaction with p-toluenesulfonyl chloride (tosyl chloride, p-TosCl) in pyridine yields alkyl tosylates, ROTos • Formation of the tosylate does not involve the C–O bond so configuration at a chirality center is maintained • Alkyl tosylates react like alkyl halides

34. Oxidation of Alcohols • Can be accomplished by inorganic reagents, such as KMnO4, CrO3, and Na2Cr2O7 or by more selective, expensive reagents

35. Oxidation of Primary Alcohols • To aldehyde: pyridinium chlorochromate (PCC = C5H6NCrO3Cl) in dichloromethane • Other reagents produce carboxylic acids

36. Oxidation of Secondary Alcohols • Effective with inexpensive reagents such as Na2Cr2O7 in acetic acid • PCC is used for sensitive alcohols at lower temperatures

37. Mechanism of Oxidation • Chromium Starting Material • Chromium (VI) – yellow orange • Chromium Product • Chromium (III) – green • Cr (VI) Cr (IV) • Cr (IV) + Cr (VI) Cr (V) • Cr(V) Cr (III)

38. Preparation and Uses of Phenols • Industrial process from readily available cumene • Forms cumene hydroperoxide with oxygen at high temperature • Converted into phenol and acetone by acid

39. Industrial Preparation of Phenol

40. Laboratory Preparation of Phenols • From aromatic sulfonic acids by melting with NaOH at high temperature • Limited to the preparation of alkyl-substituted phenols

41. Reactions of Phenols • The hydroxyl group is a strongly activating, making phenols substrates for electrophilic halogenation, nitration, sulfonation, and Friedel–Crafts reactions • Reaction of a phenol with strong oxidizing agents yields a quinone • Fremy's salt [(KSO3)2NO] works under mild conditions through a radical mechanism

42. Quinones in Nature • Ubiquinones mediate electron-transfer processes involved in energy production through their redox reactions

43. Preparation of Thiols • From alkyl halides by displacement with a sulfur nucleophile such as SH • The alkylthiol product can undergo further reaction

44. Preparation of Thiols • Thiourea (NH2(C=S)NH2) as a nucleophile • Gives an intermediate alkylisothiourea salt • Hydrolyzed cleanly to the alkyl thiourea

45. Oxidation of Thiols to Disulfides • Reaction of an alkyl thiol (RSH) with bromine or iodine gives a disulfide (RSSR) • The thiol is oxidized in the process and the halogen is reduced

46. Ethers and Sulfides • An ether has two organic groups (alkyl, aryl, or vinyl) bonded to the an oxygen atom • General Formula is R–O–R • Diethyl ether is used industrially as a solvent • Tetrahydrofuran (THF) is a solvent that is a cyclic ether • Stable and un-reactive • Sulfides (R–S–R) are sulfur analogs of ethers

47. Nomenclature of Ethers • Simple ethers are named by identifying the two organic substituents and adding the word ether • If other functional groups are present, the ether part is considered an alkoxy substituent

48. Common Names • Anisole • Tetrahydrofuran (THF)

49. Nomenclature of Sulfides • Sulfides (RSR), are sulfur analogs of ethers • Named by rules used for ethers, with sulfide in place of ether for simple compounds • alkylthio in place of alkoxy

50. Structure and Properties of Ethers • R–O–R ~ tetrahedral bond angle (112° in dimethyl ether) • Oxygen is sp3-hybridized • Oxygen atom gives ethers a slight dipole moment