2. WWU -- Chemistry Oxidative preparation of aldehydes and ketones Sirromet Wines Pty Ltd 850-938 Mount Cotton Rd Mount Cotton Queensland, Australia 4165 www.sirromet.com Courtesy of Jessica Ferguson Assistant Winemaker & Site Chemist Downloaded from seniorchem.com/eei.html

3. WWU -- Chemistry 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).

4. WWU -- Chemistry Oxidations NOTE: A dehydrogenation is also a form of oxidation!

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

6. WWU -- Chemistry Oxidation of Secondary Alcohols

7. WWU -- Chemistry Oxidation of Tertiary Alcohols

8. WWU -- Chemistry Oxidation of Primary Alcohols with KMnO 4 You can’t pull the aldehyde out of this reaction, so the only product is the carboxylic acid.

9. WWU -- Chemistry Specifically...

10. 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 (KMnO 4 ) changes to a brown mud (MnO 2 )

11. WWU -- Chemistry 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!!!

12. WWU -- Chemistry 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.

13. WWU -- Chemistry 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.

14. WWU -- Chemistry Oxidation of Primary Alcohols with K 2 Cr 2 O 7 This reaction can also be done using CrO 3 (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.

15. WWU -- Chemistry The acidic conditions keep the chromium in the Cr 2 O 7 2- 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 Cr 3+ ion. This is not the world’s greatest way to prepare an aldehyde!

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

17. WWU -- Chemistry 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!

18. WWU -- Chemistry “Mechanism” of Oxidation

19. WWU -- Chemistry 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.

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

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

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

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

24. WWU -- Chemistry Example

25. … 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.

26. WWU -- Chemistry … 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...

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

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

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

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

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

32. WWU -- Chemistry The reagent is prepared by dissolving CrO 3 in hydrochloric acid and then adding pyridine. The reagent precipitates as a solid, with the formula:

33. WWU -- Chemistry 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.

34. WWU -- Chemistry Example

35. Example #2 Getting better !

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

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

38. WWU -- Chemistry 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 + Cu 2+

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

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

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

42. WWU -- Chemistry  D-(+)-Glucopyranose Notice that this is a hemiacetal

43. WWU -- Chemistry 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.

44. WWU -- Chemistry  D-(-)-Fructofuranose This is a hemiacetal

45. WWU -- Chemistry 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!

46. WWU -- Chemistry 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:  hydroxyketones also give a positive test! Fructose is an  -hydroxyketone (go back and check out its structure).

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

48. WWU -- Chemistry 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!

49. WWU -- Chemistry 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

50. WWU -- Chemistry 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.

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

52. WWU -- Chemistry The reactive portion is the hydrogen attached to Carbon #4 of the pyridine ring (see previous slide) NADH acts as a reducing agent by transfering a hydride from the C-4 position.

53. WWU -- Chemistry Reduction of Acetaldehyde in Fermentation

54. WWU -- Chemistry Reduction of Pyruvic Acid in Muscle Tissue

55. WWU -- Chemistry A biological oxidation would take place as the reverse of the reactions shown.

56. WWU -- Chemistry