P.1
Amines
A.
Structure and nomenclature:
Amines can be regarded as organic derivatives of ammonia. There exist 3 classes of
amines.
As nitrogen atom is sp3 hybridized, the shape of the molecules are trigonal
pyramidal.
For 1o amines:
CH3NH2
methylamine
(methanamine)
NH2
CH3CH2NH2 ethylamine
(ethanamine)
CH3CHCH3
NH2
CH3CH2CH2NH2
CH2NH2
propylamine
(propanamine)
benzenamine
(aniline)
1-methyl-1-propanamine
For 2o amines:
CH3 N H
CH3
dimethylamine
CH3N H
C2H5
methylethanamine
NHCH3
N-methylaniline
(N-methylbenzenamine)
For 3o amines:
CH3 N CH3
CH3
trimethylamine
CH3CH2CH2-N-CH2CH3
CH3
ethylmethylpropylamine
CH3 N CH3
(ethylmethylpropanamine)
C2H5
N,N-dimethylethanamine
Aromatic amines are those compounds in which the N atom is directly attached to the
aromatic ring.
Quaternary ammonium compounds are compounds in which containing a tetravalent
N atom.
For example,
CH3
CH3 N+ CH3 Br- tetramethylammonium bromide
CH3
P.2
mine salts:
For example,
(CH3)3NH+ I- trimethylammonium iodide
In naming complicated amines, -NH2 group is named as the group amino-.
H2NCH2CH2OH
2-aminoethanol
CH3CHCH2OH
2-(N-methylamino)propanol CH3CHCH2COOH
H2NCH2CH2COOH
3-aminopropanoic acid
N(CH3)2
NHCH3
2-(N,N-dimethylamino)butanoic acid
B.
Preparation
1.
Reduction of nitro-compounds
---
production of 1o amines
[H]
R-NO2
RNH2
The reducing agent is usually H2, with Ni catalyst.
The most widely used method for preparing aromatic amines is as follow:
HNO3
Ar-H
[H]
ArNO2
ArNH2
H2SO4
Iron and hydrochloric acid are used to reduce aromatic nitro-compounds, the
amine is produced as a complex salt from which it is liberated with alkali.
(other reagents for examples, acid and iron or zinc, a metal salt e.g. SnCl2 can
also be used.)
2.
Reduction of nitriles and amides
1. LiAlH4 in ether
RCN
2. H+/H2O
1. LiAlH4 in ether
RCONH2
3.
2. H+/H2O
Hofmann degradation of amides
R - C - NH2
O
+
Br2
+
4NaOH
H2O
P.3
It gives a good yield of primary amines uncontaminated with 2o and 3o amines.
However the yield is not so good by using high molecular mass amides but it
can be improved by using bromine and sodium methoxide in methanol
solution.
Br2, CH3OCH3(CH2)14CONH2
CH3(CH2)13CH2NH2
methanol
4.
From alkyl halides (alkylation)
OHH3N:
+
R-X
RNH3+X-
RNH2 + X- + H2O
This method is often limited synthetic applications because multiple alkylation
may occur also.
And aromatic halides,
X is unreactive towards ammonia.
copper(I) salt (cat.)
But,
C.
Cl + 2NH3
200oC, 50 atm
NH2 + NH4Cl
Physical properties
Simple aliphatic amines are gases at room conditions. Higher members are liquids,
and even higher, they are solids. Lower members of amines are usually with ammonia
smell, while for the higher members, they have distinctive 'fishy' odour.
Simple amines are fairly soluble in water, but with a general decrease in solubility as
HC content increases. However, they are soluble in many organic solvents.
Because amines are polar compounds, they have higher boiling points than those of
corresponding molecular mass alkanes but generally lower than those of alcohols.
Boiling point of 1o amines > 2o amines > 3o amines.
Phenylamine is toxic compound and only slightly soluble in water.
D.
Chemical properties:
1.
As a base (basicity of amines):
Amines are relatively weak bases. They are stronger bases than water and
ammonia but are far weaker bases than hydroxide ions, alkoxide ions and
carbanions.
A convenient expression for relating basicities is a quantity called the basicity
constant, Kb.
RNH2 + H2O ٛ
RNH3+ + OH-
Kb=
P.4
NH3
Kb
CH3NH2
1.8x10-5
4.4x10-4
CH3CH2NH2
CH3CH2CH2NH2
5.6x10-4
4.7x10-4
When examine the basicity constants of 1o, 2o, 3o amines, the following trend
is shown
Most 1o and 2o amines are stronger bases than ammonia.(Why?)
For example, CH3NH2
: 4.4x10-4
(CH3)2NH
: 5.2x10-4
3o amines are usually stronger base than NH3 but weaker than comparable 2o
amines.(Why?)
