1. Dr. Wolf's CHM 201 & 202 18-1 Chapter 18 Carboxylic Acids

2. Dr. Wolf's CHM 201 & 202 18-2 Carboxylic Acid Nomenclature

3. Dr. Wolf's CHM 201 & 202 18-3 Table 18.1 Systematic Name OHCOH methanoic acid O CH 3 COH ethanoic acid O CH 3 (CH 2 ) 16 COH octadecanoic acid systematic IUPAC names replace "-e" ending of alkane with "oic acid"

4. Dr. Wolf's CHM 201 & 202 18-4 Table 18.1 Systematic Name Common Name OHCOH methanoic acid formic acid O CH 3 COH ethanoic acid acetic acid O CH 3 (CH 2 ) 16 COH octadecanoic acid stearic acid common names are based on natural origin rather than structure

5. Dr. Wolf's CHM 201 & 202 18-5 Table 18.1 Systematic Name Common Name 2-hydroxypropanoic acid lactic acid (Z)-9-octadecenoic acid oleic acid O CH 3 CHCOH OH O (CH 2 ) 7 COH C C HH CH 3 (CH 2 ) 7

6. Dr. Wolf's CHM 201 & 202 18-6 Structure and Bonding

7. Dr. Wolf's CHM 201 & 202 18-7 Formic acid is planar

8. Dr. Wolf's CHM 201 & 202 18-8 Formic acid is planar CO H H O 120 pm 134 pm

9. Dr. Wolf's CHM 201 & 202 18-9 Electron Delocalization R C O H O R C O H O + –

10. Dr. Wolf's CHM 201 & 202 18-10 Electron Delocalization stabilizes carbonyl group R C O H O R C O H O + – R C O H O + –

11. Dr. Wolf's CHM 201 & 202 18-11 Physical Properties

12. Dr. Wolf's CHM 201 & 202 18-12 Boiling Points Intermolecular forces, especially hydrogen bonding, are stronger in carboxylic acids than in other compounds of similar shape and molecular weight bp 31°C80°C99°COH 141°C OHO O

13. Dr. Wolf's CHM 201 & 202 18-13 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. H 3 CC OH O CCH 3 O HO

14. Dr. Wolf's CHM 201 & 202 18-14 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.

15. Dr. Wolf's CHM 201 & 202 18-15 carboxylic acids are similar to alcohols in respect to their solubility in water form hydrogen bonds to water Solubility in Water H 3 CC OH O O H OHH H

16. Dr. Wolf's CHM 201 & 202 18-16 Acidity of Carboxylic Acids Most carboxylic acids have a pK a close to 5.

17. Dr. Wolf's CHM 201 & 202 18-17 but carboxylic acids are far more acidic than alcohols Carboxylic acids are weak acids CH 3 COH O CH 3 CH 2 OH K a = 1.8 x 10 -5 pK a = 4.7 K a = 10 -16 pK a = 16

18. Dr. Wolf's CHM 201 & 202 18-18  G°= 91 kJ/mol  G°= 27 kJ/mol  G°= 64 kJ/mol Free Energies of Ionization CH 3 CH 2 O – + H + CH 3 CH 2 OH CH 3 COH O CH 3 CO – + H + O

19. Dr. Wolf's CHM 201 & 202 18-19 Greater acidity of carboxylic acids is attributed stabilization of carboxylate ion by inductive effect of carbonyl group resonance stabilization of carboxylate ion RCOO ++++ – RC O O – RC O O–

20. Dr. Wolf's CHM 201 & 202 18-20 Figure 19.4: Electrostatic potential maps of acetic acid and acetate ion Acetic acid Acetate ion

21. Dr. Wolf's CHM 201 & 202 18-21 Substituents and Acid Strength

22. Dr. Wolf's CHM 201 & 202 18-22 standard of comparison is acetic acid (X = H) Substituent Effects on Acidity X CH 2 COH O K a = 1.8 x 10 -5 pK a = 4.7

