CHM301

ORGANIC CHEMISTRY II

CHAPTER 9
AMINE

Puan Nordiana Suhada Mohmad Tahiruddin

 SUBTOPICS
o Structure of amines
o Naming amines
o Preparations
o Reactions
 STRUCTURE OF AMINES

Amines:
organic derivatives of ammonia with one
or more alkyl or aryl groups bonded to the
nitrogen atom.

General formula:
RNH2 and ArNH2 (Ar = aryl)
Functional group:
Classification of amines:

Primary amine Secondary amine Tertiary amine

• Primary (1o) amine: one alkyl or aryl group attached to the
nitrogen atom.
• Secondary (2o) amine: two alkyl or aryl group attached to
the nitrogen atom.
• Tertiary (3o) amine: three alkyl or aryl group attached to
the nitrogen atom.
• Quaternary (4o) amine: an ion in which nitrogen is bonded
to four alkyl or aryl groups and bears a positive charge.

CH3
H3C N CH3
CH3
 NAMING AMINES

Common names:
- formed from the names of the alkyl groups
bonded to nitrogen, followed by the suffix –
amine.

- the prefixes di-, tri-, and tetra- are used to

describe two, three or four identical
substituents.
 CH3
CH3 CH2 NH2 CH3 CH2 N (CH3CH2CH2CH2)4N+ -CI
CH3
ethylamine
ethyldimethylamine tetrabutylammonium chloride

CH3
N
CH3
cyclohexyldimethylamine
IUPAC names:

- similar to that alcohols.

- the longest continuous chain of carbon atoms

determine the root name.

- the –e in alkane name is changed to –amine, and a

number shows the position of the amino group along
the chain.

- other substituents on the carbon chain are given

numbers, and the prefix N- is used for each
substituent on nitrogen.
 NH2 CH3 NH2
CH3 CH2 CH CH3 CH3 CH CH2 CH2
4 3 2 1 4 3 2 1

2-butanamine 3-methyl-1-butanamine

CH3 CH3
NHCH3 CH3 CH2 CH CH CH CH3
CH3 CH2 CH CH3 N CH3
4 3 2 1
CH3
N-methyl-2-butanamine N, N,2,4 -tetramethyl-3-hexanamine
 The prefix amino is used to indicate the
presence of an –NH 2 group in a molecule
containing more than one functional group or in
compound with complicated structures.
 For examples,
NH2CH2COOH H2NCH2CH2OH
aminoethanoic acid 2-aminoethanol

OH
NH2 CHO

NH2 NH2
2,4-diaminophenol 3-aminobenzaldehyde

COOH
NH2
H2N
3-aminocyclopentene p-aminobenzoic acid
 NAMING CYCLIC AMINES

• The –e in cycloalkane name is changed to –amine

• Examples: cyclohexane → cyclohexanamine

cyclobutane → cyclobutanamine

• The amino group is assumed to be on C1.

 NH2CH2COOH H2NCH2CH2OH
aminoethanoic acid 2-aminoethanol

OH
NH2 CHO

NH2 NH2
2,4-diaminophenol 3-aminobenzaldehyde

COOH
NH2
H2N
3-aminocyclopentene p-aminobenzoic acid
 NH2
1
NH2 6 2
3
5
4 CH3
cyclohexanamine 3-methylcyclohexanamine

NHCH3
1
5
2
4 3
CH2CH3
3-ethyl-N-methylcyclopentanamine
 NAMING AROMATIC AMINES

Aromatic amines have an amine group (-NH2)

attached directly to the aromatic ring.
Aromatic amines known as arylamines.
Examples:
 NH2
NH2 CH3 1
2 6 2
NH2
3 1 5 3
4 6 4
5 NO2
phenylamine 2-methylphenylamine 4-nitrophenylamine
(aniline) (2-methylaniline) (4-nitroaniline)

H CH2CH3
N CH3 N CH3

N-methylaniline N-ethyl-N-methylaniline
Compounds with two –NH2 groups are named by
adding the suffix ‘diamine’ to the name of the
corresponding alkane or aromatic compounds.

