Introduction to Organic Chemistry 2 ed William H. Brown

1. Introduction to Organic Chemistry2 edWilliam H. Brown

2. Aldehydes & Ketones Chapter 15 Chapter 11

3. The Carbonyl Group • In this and three following chapters we study the physical and chemical properties of classes of compounds containing the carbonyl group, C=O • aldehydes and ketones (Chapter 11) • carboxylic acids (Chapter 12) • carboxyl derivatives (Chapter 13) • enolate anions (Chapter 14)

4. The Carbonyl Group • Consists of • one sigma bond formed by overlap of sp2 hybrid orbitals • one pi bond formed by overlap of parallel 2p orbitals

5. Structure of Aldehydes • The functional group of an aldehyde is a carbonyl group bonded to a H atom • in methanal, it is bonded to two H atoms • in all other aldehydes, it is bonded to one H and one carbon atom

6. Structure of Ketones • The functional group of a ketone is a carbonyl groups bonded to two carbon atoms

7. Nomenclature - Aldehydes • IUPAC names: select as the parent alkane the longest chain of carbon atoms that contains the carbonyl group • because the carbonyl group of the aldehyde must be on carbon 1, there is no need to give it a number • For unsaturated aldehydes, show the presence of the C=C by changing the infix -an- to -en- • the location of the suffix determines the numbering pattern

8. Nomenclature - Aldehydes

9. Nomenclature - Aldehydes • For cyclic molecules in which the -CHO group is attached to the ring, the name is derived by adding the suffix -carbaldehydeto the name of the ring

10. Nomenclature - Ketones • IUPAC names: • select as the parent alkane the longest chain that contains the carbonyl group, • changing the suffix -e to -one • number to give C=O the smaller number

11. Nomenclature - Ketones • The IUPAC system retains these names

12. Order of Precedence • For compounds that contain more than one functional group indicated by a suffix

13. Physical Properties • Oxygen is more electronegative than carbon (3.5 vs 2.5) and, therefore, a C=O group is polar • aldehydes and ketones have higher boiling points and are more soluble in water than nonpolar compounds of comparable molecular weight

14. Reaction Theme • One of the most common reaction themes of the carbonyl group is addition of a nucleophile to form a tetrahedral carbonyl addition compound

15. Add’n of C Nucleophiles • Addition of carbon nucleophiles is one of the most important types of nucleophilic additions to a C=O group • a new carbon-carbon bond is formed in the process • We study addition of carbon nucleophiles called Grignard reagents • Victor Grignard was awarded the Nobel Prize for Chemistry in 1912 for their discovery and application to organic synthesis

16. Grignard Reagents • Magnesium metal reacts with alkyl and aryl halides to give organomagnesium halides

17. Grignard Reagents • Given the difference in electronegativity between carbon and magnesium (2.5 - 1.3), the C-Mg bond is polar covalent, with Cd- and Mgd+ • a Grignard reagent behaves as a carbanion and as a nucleophile • Carbanion: an anion in which carbon has an unshared pair of electrons and bears a negative charge

18. Grignard Reagents • Grignard reagents are very strong bases and react with a variety of acids to give alkanes

19. Grignard Reagents • they also react with these acids ( proton donors) to give alkanes

20. Grignard Reagents • Grignard reagents provide a way to form new carbon-carbon bonds • a carbanion is a good nucleophile and adds to the carbonyl group of an aldehyde or ketone to form a tetrahedral carbonyl addition compound • the driving force for this reaction is the attraction of the partial negative charge on the carbon of the Grignard reagent for the partial positive carbon of the carbonyl group

21. Grignard Reagents • addition of a Grignard reagent to formaldehyde followed by H3O+ gives a 1° alcohol

22. Grignard Reagents • addition to any other RCHO gives a 2° alcohol

23. Grignard Reagents • addition to a ketone gives a 3° alcohol

24. Grignard Reagents • addition to CO2 gives a carboxylic acid

25. Grignard Reagents • addition to ethylene oxide gives a 1° alcohol

26. Grignard Reagents • Problem: 2-phenyl-2-butanol can be synthesized by three different combinations of a Grignard reagent and a ketone. Show each combination

