Download A2 Module 2814: Chains, Rings and Spectroscopy

RPA5 14-15 nitrogen compounds p.1
A2 Module F324: Rings, Polymers and Analysis
RPA 5: Organic Nitrogen Compounds
Primary amines
A primary (1°) amine is one in which a single alkyl (or aryl) group is attached to the nitrogen, e.g.
RNH2. A secondary (2°) amine has two alkyl groups, and a tertiary (3°) one three, directly attached
to the nitrogen:
primary
amine
secondary
amine
NH2
NH
tertiary
amine
N
Amines as bases
Amines have a lone pair of electrons on the N atom, and so can act as proton acceptors by
donating that lone pair of electrons to an H+. Ethylamine is a slightly stronger base than ammonia,
while phenylamine is considerably weaker:
Basic character:
ethylamine > ammonia >
phenylamine
Both ethylamine and phenylamine react readily with strong acids to form ionic salts. These salts,
like ammonium salts, are fully soluble in water, since they are ionic:
 C2H5NH3+ + Cl – (ethylammonium chloride)
 C6H5NH3+ + Cl – (phenylammonium chloride)
C2H5NH2 + HCl
C6H5NH2 + HCl
Synthesis of Amines
Aliphatic (i.e. non-aromatic) amines can be prepared by reacting haloalkanes with excess ammonia
dissolved in ethanol. The mechanism is nucleophilic substitution:
Br
+
NH2
2 NH3
+
NH4Br
Phenylamine is prepared by reducing nitrobenzene with tin and concentrated hydrochloric acid.
NO2
+
NH2
6 [H]
Sn / c.HCl
+
2 H2O
Starting from benzene it would be necessary to react with nitrating mixture first, to make the
nitrobenzene.
RPA5 14-15 nitrogen compounds p.2
Azo Dyes
Azo dyes are highly coloured compounds that can be affixed to fibres such as cotton to dye
clothing. The synthesis has two stages:
(i) Phenylamine and nitrous acid
Hydrochloric acid and sodium nitrite are used to make Nitrous acid, HNO2 (which is unstable):
NaNO2 + HCl  NaCl + HNO2
An aromatic amine, such as phenylamine, can be reacted with the nitrous acid at a temperature
below 10°C to give a diazonium ion:
N
NH2
+
N
HNO2
+
H+
+
2 H2O
The diazonium ion is unstable (hence the low temperature), so is used in solution, immediately
after it has been prepared.
(ii) Reaction with Phenol
The cold diazonium ion in solution is added drop-wise to a solution of phenol in aqueous sodium
hydroxide, producing a yellow/orange precipitate of an azo-dye:
OH
N
N
OH
N
+
N
+
H+
With other phenols, different colours (typically orange or red) are produced.
Amino-acids and proteins
There are about twenty amino-acids which are found in nature, and which combine to make up
the proteins found in living organisms. They are all α-amino acids, i.e. the NH2 and the COOH
groups are attached to the same carbon atom. Their general formula is RCH(NH 2)COOH, where R
represents a side-chain (not just an alkyl group). Three examples are given below:
RPA5 14-15 nitrogen compounds p.3
SH
H2C
CH3
H
H2N
OH
OH
OH
H2N
H
H2N
H
H
O
O
O
glycine
alanine
cysteine
All except glycine are optically active, and normally only one of the enantiomers is found in nature.
If the side-chain has another functional group, like cysteine above, it may be possible to cross-link
a protein chain, tying the molecule up into a specific three-dimensional shape.
An amino acid reacts chemically as both an amine and an acid. Thus it can protonate itself (acid
group donates H+ to amine group) to form a zwitterion, e.g.:
H
O
H3N
H
O
The pH at which this occurs is called the isoelectric point. The nature of the R group will affect the
exact isoelectric point of different amino-acids.
As the pH changes, H+ ions will be added or removed from the amino acid accordingly. For
example, at low pH, where there is an abundance of H+ ions, the structure of the amino-acid will
be:
H
OH
H3N
H
O
At high pH, where available H+ ions are being removed by OH- ions, the structure will be:
H
O
H2N
H
O
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Peptides
When two amino acids react, they form an amide by linking the NH2 of one to the COOH of the
other, with loss of water. This is known as a peptide link:
O
OH
+
H2N
OH
H2N
H
N
+
H2N
O
H2O
OH
O
O
peptide / amide link
The loss of water means that this can be termed a condensation reaction (a reaction in which a
small molecule, such as H2O or HCl is lost), and if several amino acids are joined to form a
polypeptide, this is an example of condensation polymerisation. If more than about forty amino
acid units are involved, the polymer is classed as a protein. Natural peptides and proteins can use
any of the twenty natural amino acids, combined together in a very specific order. This produces a
vast range of molecules, including fibres like those in skin, hair and muscle, and globular proteins,
among which are enzymes and protein hormones.
Peptide bonds (in proteins and polypeptides) can be hydrolysed by the action of heat (under reflux
works best) and aqueous acid or alkali. The exact products will depend on whether acid or alkali is
used:
acid hydrolysis
H
N
H2NH2C
CH2COOH
+ H2O + 2 H+
H3N
+
dilute acid
O
OH
H3NH2C
water
CH2COOH
O
alkaline hydrolysis
H
N
H2NH2C
CH2COOH
O
+
2
OH-
water
dilute alkali
O
H2NH2C
H2N
+
O
+ H2O
CH2COO
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Chiral molecules in nature and in pharmaceuticals
The enzymes in living cells are proteins built from only one enantiomer of each type of amino acid
(called the L-series). The mirror-image molecules would not fit into the correct three-dimensional
shape. Therefore if organisms are fed on a mixture of enantiomers, they can only absorb the ones
from the correct series. It follows that chiral molecules synthesised in cells (proteins,
carbohydrates etc) normally consist of only one enantiomer.
Pharmaceuticals (medical drugs) are synthetic chemicals which alter the way in which an organism
functions. Frequently they work by interacting with chiral molecules in the organism, and many
drugs are themselves chiral. This means that one enantiomer of the drug is likely to be much more
effective than its mirror image. If we can manufacture a sample of the drug which contains only
one optical isomer there are potential advantages:



a much smaller dose is needed (only half the amount, compared to a racemic mixture)
fewer side effects (as the unwanted enantiomer is not present)
improved pharmacological activity.
However, a drawback may be that the procedure for synthesizing only one enantiomer is much
more costly for the pharmaceutical company.
Chemists have responded to the need for one optical isomer by various methods:



using enzymes or bacteria which promote stereoselectivity (the formation of one
stereoisomer only)
using chemical chiral synthesis or chiral catalysts (where the reagents and/or catalyst are
chiral, promoting the formation of the desired enantiomer)
using natural chiral molecules, such as L-amino acids or sugars, as starting materials