1. Chapter 11 Carboxylic Acid Derivatives

2. Acid Derivatives
All acid derivatives can be converted to the carboxylic acid by acidic or basic hydrolysis.
Esters and amides are common in nature.
Chapter 11

3. Naming Esters IUPAC Nomenclature Common Nomenclature
As usual the long chain will contain the carbonyl carbon. Drop the “e” then add oate suffix. The remaining carbon chain is named as substituent and used as a prefix.
Common Nomenclature
Esters are named from the common name of the acid used to form them. Drop the “oic acid” from the common acid name and att the suffix “ate”. The other carbon group is named as a substituent.
ethanol
ethyl alcohol
ethanoic acid
acetic acid
Chapter 11

4. Naming Esters IUPAC Nomenclature Common Nomenclature
As usual the long chain will contain the carbonyl carbon. Drop the “e” then add oate suffix. The remaining carbon chain is named as substituent and used as a prefix.
Common Nomenclature
Esters are named from the common name of the acid used to form them. Drop the “oic acid” from the common acid name and att the suffix “ate”. The other carbon group is named as a substituent.
ethanol
ethyl alcohol
ethanoic acid
acetic acid
ethyl ethanoate
ethyl acetate
Chapter 11

5. Name These
Chapter 11

6. Name These
(Common)
Chapter 11

7. isobutyl acetate (Common)
Name These
isobutyl acetate (Common)
Chapter 11

8. Name These isobutyl acetate (Common) benzyl formate (common)
Chapter 11

9. Name These isobutyl acetate (Common) benzyl formate (common)
2-methylpropyl ethanoate (IUPAC)
benzyl formate (common)
Chapter 11

10. Name These isobutyl acetate (Common) benzyl formate (common)
2-methylpropyl ethanoate (IUPAC)
benzyl formate (common)
benzyl methanoate (IUPAC)
Chapter 11

11. 4-hydroxy-2-methylpentanoic acid lactone
Cyclic Esters
Reaction of -OH and -COOH on same molecule produces a cyclic ester, lactone.
To name, add word lactone to the IUPAC acid name or replace the -ic acid of common name with -olactone.
4-hydroxy-2-methylpentanoic acid lactone
Chapter 11

12. Cyclic Esters
Reaction of -OH and -COOH on same molecule produces a cyclic ester, lactone.
To name, add word lactone to the IUPAC acid name or replace the -ic acid of common name with -olactone.
4-hydroxy-2-methylpentanoic acid lactone
-methyl--valerolactone
Chapter 11

13. Amides
Product of the reaction of a carboxylic acid and ammonia or an amine.
Not basic because the lone pair on nitrogen is delocalized by resonance.
Bond angles around N
are close to 120.
Chapter 11

14. Classes of Amides 1 amide has one C-N bond (two N-H).
2 amide or N-substituted amide has two C-N bonds (one N-H).
3 amide or N,N-disubstituted amide has three C-N bonds (no N-H).
Chapter 11

15. Naming Amides
For 1 amide, drop -ic or -oic acid from the carboxylic acid name, add -amide.
For 2 and 3 amides, the alkyl groups bonded to nitrogen are named with N- to indicate their position.
Chapter 11

16. Naming Amides
For 1 amide, drop -ic or -oic acid from the carboxylic acid name, add -amide.
For 2 and 3 amides, the alkyl groups bonded to nitrogen are named with N- to indicate their position.
N-ethyl-N,2-dimethylpropanamide
N-ethyl-N-methylisobutyramide
Chapter 11

17. Cyclic Amides
Reaction of -NH2 and -COOH on same molecule produces a cyclic amide, lactam.
To name, add word lactam to the IUPAC acid name or replace the -ic acid of common name with -olactam.
Chapter 21

18. 4-aminopentanoic acid lactam
Cyclic Amides
Reaction of -NH2 and -COOH on same molecule produces a cyclic amide, lactam.
To name, add word lactam to the IUPAC acid name or replace the -ic acid of common name with -olactam.
4-aminopentanoic acid lactam
-valerolactam
Chapter 21

19. Nitriles
-CN can be hydrolyzed to carboxylic acid, so nitriles are acid derivatives.
Nitrogen is sp hybridized, lone pair tightly held, so not very basic (pKb about 24).
Chapter 11

20. Naming Nitriles For IUPAC names, add -nitrile to the alkane name.
Common names come from the carboxylic acid. Replace -ic acid with -onitrile.
Chapter 11

21. Naming Nitriles For IUPAC names, add -nitrile to the alkane name.
Common names come from the carboxylic acid. Replace -ic acid with -onitrile.
5-bromohexanenitrile
-bromocapronitrile
Cyclohexanecarbonitrile
Chapter 11

22. Acid Halides
More reactive than acids; the halogen withdraws e- density from carbonyl.
Named by replacing -ic acid with -yl halide.
Chapter 11