H2N (CH2)6 NH2 H2N NH2

hexane-1,6-diamine benzene-1,4-diamine
(1,6-hexanediamine) (1,4-benzenediamine)
 PREPARATION OF AMINES

 Reactions of alkyl halides with NH3 or RNH2.

 Reduction of nitriles (Preparing primary amines).
 Reduction of amides.
 The Hoffman degradation.
 Reduction of nitrobenzene.
 REACTIONS OF ALKYL HALIDES WITH
NH3 AND RNH2

Alkyl halides react with concentrated solution of

ammonia in ethanol to form primary amines via SN2
mechanism to give alkylammonium salt, RNH3+X-.

R X NH3 RNH3+X
alkylammonium salt
Proton transfer between alkyl ammonium salt and
ammonia yields primary amine and ammonium salt.

RNH3+X NH3 RNH2 NH4+X

alkylammonium salt ammonium salt
• The reaction continues in excess alkyl halides to form
secondary, tertiary amines and quaternary ammonium
salts, R4N+X-

• The alkyl halide is heated with a concentrated solution of

NH3 in ethanol in a sealed tube.

• The mixture cannot be heated under reflux because NH3

would simply escape up the condenser as a gas.
 H H
R N H R' X R N R' HX
primary amine secondary amine

H R''
R N R' R'' X R N R' HX
secondary amine tertiary amine

R'' R''
R N R' R''' X R N R' X
tertiary amine
R'''
quaternary ammonium salts
Examples:

CH3CH2Br 2NH3 CH3CH2NH2 NH4Br

primary amine

CH3CH2Br CH3CH2NH2 (CH3CH2)2NH HBr

secondary amine

(CH3CH2)2NH CH3CH2Br (CH3CH2)3N HBr

tertiary amine

(CH3CH2)3N CH3CH2Br (CH3CH2)4N+Br

quaternary ammonium salts
 REDUCTION OF NITRILES
(PREPARING PRIMARY AMINES)

• Nitriles react with strong reducing agent like H2

with catalyst (example Ni) or LiAlH4 to yield
primary amines via nucleophilic addition reaction.
• NaBH4 cannot reduce nitriles.

2H2, catalyst
R CN R CH2NH2
or LiAlH4, ether
Examples:
2H2, Ni
CH3CH2C N CH3CH2CH2NH2

CH2CN 2H2, Ni CH2CH2NH2

140OC
 REDUCTION OF AMIDES

• Amides is reduced to the amines by using strong

reducing agent like LiAlH4.

• The oxygen atom is replaced by two hydrogen atoms.

• Reaction occurs via nucleophilic acyl substitution

then nucleophilic addition.
 O
i) LiAlH4, ether
R C NH2 R CH2 NH2
1o amide ii) H2O 1o amine

O
i) LiAlH4, ether
R C NHR R CH2 NHR
2o amide ii) H2O 2o amine

O
i) LiAlH4, ether
R C NR2 R CH2 NR2
3o amide ii) H2O 3o amine
 THE HOFMANN DEGRADATION

Hoffman degradation:
- Heating the amides with a mixture of bromine and
KOH or NaOH.

- amides will change to amines.

- is used to shorten the chain by one carbon.

 O
KOH, Br2
R C NH2 R NH2 CO2
amide H2O, amine

Complete chemical equation:

RCONH2 + 4KOH + Br2 → RNH2 + K2CO3 + 2KBr + 2H2O

 REDUCTION OF NITROBENZENE

• Aniline is prepared from nitrobenzene.

• Firstly, benzene is converted to nitrobenzene and
then further reduced to form aniline.

NO2 H2, catalyst (eg: Ni)

NH2
H2SO4
HNO3
or 1) Fe, HCl
benzene nitrobenzene 2) OH- aniline
• The reaction can also applied to substituted
nitrobenzenes.
• Reducing agents: Fe/H+, Sn/H+ or catalytic
hydrogenation (example, H2/Pd or Pt or Ni).