For example, (CH3)3N
: 6.3x10-5
Aromatic amines are considerably weaker bases than ammonia.(Why?)
For example, C6H5NHCH3 : 2.5x10-10
2.
Salt formation:
Aliphatic and aromatic amines from stable crystalline salts with mineral acids
(this salt can react with base to regenerate amines).
Phenylamine deterioates on exposure to light (owing to oxidation). It is often
stored in the form of phenylammonium chloride; free phenylamine can be
regenerated by treating the salt with excess aqueous sodium hydroxide.
NH3+Cl-
NH2
+ NaOH(aq)
3.
+
Alkylation of amines:
R'X
RNH2
Reactivity :
CH3I, C2H5I, C3H7I
decreasing
CH3I, CH3Br, CH3Cl
Further alkylation may take place:
C2H5NH + CH3I
NaCl(aq) + H2O(l)
P.5
4.
Acylation of amines:
Common reagents for acylation are :
Acid halides {R'COCl},
acid anhydrides {(R'CO)2O} in cold
For example:
O
R
R"COCl
R
NH
N-C-R"
R'
or (R"CO)2O R'
C2H5NH2
+
CH3COCl
C2H5NHCOCH3
+
HCl
3o amines have no such reaction.
a.
Ethanoylation of phenylamine:
i)
by CH3COCl: same as aliphatic amines
NH2
NHCOCH3
+ CH3COCl
ii)
by (CH3CO)2O:
NH2
NHCOCH3
heat
+
b.
(CH3CO)2O
+ CH3COOH
benzoylation of phenylamine:
O
NH2
O
C Cl
NH
C
excess
+
NaOH
5.
with nitric(III) acid (HNO2):
HONO (HNO2) is a weak unstable acid, it is usually prepared by treating
NaNO2 with aqueous solution of strong acid as HONO is highly unstable
HCl + NaNO2
H2SO4 + NaNO2
HONO + NaCl
2HONO + Na2SO4
P.6
a.
1o aliphatic amine:
RNH2
+ NaNO2
- N2
R+ +
+
[R-N+=N:X-]
aliphatic diazonium salt,
HX
X-
alcohols, alkene, alkyl halides
For example:
CH3CH2CH2CH2NH2 + NaNO2
+
HCl
[CH3CH2CH2CH2-N+=N:]Cl-
CH3CH2CH2CH2+
CH2=CHCH2CH3
+
CH3CH=CHCH3
+
CH3CH2CH2CH2OH
+
CH3CH2CHCH3
OH
b.
+
CH3CH2CH2CH2Cl + CH3CH2CHCH3
OH
1o aryl amines:
Ar-NH2
+ NaNO2
+
2HX
Ar-N2+
arenediazonium salt
(stable if kept below 5oC)
The reaction proceeds by NO+ attack (a weak electrophile), thus for
NO+ to react with an aromatic ring, the ring must have a powerful
activating group such as -OH or -NR2.
c.
Diazonium ions are weak electrophiles; they react with highly reactive
aromatic compounds - with phenols and tertiary aromatic amines - to
yield azo compounds. This electrophilic aromatic substitution is often
called a diazo coupling reaction.
General reaction:
Examples:
P.7
E.
Tests for amines:
Amines are characterised by their basic property and their ability to dissolve in dilute
aqueous acids.
Amine solutions in water are alkaline and have a fishy smell; amine salts are soluble
in water, acidic and give the fishy smell on treatment with an alkali.
F.
Uses of amines and their derivatives:
a.
b.
c.
d.
manufacturing of plastics: e.g. hexane-1,6-diamine is used in the manufacture
of nylon-6,6.
as inhibitors : amines are effective at preventing the deterioration of rubber
through oxidation by atmospheric oxygen.
making dye-stuffs : primary aromatic amines are used to make azo-dyes.
As azo-compounds are highly coloured, they are widely used in dyeing
industry. Some examples of organic dyes are shown below. A recognition of
the azo group, -N=N-, is all that is required.
making
medicines
:
e.g.
chlorpheniramine,
chlorpromazine
and
P.8
acetaminophen.
Chlorpheniramine - an antihistamine that helps to relief allergic disorders due
to cold (runny nose, watery eyes), hay fever, itchy skin, insect bites and stings,
etc. It is present in some over-the-counter drugs such as Coltalin, Coricidin,
Dristan and Piriton.
Chlorpromazine - a tranquillizer that sedates without inducing sleep. It is used
to relieve anxiety, excitement, restlessness or even mental disorders.
Acetaminophen (also known as paracetamol, or p-acetaminophenol) - an
analgesic that relieves pains such as headaches. It is believed to be less
corrosive to the stomach and is an alternative to aspirin.