OXIDATIVE PREPARATION OF ALDEHYDES AND KETONES

1. OXIDATIVE PREPARATION OF ALDEHYDES AND KETONES WWU -- Chemistry

2. REMEMBER: • Go back to Special Topics Box at the beginning of Chapter 14. • Conversion of an alcohol to an aldehyde or ketone represents an oxidation (removal of H atoms). • Conversion of an aldehyde to a carboxylic acid is also an oxidation (addition of an O atom). • Oxidation can involve the addition of oxygen atoms or it can involve the removal of hydrogen atoms (dehydrogenation). WWU -- Chemistry

3. Oxidations NOTE: A dehydrogenationis also a form of oxidation! WWU -- Chemistry

4. Oxidation of Primary Alcohols The aldehyde can be oxidized in a second step [O] represent an oxidation WWU -- Chemistry

5. Oxidation of Secondary Alcohols WWU -- Chemistry

6. Oxidation of Tertiary Alcohols WWU -- Chemistry

7. Oxidation of Primary Alcohols with KMnO4 You can’t pull the aldehyde out of this reaction, so the only product is the carboxylic acid. WWU -- Chemistry

8. Specifically... WWU -- Chemistry

9. The aldehyde is formed as an intermediate, but it is unstable under the reaction conditions and cannot be isolated. • There is a color change that accompanies the reaction -- the purple solution (KMnO4) changes to a brown mud (MnO2) WWU -- Chemistry

10. Primary alcohols are oxidized by atmospheric oxygen to aldehydes and carboxylic acids. This reaction is very slow. It is catalyzed by enzymes (Acetobacter) This is how wine turns to vinegar!!! WWU -- Chemistry

11. Oxidation of Primary Alcohols to Aldehydes • Requires less vigorous oxidation conditions. • We can try to remove the aldehyde from the reaction medium as quickly as it is formed • Generally, the aldehyde has a lower boiling point than either the corresponding alcohol or carboxylic acid • We can also try to find a milder oxidizing agent. WWU -- Chemistry

12. Dehydrogenation over Copper • This reaction is generally done by passing the vapors of the alcohol through a tube furnace in a stream of inert carrier gas. • This is not a practical laboratory method -- it is better suited to industrial processes. • The reaction stops at the aldehyde stage -- no more removal of hydrogen can take place. WWU -- Chemistry

13. Oxidation of Primary Alcohols with K2Cr2O7 • This reaction can also be done using CrO3 (chromic oxide) in sulfuric acid. • The aldehyde is distilled away from the reaction vessel as quickly as it is formed. If the aldehyde is not removed, it will suffer a second oxidation, and the product will be the carboxylic acid. WWU -- Chemistry

14. The acidic conditions keep the chromium in the Cr2O72- state. • Potassium dichromate is not as powerful an oxidizing agent as is potassium permanganate • Sodium dichromate can be substituted for potassium dichromate -- it makes no difference. • There is a color change during the reaction. The orange color of the dichromate changes to the green of Cr3+ ion. • This is not the world’s greatest way to prepare an aldehyde! WWU -- Chemistry

15. Dichromate Oxidation of Ethanol Orange solution Green precipitate WWU -- Chemistry

16. Secondary alcohols are oxidized to ketones Here, it doesn’t really matter whether you use potassium permanganate, potassium dichromate, nitric acid, sodium hypochlorite (Bleach), or other oxidizing agents. Actually, it does matter, but here we are presenting the simple introduction! WWU -- Chemistry

17. “Mechanism” of Oxidation WWU -- Chemistry

18. The important point about the mechanism is that the loss of the alcohol C-H occurs during the rate-determining step. • What is not well understood is what happens to the chromium after the formation of the ketone. There is some sort of cascading down through a series of oxidation states, but no one is sure exactly how this happens. WWU -- Chemistry

19. Which would react faster? There is a primary isotope effect -- C-H bond-breaking occurs during the rate-determining step! WWU -- Chemistry

20. Tertiary alcohols are not oxidized Under acidic conditions, the only available reaction is dehydration. WWU -- Chemistry

21. Let’s re-examine methods for oxidizing primary alcohols to aldehydes and secondary alcohols to ketones (and let’s try some modern reactions!) WWU -- Chemistry

