Chapter 28

Aliphatic Amines

Amines are typical organic bases structurally related to the inorgatlic base ammonia.
They contain alkyl groups attached directly to nitrogen atom. They could be thought of as
derivatives of ammonia (NI-I3 ) in which one, two or all the three hydrogens have been replaced
by alkyl groups. Thus,
H H CH

H—N—H CH,—N--H CH,—N—H CH3—N---CH8
ammonia methylamine dimethylamine trimethylamine

Primary, Secondary and Tertiary Amines. Amities are designated as primary (1),
secondary (2°), or tertiary according as one, two or three hydrogen atoms in ammonia molecule
have been substituted by alkyl groups (R). The general formula and the characteristic
functional groups of the three classes of amities are stated below.

Class General Formu1 Functional Group

I-I H
Primary (10) R—N" or RNH —N( or —NH3 amino
"H "H

Secondary (2) or RINH _N( or >NH imino

R
Tertiary (3') R—N( or R3N or -N tertiary
/ nitrogen atom

In secondary and tertiary amities, the alkyl groups bonded to the nitrogen atom may
be same or different. When all the alkyl groups are same the amine is referred to as a Simple
Amine or Symmetrical Amine and when two or all the three a)kvl oroiin't are different, the
amine is often called a Mixed Amine or Unsymmetrical

R
,R—N R—N"

simple 2° amine mixed 2° amine

Tetrulkylammonlum Salts or Quaternary Saii... .

symmetrical ion having a structure, quite similar to that of u...... .oaioIe to replace
one or more of the H atoms of the ammonium ion by alkyl groups. When all the four
hydrogens of ammonium ion have been replaced by alkyl groups, we have tetraalkylammonium
ion or quaternary ammonium ion.

669


670 Advanced Organic Chemistry

H H R

H H

methane ammonium ion tctraaikylammonium ion

The tetraalkylammonium ion has "built in" ionic charge and interacts with anions (X-) to form
salts analogous to ammonium salts.

H + R +
H1!4H X

1i I.
ammonium salt tetraalkylainmoajum salt

Here X may be Cl, I, HS01 or OH. For example.

CH, CH, +

CH1—N—CH 3 Ci + CH5—N—CH3 OH
(H3
CH5CH3J
tetramethytammonium chloride e thyltjmtthvlammonjurn hydroxide

Diamines and TriaLnines. It is possible that a single organic molecule may contain
two or more amino groups in its structure. If two are present, the compound is named as a
dlnmftie ; if there are three —NH 1 groups present it is referred to as a triamine, and so on.

I H H 14
H—C--ç--H H—C—C----- C—I-i
NH I'IH, H1 NH, NH,
ethylene dmne Propylene triamine
The term 'amine is widely used in organic chemistry for those compounds in which
the carbon attached directly to N has single hoods to other groups. Thus,

0
I H
R—C---N' or R—CO—NH, IS NOT AN AMINE

OH
ii I
but R—C--C—N or R—CO—CH1—NH5 IS AN AMINE
'H
Aliphatic Amines 671

Any compound, regardless of structure, which has a 1°, 2°, or 3° function in its molecule is
termed an amine. This large class of organic compounds includes many substances that are
biologically important. Both as free materials and in chemical combination with other
molecules, amines are widely distributed iii nature. They as particularly present in the
nervous systems of vertebrates. Adrenaline which is rapidly released in the body during times
of stress is a secondary amine. Benzedrine is a primary amine which produces frenetic "highs"
in the nervous system. Benadryl, a tertiary amine, is useful in inducing sleep as also in treating
the symptoms of allergies. Some of the most valuable drugs (confine, nicotine, amphetamine)
obtained from plant extracts contain one or more basic nitrogims in their structures and have,
therefore, been assigned the general name alkaloids.

NOMENCLATURE

Amines are named both by Common and IUPAC systems.

(I) Common System. In this system the name of an individual amine is derived by
listing the alkyl group(s) attached to N atom in order of increasing size and adding the word
amine. The name of the amine emerges as a single continuous one word. If an alkyl group
occurs twice or thrice on the N-atom, the prefix di- or tel- is placed before the name of the alkyl
group.

Table. Common Names of Amines.

Structure Name Structure Name

CH,–NH, metylami ne C14,—NH—CH, dimethylamir I:

CH,—CH,--NH, ethylamine CH,—N--CH, trimethylarnine

CH,
CH,—CH,—CH,—NH, n-propylamine CH,—CH,--NH—CH, methylethylamifle
CH,—CH--NH, isopropylamine CH,_CH,—ffCHt dimethlethylamifle

CH,
CH,

C}l,---NH, tert-butylamine CH1CH1NCH1 methylethyl

isopropylamine
CH
CH, CM,

The prefix see- or ten- is used just to indicate the type of amine and has no structural bearing
as in the case of alcohols.

(2) IUPAC SYSTEM. This system adopts the common names for lower members.
However, in modern practice the alkyl groups on nitrogen are written in alphabetical order and
not in order of size or complexity. For example,

CH,—CH,—NH—CH, CH,—N—CH,--CH,
ethylmethylamine I CH,
CH
CH,
ethyl isopropyl rncthylamioc

WiICLA nu ol the alkyl groups attached to N atom are identical, they are written as
dialkl and aiphahetised. Thus,

672 Advanced Organic Chemistry

CH
CH,1—CH, C1{,—CH,---N—CH(
CHt\ CH,
CH,—CFJ
dlmethylethylamine CH/
diisopropylethylamine
The !UPAC System is only used to name long chain substituted amines. These names
are derived by regarding the amino group (---NH,) as a substituent and naming the given amine
as aminoalkanc. As usual the longest continuous hydrocarbon chain containing the amino
group is the parent structure and the position on this chain is indicated by arabic numerals.
The counting of the carbons is done from the end that gives lowest number to the amino group.
For example,
C
1 2 I I 1 2 ii 4 3
CU3 CR—CU2--NH2 CH,---CFEI `&-6H,—NH, CHI -cH 3--CU-C I-{2—CH,
i-amjnoprpane 1-aniino-2-nicthylpropane
NH2
2-amino -3-methy1penianc
Further, if the amino group contains alk y l groups R) is substituent, the word V-alk',l
or N, N•dialkyl is prefixed to the word amino'. Thus,
CH,
I
CHs—NH--CH,—CH,—CI-I,---CH, CH,-- .N - CH—CU 3 CLI, CH, CII, CH,
I-(N-inethylansino)-butane I
,CH3
2-(N', NdimetbyIaniino)-heptanc
If the amino group ( .—NH) or substituted amino group (-- NHR or NR 3) is part of a
molecule that contains another functional group, the second functional group (say - COOH or
—OH) determines the parent name of the compound.
NH, CH,
2 i
CH,—CFI—CH 3—000H CF—NH—CH2—CH,—OH CH,NCH—CH2—CH3—OH
A 1 3 1 W-mcthylamino-I-ethanol
3-amino-I-butanojc acid ,CHI
3-(N, N-dimcthylamino) . 1-butanol
ISOMERISM
Amines exhibit the following types of isomerism.
(1) Chain Isomerism. Like other classes of organic compounds, amines show chain
isomerism arisine rom the different structure of the alkyl groups bonded to the amine function.
Thus
CHI
CHI—CH,----CH,--CH,—NH, CH.—CH—CH,—NH, -
n-butylamino isobutylaminc
) Position Isomerism. Amines show position isomerism due to different location of
the '- in function —NH,, —NHR or —NR, on the carbon chain. For example,

CH,—CH,--CH,—CH,—CH,—NH. CH,_CH,_CH 1_tbH_CH3 CH,—CH,_.H - CH2—CH3

t-aminopenin, 2-amtnopeniane 3-amiriopemane
(3) Metanierism in amines is exhibited because of the different alkyl groups bonded to
the amine tu p tion, molecular formula 01 the amine remaining the same.
Aliphatic AmInes , 673

CH 3—CJ3 CH,
/
CH 1—CH 1 CH,—CH,--CH, / CH. \ "NH
dleiliyliminc methyl-a-projylamine CH /
CH'/
inetbyiisopropylaminc
(4) Same Molecular Formula represents 1', 2 0, 30 amine. Amines show another type of
isomerism in which the same molecular formula may stand for a primary, a secondary anda
tertiary amine. Thus C1 H9N represents the following amines
CH

CH,—CH,- CH,—NH, CH— NH—CH 1 --CH, CH3—N—CH,

propylamiiie ethylmethylamfric inmethylamine
2' 3°
STRUCfURE
The electronic configuration of N atom can be written as I S3, 231,
2s orbital and three 2p orbitals hybridise to give four sp 3 2pI , 2pl , 2p,1 . The
orbitals. Thus as in case of carbon
atom, the four sp° orbitals of nitrogen are directed towards the four corners of a regular tetra-
hedron.

