1. Chem 2412: Ch. 18 Aldehydes and Ketones

2. Classes of Carbonyl Compounds

3. © 2013 Pearson Education, Inc. Chapter 18 3 Structure of the Carbonyl Group Carbon is sp 2 hybridized. C ═ O bond is shorter, stronger, and more polar than C ═ C bond in alkenes.

4. © 2013 Pearson Education, Inc. Chapter 18 4 Resonance The first resonance is better because all atoms complete the octet and there are no charges. The carbonyl carbon has a partial positive and will react as an electrophile.

5. © 2013 Pearson Education, Inc. Chapter 18 5 Ketone Nomenclature Select the longest continuous carbon chain that includes the carbonyl carbon. Number the chain so that the carbonyl carbon has the lowest number. Replace the alkane -e with the suffix -one.

6. © 2013 Pearson Education, Inc. Chapter 18 6 Cyclic Ketone Nomenclature For cyclic ketones, the carbonyl carbon is assigned the number 1. When the compound has a carbonyl and a double bond, the carbonyl takes precedence.

7. Examples of Ketones

8. © 2013 Pearson Education, Inc. Chapter 18 8 Aldehydes Nomenclature The aldehyde carbon is number 1. IUPAC: Replace -e with -al. If the aldehyde group is attached to a ring, the suffix carbaldehyde is used.

9. Examples of Aldehydes

10. Ketones/Aldehydes as minor FGs, benzaldehydes If C=O is lower priority functional group Ketone/aldehyde is oxo group Aldehyde is formyl group (on benzene) Aldehyde is higher priority than ketone

11. Common Names for Ketones Named as alkyl attachments to —C ═ O Use Greek letters instead of numbers.

12. Historical Common Names

13. Common Aldehydes and Ketones Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011

14. © 2013 Pearson Education, Inc. Chapter 18 14 Boiling Points Ketones and aldehydes are more polar, so they have a higher boiling point than comparable alkanes or ethers. They cannot hydrogen-bond to each other, so their boiling point is lower than the comparable alcohol.

15. Boiling Points  Ketones and aldehydes are more polar, so they have a higher boiling point than comparable alkanes or ethers.  They cannot hydrogen-bond to each other, so their boiling point is lower than the comparable alcohol. δ-δ- δ-δ- δ+δ+ δ+δ+ Intermolecular dipolar Hydrogen bond δ+δ+ δ-δ- Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011

16. © 2013 Pearson Education, Inc. Chapter 18 16 Solubility of Ketones and Aldehydes Good solvent for alcohols Lone pair of electrons on oxygen of carbonyl can accept a hydrogen bond from O—H or N—H. Acetone and acetaldehyde are miscible in water.

17. © 2013 Pearson Education, Inc. Chapter 18 17 Infrared (IR) Spectroscopy Very strong C ═ O stretch around 1710 cm -1 for ketones and 1725 cm -1 for simple aldehydes Additional C—H stretches for aldehyde: Two absorptions at 2710 cm -1 and 2810 cm -1

18. © 2013 Pearson Education, Inc. Chapter 18 18 Proton NMR Spectra Aldehyde protons normally absorb between  9 and  10. Protons of the α carbon usually absorb between  2.1 and  2.4 if there are no other electron- withdrawing groups nearby.

19. © 2013 Pearson Education, Inc. Chapter 18 19 1 H NMR Spectroscopy Protons closer to the carbonyl group are more deshielded. The , and  protons appear at values of  that decrease with increasing distance from the carbonyl group.

20. © 2013 Pearson Education, Inc. Chapter 18 20 Carbon NMR Spectra of Ketones The spin-decoupled carbon NMR spectrum of 2- heptanone shows the carbonyl carbon at 208 ppm and the α carbon at 30 ppm (methyl) and 44 ppm (methylene).

21. Mass Spectrometry (MS)

22. MS for Butyraldehyde

23. © 2013 Pearson Education, Inc. Chapter 18 23 McLafferty Rearrangement Occurs during MS analysis. The net result of this rearrangement is the breaking of the  bond and the transfer of a proton from the  carbon to the oxygen. An alkene is formed as a product of this rearrangement through the tautomerization of the enol.

