Amines

1
 Introduction
• Definition: “Amines are organic (aliphatic and aromatic) derivatives of
ammonia, wherein one or more hydrogen atoms have been replaced
by a substituent such as an alkyl or aryl group.”

• These may respectively be called alkylamines and arylamines; while

amines in which both types of substituent are attached to one
nitrogen atom may be called alkylarylamines.

• Examples:

2
 Classification of Amines
• Amines are classified as primary (1°), secondary (2°), or tertiary (3°)
amines, depending on the number of carbon groups bonded to
nitrogen atom.

• Those amine compounds that have only one group attached to the
nitrogen atom are primary, while those with two or three groups
attached to the nitrogen atom are secondary and tertiary,
respectively.

• General Formulae:

3
Examples:

Amines are further classified as aliphatic or aromatic.

[1]. Aliphatic amine: An amine in which nitrogen is bonded only to alkyl

groups or hydrogens.
[2]. Aromatic amine: An amine in which nitrogen is bonded to one or
more aromatic rings.

4
• Aromatic amines belong to specific families, which act as parent molecules.
For example, an amino group (—NH2) attached to benzene produces the
parent compound “aniline”.

[3]. Heterocyclic Amine: An amine in which the nitrogen atom is part of a ring
is classified as a heterocyclic amine. It may be aliphatic or aromatic as well.
i. Heterocyclic aliphatic Amine: When the ring is saturated, the amine is
classified as a heterocyclic aliphatic amine.
ii. Heterocyclic Aromatic Amine: When the nitrogen is part of an aromatic
ring, the amine is classified as a heterocyclic aromatic amine.
• Examples: Two of the most important heterocyclic aromatic amines are 5
pyridine and pyrimidine, in which nitrogen atoms replace first one and then
two CH groups of a benzene ring. Pyrimidine and purine serve as the
building blocks for the amine bases of DNA and RNA.
• An Important Exercise Note: Isopropylamine is a primary amine even
though its NH2 group is attached to a secondary carbon atom. It is a
primary amine because only one organic group is attached to the
nitrogen atom.
• Notice that this is quite different from the way alcohols and alkyl
halides are classified.

6
 Nomenclature of Amines
[A]. IUPAC Names: IUPAC names for aliphatic amines are derived just as
they are for alcohols.
• The final –e of the parent alkane is dropped and replaced by -amine.
The location of the amino group on the parent chain is indicated by a
number.

• IUPAC nomenclature retains the common name “aniline” for C6H5NH2,

the simplest aromatic amine.
• Its simple derivatives are named using numbers to locate
substituents or, alternatively, using the locators ortho (o), meta (m), 7
and para (p).
• Several derivatives of aniline have common names that remain in use.
Among them is “toluidine” for a methyl-substituted aniline.

• Unsymmetrical secondary and tertiary amines are commonly named

as N-substituted primary amines.

• The largest group bonded to nitrogen is taken as the parent amine;

the smaller groups bonded to nitrogen are named, and their locations
are indicated by the prefix N (indicating that they are bonded to
nitrogen).

8
[B]. Common Names:
• Common names for most aliphatic amines list the groups bonded to
nitrogen in alphabetical order in one word ending in the suffix -amine.

• Salts: When four atoms or groups of atoms are bonded to a nitrogen

atom—as, for example, in NH4+ and CH3NH3+ —nitrogen bears a
positive charge and is associated with an anion as a salt.
• The compound is named as a salt of the corresponding amine.
• The ending –amine (or aniline, pyridine, or the like) is replaced by –
ammonium (or anilinium, pyridinium, or the like) and the name of the
anion (chloride, acetate, and so on) is added.
9
• Arylamines: Some common arylamines have the following names:

Note: Common names are mentioned in black and systemic names in blue
colour.

Heterocyclic Amines:
• The important heterocyclic amines all have common names.
• In systematic replacement nomenclature, the prefixes aza-, diaza-, and triaza-
are used to indicate that nitrogen atoms have replaced carbon atoms in the
10
corresponding hydrocarbon.
• A nitrogen atom in the ring (or the highest atomic weight heteroatom, as in
the case of thiazole) is designated position 1 and numbering proceeds to give
11
 Physical Properties
[1]. Physical state and smell:
• Among aliphatic amines, the lower members are gases while higher
members are liquids. Among arylamines the lower members are liquids
while higher members are solids.