23. Dr. Wolf's CHM 201 & 202 18-23 Substituent Effects on Acidity alkyl substituents have negligible effect X CH 2 COH O X KaKaKaKa pKapKapKapKaH CH 3 CH 3 (CH 2 ) 5 1.8 x 10 -5 4.7 1.3 x 10 -5 4.9 4.9

24. Dr. Wolf's CHM 201 & 202 18-24 Substituent Effects on Acidity electronegative substituents increase acidity X CH 2 COH O X KaKaKaKa pKapKapKapKaH F Cl 1.8 x 10 -5 4.7 2.5 x 10 -3 2.6 1.4 x 10 -3 2.9

25. Dr. Wolf's CHM 201 & 202 18-25 Substituent Effects on Acidity electronegative substituents withdraw electrons from carboxyl group; increase K for loss of H + X CH 2 COH O

26. Dr. Wolf's CHM 201 & 202 18-26 Substituent Effects on Acidity effect of substituent decreases as number of bonds between X and carboxyl group increases X CH 2 COH OX KaKaKaKa pKapKapKapKa H 1.8 x 10 -5 4.7 1.4 x 10 -3 2.9 1.0 x 10 -4 4.0 ClCH 2 Cl 3.0 x 10 -5 4.5 ClCH 2 CH 2

27. Dr. Wolf's CHM 201 & 202 18-27 Ionization of Substituted Benzoic Acids

28. Dr. Wolf's CHM 201 & 202 18-28 Hybridization Effect KaKaKaKa pKapKapKapKa 6.3 x 10 -5 4.2 5.5 x 10 -5 4.3 1.4 x 10 -2 1.8 COH O H2CH2CH2CH2C CH COH O COH O HC C sp 2 -hybridized carbon is more electron- withdrawing than sp 3, and sp is more electron-withdrawing than sp 2

29. Dr. Wolf's CHM 201 & 202 18-29 pK a Substituentorthometapara H4.24.24.2 CH 3 3.94.34.4 F3.33.94.1 Cl2.93.84.0 CH 3 O4.14.14.5 NO 2 2.23.53.4 Ionization of Substituted Benzoic Acids COHOX effect is small unless X is electronegative; effect is largest for ortho substituent

30. Dr. Wolf's CHM 201 & 202 18-30 Salts of Carboxylic Acids

31. Dr. Wolf's CHM 201 & 202 18-31 Carboxylic acids are neutralized by strong bases equilibrium lies far to the right; K is ~ 10 11 as long as the molecular weight of the acid is not too high, sodium and potassium carboxylate salts are soluble in water stronger acid weaker acid RCOH + HO – RCO – + H2OH2OH2OH2OOO

32. Dr. Wolf's CHM 201 & 202 18-32 unbranched carboxylic acids with 12-18 carbons give carboxylate salts that form micelles in water MicellesMicellesOONa sodium stearate (sodium octadecanoate) CH 3 (CH 2 ) 16 CO O Na + –

33. Dr. Wolf's CHM 201 & 202 18-33 MicellesMicellesOONa polar nonpolar sodium stearate has a polar end (the carboxylate end) and a nonpolar "tail" the polar end is "water-loving" or hydrophilic the nonpolar tail is "water-hating" or hydrophobic in water, many stearate ions cluster together to form spherical aggregates; carboxylate ions on the outside and nonpolar tails on the inside

34. Dr. Wolf's CHM 201 & 202 18-34 MicellesOONa polar nonpolar

35. Dr. Wolf's CHM 201 & 202 18-35 Figure 19.5 A micelle

36. Dr. Wolf's CHM 201 & 202 18-36 MicellesMicelles The interior of the micelle is nonpolar and has the capacity to dissolve nonpolar substances. Soaps clean because they form micelles, which are dispersed in water. Grease (not ordinarily soluble in water) dissolves in the interior of the micelle and is washed away with the dispersed micelle.

