Organic Nitrogen Compounds

Learning Objectives
Describe with equations and the required reagents and conditions , the formation
of ethylamine (by nitrile reduction) and phenylamine (by reduction of
nitrobenzene)
Describe basicity of amine relative to the proton accepting tendency of the lone
pair of nitrogen
Explain relative basicity of ammonia, ethylamine and phenylamine
Describe reactions of phenylamine with aqueous bromine and nitrous acid to
produce diazonium salt and phenol. Write equations , reagents and conditions
Describe the coupling reaction of benzene diazonium chloride and phenol and of
similar reaction to form dye stuff
Explain stability of diazonium salt and importance in the dye industry
Describe formation of amides from reaction between alkylamine and acyl
chlorides
Describe amide hydrolysis on treatment with aqueous alkali or acid
Describe the acid base properties of amino acids and the formation of zwitterions
Describe formation of peptide bond between amino acids and hence formation of
protein
Describe hydrolysis of protein

STRUCTURE & CLASSIFICATION
Structure Amines contain the NH
2
group

Classification




primary (1) amines secondary (2) amines






tertiary (3) amines quarternary (4) ammonium salts


Aliphatic methylamine, ethylamine, dimethylamine
Aromatic NH
2
group is attached directly to the benzene ring (phenylamine)
R N:
H
H
R N:
R
H
R N:
R
R
R
+
R N R
R
NOMENCLATURE
Nomenclature

C
2
H
5
NH
2
ethylamine


(CH
3
)
2
NH dimethylamine


(CH
3
)
3
N trimethylamine


C
6
H
5
NH
2
phenylamine (aniline)
PHYSICAL PROPERTIES
The LONE PAIR on the nitrogen atom in 1, 2 and 3 amines makes them ...

LEWIS BASES - can be lone pair donors



BRNSTED-LOWRY BASES - can be proton acceptors

RNH
2
+ H
+
> RNH
3
+



NUCLEOPHILES - provide a lone pair to attack an electron deficient centre
PHYSICAL PROPERTIES
Boiling point Boiling points increase with molecular mass

Amines have higher boiling
points than corresponding
alkanes because of their
intermolecular hydrogen bonding

Quarternary ammonium
salts are ionic and exist as salts


Solubility Lower mass compounds are
soluble in water due to hydrogen
bonding with the solvent.

Solubility decreases as the
molecules get heavier.

Soluble in organic solvents.
BASIC PROPERTIES
Bases The lone pair on the nitrogen atom makes amines basic;

RNH
2
+ H
+
> RNH
3
+
a proton acceptor



Strength depends on the availability of the lone pair and its ability to pick up protons
the greater the electron density on the N, the better it can pick up protons
this is affected by the groups attached to the nitrogen


electron withdrawing substituents (benzene rings)
decrease basicity as the electron density on N is
lowered and the lone pair is less effective



electron releasing substituents (CH
3
groups)
increase basicity as the electron density is
increased and the lone pair is more effective
CH
3
N:
H
H
C
6
H
5
N:
H
H
BASIC PROPERTIES
Measurement the strength of a weak base is given by its pK
b
value
the smaller the pK
b
the stronger the base

the pK
a
value can also be used;
it is worked out by applying pK
a
+ pK
b
= 14
the smaller the pK
b
, the larger the pK
a
.


Compound Formula pK
b
Comments
ammonia NH
3
4.76
methylamine CH
3
NH
2
3.36 methyl group is electron releasing
phenylamine C
6
H
5
NH
2
9.38 electrons delocalised into the ring


strongest base methylamine > ammonia > phenylamine weakest base
smallest pK
b
largest pK
b
Effect of substituent groups on base strength:
NH
2
+ H
2
O
NH
3
+ OH
G
G
Electron donating groups will stabilize the resulting ion,
making the compound a stronger base.
Electron withdrawing groups destabilize the resulting ion,
making the compound a weaker base.
CHEMICAL REACTIONS - WEAK BASES
Amines which dissolve in water produce weak alkaline solutions

CH
3
NH
2
(g) + H
2
O(l) CH
3
NH
3
+
(aq) + OH(aq)

Amines react with acids to produce salts

C
6
H
5
NH
2
(l) + HCl(aq) > C
6
H
5
NH
3
+
Cl(aq)
phenylammonium chloride

This reaction allows one to dissolve an amine in water as its salt

Addition of aqueous sodium hydroxide liberates the free amine
from its salt

C
6
H
5
NH
3
+
Cl(aq) + NaOH(aq) > C
6
H
5
NH
2
(l) + NaCl(aq) + H
2
O
almost any nitrogen-containing compound can
be reduced to an amine, including:
azides
nitriles
nitro-substituted benzene derivatives
amides
Preparation of Amines by Reduction
S
N
2 reaction

