1. Aldehydes and Ketones

2. Introduction: Types of Carbonyl Compounds

3. Carbonyl Reactivity

4. Carbonyl Structure
Carbonyl carbon is sp2 hybridized, like an alkene

5. Carbonyl Geometry/Bond Properties
The double bond between C and O is shorter and stronger than a single bond.
Due to EN of O, electron density moves from C to O, leaving a partial positive charge on the carbonyl carbon.

7. 2 Major Pathways for Nucleophilic Addition

8. Examples of First Major Pathway

9. Second Major Pathway: Imine Formation

10. Reactions with CA Derivatives

11. Esterification

12. Alpha Substitution Rxns (Ch. 22)

13. Carbonyl Condensation Rxns
Treatment of acetaldehydes with strong base leads to formation of aldol

14. Mechanism of Carbonyl Condensation

15. Nucleophilic Addition Reactions

16. 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

17. Functional Group Priority
Carboxylic Acids (3 O bonds, 1 OH)
Esters (3 O bonds, 1 OR)
Amides
Nitriles
Aldehydes (2 O bonds, 1H)
Ketones (2 O bonds)
Alcohols (1 O bond, 1 OH)
Amines
Alkenes, Alkynes
Alkanes
Ethers
Halides
The parent will be determined based on the highest priority functional group.

18. 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

19. Naming Aldehydes pentanal 5-chloropentanal 2-ethylbutanal
m-chloro-benzaldehyde
5-chloro-2-methylbenzaldehyde
3,4-dimethylhexanal
5-methoxy-2-methylbenzaldehyde

20. 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

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

22. 2-fluoro-5-methyl-4-octanone
Naming Ketones
2-pentanone
5-chloro-2-pentanone
1-chloro-3-pentanone
4-ethylcyclohexanone
2-fluoro-5-methyl-4-octanone

23. Naming Ketones

24. 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 (lower priority functional group)

25. Ketones/Aldehydes as minor FGs, benzaldehydes

26. Solubility of Ketones and Aldehydes
Good solvent for alcohols
Lone pair of electrons on oxygen of carbonyl can accept a hydrogen bond from O—H or N—H.
Acetone and acetaldehyde are miscible in water.

27. Preparing Aldehydes and Ketones
Oxidize primary alcohols using PCC (in dichloromethane)
Alkenes with a vinylic hydrogen can undergo oxidative cleavage when treated with ozone, yielding aldehydes
Reduce an ester with diisobutylaluminum hydride (DIBAH)
Like LiAlH4

28. Preparing Ketones
Oxidize a 2° alcohol (See chapter on alcohols)

29. Ketones from Ozonolysis
Ozonolysis of alkenes yields ketones if one of the unsaturated carbon atoms is disubstituted

30. Aryl Ketones by Acylation
Friedel–Crafts acylation of an aromatic ring with an acid chloride in the presence of AlCl3 catalyst

31. Limitations of FC Acylation
Does not occur on rings with electron-withdrawing substituents or basic amino groups

32. Mechanism of FC Acylation
Not subject to rearrangement like FC alkylation.

33. Mercury catalyzed hydration of terminal alkyne
Hydration of terminal alkynes in the presence of Hg2+
Markovnikov addition
Produces enol that tautomerizes to ketone
Works best with terminal alkyne

34. Oxidation of Aldehydes
CrO3 in aqueous acid oxidizes aldehydes to carboxylic acids efficiently
Silver oxide, Ag2O, in aqueous ammonia (Tollens’ reagent) oxidizes aldehydes

35. Oxidation of Ketones Ketones oxidize with difficulty
Undergo slow cleavage with hot, alkaline KMnO4
C–C bond next to C=O is broken to give carboxylic acids
Reaction is practical for cleaving symmetrical ketones

36. Nucleophilic Addition Reactions of Aldehydes and Ketones
Nu- approaches 75° to the plane of C=O and adds to C
A tetrahedral alkoxide ion intermediate is produced

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

38. 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)
Aldehydes have one large substituent bonded to the C=O: ketones have two

39. 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

40. Reactivity of Aromatic Aldehydes
Less reactive in nucleophilic addition reactions than aliphatic aldehydes
Electron-donating resonance effect of aromatic ring makes C=O less reactive electrophile than the carbonyl group of an aliphatic aldehyde

41. 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

42. Hydration of Aldehydes
Aldehyde hydrate is oxidized to a carboxylic acid by usual reagents for alcohols
Relatively unreactive under neutral conditions, but can be catalyzed by acid or base.