• Like ammonia, low-molecular-weight amines have very sharp, penetrating

odors. Methyl amine and ethyl amine have ammonical smell but higher
amines have fishy smell. Trimethylamine, for example, is the pungent
principle in the smell of rotting fish.

• Most of the aromatic amines are colourless in pure form. However, they
become coloured on keeping, due to oxidation on air. Aromatic amines are
generally toxic. They are easily absorbed through the skin.

[2]. Polarity: Amines are moderately polar substances. They are polar
compounds because of the difference in electronegativity between nitrogen 12
and hydrogen.
[3]. Hydrogen Bonding and Boiling Points:
• Both primary and secondary amines have N-H bonds, and can form
hydrogen bonds with one another and to water.
• Tertiary amines do not have a hydrogen bonded to nitrogen and,
therefore, do not form hydrogen bonds with one another.

• The H-bonding causes intermolecular association of amines and as a

result of this, amines have higher boiling points than the non-polar
compounds of comparable molar masses.

• However, amines have lower boiling points than those of

corresponding alcohols or carboxylic acids.

• This is due to the reason that O – H bond is more polar than N – H 13

bond and therefore, intermolecular hydrogen bonds in alcohols and
carboxylic acids are relatively stronger than those in amines.
 Hydrogen bonding between
two molecules of a secondary
amine.

• Molecules of tertiary amines can form hydrogen bonds to molecules of water or

other hydroxylic solvents. As a result, tertiary amines generally boil at lower
temperatures than primary and secondary amines of comparable molecular
weight, but all low-molecular-weight amines are very water soluble.

[4]. Solubility:
• Aliphatic amines of lower molar mass are soluble in water. With increase in molar
mass the hydrocarbon part of the molecules become larger and consequently, the
solubility in water gradually decreases; the borderline being reached at about six
carbon atoms. The higher amines are more soluble in less polar solvents such as
ethers, alcohols and benzene. The solubility of lower aliphatic amines in water is
due to their capability to form hydrogen bonds with water molecules. 14
• Aromatic amines are insoluble in water but soluble in ether, alcohols and
benzene. Their inability to dissolve in water is due to more dominant aryl part
which is non-polar and decreases tendency of H-bonding with water molecules.
 Methods of Preparation of Amines
[1]. By Alkylation of Ammonia: Salts of primary amines can be
prepared from ammonia and alkyl halides by nucleophilic substitution
reactions. Subsequent treatment of the resulting aminium salts with a
base gives primary amines:

• This method is of very limited synthetic application because multiple

alkylations occur.

• The primary amine that is formed can also react with the alkyl halide,
which leads to a disubstituted amine that can further react to form a
trisubstituted amine.

15
• Therefore, the alkylation of ammonia leads to a mixture of products.
16
[2]. Alkylation of Azide Ion and Reduction: A much better method for
preparing a primary amine from an alkyl halide is first to convert the alkyl
halide to an alkyl azide (R-N3) by a nucleophilic substitution reaction, then
reduce the azide to a primary amine with sodium and alcohol or with lithium
aluminum hydride.

Example 1:

Example 2:

17
• A Word of Caution: Alkyl azides are explosive, and low-molecular-weight
alkyl azides should not be isolated but should be kept in solution.
[3]. The Gabriel Synthesis: In the Gabriel synthesis, potassium phthalimide is
reacted with an alkyl halide to produce an N‐alkyl phthalimide.
• This N‐alkyl phthalimide can be hydrolyzed by aqueous acids or bases into
the primary amine. This synthesis also avoids the complications of multiple
alkylations that occur when alkyl halides are treated with ammonia:

18
Explanation:
• Phthalimide is quite acidic; it can be converted to potassium phthalimide by
potassium hydroxide (step 1).
• The phthalimide anion is a strong nucleophile and (in step 2) it reacts with
an alkyl halide by an SN2 mechanism to give an N-alkylphthalimide.
• At this point, the N-alkylphthalimide can be hydrolyzed with aqueous acid or
base, but the hydrolysis is often difficult.
• It is often more convenient to treat the N-alkylphthalimide with hydrazine
(NH2NH2) in refluxing ethanol (step 3) to give a primary amine and
phthalazine-1,4-dione.
• Example:

19
[4]. Reduction of Nitro Compounds:
• Aromatic amines are normally prepared by reduction of the
corresponding aromatic nitro compound.
• Reducing agents: Fe/H+, Sn/H+ or catalytic hydrogenation (example,
H2/Pd or Pt or Ni).

