Introduction:

AMINE:
amine, Any of a class of nitrogen-containing organic
compounds derived, either in principle or in practice,
from ammonia (NH3). Almost all their chemical names
end in -ine. Replacement of one, two, or all three of
the hydrogen atoms in ammonia with organic groups
yields primary, secondary, or tertiary amines,
respectively. Addition of a fourth hydrogen with an
accompanying positive charge on the nitrogen atom
results in a quaternary amine. Naturally occurring
amines include alkaloids, present in certain plants; some
neurotransmitters, including dopamine
and epinephrine; and histamine. Industrially important
amines include aniline, ethanolamine, and others, used
in making rubber, dyes, pharmaceuticals, and synthetic
resins and fibres and in a host of other applications. A
nitrogen atom with one or two hydrogens is often
referred to as an amino group.
Classification of amines
Amines can be classified according to the nature and
number of substituents on nitrogen. Aliphatic
amines contain only H and alkyl substituents. Aromatic
amines have the nitrogen atom connected to
an aromatic ring.
Amines, alkyl and aryl alike, are organized into three
subcategories based on the number of carbon atoms
adjacent to the nitrogen(how many hydrogen atoms of
the ammonia molecule are replaced by hydrocarbon
groups):
 Primary (1°) amines—Primary amines arise
when one of three hydrogen atoms in ammonia is
replaced by an alkyl or aromatic group. Important
primary alkyl amines include, methylamine,
most amino acids, and the buffering agent tris,
while primary aromatic amines include aniline.
 Secondary (2°) amines—Secondary amines

have two organic substituents (alkyl, aryl or both)

bound to the nitrogen together with one
hydrogen. Important representatives
include dimethylamine, while an example of an
aromatic amine would be diphenylamine.
 Tertiary (3°) amines—In tertiary amines,

nitrogen has three organic substituents.

Examples include trimethylamine, which has a
distinctively fishy smell, and EDTA.
A fourth subcategory is determined by the connectivity
of the substituents attached to the nitrogen:
 Cyclic amines—Cyclic amines are either
secondary or tertiary amines. Examples of cyclic
amines include the 3-membered
ring aziridine and the six-membered
ring piperidine. N-methylpiperidine and N-
phenylpiperidine are examples of cyclic tertiary
amines.
It is also possible to have four organic substituents on
the nitrogen. These species are not amines but
are quaternary ammonium cations and have a charged
nitrogen center. Quaternary ammonium salts exist with
many kinds of anions.
Physical properties
Hydrogen bonding significantly influences the properties
of primary and secondary amines. For
example, methyl and ethyl amines are gases under
standard conditions, whereas the
corresponding methyl and ethyl alcohols are liquids.
Amines possess a characteristic ammonia smell, liquid
amines have a distinctive "fishy" smell.
The nitrogen atom features a lone electron pair that can
bind H+ to form an ammonium ion R3NH+. The lone
electron pair is represented in this article by a two dots
above or next to the N. The water solubility of simple
amines is enhanced by hydrogen bonding involving
these lone electron pairs. Typically salts of ammonium
compounds exhibit the following order of solubility in
water: primary ammonium (RNH+
3) > secondary ammonium (R
2NH
+

2) > tertiary ammonium (R3NH ). Small aliphatic amines

+

display significant solubility in many solvents, whereas

those with large substituents are lipophilic. Aromatic
amines, such as aniline, have their lone pair
electrons conjugated into the benzene ring, thus their
tendency to engage in hydrogen bonding is diminished.
Their boiling points are high and their solubility in water
is low.
Spectroscopic identification
Typically the presence of an amine functional group is
deduced by a combination of techniques, including mass
spectrometry as well as NMR and IR spectroscopies. 1H
NMR signals for amines disappear upon treatment of the
sample with D2O. In their infrared spectrum primary
amines exhibit two N-H bands, whereas secondary
amines exhibit only one.
Structure
Alkyl amines
Alkyl amines characteristically feature tetrahedral
nitrogen centers. C-N-C and C-N-H angles approach the
idealized angle of 109°. C-N distances are slightly
shorter than C-C distances. The energy barrier for
the nitrogen inversion of the stereocenter is about
7 kcal/mol for a trialkylamine. The interconversion has
been compared to the inversion of an open umbrella into
a strong wind.
Amines of the type NHRR′ and NRR′R″ are chiral: the
nitrogen center bears four substituents counting the lone
pair. Because of the low barrier to inversion, amines of
the type NHRR′ cannot be obtained in optical purity. For
chiral tertiary amines, NRR′R″ can only be resolved
when the R, R′, and R″ groups are constrained in cyclic
structures such as N-substituted aziridines (quaternary
ammonium salts are resolvable).