37. Dr. Wolf's CHM 201 & 202 18-37 Dicarboxylic Acids

38. Dr. Wolf's CHM 201 & 202 18-38 Dicarboxylic Acids one carboxyl group acts as an electron- withdrawing group toward the other; effect decreases with increasing separation Oxalic acid Malonic acid Heptanedioic acid 1.2 2.8 4.3 COHOHOCO pKapKapKapKa HOCCH 2 COH OO HOC(CH 2 ) 5 COH OO

39. Dr. Wolf's CHM 201 & 202 18-39 Carbonic Acid

40. Dr. Wolf's CHM 201 & 202 18-40 Carbonic Acid HOCOHO CO 2 + H2OH2OH2OH2O 99.7%0.3%

41. Dr. Wolf's CHM 201 & 202 18-41 Carbonic Acid HOCOHO CO 2 + H2OH2OH2OH2O HOCO – O H+H+H+H+ +

42. Dr. Wolf's CHM 201 & 202 18-42 Carbonic Acid HOCOHO CO 2 + H2OH2OH2OH2O HOCO – O H+H+H+H+ + overall K for these two steps = 4.3 x 10 -7 CO 2 is major species present in a solution of "carbonic acid" in acidic media

43. Dr. Wolf's CHM 201 & 202 18-43 Carbonic Acid HOCO – O – OCO – O H+H+H+H+ + K a = 5.6 x 10 -11 Second ionization constant:

44. Dr. Wolf's CHM 201 & 202 18-44 Sources of Carboxylic Acids

45. Dr. Wolf's CHM 201 & 202 18-45 side-chain oxidation of alkylbenzenes (Chapter 11) oxidation of primary alcohols (Chapter 15) oxidation of aldehydes (Chapter 17) Synthesis of Carboxylic Acids: Review

46. Dr. Wolf's CHM 201 & 202 18-46 Synthesis of Carboxylic Acids by the Carboxylation of Grignard Reagents

47. Dr. Wolf's CHM 201 & 202 18-47 Carboxylation of Grignard Reagents RX Mg diethyl ether RMgX CO2CO2CO2CO2 H3O+H3O+H3O+H3O+ RCOMgX O RCOH O converts an alkyl (or aryl) halide to a carboxylic acid having one more carbon atom than the starting halide

48. Dr. Wolf's CHM 201 & 202 18-48RMgX C O MgX+ –––– H3O+H3O+H3O+H3O+ diethyl ether O – R C O O R C OH O Carboxylation of Grignard Reagents

49. Dr. Wolf's CHM 201 & 202 18-49 Example: Alkyl Halide CH 3 CHCH 2 CH 3 (76-86%) 1. Mg, diethyl ether 2. CO 2 3. H 3 O + CH 3 CHCH 2 CH 3 Cl CO2HCO2HCO2HCO2H

50. Dr. Wolf's CHM 201 & 202 18-50 Example: Aryl Halide (82%) 1. Mg, diethyl ether 2. CO 2 3. H 3 O + CH 3 CO2HCO2HCO2HCO2H Br

51. Dr. Wolf's CHM 201 & 202 18-51 Synthesis of Carboxylic Acids by the Preparation and Hydrolysis of Nitriles

52. Dr. Wolf's CHM 201 & 202 18-52 Preparation and Hydrolysis of Nitriles RX RCOH O 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 S N 2 mechanism, i.e. best with primary, then secondary…… tertiary gives elimination – C N RCRCRCRC N SN2SN2SN2SN2 H3O+H3O+H3O+H3O+ heat + NH 4 +

53. Dr. Wolf's CHM 201 & 202 18-53 Example NaCN DMSO (77%) H2OH2OH2OH2O H 2 SO 4 heat (92%) CH 2 Cl CH 2 CN CH 2 COH O

54. Dr. Wolf's CHM 201 & 202 18-54 Example: Dicarboxylic Acid BrCH 2 CH 2 CH 2 Br NaCN H2OH2OH2OH2O H 2 O, HCl heat (77-86%) NCCH 2 CH 2 CH 2 CN (83-85%) HOCCH 2 CH 2 CH 2 COH OO

