Preparation of amines
Amines are prepared by aminolysis of alkyl halides, and also reductive
amination (reduction in the presence of ammonia) of aldehydes and ketones
(see Section 5.7.19). They are obtained conveniently from Hofmann
rearrangement of amides.
Aminolysis of halides Amines are prepared from primary alkyl halides by
treatment with an aqueous or alcoholic solution of ammonia. This reaction
is known as aminolysis; it is not product specific, and produces more than
one class of amine. Therefore, it is difficult to prepare pure primary amines
using this method. The primary amines can be separated by distillation from
these by-products, but the yield is poor. However, this can be avoided using
a large excess of ammonia.
X
R
R C Y
O
H 2 O or
+ NH 3
RCH 2 NH 2
1 o Amine
Excess
Y = H or R
Aldehyde or ketone
Alcohol
NH 3
NaBH 3 CN or H 2 /Pd-C
Hofmann rearrangement In this reaction, amines (with one less carbon)
are prepared from amides by the treatment of halides (Br 2 or Cl 2 ) in aqueous
sodium or potassium hydroxide (NaOH or KOH).
C
H 3 C
CH 3
C
H 3
C
O
NH 2
C
H 3 C
CH 3
CH 3
NH 2
Br 2 , NaOH
H 2 O
tert-Butylamide
tert-Butylamine
Catalytic hydrogenation or LiAlH 4 reduction of amides, azides or nitriles
produces amines (see Section 5.7.23).
R C NH 2
O
R C N
RCH 2 N N N
RCH 2 NH 2
1 o Amide
1 o Amine
Nitrile
H 2 /Pd-C or
H 2 /Pd-C or
+
_
i. LiAlH 4 ii. H 2 O
2 H 2 /Pd-C or
Alkyl azide
i. LiAlH 4 ii. H 2 O
i. LiAlH 4 ii. H 2 O
Reactions of amines
Primary (RNH 2 ) and secondary (R 2 NH) amines undergo nucleophilic acyl
substitution with acid chlorides and anhydrides in pyridine or Et 3 N to give
2
and 3
amides (see Section 5.5.5). Primary amines (RNH 2 ) react with
84
CH4 ORGANIC FUNCTIONAL GROUPS
Amines are prepared by aminolysis of alkyl halides, and also reductive
amination (reduction in the presence of ammonia) of aldehydes and ketones
(see Section 5.7.19). They are obtained conveniently from Hofmann
rearrangement of amides.
Aminolysis of halides Amines are prepared from primary alkyl halides by
treatment with an aqueous or alcoholic solution of ammonia. This reaction
is known as aminolysis; it is not product specific, and produces more than
one class of amine. Therefore, it is difficult to prepare pure primary amines
using this method. The primary amines can be separated by distillation from
these by-products, but the yield is poor. However, this can be avoided using
a large excess of ammonia.
X
R
R C Y
O
H 2 O or
+ NH 3
RCH 2 NH 2
1 o Amine
Excess
Y = H or R
Aldehyde or ketone
Alcohol
NH 3
NaBH 3 CN or H 2 /Pd-C
Hofmann rearrangement In this reaction, amines (with one less carbon)
are prepared from amides by the treatment of halides (Br 2 or Cl 2 ) in aqueous
sodium or potassium hydroxide (NaOH or KOH).
C
H 3 C
CH 3
C
H 3
C
O
NH 2
C
H 3 C
CH 3
CH 3
NH 2
Br 2 , NaOH
H 2 O
tert-Butylamide
tert-Butylamine
Catalytic hydrogenation or LiAlH 4 reduction of amides, azides or nitriles
produces amines (see Section 5.7.23).
R C NH 2
O
R C N
RCH 2 N N N
RCH 2 NH 2
1 o Amide
1 o Amine
Nitrile
H 2 /Pd-C or
H 2 /Pd-C or
+
_
i. LiAlH 4 ii. H 2 O
2 H 2 /Pd-C or
Alkyl azide
i. LiAlH 4 ii. H 2 O
i. LiAlH 4 ii. H 2 O
Reactions of amines
Primary (RNH 2 ) and secondary (R 2 NH) amines undergo nucleophilic acyl
substitution with acid chlorides and anhydrides in pyridine or Et 3 N to give
2
and 3
amides (see Section 5.5.5). Primary amines (RNH 2 ) react with
84
CH4 ORGANIC FUNCTIONAL GROUPS