148Exam 2 notes
LSW S03
Organic Chemistry
Amines
Amines
Amines (e.g. RNH2) are organic derivatives of ammonia,
NH3
similar to ammonia
Nomenclature:
suffix
NH 2
O
prefix
NH 2
N(CH 3)2
Types: Primary (1o), secondary (2o), tertiary (3o) or
quaternary ammonium cations (4o).
Structure :NH3
Name
ammonia
+
NH 2
NH
ethyl
amine
dimethyl
amine
Type
148
N
trimethyl
amine
N
_
Cl
tetramethyl
ammonium
149Exam 2 notes
LSW S03
Organic Chemistry
Amines
Physical Properties:
Hydrogen bonding?
H
N
H
H N
H
Melting points:
Boiling points:
Solubility in aqueous media:
Structure:
Reactivity:
The important organic reactions of amines
1. As bases with common acids:
2. As nucleophiles with the common electrophiles:
A)
B)
C)
149
150Exam 2 notes
LSW S03
Organic Chemistry
Amines
Acidity:
RNH3
+ Na
NaRN H2
1. NaNH2
R C
C H
H
R C
H
X
C H
X
X
R C
H
X
C H
H
R C
2. R'X
NaNH2
NaNH2
C R'
C
C
+ 2 H-X
C
C
+ 2 H-X
Basicity:
RNH3
RNH3+ + OH
+ H2O
150
151Exam 2 notes
LSW S03
Organic Chemistry
Amines
Aryl amines:
NH2
The basicity of aryl amines is:
Increased by:
Decreased by:
NH2
C
N
Heteroaromatic compounds:
N
N
H+
H
HN
151
N
H
H
N
N
H
152Exam 2 notes
LSW S03
Organic Chemistry
Amines
Preparation of Amines
Ammonia
Alkylation
R-NH2 + NH4+X-
2 NH3
R-X +
O
O
Phthalimide
Alkylation
N H
1. KOH
2. R-X
3. NH2-NH2
NH
NH
R-NH2 +
O
O
Reductions:
Azides
R
N N N
Nitriles
R
C N
Nitro
Ar
NO2
[R]
[R]
[R]
R
R
NH2
CH2NH2
Ar
NH2
O
Amides
R CH2 NH2
R C NH2 + LiAlH4
O
Reductive
Amination
R C R'
+ R"2NH
2. [R]
R
CH NR"2
R'
152
153Exam 2 notes
LSW S03
Organic Chemistry
Amines
Alkylation of Ammonia by Alkyl Halides
R-X +
NH3
R-X
R-NH2 + NH4+X-
2 NH3
RNH2
R-X
R2NH
R-X
R3N R-X R4NX
MECHANISM OF AMMONIA ALKYLATION
R' NH2
_
RCH2 Br
RCH2 NHR'
H
R' NH2
R' NH2 + RCH2 NHR'
153
154Exam 2 notes
LSW S03
Organic Chemistry
Amines
Alkylation of Phthalimide
O
O
N H
1. KOH
2. R-X
3. NH2-NH2
NH
NH
R-NH2 +
O
O
Reaction type:
Advantage:
Disadvantage:
Mechanism:
O
N H
O
_
OH
NH
O
O
O
RCH2 Br
O
NH2NH
N
O
H2O
O
O
O
+
O
O
154
155Exam 2 notes
LSW S03
Organic Chemistry
Amines
Reduction of Azides
[R]
R NN N
R NH2
Reaction type :
Overall reaction:
Reagents :
Reduction of Nitriles
R CN
[R]
R CH2NH2
Oxidation number
Reaction type:
Overall Reaction:
Reagents :
Reduction of Nitro Compounds
Ar NO2
[R]
Ar NH2
Reaction type :
Nitroarenes can be reduced to primary aryl amines
Reagents:
Importance:
Reduction of Amides
O
R C NH2 + LiAlH4
R CH2NH2
Reaction type:
Overall reaction: RCONR'2, reduced to, RCH2NR'2
Typical reagents :
Products:
155
156Exam 2 notes
LSW S03
Organic Chemistry
Amines
O
H
LiAlH4 + R C N H
R
C
H
O
R
H
H
H
C
N
R'
R
Mechanism:
O
NR'R"
R
NR'R"
H
R
AlR2
O
Li H AlH3
H
N
R'
H
H
R"
R
H
C
O
R
N
H
LiAlH4 + R C N R'
LiAlH4 +
H
H
NR'R"
NR'R"
Li H AlH3
H
R
156
C
H
N
R"
R'
157Exam 2 notes
LSW S03
Organic Chemistry
Amines
Reductive Amination via Imines or Eneamines
O
R C
R'
Then
Reduce
+ R"2NH
R
CH NR"2
R'
Reaction type :
Overall Reaction:
Typical reagents :
step 1 :
step 2 :
Importance:
Reactions of Amines
1. Nucleophilic substitution alkyl halides
2. Nucleophilic addition aldehydes or ketones
3. Nucleophilic acyl substitution carboxylic acid derivatives,
157
158Exam 2 notes
LSW S03
Organic Chemistry
Amines
Alkyl Halides R-X
2 RNH2
+
O
Aldehydes
R
and
Ketones
C
CH2R'
+ R"2NH
R2NH
Then
Reduce
+
RNH3+X-
R C NR"2 + H2O
CHR'
O
R C
R
R' + R"NH2
NR" + H2O
C
R'
O
R'2NH
O
Base
C
Carboxylic R C Cl
acid
O
O
deriviatives
R
Hofmann
Elimination
Electrophilic
Aromatic
Substitution
O
C
R
R
1. Excess CH3I
H C C NH2 2.
Ag2O / H2O
NH2
R
C
C
NH2
NR'2
C + N(CH3)3 + H2O
NH2
E
E+
+
+ H+
E
Diazotization HNO2 + RNH2
Nitrosation
O
R'2NH
Base
NR'2
RN
HNO2 + R'NH2
R
N
+ 2 H2O
R'N N O + 2 H2O
R
158
159Exam 2 notes
LSW S03
Organic Chemistry
Amines
Alkylation of Amines by Alkyl Halides
NH3
2 R'NH3
+
R-X
R-X
RNH2
RNH
R'
R-X
R-X
R2NH
R'NH3+X-
+
R3N R-X R4NX
Reaction of Amines with Aldehydes and Ketones
O
Primary
amines
R C
R
R' + R"NH2
C
NR" + H2O
R'
O
Then
Reduce
Secondary
C
+ R"2NH
amines
CH2R'
R
R C NR"2 + H2O
CHR'
Reaction type: Nucleophilic Addition then Elimination
1 amines:
2 amines:
Preparation of Amides
O
R'2NH
O
C
Base
C
R
O
R
O
R
Cl
O
R'2NH
C
Base
R
Reaction type:
Reagents:
Limitations:
159
NR'2
O
R
C
NR'2
160Exam 2 notes
LSW S03
Organic Chemistry
Amines
Hofmann Elimination
H C C NH2
1. Excess CH3I
C
2. Ag2O / H2O
C
+ N(CH3)3 + H2O
Reaction type:
Reagent:
Mechanism:

CH3I
H C C NH2
H C C N
Ag2O
H2O
C=C
+ :N(CH3)3
+ H2O
H C C
N
Regioselectivity: Hofmann product
1. Excess CH3I
NH2
+
2. Ag2O / H2O
HEAT
+ N(CH3)3
Selectivity:
B H
+
BH3 H
NR3
H
BH3
+ NR3
NR3
160
161Exam 2 notes
LSW S03
Organic Chemistry
Amines
Electrophilic Aromatic Substitution
NH2
NH2
E
E+
+
E
Limitation:
Problem:
NH2
NH2
Br2
NH2
O
O
O
or
Cl
NH2
O
161
+ H+
162Exam 2 notes
LSW S03
Organic Chemistry
Amines
Diazotization of primary amines
HNO2 + RNH2
RN
+ 2 H2O
N
Nitrosation of secondary amines
HNO2 + R'NH2
R
R'N N O + 2 H2O
R
Reagents:
Mechanism for diazotization reaction of Primary alkyl or aryl amines
HO N O
H+
HO N O
H+
HO N O
HO
H
+
N O
RNH2
R N N OH
R N N O
H
R N
HO
H
H
NH
R
H
R N N O
H
N
N
162
R
HN
N
163Exam 2 notes
LSW S03
Organic Chemistry
Amines
Mechanism for Secondary alkyl or aryl amines
H
O H O N N R
HNR2
O N
O N N R H
R
R
Tertiary alkyl amines
Tertiary aryl amines
CH2CH3 CH3CH2
CH3CH2
CH2CH3
N
N
O N
Useful Reactions Aryl Diazonium Ions
Schiemann reaction
Sandmeyer reactions
N
N
Azo Dyes
OH
Cl
CuCl
OH
Br
CuBr
H3PO2
or
Ethanol
N2
HBF4
H2O, H2SO4
o
Heat (100 C)
OH
KI
CuCN
CN
163
I
F
164Exam 2 notes
LSW S03
Organic Chemistry
Amines
Spectroscopic Analysis
IR
Absorbance
(cm-1)
3500 - 3100
1350 - 1000
1
H NMR -
Interpretation
Resonance (ppm)
0.5 - 5.0 (broad, exchangeable)
1.5 - 3.0
13
Interpretation
C NMR
Resonance (ppm)
35- 50
Interpretation
UV-VIS



Mass Spectrometry

CH2CH2CH3
(CH3)3N CH2 CH2CH2CH3
+
(CH3)3N
The nitrogen rule:
1. No nitrogens
2. odd number of N atoms
3. even number of N atoms
164
CH2