55. Dr. Wolf's CHM 201 & 202 18-55 via Cyanohydrin 1. NaCN 2. H + (60% from 2-pentanone) H2OH2OH2OH2O HCl, heat CH 3 CCH 2 CH 2 CH 3 O OH CNCNCNCN OH CO2HCO2HCO2HCO2H

56. Dr. Wolf's CHM 201 & 202 18-56 Reactions of Carboxylic Acids: A Review and a Preview

57. Dr. Wolf's CHM 201 & 202 18-57 Reactions of Carboxylic Acids Acidity (Chapter 18) Reduction with LiAlH 4 (Chapter 15) Esterification (Chapter 15) Reaction with Thionyl Chloride (Chapter 12) Reactions already discussed

58. Dr. Wolf's CHM 201 & 202 18-58 Reactions of Carboxylic Acids Decarboxylation But first we revisit acid-catalyzed esterification to examine its mechanism. New reaction in this chapter

59. Dr. Wolf's CHM 201 & 202 18-59 Mechanism of Acid-Catalyzed Esterification

60. Dr. Wolf's CHM 201 & 202 18-60 Acid-catalyzed Esterification + CH 3 OH COHO H+H+H+H++ H2OH2OH2OH2O COCH 3 O Important fact: the oxygen of the alcohol is incorporated into the ester as shown. (also called Fischer esterification)

61. Dr. Wolf's CHM 201 & 202 18-61 The mechanism involves two stages: 1)formation of tetrahedral intermediate (3 steps) 2)dissociation of tetrahedral intermediate (3 steps) Mechanism of Fischer Esterification

62. Dr. Wolf's CHM 201 & 202 18-62 The mechanism involves two stages: 1)formation of tetrahedral intermediate (3 steps) 2)dissociation of tetrahedral intermediate (3 steps) Mechanism of Fischer Esterification COHOH OCH 3 tetrahedral intermediate in esterification of benzoic acid with methanol

63. Dr. Wolf's CHM 201 & 202 18-63 First stage: formation of tetrahedral intermediate COHOH OCH 3 + CH 3 OH COHO H+H+H+H+ methanol adds to the carbonyl group of the carboxylic acid the tetrahedral intermediate is analogous to a hemiacetal

64. Dr. Wolf's CHM 201 & 202 18-64 Second stage: conversion of tetrahedral intermediate to ester COHOH OCH 3 + H2OH2OH2OH2O H+H+H+H+ this stage corresponds to an acid-catalyzed dehydration COCH 3 O

65. Dr. Wolf's CHM 201 & 202 18-65 Mechanism of formation of tetrahedral intermediate

66. Dr. Wolf's CHM 201 & 202 18-66 Step 1 C O OH O + H CH 3 H

67. Dr. Wolf's CHM 201 & 202 18-67 Step 1 C O OH O + H CH 3 H C O OH + H O CH 3 H

68. Dr. Wolf's CHM 201 & 202 18-68 Step 1 C O OH + H carbonyl oxygen is protonated because cation produced is stabilized by electron delocalization (resonance) C OOH + H

