Organic Chemistry II
The Chemistry of Amines
Dr. Ralph C. Gatrone
Department of Chemistry and Physics
Virginia State University
Spring, 2010
1
Chapter Objectives
• Nomenclature
• Properties
• Preparation
• Reactions
• Spectroscopy
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Nomenclature
NH
H3C
• Alkyl amines
H3C
NH2
primary amine
CH3
secondary amine
CH3
H3C
N
CH3
H3C
CH3
+
N
CH3
CH3
tertiary amine
quaternary
ammonium salt
NH
Ph
Ph
NH2
primary amine
• Aryl amines
secondary amine
Ph
Ph
N
Ph
Ph
tertiary amine
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Ph
H3C
+
N
CH3
CH3
quaternary
ammonium salt
3
Alkyl Amines and Aryl Amines
• Much of their chemistry is similar
• Differences are substantial
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Nomenclature
• Primary Amines
– Add the word amine to the akyl substituent
H3C
NH2
methyl amine
– Replace e with suffix “amine” in parent
NH2
cyclopentanamine
– Use “amino” as substituent when two
functional groups are present
COOH
o-aminobenzoic acid
NH2
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Nomenclature
• Secondary and Tertiary Amines
– Symmetrical – add “di” or “tri” to alkyl group
H3C
NH
CH3
dimethylamine
CH3
trimethylamine
CH3
H3C
N
– Unsymmetrical – N-substituted primary amine
CH3
N
H3C
CH3
N,N-dimethylpropylamine
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Aryl Amines
• Phenylamine
NH2
aniline
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NH
CH3
N-ethylaniline
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Heterocyclic Amines
N
H
N
pyridine
pyrrole
N
H
indole
N
H
N
H
piperdine
N
pyrroidine
quinoline
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Heterocyclic Amines
N
N
quinolizidine
indolizidine
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Properties of Amines
• Similar to ammonia
• sp3 hybridized N
• Tetrahedral geometry
• Can be chiral
• Generally not resolvable
• due to pyramidal inversion process
• Barrier to inversion is ~25kJ/mol
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Properties
•
•
•
•
•
•
Amines with < 5 carbons are water soluble
Readily hydrogen bond
Highly associated structures
Higher boiling points than alkanes of similar MW
Low MW amines have distinctive fish-like odor
Pentane-1,5-diamine (cadaverine) has disgusting
odor
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Industrial Applications
• Insecticides
• Pharmaceuticals
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12
Basicity of Amines
• Nitrogen has lone pair of electrons
• Dominates chemistry of amines
• Basic and nucleophilic
– React with acids accepting a proton
– React with alkyl halides
• Stronger bases than alcohols and ethers
• Kb values indicate base strength
• Large Kb (small pKb) indicates stronger base
• Generally consider the pKa of ammonium salt
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pKa value
R
+
NH3
+ H2O
R
NH2 + H3O+
R
NH2
H3O+
Ka =
R
+
NH3
(Ka)(Kb) = Kw = 1.0 X 10-14
pKa + pKb = 14
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Some Amines and pKa Values
of the ammonium ion
NH3 9.26
H3C NH2 10.65
11.27
N
H
10.76
Et3N
5.25
NH2 4.63
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N
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Basicity
• Aryl amines are less basic than alkyl amines
• The N in amides are non-basic
• Poor nucleophile as well
• Primary and secondary amines are acidic as well
• pKa value is approximately 40
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Basicity
• Aryl amines are less basic because the lone
pair is often delocalized in the aromatic ring
• Substituents on ring can make the nitrogen
•
•
more or less basic
Electron donating groups increase basicity
Electron withdrawing groups decrease
basicity
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Preparation of Amines
• Reduction
LAH
R
C
O
R
R
LAH
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NH2
R
NH2
CH2 N
NH2
H2 /Pt or SnCl2/HCl
NO2
R
NH2
N
+
N
N
-
LAH
R
CH2 NH2
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Preparation of Amines
• Nucleophilic substitution
NH3
R
R2NH
R
X
NH2
R
R
R
X
N
R
RNH2
R
X
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R
R3N
R
NH
R
R
X
R
+
N R
R
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Preparation of Amines
• Reductive Amination of Ketones/Aldehydes
O
NH2
NH3
H2-Ni or NaBH4
• Reaction proceeds via the imine
• NH3, primary and secondary amines work
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Reactions of Amines
• Alkylation and Acylation of Amines
• Most general reactions
• Fully covered elsewhere
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Reactions of Amines
• Hoffmann Elimination
• Alkene formation
• NH2 is poor leaving group
• Reaction requires making it a better LG
• Hoffmann Elimination coverts amine into
quaternary ammonium salt by reacting
with CH3I
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Hoffmann Elimination Details
NH2
xs CH3I
H3C
+
N CH3 I
H3C
Ag2O
Reaction proceeds via E2 mechanism
Product is the less substituted alkene
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Aromatic Substitution of Amines
• NR2 strongly activating
• o, p directing
• Often get poly substituted products
Br
NH2
NH2
Br2 in HOAc
Br
Br
difficult to not get tri-substituted product
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Aromatic Substitution of Amines
• Friedal-Crafts akylation
• Does not work with amines
• Fridal-Crafts acylation
• Does not work with amines
• Amides provide less reactive alternative to
amines which allow substitution to occur
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Substitution of Amides
O
NH
Br2 in HOAc
Br
O
NH2 Ac O
2
NH
CH3
CH3
O
NH
O
H3C
Cl
AlCl3
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CH3
H3C
O
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Substitution of Amides
• Amide provides
– Less activating, o,p directing substituent
– Readily removed if needed using aqueous
base
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