C
4.71

Orb ital structure

structure of C Orbital structure of N
In coiiirdsi to carbon, three of the sp 3 hybrid orbitals in nitrogen are occupied by single
clectrns while the fourth has a pair of electrons. The three half-filled orbitals are capable of
forming bonds by overlap with a orbital of hydrogen atoms or sp3 orbitals of carbons of alkyl
groups (R). Thus the orbital structure of I', 2° and 3° amines can be drawn as

r) SP
N
it

R^v
Sb'-5PO3O,.5 R

Fig. 281. Orbital structure of 1', 2' and 3' amines.

Simplifying, the structure of the three types of aines RNH, (I'), R 2NH (2°) and R 3 N(3°) may
he shown as in Fig. 282.
It may be noted that in contrast to tetrahedral carbon in methane, the fourth vertex of
tetrahedral nhtroget in amines is occupied by the unshared electron pair. Thus amines have
the pyramidal molecules. The N . atom occupies the apex of the pyramid, while the rest of the H
atoms or R groups be the at the corners of a triangular bases.
The geometry of amines is supported by the electron diffraction studies of trimethy.
lamines which have shown that its molecule is pyramidal having C—N -C bond angle of 108'

674 Advanced Organic Chemistry

0
This is very nearly the same as the H—N—H bond angle in ammonia and H—C—H angle in
tetrahedral carbon in methane.

R
R
0
Fig. 282. Structural rereaentatioa of the three types of anmines.
The value of bond angle of 107° in ammonia is accounted by the fact that lone pair-bond pair
interactions are greater than bond pair—bond pair interactions thereby contracting the angle
from normal tetrahedral value of 1095° to 107°. The bond angle in trimethylarnine is 108'
which is slightly more than the bond angle of ammonia. This can be attributed to greater
H

0 CH3
10
CH3

8\ -
H
TRIMETHYLAMINE
METHA NE AMMONIA
steric hindrance between the two adjacent methyl groups than that between two hydrogen
atoms, thereby widening the bond angle from 107° (in ammonia) to 108° (in trimethylainine).

FORM I

AIIRRO

FORM!

Fig. 28'3. Mirror image forms of a tertiary amine.


Aliphatic Mimes 675

Why Asymmetric Ainlies cannot be Resolved Into Ecantloucra? Let us examine the mole.
cule of an amine containing three different alkyl groups attached to nitrogen in light of the
orbital structure discussed above. It will be revealed (Fig. 28-3) that this is not superimposable
on its mirror image. Therefore, such an amine is asymmetric or disymmetric and should exist in
two enantiomeric forms (1 and II) similar to compounds with an asymmetric carbon atom. But
all attempts to resolve this type of amine e.g., ethyl methyl•npropy1amine, have failed. Spectro-
scopic evidence, however, suggests that an asymmetric amine undergoes a rapid inversion of
FORM Ito its mirror image FORM II. This inversion of Ito It could be visualised to take

0
place through a planar transition siate like the umbrella in a windstorm.

FAST 45T
—

r (oi&ia L 4 0 PM) (Pi ANA P rRNs/TION FORM) D('INvERTEO FORM)

The inversion from form Ito II requires only a small amount of energy (a L,=5
kcal/mole).
This energy barrier of 5 kcal/mole is easily met at room temperature by the thermal collisions of
amine molecules. Therefore, a fast transformation between the forms I and II takes place. For
that reason, no resolution of the enantiomers of asymmetric amines is possible.
However, the inversion of enantiomers in asymmetric amines can be suppressed by
ammonium cation formation. The coordination of the nonbonding electron pair with a proton
fixes them in a a bond and thus prevents the inversion.

—v-" -. —

R2
substituted ammonium cation
asymmetric 3 amine
can undergo inversion does not undergo inversion

Substituted atñmonium cations, therefore, are capable of exhibiting enantiomerism.

M,PJ?O
Ill

I
14 j
RN\R3 .

P.z

Enantlomèts of substituted ammobium cation


676 Advanced Organic Chemistry

This has been confirmed experimentally. Alkylbenzylmethylphenylammonium iodide

in which four different groups are attached to nitrogen atom of the substituted ammonium ion,
has been relved into two enantionjeric forms each of which is optically active,
MI,POR

CH2CH'C$4 CHCH =C

CH2C6H H CH4
CH5

CH CHi
Enantiomeiic forms of alkylbenzylmethylphenylarnmonium iodide

METHODS OF PREPARATION OF PRIMARY AMINES

The synthetic methods for the preparation of primary amines (R—NH 1 ) are listed
below.
(I) Reaction of Alkyl halides with Ammonia. Primary amines can be obtained by reaction
of alkyl halides with excess of ammonia.
H

R—X t :N—H [R:H]

alkyl halide
H
ammonia alkylamnionium halide

The resulting alkylammonium salt (RNH 5 X) on subsequent treatment with a strong base
(NaOH) liberates the free primary amine.

H.
- + -
R—N--H X 4- NaOH + NaX + HO

I-I H
1 amine

Although this method appears so simple it is not suitable for laboratory synthesis. The
replacement of hydrogens on N atom in ammonia does not stop at the first stage when a primary
amine is produced as shown above. The process of alkylation of hydrogens on Naiom
continues to form a secondary and a tertiary amine. The tertiary amine reacts with a fourth
miolecule of alkyl halide to produce a tetraalkylammonium salt. The following series of reaction
illustrate the progressive alkylation of ammonia to form secondary amines, tertiary amines along
with tetraalkylammonium salts.
-
(1) RNH. + RX RnNFI1X
P amine dialkylamanonium halide

R,N}-12 X + NaOH -. R,NI-1 ± NaX + H20

2' amine

(ii) RnNH + RX - R3NHX

2' amine trinikylammonium hal.i


Mlpliotic Amines 677

R1NX + NaOH - R 3 N + NaX + HSO

3° amIne

.1--
R3 N + RX — RINX
3' amine tetraalkylammonium salt
4--
RI NX + NaOH -i No Reaction
The resultant mixture of a primary amine, a secondary amine, a tertiary amine and a
quaternary salt is not easily separated. Hence this method of preparing a primary amine by
reaction of alkyl halide on ammonia is of limited application, it is generally used on industrial
scale where special processes are employed for the isolation of the primary amine from the rest
of the components.
(2) Reaction of Alcohols with Ammonia. When a mixture of excess of ammonia and
alcohol vapours is passed over a dehydrating catalyst such as alumina or thoria at 300-400, a
primary amine results.
Th01
CH,—OH + H—NH —^ CI-I I --NH + H10
methanol ammonia 300-400' methylamine
(I' amine)
Unfortunately the reaction does not stop here. The methylamine produced in the lirat step
reacts with a second molecule of methanol to give a secondary amine. The secondary amine
further reacts with a third molecule of methanol to yield a tertiary amine.
Th02
CH,—NH, + CH I—OH , (CH),NH + l-1O
methanol 300°-400' dimethylamine
(2° amine)
similar
condirkini
(CH,)1NH + CH., —OH —.- (CH3 )3 N + E'120
methanol trimethylaniiae
(3' amine)
Thus the resulting mixture contains primary, secondary and tertiary amines. However
when a large excess of ammonia vapours are used in the initial mixture, primary amine is the
chief product.
(3) Reduction of Nitroalkanes. Primary amines can be obtained by reduction of nitro.
alkanes which can best be effected with lithium aluminium hydride.
LiAIH4
R—CH,—NO 2 - 6H --+ R—CH—NH 2 ± 2I'iO
nitroalkane ether alkylamine
This reduction can also be carried by using hydrogen in the presence of a metal catalyst (Raney
nickel or platinum), or with meta' aLnd acid (Sn/HCL or Fe/HCI). For example,
FC/HCI
CH,—CH,—CH,—NO, + CH,—CH,—CE,—NH,
1-niteopropane n-propylamioe

NO, NH,
LiAIH4
CH, — CH,--CH — CH, CH, — CH, — CH — CH,
2-nitrobutane ether 2.aminobutane

However, nitroalkanes are not easily prepared. Only the lower members nitromethane,
rc.hane,and the nitropropanes are commonly available from vapour-phase nitration of
alkanes. Therefore, this method although most useful for the synthesis of aromatic amines has
limited utility for the preparation of alkylamines.


