1. Chapter 9 Aldehydes and Ketones: Nucleophilic Addition Reactions
Suggested Problems: 24-5,29-34,37-9,41-43,45-6,53

2. Aldehydes and Ketones
Aldehydes (RCHO) and ketones (R2CO) are characterized by the carbonyl functional group (C=O)
The compounds occur widely in nature as intermediates in metabolism and biosynthesis

3. 9.1 The Nature of Carbonyl Compounds
Two general categories based on the kinds of chemistry they undergo although both contain C=O
Aldehydes and ketones: do not stabilize negative charge and can’t act as leaving groups
Carboxylic acids and their derivatives: can stabilize negative charge and can act as leaving groups

4. 9.1 The Nature of Carbonyl Compounds

5. Electronic Structure of the Carbonyl Group
C=O, the carbon atom (Lewis acidic) is positively polarized relative to the oxygen atom (Lewis basic)

6. 9.2 Naming Aldehydes and Ketones
Aldehydes are named by replacing the terminal –e of the corresponding alkane name with –al
The parent chain must contain the –CHO group
The –CHO carbon is numbered as C1
If the –CHO group is attached to a ring, use the suffix carbaldehyde

7. Naming Ketones Replace the terminal -e of the alkane name with –one
Parent chain is the longest one that contains the ketone group
Numbering begins at the end nearer the carbonyl carbon

8. Ketones with Common Names
IUPAC retains well-used but unsystematic names for a few ketones

9. Ketones and Aldehydes as Substituents
The R–C=O as a substituent is an acyl group, used with the suffix -yl from the root of the carboxylic acid
CH3CO: acetyl; CHO: formyl; C6H5CO: benzoyl
The prefix oxo- is used if other functional groups are present and the doubly bonded oxygen is labeled as a substituent on a parent chain

10. 9.3 Synthesis of Aldehydes and Ketones
Preparing Aldehydes
Oxidize primary alcohols using pyridinium chlorochromate
Alkenes with a vinylic hydrogen can undergo oxidative cleavage when treated with ozone, yielding aldehydes
Reduce an ester with diisobutylaluminum hydride (DIBAH)

11. 9.3 Synthesis of Aldehydes and Ketones
Oxidization of alcohols
Primary alcohols yield aldehydes (periodinane in CH2Cl2)
Secondary alcohols yield ketones (CrO3 or Na2Cr2O7)

12. 9.3 Synthesis of Aldehydes and Ketones
Ketones can be produced by
The hydration of a terminal alkyne
Friedal-Crafts acylation of an aromatic ring

13. 9.4 Oxidation of Aldehydes
CrO3 in aqueous acid oxidizes aldehydes to carboxylic acids efficiently

14. Hydration of Aldehydes
Aldehyde oxidations occur through 1,1-diols (“hydrates”)
Reversible addition of water to the carbonyl group
Aldehyde hydrate is oxidized to a carboxylic acid by usual reagents for alcohols

15. 9.5 Nucleophilic Addition Reactions
Most common reaction of aldehydes and ketones is the nucleophilic addition reaction
Nu– adds to the C of the C=O
A tetrahedral alkoxide ion intermediate is produced
Can occur under acidic or basic conditions.

16. 9.5 Nucleophilic Addition Reactions

17. Nucleophiles
Nucleophiles can be negatively charged ( :Nu) or neutral ( :Nu) at the reaction site
The overall charge on the nucleophilic species is not considered

18. Electrophilicity of Aldehydes and Ketones
Aldehyde C=O is more polarized than ketone C=O
As in carbocations, more alkyl groups stabilize the + character of the carbonyl carbon
Ketone has more alkyl groups, stabilizing the C=O carbon inductively

19. 9.6 Nucleophilic Addition of Grignard Reagents and Hydride Reagents: Alcohol Formation
Aldehydes are reduced to primary alcohols and ketones to secondary alcohols
Convert C=O to CH-OH
LiAlH4 and NaBH4 react as donors of hydride ion
Protonation after addition yields the alcohol

20. 9.6 Nucleophilic Addition of Grignard Reagents and Hydride Reagents: Alcohol Formation
Treatment of aldehydes or ketones with Grignard reagents yields an alcohol
Nucleophilic addition of the equivalent of a carbon anion, or carbanion. A carbon–magnesium bond is strongly polarized, so a Grignard reagent reacts for all practical purposes as R:  MgX+.

21. Mechanism of Addition of Grignard Reagents
Complexation of C=O by Mg2+, Nucleophilic addition of R: , protonation by dilute acid yields the neutral alcohol
Grignard additions are irreversible because a carbanion is not a leaving group

22. Limitations of the Grignard Reaction
Grignard reagents cannot be prepared from compounds that contain the following functional groups.

23. 9.7 Nucleophilic Addition of H2O: Hydrate Formation
Aldehydes and ketones react with water to yield 1,1-diols (geminal (gem) diols)
Hyrdation is reversible: a gem diol can eliminate water

24. Base-Catalyzed Addition of Water
Addition of water is catalyzed by both acid and base
The base-catalyzed hydration nucleophile is the hydroxide ion, which is a much stronger nucleophile than water

25. Acid-Catalyzed Addition of Water
Protonation of C=O makes it more electrophilic

26. 9.8 Nucleophilic Addition of Alcohols: Acetal Formation
Alcohols are weak nucleophiles but acid promotes addition forming the conjugate acid of C=O
Addition yields a hydroxy ether, called a hemiacetal (reversible); further reaction can occur to produce an acetal, (R2CO(OR′)2
Protonation of the –OH and loss of water leads to an oxonium ion, R2C=OR+ to which a second alcohol adds to form the acetal

27. Mechanism Converting a Hemiacetal to an Acetal

28. Acetals in Carbohydrate Chemistry

29. 9.9 Nucleophilic Addition of Amines: Imine Formation
Ammonia and primary amines, RNH2, add to aldehydes and ketones to form imines, R2C=NR′
Occurs by nucleophilic addition of the amine to the carbonyl group followed by loss of water

30. Imines as Intermediates in Biological Reactions

31. 9.10 Conjugate Nucleophilic Addition Reactions
A nucleophile can add to the C=O double bond of an aldehyde or a ketone (direct addition, or 1,2 addition)

32. 9.10 Conjugate Nucleophilic Addition Reactions
A nucleophile can add to the C=C double bond of an ,b-unsaturated aldehyde or a ketone (conjugate addition, or 1,4 addition)
The initial product is a resonance-stabilized enolate ion, which is then protonated

33. 1,4 or Conjugate Addition
Conjugate addition occurs due to the effect of the eletronegative oxygen atom on the b carbon
Common with amine nucleophiles and water
Occurs in many biological pathways