TOPIC 3. ALDEHYDES AND KETONES (Chapters 12 and 16)

1. TOPIC 3. ALDEHYDES AND KETONES(Chapters 12 and 16)

2. OBJECTIVES • Describe the synthesis aldehydes and ketones. • Describe the carbonyl group and oxidation-reductions reactions associated with alcohols and carbonyl groups. • Describe some the addition reactions of aldehydes and ketones in which nucleophiles add to the electrophilic carbonyl. • Describe the mechanisms by which carbonyl groups are transformed to alcohols in C-C bond forming reactions. • Describe how C-C bonds can be formed by other reactions of organometallic compounds (not involving the formation of alcohols). • Use this knowledge to predict the products of reactions and synthesize complex compounds using these procedures.

3. ALDEHYDES AND KETONES S:12.1; 16.1 Carbonyls are electrophilic Carbonyls are weakly basic; protonation makes the carbonyl more electrophilic

4. Nomenclature S:16.2Prob:16.23

5. Physical Properties S:16.3 The carbonyl group has a permanent dipole moment and is therefore much more polar than a hydrocarbon, but less polar than an alcohol

6. SYNTHESIS OF ALDEHYDES AND KETONES S:12.2 Oxidation-Reduction Reactions in Organic Chemistry Reduction - adding electrons, more hydrogens, less oxygen Oxidation - removing electrons, less hydrogens, more oxygen Calculating Oxidation State of Carbon Atoms in Organic Molecules The oxidation state of a carbon balances the contributions from each of the bonds to its substituents: H = +1 O and other electronegative atoms = -1 C = 0

7. OXIDATION OF ALCOHOLS TO GIVE CARBONYL COMPOUNDS S:12.4Prob:12.14 1°, 2° and 3° Alcohols

8. Strong Oxidants

9. Oxidation of 1° Alcohols with Mild Oxidants

10. REDUCTION OF ALDEHYDES AND KETONES, ACIDS, ACID DERIVATIVES S:16.4Prob:16.27,29a,30a,b Reduction with strong reducing agents: LiAlH4 and NaBH4 Aldehydes Ketones Esters and Acids

11. Reduction of Carboxylic Acid Derivatives with Mild Reducing Agents

12. SYNTHESIS OF ALDEHYDES S:16.5 Review Oxidation of 1° Alcohols • Reduction of Acid Derivatives

13. SYNTHESIS OF KETONES S:16.5 Review Ozonolysis Friedel-Crafts acylation From alkynes

14. ? Problem - Provide a synthesis of 3-hexanone from starting materials with three of fewer carbon atoms.

15. Problem - Provide a synthesis of cyclohexanone from cyclohexane ?

16. OXIDATION OF ALDEHYDES AND KETONES S:16.12,13Prob:16.24,28,31 Oxidation of Aldehydes

17. Oxidation of Ketones Oxidation with peracids: The Baeyer-Villiger reaction

18. NUCLEOPHILIC ADDITION AND ADDITION-ELIMINATION TO ALDEHYDES AND KETONES S:16.6S:12.1B • General reaction • Examples

19. Catalysis of Nucleophilic Addition to Aldehydes and Ketones Acid catalysis increases the electrophilicity of the carbonyl

20. Base catalysis increases the nucleophilicity of the nucleophile

21. Relative reactivity of aldehydes and ketones Inductive electronic factors Electron donating groups decrease electrophilicity of carbonyl (and visa versa) Steric factors Bulky groups hinder attack of nucleophile and cause steric crowding in product sp3, 120°sp2, 109.5°

22. ? Prob:16.27,29a,30a,b ?

23. ?Prob: 12.4,14; 16.23? ?

24. OXYGEN NUCLEOPHILES: ADDITION OF WATER AND ALCOHOLS S:16.7Prob: 16.48 • Structure

25. Hydrates Mechanism of acid catalyzed reaction Mechanism of base catalyzed reaction Example

26. Equilibrium constants for Hydrate Formation % hydrate at equilibrium 99.96 50 19 0.14 99.9996 Keq 41 1.8 x 10-2 4.1 x 10-3 2.5 x 10-5 22,000 X H CH3 C(CH3)3 CH3 CF3 Y H H H CH3 CF3 1 M carbonyl compound dissolved in H2O

27. Hemiacetals Formation: Base-catalyzed reaction [Draw the acid catalyzed reaction yourself] e.g. Glucose

28. Acetals Formation: Only formed under acidic condition All steps are reversible – must remove H2O to drive reaction to completion. Why doesn’t this reaction proceed under basic conditions?

29. Examples Acetals are important as protecting groups (see later)

30. Sucrose (Sugar) – A Disaccharide

31. Hydrolysis of Acetals Principle of microscopic reversibility: Forward and back reactions take place via the same intermediates and transition states.

32. Problem [Solomons 16.46] - Multistriatin is an aggregating pheromone of the European elm bark beetle, the vector of Dutch elm disease. Multistriatin is an acetal. What is the product of hydrolysis of multistriatin formed upon treatment with aqueous acid? ?

33. NITROGEN NUCLEOPHILES:ADDITION-ELIMINATION S:16.8Prob:16.24 Addition-elimination of 1º Amines

34. Mechanism Acid or base catalyzed, but requires careful control of pH

35. Examples

36. CARBON NUCLEOPHILES: ADDITION OF HYDROGEN CYANIDE S:16.9 General Reaction Example

37. ORGANOMETALLIC COMPOUNDS AS NUCLEOPHILES S:12.5 Organometallic Compounds Examples: • RMgHal RLi RCCNa RZnHal R2CuLi • C-Mg C-Li C-Na C-Zn C-Cu Contrast reactivity: • C-O • C-M • C-Br 2.5 1.2 2.5 1.0 2.5 1.0 2.5 1.7 2.5 1.8

38. PREPARATION OF ORGANOLITHIUM, MAGNESIUM, ZINC AND COPPER COMPOUNDS S:12.6 Halogen-Metal Exchange

39. R-Li AND R-MgHal AS BASESAND NUCLEOPHILES S:12.7Prob:12.12 Grignard and Lithium Reagents as Bases

40. Grignard And Lithium Reagents As Nucleophiles Nucleophilic Ring opening of Epoxides (example from Organic-I) Organometallics as Nucleophiles

41. RMgX and RLi do not undergo SN reactions with alkyl halides

42. CARBONYLS AS ELECTROPHILES: PREPARATION OF ALCOHOLS S:12.8C-DProb:12.12,19,20,21,24 Lithium, Magnesium and Sodium Reagents Add to Carbonyl Groups

43. Problem - Identify the structures of compounds A-E in the following scheme. ?

44. Designing Organic Synthesis: Retroanalysis S:12.8A

45. Other ways to disconnect bonds in a Grignard alcohol synthesis

46. Preparation of 1° Alcohols Preparation of 2° Alcohols

47. Preparation of 3° Alcohols

48. Problem - Propose a synthesis of 2-methyl-2-hexanol from starting materials with four or fewer carbon atoms ?

49. ? Prob:12.12,19,20,21,24 ?

50. RESTRICTIONS ON THE USE OFORGANOMETALLIC REAGENTS S:12.8B Lithium, magnesium and sodium reagents are very reactive as nucleophiles and bases, limiting other functional groups in these reagents