24. © 2013 Pearson Education, Inc. Chapter 18 24 Review: Grignards as a Source for Ketones and Aldehydes A Grignard reagent can be used to make an alcohol, and then the alcohol can be easily oxidized. Aldehyde  Ketone

25. Review: Oxidation of Primary Alcohols to Aldehydes PCC is selectively used to oxidize primary alcohols to aldehydes. The Swern oxidation could also be used. Review: Ozonolysis of Alkenes Double bond is oxidatively cleaved by ozone followed by reduction. Ketones and aldehydes can be isolated as products under these conditions.

26. © 2013 Pearson Education, Inc. Chapter 18 26 Friedel–Crafts Reaction Reaction between an acyl halide and an aromatic ring will produce a ketone.

27. © 2013 Pearson Education, Inc. Chapter 18 27 Review: Hydration of Alkynes The initial product of Markovnikov hydration is an enol, which quickly tautomerizes to its keto form. Internal alkynes can be hydrated, but mixtures of ketones often result.

28. © 2013 Pearson Education, Inc. Chapter 18 28 Review: Hydroboration–Oxidation of Alkynes Hydroboration–oxidation of an alkyne gives anti- Markovnikov addition of water across the triple bond.

29. © 2013 Pearson Education, Inc. Chapter 18 29 Synthesis of Ketones from Carboxylic Acids Organolithiums will attack the lithium salts of carboxylate anions to give dianions. Protonation of the dianion forms the hydrate of a ketone, which quickly loses water to give the ketone. Product different than addition of R to esters, acid chlorides (Chapter 10).

30. © 2013 Pearson Education, Inc. Chapter 18 30 Ketones and Aldehydes from Nitriles A Grignard or organolithium reagent can attack the carbon of the nitrile. The imine is then hydrolyzed to form a ketone.

31. © 2013 Pearson Education, Inc. Chapter 18 31 Reduction of Nitriles to Aldehydes Aluminum hydrides can reduce nitriles to aldehydes. Diisobutylaluminum hydride, abbreviated (i-Bu) 2 AlH or DIBAL-H, is commonly used for the reduction of nitriles.

32. © 2013 Pearson Education, Inc. Chapter 18 32 Aldehydes from Acid Chlorides Lithium aluminum tri(t-butoxy)hydride is a milder reducing agent that reacts faster with acid chlorides than with aldehydes. Similar to LAH, which adds H- as nucleophile to carbonyls, producing primary or secondary alcohols (chapter 10).

33. © 2013 Pearson Education, Inc. Chapter 18 33 Lithium Dialkyl Cuprate Reagents A lithium dialkylcuprate will transfer one of its alkyl groups to the acid chloride. Grignards and organolithiums cannot do this reaction.

34. © 2013 Pearson Education, Inc. Chapter 18 34 Nucleophilic Addition A strong nucleophile attacks the carbonyl carbon, forming an alkoxide ion that is then protonated. Aldehydes are more reactive than ketones.

35. © 2013 Pearson Education, Inc. Chapter 18 35 The Wittig Reaction The Wittig reaction converts the carbonyl group into a new C ═ C double bond where no bond existed before. A phosphorus ylide is used as the nucleophile in the reaction.

36. © 2013 Pearson Education, Inc. Chapter 18 36 Preparation of Phosphorus Ylides Prepared from triphenylphosphine and an unhindered alkyl halide. Butyllithium then abstracts a hydrogen from the carbon attached to phosphorus.

37. © 2013 Pearson Education, Inc. Chapter 18 37 Mechanism of the Wittig Reaction Betaine formation Oxaphosphetane formation

38. © 2013 Pearson Education, Inc. Chapter 18 38 Mechanism for Wittig The oxaphosphetane will collapse, forming carbonyl (ketone or aldehyde) and a molecule of triphenyl phosphine oxide.

39. © 2013 Pearson Education, Inc. Chapter 18 39 In an aqueous solution, a ketone or an aldehyde is in equilibrium with its hydrate, a geminal diol. With ketones, the equilibrium favors the unhydrated keto form (carbonyl). Hydration of Ketones and Aldehydes

40. © 2013 Pearson Education, Inc. Chapter 18 40 Hydration of Carbonyls Hydration occurs through the nucleophilic addition mechanism, with water (in acid) or hydroxide (in base) serving as the nucleophile. Acid catalyzed Base catalyzed The hydroxide ion attacks the carbonyl group. Protonation of the intermediate gives the hydrate.

41. © 2013 Pearson Education, Inc. Chapter 18 41 Cyanohydrin Formation The mechanism is a base-catalyzed nucleophilic addition: Attack by cyanide ion on the carbonyl group, followed by protonation of the intermediate. HCN is highly toxic.