20
[5]. Reductive amination of aldehydes and ketones:
• Aldehydes or ketones can be reduced by catalytic or chemical
reductions in the presence of ammonia or primary or secondary
amines, producing primary, secondary, or tertiary amines.

• (a). The reaction of a ketone with ammonia, followed by catalytic

reduction or reduction by sodium cyanoborohydride, produces a 1° 21
amine.
• (b). N‐substituted amines are produced by reaction of ketones with primary
amines, followed by reduction.

• (c). N,N‐disubstituted amines can be produced by reaction of 2° amines

with ketones followed by reduction.

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• Three specific aromatic/cyclic examples of reductive aminations:

23
• Preparation of Primary, Secondary, or Tertiary Amines through
Reduction of Nitriles, Oximes, and Amides: Nitriles, oximes, and
amides can be reduced to amines. Reduction of a nitrile or an oxime
yields a primary amine; reduction of an amide can yield a primary,
secondary, or tertiary amine:

24

• (In case of amides, if both R’ and R’’ = H, the product is a 1° amine and
• All of these reductions can be carried out with hydrogen and a
catalyst or with LiAlH4.

[6]. Reduction of nitriles: Nitriles can be reduced by lithium aluminum

hydride (LiAIH4) to primary amines.

[7]. Reduction of Oximes: Oximes are also conveniently reduced with

sodium in ethanol. Example:

25
[8]. Reduction of amides: Amides yield primary amines on reduction by
lithium aluminum hydride, while N‐substituted and N, N‐disubstituted amides
produce secondary and tertiary amines, respectively.
• The oxygen atom is replaced by two hydrogen atoms.

26
[9]. Hoffmann degradation of amides:
• Hofmann degradation is a reaction between an amide and a mixture of
bromine and sodium hydroxide solution. Heat is needed. The net effect of
the reaction is a loss of the –C=O part of the amide group. A primary amine
is obtained with one less carbon atom than the original amide had.

27
[10]. From Grignard Reagent:
• Primary amines are formed when a Grignard reagent is treated with
chloramine.

[11]. By Ammonolysis of Alcohols:

• When vapours of mixture of alcohol and ammonia are passed over
heated alumina (Al2O3) or thoria (ThO2) at 630 K, a mixture of amines
is formed.

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 Reactions or Chemical Properties of Amines
[1]. Basicity of Amines: Like ammonia, amines are weak bases, and aqueous
solutions of amines are basic.

• Reason of Basic Nature: Due to the unshared electron pair which they can
share with other atoms, amines can act as both bases and nucleophiles.
These unshared electrons create an electron density around the nitrogen
atom. The greater the electron density, the more basic the molecule.

• Example: In the acid–base reaction between an amine and water, the

unshared pair of electrons on nitrogen forms a new covalent bond with
hydrogen and displaces a hydroxide ion.

29
• Aliphatic amines are weak bases as compared to inorganic bases such
as NaOH, but they are strong bases among organic compounds.

• Nonaromatic heterocyclic amines have basicities that are

approximately the same as those of acyclic amines.

• Aliphatic amines are stronger bases than ammonia because the alkyl
groups are electron donors relative to hydrogen. 30
• The basicity of an amine is influenced by the number and types of
carbon groups attached to the nitrogen atom.

• Aromatic amines are weaker bases than ammonia because

delocalization of the unshared electron pair on the nitrogen into the
ring lowers the electron density on the nitrogen.

• Important Note: Groups that donate or supply electrons will increase

the basicity of amines while groups that decrease the electron density
around the nitrogen decrease the basicity of the molecule.
31
[2]. Reaction with Inorganic Acids (Formation of Aminium Salts and
Quaternary Ammonium Salts): When primary, secondary, and tertiary
amines act as bases and react with inorganic acids, they form
compounds called aminium salts. In an aminium salt the positively
charged nitrogen atom is attached to at least one hydrogen atom.
Examples:

32
• When the central nitrogen atom of a compound is positively charged
but is not attached to a hydrogen atom, the compound is called a
quaternary ammonium salt.

