AMINES

LEARNING OBJECTIVES:
Preparation:
 From halides – Limitations

 Reductive amination

 Reduction of Nitro compounds and Nitriles

 Gabriel Synthesis

 Hofmann Rearrangements

 Curtius & Losen Rearrangements

Reactions:
 Salt formation & Oxidation

 N- alkylation- Limitations

 Hofmann Elimination & Degradations

 Conversion to Amides, sulfanomides –

(Hinsberg test)
 Reactions with Nitrous acid

 Mannich Reaction
 From halides - Limitations
1. Alkylation of NH3:
The alkylation agent is an alkyl halide.

1◦ amines will undergo further alkylation to form 2◦ amines and so on. The
multiple alkylations can be minimised by using a large excess of NH3.

Reaction mechanism:

*The alkyl halide has to be a

limiting reagent to stop step 3
from occurring.
2. Alkylation of azide ion and reduction
• Better way to convert alkyl halide to 1◦ amine

with no further alkylation.

• Convert alkyl halide to alkyl azide.
 Reductive Amination of aldehydes and
ketones

•Aldehydes and ketones can be

converted to amines through
catalytic reduction in the
presence of ammonia or an
amine as summarised:

•The reducing agents employed include hydrogen and a catalyst

(such as nickel) or
•NaBH3CN or LiBH3CN (sodium or lithium cyanoborohydride).
General Reaction Mechanism:

•When ammonia or a 1◦ amine is used, there are two possible pathways to

the product via an amino alcohol that is similar to a hemiacetal and is called
a hemiaminal or via an imine .
•When secondary amines are used, an imine cannot form, and therefore, the
pathway is through the hemiaminal or through an iminium ion.
Reduction of Nitro compounds & Nitriles
Reduction of nitriles:

Reduction of oximes:

Reduction of nitrobenzene :
 Gabriel Synthesis
 Potassium phthalimide can also be used to prepare 1◦ amines by a
method known as the Gabriel synthesis.
 This synthesis also avoids the complications of multiple
alkylations that occur when alkyl halides are treated with NH3.

*Reaction occurs under reflux.

Syntheses of amines using the Gabriel synthesis are restricted to the use of
methyl, primary, and secondary alkyl halides.
Reaction mechanism:

•Phthalimide can be converted to

potassium phthalimide by
potassium hydroxide. The
phthalimide anion is a strong
nucleophile and it reacts with an
alkyl halide by an SN2
mechanism to give an N-
alkylphthalimide.
•The N-alkylphthalimide can be
hydrolyzed with aqueous acid or
base, but the hydrolysis is often
difficult.
•It is often more convenient to
treat the N-alkylphthalimide
with hydrazine (NH2NH2) in
refluxing ethanol to give a
primary amine and phthalazine-1,4-
dione.
 Hofmann Rearrangement
 Amides with no substituent on the nitrogen
react with solutions of bromine or chlorine in
sodium hydroxide to yield amines through a
reaction known as the Hofmann rearrangement or
Hofmann degradation:
Reaction mechanism:
 Lossen Rearrangement:
This is the conversion of a hydroxamic acid to an isocyanate.
The isocyanate is then reacted with H2O to produce an
amine.
 Curtius Rearrangement (Reduction of Azyl
Azide):
Reaction mechanism:
 Salt Formation & Oxidation
 Oxidation of amines
Amines are easily oxidised in air. Common oxidising agents are
H2O2 and metachloroperoxy benzoic acid (MCPBA). Primary and
secondary aliphatic amines are subject to oxidation, although in
most instances useful products are not obtained.
Salt Formation:
Amine acts as a bronsted base by accepting a
proton.
 N- Alkylation - Limitation
N- alkylation is generally limited to the synthesis
of 3◦ amines and
Hofmann Elimination & Degradations
 Hofmann elimination is also known as
exhaustive methylation. It involves the
conversion of an amine with β-hydrogen to an
alkene.
Reaction Mechanism:
 Conversion to amides, sulfanomides
(Hinsburg Test)
 Conversion to amides:

*1◦ and 2◦ amines react with acyl chlorides to form amides. 3◦ do not
undergo same reaction because there is no replacement hydrogen.
Reaction Mechanism:
 Hinsberg Test(Sulfanomides)

 Sulfonamide formation is the basis for a

chemical test, called the Hinsberg test, that can
be used to demonstrate whether an amine is
primary, secondary, or tertiary.
3◦ amines do not have a replacement hydrogen, so no sulfanomide conversion takes
place.
 Reactions with Nitrous acid
Reaction of 1◦ amines with nitrous acid:
•Primary aliphatic amines react with nitrous acid through a
reaction called diazotization to yield highly unstable aliphatic
diazonium salts.

Reaction of 1◦ arylamines with nitrous acid:

*Primary arylamines react with nitrous acid to give arenediazonium salts. Even though
arenediazonium salts are unstable, they are still far more stable than aliphatic
diazonium salts
 Diazotisation Reaction Mechanism:

Reactions of 2◦ amines with nitrous acid:

Secondary amines—both aryl and alkyl—react with nitrous acid to yield N-nitrosoamines.
N-Nitrosoamines usually separate from the reaction mixture as oily yellow liquids.
 Although N-nitrosoammonium compounds are stable at low temperatures,
at higher temperatures and in aqueous acid they decompose to produce
aldehydes or ketones.

Reactions of 3◦ amines with nitrous acid:

When a tertiary aliphatic amine is mixed with nitrous acid, an equilibrium is

established among the tertiary amine, its salt, and an N-nitrosoammonium
compound.

Tertiary arylamines react with nitrous acid to form C-nitroso aromatic compounds.
 Mannich Reaction
 Compounds capable of forming an enol react
with imines from formaldehyde and a 1◦ or 2◦
amine to yield β-aminoalkyl carbonyl
compounds called Mannich bases.
 References:
Organic Chemistry, Authors T.W Graham Solomons & Craig B Fryle
http://exxamm.com
https://www.cliffnotes.com
https://www.chem.ucalgary.com
https://minfographic.files.wordpress.com
https://www.brainyresort.com
https://www.chemistryscore.com
https://www.study.com – Diazonium salts
https://www.name-reaction.com