Inversion of an amine. The pair of dots

represents the lone electron pair on the
nitrogen atom. amine is the function
 group whose formula is nh2

Aromatic amines
In aromatic amines ("anilines"), nitrogen is often
nearly planar owing to conjugation of the lone pair
with the aryl substituent. The C-N distance is
correspondingly shorter. In aniline, the C-N
distance is the same as the C-C distances.
Basicity
Like ammonia, amines are bases. Compared to alkali
metal hydroxides, amines are weaker (see table for
examples of conjugate acid Ka values).
Alkylamine or aniline pKa of protonated amine Kb

methylamine (MeNH2) 10.62 4.17E-04

dimethylamine (Me2NH) 10.64 4.37E-04

trimethylamine (Me3N) 9.76 5.75E-05

ethylamine (EtNH2) 10.63 4.27E-04

aniline (PhNH2) 4.62 4.17E-10

4-methoxyaniline (4-MeOC6H4NH2) 5.36 2.29E-09

N,N-Dimethylaniline (PhNMe2) 5.07 1.17E-09

3-Nitroaniline (3-NO2-C6H4NH2) 2.46 2.88E-12

4-Nitroaniline (4-NO2-C6H4NH2) 1 1.00E-13

4-trifluoromethylaniline (CF3C6H4NH2) 2.75 5.62E-12

The basicity of amines depends on:

 1. The electronic properties of the substituents
(alkyl groups enhance the basicity, aryl groups
diminish it).
2. The degree of solvation of the protonated
amine, which includes steric hindrance by the
groups on nitrogen.
Electronic effects:
Owing to inductive effects, the basicity of an amine
might be expected to increase with the number of alkyl
groups on the amine. Correlations are complicated
owing to the effects of solvation which are opposite the
trends for inductive effects. Solvation effects also
dominate the basicity of aromatic amines (anilines). For
anilines, the lone pair of electrons on nitrogen
delocalizes into the ring, resulting in decreased basicity.
Substituents on the aromatic ring, and their positions
relative to the amino group, also affect basicity as seen
in the table.
Solvation effects:
Solvation significantly affects the basicity of amines. N-H
groups strongly interact with water, especially in
ammonium ions. Consequently, the basicity of ammonia
is enhanced by 1011 by solvation. The intrinsic basicity of
amines, i.e. the situation where solvation is unimportant,
has been evaluated in the gas phase. In the gas phase,
amines exhibit the basicities predicted from the electron-
releasing effects of the organic substituents. Thus
tertiary amines are more basic than secondary amines,
which are more basic than primary amines, and finally
ammonia is least basic. The order of pKb's (basicities in
water) does not follow this order. Similarly aniline is
more basic than ammonia in the gas phase, but ten
thousand times less so in aqueous solution.
In aprotic polar solvents such as DMSO, DMF,
and acetonitrile the energy of solvation is not as high as
in protic polar solvents like water and methanol. For this
reason, the basicity of amines in these aprotic solvents
is almost solely governed by the electronic effects.
Synthesis:
From alcohols:
Industrially significant alkyl amines are prepared from
ammonia by alkylation with alcohols:
ROH + NH3 → RNH2 + H2O
From alkyl and aryl halides:
Unlike the reaction of amines with alcohols the
reaction of amines and ammonia with alkyl
halides is used for synthesis in the laboratory:
RX + 2 R′NH2 → RR′NH + [RR′NH2]X
In such reactions, which are more useful for
alkyl iodides and bromides, the degree of
alkylation is difficult to control such that one
obtains mixtures of primary, secondary, and
tertiary amines, as well as quaternary
ammonium salts.
Selectivity can be improved via the Delépine
reaction, although this is rarely employed on
an industrial scale. Selectivity is also assured
in the Gabriel synthesis, which
involves organohalide reacting with potassium
phthalimide.
Aryl halides are much less reactive toward
amines and for that reason are more
controllable. A popular way to prepare aryl
amines is the Buchwald-Hartwig reaction.
From alkenes:
Disubstituted alkenes react with HCN in the
presence of strong acids to give formamides, which
can be decarbonylated. This method, the Ritter
reaction, is used industrially to produce tertiary
amines such a tert-octylamine.
Hydroamination of alkenes is also widely practiced.
The reaction is catalyzed by zeolite-based solid
acids.
Reductive routes
Via the process of hydrogenation, unsaturated N-
containing functional groups are reduced to amines
using hydrogen in the presence of a nickel catalyst.
Suitable groups
include nitriles, azides, imines including oximes,
amides, and nitro. In the case of nitriles, reactions
are sensitive to acidic or alkaline conditions, which
can cause hydrolysis of the –CN group. LiAlH4 is
more commonly employed for the reduction of
these same groups on the laboratory scale.
Many amines are produced from aldehydes and
ketones via reductive amination, which can either
proceed catalytically or stoichiometrically.
 Aniline (C6H5NH2) and its derivatives are prepared
by reduction of the nitroaromatics. In industry,
hydrogen is the preferred reductant, whereas, in
the laboratory, tin and iron are often employed.
Reactions
Alkylation, acylation, and sulfonation
Aside from their basicity, the dominant reactivity of
amines is their nucleophilicity. Most primary amines are
good ligands for metal ions to give coordination
complexes. Amines are alkylated by alkyl halides. Acyl
chlorides and acid anhydrides react with primary and
secondary amines to form amides (the "Schotten–
Baumann reaction").