Synthesis of Amines via Nitriles
CH
3
CH
2
CH
2
CH
2
Br
Halogenoalkane
NaCN
CH
3
CH
2
CH
2
CH
2
CH
2
NH
2

Primary alkyl amine

CH
3
CH
2
CH
2
CH
2
CN
Nitrile
H
2
(100 atm), Ni
followed by
reduction, gives

S
N
2 reaction, followed by reduction, gives alkylamine
Synthesis of Amines via Nitriles
CH
3
CH
2
CH
2
CH
2
Br
NaCN
CH
3
CH
2
CH
2
CH
2
CH
2
NH
2
CH
3
CH
2
CH
2
CH
2
CN

lithium aluminum hydride
in dry ether


Reduction of nitrile may also
be brought about by LiAlH
4
in
dry ether.
Amines
Amines are essentially molecules of ammonia
One or more of the hydrogen atoms have been
replaced with an alkyl group
H
N
H
H
Amines

Replacing one hydrogen atom in NH
3
with an alkyl
group gives primary amine, replacing 2 H atoms
gives secondary amine
R NH
2
Primary amine
R
NH
R'
Secondary amine
R
N
R'
R''
Tertiary amine
R
N
+
R''
R'''
R'
Quaternary ammonium salt
Reduction of nitrobenzene to give phenylamine

NO
2
+ 6[H]
i) conc. HCl/Sn
ii) NaOH(aq)
NH
2
+ H
2
O
Conditions are reflux, this is important in the production of
compounds called azo-dyes

The NaOH is essential to liberate the phenylamine from the salt
C
6
H
5
NH
3
+
Cl formed during the reaction with HCl
Reactions of amines
As bases
As nucleophiles
With nitrous acid
R NH
2
as bases
RNH
3
+
Cl
-
e.g. HCl
as
nucleophiles
RNHR'
Aliphatic
Aromatic
ROH
with HNO
2
RN
2
+
Reactivity of Amines
Is due to
The availability of the lone pair of electrons
on the nitrogen
Though Nitrogen is less electronegative than
oxygen
The lone pair is more available on nitrogen in
amines than it is on oxygen in alcohols
Amines are
fairly good bases (donating a lone pair to an
H
+
atom)
Excellent ligands (in transition metal
chemistry)
Good nucleophiles able to attack the
positive end of a polarised bond
Amines as bases

Bases are proton acceptors.
Amines accept protons, by donating a lone pair
of electrons to the hydrogen atom to form a
dative bond.
Ammonia and bases can do this with any
suitable acid to give a salt.
H
3
N H Cl NH
4
+
Cl
-
Amines an bases
An alkyl group is slightly electron donating
This is because the electron pairs around the
carbon repel the electron pair in the bond
between the carbon and the functional group
C X
Replacing a hydrogen in ammonia has the
following effect
Causes increased electron donation in the C-
N bond
Becomes polar, and nitrogen becomes
slightly negative
Lone pair on nitrogen becomes more
available
Can be donated to a proton more easily
1 amines are more basic than ammonia
What about secondary and tertiary?
Following the same argument, 2 amines will
be more basic still, as the lone pair will be
even more available, due to greater electron
donating effect of alkyl groups.
In phenylamine, the lone pair becomes
involved in the aromaticity, so it is less basic.
The lone pair as part of the rings delocalised
system, is less readily donated to a proton.
A tertiary amine will be more basic still.
Reaction of amines with acids

A standard Acid Base reaction
CH
3
CH
2
NH
2
+ HCl CH
3
CH
2
NH
3
+
+ Cl
-
Diazonium Salts
Diazonium: there are 2 nitrogen atoms joined
together in the positive ion.
In French, nitrogen is still called by its old name
azote which means unable to support life.
N N Cl
diazonium chloride
Diazonium Salts
Notice the triple bond between the nitrogen
atoms
The positive charge is on the nitrogen that is
attached to the benzene ring
N N Cl
diazonium chloride


Why are diazonium salts important? They look pretty
weird!

They are essential in the dye industry.

A Diazonium salt is produced then reacted with a
phenol.

If the correct phenol is used, almost any colour can
be produced.

you need to know this reaction with the structures
of the molecules. (The way it was taught in the class
with structures drawn on the board)
Formation of the Diazonium salt

Formed by reacting phenylamine with nitrous
acid.

Sodium nitrite and hydrochloric acid are
used to get nitrous acid

These reagents form in situ nitrous acid HNO
2

because nitrous acid is unstable.
Formation of the Diazonium salt

The Diazonium salt is unstable above 5C, so the reaction is
normally carried out in ice.

An aliphatic Diazonium salt is very unstable, and
decomposes readily. So only aromatics are used.

The lone pairs present on the N in the salt get delocalised
on the benzene ring, making it more stable. This is due to
overlap of p-orbitals in the diazo group with the pi-system in
the ring.

