1. Chapter 19 Carboxylic Acids

2. 19.2 Structure and Bonding 4

3. Formic Acid Is Planar C O H
120 pm
134 pm 5

4. Electron Delocalization
Stabilizes carbonyl group R C O H ••
• • + – R C O H ••
• • R C O H ••
• • + – 6

5. 19.3 Physical Properties 7

6. Boiling Points O OH 141°C OH O bp (1 atm) 31°C 80°C 99°C
Intermolecular forces, especially hydrogen bonding, are stronger in carboxylic acids than in other compounds of similar shape and molecular weight 8

7. Hydrogen-Bonded Dimers
H3CC O H
CCH3
Acetic acid exists as a hydrogen-bonded dimer in the gas phase. The hydroxyl group of each molecule is hydrogen-bonded to the carbonyl oxygen of the other. 8

8. Hydrogen-Bonded Dimers
Acetic acid exists as a hydrogen-bonded dimer in the gas phase. The hydroxyl group of each molecule is hydrogen-bonded to the carbonyl oxygen of the other. 8

9. Form hydrogen bonds to water.
Solubility in Water
Carboxylic acids are similar to alcohols with respect to their solubility in water.
Form hydrogen bonds to water.
H3CC O H 10

10. 19.4 Acidity of Carboxylic Acids
Most carboxylic acids have a pKa close to 5. 7

11. Carboxylic Acids Are Weak Acids
But carboxylic acids are far more acidic than alcohols.
CH3COH O
CH3CH2OH
pKa = 4.7
pKa = 16 12

12. Free Energies of Ionization
CH3CH2O– + H+
G° = 64 kJ/mol
CH3CO– + H+ O
G° = 91 kJ/mol
G° = 27 kJ/mol
CH3COH O
CH3CH2OH 13

13. Inductive effect of carbonyl group:
Greater Acidity of Carboxylic Acids Is Due to Stabilization of Carboxylate Ion
Inductive effect of carbonyl group: RC O + –
Resonance stabilization of carboxylate ion: RC O – ••
• • 14

14. Electrostatic Potential Maps of Acetic Acid and Acetate Ion14

15. 19.6 Substituents and Acid Strength21

16. Substituent Effects on Acidity
Standard of comparison is acetic acid (X = H) X
CH2COH O
pKa = 4.7 22

17. Substituent Effects on AcidityX
CH2COH O X H
CH3
CH3(CH2)5
pKa
4.7
4.9
Alkyl groups have negligible effect X H F Cl
pKa
4.7
2.6
2.9
Electronegative groups increase acidity 23

18. Substituent Effects on AcidityX
CH2COH O
Electronegative substituents withdraw electrons from carboxyl group; increase K for loss of H+. 23

19. Effect of Electronegative Substituent Decreases as Number of Bonds between It and Carboxyl Group Increases.
pKa
CH3CH2CHCO2H Cl
2.8
4.1
4.5
CH3CHCH2CO2H Cl
ClCH2CH2CH2CO2H 23

20. 19.7 Ionization of Substituted Benzoic Acids26

21. Hybridization Effect pKa 4.2 4.3 1.8 COH O H2C CH HC C
sp2-Hybridized carbon is more electron-withdrawing than sp3, and sp is more electron-withdrawing than sp2. 23

22. Ionization of Substituted Benzoic Acids
COH O X
Effect is small unless X is electronegative; effect is largest for ortho substituent.
pKa
Substituent Ortho Meta Para H CH F Cl
CH3O NO 28

23. 19.10 Sources of Carboxylic Acids

24. Synthesis of Carboxylic Acids: Review
Side-chain oxidation of alkylbenzenes (11.13)
Oxidation of primary alcohols (15.10)
Oxidation of aldehydes (17.15) 2

25. Synthesis of Carboxylic Acids: Review

26. 19.11 Synthesis of Carboxylic Acids by the Carboxylation of Grignard Reagents4

27. Carboxylation of Grignard Reagents
RCOMgX O Mg
CO2 RX
RMgX
diethyl ether
H3O+
Converts an alkyl (or aryl) halide to a carboxylic acid having one more carbon atom than the starting halide.
RCOH O 5

28. Carboxylation of Grignard Reagents
MgX + – R C O ••
• • O
• • ••
diethyl ether – R
MgX C O
• • ••
H3O+ R C OH ••
• • O 23

29. Example: Alkyl Halide 1. Mg, diethyl ether CH3CHCH2CH3 CH3CHCH2CH3
2. CO2
3. H3O+ Cl
CO2H
(76-86%) 8

30. Example: Aryl Halide 1. Mg, diethyl ether 2. CO2 3. H3O+ CH3 CH3 Br
(82%) 8

31. 19.12 Synthesis of Carboxylic Acids by the Preparation and Hydrolysis of Nitriles11

32. Preparation and Hydrolysis of Nitriles
RCOH O –
• • C N
H3O+ RX RC
• • N
SN2
heat
+ NH4+
Converts an alkyl halide to a carboxylic acid having one more carbon atom than the starting halide.
Limitation is that the halide must be reactive toward substitution by SN2 mechanism. 5

33. Example
CH2Cl
NaCN
CH2CN
DMSO
(92%)
(77%)
H2O,
H2SO4,
heat
CH2COH O 13

34. Example: Dicarboxylic Acid
BrCH2CH2CH2Br
NaCN
H2O
NCCH2CH2CH2CN
(77-86%)
H2O, HCl
heat
(83-85%)
HOCCH2CH2CH2COH O 14

35. Example: -Hydroxy Acid from Ketone via Cyanohydrin
CH3CCH2CH2CH3 O
CH3CCH2CH2CH3 OH CN
1. NaCN
2. H+
H2O,
CH3CCH2CH2CH3 OH
CO2H
HCl, heat
2-Hydroxy-2-methylpentanoic acid, an -hydroxy acid (60% from 2-pentanone) 13

