Chemistry: CIX Organic Chemistry -III

Lesson: Nitrogen Containing

Functional Groups
Unit-1: Amines-Preparation and Properties
Lesson Developer: Dr. S.P Bhutani
College/Dept: Formerly Associate Professor
Department of Chemistry
Rajdhani College, University of Delhi
Lesson Editor:Dr.N.K Gautam
Advisor (Sciences)
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Contents:
1.Amines Introduction
2. Classification Of Amines
3.Nomenclature Of Amines
A. Common Names
B. Iupac Names
4.Physical Properties Of Amines
5. Basicity Of Amines
A. Pkb And Pka Values
B. Effects On Amine Basicity
C. Basicity Of Aromatic Amines
6. Preparation Of Amines
A.Direct Alkylation Of Ammonia-Ammolysis Of Halides
B. Indirect AlkylationThe Gabriel Synthesis
C. Reduction Of Nitro Compounds
D. Reduction Of Amides, Oximes And Nitriles
(I) Reduction Of Nitriles
(Ii) Reduction Of Oximes
(Iii) Reduction Of Amides
E. Reductive Amination
F. Preparation Of Amines Through The Hofmann, Curtius And Schmidt
Rearrangements
(I) The Hofmann Rearrangement
(Ii) Curtius Rearrangement
(Iii) Schmidt Reaction
7. References

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 1.AMINES - INTRODUCTION
Amines are compounds in which one or more alkyl or aryl groups are attached to
nitrogen. They may be considered to be the organic derivatives of ammonia

Aromatic and heterocyclic amines are generally known by historical names. Phenylamine
is called aniline and its derivatives are named as derivatives of aniline.

The names and structures of some common heterocyclic amines are shown below:

Amines serve many functions in living organisms. Because of their high degree of
biological activity, many amines are used as drugs and medicines. The structures and uses
of some important biologically active amines are given below:

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 The alkaloids are an important group of biologically active amines. The chemistry of
some typical alkaloids has been discussed in chapter 5 of this book.

2. CLASSIFICATION OF AMINES
Amines are classified as primary (1), secondary (2) or tertiary (3) corresponding to
one, two or three alkyl groups attached to nitrogen. In secondary and tertiary amines, the
alkyl or aryl groups may be the same or different.

Quaternary ammonium salts have four alkyl or aryl groups attached to nitrogen atom.
Thus, the nitrogen atom bears a positive charge. The four groups joined to nitrogen in the
ammonium ion may be same or different. For example,

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 3.NOMENCLATURE OF AMINES
A. Common Names
Simple amines are usually referred to by their common names. In common
nomenclature, most primary aliphatic amines are named by using the alkyl group or groups
attached to nitrogen followed by the suffix-amine. The names are written as one word.
Some examples are,

Primary Amines

Secondary and tertiary aliphatic amines are named in a similar way. We either designate
the alkyl/aryl groups individually if they are different or use prefixes dior tri- if they are
same. Some examples are given below:

Secondary Amines

Tertiary Amines

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 Aromatic amines are named as derivatives of the simplest aromatic amine, aniline.
Amino toluene is named as toluidine.

When it is necessary to name a compound containing the amino group as a derivative of

some other function, the prefix -amino is used. For example,

B. IUPAC Names

Under the IUPAC nomenclature, amines are named by adding the suffix -amine to the
name of the chain or ring system to which the amino group is attached with removal of the
final e.

Primary Amines

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 Secondary Amines

Tertliary Amines

4.PHYSICAL PROPERTIES OF AMINES

Amines are strongly polar compounds because the large dipole moment of the lone pair
of electrons adds to the dipole moments of C N and H N bonds. Primary and
secondary amines have NH bonds, therefore they form hydrogen bonds. Tertiary amines
cannot engage in hydrogen bonding because they do not have NH bonds.

Amines have higher boiling points than non-polar compounds of the same molecular
weight but lower boiling points than alcohols or carboxylic acids. Because nitrogen is less
electronegative than oxygen, the NH bond is less polar than the OH bond. Therefore,
amines form weaker hydrogen bonds than do alcohols of similar molecular weights. Primary
and secondary amines have boiling points that are lower than those of alcohols but higher
than those of ethers of similar molecular weights.

