1. ALDEHYDES
AND KETONES

2. CARBONYL COMPOUNDS
ALDEHYDES
KETONES

3. EXAMPLES
Formaldehyde
Acetaldehyde
Acetone

4. MOLECULAR MODELS
Formaldehyde
Acetaldehyde
Acetone

5. INDUSTRIAL PRODUCTION
Catalytic dehydrogenation (oxidation) of alcohols

6. Common names of simple carbonyl compounds
Formula
Common name
Systematic name
HCHO
CH3CHO
CH3CH2CHO
CH3CH2CH2CHO
CH3CH2CH2CH2CHO
H2C=CHCHO
PhCHO
CH3COCH3
CH3COCH2CH3
CH3CH2COCH2CH3
Formaldehyde
Acetaldehyde
Propionaldehyde
Butyraldehyde
Valeraldehyde
Acrolein
Benzaldehyde
Acetone
Methyl ethyl ketone
Ethyl ketone
Methanal
Ethanal
Propanal
Butanal
Pentanal
2-Propenal
Benzenecarbaldehyde
Propan-2-one
Butan-2-one
Pentan-3-one

7. Physical properties of aldehydes and ketones
More polar than alkanes, higher melting and boiling points
No hydrogen bonds formation – lower boiling points than alcohols
Solubility in water – only formaldehyde,
acetaldehyde and acetone

8. Physical properties of carbonyl compounds
M.p (°C)
B.p (°C)
Formaldehyde
Acetaldehyde
Propanal
Butanal
Pentanal
Benzaldehyde
Acetone
2-Butanone
2-Pentanone
3-Pentanone
Cyclohexanone
-92
-121
-81
-99
-26
-95
-86
-78
-40
-16
-21 21 49 76
103
178 56 80
102
156

9. Preparation of aldehydes
Oxidation of primary alcohols
Aldehyde which boils at lower temperature
than alcohol is distilled off the reaction mixture
immediately after formation

10. Preparation of aldehydes
Ozonolysis of di- or trisubstituted alkenes

11. Preparation of aldehydes
Reduction of carboxylic acids esters
DIBAH – diisobutylaluminum hydride
(aldehyde is not reduced further to primary alcohol)

12. Preparation of aldehydes
Reduction of carboxylic acids chlorides
8 October 2018
Tri-tert-butoxylithiumaluminum hydride

13. Preparation of aldehydes
Oxidation of methylarenes

14. Preparation of ketones
Oxidation of secondary alcohols
90% yield

15. Preparation of ketones
Ozonolysis of alkenes

16. Preparation of ketones
Friedel-Crafts acylation of arenes (electrophilic aromatic substitution)
95% yield

17. Preparation of ketones
Hydration of alkynes (terminal or symmetric)
78% yield

18. Preparation of ketones
Reaction of acid chloride and diorganocopper reagent
81% yield

19. Oxidation of aldehydes and ketones

20. Oxidation of aldehydes and ketones
Tollens oxidation
Reaction used as laboratory test to distinguish aldehyde and ketone

21. Reaction limited to symmetric cyclic ketones
Oxidation of ketones
Reaction limited to symmetric cyclic ketones

22. Nucleophilic addition reactions of aldehydes and ketones
Alcohol
Alcohol
Cyanohydrin
Alkene
Imine
Alkane
Acetal
Enamine

23. Aldehydes are more reactive than ketones Nu
Formaldehyde Acetaldehyde Acetone
Steric factor
Access of nuclephile to carbonyl carbon is less hindered in aldehyde
(hydrogen is smaller than any alkyl substituent)

24. Aldehydes are more reactive than ketones
Electronic factor
Positive charge on carbon is stronger stabilized by inductive effect
of two alkyl groups
Ketones are more stable – less reactive

25. Nucleophilic addition of H2O
(hydration)
A gem-diol
A gem-diol

26. Base-catalyzed addition of H2O
Hydroxide anion is more reactive
nucleophile than neutral water

27. Acid-catalyzed addition of H2O
Protonated carbonyl is more
electrophilic and more reactive

28. Nucleophilic addition of HCN
(cyanohydrins)
In practice HCN is generated during reaction
by adding acid (like H2SO4) to a mixture of
carbonyl compound and NaCN (or KCN).
Cyanide anion is nucleophile

29. Reactions of cyanohydrins
Cyanohydrin formation from ketone or aldehyde provides compounds
with new functional groups while lenghtening the carbon chain by one unit

30. Nucleophilic addition of Grignard reagents
(alcohol formation)
New alcohol with larger
hydrocarbon framework
is obtained

31. Nucleophilic addition of hydride
(reduction)
Alcohol with the same
hydrocarbon framework as
starting ketone or aldehyde
is formed

