Ch. 16 - 1

1
Chapter 16

• Aldehydes Ketones
• Nucleophilic Addition
• to the Carbonyl Group

2
About The Authors

• These PowerPoint Lecture Slides were created and
  prepared by Professor William Tam and his wife,
  Dr. Phillis Chang.
• Professor William Tam received his B.Sc. at the
  University of Hong Kong in 1990 and his Ph.D. at
  the University of Toronto (Canada) in 1995. He
  was an NSERC postdoctoral fellow at the Imperial
  College (UK) and at Harvard University (USA). He
  joined the Department of Chemistry at the
  University of Guelph (Ontario, Canada) in 1998
  and is currently a Full Professor and Associate
  Chair in the department. Professor Tam has
  received several awards in research and teaching,
  and according to Essential Science Indicators, he
  is currently ranked as the Top 1 most cited
  Chemists worldwide. He has published four books
  and over 80 scientific papers in top
  international journals such as J. Am. Chem. Soc.,
  Angew. Chem., Org. Lett., and J. Org. Chem.
• Dr. Phillis Chang received her B.Sc. at New York
  University (USA) in 1994, her M.Sc. and Ph.D. in
  1997 and 2001 at the University of Guelph
  (Canada). She lives in Guelph with her husband,
  William, and their son, Matthew.

3

1. Introduction

• Carbonyl compounds

4

1. Nomenclature of Aldehydes Ketones

• Rules
• Aldehyde as parent (suffix)
• Ending with al
• Ketone as parent (suffix)
• Ending with one
• Number the longest carbon chain containing the
  carbonyl carbon and starting at the carbonyl
  carbon

5

• Examples

6

• group as a prefix methanoyl or formyl
  group

• group as a prefix ethanoyl or acetyl
  group (Ac)

• groups as a prefix alkanoyl or acyl
  groups

7
(No Transcript)
8

1. Physical Properties

9

1. Synthesis of Aldehydes

4A. Aldehydes by Oxidation of 1o Alcohols
10

• e.g.

11
4B. Aldehydes by Ozonolysis ofAlkenes
12

• e.g.

13
4C. Aldehydes by Reduction of AcylChlorides,
Esters, and Nitriles
14

• LiAlH4 is a very powerful reducing agent, and
  aldehydes are easily reduced
• Usually reduced all the way to the corresponding
  1o alcohol
• Difficult to stop at the aldehyde stage
• Not a good method to synthesize aldehydes using
  LiAlH4

15

• Two derivatives of aluminum hydride that are less
  reactive than LAH

16
(No Transcript)
17

• Aldehydes from acyl chlorides RCOCl ? RCHO

• e.g.

18

• Reduction of an Acyl Chloride to an Aldehyde

19

• Aldehydes from esters and nitriles RCO2R ? RCHO
• RCN ? RCHO
• Both esters and nitriles can be reduced to
  aldehydes by DIBAL-H

20

• Reduction of an ester to an aldehyde

21

• Reduction of a nitrile to an aldehyde

22

• Examples

23

1. Synthesis of Ketones

5A. Ketones from Alkenes, Arenes,and 2o Alcohols

• Ketones (and aldehydes) by ozonolysis of alkenes

24

• Examples

25

• Ketones from arenes by FriedelCrafts acylations

26

• Ketones from secondary alcohols by oxidation

27
5B. Ketones from Nitriles
28

• Examples

29

• Suggest synthesis of

from and
30

• Retrosynthetic analysis

need to add one carbon
?
31

• Retrosynthetic analysis

32

• Synthesis

33

• Suggest synthesis of

from and
34

• Retrosynthetic analysis

no need to add carbon
?
35

• Retrosynthetic analysis

36

• Synthesis

37

1. Nucleophilic Addition to theCarbonOxygen Double
   Bond

• Structure

Nu?

• Carbonyl carbon sp2 hybridized
• Trigonal planar structure

38

• Polarization and resonance structure

• Nucleophiles will attack the nucleophilic
  carbonyl carbon
• Note nucleophiles usually do not attack
  non-polarized CC bond

39

• With a strong nucleophile

40

• Also would expect nucleophilic addition reactions
  of carbonyl compounds to be catalyzed by acid (or
  Lewis acid)

• Note full positive charge on the carbonyl carbon
  in one of the resonance forms
• Nucleophiles readily attack

41

• Mechanism

42

• Mechanism

43
6A. Reversibility of NucleophilicAdditions to
the CarbonOxygenDouble Bond

• Many nucleophilic additions to carbonoxygen
  double bonds are reversible the overall results
  of these reactions depend, therefore, on the
  position of an equilibrium

44
6B. Relative Reactivity Aldehydesvs. Ketones
45

• Steric factors

46

• Electronic factors

(positive inductive effect from both R R'
groups) ? carbonyl carbon less d (less
nucleophilic)
(positive inductive effect from only one R group)
47

1. The Addition of AlcoholsHemiacetals and Acetals

• Acetal Ketal Formation Addition of Alcohols
  to Aldehydes

Catalyzed by acid
48

• Mechanism

49

• Mechanism (Contd)