43. Hydration of Carbonyls
Acid catalyzed
Hydration occurs through the nucleophilic addition mechanism, with water (in acid) or hydroxide (in base) serving as the nucleophile.
Base catalyzed
The hydroxide ion attacks the carbonyl group.
Protonation of the intermediate gives the hydrate.

44. 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 (unstable alcohol)

45. Nucleophilic Addition of HCN: Cyanohydrin Formation
Aldehydes and unhindered ketones react with HCN to yield cyanohydrins, RCH(OH)CN
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. Nucleophilic Addition of Grignard Reagents and Hydride Reagents: Alcohol Formation
Treatment of aldehydes or ketones with Grignard reagents yields an alcohol
Nucleophilic addition of a carbanion. A carbon–magnesium bond is strongly polarized, so a Grignard reagent reacts for all practical purposes as R:  MgX+.

47. 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

48. 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

49. Nucleophilic Addition of Amines: Imine and Enamine Formation
RNH2 adds to R’2C=O to form imines, R’2C=NR (after loss of HOH)
R2NH yields enamines, R2NCR=CR2 (after loss of HOH) (ene + amine = unsaturated amine)

50. Mechanism of Formation of Imines
Primary amine adds to C=O
Proton is lost from N and adds to O to yield an amino alcohol (carbinolamine)
Protonation of OH converts it 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
Optimum pH = 4.5

51. Imine Formation Reactions

52. Enamine Formation
After addition of R2NH and loss of water, proton is lost from adjacent carbon

53. The Wolff–Kishner Reaction: Convert ketone to alkane
Treatment of an aldehyde or ketone with hydrazine, H2NNH2, and KOH converts the compound to an alkane
Can be conducted near room temperature using dimethyl sulfoxide as solvent
Works well with both alkyl and aryl ketones

54. 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

55. Addition of alcohol to aldehydes and ketones
Hemiacetal intermediate
acetal
Hemiketal intermediate
ketal
Hemiacetal is unstable, hard to isolate.
With excess alcohol and an acid catalyst, a stable acetal is formed.
Note the bidirectional arrows

56. Mechanism of Acetal Formation

57. Mechanism of Acetal Formation

58. Acetals as Protecting Groups
Acetals can serve as protecting groups for aldehydes and ketones
Aldehydes more reactive than ketones
It is convenient to use a diol to form a cyclic acetal (the reaction goes even more readily)

59. Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction
The sequence converts C=O 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

60. Mechanism of the Wittig Reaction

61. Product of Wittig Rxn
The Wittig reaction converts the carbonyl group into a new C═C double bond where no bond existed before.
A phosphorus ylide is used as the nucleophile in the reaction.
Ylide usually CH2 or monosubstituted, but not disubstituted.
Unstabilized ylide tends to favor Z-alkene.

62. Conjugate Nucleophilic Addition to -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

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

64. Conjugate Addition of Alkyl Groups: Organocopper Reactions
Reaction of an ,b-unsaturated ketone with a lithium diorganocopper reagent
Diorganocopper (Gilman) reagents form 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

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

66. Spectroscopy of Aldehydes and Ketones
Infrared Spectroscopy
Aldehydes and ketones show a strong C=O peak 1660 to 1770 cm1
aldehydes show two characteristic C–H absorptions in the 2720 to 2820 cm1 range.
Skip the rest

67. C=O Peak Position in the IR Spectrum
The precise position of the peak reveals the exact nature of the carbonyl group

68. NMR Spectra of Aldehydes
Aldehyde proton signals are near  10 in 1H NMR - distinctive spin–spin coupling with protons on the neighboring carbon, J  3 Hz

69. No other kinds of carbons absorb in this range
13C NMR of C=O
C=O signal is at  190 to  215
No other kinds of carbons absorb in this range

70. Mass Spectrometry – McLafferty Rearrangement
Aliphatic aldehydes and ketones that have hydrogens on their gamma () carbon atoms rearrange as shown

71. Mass Spectroscopy: -Cleavage
Cleavage of the bond between the carbonyl group and the  carbon
Yields a neutral radical and an oxygen-containing cation