23. Acid Halides
More reactive than acids; the halogen withdraws e- density from carbonyl.
Named by replacing -ic acid with -yl halide.
3-bromobutanoyl bromide
-bromobutyryl bromide
benzoyl chloride
Chapter 11

24. Acid Anhydrides
Two molecules of acid combine with the loss of water to form the anhydride.
Anhydrides are more reactive than acids, but less reactive than acid chlorides.
A carboxylate ion is the leaving group in nucleophilic acyl substitution reactions.
Chapter 11

25. Naming Anhydrides The word acid is replaced with anhydride.
For a mixed anhydride, name both acids.
Diacids may form anhydrides if a 5- or 6-membered ring is the product.
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Chapter 11

26. 1,2-benzenedicarboxylic anhydride
Naming Anhydrides
The word acid is replaced with anhydride.
For a mixed anhydride, name both acids.
Diacids may form anhydrides if a 5- or 6-membered ring is the product.
ethanoic anhydride
acetic anhydride
1,2-benzenedicarboxylic anhydride
phthalic anhydride
=>
Chapter 11

27. Multifunctional Compounds
The functional group with the highest priority determines the parent name.
Acid > ester > amide > nitrile > aldehyde > ketone > alcohol > amine > alkene > alkyne.
Chapter 11

28. Multifunctional Compounds
The functional group with the highest priority determines the parent name.
Acid > ester > amide > nitrile > aldehyde > ketone > alcohol > amine > alkene > alkyne.
ethyl o-cyanobenzoate
Chapter 11

29. Boiling Points
Even 3 amides have
strong attractions.
Chapter 11

30. Melting Points Amides have very high melting points.
Melting points increase with increasing number of N-H bonds.
m.p. -61C
m.p. 28C
m.p. 79C
Chapter 11

31. Solubility
Acid chlorides and anhydrides are too reactive to be used with water or alcohol.
Esters, 3 amides, and nitriles are good polar aprotic solvents.
Solvents commonly used in organic reactions:
Ethyl acetate
Dimethylformamide (DMF)
Acetonitrile
Chapter 11

32. Interconversion ofAcid Derivatives
Nucleophile adds to the carbonyl to form a tetrahedral intermediate.
Leaving group leaves and C=O regenerates.
Chapter 11

33. Reactivity Reactivity decreases as leaving group becomes more basic.
Chapter 11

34. Interconversion of Derivatives
More reactive derivatives can be converted to less reactive derivatives.
Chapter 11

35. Acid Chloride to Anhydride
Acid or carboxylate ion attacks the C=O.
Tetrahedral intermediate forms.
Chloride ion leaves, C=O is restored, H+ is abstracted.
Chapter 11

36. Acid Chloride to Ester Alcohol attacks the C=O.
Tetrahedral intermediate forms.
Chloride ion leaves, C=O is restored, H+ is abstracted.
Chapter 11

37. Acid Chloride to Amide Ammonia yields a 1 amide
A 1 amine yields a 2 amide
A 2 amine yields a 3 amide
Chapter 11

38. Anhydride to Ester Alcohol attacks one C=O of anhydride.
Tetrahedral intermediate forms.
Carboxylate ion leaves, C=O is restored, H+ is abstracted.
Chapter 11

39. Anhydride to Amide Ammonia yields a 1 amide
A 1 amine yields a 2 amide
A 2 amine yields a 3 amide
Chapter 11

40. Ester to Amide Nucleophile must be NH3 or 1 amine.
Prolonged heating required.
Surprise!
Chapter 11

41. Leaving Groups
A strong base is not usually a leaving group unless it’s in an exothermic step.
Chapter 11

42. Transesterification
One alkoxy group can be replaced by another with acid or base catalyst.
Use large excess of preferred alcohol.
Chapter 11

43. TRANSESTERIFICATION OF COCAINE

44. Hydrolysis of Acid Chlorides and Anhydrides
Hydrolysis occurs quickly, even in moist air with no acid or base catalyst.
Reagents must be protected from moisture.
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Chapter 11

45. Acid Hydrolysis of Esters
Reverse of Fischer esterification.
Reaches equilibrium.
Use a large excess of water.
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Chapter 11

46. Saponification Base-catalyzed hydrolysis of ester.
“Saponification” means “soap-making.”
Soaps are made by heating NaOH with a fat (triester of glycerol) to produce the sodium salt of a fatty acid - a soap.
One example of a soap is sodium stearate, Na+ -OOC(CH2)16CH3.
Chapter 11

47. Hydrolysis of Amides
Prolonged heating in 6 M HCl or 40% aqueous NaOH is required.
Chapter 11

48. Hydrolysis of Nitriles
Under mild conditions, nitriles hydrolyze to an amide.
Heating with aqueous acid or base will hydrolyze a nitrile to an acid.
Chapter 11

