Organic Chemistry: Second Edition

Organic Chemistry
Second Edition
David Klein
Chapter 23
Amines
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e
23.1 Introduction to Amines
• Amines are derivatives of ammonia
• Amines are designated as primary, secondary, or tertiary

• The terms, 1°, 2°,and 3° are used differently for amines
than for alcohols. HOW?
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 23-2 Klein, Organic Chemistry 2e
• There are hundreds of examples of amines found in
natural products
• Some naturally occurring amines take part in
neurochemistry
• The trigonal pyramidal nitrogen atom of an amine
carries a partial negative charge on its lone pair
• HOW do you think the amine is likely to react?
• Amines often react as a base or as a nucleophile
• What feature(s) of
the amine do you
think might
determine
whether it is more
likely to act as a
base or as a
nucleophile?
23.3 Properties of Amines
• The N atom in typical amines is sp3 hybridized
• The angles are 108 degrees. WHY?

• The C-N bond lengths are 147 pm, which is slightly
shorter than C-C bonds. WHY?
• Under what circumstances would the nitrogen be sp2
hybridized?
• N atoms with three
different alkyl groups
are chiral
• Chiral compounds are
generally optically
active. WHAT does that
mean?
• Amine are generally not
optically active. WHY?
See next slide
• Many small molar mass amines have unpleasant odors
• Practice with conceptual checkpoint 23.4 and 23.5
23.4 Preparation of Amines: A
Review
• Let’s review all of the methods we’ve learned in
previous chapters to synthesize amines
1.
• Carbon skeleton expanded by 1 carbon
Review
2.
• Carbon skeleton is not changed
Review
3.
• Reduction with a metal is a bit more mild than reduction

with H2. WHY might mild conditions be preferred?
Review
3.
• Why is NaOH used in a final step?

• Practice with conceptual checkpoints
23.10 and 23.11 23-14
23.5 Preparation of Amines via
Substitution Reactions
• Let’s learn some new amine syntheses
• Explain WHY the reaction will not stop at the primary

amine but will continue to form a quaternary
ammonium salt
• Let’s learn some new amine syntheses
• See mechanism on next few slides
• N2 is a great leaving group. WHY?

• Does the N2 technically act as a leaving group in the
mechanism?
• The Gabriel synthesis produces primary amines as well
• First, potassium phthalimide is formed
• Although the N1- is stabilized by resonance, it is still

nucleophilic
• The attack works best on 1° amines and does not work

for 3° amines. WHY?
• The last step generally employs aqueous acid or
hydrazine
• Practice with SkillBuilder 23.2

Reductive Amination
• Recall the method for forming imines
• If a reducing agent is present, the imine can be reduced

in situ to form an amine
• Reductive amination can be accomplished with a variety
of reducing agents
Reductive Amination
• Sodium cyanoborohydride, which is similar to NaBH4, is
commonly used
• The inductive effects of the –CN group make the

cyanoborohydride reagent more selective
• HOW?
Reductive Amination
• Why can’t NaBH4 be used for reductive aminations?
• Practice
with
SkillBuilder
23.3
23.7 Synthetic Strategies
• Let’s review reactions that form amines
23.7 Synthetic Strategies
• Let’s review reactions that form amines
• Practice with
SkillBuilder 23.4
23.8 Acylation of Amines
• Recall that amines can attack acyl chlorides
• Two moles of the amine are used. WHY?

• Polysubstitution is not observed. WHY?
• An acyl group can act as a protecting group. HOW?
• An acyl group can help to limit the reactivity of amines
in EAS reactions – see next slide
• How might you perform the following synthesis?
• Adding bromine won’t work, because polysubstitution

can not be avoided
• How might you perform the following synthesis?
• The disadvantage of this synthesis is that amide

hydrolysis requires harsh conditions
• Aromatic amines also can not undergo Friedel Crafts
directly
• How does the addition of the AlCl3 group deactivate the

ring?
• To achieve ring alkylation, first the amine must be
acylated
• Practice with conceptual checkpoints 23.22 through

23.24
23.9 The Hofmann Elimination
• Like alcohols, amines can be converted into leaving
groups for elimination reactions
• Like alcohols, amines can be converted into leaving
groups for elimination reactions
• Unexpectedly, the less substituted (less stable) product

is observed – see next slide
• Sterics in the anticoplanar conformation hinders attack
at the more substituted site. Draw an energy diagram
23.11 Reactions of Aryldiazonium
Ions
• Alkyl diazonium salts are extremely reactive (potentially
explosive) because of the excellent N2 leaving group
• Aryl diazonium salts are a bit more stable and
synthetically versatile
Ions
• Treatment with a copper salt yields an aryl halide or
nitrile
Ions
• Explain each step in the synthesis below
• A fluorine can also be installed
Ions
• There are many other diazonium salt substitutions
• Using this synthesis, amines can be used as a directing

group and subsequently replaced with a –H atom
• Practice with conceptual checkpoint

23-50 23.30
Klein, Organic Chemistry 2e
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Ions
• Diazonium salts can also be attacked by aromatic rings
with an activating group – EAS mechanism
• Draw each resonance contributor of the sigma complex
Ions
• Azo coupling produces azo dyes
• WHY are azo compounds colored?
• Varying the substitution on the rings affects the specific

dye color
• Practice with SkillBuilder 23.6
Additional Practice Problems
• Give an appropriate name for the following molecule
Cl
• Predict the major product for the following reaction
1) NaCN
Br 2) LiAlH4 / ether
3) H2O
• Give necessary reagents to make the secondary amine
below
NH
• Give necessary reagents for the synthesis below
H
N

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Organic Chemistry

• Amines are designated as primary, secondary, or tertiary

• HOW do you think the amine is likely to react?

• The angles are 108 degrees. WHY?

• Practice with conceptual checkpoint 23.4 and 23.5

• Carbon skeleton expanded by 1 carbon

• Carbon skeleton is not changed

• Reduction with a metal is a bit more mild than reduction

• Why is NaOH used in a final step?

• Explain WHY the reaction will not stop at the primary

• See mechanism on next few slides

• N2 is a great leaving group. WHY?

• Although the N1- is stabilized by resonance, it is still

• The attack works best on 1° amines and does not work

• Practice with SkillBuilder 23.2

• If a reducing agent is present, the imine can be reduced

• The inductive effects of the –CN group make the

• Two moles of the amine are used. WHY?

• Adding bromine won’t work, because polysubstitution

• The disadvantage of this synthesis is that amide

• How does the addition of the AlCl3 group deactivate the

• Practice with conceptual checkpoints 23.22 through

• Unexpectedly, the less substituted (less stable) product

• A fluorine can also be installed

• Using this synthesis, amines can be used as a directing

• Practice with conceptual checkpoint

• Draw each resonance contributor of the sigma complex

• Varying the substitution on the rings affects the specific

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