Hydrogen bonding is more important with 1 than with 2 amines. Therefore, primary
amines have higher boiling points than those of secondary amines. Tertiary amines have no
hydrogen bonding, they have lower boiling points than primary and secondary amines of
similar molecular weights. Table 1. gives melting points, boiling points and water
solubilities of some simple aliphatic and aromatic amines. All these properties increase with
increasing molecular weight as a result of the greater intermolecular attraction with the
larger members in the series.

Thus, we observe a primary amine always boils higher than a secondary amine of the
same molecular weight.

All amines, even tertiary ones, form hydrogen bonds with hydroxylic solvents such as
water and alcohols. Therefore, amines tend to be soluble in alcohols and lower molecular
weight amines (up to about six carbon atoms) are relatively soluble in water.

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 TABLE 1.Physical Properties of Amines

Amine Molecular Melting Boiling Water

weight point C point C solubility

Primary Amines

Methylamine 31 93 7 Very soluble

Ethylamine 45 81 17 Very soluble

n-Propylamine 59 83 48 Very soluble

n-Butylamine 73 50 77 Very soluble

Aniline 93 6 184 Less soluble

Cyclohexylamine 99 134 Slightly soluble

Benzylamine 107 53 Very soluble

Secondary Amines

Dimethylamine 45 96 7 Very soluble

Ethylmethylamine 59 37 Very soluble

Diethylamine 73 42 56 Very soluble

Di-n-propylamine 101 40 111 Slightly soluble

N-Methylaniline 107 57 196 Slightly soluble

Diphenylamine 169 54 302 Insoluble

Tertiary Amines

Trimethylamine 59 117 3.5 Soluble

Triethylamine 101 115 90 Less soluble

N, N-Dimethylaniline 121 2 194 Low solubility

Triphenylamine 251 126 365 Insoluble

The most important property of amines is their characteristic odour of rotting fish. Some
of the diamines are particularly pungent. However, the methylamines and ethylamines
smell like ammonia.
Aromatic amines are generally very toxic. They are readily absorbed through the skin
often with fatal results. Aromatic amines are very easily oxidised by air. Most are colourless
when pure, they are often discoloured due to the presence of oxidation products.

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 5. BASICITY OF AMINES
A. pKb and pKa Values
Amines are Lewis bases (nucleophiles) because of the presence of a nonbinding
electrons on nitrogen, which can form a bond with an electrophile. An amine can also act as
a Bronsted-Lowry base accepting a proton from a proton acid.
Reaction of an amine as a nucleophile

Reaction of an amine as a base

As nitrogen is less electronegative than oxygen, amines are more basic than alcohols.

However, amines are stronger bases than water, but are far weaker bases than
hydroxide ions, alkoxide ions and carbanions.

Since amines are much more basic than water, aqueous solutions of amines have basic
properties. An amine can abstract a proton from water giving an ammonium ion and a
hydroxide ion.

The equilibrium constant for this reaction is called the base-dissociation constant
(basicity constant) and is denoted by Kb . Kb is given by the expression
+
[R - NH3 ][OH- ]
Kb =
[R - NH2 ]

water being in large excess, concentration of water is not included in the above expression.

This gives us a convenient method of comparing the relative basicities of amines. Values
of Kb for most amines are fairly small and the equilibrium for this dissociation constant lies

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toward the left, we use its negative logarithm, pK b values to compare the relative strengths
of amines as polar bases.

pKb = log Kb
The values of Kb, pKb and pKafor some amines are listed in Table 2.

The larger the value of Kb (or smaller the value of pKb), the greater is the tendency of
the amine to accept a proton from water and thus the greater will be theconcentrations of
+
R - NH3 and OH in the solution. Larger values of Kb are associated with those amines that
are stronger bases and smaller values of Kb are associated with those amines that are
weaker bases. Just the opposite is true for values of pK b.

The basicity constant for ammonia at 25C is 1.8 10 5, we can have its pKb as given
below:

[NH4+ ][OH- ]
K b= = 1.8 105
[NH2 ]

pKb = log (1.8 105)

= 4.74

Another way to compare the basic strengths of amines is to compare the acidity
constants or pKa values of their conjugate acids, the alkylammonium ions. We have the
equilibrium as

[R - NH2 ][H3O+ ]
Kb =
[R - NH3+ ]

pKa = log Ka

Multiplying Kawith Kb, we get

Ka Kb = [H3O+] [OH]

= Kw = 1.0 1014
pKa + pKb = 14

pKb = 14 pKa

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 Thus, it is possible to convert values of K a (or pKa) for the ammonium ion into Kb (or
pKb) for the amine.