50

• Mechanism (Contd)

51

• Note All steps are reversible. In the presence
  of a large excess of anhydrous alcohol and
  catalytic amount of acid, the equilibrium
  strongly favors the formation of acetal (from
  aldehyde) or ketal (from ketone)
• On the other hand, in the presence of a large
  excess of H2O and a catalytic amount of acid,
  acetal or ketal will hydrolyze back to aldehyde
  or ketone. This process is called hydrolysis

52

• Acetals and ketals are stable in neutral or basic
  solution, but are readily hydrolyzed in aqueous
  acid

53

• Aldehyde hydrates gem-diols

54

• Mechanism

55
7A. Hemiacetals
Hemiacetal OH OR groups bonded to the same
carbon
56
Hemiacetal OH OR groups bonded to the same
carbon
57
7B. Acetals
A ketal
An acetal
58

• Cyclic acetal formation is favored when a ketone
  or an aldehyde is treated with an excess of a
  1,2-diol and a trace of acid

59

• This reaction, too, can be reversed by treating
  the acetal with aqueous acid

60
7C. Acetals Are Used as Protecting Groups

• Although acetals are hydrolyzed to aldehydes and
  ketones in aqueous acid, acetals are stable in
  basic solutions

• Acetals are used to protect aldehydes and ketones
  from undesired reactions in basic solutions

61

• Example

62

• Synthetic plan

• This route will not work

63
Reason
(a) Intramolecular nucleophilic addition
(b) Homodimerization or polymerization
64

• Thus, need to protect carbonyl group first

65
7D. Thioacetals

• Aldehydes ketones react with thiols to form
  thioacetals

66

• Thioacetal formation with subsequent
  desulfurization with hydrogen and Raney nickel
  gives us an additional method for converting
  carbonyl groups of aldehydes and ketones to CH2
  groups

67

1. The Addition of Primary andSecondary Amines

• Aldehydes ketones react with 1o amines to form
  imines and with 2o amines to form enamines

From a 1o amine
From a 2o amine
68
8A. Imines

• Addition of 1o amines to aldehydes ketones

69

• Mechanism

70

• Similar to the formation of acetals and ketals,
  all the steps in the formation of imine are
  reversible. Using a large excess of the amine
  will drive the equilibrium to the imine side
• Hydrolysis of imines is also possible by adding
  excess water in the presence of catalytic amount
  of acid

71
8B. Oximes and Hydrazones

• Imine formation reaction with a 1o amine

• Oxime formation reaction with hydroxylamine

72

• Hydrazone formation reaction with hydrazine

• Enamine formation reaction with a 2o amine

73
8C. Enamines
74

• Mechanism

75

• Mechanism (Contd)

76

• Mechanism (Contd)

77

1. The Addition of HydrogenCyanide Cyanohydrins

• Addition of HCN to aldehydes ketones

78

• Mechanism

79

• Slow reaction using HCN since HCN is a weak acid
  and a poor source of nucleophile
• Can accelerate reaction by using NaCN or KCN and
  slow addition of H2SO4

80

• Synthetic applications

81

1. The Addition of Ylides TheWittig Reaction

82

• Phosphorus ylides

83

• Example

84

• Mechanism of the Wittig reaction

85
10A. How to Plan a Witting Synthesis

• Synthesis of
• using a Wittig reaction

86

• Retrosynthetic analysis

87

• Synthesis Route 1

88

• Synthesis Route 2

89
10B. The HornerWadsworthEmmons Reaction
90
(No Transcript)
91

• The phosphonate ester is prepared by reaction of
  a trialkyl phosphite (RO)3P with an appropriate
  halide (a process called the Arbuzov reaction)

92

1. Oxidation of Aldehydes

93

1. Chemical Analyses for Aldehydes and Ketones

12A. Derivatives of Aldehydes Ketones
94
12B. Tollens Test (Silver Mirror Test)
95

1. Spectroscopic Properties of Aldehydes and Ketones

13A. IR Spectra of Aldehydes and Ketones
96

• Conjugation of the carbonyl group with a double
  bond or a benzene ring shifts the CO absorption
  to lower frequencies by about 40 cm-1

97
(No Transcript)
98
13B. NMR Spectra of Aldehydes and Ketones

• 13C NMR spectra
• The carbonyl carbon of an aldehyde or ketone
  gives characteristic NMR signals in the d 180220
  ppm region of 13C spectra

99

• 1H NMR spectra
• An aldehyde proton gives a distinct 1H NMR signal
  downfield in the d 912 ppm region where almost
  no other protons absorb therefore, it is easily
  identified
• Protons on the a carbon are deshielded by the
  carbonyl group, and their signals generally
  appear in the d 2.02.3 ppm region
• Methyl ketones show a characteristic (3H) singlet
  near d 2.1 ppm

100
(No Transcript)
101
(No Transcript)
102

1. Summary of Aldehyde and Ketone Addition Reactions

103
? END OF CHAPTER 16 ?