1. March 3oth , 2011 Goals for the day:
Naming Amines
Physical Properties of Amines
Amine reactions
* Conversion of an alkyl halide
* Gabriel Synthesis
* Hoffman Elimination
4) IR/NMR of Amines
5) Multiple Choice Questions…

2. Chapter 24 Amines NH3 ammonia methyl amine isopropyl methyl amine
Name the groups (up to 3) that are attached.
Di & tri prefixes are used if groups are the same
NH3 ammonia
methyl amine
isopropyl methyl amine

3. Degree of substitution…
Substitution on the nitrogen is important …
The number of carbons directly attached to the nitrogen is what
You want to look at
Primary secondary tertiary

5. 24.2 Properties of Amines Bonding to N is similar to that in ammonia
N is sp3-hybridized
C–N–C bond angles are close to 109° tetrahedral value

6. Amines Form H-Bonds
Amines with fewer than five carbons are water-soluble
Primary and secondary amines form hydrogen bonds, increasing their boiling points

7. 24.3 Basicity of Amines
The lone pair of electrons on nitrogen makes amines basic and nucleophilic
They react with acids to form acid–base salts and they react with electrophiles

8. Amides
Amides (RCONH2) in general are not proton acceptors except in very strong acid
The C=O group is strongly electron-withdrawing, making the N a very weak base
Addition of a proton occurs on O but this destroys the double bond character of C=O as a requirement of stabilization by N=

9. SN2 Reactions of Alkyl Halides
Ammonia and other amines are good nucleophiles

10. Problem: Uncontrolled Multiple Alkylation (i. e
Problem: Uncontrolled Multiple Alkylation (i.e. can’t stop the reaction! ).
Primary, secondary, and tertiary amines all have similar reactivity, the initially formed monoalkylated substance undergoes further reaction to yield a mixture of products

11. Gabriel Synthesis of Primary Amines
A phthalimide alkylation for preparing a primary amine from an alkyl halide
The N-H in imides (–CONHCO–) can be removed by KOH followed by alkylation and hydrolysis

12. Hofmann Elimination Converts amines into alkenes
NH2 is very a poor leaving group so it is converted to an alkylammonium ion, which is a good leaving group

13. The Elimination Step
Exchanges hydroxide ion for iodide ion in the quaternary ammonium salt, thus providing the base necessary to cause elimination

14. Orientation in Hofmann Elimination
We would expect that the more highly substituted alkene product predominates in the E2 reaction of an alkyl halide (Zaitsev's rule)
However, the less highly substituted alkene predominates in the Hofmann elimination due to the large size of the trialkylamine leaving group
The base must abstract a hydrogen from the most sterically accessible, least hindered position

15. Steric Effects Control the Orientation

16. Polycyclic Heterocycles

17. 24.10 Spectroscopy of Amines -Infrared
Infrared Spectroscopy:
Characteristic N–H stretching absorptions 3300 to 3500 cm1
Amine absorption bands are sharper and less intense than hydroxyl bands
Protonated amines show an ammonium band in the range 2200 to 3000 cm1

18. Examples of Infrared Spectra

19. NMR
Hydrogens on a carbon attached to an oxygen (or nitrogen) are around 3-4 ppm.
Hydrogens on a carbon next to a carbonyl are around 2 ppm.

20. Putting it all together…
Reactions for exam three are on the following pages.
Note that reactions with a *** you need to know the mechanism…

21. Oxidation of primary alcohols
Reagents can be H2CrO4, CrO3, [O], PCC
Primary alcohols can be oxidized to carboxylic acids
Reaction of CO2 with a Grignard reagent ***

22. Reactions that Carboxylic Acids do…
React with bases… ***
Makes acid halides
(do the same reactions as
acids, but are faster)…
Reduces to a primary alcohol
(goes through an aldehyde)…

23. Two main Carboxylic Acid Reactions (need to be acid or base catalyzed)…
Esterification…***
Important in fats
Amide formation…***
Important in proteins (amide bonds)
Note: You will need to know all of the mechanisms, but the good news
is that they are very similar! (We will review them with the acid derivatives…)