So phenylamine would give benzene diazonium chloride.
Formation of the Diazonium salt

N N Cl
NH
2
+ HONO(aq) + HCl(aq)
+ 2H
2
O(l)
Formation of the Diazonium salt
The conditions are 5C and remember the
HNO
2
(nitrous acid) is prepared in situ by
reacting sodium nitrite with hydrochloric
acid.
The diazonium salt decomposes to give
phenol, N
2
and HCl at a temperature higher
than 5C.
Reactions of aromatic diazonium salts

N N Cl
hydrolysis
room temperature
OH
Coupling reaction
5 degrees Celcius
with phenol
N N
OH
Hydrolysis

The following occurs if a solution of a diazonium
salt is warmed up or temperature is raised
above 5C
C
6
H
5
N
2
+
Cl
-
(aq) + H
2
O(l) C
6
H
5
OH + N
2
(g) + HCl(aq)
Coupling reactions

The mechanism is for
interest only, you do
Not need to know it.
N N
O H
N
N
OH
H
H
O
H
N
N
OH
General method for synthesis of azo dyes

Add a cold aqueous solution of sodium nitrite
slowly (with cooling and stirring) to a cold solution
of the amine compound in excess hydrochloric acid
The temperature must not rise above 5C.
This solution (still cold) should then be added
slowly with stirring to a solution of the coupling
compound.
The temperature should be kept below 5C the
whole time.
Amino Acids

These are bi-functional compounds. They
contain 2 functions groups:
A primary amine (in most cases) NH
2
The carboxylic acid group COOH
An amino acid must contain both of these
functional groups.
Amino Acids

The simplest amino acid is glycine.
C C N
H
H
H
H
O
O H
Amino Acids
All the amino acids (the twenty vitally important
ones biologically) are 2-amino acids.
The amine and acid groups are both attached to the
same carbon.
All can be named systematically, but in most cases
the old names are used.
Alanine is also known as 2-aminopropanoic acid,
but alanine is the acceptable name to use.
Alanine
C C N
H
H
H
O
O H
C
H
H H
General Formula
C C N
H
H
O
O H
H
R
Physical Properties
White solids
With relatively high melting points glycine
(the simplest) has a melting point of 235C.
Normally readily soluble in water
Almost totally insoluble in non-polar solvents
Acid Base Properties
They are very largely ionic compounds.
The carboxyl group can lose a proton
The amine group can gain a proton
The result is a ZWITTERION. From the
German for hermaphrodite, hybrid or
mongrel!
Zwitterions
Glycine mainly exists as
H
3
N
+
CH
2
COO
-
Zwitterions
The strong attractions in the crystal cause the
high melting point
In aqueous solution depending on the pH,
they form either the neutral form,
or the carboxylate will lose a proton,
or the amino group will gain a proton.
Zwitterions
C C N
H
H
O
O H
H
H
+ H
+
in strong acid
C C
O
O H
H
H
H
3
N
+
-H
+
in strong alkali
C C N
H
H
O
H
H
O
-
Isoelectric Point
For each amino acid there is a definite pH
the isoelectric point at which the acid and
basic ionisations are equal.
The molecule is effectively neutral it carries
equal and opposite charges
This is rarely near pH 7 because the molecule
ionisation tendencies are affected by the
other groups in the molecule.
Isoelectric Point
Aspartic acid which has 2 COOH groups
is acidic in aqueous solution.
Lysine with more amino than carboxyl groups
is alkaline.
Due to this dual functionality, they are able
to act as buffer solutions (able to maintain a
reasonably constant pH with small additions
of acid or alkali).
They also have optical activity.
How amino acids join together

Amino acids join together in specific ways to form
specific proteins.
One amino acid can join to another to form a
dipeptide.
H
C COOH
R'
H
2
N +
H
C COOH H
2
N
R''
H
2
N C
H
R'
C
O
N
H
C
H
R''
COOH + H
2
O
How amino acids join together

This kind of bond between 2 amino acids is
called a peptide bond or a peptide link.
C
O
N
H
How amino acids join together

N C
H
H
H
R'
C
O
OH
N C
H
H
H
R'
C
O
OH
+
N C
H
R'
C
O
OH
C
R'
H
H
H
C N
O
H
How amino acids join together
Two joined amino acids form a dipeptide
Three join to form a tripeptide
Many join to form a polypeptide
At some point a polypeptide becomes a
protein. This can be put at 40 amino acids.
Acid Hydrolysis of proteins

Proteins and peptides can be hydrolysed with
hot concentrated (6 mol dm-3) HCl.
The protein is refluxed for about 24 hours.
This hydrolysis is the exact reverse of the
formation of the peptide bond.
A molecule of water is in effect added across
the linkage to regenerate the original amino
acid and carboxyl groups.