22. Oxidation of Secondary Alcohols Jones Oxidation WWU -- Chemistry

23. Example WWU -- Chemistry

24. … but what if you want to make an aldehyde? • The problem is how to stop the oxidation at the aldehyde stage. • We need mild oxidizing conditions -- strong enough to do one 2-electron oxidation, but not strong enough to do the second 2-electron oxidation. • We can use the Jones oxidation (potassium dichromate and sulfuric acid) and try to distill the aldehyde out of the reaction vessel before it gets oxidized a second time. WWU -- Chemistry

25. … but what if you want to make an aldehyde? (Part Two) • Or, we can tinker with the oxidizing agent, to attenuate its properties -- i.e., we can try to “dial in” the power of the oxidizing agent to just the right level. • Which brings us to... WWU -- Chemistry

26. Oxidation with Chromic Oxide and Pyridine Sarett Oxidation WWU -- Chemistry

27. The oxidizing reagent is a type of complex between the chromic oxide and the pyridine. WWU -- Chemistry

28. Preparation of an Aldehyde Note that the reaction does not affect other functional groups. WWU -- Chemistry

29. Another useful reagent for oxidizing alcohols to aldehydes or ketones -- in good yield (!) -- is pyridinium chlorochromate (PCC). WWU -- Chemistry

30. Oxidation with Pyridinium Chlorochromate “PCC” Oxidation WWU -- Chemistry

31. The reagent is prepared by dissolving CrO3 in hydrochloric acid and then adding pyridine. The reagent precipitates as a solid, with the formula: WWU -- Chemistry

32. The reagent is used in nearly stoichiometric ratios to perform oxidations under mild conditions. Because the reagent is mildly acidic, however, it may not be suitable for use with acid-sensitive compounds. WWU -- Chemistry

33. Example WWU -- Chemistry

34. Example #2 Getting better! WWU -- Chemistry

35. Example #3 WOW!!! WWU -- Chemistry

36. Notice how the other functional groups survive without being changed. WWU -- Chemistry

37. CHANGE OF GEARS: • Aldehydes can be oxidized to carboxylic acids. • This oxidation can take place under very mild oxidizing conditions. • Aldehydes can be oxidized with such weak oxidizing agents as metal cations, especially: • Ag+ Cu2+ WWU -- Chemistry

38. The Tollens Test silver mirror This test is specific for aldehydes -- ketones will not react with silver ion. WWU -- Chemistry

39. The Tollens test is important in carbohydrate chemistry, for proof of structure. WWU -- Chemistry

40. These monosaccharides cyclize to form hemiacetals WWU -- Chemistry

41. b-D-(+)-Glucopyranose Notice that this is a hemiacetal WWU -- Chemistry

42. The hemiacetal form is in equilibrium with the open-chain free aldehyde form (remember mutarotation?). • While in the free aldehyde form, glucose can reduce silver ion (give a silver mirror -- a positive Tollens test). • Because it can reduce silver ion, glucose is considered a reducing sugar. WWU -- Chemistry

43. b-D-(-)-Fructofuranose This is a hemiacetal WWU -- Chemistry

44. Being a hemiacetal, the cyclic form of fructose is in rapid equilibrium with the open-chain, free ketone form. • Therefore, fructose is also capable of reducing silver ion, and is thus classified a reducing sugar! WWU -- Chemistry

45. Yeah, but…. • I thought you said that only aldehydes were capable of giving a positive Tollens test, and fructose is a ketone! • There is an exception: a-hydroxyketones also give a positive test! • Fructose is an a-hydroxyketone (go back and check out its structure). WWU -- Chemistry

46. Maltose: A Disaccharide Position (b) is now an acetal Position (a) is still a hemiacetal Maltose is a reducing sugar WWU -- Chemistry

47. Sucrose: A Disaccharide Both positions (a) and (b) are now acetals. Neither is in equilibrium with the open-chain free carbonyl form. Sucrose is a non-reducing sugar! WWU -- Chemistry

48. What about a monosaccharide-ether (a glycoside)? This is an acetal -- it is not in equilibrium with a free aldehyde form This is a non-reducing sugar WWU -- Chemistry

49. How do hydride transfer (oxidation-reduction) reactions take place in biological systems? • We can’t use lithium aluminum hydride or pyridinium chlorochromate inside a living cell! • Any reagent has to be water-soluble, capable of being transported across cell membranes, and able to act in concert with an enzyme. WWU -- Chemistry

50. Nicotinamide Adenine Dinucleotide “NADH” WWU -- Chemistry