24. Reactions of Acid Derivatives…
Ester and amide formation using an acid halide

25. More reactions of Acid Derivatives…
X = halogen, OR, or NHR
Hydrolysis ***
(very important for both
esters and amides)
Reduction using LAH
(gives an amine if starting
with an amide)
Goes through a ketone ***

26. Summary of the reactions thus far…
***
***

27. Next three (Aldol, acetoacetate synthesis & claisen)…
***

28. Chain lengthening of amines (from an alkyl halide)…
***
Gabriel Synthesis…
Hoffman Elimination…

30. Which of the following is not an acyl derivative?1. 2. 3. 4. 5. 1 2 3 4 5

31. Answer 5.

32. What is the IUPAC name for the following carboxylic acid?
3-bromo-4-methylbenzoic acid
4-methyl-3-bromobenzoic acid
phthalic acid
4-carboxy-2-bromotoluene
5-carboxy-2-methyl-1-bromobenzene

33. Answer
1. 3-bromo-4-methylbenzoic acid

34. What is the IUPAC name for the following carboxylic acid?
2-propylhexanoic acid
4-propylhexanoic acid
2-butylpentanoic acid
4-carboxyoctane
5-carboxyoctane

35. Answer
1. 2-propylhexanoic acid

36. The structure for oleic acid is shown below
The structure for oleic acid is shown below. What is the IUPAC name of this compound?
a. (Z)-octadec-9-enoic acid
b. (E)- octadec-9-enoic acid

37. Answer
a. (Z)-octadec-9-enoic acid

38. Rank the following molecules in acidity from least acidic to most acidic.
A, C, B
B, A, C
C, B, A
B, C, A
C, A, B

39. Answer
2. B, A, C

40. Chloroacetic acid is a stronger acid than acetic acid
Chloroacetic acid is a stronger acid than acetic acid. Which is the best explanation?
More resonance structures can be drawn for chloroacetic acid than for acetic acid.
More resonance structures can be drawn for chloroacetate ion than for acetate ion.
Because of its high electronegativity, chlorine is able to donate electrons to the chloroacetate ion by the inductive effect, thereby stabilizing this ion.
Because of its high electronegativity, chlorine is able to withdraw electrons from the chloroacetate ion by the inductive effect, thereby stabilizing this ion.
Chlorine is larger than hydrogen and can better hold a negative charge.

41. Answer
Because of its high electronegativity, chlorine is able to withdraw electrons from the chloroacetate ion by the inductive effect, thereby stabilizing this ion.

42. p-Chlorobenzoic acid is more acidic than p-methylbenzoic acid.
True
False

43. Answer
1. True

44. Which of the following is not an ester?1. 2. 4. 3. 1 2 3 4

45. Answer 2.

46. Determine the IUPAC name for the following molecule.
3,4-dimethylphenyl pentanoate
3,4-dimethylpentyl benzenoate
3,4-dimethylpentyl benzoate
benzyl 3,4-dimethylpentanoate
phenyl 3,4-dimethylpentanoate

47. Answer
5. phenyl 3,4-dimethylpentanoate

48. Which of the statements is true concerning the following two carboxylic acid derivatives?
Only molecule A can be hydrolyzed.
Only molecule B can be hydrolyzed.
Both molecules can be hydrolyzed, but A will react faster than B.
Both molecules can be hydrolyzed, but B will react faster than A.
A and B can be hydrolyzed at roughly the same rate.

49. Answer
Both molecules can be hydrolyzed, but B will react faster than A.

50. Predict the outcome of the following reaction.1. 2. 3. 4. 5. 1 2 3 4 5

51. Answer 3.

52. Which of the following steps occurs first in the mechanism of Fischer esterification?
attack of the nucleophile on the carbonyl carbon
protonation of the carbonyl oxygen
loss of water from the tetrahedral carbonyl addition intermediate
protonation of the alcohol oxygen
formation of the tetrahedral carbonyl addition intermediate

53. Answer
2. protonation of the carbonyl oxygen

54. Which of the following is the tetrahedral intermediate that appears in the Fischer esterification of ethanol and benzoic acid? 1. 2. 3. 4. 5. 1 2 3 4 5