33
• Quaternary ammonium halides—because they do not have an
unshared electron pair on the nitrogen atom—cannot act as bases.
• For example,

• Quaternary ammonium hydroxides, however, are strong bases (as

strong as sodium or potassium hydroxide).

• Quaternary ammonium hydroxides react with acids to form

quaternary ammonium salts:

34
• Solubility of Aminium salts in Water: Almost all alkylaminium
chloride, bromide, iodide, and sulfate salts are soluble in water.
• Thus, primary, secondary, or tertiary amines that are not soluble in
water will dissolve in dilute aqueous HCl, HBr, HI, and H2SO4.

• Amines, whether soluble or insoluble in water, react quantitatively

with strong acids to form water-soluble salts e.g.:

35
[3]. Alkylation-Reaction with alkyl halides:
• The process of introducing an alkyl group into any molecule is called
alkylation.

• Amines react as a nucleophiles with alkyl halides via SN2 substitution

reaction to form amines of higher class.

• 3o amines make Quaternary Ammonium salt.

Example:
• Aniline when heated with excess of methyliodide under pressure,
36
gives first N-methylaniline, then N,N-Dimethylaniline and finally
trimethylanilinium iodide.
Note: The process of converting an amine (1o, 2o or 3o) into its quaternary
ammonium salt on treatment with excess of an alkyl halide is called exhaustive 37
alkylation. If the alkyl halide used is methyl iodide, the process is known as
exhaustive methylation.
38
[4]. Reaction of Amines with Carboxylic Acids (Amide formation): Amines are
basic, they neutralize carboxylic acids to form the corresponding ammonium
salts. These salts thermally dehydrate to form the corresponding amides.
Secondary and tertiary amides can be synthesised by using primary amines
and secondary amines respectively.

39
[5]. Reaction of Amines with acyl chlorides (Amide formation):
Primary and secondary amines are acylated at room temperature by
acyl chlorides to form N-substituted amides.
RNH2 + CH3COCl → RNHCOCH3 + HCl
R2NH + CH3COCl → R2NCOCH3 + HCl
• Tertiary amines are NOT acylated because they do not have hydrogen
atom attached to the nitrogen atom.
40
Note: A base such as sodium hydroxide is normally added to react with
the hydrogen chloride produced.
41
[6]. Reaction of Amines with acid anhydrides (Amide formation):
• Primary and secondary amines are readily acylated by acid anhydrides
to yield the corresponding amides.
• For example,

[7]. Reaction with Esters:

• Esters reacts with ammonia, primary and secondary amines to
42
produce amides and alcohols.
• ,
43
[8]. Reaction of Amines with Aldehydes and ketones: Aldehydes and ketones
react with primary amines to give a reaction product (a carbinolamine) that
dehydrates to yield aldimines and ketimines (Schiff bases).

• If you react secondary amines with aldehydes or ketones, enamines form.

44
[9]. Reaction of Amines with sulfonyl chlorides:

Amines react with sulfonyl chlorides to produce sulfonamides (a

number of antibiotics belong to this class).

A typical example is the reaction of benzene sulfonyl chloride with

aniline.
45
[10]. Oxidation of Amines:
• Primary and secondary aliphatic amines are subjected to oxidation,
although in most instances useful products are not obtained.

• Serious Flaw: Complicated side reactions often occur, causing the

formation of complex mixtures.

46
• Arylamines tend to be easily oxidized, with oxidation occurring on the
amine group as well as in the ring.

• Tertiary amines can be oxidized cleanly to tertiary amine oxides. This

transformation can be brought about by using hydrogen peroxide or a
peroxy acid:

47
[11]. Electrophilic substitution in Benzene Ring of Aniline: Due to the
displacement of the lone pair of electrons on nitrogen towards the benzene
ring, the electron density increases at o- and p- positions as compared to m-
position.
Hence, the -NH2 group directs the incoming group to o- and p- positions i.e. -
NH2 is an o-, p- directing group and it is a powerful activating group.

