1. Chapter 11 Reactions of Alcohols Jo Blackburn Richland College, Dallas, TX Dallas County Community College District  2003,  Prentice Hall Organic Chemistry, 5 th Edition L. G. Wade, Jr.

2. Chapter 112 Types of Alcohol Reactions Dehydration to alkene Oxidation to aldehyde, ketone Substitution to form alkyl halide Reduction to alkane Esterification Tosylation Williamson synthesis of ether =>

3. Chapter 113 Summary Table =>

4. Chapter 114 Oxidation States Easy for inorganic salts  CrO 4 2- reduced to Cr 2 O 3  KMnO 4 reduced to MnO 2 Oxidation: loss of H 2, gain of O, O 2, or X 2 Reduction: gain of H 2 or H -, loss of O, O 2, or X 2 Neither: gain or loss of H +, H 2 O, HX =>

5. Chapter 115 1º, 2º, 3º Carbons =>

6. Chapter 116 Oxidation of 2° Alcohols 2° alcohol becomes a ketone Reagent is Na 2 Cr 2 O 7 /H 2 SO 4 Active reagent probably H 2 CrO 4 Color change: orange to greenish-blue =>

7. Chapter 117 Oxidation of 1° Alcohols 1° alcohol to aldehyde to carboxylic acid Difficult to stop at aldehyde Use pyridinium chlorochromate (PCC) to limit the oxidation. PCC can also be used to oxidize 2° alcohols to ketones. =>

8. Chapter 118 3° Alcohols Don’t Oxidize Cannot lose 2 H’s Basis for chromic acid test =>

9. Chapter 119 Other Oxidation Reagents Collins reagent: Cr 2 O 3 in pyridine Jones reagent: chromic acid in acetone KMnO 4 (strong oxidizer) Nitric acid (strong oxidizer) CuO, 300°C (industrial dehydrogenation) Swern oxidation: dimethylsulfoxide, with oxalyl chloride and hindered base, oxidizes 2  alcohols to ketones and 1  alcohols to aldehydes. =>

10. Chapter 1110 Biological Oxidation Catalyzed by ADH, alcohol dehydrogenase. Oxidizing agent is NAD +, nicotinamide adenine dinucleotide. Ethanol oxidizes to acetaldehyde, then acetic acid, a normal metabolite. Methanol oxidizes to formaldehyde, then formic acid, more toxic than methanol. Ethylene glycol oxidizes to oxalic acid, toxic. Treatment for poisoning is excess ethanol. =>

11. Chapter 1111 Alcohol as a Nucleophile ROH is weak nucleophile RO - is strong nucleophile New O-C bond forms, O-H bond breaks. =>

12. Chapter 1112 Alcohol as an Electrophile OH - is not a good leaving group unless it is protonated, but most nucleophiles are strong bases which would remove H +. Convert to tosylate (good leaving group) to react with strong nucleophile (base) =>  + + C-Nuc bond forms, C-O bond breaks

13. Chapter 1113 Formation of Tosylate Ester p-toluenesulfonyl chloride TsCl, “tosyl chloride” ROTs, a tosylate ester =>

14. Chapter 1114 S N 2 Reactions of Tosylates With hydroxide produces alcohol With cyanide produces nitrile With halide ion produces alkyl halide With alkoxide ion produces ether With ammonia produces amine salt With LiAlH 4 produces alkane =>

15. Chapter 1115 Summary of Tosylate Reactions =>

16. Chapter 1116 Reduction of Alcohols Dehydrate with conc. H 2 SO 4, then add H 2 Tosylate, then reduce with LiAlH 4 =>

17. Chapter 1117 Reaction with HBr -OH of alcohol is protonated -OH 2 + is good leaving group 3° and 2° alcohols react with Br - via S N 1 1° alcohols react via S N 2 =>

18. Chapter 1118 Reaction with HCl Chloride is a weaker nucleophile than bromide. Add ZnCl 2, which bonds strongly with -OH, to promote the reaction. The chloride product is insoluble. Lucas test: ZnCl 2 in conc. HCl  1° alcohols react slowly or not at all.  2  alcohols react in 1-5 minutes.  3  alcohols react in less than 1 minute. =>

19. Chapter 1119 Limitations of HX Reactions HI does not react Poor yields of 1° and 2° chlorides May get alkene instead of alkyl halide Carbocation intermediate may rearrange. =>

20. Chapter 1120 Reactions with Phosphorus Halides Good yields with 1° and 2° alcohols PCl 3 for alkyl chloride (but SOCl 2 better) PBr 3 for alkyl bromide P and I 2 for alkyl iodide (PI 3 not stable) =>

21. Chapter 1121 Mechanism with PBr 3 P bonds to -OH as Br - leaves Br - attacks backside (S N 2) HOPBr 2 leaves =>

22. Chapter 1122 Reaction with Thionyl Chloride Produces alkyl chloride, SO 2, HCl S bonds to -OH, Cl - leaves Cl - abstracts H + from OH C-O bond breaks as Cl - transferred to C =>

23. Chapter 1123 Dehydration Reactions Conc. H 2 SO 4 produces alkene Carbocation intermediate Saytzeff product Bimolecular dehydration produces ether Low temp, 140°C and below, favors ether High temp, 180°C and above, favors alkene =>

24. Chapter 1124 Dehydration Mechanisms =>

25. Chapter 1125 Energy Diagram, E1 =>

26. Chapter 1126 Unique Reactions of Diols Pinacol rearrangement Periodic acid cleavage =>

27. Chapter 1127 Pinacol Rearrangement Pinacol: 2,3-dimethyl-2,3-butanediol Dehydration with sulfuric acid =>

28. Chapter 1128 Periodic Cleavage of Glycols Same products formed as from ozonolysis of the corresponding alkene. =>

29. Chapter 1129 Esterification Fischer: alcohol + carboxylic acid Tosylate esters Sulfate esters Nitrate esters Phosphate esters =>

30. Chapter 1130 Fischer Esterification Acid + Alcohol yields Ester + Water Sulfuric acid is a catalyst. Each step is reversible. =>

31. Chapter 1131 Tosylate Esters Alcohol + p-Toluenesulfonic acid, TsOH Acid chloride is actually used, TsCl =>

32. Chapter 1132 Sulfate Esters Alcohol + Sulfuric Acid =>

33. Chapter 1133 Nitrate Esters =>

34. Chapter 1134 Phosphate Esters =>

35. Chapter 1135 Phosphate Esters in DNA =>

36. Chapter 1136 Alkoxide Ions ROH + Na (or NaH) yields sodium alkoxide RO - + 1° alkyl halide yields ether (Williamson ether synthesis) =>

37. Chapter 1137 End of Chapter 11