678 Advancei Organic Chemistry

(4) Reduction of Amides. Primary amines are formed by the reduction of unsubstituted
amides with lithium aluminium hydride,
0
II L1AIH4
R—CH,—NH,
amide ether a primary amine

0
II LãAIH4
CH,—CH2—C—NH3CH,—CH,—CH,--NH,
-.----_+
propionamide n-propylamine
The amide required in this method can be readily prepared by the reaction of the
corresponding acyl halide with ammonia, For example, the following sequence shows how this
reaction may be used to good advanta g e for obtaining ethytamine from ethyl alcohol.
0 0
H jCr,07 SOCI 1 NHa II
CH3CH1 OH -_. CHCO0H —o CH, —C—Cl -. CfJ 1—C—NHLiAIH4 -. CHCH1—NH
ethyl alcohol acetic acid acetyl chloride acelamidc ethylamjne
(5) Reduction of Oxirnes of Aldehydes and Ketones. Good yields of primary amines are
obtained by reducing oximes of aldehydes and ketones. The common reducing agents are
sodium and absolute ethanol or hydrogen and nickel catalyst.
R\ 2(HJ R 2(H) R
"C=N—OH-----.CH--NI-1OH -. ICH—NHI + HO
V R—
an oxime , a primary amine
e.g., CH, CH, CH,
I 2(H) I 21111
i
cH (CH,)a_c = N—OH CH1(CH1)a—CH-_NH0H —o CH3(CH1 ) 5_ CH_NH1 + H2O
an oxime 2-aminooctaite
This reaction provides a method for converting aldehydes and ketones to primary amines
(6) Reduction of Alkyl Cyanides or Nitrites. Alkyl nitriles are reduced to primary
amines by catalytic hydrogenation (nickel catalyst), sodium metal in ethanol (Mendius
Reaction) or lithium aluminium hydride in ether,
R—CneN + 411 -+ R—CH--NH,
alkyl nitrile IP amine
This method is particularly useful for the preparation of alkylamines because alkyl
nitriles are easily made by the reaction of alkyl halides with cyanide ion. For example,
n-butylainine can be synthesised from n-propyl bromide as follows.

NaCN - LiAIH4
CH1CH1CH,—fir -_-, CH3CH±CH3—.C=N -_ CH1CHCH,CFINH1
'i-propylbromjdc n.buEyoitijle ether n-butylsnaine
H3JNI
OR CiiCH5CH
1400, 130 aim
The above sequence converts an alkyl halide to a 10 amine with extension of the carbon chain.
(7) Reductive Amination of Aldehydes and Ketones. Primary amines may also be prepared
by passing a mixture of an aldehyde or a ketone. and a large excess of ammonia and hydrogen
over nickel at 150°.
.0
Ni, 1500.
R—C---H + NH 3 - H -.. R—CH2--NH2 + H10
in aldehyde 300 aim primary amine


Allphotk Amlnes 679

0 ,imitar
II conditions I
R—C—CH, + NH3 + H, -k
R—CH—NH, + H,0
a ketone an alkylmethylaminc
The reaction probably lakes place by formstion of Schiff's base first, which on catalytic
hydrogenation yields a primary amine,
- H2 O +H,(cat)
/ C=O - H 3 N -+ / C=NH )CH • NHt

Schilt's base psiinaxy aminc

This process of introducing an amino group into the molecule of an a 1 'lchyde or ketone
is termed Reductive arnination. It may be illustrated by the following example.

o
NH,
II Ni, 150-
CH 3 —C—CH,---CH,—CH 3 + NH 3 + H, CH,—CH—CH,—CH,---CH, + H2O
2-pentanone 300 atm 2-rnninopeotane

(8) Hydrolysis of Isocyanides and Isocyatiates. Primary amines are produced by the
hydrolysis of alkyl isocyanides with an aqueous mineral acid.

+ - MCI
R—NC + 2H,0 -. R—NH, + HCOOH
alkyl i,ocyanide I amine formic acid

+ -
e.g., CH,CH5CH,—NC + 21-110 -. CH3CH,CH.—NH 1 + HCOOH
propyl liocyatilde propylamine
Alkyl isocyanates when hydrolysed with alkali also yield primary amines.
R—N=C"=0 + 2KOH - p R—NH, + KIC0I
alkyl isocyanatc V amine

e.g.. CH,CH,—N=C=O + 2KOH -, CH,CH,—NH. + K,CO

ethyl isocyanate ethylamme
The isocyanate required for the reaction is obtained from alkyl halides by interaction
with silver isocyanate.

CH5CH,—! + Ag—N=C=O -i CH,CH,—N=C=O + Ag!

silver isocyanate ethyl isocyanatc

(9) Hofmann Degradation. It is a simple laboratory method for conversion of an amide

to primary amine having one less carbon atom. The amide is treated with bromine in the
presence of alkali (NaOH), and the overall reaction may be written as

R—C--N11 3 + Br, + 3NaOH - R—NH, + 2NaBr + NaH0, + H,0

an amide t amine

For example,

II Br&NaOH
() CH,—CF1,—C—NH, -+ CH,—CH1--NH1
peopionan'ide ethylarnine

0 çH, çHa
I Sr,JNaOH I
(ii) CH,—C—CH,—C—NH, -+ CH3—C_-CH,—NH,

CH, CH,
ten-butylacctamide neopeiitylamine


680 Advanced Urganic Chemistry

This reaction, also known as Hofmann Rearrangement, gives an amine with one less
carbon, in contrast to straight reduction of amide with LiA1H 4 which yields an amine with the
same number of carbon atoms.
(10) Curlius Degradation. Primary amines can be prepared in good yield by treating
acyl azides (RCON,) in acidic or alkaline medium. The overall reaction which proceeds by
the elimination of nitrogen from acyl azide yields a 1° amine containing one carbon less, is called
Cursius Degradation.
0
ii —N1 H2OIH+
K—%--Ns —, R—N=C=O —+ R—NH,
acyl azide
alkyl isocyanaic V amine
Alkyl isocyanate is obtained as an intermediate which is hydrolysed to give the respective
primary amine.

The acid azide required in this method is prepared from the corresponding acyl
chloride by reaction with sodium azide (NaN 1 ). Thus the sequence leading to the production
of a primary amine from a carboxylic acid would be

0 • 0 +. 0
If II NaN3 II
R—C—OH —p R—C—CI —* -. R—N=C=O —p R—NH,
carboxylic acid acyl chloride acyl azide isocyanate V amine
The conversion RCOOH -.. RNH, can also be carried with the help of Schmidt
Reaction which is a modification of Curtius Degradation. In this reaction, a carboxylic acid is
warmed with sodium azide (Na + N 3 ) and concentrated sulphuric acid. The carboxylic acid is
directly converted to the corresponding primary amine without the necessity of isolating
.
alkyl azide.

II
0
NaN3
R—C—OH - R—NH, + N 1 + CO,
conc Hesog,
warm
Schmidt rectjo.i has the advantage of experimental simplicity as compared to the Hofmann and
Curtius degradatons.

(11) Gabriel Synthesis. In this method advantage is taken of the fact that phthalimide
readily forms potassium p hthalimide when treated with potassium hydroxide. The potassium
phtbalimide when reacted with an alkyl halide, is converted to N-alkylpbthalimide. This upon
hydrolysis with hydrochloric acids yields a primary amine.
CO CO

(§^>NH + KOH —+ + H10

phthalimide potassium phthalimide

CO . CO COOH

/\NIt+ R(
21F( + Primary
@
^Co
>NR
_^© COOH amines
pot phihalimide N-alkylphthaljmj phthalic acid
N-alkyiphthaiimide is often resistant. to hydrolysis but it readily reacts with hydrazini
(H,N—NH,) to give phthalolhydrazide and a primary amine.


Aliphatic Amines 68
Co Co
warm \NH
N—R + HN—NH, -+ I + R—N H3
bydra4ne (6O-8O
/NH
9CO/ (aco
phthaloylhyrazidc
Gabriel's synthesis provides an indirect method of carrying on the transformation
RX-RNi-I, without the formation of secondary or tertiary amine as by-products.
(12)From Chloramine and Crignard Reagents. Primary amines can be obtained by
coupling chioraminc with Grignard reagents.
ether
R—MgCI + Cl—NH, —. R—NH, + MgCI1
Grignard reagent chioramine ie amine
Chloramine required for the process is derived from ammonia and sodium hypochiorite.
-+
NH, + CIONa —s NH—CI + NaOH
sodium
hypochiorite chioramine
(13) Ritter Reaction. It is an important method for preparing primary amines having
a tertiary group. Thus tert-butyl alcohol is reacted with hydrogen cyanide In the presence of
conc sulphuric acid to give /ers.butylamine.
CH, CH,
CHr--OH + H1SO4 + HCN

H,
rert-butyl alcohol tert-butylamine (1 amine)
If the carbonium ion derived from alcohol be represented as R, the course of the above
reaction would be as follows.
- 0S0311 0-
+ + HSO4
ROH — R-l- HCN: —s HCN—R -p HCNR —s HCNHR—.iHCO
I B4O I OH -
+RNH,
Ia5nine
METHODS OF PREPARATION OF SECONDARY AMINES
below. The general methods of synthesis of secondary amine, (R—NH—R) are discussed
(1) Alkylatlon or Primary Amines. When one mole of a primary amine in ethanolic
solution is heated with one mole of alkyl halide, a dialkylammonium salt is produced. This
when treated with NaOH solution gives the free secondary amine.
H H i
1i
[R—N:RIx
*lk)l halide
H
1. amine diaIkytamm uit
F1+ R—l4--R X + NaOH —s R—H—R + NaX + H2O

HH
For example,
r amino

CH—NH, + C,H,! -, [CH,_NH,--C,H,) I

ethylamicie ethyl Iodide diethylimmoninim iodide
[CSUI—NHI--C,HI + NaOH -. C,H,—NH---C,H, -- ai .f H2O
dkthylamine

Organic Chemistry - 44


82 Advanced Organic Chemistry

This is not a method of choice for the preparation of secondary amines. The product
ivariably contains tertiary amine and tetranikylammonium salt.