Halogination: Due to the strong activating effect of the amino group,

halogenation of amines occurs very fast and the halogen enters the p- and
both the o- positions even in the absence of a catalyst.

For example, aniline reacts with bromine water to give a white precipitate of
2,4,6-tribromoaniline.

48
[12]. Reaction with nitrous acid: Nitrous acid is unstable and must be
prepared in the reaction solution by mixing sodium nitrite (NaNO2) with
an aqueous solution of a strong acid:

• Reactions of Primary Aliphatic Amines with Nitrous Acid:

• Primary aliphatic amines react with nitrous acid through a reaction
called diazotization to yield highly unstable aliphatic diazonium salts.

• Even at low temperatures, aliphatic diazonium salts decompose

spontaneously by losing nitrogen to form carbocations that is
capable of reaction with any nucleophile in solution.

• The carbocations go on to produce mixtures of alkenes, alcohols, and

alkyl halides by removal of a proton, reaction with H2O, and reaction 49
with X- respectively.
• n

50
(a). Reactions of Primary Arylamines with Nitrous Acid:
• Primary arylamines react with nitrous acid to give arene diazonium
salts.
• Even though arene diazonium salts are unstable, they are still far
more stable than aliphatic diazonium salts; they do not decompose at
an appreciable rate in solution when the temperature of the reaction
mixture is kept below 5°C:

• Example:

51
(b). Reactions of Secondary Amines with Nitrous Acid:
• Secondary amines—both aryl and alkyl—react with nitrous acid to
yield N-nitrosoamines.

• N-Nitrosoamines usually separate from the reaction mixture as oily

yellow liquids:

52
(c). Reactions of Tertiary Amines with Nitrous Acid:
• When a tertiary aliphatic amine is mixed with nitrous acid, an equilibrium is
established among the tertiary amine, its salt, and an N-nitrosoammonium
compound:

• Tertiary arylamines react with nitrous acid to form C-nitroso aromatic

compounds. Nitrosation takes place almost exclusively at the para position if
it is open and, if not, at the ortho position.

53
[13]. Benzoylation: When amines react with benzoyl chloride, the
reaction is also known as benzoylation. For example,

[14]. Reaction of Amines with Grignard reagent: The amines on

treatment with the Grignard reagent forms the alkanes. Secondary and
Primary amines both respond to this reaction. For example,

54
[15]. Reaction with metal ions: Like ammonia, amines also form water
soluble co-ordination compounds with metal ions like Ag+ and Cu2+.
• For example, AgCl disssolves in aqueous solution of ethylamine.

• Similarly, ethylamine reacts with Cu2+ ions to form a deep blue

solution of a soluble co-ordination compound.

55
[16]. Reaction with AlCl3:
• Aniline does not undergo Friedel-Craft's reaction (Alkylation or
acylation).

• It is because, AlCl3, which is used as the catalyst, is a Lewis acid and it

forms a salt with aniline due to its basic nature.

• Due to this, nitrogen of aniline acquires positive charge and it produces

a strong deactivating effect on the ring and hence electrophilic attack 56
will not take place.
 Identification Tests of Amines
• Each of the three types of amines (primary amines, secondary amines
and tertiary amines) exhibit different physical and chemical
properties.

• Certain tests are carried out for the identification of primary amines,
secondary amines and tertiary amines.

[1]. Hinsberg test:

• Hinsberg test is a popular chemical test for the identification and
distinguishing of primary amines, secondary amines and tertiary
amines.

• Sulfonamide formation is the basis of this test.

• In this reaction, an amine is treated with Hinsberg reagent 57

(Benzenesulphonyl chloride) in the presence of aqueous alkali (KOH or
NaOH).
• A Hinsberg test involves two steps.

• First, a mixture containing a small amount of the amine and benzene

sulfonyl chloride is shaken with excess potassium hydroxide.
• Next, after allowing time for a reaction to take place, the mixture is acidified.

• Each type of amine—primary, secondary, or tertiary—gives a different set of

visible results after each of these two stages of the test.

• Following observations are noted:

• (a). Primary amines react with benzene sulfonyl chloride to form water-
insoluble N-substituted benzene sulfonamides.