42. © 2013 Pearson Education, Inc. Chapter 18 42 Formation of Imines Ammonia or a primary amine reacts with a ketone or an aldehyde to form an imine. Imines are nitrogen analogues of ketones and aldehydes with a C ═ N bond in place of the carbonyl group. Optimum pH is around 4.5.

43. Mechanism of Imine Formation Acid-catalyzed addition of the amine to the carbonyl compound group Acid-catalyzed dehydration

44. Formation of Acetals

45. Addition of alcohol to aldehydes and ketones  Hemiacetal is unstable, hard to isolate (see next slide).  With excess alcohol and an acid catalyst, a stable acetal is formed. Hemiacetal intermediate acetal Hemiketal intermediate ketal

46. © 2013 Pearson Education, Inc. Chapter 18 46 Mechanism for Stable Hemiacetal Formation Must be acid-catalyzed. Adding H + to carbonyl makes it more reactive with weak nucleophile, ROH.

47. Acetal Formation

48. Hydrolysis of acetals and ketals  “Cutting by water” is essentially the reverse of the addition of alcohol to either aldehyde or ketone. aldehyde acetalalcohol ketone ketalalcohol

49. © 2013 Pearson Education, Inc. Chapter 18 49 Cyclic Acetals Addition of a vicinal diol produces a cyclic acetal. The reaction is reversible. This reaction is used in synthesis to protect carbonyls from reaction.

50. © 2013 Pearson Education, Inc. Chapter 18 50 Acetals as Protecting Groups Hydrolyze easily in acid; stable in base Aldehydes are more reactive than ketones.

51. © 2013 Pearson Education, Inc. Chapter 18 51 Reaction and Deprotection The acetal will not react with NaBH 4, so only the ketone will get reduced. Hydrolysis conditions will protonate the alcohol and remove the acetal to restore the aldehyde.

52. © 2013 Pearson Education, Inc. Chapter 18 52 Review: Oxidation of Aldehydes Aldehydes are easily oxidized to carboxylic acids.

53. Summary of Reduction Reagents Sodium borohydride, NaBH 4, can reduce ketones to secondary alcohols and aldehydes to primary alcohols. Lithium aluminum hydride, LiAlH 4, is a powerful reducing agent, so it can also reduce carboxylic acids and their derivatives. Hydrogenation with a catalyst can reduce the carbonyl, but it will also reduce any double or triple bonds present in the molecule.

54. © 2013 Pearson Education, Inc. Chapter 18 54 Review: Sodium Borohydride NaBH 4 can reduce ketones and aldehydes, but not esters, carboxylic acids, acyl chlorides, or amides.

55. © 2013 Pearson Education, Inc. Chapter 18 55 Review: Lithium Aluminum Hydride LiAlH 4 can reduce any carbonyl because it is a very strong reducing agent. Difficult to handle

56. © 2013 Pearson Education, Inc. Chapter 18 56 Catalytic Hydrogenation Widely used in industry Raney nickel is finely divided Ni powder saturated with hydrogen gas. It will attack the alkene first, then the carbonyl.

57. © 2013 Pearson Education, Inc. Chapter 18 57 Deoxygenation of Ketones and Aldehydes The Clemmensen reduction or the Wolff–Kishner reduction can be used to deoxygenate ketones and aldehydes.

58. Clemmensen Reduction

59. © 2013 Pearson Education, Inc. Chapter 18 59 Wolff–Kishner Reduction Forms hydrazone, then heat with strong base like KOH or potassium tert-butoxide Use a high-boiling solvent: ethylene glycol, diethylene glycol, or DMSO. A molecule of nitrogen is lost in the last steps of the reaction.

60. Intramolecular addition of alcohols to aldehyde  C1 is hemiacetal carbon.  Attached to it you will find: H, OH, OR and R, just like non-cyclical compounds. Intramolecular hemiacetal glucose C C C C CH 2 C OH HOH H H H H O 1 2 3 4 5 6 * CH 2 OH C C C C O C 6 5 4 32 1 OHOH H OH H H H H

61. Aldehyde Rxns – Testing for Aldehydes  Tollens’ reagent reduces silver ions to metallic silver  Benedict’s Reagent reacts with ketones that have an alcohol on the adjacent carbon (e.g., glucose)  Products include a red precipitate of copper (I) oxide Tollens’ Reagent (reacts with all aldehydes) Benedict’s Reagent (reacts with aldehydes, some ketones)