1. Chapter 16 Aldehydes and Ketones I
Chapter 16 Aldehydes and Ketones I. Nucleophilic Addition to the Carbonyl Group

2. Nomenclature of Aldehydes and Ketones
Aldehydes are named by replacing the -e of the corresponding parent alkane with -al
The aldehyde functional group is always carbon 1 and need not be numbered
Some of the common names of aldehydes are shown in parenthesis
Aldehyde functional groups bonded to a ring are named using the suffix carbaldehyde
Benzaldehyde is used more commonly than the name benzenecarbaldehyde
Chapter 16

3. Common names of ketones that are also IUPAC names are shown below
Ketones are named by replacing the -e of the corresponding parent alkane with -one
The parent chain is numbered to give the ketone carbonyl the lowest possible number
In common nomenclature simple ketones are named by preceding the word ketone with the names of both groups attached to the ketone carbonyl
Common names of ketones that are also IUPAC names are shown below
Chapter 16

4. The methanoyl or formyl group (-CHO) and the ethanoyl or acetyl group (-COCH3) are examples of acyl groups
Chapter 16

5. Physical Properties
Molecules of aldehyde (or ketone) cannot hydrogen bond to each other
They rely only on intermolecular dipole-dipole interactions and therefore have lower boiling points than the corresponding alcohols
Aldehydes and ketones can form hydrogen bonds with water and therefore low molecular weight aldehydes and ketones have appreciable water solubility
Chapter 16

6. Synthesis of Aldehydes
Aldehydes by Oxidation of 1o Alcohols
Primary alcohols are oxidized to aldehydes by PCC
Aldehydes by Reduction of Acyl Chlorides, Esters and Nitriles
Reduction of carboxylic acid to aldehyde is impossible to stop at the aldehyde stage
Aldehydes are much more easily reduced than carboxylic acids
Chapter 16

7. Reduction to an aldehyde can be accomplished by using a more reactive carboxylic acid derivatives such as an acyl chloride, ester or nitrile and a less reactive hydride source
The use of a sterically hindered and therefore less reactive aluminum hydride reagent is important
Acid chlorides react with lithium tri-tert-butoxyaluminum hydride at low temperature to give aldehydes
Chapter 16

8. Synthesis of Ketones Ketones from Alkenes, Arenes, and 2o Alcohols
Ketones can be made from alkenes by ozonolysis
Aromatic ketones can be made by Friedel-Crafts Acylation
Ketones can be made from 2o alcohols by oxidation
Chapter 16

9. Ketones from Alkynes
Markovnikov hydration of an alkyne initially yields a vinyl alcohol (enol) which then rearranges rapidly to a ketone (keto)
The rearrangement is called a keto-enol tautomerization (Section 17.2)
This rearrangement is an equilibrium which usually favors the keto form
Chapter 16

10. Terminal alkynes yield ketones because of the Markovnikov regioselectivity of the hydration
Ethyne yields acetaldehyde
Internal alkynes give mixtures of ketones unless they are symmetrical
Chapter 16

11. Ketones from Lithium Dialkylcuprates
An acyl chloride can be coupled with a dialkylcuprate to yield a ketone (a variation of the Corey-Posner, Whitesides-House reaction)
Chapter 16

12. Ketones from Nitriles
Organolithium and Grignard reagents add to nitriles to form ketones
Addition does not occur twice because two negative charges on the nitrogen would result
Chapter 16

13. Nucleophilic Addition to the Carbonyl Groups
Addition of a nucleophile to a carbonyl carbon occurs because of the d+ charge at the carbon
Addition of strong nucleophiles such as hydride or Grignard reagents result in formation of a tetrahedral alkoxide intermediate
The carbonyl p electrons shift to oxygen to give the alkoxide
The carbonyl carbon changes from trigonal planar to tetrahedral
Chapter 16

14. An acid catalyst is used to facilitate reaction of weak nucleophiles with carbonyl groups
Protonating the carbonyl oxygen enhances the electrophilicity of the carbon
Chapter 16

15. The Addition of Alcohols: Hemiacetals and Acetals
An aldehyde or ketone dissolved in an alcohol will form an equilibrium mixture containing the corresponding hemiacetal
A hemiacetal has a hydroxyl and alkoxyl group on the same carbon
Acylic hemiacetals are generally not stable, however, cyclic five- and six-membered ring hemiacetals are
Chapter 16

16. Hemiacetal formation is catalyzed by either acid or base
Chapter 16

17. Acetals
An aldehyde (or ketone) in the presence of excess alcohol and an acid catalyst will form an acetal
Formation of the acetal proceeds via the corresponding hemiacetal
An acetal has two alkoxyl groups bonded to the same carbon
Chapter 16

18. Acetals are stable when isolated and purified
Acetal formation is reversible
An excess of water in the presence of an acid catalyst will hydrolyze an acetal to the corresponding aldehyde (or ketone)
Chapter 16

19. The Addition of Primary and Secondary Amines
Aldehydes and ketones react with primary amines (and ammonia) to yield imines
They react with secondary amines to yield enamines
Chapter 16

20. Imines These reactions occur fastest at pH 4-5 Chapter 16
Mild acid facilitates departure of the hydroxyl group from the aminoalcohol intermediate without also protonating the nitrogen of the amine starting compound
Chapter 16

21. The Acidity of the a Hydrogens of Carbonyl Compounds: Enolate Anions
Hydrogens on carbons a to carbonyls are unusually acidic
The resulting anion is stabilized by resonance to the carbonyl
Chapter 17

22. The enolate anion can be protonated at the carbon or the oxygen
The resultant enol and keto forms of the carbonyl are formed reversibly and are interconvertible
Chapter 17

23. Keto and Enol Tautomers
Enol-keto tautomers are constitutional isomers that are easily interconverted by a trace of acid or base
Most aldehydes and ketones exist primarily in the keto form because of the greater strength of the carbon-oxygen double bond relative to the carbon-carbon double bond
Chapter 17

24. Haloform Reaction Insert mechanism page 777
Reaction of methyl ketones with X2 in the presence of base results in multiple halogenation at the methyl carbon
Insert mechanism page 777
Chapter 17

25. When methyl ketones react with X2 in aqueous hydroxide the reaction gives a carboxylate anion and a haloform (CX3H)
The trihalomethyl anion is a relatively good leaving group because the negative charge is stabilized by the three halogen atoms
Chapter 17

26. The Aldol Reaction: The Addition of Enolate Anions to Aldehydes and Ketones
Acetaldehyde dimerizes in the presence of dilute sodium hydroxide at room temperature
The product is called an aldol because it is both an aldehyde and an alcohol
Chapter 17

27. The mechanism proceeds through the enolate anion
Chapter 17

28. Dehydration of the Aldol Product
If the aldol reaction mixture is heated, dehydration to an a,b-unsaturated carbonyl compound takes place
Dehydration is favorable because the product is stabilized by conjugation of the alkene with the carbonyl group
In some aldol reactions, the aldol product cannot be isolated because it is rapidly dehydrated to the a,b-unsaturated compound
Chapter 17

29. Chapter 12