• Due to the presence of strong electron withdrawing sulphonyl group, the

hydrogen attached to nitrogen in sulphonamide is strongly acidic.
58
• Thus the suiphonamide is soluble in alkali because it undergoes acid–base
reactions with the excess potassium hydroxide to form water-soluble
potassium salts.
• At this stage test tube contains a clear solution.

• The solution thus obtained on acidification gives a precipitate of free

sulfonamide which is insoluble in HCl.

59
• (b). Secondary Amines: When a secondary amine is treated with Hinsberg
reagent (benzenesulphonyl chloride) in aqueous potassium hydroxide, N,N-
disubstituted sulfonamide is formed that precipitate after the first stage.

• N,N Disubstituted sulfonamides do not dissolve in aqueous potassium

hydroxide because they do not have an acidic hydrogen. Hence it is insoluble
in alkali.
• Acidification of the mixture obtained from a secondary amine produces no
visible result; the nonbasic N,N-disubstituted sulfonamide remains as a
precipitate and no new precipitate forms:

60
• (c). If a tertiary amine is shaken with benzene sulfonyl chloride and
aqueous KOH, no reaction takes place.

• Hence it remains insoluble in the alkaline solution but dissolves on

acidification to give a clear solution because it forms a water-soluble
salt.

[2]. Solubility Test: All the three classes of amines (1o, 2o & 3o) being
basic, dissolve in dilute mineral acids to form salts.

[3]. Litmus/pH Paper Test: Litmus paper as well as a moist pH paper can
be used to test for the presence of an amine functional group in an 61
unknown compound.
• If the compound is an amine, the red litmus will be turned blue and
[4]. Acid Chloride Test: Amines react as nucleophiles toward acyl (acid)
chlorides to give amides. This reaction can be used to indicate the possibility
of an amine functional group.
• The suspected amine is added to benzoyl chloride, as the reaction occurs
heat is released, and the test tube gets warm.

• During the course of this reaction HCl, a gas, is formed, but no bubbling of
gas is observed because the HCl reacts with unrected amine forming the
hydrochloride salt.

[5]. Nitrous Acid Test:

• Amines undergo a variety of reactions with nitrous acid (HNO2) depending
62
on whether the amine is primary, secondary or tertiary and whether the
amine is aliphatic or aromatic.
• Note: This test is also called azo dye test. An aromatic primary amine
can be identified by this test.

• The reaction of primary amines (either aliphatic or aromatic) with

63
nitrous acid initially results in the formation of a diazonium salt.
• The diazonium salts of primary aliphatic amines are unstable and quickly
decompose to give carbonium ions and N2, with the gas rapidly bubbling
out of solution.

• The diazonium salts of primary aromatic amines, on the other hand, are
stable in aqueous solutions at temperatures or 0-5 C˚.

• At higher temperatures they decompose with loss of N2. If the aromatic

diazonium salts are kept at low temperatures and treated with a
nucleophile such as a phenol, they will form colored azo dyes.

• When β-naphthol is added to the suspected diazonium salt, the formation 64

of a redish orange color or precipitate is indication of the formation of an
azo dye.
Primary Aromatic Amine:

65
• Secondary amines (both aliphatic and aromatic) do not form
diazonium salts upon treatment with nitrous acid.
• However, the do form N-nitroso compounds (N-nitrosoamine), which
will then separate out of solution as yellow oils or solids.

• Tertiary amine reacts with nitrous acid to form soluble nitrite salt.

[6]. Copper ion test:

• Low molecular weight amines that ere soluble in water including
amino alcohols, may be detected by 10 percent copper sulphate
solution. Formation of a blue or blue-green coloration or precipitate 66
with the reagent indicates the presence of an amine.
[7]. Carbylamine reaction:
• Carbylamine reaction is used as a test for the identification of primary
amines.
• When aliphatic and aromatic primary amines are heated with
chloroform and ethanolic potassium hydroxide, carbylamines (or
isocyanides) are formed.
• These carbylamines have very unpleasant odours.
• Secondary and tertiary amines do not respond to this test.

67
 Pharmaceutical Applications of Amines
• Amines are largely used in pharmaceutical industry. Many drugs are
the amine drugs:
[1]. Chlorpheniramine is an antihistamine that helps to relieve allergic
disorders due to cold, hay fever, itchy skin, insect bites and stings.
[2]. Chlorpromazine is a tranquilizer that sedates without inducing
sleep. It is used to relieve anxiety, excitement, restlessness or even
mental disorder.
[3]. Ephedrine and phenylephrine, as amine hydrochlorides, are used
as decongestants.

