1. CH 19: Aldehydes and Ketones
Renee Y. Becker
Valencia Community College
CHM 2211

2. Some Generalizations About Carbonyl Compounds
The most important functional group in organic chemistry.

3. Some Generalizations About Carbonyl Compounds
carbonyl compounds are planar about the double bond with bond angles  120 due to the sp2 hybridized carbon.
Many types of carbonyl compounds have significant dipole moments.
The polarity of the C-O bond plays a significant role in the reactivity of carbonyl compounds.

4. Aldehydes and Ketones

5. Aldehydes and Ketones
Due to the polarity of the carbonyl C-O bond, aldehydes and ketones have higher BPs than alkanes with similar molecular weights.
The lack of H-bonding hydrogens, results in lower BPs than similar alcohols.

6. The parent chain must contain the CHO group
Naming Aldehydes
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 Aldehydes

8. Naming Aldehydes

9. Example 1: Name

10. cis-3-tert-Butylcyclohexanecarbaldehyde
Example 2: Draw
3-Methylbutanal
3-Methyl-3-butenal
cis-3-tert-Butylcyclohexanecarbaldehyde

11. Replace the terminal -e of the alkane name with –one
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

12. Naming Ketones

13. Ketones with Common Names
Naming Ketones
Ketones with Common Names

14. Ketones and Aldehydes as Substituents
The R–C=O as a substituent is an acyl group is used with the suffix -yl from the root of the carboxylic acid
CH3CO: acetyl; CHO: formyl; C6H5CO: benzoyl

15. Ketones and Aldehydes as Substituents
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

16. Example 3: Name 1. 3. 4. 2.

17. 3-ethyl-4-methyl-2-hexanone
Example 4: Draw
4-Chloro-2-pentanone
P-bromoacetophenone
3-ethyl-4-methyl-2-hexanone

18. Preparation of Aldehydes
Oxidize primary alcohols using pyridinium chlorochromate

19. Preparation of Aldehydes
Oxidation of alkenes with a vinylic hydrogen

20. Preparation of Aldehydes
The partial reduction of certain carboxylic acid derivatives. (esters)

21. How would you prepare pentanal from the following:
Example 5
How would you prepare pentanal from the following:
1. 1-Pentanol
1-Hexene

22. Oxidation of secondary alcohols
Preparing Ketones
Oxidation of secondary alcohols

23. Oxidation of alkenes if one unsaturated carbon is disubstituted
Preparing Ketones
Oxidation of alkenes if one unsaturated carbon is disubstituted

24. Friedel-Crafts acylation of aromatic compounds with an acid chloride.
Preparing Ketones
Friedel-Crafts acylation of aromatic compounds with an acid chloride.
Occurs only once!

25. Hydrations of terminal alkynes
Preparing Ketones
Hydrations of terminal alkynes
Methyl ketone synthesis
Hg2+ catalyst

26. 2. Benzene  m-Bromoacetophenone
Example 6
How would you carry out the following reactions? More than 1 step might be necessary.
1. 3-Hexyne  3-Hexanone
2. Benzene  m-Bromoacetophenone
3. Bromobenzene  Acetophenone

27. Reactions of Aldehydes and Ketones
Oxidation reactions
Nucleophilic addition reactions
Conjugate nucleophilic addition reactions

28. Oxidation of Aldehydes
Jones’ Reagent (preferred)
Preferred over other oxidation reagents due to Room temp. reaction with high yields
Run under acidic conditions (con)
Will react with C=C and any acid sensitive functionality

29. Oxidation of Aldehydes
Tollen’s reagent
For use with C=C double bonds

30. Oxidation of Ketones
Ketones are resistant toward oxidation due to the missing hydrogen on the carbonyl carbon
Treatment of ketones with hot KMnO4 will cleave the C-C bond adjacent to the carbonyl group:

31. Nucleophilic Addition Reactions of Aldehydes and Ketones
Nu- approaches 45° to the plane of C=O and adds to C
A tetrahedral alkoxide ion intermediate is produced

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

34. Nucleophilic Addition Reactions

35. Relative Reactivity of Aldehydes and Ketones
Aldehydes are generally more reactive than ketones in nucleophilic addition reactions
The transition state for addition is less crowded and lower in energy for an aldehyde (a) than for a ketone (b)

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

37. Reactivity of Aromatic Aldehydes
Aromatic aldehydes are less reactive in nucleophilic addition than straight chain aldehydes
Due to electron-donating resonance effect of aromatic ring
Makes carbonyl group less electrophilic

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

39. Acetone in water is 99.9% ketone form Exception: simple aldehydes
Relative Energies
Equilibrium generally favors the carbonyl compound over hydrate for steric reasons
Acetone in water is 99.9% ketone form
Exception: simple aldehydes
In water, formaldehyde consists is 99.9% hydrate