If the amine is strongly basic, the ammonium ion will hold the proton tightly, it will have
larger pKai.e., it will not be very acidic. On the otherhand, if the amine is weakly basic the
ammonium ion will not hold the proton tightly and will be much more acidic (it will have a
small pKa).

TABLE 2. Values of Kb, pKb and pKa of some Amines

Amine Kb pKb pKa

Ammonia 1.8 105 4.75 9.25

Primary Amines

Methylamine 4.3 104 3.36 10.64

4
Ethylamine 4.4 10 3.33 10.67

n-Propylamine 4.7 104 3.32 10.68

Cyclohexylamine 4.7 104 3.32 10.68

5
Benzylamine 2.0 10 4.67 9.33

Aniline 4.0 1010 9.38 4.62

p-Toluidine 1.2 109 8.90 5.10

9
p-Methoxyaniline 2.0 10 8.71 5.29

p-Nitroaniline 1.0 1013 13.0 1.0

Secondary Amines

Dimethylamine 5.3 104 3.23 10.77

Diethylamine 9.8 104 3.67 10.93

Di-n-propylamine 10.0 104 3.0 11.0

10
N-Methylaniline 6.1 10 9.16 4.84

Tertiary Amines

Trimethylamine 5.5 105 4.20 9.80

Triethylamine 5.7 104 3.12 10.88

4
Tri-n-propylamine 4.5 10 3.35 10.65

N, N-Dimethylaniline 11.6 1010 8.85 5.15

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 B. Effects on Amine Basicity
When we examine the pKb values of the amines given in Table 2, we see that most
primary amines are stronger bases than ammonia.

We can explain this on the basis of electron-releasing ability (+I effect) of an alkyl
group. An alkyl group has +I effect, it releases electrons and stabilises the alkyl ammonium
ion that results from the acid-base reaction.

This explanation is supported by measurements in the gas phase. The basicities of the
following amines increase with increasing methyl substitution.

We might expect secondary amines to be stronger than primary amines and tertiary
amines to be the strongest of all. This is not the order of basicity of these amines in
aqueous solution. In aqueous solution the order is

It is observed that the introduction of an alkyl group into ammonia increases the basic
strength markedly as expected. The introduction of second alkyl group further increases the
basic strength but the effect of introducing the second alkyl group is much less marked. The
introducing of a third alkyl group to yield a tertiary amine, however, decreases the basic
strength. It becomes even less basic than a primary amine. This is due to solvation effects.

The basicity of an amine in water is determined not only by the availability of electrons
on the nitrogen atom but also by the extent to which cation, formed by uptake of a proton,
stabilises by solvation. The more the number of hydrogen atoms attached to nitrogen in the
cation the greater is the possibility of solvation via. hydrogen bonding between these and
hydrogen.

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 As we go along the series NH3 RNH2 R2NH R3N, the inductive effect will
tend to increase the basicity but less stabilisation of the cation by hydrogen bonding will
occur, which will tend to decrease the basicity. The net effect of introducing alkyl groups
becomes smaller and actual change over takes place on going from secondary to tertiary
amine. We observe that order of basicity of the butyl amines in chlorobenzene as solvent is
BuNH2 > Bu2NH > Bu3N

Whereas their related pKa values in water are 10.61, 11.27 and 9.87. There is no
solvation of butylamines in chlorobenzene.

The effect of introducing electron-withdrawing groups e.g., Cl, NO2, close to the basic

centre NH 2 is to decrease the basicity due to their I effect. Thus, we observe the amine

is found to be virtually non basic due to the three powerful electron-withdrawing CF3
groups.

Amides are found to be very weakly basic in water. Thus, acetamide pK a ~ 0.5 is very
weak in comparison to ammonia pKa = 9.25. This is due to electronwithdrawing mesomeric
effect of C = O group.

The lone pair of electrons on the nitrogen are withdrawn by the adjacent C = O group.