68
[4]. Opiate analgesics (pain killers) such as morphine, codeine, and
heroin are tertiary amines.

[5]. Amphetamines are widely prescribed to counter mild depression, to

reduce fatigue, reduce hyperactivity in children, and suppress appetite
in people who are trying to lose weight and elevate mood.
69
Examples: Amphetamine, methamphetamine, and phentermine—all
synthetic amines—are powerful stimulants of the central nervous
[6]. Amitriptyline, imipramine and clomipramine are tricyclic
antidepressants and tertiary amines.

70
[7]. Librium, Valium, and other benzodiazepines are central nervous
system sedatives/hypnotics.

• As sedatives, they diminish activity and excitement, thereby exerting a

calming effect. As hypnotics, they produce drowsiness and sleep.

[8]. Methadone, a narcotic analgesic, is marketed as its water soluble

hydrochloride salt. 71

[9]. Novocain, one of the first local anesthetics, is the hydrochloride salt
[10]. Quinine is a medication to
treat malaria. It also a mild
antipyretic and analgesic.

[11]. Atropine from belladonna

is used in low concentrations to
accelerate slow heart rates and
72
as an anesthetic for eye
examinations.
[12]. Vitamins:
• A number of amines are vitamins. These include nicotinic acid,
pyridoxine (vitamin B6), and thiamine chloride (vitamin B1).

[13]. Tranquilizers:
• Valium (diazepam) is a widely prescribed tranquilizer.
• Tranquilizer is used to reduce anxiety, fear, tension, agitation, and
related states of mental disturbance.

73
[14]. Cocaine is a powerfully addictive stimulant drug made from the
leaves of the coca plant. It affects the body significantly in both the
short and long-term and can include, heart attacks, stroke, and even
death.
[15]. Procaine is a local anesthetic drug of the amino ester group.
[16]. Lidocaine (also known as xylocaine) is a medication used to numb
tissue in a specific area and to treat ventricular tachycardia.

74
[17]. Neurotransmitters: Many neurotransmitters are amines, including
epinephrine, norepinephrine, nicotine, dopamine, serotonin, and
histamine.

75
[18]. Two of the most important heterocyclic aromatic amines are pyrimidines
and purines which serve as the building blocks for the amine bases of DNA and
RNA.

[19]. Dyes: Primary aromatic amines are used as a starting material for the
manufacture of azo dyes. It reacts with nitrous acid to form diazonium salt,
which can undergo coupling reaction to form azo compound. As azo-
76
compounds are highly coloured, they are widely used in dyeing e.g. methyl
orange, direct brown 138 etc.
[20]. Synthesis of other Aromatic Compounds:
• Arenediazonium salts are highly useful intermediates in the synthesis
of other aromatic compounds, because the diazonium group can be
replaced by any one of a number of other atoms or groups, including
-F, -Cl, -Br, -I, -CN, -OH, and -H.

• Because aromatic diazonium salts are only stable at very low

temperatures (zero degrees and below), warming these salts initiates
decomposition into highly reactive cations. 77

• These cations can react with any anion present in solution to form a
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[21]. Amines as Resolving Agents: Enantiomerically pure amines e.g. naturally
occurring optically active amines such as (-)-quinine, (-)-strychnine and (-)-
brucine are often used to resolve racemic forms of acidic compounds by the
formation of diastereomeric salts.

• Example with Explanation: In this procedure the single enantiomer of an

amine, (R)-1-phenylethylamine, is added to a solution of the racemic form of
an acid. The salts that form are diastereomers.

• The chirality centers of the acid portion of the salts are enantiomerically
related to each other, but the chirality centers of the amine portion are not.

• The diastereomers have different solubilities and can be separated by careful

crystallization.

• The separated salts are then acidified with hydrochloric acid. Acidification of
the separated diastereomeric salts causes the enantiomeric acids to
precipitate (assuming they are insoluble in water) and the enantiomeric acids
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are obtained from the separate solutions.

• The resolving agent amine remains in solution as its hydrochloride salt.

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