36. 19.13 Reactions of Carboxylic Acids: A Review and a Preview

37. Reactions of Carboxylic Acids
Reactions already discussed:
Acidity (19.4, )
Reaction with thionyl chloride (12.7; will also see in 20.4)
Reduction with LiAlH4 (15.3)
Acid-catalyzed esterification (15.8) 2

38. Reactions of Carboxylic Acids: Review

39. Reactions of Carboxylic Acids: Review1

40. 19.14 Mechanism of Acid-Catalyzed Esterification (Fischer Esterification)

41. Acid-Catalyzed Esterification
COH O H+ +
CH3OH
COCH3 O +
H2O
Important fact: the oxygen of the alcohol is incorporated into the ester as shown. 4

42. Mechanism of Fischer Esterification
The mechanism involves two stages:
1) Formation of tetrahedral intermediate (3 steps)
2) Dissociation of tetrahedral intermediate (3 steps) 5

43. Mechanism of Fischer Esterification
The mechanism involves two stages:
1) Formation of tetrahedral intermediate (3 steps)
2) Dissociation of tetrahedral intermediate (3 steps) C OH
OCH3
Tetrahedral intermediate in esterification of benzoic acid with methanol 5

44. First Stage: Formation of Tetrahedral Intermediate
COH O +
CH3OH
Methanol adds to the carbonyl group of the carboxylic acid.
The tetrahedral intermediate is analogous to a hemiacetal. H+ C OH
OCH3 5

45. Second Stage: Conversion of Tetrahedral Intermediate to Ester
COCH3 O +
H2O
This stage corresponds to an acid-catalyzed dehydration. H+ C OH
OCH3 5

46. Mechanism of Formation of Tetrahedral Intermediate8

47. Step 1 O
• • + H
CH3 C O H ••
• • •• C O H
• • +
CH3 8

48. Step 1 C O H ••
• • +
Carbonyl oxygen is protonated because cation produced is stabilized by electron delocalization (resonance). C O H ••
• • + •• 8

49. Step 2 C OH ••
• • O +
CH3 H C O H ••
• • +
• • O
CH3 H •• 8

50. Step 3 •• C OH
• • O
CH3 H +
• • O
CH3 H O
• •
CH3 H + •• C OH 8

51. Tetrahedral Intermediate to Ester Stage8

52. Step 4 •• C OH O
• •
OCH3 H +
CH3 •• C OH O
• •
OCH3 H O
• •
CH3 H + 8

53. Step 5 •• C OH O
• •
OCH3 H +
+ H2O C OH ••
OCH3 + 8

54. Step 6 + O H
CH3 •• C
OCH3
• • O •• H
CH3 C O ••
OCH3 + H 8

55. Key Features of Mechanism
Activation of carbonyl group by protonation of carbonyl oxygen.
Nucleophilic addition of alcohol to carbonyl group forms tetrahedral intermediate.
Elimination of water from tetrahedral intermediate restores carbonyl group. 17

56. Review of Fischer Esterification17

57. Industrial Use of Fischer Esterification:
Synthesis of Dacron® Polyester 17

58. A Waste of Good Chemistry17

59. 19.15 Intramolecular Ester Formation: Lactones

60. Lactones are cyclic esters.
Formed by intramolecular esterification in a compound that contains a hydroxyl group and a carboxylic acid function. 17

61. 4-Hydroxybutanoic acid 4-Butanolide
Example
HOCH2CH2CH2COH O O +
H2O
4-Hydroxybutanoic acid
4-Butanolide
IUPAC nomenclature: replace the -oic acid ending of the carboxylic acid by -olide.
Identify the oxygenated carbon by number. 19

62. 4-Hydroxybutanoic acid 4-Butanolide
Examples
HOCH2CH2CH2COH O O +
H2O
4-Hydroxybutanoic acid
4-Butanolide
HOCH2CH2CH2CH2COH O +
H2O
5-Hydroxypentanoic acid
5-Pentanolide 19

63. Ring size is designated by Greek letter.
Common names    O O    
-Butyrolactone
-Valerolactone
Ring size is designated by Greek letter.
A  lactone has a five-membered ring.
A  lactone has a six-membered ring. 19

64. Lactones
Reactions designed to give hydroxy acids often yield the corresponding lactone, especially if the resulting ring is 5- or 6-membered. 17

65. Example CH3CCH2CH2CH2COH O via: CH3CHCH2CH2CH2COH O OH 1. NaBH4
2. H2O, H+ O
H3C
5-hexanolide (78%) 20

66. Section 19.18 Spectroscopic Analysis of Carboxylic Acids

67. Infrared Spectroscopy
A carboxylic acid is characterized by peaks due to OH and C=O groups in its infrared spectrum.
C=O stretching gives an intense absorption near 1700 cm-1.
OH peak is broad and overlaps with C—H absorptions. 6

68. Infrared Spectrum of 4-Phenylbutanoic Acid8

69. 1H NMR
Proton of OH group of a carboxylic acid is normally the least shielded of all of the protons in 1H NMR spectra: ( ppm; broad). 6

70. 4-Phenylbutanoic Acid O CH2CH2CH2COH 1 Chemical shift (, ppm) 1.0 2.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
10.0
11.0
12.0
Chemical shift (, ppm) 1

71. 13C NMR
Carbonyl carbon is at low field ( ppm), but not as deshielded as the carbonyl carbon of an aldehyde or ketone ( ppm).