(2) Reduction of N-snbstlt.ted insides. N.substituted amides when reduced with LiAIH4,
icld secondary amines.

0
LiMH4
R—C—NH—R + 4 1t —s J&—CH,—N11—R + H2O
N -alkylainide ? amine

0
II IJAIH1
.g. CH,—CH,—C—NH—CH, + CH,—CH,--CH,—NH—CH,
4H -+ + H10
N-methylpoprionamida methylpropylvnlne

(3) Reduction of Alkyl Isocyuldes or Isonitriles. When alkyl isocyanides or isonitriles

re reduced with nascent hydrogen, alkylmethylamines are obtained.

+ -
R—NC + 4H -. R—NH—CH3
alkyl isocyanidc alkylrnethylamlnc
(21 amine)
- This method is of academic interest only.

(4) Redaction of SchitFs Bases. Primary amines react with aldehydes and ketones to give
ichilT's bases. The Sehiff's bases so obtained upon reduction with hydrogen and platinum yield
econdary amines.
H

P—C=O + H,N—R' -, R—CH=N--R' + H,0

aldehyde Schiff's base
Pt
R—CH=N—R' + 3/2 H 2 -. R—CH,—NH—R'
2 amine
(S) Reductive Alkylation of Aldehydes and Ketones. When a primary amine is reacted
iitli an aldehyde or a ketone , imines are formed. The imines are readily reduced with hydrogen
nd Raney nickel or sodium boroflaoride to give a secondary amine.

R R
R---NH, + oc( - R--N=C( + H20
I' amine
ketone imine

R RaneyNi R
R—N=C(' + H, -. R—NH—CFI('

2amine

CF!3 —H,CH, +H, CF!,

6. g., CH,NH, + oc -p CH 3N_C ' CHNH—CH(
methylamine \CH, CH, Ni CK1
acetone imine isopropyl meittylarnine

The advantage of this method over alkylation with alkyl halide is that over alkylation
with the formation of tertiary amine and tetraalkylammonium salt cannot lake place.

• (6) Hydrolysis of p-Nitroso.N. N.dislkylanillnes. In this method aniline is first heated

with an alkyl halide to form N, N dialkytaninc. Th i s i s then nitroacted by reacicn with nitcua
icid when p . iutroso . , N. dialkylaniline is obtained which upon boiling with sodium hydroxide
yields a pure secondary amine.
 Aliphatic Amines 683

NH2 NR
R—X NR, HO—NO

( I —H10
-
ON
anilIne N Ndialkdanllioe p-nitroso-N N.dialkylanillne

NR, OH

(ii) 0 + HO—H
NaOH

ON
+ 2NmiE:e

p-nitrosophenol
(7) Hydrolysis of Dialkykyanamides. Pure secondary amines may be obtained by
synthesising dialkylcyanamides by the action of alkyl halide on sodium cyanamide. The dia t kyl-
cyanamide is then hydrolysed by aqueous acids or bases to produce a secondary amine.

I- I-
1+
(1) Na,: N—CN -.* 2Na + N—C=N
sodium cyanamide cynamide ion

R—X
NC—N: + R—X -, NesC—N—R - N=C—N" + X

cyanamide ion dialkyl cyanamide

R,\ -i-2HSO R11' R.

(II) ,N—CN —s NH, + ')N—C—OH -.- NH + CO.
Rf
N, Ndialkylcarbonlc acid 2' amine
(—table)
(8) From chioroamines and Grigurd Reagents. Secondary amines can also be prepared
by reaction between the corresponding chioroamines (RNHCI) and Grignard reagents. The
chioroamine needed for the reaction is obtained by the reaction of a primary amine with sodium
hypochlorite (NaClO-),

R—NH, + CION ----- p R—NH—C1 + NOH

1 amine cbloroamlne
ether
R—NH--Cl + R'---MgCI -p R—NH--R' + MgCl,
2' amine
This method is particularly suited for the preparation of secondary amines having two
tertiary alkyl groups, such as di-tert-butyl amine, (CH3)1C—NH—C(CH3).

METHODS OF PREPARATION OF TERTIARY AMINES

The methods listed below are available for the preparation of tertiary amines (R1N).

(I) Alkylation of a Secondary Amine. When a secondary amine in ethanolic solution is

heated with a calculated amount of the appropriate alkythalide, the corresponding Irialkyl.
ammonium salt is obtained. This on treatment with NaOH liberates the tertiary amine.
R +

R----H + R—x - p R—N—H X

alkyl halide
R R
2' amine trial kylammonium salt


684 Advanced Organic Chemistry

R +

R—N--H X + NaOH
T R—:+NX+HO

3° amine

This is a fairly practical method for the preparation of tertiary amines. The teraalkyl-
amrnonium salt is also produced which is stable to alkali. Thus upon distillation of the reaction
mixture after treatment with alkali yields the tertiary amine.

(2) Reduction of N, N-Disubstituted Amides. Tertiary amines may be prepared by reduction

of N, N.disubstituted amides with LiAIH4.
0
I R LiAIH1 R
R_C_N( + 4 [H] -p R-_CH_N( + H10

N, N-disubstituted 3' amJne

amide

11Cl-I3 LiAIH4 CHa

e.g., CFI 3CH5_C_N( + 4 [H] -p CHCH—N
—N <
/' + H,0
'CR3 CH
M. N-dimethylnropionamidc dlmethylpropylamine

(3) Reductive Alkylation. Tertiary amines can be obtained by methylation of a primary

or secondary amine by a mixture of formic acid and formaldehyde. This is referred to as
Eschwi1er.C!ark3 reaction
- CH,
R—NH + 2 CHIO + 2 HCOOH R—N( +2H2O+2CO3
1 amine formaldehyde formic acid CH1
3° amine
e.g., (CH,)1C.—NH, + 2CH20 -4- 2HCOOH - (CI1 3W—N(CH3), + 2R102CO1
Iert-butylamine dimetbyl-trt-butylamine

(4) Decomposition of Tetrealkylammonium Hydroxides. Tertiary amines are best prepared

by decomposing the tetraalkylamcnonium hydroxide upon heating strongly. The required
tctraalkylarnmonium hydroxide is obtained by treating the corresponding tetraalky!ammoni urn
salt with moist silver oxide (AgOH). For example,

CH,
1 + -
CH51CH5 1 + AgOH -_- + CH* OH + Ag! 4
CH'—N-

CH, CH1
Ietrirncthylammoaium iodide tctrvthylamnos!'1M hydroxide
CH CH,
4- - A
CH1CHa OH 4H5—OH

CH, CH,
Crimethylamine

With a higher tetraalkylammooium hydroxide, however, the decomposition follows a

different route.


Aliphatic Amines 685

CH—CH2
ink
Iii(C2H5)3N + CH 2 CH 2 + H20
' rRIEn/y1AwE
4 (rIlytFMC
15 rRAF1HyLAMAxw,oaq
HYDROXIDE

(5) From CbIoroamnes and Crinard Reagents. Tertiary amines can also be prepared
by coupling the corresponding chioramine (R I Nd) with Grignard Reagents in ether. The
required chioroamine is derived from a secondary amine by reaction with sodium hypochiorile
(Na4CIO).
R -+ R -
"N—H ± CIONa —+ R" "N—Cl + NaOH

- 2' amine chloroaminc

R ether R'
")N—Cl + R'—MgCI —i', N—R' + MgCI1
R1 Grignard reagent R'
3amines
This is the only satisfactory method for the preparation of tertiary amines having two
or more tertiary alkyl groups e.g., tri-ter-butylamine, (CI-i5)5--C]5N.