32. Nucleophilic addition of amines to carbonyl group

33. Water elimination from carbinolamine

34. Crystalline imines

35. Crystalline imines
m. p. 126°C

36. Nucleophilic addition of hydrazine (Wolff-Kishner reaction)

37. Nucleophilic addition of alcohols (acetal formation)
Protonated carbonyl group
is strongly electrophilic
and highly reactive towards nucleophiles

38. Nucleophilic addition of alcohols
(acetal formation)

39. Mechanism of acetal formation

40. Acetal as carbonyl protective group
How to reduce ester carbonyl
without
reducing ketone carbonyl?

41. Acetal as carbonyl protective group

42. Nucleophilic addition of thiols (thioacetal formation)
Conversion of carbonyl
to thioacetal
and subsequent desulfurization
is a method
for reducing C=O to CH2

43. Nucleophilic addition of phosphorus ylides (The Wittig reaction)
New molecule containing
C=C bond
instead of carbonyl group
is synthesized

44. Conjugate nucleophilic addition to ,-unsaturated carbonyl
,-unsaturated carbonyl compounds
possess 2 electrophilic carbons
Conjugate addition product

45. Conjugate nucleophilic addition to ,-unsaturated carbonyl

46. Some biological nucleophilic additions Synthesis of -amino acid
from -ketoacid
in living cells

47. Biological reaction reverse to nucleophilic addition
Millipede Apheloria corrugata and its predator – an ant

48. The Cannizzaro reaction
The only example when hydride ion is expelled from aldehyde
as leaving group (like in nucleophilic acyl substitution)
Nucleophilic acyl substitution

49. The Cannizzaro reaction (disproportionation) -carbon react this way
Only aldehydes
without protons at
-carbon react this way
in the presence of base

50. The Cannizzaro reaction as model for biological reductions
NADPH functions as hydride donor in biological reductions

51. The Cannizzaro reaction as model for biological reductions
NADPH reduction of carbonyl to hydroxyl
– one of the key steps during fatty acid biosynthesis

52. -Substitution reactions of aldehydes or ketones

53. Keto-enol tautomerism Concentration of enol form at equilibrium

54. Enol formation is catalyzed by base or acid
Acid-catalyzed enol formation

55. Enol formation is catalyzed by base or acid
Base-catalyzed enol formation

56. Only the protons on the  position are acidic
Not acidic
Not acidic    
acidic
Not acidic

57. Mechanism of -substitution in aldehydes or ketones
Net effect –
substitution of -hydrogen
by group E

58. -Substitution in aldehydes or ketones
Examples: -halogenation

59. -Substitution in aldehydes or ketones
-Halogenation of enolate ions (iodoform reaction)
Bromine and chlorine react in the same way

60. Two modes of enolate ion reactivity
An enol derivative
An -substituted
carbonyl compound
More commonly followed path

61. Condensation of aldehydes and ketones
(aldol condensation)
Nucleophilic donor
Mechanism
Electrophilic acceptor
Aldol - -hydroxyaldehyde

62. Condensation of aldehydes
Examples:

63. Condensation of ketones
Examples:

64. Mixed aldol reactions (useless)
Symmetrical
products
Mixed
products

65. Mixed aldol reactions
(useful)

66. Brief summary
Aldol self-condensation cannot occur for aldehydes or ketones without -hydrogens
Aldehydes containing -hydrogens are more reactive than ketones
Aldol equilibrium is favorable for aldehydes without branching
at -carbon
Aldol equilibrium is not favorable for -branched aldehydes
Mixed aldol reaction between two different carbonyl partners with -hydrogens leads to a mixture of products (useless as synthetic method)
Mixed aldol reaction is very efficient when one partner is an unusally good nucleophilic donor or is a good electrophilic acceptor
29 October 2018

67. 1,3-Dicarbonyl compounds are excellent nucleophilic donors
Enolate ion stabilized by three resonance structures

68. Acidity constants for some organic compounds
Compound type
Formula
pKa
Carboxylic acid
1,3-Diketone
1,3-Ketoester
1,3-Dinitrile
1,3-Diester
WATER
Primary alcohol
Acid chloride
Aldehyde
Ketone
Ester
Nitrile
Dialkylamide
AMMONIA
Dialkylamine
CH3COOH
CH2(COCH3)2
CH3COCH2CO2C2H5
CH2(CN)2
CH2(CO2C2H5)2
H2O
CH3CH2OH
CH3COCl
CH3CHO
CH3COCH3
CH3CO2C2H5
CH3CN
CH3CON(CH3)2
NH3
HN(i-C3H7)2 5 9 11 13 16 17 19 25 30 35 40

69. Dehydration of aldol products
NOT FORMED

70. Dehydration of aldol products

71. Recognizing aldol products (Retrosynthetic analysis)

72. Intramolecular aldol reactions

73. Intramolecular aldol reactions