Download Chapter 24. Amines

Chapter 24. Amines
and Heterocycles
Based on McMurry’s Organic Chemistry, 7th edition
Amines – Organic Nitrogen
Compounds
 Organic derivatives of ammonia, NH3,
 Nitrogen atom with a lone pair of electrons, making
amines both basic and nucleophilic
 Occur in plants and animals
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Why this Chapter?
 Amines and carbonyl compounds are the
most abundant and have rich chemistry
 In addition to proteins and nucleic acids, a
majority of pharmaceutical agents contain
amine functional groups
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Common Names of Heterocyclic
Amines
 If the nitrogen atom occurs as part of a ring, the
compound is designated as being heterocyclic
 Each ring system has its own parent name
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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
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Chirality Is Possible (But Not
Observed)
 An amine with three different substituents on nitrogen
is chiral (in principle but not in practice): the lone pair
of electrons is the fourth substituent
 Most amines that have 3 different substituents on N
are not resolved because the molecules interconvert
by pyramidal inversion
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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
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24.5 Biological Amines and the
Henderson-Hasselbalch Equation
 What form do amines exist at physiological pH inside
cells
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Selective Preparation of Primary Amines:
the Azide Synthesis
 Azide ion, N3 displaces a halide ion from a primary
or secondary alkyl halide to give an alkyl azide, RN3
 Alkyl azides are not nucleophilic (but they are
explosive)
 Reduction gives the primary amine
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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
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Reductive Amination of Aldehydes
and Ketones
 Treatment of an aldehyde or ketone with ammonia or
an amine in the presence of a reducing agent
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Mechanism of Reductive Amination
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Reducing Step
 Sodium cyanoborohydride, NaBH3CN, reduces C=N
but not C=O
 Stable in water
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Hofmann and Curtius
Rearrangements
 Carboxylic acid derivatives can be converted into
primary amines with loss of one carbon atom by both
the Hofmann rearrangement and the Curtius
rearrangement
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24.7 Reactions of Amines
 Alkylation and acylation have already been presented
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Hofmann Elimination
 Converts amines into alkenes
 NH2 is very a poor leaving group so it converted to
an alkylammonium ion, which is a good leaving group
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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
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24.8 Reactions of Arylamines
 Amino substituents are strongly activating, ortho- and
para-directing groups in electrophilic aromatic
substitution reactions
 Reactions are controlled by conversion to amide
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Arylamines Are Not Useful for
Friedel-Crafts Reactions
 The amino group forms a Lewis acid–base complex
with the AlCl3 catalyst, preventing further reaction
 Therefore we use the corresponding amide
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Diazonium Salts: The Sandmeyer
Reaction
 Primary arylamines react with HNO2, yielding stable
arenediazonium salts
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Uses of Arenediazonium Salts
 The N2 group can be replaced by a nucleophile
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Reduction to a Hydrocarbon
 By treatment of a diazonium salt with
hypophosphorous acid, H3PO2
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Mechanism of Diazonium
Replacement
 Through radical (rather than polar or ionic) pathways
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Diazonium Coupling Reactions
 Arenediazonium salts undergo a coupling reaction
with activated aromatic rings, such as phenols and
arylamines, to yield brightly colored azo compounds,
ArN=NAr
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How Diazonium Coupling Occurs
 The electrophilic diazonium ion reacts with the
electron-rich ring of a phenol or arylamine
 Usually occurs at the para position but goes ortho if
para is blocked
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Azo Dyes
 Azo-coupled products have extended  conjugation
that lead to low energy electronic transitions that
occur in visible light (dyes)
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24.9 Heterocycles
 A heterocycle is a cyclic compound that
contains atoms of two or more elements in its
ring, usually C along with N, O, or S
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Pyrole and Imidazole
 Pyrole is an amine and a conjugated diene,
however its chemical properties are not
consistent with either of structural features
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Chemistry of Pyrole
 Electrophilic
substitution
reactions occur at
C2 b/c it is position
next to the N
 A more stable
intermediate cation
having 3 resonance
forms
 At C3, only 2
resonance forms
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Polycyclic Heterocycles
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24.10 Spectroscopy of Amines Infrared
 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
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Nuclear Magnetic Resonance
Spectroscopy
 N–H hydrogens appear as broad signals without
clear-cut coupling to neighboring C–H hydrogens
 In D2O exchange of N–D for N–H occurs, and the N–
H signal disappears
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13C
NMR
 Carbons next to amine N are slightly deshielded -
about 20 ppm downfield from where they would
absorb in an alkane
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