27. Addition of Alcohols • Addition of one molecule of alcohol to the C=O group of an aldehyde or ketone gives a hemiacetal • Hemiacetal: a molecule containing an -OH and an -OR or -OAr bonded to the same carbon

28. Addition of Alcohols • Hemiacetals are only minor components of an equilibrium mixture, except where a five- or six-membered ring can form • (the trans isomer is shown here)

29. Addition of Alcohols • Hemiacetals react with alcohols to form acetals • Acetal: a molecule containing two -OR or -OAr groups bonded to the same carbon

30. Addition of Alcohols • Steps 1 and 2: proton transfer from the acid catalyst, HA, to the carbonyl oxygen followed by loss of H2O

31. Addition of Alcohols • Steps 3 and 4: reaction of the oxonium ion with ROH followed by proton transfer to A-

32. Addition of Alcohols • with a glycol, such as ethylene glycol, the product is a five-membered cyclic acetal

33. Add’n of N Nucleophiles • Ammonia, 1° aliphatic amines, and 1° aromatic amines react with the C=O group of aldehydes and ketones to give imines (Schiff bases)

34. Add'n of N Nucleophiles • Formation of an imine occurs in two steps • Step 1: formation of a TCAI • Step 2: loss of water

35. Add'n of N Nucleophiles • Rhodopsin (visual purple) is the imine formed between 11-cis-retinal (vitamin A aldehyde) and the protein opsin

36. Rhodopsin

37. Keto-Enol Tautomerism • A carbon adjacent to a carbonyl group is called an a-carbon, and a hydrogen atom bonded to it is called an a-hydrogen.

38. Keto-Enol Tautomerism • A carbonyl compound with an a-hydrogen is in equilibrium with a constitutional isomer called an enol (an alkene + an alcohol)

39. Keto-Enol Tautomerism • keto-enol equilibria for simple aldehydes and ketones lie far toward the keto form

40. Keto-Enol Tautomerism • Keto-enol tautomerism is acid catalyzed Step 1: proton transfer from H-A Step 2: proton transfer to A-

41. Racemization • Racemization at an a-carbon is catalyzed by acid

42. Oxidation of Aldehydes • Aldehydes are oxidized to carboxylic acids by a variety of oxidizing agents, including chromic acid

43. Oxidation of Aldehydes • Aldehydes are also oxidized by Ag(I) • in one method, a solution of the aldehyde in aqueous ethanol or THF is shaken with a slurry of silver oxide

44. Oxidation of Aldehydes • Tollens’ reagent, another form of Ag(I), is prepared by dissolving silver nitrate in water, adding NaOH to precipitate Ag(I) as Ag2O, and then adding aqueous ammonia to redissolve Ag(I) as a silver-ammonia complex ion

45. Oxidation of Aldehydes • Tollens’ reagent oxidizes an aldehyde to a carboxylic anion and silver(1) is reduced to metallic silver • this reaction is used to silver mirrors

46. Oxidation of Aldehydes • aldehydes are oxidized by molecular oxygen and by hydrogen peroxide • liquid aldehydes are so sensitive to air that they must stored under N2

47. Reduction • An aldehyde can be reduced to a 1° alcohol and a ketone to a 2° alcohol

48. Catalytic Reduction • Catalytic reductions are generally carried out from 25° to 100°C under 1 to 5 atm H2

49. Catalytic Reduction • A carbon-carbon double bond may also be reduced under these conditions • by careful choice of experimental conditions, it is often possible to selectively reduce a carbon-carbon double in the presence of an aldehyde or ketone

50. Metal Hydride Reduction • The most common laboratory reagents for the reduction of aldehydes and ketones are NaBH4 and LiAlH4 • both reagents are sources of hydride ion, H:-, a very powerful nucleophile