HOW TO SEPARATE MIXTURES OF AMINES

When the mixture contains salts of primary, secondary and tertiary amines along with
the tctraalkylammonium salt, it is first distilled with potassium hydroxide solution. The three
amines are salt free and distil over, The tetraalkylammonium hydroxide, however, remains
unaffected by alkali and being nonvoltatile is left behind. Thus,

R—NH J Cl + KOH —p R—NH, + KCI -- HSO

1 . amine salt I' amine
(volatile)

R—NH1 Cl + KOH —p R—NH + KCI + H2O

2imine salt ram Inc

(volatile)
R
1+- +-
R_lj4H Cl + KOR —' R—N + KCI + H10
I
R R

3' amine salt 3 amino

- (volatile)

R-1j—R Cl -j- KOH - No Rection

R
tetraalkylammonium
salt (nonvolatile)

The distillate contains the three free amines i.e., primary, secondary and tertiary, which may
thco be separated by the following methods.


686 Advanced Organic Chemistry

(I) Fractional Distillation. A mixture of primary, secondary and tertiary amines can be
separated into the individual components by fractional distillation since their bailing points are
fairly apart. For example,

CH,CH NH, + (CH,CFI )

1 1 1 NH
PD. (1) CHICH1NH,

I' amine (bp 17°) 2' amine (bp 56)

± (CHCH,)1N -p (2) (CHaCHI)INH
3° amIne (bp 98°) (3) (CH,CHI)1N
This is the most satisfactory method and is used industrially. The success of this method is
primarily due to the high efficiency of the modern industrial fractionation apparatus which
ensures almost complete separation of the amines,
(2) By reaction with Diethyl oxalate Hofmann Method, The given mixture of 1°, 20 and
30 amincs is heated with diethyl oxalate, when
(I) the 10 amine forms a dialkyl oxamide which is crystalline solid.
0 —oC1H6
+ H—HN—RZNH—R
NH—R + 2CIHSOH
CQ-0C H H—HN—R
I 6
-
diethyl oxalate I . amine dialkylosamide
(crystalline solid)
(ii) the 20 amine forms dialkvloxamic ester which is an oily liquid.

FJ + H—N\p.
CO-0C1 5 ('
P.

A
CO—N' + C1H1OH
P.

CO—OC,H
diethyl oxalate
CO-0C1H5
dielkytoxarnlc ester
(oily liquid)
The second ester group does not react presumably because of steric hindrance,
30
(iii) the amine does not react as it does not contain a replaceable hydrogen atom on
nitrogen.
The reaction mixture is now fractionally distilled. The 3° amine distils over and forms
the first fraction. This is followed by dialkyloxamic ester which forms the second fraction.
The dialkyloxamide remains behind in the distillation flask.
The dialkyloxamide and the dialk y loxamic ester separated as above are hydrolysed with
KOH to generate the free amines which are distilled off.
-.4.
CO—NH—R co—OK
I + 2 KOH - + + 2 R—NH, I -
CO—NH--P. CO—OK 1° amine
diethyl oxamidc pot oxalate
R -+
CO—N / CO—OK R
+ 2 KOH + + C1H5OH
R"
COOCoHa CO—OK 2° amine
diethyl oxamic ester
(2) Reaction with ftenzenesulphooyl chloride Hinsberg Method.
This method makes
use of the different reaction 01 l, 2° and tertiary amines with benrenesulphonyl chloride,
(Hrnsberg reagent) i.e.,

c1
o
ro Tor C,H5 _-LCI or


Niphatic Amines 68

The given mixture of three amines is treated with benzenesulphonyl chloride and then rikalifie
with aqueous sodium hydroxide.
jb amine forms N.alkylbenzenesulphonamide which is soluble in base.
(I)
c,He—SOrCl + HN—R- CH 6—SO1 NHR + HCL
benzeneeulphoflyt V amine N-aikyt-benzenesuiphon-
chloride amide

C,H5-50,-14H—R + NaOH -+ [CH 6 —SO—N--R]Na + HO

N-alkyl . sodium benzene-
sulphonamide
(soluble)

(ii) 2° amine forms N, N-diaikylbenzenesuiphonamidc which is insoluble in NaOl-

sohition. This is so because the resulting sulphonamide has no replaceable hydrogen atom ti
yield the sodium salt.
R
C6H 6 —S01—Cl + H—N' -. CA—S01—N" +. HO
benzeriesulphonyl "R
chloride 2° amine N, N. dlalkyl-berszene-
suiphonamide
(Insoluble)

(iii) 3' amine does not react with benzenesulphonyl chloride at all.
The reaction mixture obtained after treatment with benzeneulphonyl chloride in thi
presence of NaOH is now distilled, The tertiary amine passes over first. The remainin
mixture is filtered and the filtrate on acidification gives the sulphonamide of the 1° amine, whik
the solid residue is the sulphonamide of the 2° amine. Tbe two sulphonamides thus is lated
are hydrolysed with hydrochloric acid to regenerate the individual 1° and 2° amines which are
fractionally distilled.
(Hf)
Ci HrSOsNHR + HOH - CeHuSOs0H ± R—NH,
N-alkyl-beflzenesulphonamide bcnzenesulphonic acid i° amine
(H)
C5 H 5 S0 5 N(, -,- HO—H —s CHSOsOH + )NH
20 amine
N.dia1kyt-bnzCoe-
N,
sulphonamide
Now a days benzcnesulphonic chloride has been replaced by p.toluenesulphonyl chloride
CH—C 1 H 4 —SO,C1, since the substituted sulphonamides thus formed are stable solids which
can be easily crystallised.

PHYSICAL PROPERTIES
(1) The lower amines are colourless gases at room temperature. Those with four or
more carbons aire volatile liquids. The higher-molecular-weight amines are colourless solids

(2) Odour. Low-molecular-weight amines, such as methylamine and dimethylarnine,

have strong odours like the smell of ammonia. The odour resembles that of a decaying fish as
the size of the alkyl group attached to nitrogen increases. In general, aliphatic amines are
said to possess 'fishy' or fishlike odours.
1'', Th,, ., -. 11 l;,,hsr ,O,,n
,,ot,.r.

.......................
(4) Boiling points. Simple amines are polar compounds. Primary amines have two
polar N—H bonds, secondary amines have one 'polar N—i-I bond, while tertiary amines have
none.
I-
R—N---H R—N—H R—N—R -

R R
3iniflO
t , anthse 2°smioc


688. Advanced Organic Chemistry

Therefore, primary and secondary amines are polar and capable of forming intermolecular
hydrogen bonds by virtue of the presence of unshared electron pair on nitrogen atom. Tertiary
amines are also polar but they are not capable of intermolecular hydrogen bonding.

R H R R R R R R R
r!l_H ... lT_H,..l%LH...
1—R NI —R ILR

RH R R 1t. )R R

i amine associated by ? amine associated by

hydrogen bonds ( ... ) hydrogen bonding absent
hydrogen bonds (...) in 3 amlrscl

The hydrogen bonds formed by amines (N—HN) are not as strong as the hydrogen bonds
for alcohols (O-.-H•0) of comparable molecular weight. This is so because nitrogen is less
electronegative than oxygen.

On account of their less degree of intermolecular associat i on.' the boiling points of
primary and secondary amines are lower than those of alcohols of comparable molecular weight.
The boilin points of tertiary amities which form no hydrogen bonds are near those of alkanes
of comparable molecular weight.

Table. Boiling Points of Amines, Alcohols and Alkanea of comparable molecular weight.

Structure Name Molecular Weight Boiling Point C

CH,—OH methyl alcohol 32 65
CH,—NH,
methylamine 31 —6
CH,—CH,
ethane 30 —89

CH,—CH,—OH ethyl alcohol 46 78
CH,—CH,—NH,
ethylamine 45 17
CH,—NH—CH,
dimethylansine 45 7,
CH,—CH,—CH,
propane 44 —42

CHI—CH,—CH,_OH n-propyl alcohol 60 97
CH,—CH,—CH,—NH,
n-propylamrne 59 48
CH3—C111—NH—CH,
ethylmethylamine 59 35
CH,—CH,—CH,—.CH,
n-butane 58 —0-5

CH,—CH—OH isopropyl alcohol 60 82
CR,
CH,—CH—NH, i q nnrnnvlondn.
-co 33

CH,—N— CH, trimethylaminc 59 4

CR1
CH,—CH—CH, isobutane 58 MI
CR,


Aliphatic Amines 689

(5) Solubility. All amines including tertiary amines are capable of hydrogen-bond
association with water molecules.

H R H R U R R R
II I
O—H • N— HO—H• — 'N—.H•O—H•N--H• R—NO—H"N—R

H R R R R
10 amine associated with water 2 amine associated with water 3 amine associated with water
Therefore, low-molecular-weight amines (less than six carbon atoms) are very soluble in water.
The water solubility of amines decreases with increasing size of the alkyl group.
Amine CH3NH2 (CI102Nft (CH3 ) 3NH CHCNF{2 (CH 3CI1 2)2NH (CH3CH)33N
Solubility in very soluble very soluble 91 g very soluble very soluble 14 g
100 g 1(O

Large aliphatic amines are soluble in organic solvents such as benzene, ethanol, ether and
chloroform.
(6) Many amines are capable of producing serious physiologiral effects. The low-
molecular weight volatile amines are irritants and cardiac stimulants, like ammonia.