If two C = O groups are present, the resultant imides are often sufficiently acidic to form
alkali metal salts, e.g., phthalimide is so acidic that on treatment with potassium hydroxide
it forms potassium phthalimide because the conjugate base can stabilise by resonance.

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 The resonance effect in increasing the basic strength of an amine is seen in guanidine,
HN = C (NH2)2, which is a very strong organic nitrogenous base withpK a of ~ 13.6. Both

the neutral molecule and the cation H2N = C(NH2)2 resulting from its protonation are
stabilised by delocalisation.

The cation is greatly stabilised with respect to the neutral molecule because the
structures are equivalent and there is no charge separation. Thus, protonation of guanidine
makes it energetically favourable and guanidine becomes an extremely strong base.

Urea has two amino groups joined to aC=O group. On protonation we get two equivalent
resonating structures. Therefore, it acts as a monoacidic base.

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 C. Basicity of Aromatic Amines

Aromatic amines are much weaker bases than the corresponding non aromatic amine,
cyclohexylamine. For example, aniline is a very weak base (pK a = 4.62) compared to
ammonia (pKa = 9.25) or cyclohexylamine (pKa = 10.68).

We attribute this due to the resonance contributions to overall hybrid of aniline. In

aniline, the nitrogen is bonded to sp2 hybridised carbon atom, the lone pair of electrons on
nitrogen conjugate with electrons of the benzene nucleus and we get various resonating
structures. This delocalisation of the electron pair stabilses aniline. Moreover, there is I
effect of the phenyl group. Electrons are withdrawn and less available for protonation.
Hence, aniline becomes a weaker base than ammonia itself.

When anilne is protonated, it become anilinium ion,

Anilinium ion has got only two resonating structures and consequently resonance does
not stabilise the anilinium ion to as extent as it does aniline itself. The aniline is thus
stabilised to a greater extent with respect to the anilinium cation and it is energetically
unfavourable for aniline to take a proton. Therefore, aniline acts as a weaker base (pKa =
4.62) compared to cyclohexylamine, pKa = 10.68.

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 The base wreaking effect is more pronounced when further phenyl groups are introduced
on the nitrogen atom. Thus, diphenylamine is an extremely weak base (pK a = 0.8) whereas
triphenylamine is not basic at all.

Electrons on nitrogen atom are withdrawn by phenyl groups and are not available for
protonation.

Introduction of alkyl e.g., CH3 groups on to the nitrogen of aniline results in increase in
basic strength. Thus, dimethyl aniline is a stronger base than methylaniline which is
stronger than aniline.

Irregular effects of introduction of methyl group into o-, m-, and p-positions in aniline
have been observed. When a methyl group is attached to the benzene nucleus in aniline,
the basicity increases only if the group is at para position. Thus, we have

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 A group with a more powerful inductive effect is found to have more influence. For
example, electron withdrawl is intensified when the NO2 group is in the o-, or p-position
due to extended conjugation of the lone pair of electrons with electrons of the benzene
nucleus. Thus, nitroanilines are found to have low pK a values.

We observe that o-nitrotoluene is a much weaker base than other nitroanilines.This is

due to the fact that inductive effect is more powerful in o-nitroaniline dueto short distance.
Moreover, there is streric interaction and hydrogen bonding ino-nitroaniline as shown
below:

o-Nitroaniline is such a weak base that its salts are largely hydrolysed in aqueous
solution, while 2,4-dinitroaniline is insolube in aqueous acid and 2,4,6trinitroaniline behaves
as an amide, called picramide. It readily undergoes hydrolysis to picric acid.

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 When electron-donating groups such as OH and OCH3 are present at o-, mor
p-positions, the mesomeric effect can be exerted from the o- and p-and not from the
m-position. The m-substituted compound is a weaker base than aniline itself due to
electron-withdrawing inductive effect exerted by the oxygen atom in each case. However,
effect is more pronounced in the p-substituted aniline. In case of o-substituted aniline, the
pKa values do not change appreciably due to steric and polar effects as is evident from the
pKa values given below:

We show below the conjugation of lone pair of electrons of OCH3 group with the
electrons of the benzene nucleus. This results in increasing basicity when OCH3 group is
there at the p-position.

