Organic Chemistry II Alcohols, Phenols, Thiols

1. Organic Chemistry IIAlcohols, Phenols, Thiols Dr Seemal Jelani Chem-240

2. Chapter Objectives • Nomenclature • Properties • Preparation • Reaction Dr Seemal Jelani Chem-240

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 Dr Seemal Jelani Chem-240

4. Ethanol, CH3CH2OH, common name is ethyl alcohol, a solvent, fuel, beverage, produced in large quantities Dr Seemal Jelani Chem-240

5. Alcohols, Phenols, Thiols, Ethers • Considered derivatives of water Dr Seemal Jelani Chem-240

6. 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 Dr Seemal Jelani Chem-240

7. Examples Dr Seemal Jelani Chem-240

8. 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 Dr Seemal Jelani Chem-240

9. Examples Dr Seemal Jelani Chem-240

10. Common Names Dr Seemal Jelani Chem-240

11. Phenols • Common natural source – coal tar • Found in many plants Dr Seemal Jelani Chem-240

12. Phenols Dr Seemal Jelani Chem-240

13. 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 Dr Seemal Jelani Chem-240

14. Common Names • Many common names in use Dr Seemal Jelani Chem-240

15. Nomenclature of Thiols • Same naming system as alcohols • Suffix is –thiol • Sometimes named as mercaptans Dr Seemal Jelani Chem-240

16. Biosynthesis of Ethanol(Fermentation) Dr Seemal Jelani Chem-240

17. 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 Dr Seemal Jelani Chem-240

18. Acidity Constants Dr Seemal Jelani Chem-240

19. 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) Dr Seemal Jelani Chem-240

20. Reactions with Bases Dr Seemal Jelani Chem-240

21. 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 Dr Seemal Jelani Chem-240

22. 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 Dr Seemal Jelani Chem-240

23. Preparation Dr Seemal Jelani Chem-240

24. 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) Dr Seemal Jelani Chem-240

25. 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 Dr Seemal Jelani Chem-240

26. Reduction of Ketones Dr Seemal Jelani Chem-240

27. Preparation of Alcohols • From carboxylic acids • Reduction with LiAlH4 is slow • Reduction with NaBH4 doesn’t occur • Reduction with BH3 is preferred method Dr Seemal Jelani Chem-240

28. From Alkyl halides • RX + Mg provides the Grignard reagent • Grignard reagents react with carbonyls to provide the alcohols Dr Seemal Jelani Chem-240

29. Grignard Reactions • With aldehydes or ketones • With esters Dr Seemal Jelani Chem-240

30. Grignard Reactions • With carboxylic acids • Grignard's are strong bases • React with the acidic proton Dr Seemal Jelani Chem-240

31. Reactions Dr Seemal Jelani Chem-240

32. Reactions of Alcohols • Alcohols react at • the O-H bond • the C-O bond Dr Seemal Jelani Chem-240

33. Alcohols to Alkyl Halides Dr Seemal Jelani Chem-240

34. Alcohols to Alkenes • Dehydration • Acid catalyzed reaction • Excellent reaction for tertiary alcohols (E1) • Provides the Zaitsev product Dr Seemal Jelani Chem-240

35. When the substrate is asymmetric, regioselectivity is determined by Zaitsev’s rule • The one -step mechanisms is E2 reaction and two step reaction mechanism is called E1 reaction, respectively. Dr Seemal Jelani

36. What is regioselectivity • It is the preference of one direction of chemical bond making or breaking over all other possible directions Dr Seemal Jelani

37. What is Zaitsev’s rule • In chemistry, Zaitsev's rule, Saytzeff's rule or Saytsev's rule is a rule that states “that if more than one alkene can be formed during dehalogenation by an elimination reaction the more stable alkene is the major product” Dr Seemal Jelani

38. Who is then stable • In general, the compound that has a more highly substituted C=C double bond is more stable. Dr Seemal Jelani

39. Dr Seemal Jelani

40. Alcohol to Alkene • Milder reaction developed • E2 process Dr Seemal Jelani Chem-240

41. Alcohols to Esters • Alcohols react with carboxylic acids • Reaction is acid catalyzed • Alcohols react with acid chlorides • Reaction is base catalyzed Dr Seemal Jelani Chem-240

42. 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 Dr Seemal Jelani Chem-240

43. Oxidation of Alcohols • Can be accomplished by inorganic reagents, such as KMnO4, CrO3, and Na2Cr2O7 or by more selective, expensive reagents Dr Seemal Jelani Chem-240

44. Oxidation of Primary Alcohols • To aldehyde: pyridinium chlorochromate (PCC = C5H6NCrO3Cl) in dichloromethane • Other reagents produce carboxylic acids Dr Seemal Jelani Chem-240

45. Oxidation of Secondary Alcohols • Effective with inexpensive reagents such as Na2Cr2O7 in acetic acid • PCC is used for sensitive alcohols at lower temperatures Dr Seemal Jelani Chem-240

46. 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 Dr Seemal Jelani Chem-240

47. Industrial Preparation of Phenol Dr Seemal Jelani Chem-240

48. Laboratory Preparation of Phenols • From aromatic sulfonic acids by melting with NaOH at high temperature • Limited to the preparation of alkyl-substituted phenols Dr Seemal Jelani Chem-240

49. 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 Dr Seemal Jelani Chem-240