2. WWU Chemistry ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITION TO CARBONYL Chapter 16

3. WWU Chemistry Reading Assignment DO: Sections 16.0 through 16.7 SKIP: Section 16.8 DO: 16.9 through 16.18 SKIP: Section 16.19 DO: Section 16.20 Organic Nomenclature: Aldehydes and Ketones

4. WWU Chemistry Problem Assignment In-Text Problems –16.1 through 16.27 End-of-Chapter –1 through 6 –7a; 7c through 7j –8 b, c, d –9 through 10 –12 through 14

5. WWU Chemistry Aldehyde Ketone

6. WWU Chemistry IUPAC Nomenclature of Ketones Choose the longest continuous carbon chain that contains the carbonyl carbon Number from the end of the chain closest to the carbonyl carbon Ending is -one Do the ketones section of Organic Nomenclature -- Assignment!

7. WWU Chemistry Example 2-Pentanone

8. WWU Chemistry Another... 4-Ethyl-3-hexanone

9. WWU Chemistry And another... 3-Isopropylcyclopentanone or 3-(1-Methylethyl)cyclopentanone

10. WWU Chemistry Common, or Trivial, Names Name each group attached to the carbonyl group as an alkyl group Combine into a name, according to: –alkyl alkyl’ ketone NOTE: This is not all one word!

11. WWU Chemistry Example of a Common Name Methyl propyl ketone

12. WWU Chemistry Another example... Diethyl ketone

13. WWU Chemistry Important example! Dimethyl ketone Acetone

14. WWU Chemistry Another Important Common Name Acetophenone (Methyl phenyl ketone)

15. WWU Chemistry IUPAC Nomenclature of Aldehydes Choose the longest continuous carbon chain that contains the carbonyl carbon Number from the end of the chain closest to the carbonyl carbon (this will automatically be carbon #1!) Ending is -al Note: The carbonyl carbon is not identified by number in the final name. Do the aldehydes section of Organic Nomenclature -- Assignment!

16. WWU Chemistry Example Hexanal Notice that there is no “-1-” in the name!

17. WWU Chemistry … another: 5-Methylhexanal

18. WWU Chemistry One more: 3-Phenylpropanal

19. WWU Chemistry For cyclic molecules, the ending is -carbaldehyde Cycloheptanecarbaldehyde

20. WWU Chemistry Two acceptable alternative names: Benzenecarbaldehyde (official IUPAC name) Benzaldehyde (acceptable IUPAC name)

21. WWU Chemistry Common Names of the Aldehydes

22. WWU Chemistry Forming Common Names of Aldehydes

23. WWU Chemistry Also: “Iso” names: Whenever there is a -CH(CH 3 ) 2 group, an alternative common name is an “iso” name. The “iso” name includes all of the carbon atoms in the molecule. The “iso” name isn’t used if there are other substituents.

24. WWU Chemistry Example  -Methylbutyraldehyde Isovaleraldehyde

25. WWU Chemistry Another example...  -Bromocaproaldehyde  -Bromocaproaldehyde

26. WWU Chemistry Benzaldehyde ortho (o-) meta (m-) para (p-) 1,2- 1,3- 1,4-

27. WWU Chemistry More than one subsituent: 4-Hydroxybutanal  -Hydroxybutyraldehyde The prefix for -OH is hydroxy

28. WWU Chemistry Also... 2-Methoxypentanal  -Methoxyvaleraldehyde

29. WWU Chemistry Bourgeonal is thought to be a chemoattractant emitted by the egg and detected by an odor receptor on the sperm cell. This guides the sperm to the egg Science, 299, 2054 (2003)

30. WWU Chemistry Structure of the Carbonyl Group Hybridization of the carbonyl carbon is sp 2. Geometry of the carbonyl carbon is trigonal planar Attack by nucleophiles will occur with equal ease from either the top or the bottom of the carbonyl group. Hybridization of the oxygen is “nominally” sp 2.

31. WWU Chemistry Prochiral The carbonyl carbon is prochiral. That is, the carbonyl carbon is not the center of chirality, but it becomes chiral as the reaction proceeds. These two products are enantiomers. In general, both enantiomers are formed in equal amount.

32. WWU Chemistry Reaction of the Carbonyl Group with Acids Typical behavior

33. WWU Chemistry Reaction of the Carbonyl Group with Bases Typical behavior

34. WWU Chemistry Nucleophilic Addition to Carbonyl -- General Mechanism NOTE: Reversible reaction

35. WWU Chemistry Nucleophilic Addition to Carbonyl -- in Acid (General Mechanism) NOTE: Reversible reaction

36. WWU Chemistry The carbocation intermediate has resonance. The positive charge character on carbon makes this an excellent site for attack by Lewis bases (nucleophiles).

37. WWU Chemistry Once we have the intermediate, what happens to it? Case 1: The Addition Product is Stable. The reaction stops here. This happens most often when the nucleophilic atom is carbon, oxygen, or sulfur.

38. WWU Chemistry Case 2: Addition-Elimination The addition product is unstable with respect to loss of a molecule of water. This is observed most often when the nucleophilic atom is nitrogen or phosphorus.

39. WWU Chemistry Case 3: Loss of Leaving Group This process is observed when X is a potential leaving group. In this case we have nucleophilic acyl substitution (see Chapter 19).

40. WWU Chemistry What are the stereochemical requirements? The hybridization of carbon in the carbonyl group is sp 2 The geometry around carbon is trigonal-planar. Nucleophile can attack the carbonyl group equally easily from top or bottom (see model) BUT: aldehydes react faster than ketones in nucleophilic addition!

41. WWU Chemistry Why? Aldehydes have a hydrogen attached to the carbonyl group, whereas ketones have an alkyl group. –Alkyl groups are much more bulky than hydrogens -- hence ketones should show some steric hindrance. Alkyl groups have a small electron-releasing inductive effect. –This should make the carbonyl carbon less favorable by attack by nucleophile. The answer is that there is a combination of steric hindrance and inductive effects that makes ketones react slower than aldehydes.

42. WWU Chemistry Addition of Cyanide (16.6) A cyanohydrin

43. WWU Chemistry Mechanism

44. WWU Chemistry Example Notice that the cyanide ion and the acid are added in two separate steps! Sodium carbonate is used to keep the reaction medium basic.

45. WWU Chemistry So, what’s it good for? Nitriles can be hydrolyzed to form carboxylic acids. This affords us with an important method of synthesizing  -hydroxy- carboxylic acids -- important intermediates in biochemical processes.

46. WWU Chemistry Reaction with Organometallic Compounds (16.7) The products of this sequence are always alcohols.

47. WWU Chemistry Addition of Organometallic Reagents The products of the addition are always alcohols.

48. WWU Chemistry Crude outline of the mechanism of organometallic addition

49. WWU Chemistry Whatever is attached to the carbonyl group will be attached to the resulting alcohol carbon.

50. WWU Chemistry Example Organometallics react with ketones to yield tertiary alcohols.

51. WWU Chemistry And another... Organometallics react with aldehydes to form secondary alcohols

52. WWU Chemistry Summary of Reactions of Organometallics with Carbonyl Compounds Organometallics with ketones yield tertiary alcohols Organometallics with aldehydes yield secondary alcohols Organometallics with formaldehyde yield primary alcohols.

53. WWU Chemistry Ethynylation One can also use a Grignard reagent to do an ethynylation.

54. WWU Chemistry To make an alkynyl Grignard... This is an acid-base reaction (the proton is transferred from the stronger acid to the stronger base).

55. WWU Chemistry A Practical Application Used in oral contraceptives