Chapter 24.

Amines
and Heterocycles

Based on McMurry’s Organic Chemistry, 7th edition

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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

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24.1 Naming Amines
 Alkyl-substituted (alkylamines) or aryl-substituted
(arylamines)
 Classified: 1° (RNH2), methyl (CH3NH2), 2° (R2NH), 3°
(R3N)

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Quaternary Ammonium Ions
 A nitrogen atom with four attached groups is
positively charged
 Compounds are quaternary ammonium salts

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IUPAC Names – Simple Amines
 For simple amines, the suffix -amine is added to the
name of the alkyl substituent

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IUPAC Names – “-amine” Suffix
 The suffix -amine can be used in place of the final -e
in the name of the parent compound

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IUPAC Names – Amines With More
Than One Functional Group
 Consider the NH2 as an amino substituent on the
parent molecule

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IUPAC Names – Multiple Alkyl
Groups
 Symmetrical secondary and tertiary amines are
named by adding the prefix di- or tri- to the alkyl
group

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IUPAC Names – Multiple, Different
Alkyl Groups
 Named as N-substituted primary amines
 Largest alkyl group is the parent name, and other
alkyl groups are considered N-substituents

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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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Amines Form H-Bonds
 Amines with fewer than five carbons are water-
soluble
 Primary and secondary amines form hydrogen
bonds, increasing their boiling points

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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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Relative Basicity
 Amines are stronger bases than alcohols, ethers, or
water
 Amines establish an equilibrium with water in which
the amine becomes protonated and hydroxide is
produced
 The most convenient way to measure the basicity of
an amine (RNH2) is to look at the acidity of the
corresponding ammonium ion (RNH3+)
 High pKa → weaker acid and stronger conjugate
base.

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General Patterns of Basicity
 Table 24.1: pKa values of ammonium ions
 Most simple alkylammmonium ions have pKa's of 10
to 11
 Arylamines and heterocyclic aromatic amines are
considerably less basic than alkylamines (conjugate
acid pKa 5 or less)

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Amides
 Amides (RCONH2) in general are not proton acceptors except in
very strong acid
 The C=O group is strongly electron-withdrawing, making the N a
very weak base
 Addition of a proton occurs on O but this destroys the double
bond character of C=O as a requirement of stabilization by N

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24.4 Basicity of Substituted
Arylamines
 The N lone-pair electrons in arylamines are
delocalized by interaction with the aromatic ring 
electron system and are less able to accept H+ than
are alkylamines

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Substituted Arylamines
 Can be more basic or less basic than aniline
 Electron-donating substituents (such as CH3,
NH2, OCH3) increase the basicity of the
corresponding arylamine
 Electron-withdrawing substituents (such as Cl,
NO2, CN) decrease arylamine basicity

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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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24.6 Synthesis of Amines
 Arylamines are prepared from nitration of an aromatic
compound and reduction of the nitro group
 Reduction by catalytic hydrogenation over platinum is suitable
if no other groups can be reduced
 Iron, zinc, tin, and tin(II) chloride are effective in acidic solution

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SN2 Reactions of Alkyl Halides
 Ammonia and other amines are good nucleophiles

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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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Reductive Amination Is
Versatile
 Ammonia, primary amines, and secondary amines yield
primary, secondary, and tertiary amines, respectively

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Mechanism of Reductive Amination

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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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Diazonium Salts
 Primary arylamines react with HNO2, yielding stable
arenediazonium salts

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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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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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Examples of Infrared Spectra

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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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Chemical Shift Effects
 Hydrogens on C next to N and absorb at lower field
than alkane hydrogens
 N-CH3 gives a sharp three-H singlet at  2.2 to  2.6

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13
C 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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