55. Answer 1.

56. Predict the product of the following reaction.1. 2. 3. 4.
5. None of these 1 2 3 4 5

57. Answer 1.

58. What is the predominant enol form of the following molecule?1. 2. 3. 5.
None of these is favored over the others. 4. 1 2 3 4 5

59. Answer 4.

60. Which of the following will occur when the following optically active compound is placed in dilute acid?
It will form an acetal.
It will form a diol.
It will become an alcohol.
It will lose its optical activity.
none of these

61. Answer
4. It will lose its optical activity.

62. Identify the expected major product of the following reaction.2. 1. 3. 4. 5. 1 2 3 4 5

63. Answer 3.

64. How many protons with a pKa < 22 exist in the following molecule?1 2 3 4

65. Answer
5. 4

66. Which of the following reagents will not form an enolate upon reaction with a ketone?2. 1. 3. 5. 4.
LiAlH4
Choice One
Choice Two
Choice Three
Choice Four
Choice Five

67. Answer
4. LiAlH4

68. Which of the above carbonyl compounds is most acidic?

69. Answer
3. C

70. Which of the following statements explains why the following aldehyde will not undergo an aldol reaction with itself?
The benzene ring makes the carbonyl group unreactive towards aldol reactions.
A carbonyl group must be connected to two alkyl groups in order to undergo an aldol reaction.
The molecule does not possess any hydrogens α to the carbonyl group.
Electrophilic aromatic substitution competes favorably with the aldol reaction.
Nucleophilic acyl substitution competes favorably with the aldol reaction.

71. Answer
The molecule does not possess any hydrogens α to the carbonyl group.

72. Predict the aldol reaction product of the following ketone.2. 1. 3. 4. 5. 1 2 3 4 5

73. Answer 2.

74. Which starting material(s) will produce the following aldol reaction product?1. 2. 3. 5. 4. 1 2 3 4 5

75. Answer 2.

76. Select the correct aldol reaction product for the following reaction.1. 2. 3. 5. 4. 1 2 3 4 5

77. Answer 4.

78. Which pair of compounds would be required to prepare the following aldol product?1. 2. 3. 4. 5. 1 2 3 4 5

79. Answer 3.

80. Select the correct Claisen condensation product for the following reaction.1. 2. 3. 4. 5. 1 2 3 4 5

81. Answer 4.

82. What type of reaction has occurred in the above biological process?
Claisen condensation
aldol reaction
nucleophilic acyl substitution
β-elimination
both Claisen condensation and nucleophilic acyl substitution

83. Answer
2. aldol reaction

84. Select the best classification for the following molecule:
1˚ aliphatic amine
2˚ aliphatic amine
3˚ aliphatic amine
aromatic amine
heterocyclic aromatic amine

85. Answer
2. 2˚ aliphatic amine

86. Determine the IUPAC name for the following molecule:
ethylpropylphenylamine
N-phenyl-N-ethylpropanamine
N-ethyl-N-phenylpropanamine
N-ethyl-N-propylaniline
N-phenyl-N-ethylaniline

87. Answer
4. N-ethyl-N-propylaniline

88. The major alkaloid present in tobacco leaves is nicotine, whose structure is shown below. Which will be the major ammonium ion formed when nicotine is treated with one equivalent of a strong acid? 1. 2. 1 2

89. Answer 2.

90. Arrange the above from strongest to weakest base:
A, B, C
B, C, A
C, A, B
A, C, B
B, A, C

91. Answer
3. C, A, B

92. Amine A is more basic than amine B.
True
False

93. Answer
1. True

94. Which of the following statements is true regarding the following two molecules?
Both A and B are aromatic.
Both A and B are aliphatic amines.
A is more basic than B.
B is more basic than A.
Both A and B are planar molecules.

95. Answer
4. B is more basic than A.

96. Select the most acidic compound from the choices provided.1. 2. 3. 4. 5. 1 2 3 4 5

97. Answer 4.

98. If a protonated amine with a pKa of 10 is placed in a solution of pH 12, the predominant form of the amine in solution will be the protonated form.
True
False

99. Answer
2. False