We have seen difference between the basicities of dimethylaniline and aniline is very
little. However, the basicity of 2,4,6-trinitro-N,N-dimethyl aniline is about40,000times than
that

of 2,6-trinitroaniline. This is due to the fact thatgroup issufficiently large to inter-

feresterically with the large NO2 groups in both the o-positions. As a result of this the
extended conjugation of the lone pair of electrons with NO2 groups is inhibited because
the p-orbitals on the N atoms are no longer parallel to the p-orbitals of the ring carbon
atoms. Thus the expected base weakening by mesomeric electron withdrawl does not take

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place. Therefore,2,4,6-trinitrodimethylaniline becomes a very strong base than 2,4,6-
trinitroaniline.

6. PREPARATION OF AMINES
A.Direct alkylation of Ammonia-Ammolysis of Halides

We know that alkyl halides undergo nucleophilic substitution reactions. Salts of primary
amines can be prepared by the reaction of alkyl halides with ammonia by nucleophilic
substitution reactions. Subsequent treatment of the resulting aminium salts with base gives
primary amines

For example,

In practice, this type of displacement reaction might be used as a method of

synthesising primary amines. But the method is of very limited synthetic application
because multiple alkylations occur. When ethyl bromide reacts with ammonia, the
ethylaminium bromide that is produced initially can react with ammonia to liberate
ethylamine. Since the primary amine is also nucleophilic, it may undergo further reaction to
give the secondary amine. Repetition of acid-base and alkylation reactions ultimately
produce some tertiary amine and even some quaternary ammonium salt if the alkyl halide
is present in excess.

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 Multiple alkylations can be minimized by using a large excess of ammonia or the amine
being alkylated. This method is only practical in cases where the amine is relatively
inexpensive and sufficiently volatile that the unreacted excess may be easily removed. An
example is the preparation of n-butylamine by the reaction of
n-butylbromide with ammonia.

We give the general scheme of reactions where overalkylations may give a mixture of
products even when equivalent molar amounts of ammonia and alkyl halide are used.

B. Indirect AlkylationThe Gabriel Synthesis

Pure primary amines can be prepared in good yield by a method known as Gabriel
Synthesis. This method involves the alkylation of a protected form of ammonia.
Phthalimide, prepared from ammonia and phthalic acid, is converted into potassium
phthalimide. Alkylation of potassium phthalimide with any alkyl halide results in the
formation of N- alkyl phthalimide. Alkaline hydrolysis produces the desired primary amine
and phthalic acid, obtained as a byproduct is recycled again.

The scheme of Gabriel Synthesis is given below:

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 Phthalimide has one acidic NH proton ( pKa = 8.3) that is abstracted by potassium
hydroxide to give the phthalimide anion, which stabilises by resonance.

The phthalimide anion is a strong nucleophile and can enter into displacement reactions
with alkyl halides. It reacts with alkyl halides by SN2 mechanism displacing a halide ion.

C. Reduction of Nitro Compounds

Nitro compounds undergo ready reduction to yield primary amines. The method gives
the most general synthesis of aromatic amines because aromatic nitro compounds of a wide

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variety are available from nitration of aromatic compounds. Nitro compounds can be
reduced in two general ways:

(i) By catalytic hydrogenation using molecular hydrogen or

(ii) By use of chemical reducing agents in acidic media using a metal and acid.

Catalytic hydrogenation of a nitro compound to a primary amine takes place smoothly. A

solution of the nitro compound in alcohol is heated with finely divided nickel or platinum
under hydrogen. For example,

This method cannot be used when some easily hydrogenated group is present in the
molecule.
Among the most common chemical reducing agents are metals and acid, usually, iron,
zinc or tin and dilute hydrochloric acid. In the laboratory, reduction of nitrobenzene to
aniline is generally carried out by using dilute hydrochloric acid and granulated tin. In the
acidic solution aniline is obtained as its salt.
The free amine is liberated from the solution by the addition of base and is
steamdistilled from the reaction mixture.

Stannous chloride, SnCl2, and hydrochloric acid are especially useful combination when
other reducible groups, such as carbonyl groups are present. For example,

Selective reduction of one nitro group of a dinitro compound can be achieved by using
sodium hydrogen sulphide in alcoholic solution.