49. Reduction to Alcohols
Lithium aluminum hydride reduces acids, acid chlorides, and esters to primary alcohols.
Chapter 11

50. Acid Chloride Synthesis
Use thionyl chloride, SOCl2, or oxalyl chloride, (COCl)2.
Other products are gases.
Chapter 11

51. Acid Chloride Reactions (1)
ester
amide
acid anhydride
Chapter 11

52. Lab Synthesis of Anhydrides
React acid chloride with carboxylic acid or carboxylate ion.
Heat dicarboxylic acids to form cyclic anhydrides.
Chapter 11

53. Anhydride Reactions
acid
ester
amide
acylbenzene
AlCl3
Chapter 11

54. Anhydride vs. Acid Chloride
Acetic anhydride is cheaper, gives a better yield than acetyl chloride.
Use acetic formic anhydride to produce formate esters and formamides.
Use cyclic anhydrides to produce a difunctional molecule.
Chapter 11

55. Synthesis of Esters acid acid chloride acid anhydride methyl ester
Chapter 11

56. Synthesis of Amides acid acid chloride acid anhydride ester nitrile
Chapter 11

57. Reactions of Amides
acid and amine
amine
1° amine
nitrile
Chapter 11

58. CHAPTER 11 REVIEW
Chapter 11

59. Name a. Ethyl ethanoate b. Propyl propanoate c. Ethyl propanoate
d. Propyl ethanoate
e. Propyl butanoate

60. Answer a. Ethyl ethanoate b. Propyl propanoate c. Ethyl propanoate
d. Propyl ethanoate
e. Propyl butanoate
The longest chain is three carbons. Propyl is the alkoxy group.

61. Name a. 3-Hydroxybutanoic acid lactone
b. 4-Hydroxybutanoic acid lactone
c. 4-Hydroxypentanoic acid lactone
d. 5-Hydroxypentanoic acid lactone

62. Answer a. 3-Hydroxybutanoic acid lactone
b. 4-Hydroxybutanoic acid lactone
c. 4-Hydroxypentanoic acid lactone
d. 5-Hydroxypentanoic acid lactone
A lactone is a cyclic ester. The hydroxy is on the fifth carbon.

63. Name a. Pentanamide b. Butanamide c. N-Ethylethanamide
d. N-Ethylpropanamide
e. N-Methylethanamide

64. Answer a. Pentanamide b. Butanamide c. N-Ethylethanamide
d. N-Ethylpropanamide
e. N-Methylethanamide
Ethyl is attached to the nitrogen. The longest chain is three carbons.

65. 21.4 Name a. 3-Aminobutanoic acid lactam
b. 4-Aminobutanoic acid lactam
c. 4-Aminopentanoic acid lactam
d. 5-Aminopentanoic acid lactam

66. Answer a. 3-Aminobutanoic acid lactam b. 4-Aminobutanoic acid lactam
c. 4-Aminopentanoic acid lactam
d. 5-Aminopentanoic acid lactam
A lactam is a cyclic amide. The amino group is on the fifth carbon.

67. Name a. Pentanenitrile b. Butanenitrile c. Propanenitrile
d. 2-Methylbutanenitrile
e. 3-Methylbutanenitrile

68. Answer a. Pentanenitrile b. Butanenitrile c. Propanenitrile
d. 2-Methylbutanenitrile
e. 3-Methylbutanenitrile
The longest chain has four carbons. The methyl is on the third carbon.

69. Name a. 1-Chloroethanoyl chloride b. 2-Chloroethanoyl chloride
c. 1-Chloropropanoyl chloride
d. 2-Chloropropanoyl chloride

70. Answer a. 1-Chloroethanoyl chloride b. 2-Chloroethanoyl chloride
c. 1-Chloropropanoyl chloride
d. 2-Chloropropanoyl chloride
The longest chain has three carbons. Chlorines are on the second carbon and the carbonyl carbon.

71. Name a. Ethanoic methanoic anhydride b. Methanoic propanoic anhydride
c. Ethanoic anhydride
d. Ethanoic propanoic anhydride
e. Propanoic anhydride

72. Answer a. Ethanoic methanoic anhydride
b. Methanoic propanoic anhydride
c. Ethanoic anhydride
d. Ethanoic propanoic anhydride
e. Propanoic anhydride
The three-carbon chain is on the left. A two-carbon chain is on the right.

73. a. Ethanoic methanoic anhydride
b. Methanoic propanoic anhydride
c. Ethanoic anhydride
d. Ethanoic propanoic anhydride

74. Answer a. Ethanoic methanoic anhydride
b. Methanoic propanoic anhydride
c. Ethanoic anhydride
d. Ethanoic propanoic anhydride
An acid halide reacts with a carboxylic acid to form an anhydride.

