21_Lecture.ppt

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Organic Chemistry 6th Edition Paula Yurkanis
Bruice
Chapter 21 More About Amines Heterocyclic
Compounds
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Nomenclature of Heterocycles
Cyclic amines (the names in quotes are preferred)
Nitrogen is 1 when numbering the ring
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Heterocycles with oxygen and sulfur heteroatoms
(the names in quotes are preferred)
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AcidBase Properties of Amines
Amines are the most common organic bases
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Saturated amine heterocycles containing five or
more atoms have physical and chemical properties
typical of acyclic amines
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Amines React as Bases and as Nucleophiles
The lone-pair electron on the nitrogen of an
amine causes it to be nucleophilic as well as
basic
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Reactions of Amines
Nucleophilic substitution reactions
Nucleophilic acyl substitution reactions
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Nucleophilic additionelimination reactions
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Conjugate addition reactions
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Reactions of Quaternary Ammonium Hydroxides
The Hofmann elimination is an E2 reaction
The leaving group of a quaternary ammonium ion
has about the same leaving tendency as a
protonated amino group
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The hydrogen is removed from the b-carbon bonded
to the most hydrogens
The least-substituted alkene elimination product
is often called the Hofmann product
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Quaternary ammonium ions, like alkyl fluorides,
are poor leaving groups
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Hofmann elimination requires exhaustive
methylation of the amine, followed by elimination
A strong base, such as hydroxide ion, must be
used in the elimination reaction
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Quaternary ammonium salts are used as phase
transfer catalysts in facilitating the reactions
between certain ionic and organic reactants
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Consider the reaction between sodium cyanide and
an alkyl halide
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Oxidation of Amines
Mechanism
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Tertiary Amine Oxides Undergo a Cope Elimination
Reaction
The proton is removed from the b-carbon bonded to
the most hydrogens
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Synthesis of Amines
Because ammonia and amines are good
nucleophiles, they readily undergo SN2 reactions
with RX
It is difficult to control the desired number of
alkyl substituents placed on the nitrogen
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The Gabriel Synthesis of Primary Amines
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Other Methods for Synthesizing Amines
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Reduction of amides with LiAlH4
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Aromatic Five-Membered Heterocycles
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Pyrrole is an extremely weak base
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The dipole moment in pyrrolidine (left) is
attributed to the electron-withdrawing property
of the nitrogen atom
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Pyrrole, furan, and thiophene undergo
electrophilic substitution, preferentially at C-2
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Electrophilic aromatic substitution reactions
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Structures of the intermediates that can be
formed from the reaction of an electrophile with
pyrrole at C-2 and C-3
Three resonance structures more stable
Two resonance structures less stable
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If both positions adjacent to the heteroatom are
occupied, electrophilic substitution occurs at
C-3
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Why? Because of cation stabilization by lone-pair
resonance release
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The relative reactivities of the five-membered
heterocycles in FriedelCrafts reaction
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The resonance hybrid of pyrrole indicates that
there is a partial positive charge on the
nitrogen
Pyrrole is unstable in strongly acid solution
because the protonated pyrrole polymerizes
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Pyrrole is more acidic than pyrrolidine because
of stabilization of its conjugated base by
resonance
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Indole, benzofuran, and benzothiophene all
contain a five-membered aromatic ring fused to a
benzene ring
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Aromatic Six-Membered-Ring Heterocycles
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The pyridinium ion is a stronger acid than a
typical ammonium ion
Pyridine reacts like a tertiary amine
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Pyridine Is Aromatic

• The nitrogen lone pair is not released into the
  aromatic system because it is perpendicular to
  the ? system.
• The nitrogen withdraws electrons by resonance,
  resulting in an electron-deficient ring system.

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Pyridine undergoes electrophilic aromatic
substitution at C-3
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The pyridine nitrogen is a meta director
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Pyridine is reactive toward nucleophilic aromatic
substitution because of the presence of the
electronegative nitrogen
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Pyridine undergoes nucleophilic aromatic
substitution at C-2 and C-4
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If the leaving groups at C-2 and C-4 are
different, the incoming nucleophile will
preferentially substitute for the weaker base
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Bromination and Oxidation of Substituted Pyridine
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Diazotization of Aminopyridine
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The a-hydrogens of alkyl substituents can be
removed by base to generate anionic nucleophiles
Pyridine a-hydrogen acidity is similar to that of
ketone a-hydrogens
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Reactions of pyridine-based anionic nucleophiles
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Quinoline and isoquinoline are ring-fused
pyridine derivatives
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Some Biologically Important Heterocycles
Imidazole
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Purine and Pyrimidine
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Porphyrin