69. Dr. Wolf's CHM 201 & 202 18-69 Step 2 C O OH + H O CH 3 H

70. Dr. Wolf's CHM 201 & 202 18-70 Step 2 C O OH + H O CH 3 H C OH OH O + CH 3 H

71. Dr. Wolf's CHM 201 & 202 18-71 Step 3 O CH 3 H C OH OH O CH 3 H +

72. Dr. Wolf's CHM 201 & 202 18-72 Step 3 O CH 3 H C OH OH O CH 3 H + O CH 3 H H + C OH OH O CH 3

73. Dr. Wolf's CHM 201 & 202 18-73 Tetrahedral intermediate to ester stage

74. Dr. Wolf's CHM 201 & 202 18-74 Step 4 C OH O OCH 3 H

75. Dr. Wolf's CHM 201 & 202 18-75 Step 4 O CH 3 H H + C OH O OCH 3 H

76. Dr. Wolf's CHM 201 & 202 18-76 Step 4 O CH 3 H H + C OH O OCH 3 H C OH O OCH 3 H H + O CH 3 H

77. Dr. Wolf's CHM 201 & 202 18-77 Step 5 C OH O OCH 3 H H +

78. Dr. Wolf's CHM 201 & 202 18-78 Step 5 C OH O OCH 3 H H + O H H+ C OH OCH 3 +

79. Dr. Wolf's CHM 201 & 202 18-79 Step 5 C OH OCH 3 + C OH +

80. Dr. Wolf's CHM 201 & 202 18-80 Step 6 C O OCH 3 + H O H CH 3 + O H H C O OCH 3

81. Dr. Wolf's CHM 201 & 202 18-81 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 Key Features of Mechanism

82. Dr. Wolf's CHM 201 & 202 18-82 Intramolecular Ester Formation: Lactones

83. Dr. Wolf's CHM 201 & 202 18-83 Lactones are cyclic esters Formed by intramolecular esterification in a compound that contains a hydroxyl group and a carboxylic acid function Lactones

84. Dr. Wolf's CHM 201 & 202 18-84 Examples HOCH 2 CH 2 CH 2 COH O OO + H2OH2OH2OH2O 4-hydroxybutanoic acid 4-butanolide IUPAC nomenclature: replace the -oic acid ending of the carboxylic acid by -olide identify the oxygenated carbon by number

85. Dr. Wolf's CHM 201 & 202 18-85 Examples HOCH 2 CH 2 CH 2 COH O HOCH 2 CH 2 CH 2 CH 2 COH O O O OO + + H2OH2OH2OH2O H2OH2OH2OH2O 4-hydroxybutanoic acid 5-hydroxypentanoic acid 4-butanolide 5-pentanolide

86. Dr. Wolf's CHM 201 & 202 18-86 Common names O O OO  -butyrolactone  -valerolactone        Ring size is designated by Greek letter corresponding to oxygenated carbon A  lactone has a five-membered ring A  lactone has a six-membered ring

87. Dr. Wolf's CHM 201 & 202 18-87 Reactions designed to give hydroxy acids often yield the corresponding lactone, especially if the resulting ring is 5- or 6-membered. Lactones

88. Dr. Wolf's CHM 201 & 202 18-88 Example 5-hexanolide (78%) O H3CH3CH3CH3C O CH 3 CCH 2 CH 2 CH 2 COH OO 1. NaBH 4 2. H 2 O, H +

89. Dr. Wolf's CHM 201 & 202 18-89 Example 5-hexanolide (78%) via: O H3CH3CH3CH3C O CH 3 CCH 2 CH 2 CH 2 COH OO 1. NaBH 4 2. H 2 O, H + CH 3 CHCH 2 CH 2 CH 2 COH O OHOHOHOH

90. Dr. Wolf's CHM 201 & 202 18-90 Decarboxylation of Malonic Acid and Related Compounds

91. Dr. Wolf's CHM 201 & 202 18-91 Decarboxylation of Carboxylic Acids Simple carboxylic acids do not decarboxylate readily. RH + CO 2 RCOHO

92. Dr. Wolf's CHM 201 & 202 18-92 Decarboxylation of Carboxylic Acids Simple carboxylic acids do not decarboxylate readily. But malonic acid does. RH + CO 2 RCOHO150°C CH 3 COH O+ CO 2 HOCCH 2 COH OO

93. Dr. Wolf's CHM 201 & 202 18-93 Mechanism of Decarboxylation One carboxyl group assists the loss of the other. OOOHHO HH OHO O O HH H

94. Dr. Wolf's CHM 201 & 202 18-94 Mechanism of Decarboxylation This compound is the enol form of acetic acid. OOOHHO HH H HOHHO OHO O O HH H + COO One carboxyl group assists the loss of the other.