Similarly, with sulfonyl chlorides, one

obtains sulfonamides. This transformation, known as
the Hinsberg reaction, is a chemical test for the
presence of amines.
Because amines are basic, they neutralize acids to form
the corresponding ammonium salts R3NH+. When
formed from carboxylic acids and primary and
secondary amines, these salts thermally dehydrate to
form the corresponding amides.
 Neutralization
Amines react with nitrous acid to give diazonium salts.
The alkyl diazonium salts are of little synthetic
importance because they are too unstable. The most
important members are derivatives of aromatic
amines such as aniline ("phenylamine") (A = aryl or
naphthyl):
Anilines and naphthylamines form more
stable diazonium salts, which can be isolated in the
crystalline form. Diazonium salts undergo a variety
of useful transformations involving replacement of
the N2 group with anions. For example, cuprous
cyanide gives the corresponding nitriles:
Aryldiazonium couple with electron-rich aromatic
compounds such as a phenol to form azo
compounds. Such reactions are widely applied to
the production of dyes.
Conversion to Imines
Imine formation is an important reaction. Primary
amines react with ketones and aldehydes to
form imines. In the case of formaldehyde (R′ = H),
these products typically exist as cyclic trimers.
RNH2 + R′2C=O → R′2C=NR + H2O
Reduction of these imines gives secondary amines:
R′2C=NR + H2 → R′2CH–NHR
Similarly, secondary amines react with ketones
and aldehydes to form enamines:
R2NH + R′(R″CH2)C=O → R″CH=C(NR2)R′ + H2O

Application of amines
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 an
azo compound. As azo-compounds are highly coloured, they
are widely used in dyeing industries, such as:

 Methyl orange
 Direct brown 138
 Sunset yellow FCF
 Ponceau
Drugs
Approximately 42% of drugs and drug candidates
contain amine functional groups:
 Chlorpheniramine is an antihistamine that helps
to relieve allergic disorders due to cold, hay
fever, itchy skin, insect bites and stings.
 Chlorpromazine is a tranquilizer that sedates
without inducing sleep. It is used to relieve
anxiety, excitement, restlessness or even mental
disorder.
 Ephedrine and phenylephrine, as amine
hydrochlorides, are used as decongestants.
 Amphetamine, methamphetamine,
and methcathinone are psychostimulant amines
that are listed as controlled substances by the
US DEA.
 Thioridazine , an antipsychotic drug, is an amide
which is believed to exhibit its antipsychotic
effects, in part, due to its effects on other amides.
  Amitriptyline, imipramine, lofepramine and clomip
ramine are tricyclic antidepressants and tertiary
amines.
 Nortriptyline, desipramine,
and amoxapine are tricyclic antidepressants and
secondary amines. (The tricyclics are grouped by
the nature of the final amino group on the side
chain.)
 Substituted tryptamines and phenethylamines are
key basic structures for a large variety
of psychedelic drugs.
 Opiate analgesics such as morphine, codeine,
and heroin are tertiary amines.
Gas treatment
Aqueous monoethanolamine (MEA), diglycolamine
(DGA), diethanolamine (DEA), diisopropanolamine
(DIPA) and methyldiethanolamine (MDEA) are widely
used industrially for removing carbon dioxide (CO2)
and hydrogen sulfide (H2S) from natural gas and refinery
process streams. They may also be used to remove
CO2 from combustion gases and flue gases and may
have potential for abatement of greenhouse gases.
Related processes are known as sweetening.
Epoxy resin curing agents
Amines are often used as epoxy resin curing agents.
These include dimethylethylamine, cyclohexylamine,
and a variety of diamines such as 4,4 -
diaminodicyclohexylmethane.
Multifunctional amines such
as tetraethylenepentamine and triethylenetetramine are
also widely used in this capacity. The reaction proceeds
by the lone pair of electrons on the amine nitrogen
attacking the outermost carbon on the oxirane ring of the
epoxy resin. This relieves ring strain on the epoxide and
is the driving force of the reaction.

SHORT NOTE ABOUT AMINE:

amine, Any of a class of nitrogen-containing organic
compounds derived, either in principle or in practice,
from ammonia (NH3). Almost all their chemical names
end in -ine. Replacement of one, two, or all three of
the hydrogen atoms in ammonia with organic groups
yields primary, secondary, or tertiary amines,
respectively. Addition of a fourth hydrogen with an
accompanying positive charge on the nitrogen atom
results in a quaternary amine. Naturally occurring
amines include alkaloids, present in certain plants; some
neurotransmitters, including dopamine
and epinephrine; and histamine. Industrially important
amines include aniline, ethanolamine, and others, used
in making rubber, dyes, pharmaceuticals, and synthetic
resins and fibres and in a host of other applications. A
nitrogen atom with one or two hydrogens is often
referred to as an amino group.