BASICITIES OF AMINES
The unshared electron pair on the nitrogen atom of ammonia and amines is responsible
for their baste character. Ammonia when dISSOlVed in water abstracts a proton from water
molecule to form ammonium ion and hydroxide ion.

H— H4—H [H__H + 0H

AMMONIA AMMONIUM ION

30)
Similarly, all the three types of amines (1°, 2° and reset reversibly with water to form
the alkyl-substituted ammonium ioos and hydroxide ions.

R—NH, + 0—H . RHI + OH

1° amine I alkylammonium ion
H H

+ 0—H R— -j- OH ...(ii)

R H R
r amine diatkylsmmonium ion
R R
I 1.1. -
-- 0—H ± R—NH + OH

r iuiun irialkylammonium ion

Evidently, aqueous solutions of ammonia and amines are alkaline in nature because of
the formation of hydroxide ions as a result of the above equilibria. The value of K (also
called dissociation constant of the base) gives a measure of the base strength. Therefore
equation (1) for a 10 amine the value of Kb may be expressed as
+ -
RNH1 1 (OHJ
Kb - !
- [RNH5J (HIOJ
 690 Advanced Organic Chemistry

Since water is present in large excess its concentration remains practically constant, and
the above expression is therefore written as
+ -
(RNH3][OH]
K
= [RNHaJ
It is clear from, this expression that larger the value of K5 , the stronger would be the
base. The value of Kb for ammonia and a few amines are given below.

Structure Name K5 Structure Name K5

NH, ammonia 0-2I0-4

CH,—NE, methylamine 4'2x 10' CHaCH—.NH, ethylamine 4'7x 10-'
CH,- NH—CH 3 dimethylgmine 6-Ox iO-' CH,CH,—NH—CHCH 3 diethylamine 35 x 10-1
CHs—N-"CH, trimethylamine 0-6x[0- 4 CH,CH 2 —N—CH I CH 3 triethylamine 5'Sx i0-

UHS CH,CH

A look at the values of Kb listed in the table shows that all amines are stronger bases
than ammonia. It is also revealed that 20 amines are more basic than 10 amities but 3' amines
are less basic than 20 amines. Thus the value of K for methylamine is 42 x 1- 4 , that of
dimethylamine is slightly higher (60 x 10- 1 ) and for trimethylamine the value of K5 again
declines to as low as 06 x 10- 1 , The sequence of basic strengths in general is

k—NH, < R—NH—R> R—N---R

1 amine 2' amine
R
3' amine
Interpretation of Relative Strengths of Amities. The differences in- the base strengths of
amines are accounted for by the degree of availability of the unshared electr9n pair on the
nitrogen of an amine. Alkyl groups are electron. releasing compared to hydrogen atom. Thus
when iii a primary amine hydrogen of ammonia is replaced by an alkyl group, electrons will
shift toward the nitrogen relative to the situation in ammonia,
-b., H —...H
H—W'
"I-I
ammonia I' amine
Pig. 284 - Shift of electronsto nitrogen (indicated by —+) enhances the availability of
unshared electron pair of qitrogen.
Hence there will be more electrons close to nitrogen in RNH1 than in ammonia, and
the unshared electron pair on nitrogen is more available to react with proton from water
molecule. That is why methylamine is a stronger base than ammonia. Following the same
line of argument dimethylamine having two electron - releasing methyl groups attached to the
nitrogen atom, is a stronger base than methylamine. If so, trimethylamine having three methyl
groups attached to nitrogen should be expected to be more basic than dimethylansine. But
actually trimethylamine is considerably less basic than dimethylamine. Why so ? In methyl.
amine and dimethylamine the 'electronic effect' described above increases the base strength of
the amine. However, in triniethylamine the overcrowding of the three metflyi groups attached
to nitrogen causes the 'steric effect' to dominate over the 'electronic effect'. This steric effect
retards the protonation of nitrogen which results in an appreciably lower base strength of
trimethylamine.

CHEMICAL PROPERTIES -
The chemical reactions of amh'es are du (i) their basic chnractr end thp.(tj'
reactive hydrogen atoms attached to nitrogen. Some of these reactions are listed below. '


Aliphotic Amlnes - 691

(1) Formation of Salts with Mineral Acids. Owing to. the presence of an unshared electron
pair on nitrogen, amines act as Lewis bases. Thus they react with aqueous riineral acids to
form substituted ammonium salts. For illustration with aqueous hydrochloric acid,

(i) 1° amines form alkylammonium calls

H H
I +- I
R—N: + HCI —i R—N: HI Cl

H H
1, amine an alkylammonium chloride

or R—NH1 + HCI - R—NH3CI

4- 4-
e.g., CH,—NH, ± HCI -.
CH,—NH3CI
methylammonium chloride

(ii) 2° amities form dialky!ammonium salts

H H +

HCI -+ R--N : HI Cl

R R
2 amine a dialkylammonium chloride
+ -
or R—!11H + HCl —f R—NH8CI

e.g., CH3—NH + HCI --p CH3—NH5CI

CH 3 CHa
dimethylamine dirnethylammonium chloride

(iii). 3° amities form tria!kylammoniu pn salts :

R R
I +- I -
R—N: + HCI .- R—N : H Cl

R 1.
3° amine trialkylammonium chloride
4- 4.
or R3N + HCI —p R3NHCI
+-
e.g., (CH3)3N + HCI -f (CH3)3NHCI
trimethylamine trimethylamine chloride
The amine salts are generally well-defined crystalline substances with •sharp welting
points and are often useful for the identification of amines. Further, these amine salts, unlike
the amines, are water soluble and regenerate the amines on treatment with a strong alkali such
dS IdJU1
+ -
R—NH3CI + NaOH -' R—NHZ + H 20 + NaCl
alkytt,nsmonium salt P amine
This property is made use of in purifying amines from nonbasic contaminants.

(2) Alkylation Reactions. The unshared electron pair on the nitrogen atom makes
am:nes behave as strong nucleophiles. Thus when a primary amine is treated with an alkyl
halide in a basic medium such as ammonia, the halogen atom of the alkyl halide is displaced


692 Ad v anced Organic Chemistry

yielding dialkylatnrnonium salt. The dialkylammonium salt in the presence of ammonia at

once gives a secondary amine.

is -
A-N--H f P.-X __
-b.. A-N--H + x

H i-I
7I2'4INE D/AL,OL4MMOIWU.f
CAT/ON

N—H
R-T—H -b + NH

DIALXTLAHMONIUM 2' AMINE

CATION
The net alkylation reaction of a primary amine with alkyl halide may be written as

R--NH + R—X -, R—NH—R + HX

1 0 amine ethyl halide 2' amine halogen acid
The secondary amine undergoes similar reaction with a second molecule of alkyl halide to form
a tertiary amine. The tertiary amine finally reacts with a third molecule of alkyl halide to
produce the tctraalkylammonium salt. These multiple alkylation reactions of amines may be
illustrated by the action of methyl bromide on methylamine.

CH3 -NH 1 + CH3 —Br -p CH,—NH—CH, + H13r

meihylamine dimettiylamine
(I' amine) (20 amine)

CH,—N H—CIT 3 + CH—Br -p

CH,—N—CH + HBr
(2ndmalecule) I
CH,
trimethylamine (30 amine)
CH, +.

CH3—N—CH, + CH,—Br ---+ CH,—N--CH 1 Br

(3rd molecule)
CH, I
CHa
tetrimethylanunonjum bromide

From the above equations it is clear that a primary amine will need three molecules of alkyl halide
per molecule of amine, secondary amine two molecules, and a tertiary amine only one molecule
to form the final tetraalkylammonium salt. Thus by experimentally determining the amount
of alkyl halide actua]13 used for the conversion of a given amine to the tetralkylammonium
salt, it is possible to distinguish between primary, secondary and tertiary amities. Also, the
alkylation of a primary and secondary amine under rcguiaicd coniiiiivus pruidca au indubirial
method for the preparation of secondary and tertiary amine respectively.

(3) Acylation. Primary and secondary amines react with acyl halides (RCOCI) and
carboxylic anhydrides whereby the hydrogen atom attached to nitrogen atom is replaced by
acyl group (RCO—). By this process of acylafion a primary amine produces N-substituted
arnide while a secondary amine yields N, N-disubstituted amide. A tertiary amine having no
available hydrogen on nitrogen, does not ,react at all either with acyl hlidca or uarboxyliu
anhydrides.