75. a. Methyl ethanoate
b. Methyl propanoate
c. Ethyl ethanoate
d. Ethyl propanoate

76. Answer a. Methyl ethanoate b. Methyl propanoate c. Ethyl ethanoate
d. Ethyl propanoate
An acid halide reacts with an alcohol to form an ester.

77. a. N-Methylethanamide
b. N-Methylpropanamide
c. N,N-Dimethylethanamide
d. N,N-Dimethylpropanamide

78. Answer a. N-Methylethanamide b. N-Methylpropanamide
c. N,N-Dimethylethanamide
d. N,N-Dimethylpropanamide
An acid halide reacts with an amine to form an amide.

79. a. Ethanoic acid + ethanol
b. Propanoic acid + methyl ethanoate
c. Ethanoic acid + ethyl ethanoate
d. Propanoic acid + methyl propanoate
e. Ethanoic acid + ethyl propanoate

80. Answer a. Ethanoic acid + ethanol b. Propanoic acid + methyl ethanoate
c. Ethanoic acid + ethyl ethanoate
d. Propanoic acid + methyl propanoate
e. Ethanoic acid + ethyl propanoate
An anhydride reacts with an alcohol to give a carboxylic acid and an ester.

81. a. N,N-Diethylpropanamide + propanoic acid
b. N-Ethylpropanamide + propanoic acid
c. N-Ethylethanamide + ethanoic acid
d. N,N-Diethylethanamide + ethanoic acid

82. Answer a. N,N-Diethylpropanamide + propanoic acid
b. N-Ethylpropanamide + propanoic acid
c. N-Ethylethanamide + ethanoic acid
d. N,N-Diethylethanamide + ethanoic acid
An anhydride reacts with an amide to form an amide and a carboxylic acid.

83. a. N-Propyl propanamide + methanol
b. N-Propyl ethanamide + ethanol
c. N-Ethyl propanamide + methanol
d. N-Ethyl ethanamide + ethanol
e. N-Ethyl ethanamide + propanol

84. Answer a. N-Propyl propanamide + methanol
b. N-Propyl ethanamide + ethanol
c. N-Ethyl propanamide + methanol
d. N-Ethyl ethanamide + ethanol
e. N-Ethyl ethanamide + propanol
An ester reacts with an amine to produce an amide and an alcohol.

85. a. Propanal + ammonia
b. Ethanoic acid + ammonia
c. Propanoic acid + methylamine
d. Ethanoic acid + methylamine

86. Answer a. Propanal + ammonia b. Ethanoic acid + ammonia
c. Propanoic acid + methylamine
d. Ethanoic acid + methylamine
An amide is hydrolyzed under acidic conditions to form a carboxylic acid and an amine.

87. a. Propylamine
b. Propanamide
c. Propanoic acid
d. Butanoic acid
e. No reaction

88. Answer a. Propylamine b. Propanamide c. Propanoic acid
d. Butanoic acid
e. No reaction
A nitrile is hydrolyzed to a carboxylic acid in the presence of acid and heat.

89. a. Methanol + ethanol
b. Methanol + propanol
c. Ethanol + propanol
d. Ethanol

90. Answer a. Methanol + ethanol b. Methanol + propanol
c. Ethanol + propanol
d. Ethanol
An ester is reduced to two alcohols.

91. a. Ethyl methyl amine
b. Ethyl propyl amine
c. Methyl propyl amine
d. Methyl amine + propanoic acid
e. Ethyl amine + propanoic acid

92. Answer a. Ethyl methyl amine b. Ethyl propyl amine
c. Methyl propyl amine
d. Methyl amine + propanoic acid
e. Ethyl amine + propanoic acid
An amide is reduced to an amine with lithium aluminum hydride.

93. a. 2-Methyl-2-butanol
b. 3-Methyl-3-pentanol
c. 1-Butanol
d. 3-Methyl-2-butanol
e. 3-Ethyl-3-pentanol

94. Answer a. 2-Methyl-2-butanol b. 3-Methyl-3-pentanol c. 1-Butanol
d. 3-Methyl-2-butanol
e. 3-Ethyl-3-pentanol
Two methyl groups add to the carbon of the carbonyl. Hydrolysis yields the tertiary alcohol.

95. a. 2-Methyl-2-butanol + ethanol
b. 2-Methyl-2-butanol + methanol
c. 2-Butanone + ethanol
d. 2-Methyl-2-butanol + ethanol

96. Answer a. 2-Methyl-2-butanol + ethanol
b. 2-Methyl-2-butanol + methanol
c. 2-Butanone + ethanol
d. 2-Methyl-2-butanol + ethanol
The reaction of an ester with a Grignard reagent forms a tertiary alcohol and an alcohol.

97. End of Chapter 11
Chapter 11