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 This reduction can also be achieved through the use of hydrogen sulphide in aqueous or
alcoholic ammonia. When this method is used, the amount of H 2S must be carefully
measured, because the use of an excess may result in the reduction of more than one nitro
group.

It is not always possible to predict which nitro group will be reduced. However, treating
2,4-dinitrotoluene with H2S and ammonia results in reduction of the 4-nitro group.

On the other hand reduction of 2,4-dinitroaniline causes reduction of the 2-nitro group.

D. Reduction of Amides, Oximes and Nitriles

Amides, oximes and nitriles can be reduced to amines. Reduction of a nitrile or an oxime
yields a primary amine whereas reduction of an amide can yield a primary, secondary or
tertiary amine.

Nitriles can be prepared from alkyl halides and CN or from aldehydes and ketones as
cyanohydrins.
Oximes can be prepared from aldehydes and ketones by the reaction with
hydroxylamine. Amides can be prepared from acid chlorides, acid anhydrides or esters.
(i) Reduction of Nitriles

Nitriles are reduced by hydrogen and a catalyst or by lithium aluminium hydride in an

ether solvent to give primary amines.

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 Example,

In the catalytic hydrogenation, secondary amines are often produced as by products.

The initially formed imine may react with some primary amine already produced in the
reduction to give a new imine. Hydrogenation of the imine gives the secondary amine

The side reaction may be suppressed by carrying out the hydrogenation in the presence
of excess ammonia.

Secondary amine formation may also be minimized by carrying out the reaction in acetic
anhydride as solvent. The primary amine produced is rapidly converted into the amide. The
amine may then be obtained by hydrolysis of the amide.

Since nitriles are easily available by several methods, many primary amines may be
synthesised by this procedure.
(ii) Reduction of Oximes

Oximes can be reduced to primary amines. Since oximes are easily generated in high
yield, this is a useful synthetic method. Reduction can be carried out with hydrogen and a
catalyst or with LiAlH4.

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 For example,

Oximes are also easily reduced with sodium in alcohol, which is a safer method than the
use of LiAlH4.

(iii) Reduction of Amides

Amides are reduced by lithium aluminium hydride in refluxing ether. We can get
primary, secondary or tertiary amine depending upon the nature of the amide.

The reduction is unusual because a C=O group is reduced to CH2. Yields are generally
good.
Examples,

Diboranl, B2H6, may also be used as the reducing agent.

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 E. Reductive Amination
Aldehydes and ketones can be converted into amines by reduction in the presence of
ammonia or an amine. Ammonia and primary amines condense with aldehydes and ketones
to give imines. In the case of ammonia, the imines are unstable and cannot be isolated.
However, if a mixture of carbonyl compound and ammonia is treated with hydrogen and a
suitable catalyst, the C=N bond of the imine is reduced and an amine results. The process is
often called reductive amination.

The reducing agents generally used are hydrogen and a catalyst (such as nickel) or
sodium cyanohydridoborate (NaBH3CN) or LiBH3CN. The reaction involves reduction of the
intermediate imine obtained from aldehyde or a ketone.

Some examples are as follows:

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 Primary amine obtained in the above reaction may condense with the starting aldehyde
to give a different imine. Reduction of this imine gives a secondary amine.

This side reaction may be minimized by using a large excess of ammonia in the reaction
medium.
However, reductive amination may also be used as a method for the synthesis of
secondary amines as shown by the following example:

Reductive amination appears to proceed through the following general mechanism:

When ammonia or a primary amine is used there are two possible pathways for the
formation of the product-via. an amino alcohol which is called 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

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 F. Preparation of Amines Through the Hofmann, Curtius and Schmidt
Rearrangements

(i) Hofmann Rearrangement

In the Hofmann rearrangement, an acid amide is converted to a primary amine on
treatment with aqueous solution of sodium hypobromite (or sodium hydroxide and
bromine). Thus, it results in shortening of the carbon chain by one atom and a change in
the functional group from an amide to an amine. The actual product is the formation of the
isocyanate. The isocyanate is generally not isolated since it is hydrolysed under the reaction
conditions to give the corresponding amine.

Here R may be an alkyl oraryl group. If the alkyl group is of six or seven carbon atoms
low yields of the product are obtained.

