23 Nitrogen compounds and synthesis

Question/key idea

Primary amines
A primary (1°) amine is one in which a single alkyl (or aryl) group is attached to the nitrogen, e.g. RNH 2 . A
secondary (2°) amine has two alkyl groups, and a tertiary (3°) one three, directly attached to the nitrogen:

primary secondary tertiary

amine amine amine

NH2 NH 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:

C 2 H 5 NH 2 + HCl → C 2 H 5 NH 3 + + Cl – (ethylammonium chloride)

C 6 H 5 NH 2 + HCl → C 6 H 5 NH 3 + + Cl – (phenylammonium chloride)

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 Question/key idea
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

The product of the reaction (the amine) is also a nucleophile as a result of the lone pair of the electrons on
the nitrogen atom. This means that a secondary amine can be produced by the reaction of a second
molecule of the haloalkane with the primary amine.

CH 3 CH 2 CH 2 NH 2 + CH 3 CH 2 CH 2 Br (CH 3 CH 2 CH 2 ) 2 NH + HBr
Secondary amine
There are then two more possible steps in this reaction:

(CH 3 CH 2 CH 2 ) 2 NH + CH 3 CH 2 CH 2 Br (CH 3 CH 2 CH 2 ) 3 N + HBr

Tertiary amine

(CH 3 CH 2 CH 2 ) 3 N + CH 3 CH 2 CH 2 Br (CH 3 CH 2 CH 2 ) 4 N+ Br-

Quaternary amine salt

The presence of an excess of the haloalkane will encourage the further steps to take place whilst an excess
of ammonia will result in the primary amine predominating.

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 Question/key idea
Phenylamine is prepared by reducing nitrobenzene with tin and concentrated hydrochloric acid.

NO2
NH2
Sn / c.HCl
+ 6 [H] + 2 H2O

Starting from benzene it would be necessary to react with nitrating mixture first, to make the nitrobenzene.

Nitriles
Nitriles contain the C≡N functional group and can be synthesised in two ways. The first involves the addition
of cyanide ions, CN-,to carbonyl compounds (aldehydes/ketones) using acidified potassium cyanide:
OH
O KCN
+ HCN
dil. H2SO4
NC
This occurs via a nucleophilic addition mechanism (see ‘carbonyls’ topic for more information). The second
method addition of cyanide ions to haloalkanes – the haloalkane is heated under reflux with a mixture of
potassium or sodium cyanide in an ethanol solvent.

CN
Br KCN
+ HCN + HBr
reflux, ethanol

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 Question/key idea
This reaction occurs via a nucleophilic substitution mechanism:

δ
Br C

δ + Br

C N

Both these reactions are excellent ways of extending the carbon chain (for other ways of extending the
chain, see Friedel-Crafts acylation and alkylation in the ‘Arenes’ topic).

Reduction of nitriles

Nitriles can be used to synthesise amines via reduction reactions using H 2 over a nickel catalyst (or lithium
aluminium hydride, LiAlH 4 , but not NaBH 4 ).

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 Question/key idea

Hydrolysis of nitriles

Nitriles can also be hydrolysed under acidic or alkaline conditions under reflux to generate a carboxylic acid
or carboxylate salt respectively:

Acid hydrolysis

N
O OH
C reflux
+ 2H2O + H+ + NH4+
dilute HCl

Alkaline hydrolysis

N
O O
C reflux
+ H2O + OH- + NH3
dilute NaOH

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 Question/key idea

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 NH 2 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:

SH
H CH3 H2C

OH OH OH
H2N H2N H2N
H 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

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 Question/key idea

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
Peptides
When two amino acids react, they form an amide by linking the NH 2 of one to the COOH of the other, with
loss of water. This is also known as a peptide link:

O
OH OH H
H2N + H2N N + H2O
H2N OH
O O
O
peptide / amide link

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 Question/key idea

The loss of water means that this can be termed a condensation reaction (a reaction in which a small
molecule, such as H 2 O 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.

Acid hydrolysis

H
H2NH2C N H3NH2C OH
CH2COOH + H2O + 2 H+ reflux H3N
+ CH2COOH
dilute HCl
O O

Alkaline hydrolysis

H
H2NH2C N H2NH2C O
CH2COOH - reflux H2N
+ 2 OH + CH2COO
dilute NaOH
O O
+ H2O

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