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

41. Mechanism 1: Base catalyzed hydration of an aldehyde/ketone

42. Mechanism 2: Acid catalyzed hydration of an aldehyde/ketone

43. Formation is readily reversible
Addition of H-Y to C=O
Reaction of C=O with H-Y, where Y is electronegative, gives an addition product (“adduct”)
Formation is readily reversible

44. Nucleophilic Addition of HCN: Cyanohydrin Formation
Aldehydes and unhindered ketones react with HCN to yield cyanohydrins, RCH(OH)CN

45. Mechanism of Formation of Cyanohydrins
Addition of HCN is reversible and base-catalyzed, generating nucleophilic cyanide ion, CN
Addition of CN to C=O yields a tetrahedral intermediate, which is then protonated
Equilibrium favors adduct

46. Mechanism 3: Formation of Cyanohydrins

47. Nitriles can be reduced with LiAlH4 to yield primary amines:
Uses of Cyanohydrins
Nitriles can be reduced with LiAlH4 to yield primary amines:

48. Uses of Cyanohydrins
Nitriles can be hydrolyzed with hot aqueous acid to yield carboxylic acids:

49. 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 +.

50. 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

51. Mechanism 4: Addition of Grignard Reagents

52. LiAlH4 and NaBH4 react as donors of hydride ion
Hydride Addition
Convert C=O to CH-OH
LiAlH4 and NaBH4 react as donors of hydride ion
Protonation after addition yields the alcohol

53. Nucleophilic Addition of Amines: Imine and Enamine Formation
RNH2 (primary amines) adds to C=O to form imines, R2C=NR (after loss of HOH)
R2NH (secondary amines) yields enamines, R2NCR=CR2 (after loss of HOH) (ene + amine = unsaturated amine)

55. Mechanism of Formation of Imines
Primary amine adds to C=O
Proton is lost from N and adds to O to yield a neutral amino alcohol (carbinolamine)
Protonation of OH converts into water as the leaving group
Result is iminium ion, which loses proton
Acid is required for loss of OH – too much acid blocks RNH2
Note that overall reaction is substitution of RN for O

56. Mechanism 5: Imine Formation

57. Imine Derivatives
Addition of amines with an atom containing a lone pair of electrons on the adjacent atom occurs very readily, giving useful, stable imines
For example, hydroxylamine forms oximes and 2,4-dinitrophenylhydrazine readily forms 2,4-dinitrophenylhydrazones
These are usually solids and help in characterizing liquid ketones or aldehydes by melting points

59. Mechanism 6: Enamine Formation

60. Nucleophilic Addition of Hydrazine: The Wolff–Kishner Reaction
Treatment of an aldehyde or ketone with hydrazine, H2NNH2 and KOH converts the compound to an alkane
Originally carried out at high temperatures but with dimethyl sulfoxide as solvent takes place near room temperature

61. Mechanism 7: The Wolff–Kishner Reaction

62. 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
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

63. Acetals can serve as protecting groups for aldehydes and ketones
Uses of Acetals
Acetals can serve as protecting groups for aldehydes and ketones
It is convenient to use a diol, to form a cyclic acetal (the reaction goes even more readily)

64. Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction
The sequence converts C=O is to C=C
A phosphorus ylide adds to an aldehyde or ketone to yield a dipolar intermediate called a betaine
The intermediate spontaneously decomposes through a four-membered ring to yield alkene and triphenylphosphine oxide, (Ph)3P=O
Formation of the ylide is shown below

65. Mechanism 8: The Wittig Reaction

66. Uses of the Wittig Reaction
Can be used for monosubstituted, disubstituted, and trisubstituted alkenes but not tetrasubstituted alkenes The reaction yields a pure alkene of known structure
For comparison, addition of CH3MgBr to cyclohexanone and dehydration with, yields a mixture of two alkenes

67. The Cannizaro Reaction
The adduct of an aldehyde and OH can transfer hydride ion to another aldehyde C=O resulting in a simultaneous oxidation and reduction (disproportionation)

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

71. Conjugate Addition of Amines
Primary and secondary amines add to , b-unsaturated aldehydes and ketones to yield b-amino aldehydes and ketones

72. Conjugate Addition of Alkyl Groups: Organocopper Reactions
Reaction of an , b-unsaturated ketone with a lithium diorganocopper reagent
Diorganocopper (Gilman) reagents from by reaction of 1 equivalent of cuprous iodide and 2 equivalents of organolithium
1, 2, 3 alkyl, aryl and alkenyl groups react but not alkynyl groups

74. Gilman Reagent

75. Mechanism of Alkyl Conjugate Addition
Conjugate nucleophilic addition of a diorganocopper anion, R2Cu, an enone
Transfer of an R group and elimination of a neutral organocopper species, RCu

76. Example 7