Aliphatic Amffi,s 693

H 0HO
II II
R—N---H + R'—C--CI —+ R—N—C--R' + HCI
1° amine acyl chloride N.atkylamidc
R o R0
I I
R—N—H + R'—C—Cl —s R—N—C—R + HCI
II
20 amine N, N-dialkylamlde
R o
I i
R—N + R'—C--Cl —, No Reaction

3° amine
(no available H-atom)

For example,
CH1 —NH, + C11 1—00—C1 - CHNHC0CH5 + HCI
ethylamine acetyl chloride N-etbylacetamldc
C1H1—N—H + CH5---CO—CI —' C2H5—N—CO--CH3 + HCI

CHs
diethylainine N. Mdleihylacctzmide
C1H5-1(--C.H + C1I1COCI -. No reaction

triethylamine
As stated above, primary and secondary amities also react with carboxylic anhydrides to
give substituted amides.

R—NH1 + CH,--COO — R—NH—COCH, + CH8COOH

11 amines CH—CO' N-alkylacetamide
CH,—CO
R—NH--R + "0 —i R—N—R + CH1COOH
2° amine CH1—CO" I
cOCH,
N, M-dialkylacetamide

In all the above reactions, acylatIon of amities is carried out effectively in the pMsence
.f tertiary amities which help the removal of the acid (HCl or CH300014). The tertiary amine
which is most often used as 'acid scavenger' is the aromatic base pyridine. Thus

R— NH2 + + —' R—NHCH3• + nj

-
- PYRIOINE H Cl
- PTRIDINIUM
- - ''lORIO
En Schoffen-Bas=aa procedure of acytation of amities, a mixture of amine, cold aqueous
base (NaOH or Na1 CO 5) is shaken together. The aqueous alkali acts as scavenger for the HX
produced.
cold
R—NH, + CH,COCI + NOH ..— R—NH—COCH 5 + NaQ- + H10
Mechanism olAcysatlon of Asnes. The usshared electron pair on nitrogen plays a key
role in amide Iormacn by acy!stion or amines. The reaction takes place by the nuleophiIj
 694 Advanced Organic Chemistry
attack of the primary or secondary amine on to the carbonyl group of acyl chloride. This is
accompanied by the los; of Cl- and a proton.

H CH, H/CM3 0
I - çí+ I _____
K N:' T'N.,0
R—N-_C=o -k K—NH—C —(H3
I N-ALKYLAff1AAf1DF
H C1 H
ACETYL
CHLORIDE

The above mechanism of acylation of ainines also shows why only one of the two
hydrogens of a primary amine is replaced by acyl group in actual practice. The N.acylamine first
produced is far less basic than the original amine, because of electron-withdrawal from the
nitrogen atom by induction and resonance. Therefore, further acylation oIN-acylamine does
not take place and as a result only one acyl group can be iqtroduced into a primary amines,

(4) Sulphonylation. Suiphonyl chlorides are the acid chlorides produced by the reaction
of phosphorus pentachioride or thionyl chloride (SOd,).
o 0
II PCI, II
R—S—OH - R—S—Cl + HCI
II orSOCi2
o 0
a suIhonic acid a suiphonyl chloride

They react with amines in a manner similar to acyl chlorides. Thus benzenesulphonyl chloride
(C1 11,SO,Cl) reacts with primary and secondary amines to from N-alkyl and N, N-dialkyl-
sulphonamides respectively-

R—NH, +
I' amine (
97 s0

bcnzcnesul phooyl chloride

R—NH_S0_(j + HCl

?(-a1ky1benzasnlpie

-, RN--S0_@ + HCl
R1H +

R . &N-dlalkylbenzcnesulphonamide
2° amine

R—t-R + lIr501_d1 -i No Reaction

R
3° amine
(no available H-atom)

Most sulphonamides are crystalline solids. Their preparation and determination of

melting point is used for the identification of primary and secondary amines.

Hinsheig Test for distinguishing 1°, 20 and 3 amines. The reactions of amines with
benzenes ulphonyl chloride form the basis of the classical Hinsberg Test to determine the class
of an amine. In this test the giv-' ' 'viinc is treated with benzenesulthonyl chloride Hinsberg
Reagent) in the presence of cold aqueous NaOH.

(a) A PRIMARY AMINE produces Nalkylsulphonamide which contains an acidic

hydrogen and hence dissolves in NaOH solution to form the soluble sodium salt. The acidifi-
cation of the solution gives a precipitate of the nonbasic free sulphonamide.


Aliphatic Amines 695

çactdic hydrogen NaOH

NaOH
RNH, + CH,—SO,--Cl - R—NH—S0,—C 6H5 R—N--SO,—.C.H-p
1. anuoc H2O NaJkylsutpbooamide sodium salt
(water johthle)

Ita
R—N—SO,—C,H, -. R--NH—S0,----C,H,
H10 free sulphonamide
(in,solable in acid)
The unusual acidity of N-alkylsulphonamides is due to the powerful electron-withdrawing
inductive effect of the suiphonyl group (—SO,--).
(b) A SECONDARY AMINE yields N, N-dialkylsuiphonamide which has no acidic
hydrogen precipitates immediately as it is incapble of forming soluble sodium salt with NaOH.

no acidic hydrogen NaOH

NaOH
R,NH + CH—SO5 —C] -' R,N—SO,--CH, -, No Reaction
r amino HSO N, N-dialkylsulphooamide
(Insoluble ppl)
(c) A TERTIARY AMINE having no available hydrogen does not react and remain as
insoluble material.
To apply the Hinsberg test, the amine to be tested is shaken with benzenesulphonyl
chloride and cold aqueous NaOH. If a homogeneous solution results which on acidification
forms a precipitate, the amine is primary. if rin insoluble material is produced in tho reaction
mixture straightaway (without acidification), the amine is either secondary (the insoluble material
being dial kylculphonanide) or tertiary (insoluble material being unreacted amine). To distin-
guish between the secondary and tertiary amines, the insoluble material is acidified. A tertiary
amine if present will form a soluble quaternary salt and dissolve, while a sulphonamide from a
secondary amine being neutral remains insoluble material.

Table. Summary of Hinsberg Test

NaOH acidifly
R—NH, + C,H,—.SO,--Cl -+ clear solution -+ insoluble material
1' amine H,0
NaOH - acidify
R—NH + C,H1—SO,—Cl - insoluble material - insoluble material

R
1 H2O

?amlns
NaOH acidify
R—N—R + C.H—SO,—Cl -* insoluble material -+ clear solution

R
I H2O

? amine

In modern practice benzenesulphonyl chloride is also replaced by ptolucnesulphonyl

chloride,

CFi./?SO.Cl

(5) Reaction with Nitrous Acid. Nitrous acid is an unstable substance prepared when
required, by reaction between a mineral acid and-sodium nitrite (t4aN05).
+ -
- NaNO, + HCl -. HO—N=O + H2O
nitrous acid
Primary, Secondary and Tertiary amines give characteristic reactions with nitrous acid.
696 Advanced Organic Chemistry

(i) Primary amines (RNH,) which have two available hydrogen atoms on nitrogen react
with nitrous acid in aqueous solution to form the corresponding alcohols.

R—NH,-4-O=N—OH -. R—N=N---OH - R—OH +N,f

1. amine nitrous add vutable alcohol

The reaction is not that simple as stated above. In fact, primary amines react with
nitrous acid to give mixtures of a variety of products which contain alcohols, alkenes, aud even
halides, if halide ion is present. For example, if the primary amine taken is n.propylamine,
the products will include n . propyl alcohol, isopropyl alcohol, propene, propyl chloride and
isopropyl chloride.

CH5CH1CH1-011

OH

CH, H--CH,

HONO
CH,CH5CH1NH, CH—CH=CH1 + N1 + H1O
n-propylamine (HCI)

CH1CH,CH,--Cl

CCl

H5—(H—CH

rhe exact nature and proportions of products obtained depends very much on the structure of
the amine an4 the specific reaction conditions employed.

The formation of various products obtained from n.propylamine by the above

mechahism may be indicated as below.

+
+ + H10 CH,—CH 5—CH,--OH, - CH5CH1CH1OH
CH,—C%—CH,
CH,—CH=CH1
+ CH,—CH,—CH5CI
+
OH, OH
—H+
+ + H1 0 - CH5 —CH—CH, ­6 CHI—CH—CH,
CH,—CH—CH, —11k CH3—CH=CH1
ll
9
+a CO5—H—CH5

It may be noted particularly that whatever may be the pruduci.s uf iis ieacton, nitrogci
always evolved.

MECHANISM. The various products obtained from primary amines by reaction with
nitrous acid are formed by the following steps.

(a) Nuclophilic addition of the amine RNHS to nitrogen-oxygen double bond of

nitrous acid to give the adduct I.
 AIIphdUc Amlnes 697

IAMINE

(b) Protonation of I followed by elimination of the molecules of water to form

alkyldiazonium ion.