When bromine and sodium methoxide are used instead of bromine and sodium
hydroxide, the product of addition to the isocyanate is the formation of a carbamate,which
is easily isolated and can be hydrolysed to the anime.

Mechanism
The mechanism of the reaction follows the following pattern:

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 Water addition to the isocyanate results in the formation of carbamic acid
whichdecarboxylates to give an amine and carbon dioxide.

The first step in the above reaction sequence is the formation of the N- bromoamide. A
proton is removed from the nitrogen atom. The deprotonated intermediate undergoes
simultaneous rearrangement with the migration of the alkyl group to give the formation of
the isocyanate.

N-Bromoamide is quite acidic and loses a proton to the base because of the presence of
two electron withdrawing groups acyl and bromine atom.

The process of migration is intramolecular.

This has been established by isotopic labelling. When two amides are rearranged,
together no cross products are obtained. The isocyanate produced may be isolated in
anhydrous conditions but the reaction is generally carried out in aqueous or alcoholic
solution in which the isocyanate is converted into an amine or a urethane respectively.

In this case it is the nucleophilicity of the migrating group that facilitates the reaction.

Hofmann rearrangement provides an efficient route for making both aliphatic and
aromatic amines. Thus, we have

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 (ii) Curtius Rearrangement

The Curtius rearrangement involves pyrolysis of acyl azides to yield isocyanates. The
reaction gives good yields of isocyanates since no water is present to hydrolyse them to
amines. However, they can be subsequently hydrolysed in the presence of water or alcohol.

The addition of water to isocyanate initially results in the formation of carbamic acid,
which is unstable and decarboxylates to give amines. With alcohols the corresponding
carbamates are obtained, which can be hydrolysed to give amines.

The azides may be prepared by nucleophilic substitution on an acyl chloride by sodium

azide or by the reaction of acyl hydrazides with nitrous acid.

Azides may be treated with caution as they may decompose explosively. The isocyanate
may be isolated by carrying out the reaction in an aprotic solvent such as chloroform.
Generally, an alcoholic solvent is used with which the isocyanate reacts to form a urethane.
The amines formed contain one carbon atom less than the original acyl azide. It is due to
this reason that the reaction is sometimes referred to as Curtius degradation rather than
Curtius rearrangement.

Mechanism

Here the azide undergoes rearrangement to give an isocyanate when a molecule of

nitrogen is expelled.

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 The Curtius rearrangement is a very general reaction and can be applied to almost any
carboxylic acid aliphatic, aromatic, alicyclic, heterocyclic, unsaturated and containing
many functional groups. For example,

(iii) Schmidt Reaction

In the Schmidt reaction, carboxylic acids react with hydrazoic acid in the presence of
sulphuric acid to give isocyanates directly. The acid azide is normally not isolated, but
allowed to rearrange to give the product. Hydrolysis of isocyanate results in the formation of
primary amine.

Sulphuric acid is the most common catalyst, but Lewis acids have also been used. Good
results are obtained for aliphatic R groups. When R is aryl, the yields are variable.
It is almost a direct method of converting carboxylic acids into primary amines, but
conditions are more drastic. Under the acid conditions employed, the isocyanate is virtually
never isolated. However, Schmidt reaction is applicable if the acid does not contain other
groups that are sensitive to concentrated sulphuric acid.

Institute of Lifelong Learning, University of Delhi 31

 Mechanism
The mechanism of Schmidt reaction follows the same pattern as seen in case of Curtius
rearrangement.

REFERENCES:

1.Organic Chemistry by Morrison, R.T. and Boyd, R.N. Darling Kindersley (India) Pvt. Ltd.
(Pearson Education).
2. Organic Chemistry by Graham Solomons, T.W. John Wiley and Sons.
3. Introduction to organic chemistry by Andrew Streitwieser, Jr. and Claylon H. Heathcock
Macmillan Publishing Company.
4. Organic Chemistry by Seyhan Ege A.I.T.B.S. Publishers and Distributers J5/6, Krishan
Nagar, Delhi- 110051.
5. Advanced Organic Chemistry by Jerry March John Wiley and Sons.
6. Organic Chemistry by L.G. Wade, Jr. Pearson Education.
7. A Guide Book to Mechanism in Organic Chemistry by Peter Sykes Pearson Education.

Institute of Lifelong Learning, University of Delhi 32