95. Dr. Wolf's CHM 201 & 202 18-95 Mechanism of Decarboxylation OOOHHO HH H HOHHO OHO O O HH H + COO One carboxyl group assists the loss of the other. HOCCH 3 O

96. Dr. Wolf's CHM 201 & 202 18-96 Mechanism of Decarboxylation OOOHHO HH H HOHHO OHO O O HH H + COO One carboxyl group assists the loss of the other. HOCCH 3 O These hydrogens play no role.

97. Dr. Wolf's CHM 201 & 202 18-97 Mechanism of Decarboxylation OOOHHO RR' R R'OHHO OHO O O RR' H + COO One carboxyl group assists the loss of the other. HOCCHR' O Groups other than H may be present. R

98. Dr. Wolf's CHM 201 & 202 18-98185°C Decarboxylation is a general reaction for 1,3-dicarboxylic acids 160°C CO 2 H H (74%) (96-99%) CH(CO 2 H) 2 CH 2 CO 2 H

99. Dr. Wolf's CHM 201 & 202 18-99 Mechanism of Decarboxylation OOOHHO RR' R R'OHHO OHO O O RR' H + COO One carboxyl group assists the loss of the other. This OH group plays no role. HOCCHR' OR

100. Dr. Wolf's CHM 201 & 202 18-100 Mechanism of Decarboxylation OOOHR" RR' R COO One carboxyl group assists the loss of the other. Groups other than OH may be present. R"CCHR' OR OO O RR' H R" R'OH+ R"

101. Dr. Wolf's CHM 201 & 202 18-101 Mechanism of Decarboxylation OOOHR" RR' This kind of compound is called a  -keto acid.   R"CCHR' OR Decarboxylation of a  -keto acid gives a ketone.

102. Dr. Wolf's CHM 201 & 202 18-102 Decarboxylation of a  -Keto Acid C CH 3 C O CH 3 CO 2 H 25°C CO 2 C CH 3 C O CH 3 H +

103. Dr. Wolf's CHM 201 & 202 18-103 Spectroscopic Analysis of Carboxylic Acids

104. Dr. Wolf's CHM 201 & 202 18-104 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. Infrared Spectroscopy

105. Dr. Wolf's CHM 201 & 202 18-105200035003000250010001500500 Wave number, cm -1 Figure 19.8 Infrared Spectrum of 4-Phenylbutanoic acid C=O O—H and C—H stretch monosubstituted benzene C 6 H 5 CH 2 CH 2 CH 2 CO 2 H

106. Dr. Wolf's CHM 201 & 202 18-106 proton of OH group of a carboxylic acid is normally the least shielded of all of the protons in a 1 H NMR spectrum: (  10-12 ppm; broad). 1 H NMR

107. Dr. Wolf's CHM 201 & 202 18-107 Chemical shift ( , ppm) Figure 19.9 CH 2 CH 2 CH 2 COH O 01.02.03.04.05.06.07.08.09.010.0 11.012.0

108. Dr. Wolf's CHM 201 & 202 18-108 13 C NMR Carbonyl carbon is at low field (  160-185 ppm), but not as deshielded as the carbonyl carbon of an aldehyde or ketone (  190-215 ppm).

109. Dr. Wolf's CHM 201 & 202 18-109 UV-VISUV-VIS Carboxylic acids absorb near 210 nm, but UV-VIS spectroscopy has not proven to be very useful for structure determination of carboxylic acids.

110. Dr. Wolf's CHM 201 & 202 18-110 Aliphatic carboxylic acids undergo a variety of fragmentations. Aromatic carboxylic acids first form acylium ions, which then lose CO. Mass Spectrometry ArCOH O ArCOH +O ArC O + Ar+

111. Dr. Wolf's CHM 201 & 202 18-111 End of Chapter 18