HOH
I }t I I —2HO +
R—N—N: —p R—NN:
alkyldiazonjum ion
H0H HOH
I II UI

(c) Alkyidlazonium ion Ill is unstable and loses nitrogen (NN) to generate carbonium
ion IV.

R + :N=—

LIT CAR8ONWM ION NSTeOFN

'V

The carbonum ion IV may rearrange to give more stable carbonium ion V (not shown).

(d) The carbonium ion IV and V may react with water (11 1 0) to form alcohols, lose
a proton to form alkanes, or add halide ion (C1) to yield alkyl halides,
(ii) Secondary amines ( R1 NH) react with nitrous acid (1-10—N =0) to give neutra:
yellow oily substances called Nitrosuamines. The process which involves the replacement of :
available hydrogen on nitrogen by nitroso group (—N=0) is termed Nitrosatiota.

+ HO—N=0 —i R—I'l—N=0 + H10

2' amine nitrous acid nitrosoamine

(yellow oil)
When warmed with a little phenol and a few drops of conc }11 SO4, nitrosoamines producL
green solution which turns deep blue or violet on alkalication with NaOH. This react
known as Liebermanu Nitrosoaunlcie Reaction is used as a test for secondary amities.
Nitrosoammes are generally poisonous and ae considered to be cancer-causing age
in some foods sodium nitrite is used as preservative and in the stomach it combines wiiij
hydrochloric acid to produce nitrous acid. This can react with any secondary amines present
in foods to form a dangerous nitrosoamine. Therefore, the intake of sodium nitrite in any
form should be avoided.
(ill) Tertiary amines (RN) having no available hydrogen on nitrogen fail to give a
replacement reaction with nitrous acid. They simply form soluble rialkylammonium salts
of nitrots acid.

1 -
H0—N=0 - [ R—N—H 0—N.=0
R L.R
3' amino Irialkylammonium nitrite
(a soluble salt)
The tertiary amine can be regenerated from the salt solution by addition of alkali.

Organic Chemistr y - 45


Advanced Organic Chemistry

698

The reaction of aliphatic amines with nitrous acid is used as a test for distinguishing
primary, secondary and tertiary amines.
(a) Primary amines react with rapid evolution of nitrogen gas.
HONO
R—NH1 -+ R + N2f
carbonium ion
(b) Secondary amines form an insoluble yellow oily layer.
HONO
R 1 NH -p R1N—NO
nitrosoamine
(c) Tertiary amines form a homogeneous solution.
HONO -
RN -+ [R 3 NH] + O—N=O
soluble saLt
(6) Reaction with Aldehydes and Ketones. (a) Primary amines add readily to the C=O
'roup of aldehydes and ketones to form a-hydroxyamines, also called Carbinolamines. These
indergo s p ontaneous elimination of a water molecule yielding substituted imines or Scuff bases.
rue reaction is catalysed by acids.
H HOH
I H I I. —HjO
R—N—H + R'—C=O ----# -+ R—N=CH—R'
I amine an aldirninc
H H
aldehyde a-hydroayamine

H 1OH
H+ 1 I —IhO
R—N—H + R—C=O —s R—N—C—R' —4 R—N=CR',
I a ketimine
R R

(b) Secondary amines react with aldehydes and ketones that have a .-H atoms when
transitory -hydroyamine at once splits out a water molecule to form compounds known as
enamines. Thus,
H OHH
H I I
R—N—H + W—C—C=O -.=t R—t—C—C—R' =± R1N.—CRCR
I I I enamine
R R' R' RR' R'
20 amine ketot booing
a-H atom
In enamine the basic nitrogen is attached directly to an olefinic carbon. These
compounds are useful synthetic intermediates.

(c) Tertiary amine, having no hydrogen on nitrogen naturally cannot react with
aldehydes and ketones.
(7) Reaction with Carbon dI.siInhicl. (al Primary aminec when rearieA with carbon
disulphide (CS 1 ) form dithiocarbamic acids which on subsequent treatment with HgCJ1 give an
alkyl isocyanate or 'mustard oil'.
S S
II Hga1
R-NH + C=S RN—C—SH -. R—N=CS + HgS + 2HCI
alkyllsotbioqyanate

1° amino dlthlocarbaanlc acid

AllphdUc AmIies 699

The isothiocyanate thus produced has a pungent 'mustard like' odour which can be easily
recognised. Hence this reaction (Hofmann Mustard Oil Reaction) is used as a test for primary
amities.
(b) Secondary amines react with carbon disuiphide to give dithiocarbamic acid which is
not decomposed by H8CI, to form alkyl iothiocyanate.
S S
IT HgCl2
RljH + C=S - R—N—C—SH —p No Reaction
R R
? amine dithiocarbamic acid

(a) Tertiary amines having no available hydrogen atom on nitrogen do not react with
CS'.

(8) Halogenation. Primary and secondary amines react rapidly with a solution of
hypochiorous acid in the presence of a base to produce N-chloroamines or N, N-dichloroamines,
H H Cl
Tioci HOCI I I
R—N--H —+ R—N--.C1 —p R—N—Gl
V amine OH- N.chloroamine OH- N, V.dichloroamine
Secondary amities give mono-N-chloroamines
R R
I HOCI I
R—N—H - R-'-N—Cl
2 amine OH- N.chloroamine

The chlorination of amities is carried more conveniently with t-butyl hypochiorite,

(CH,),C—OCI.
(9) Rtaction.with Crignard Reagents. Primary and secondary amines react with Grignard
reagents to form alkanes. Tertiary amines do not react since they do not contain a replaceable
hydrogen atom.
H
I ether
R—N —H + R'MgX —p R'H + RNHMgX
I' amine alkane
R
Iether
R'MgX —i RH + R,NMgX
T amine '' alkanc
iu) Carbylatnine Reaction. Primary amities form isocyanides or carbylamines when
warmed with chloroform (CHCI,) and an ethanolic solution of KOH.
+ -
R—NH 1 + CHCI 3 + 3KOH -.-. R—NC + 3KCI + 31410
I' amine alkyl inocyanide,
or arbylamine
The isocyanide or carbylamine so produced has an extremely unpleasant odour and hence this
reaction, frcqucnty cae.d caiby1amiz 'euciion, is used as a qualitative diagnostic test (carbyl-
amine Test) for primary amities. Secondary and tertiary amities do not respond to this test,
MECHANISM. The formatian of carbylamine takes the following pathway.
(i) Chloroform in the presence of base (KOH) produces dichlorocarbene (:CCIa).
- - slow -
CHCI, ± OH —f H1 0 + CCI, - CC], + Cl

(ii) Nocicophilic addition of primary amine to dichlorocarbene and subsequent elimina.

tion of two HCI molecules yields the isocyanide.


700 Advanced Organic Chemistry

a—NHHcI2

— HCI —HC + -
--- RN=:CHCf - p —N=C: 4 - R—NC
ALKYL ISOC VA/WOE
OR CAR8YL AM/NE
(ii) Oxidation of Amines. All types of amines are easily oxidised. The course of the
reaction is very variable and depends very much on the structure of the amine and the specific
oxidant used.
(a) Primary amines on oxidation with acidified KMnO4 give aldehydes and ammonia.
o +l1O
R—CH,—NH, —p R—CH=NH - R—CH=0 + NH
11+
aldimine aldehyde
o +H20
R—CH--NH2 - R—C=NH —p R—C=0 + NH,

R
I I
R
11+
R
ketiinine ketone
R R
I 0
R—C—NH 2 -. R—C—N01

R
a nitroalkane
(b) Secondary amines on oxidation with KMnO 4 give tetraalkylhydrazine, while with
H.O. or peracid they yield dial kyihydroxylamine.
KMnO4
2 R—N—H -i- [0] .- Rj1_N_R + H0

R RR
tctraalkylhydrazinc
Hn0?
R--N—H + [0] —+ R—N—OH
1 or peracid I
R R
dialkyihydronylarnine
(c) Tertiary amines from amine oxides when oxidised with HSO1 or peracids.
F. R
I
R—N: +0: -. R—N-0
H0 L-
I orperacid ..
R R
amine oxide
HaOn + -
e.g.,. (CHs)3N + [0] —p (CH1),N-0
trimcthyiiuiue tri,ncyrnr.c.N ccdc
IR AND NMR SPECTRA OF AMINES
A characteristic feature of infrared spectra of 1° and 20 amines in dilute solutions is the
absorption at 3500— 3300 cm- 1, corresponding to N —H stretching. 1° amines have two such
bonds, 2° amines only one, while 3° amines (which contain no N—H bond) do not absorb in
this region. Furthermore, the area generated by one or two amino protons is generally quite
small as compared with the rest of the spectrum. Hence, the amino protons are sometimes
observed by absorptions arising ftun ui'uci pans of Uc occuiar stct';. This c!ca'es
the interpretatio, of the spectrum.