Sn, HCl
H2N NO2 H2N NH2
heat

H2, Pt
CH3CH2 NO2 CH3CH2 NH2
ethanol
 REACTIONS OF AMINES

 Salt formation
 Amide formation
 Isocyanide formation
 Reaction of amines with nitrous acid, HNO2
 Substitution reactions of arenediazonium salts
 SALT FORMATION
Amine salt:
- composed of two types of ions:
i ) the protonated amine cation (an ammonium ion)
ii) anion derived from the acid or alkyl halides

Amine salts are ionic, have higher melting points,

nonvolatile solids, more soluble in water than the parent
amines and slightly soluble in nonpolar organic solvents.
i) Reaction of amines and acid

R NH2 HCl RNH3Cl

primary amine alkylammonium chloride

R2NH HCl R2NH2Cl

secondary amine dialkylammonium chloride

R3N HCl R3NHCl

tertiary amine trialkylammonium chloride
EXAMPLES:

CH3CH2CH2 NH2 HCl CH3CH2CH2 NH3Cl

n-propylamine n-propylammonium chloride

(CH3CH2)3 N HCl (CH3CH2)3 NH Cl

triethylamine triethylammonium chloride
ii) Reaction of amines and excess alkyl halides

• Amines reacts with excess alkyl halides to give alkylated

ammonium salts.

• Alkylation proceeds by the SN2 mechanism where the

amine is act as nuclephile.

RX RX RX
R-NH2 R2NH2 R3N R 4 N+ X -
1° 2° 3° Alkylammonium salt
• The initially formed salt may become deprotonated by
NaHCO3 or NaOH.
• The resulting secondary amine is nucleophilic, and it can
react with another molecule of the halide.

R NH2 R' CH2 Br R NH2 CH2 R' Br

primary amine primary halide salt of secondary amine
 H H
R N CH2 R' Br NaOH R N CH2 R' H2O + NaBr
H secondary amine

R NH CH2 R' R' CH2 Br R NH CH2 R' Br

secondary amine
CH2R'
salt of a tertiary amine

R NH CH2 R' Br NaOH

R N CH2 R' H2O + NaBr
CH2R' CH2R'
salt of a tertiary amine tertiary amine

CH2R'
R N CH2 R' R' CH2 Br R N CH2 R' Br
CH2R' CH2R'
tertiary amine alkylated ammonium salt
Example:
CH3
NaHCO3
CH3CH2CH2NH2 3CH3I CH3CH2CH2 N CH3 I 2HI
CH3

H CH3 CH3
CH3CH2CH2N H CH3 I CH3CH2CH2N H CH3 I CH3CH2CH2N CH3

CH3 I

CH3
CH3CH2CH2 N CH3 I
CH3
2HI
Example:

What is the product when ethylamine reacted with excess methyl chloride ?

H CH3
CH3CH2N H CH3Cl (excess) CH3CH2 N CH3 Cl
CH3
 FORMATION OF AMIDES

i. From acyl chlorides

O O

R C Cl 2RNH2 R C NHR RNH3+Cl-

acyl chloride amine secondary amide

O O

R C Cl 2R2NH R C NR2 R2NH2+Cl-

ii. From acid anhydrides

O O O O
+
R C O C R 2RNH2 R C NHR R C O RNH3
acid anhydride amine amide

O O O O
R C NR2 +
R C O C R 2R2NH R C O R2NH2
iii. From esters
Esters reacts with ammonia, primary and secondary amines
to produce amides and alcohols.

O H O R
R C O R H N R R C NH R OH
ester primary amine secondary amide

O R O R
R C O R H N R R C N R R OH
ester secondary amine tertiary amide

EXAMPLE
O H O
O
0-5 C
H3C C O CH2CH3 H N H H3C C NH2 CH3CH2 OH
 FORMATION OF ISOCYANIDE
(ISOCYANIDE TEST)

Isocyanide:
 An organic compound with functional group.
R N C

 The CN functionality is connected to the organic

fragment via the nitrogen atom, not via carbon
atom.
 A zwitterion (nitrogen atom carries positive
charge, carbon atom carries negative charge).
i. Formation of isocyanide:
Primary amines heated with trichloromethane
(CHCl3) and alcoholic KOH solution will produce
a foul odor of isocyanide, RNC.

RNH2 + CHCl3 + 3KOH RNC + 3KCl + 3H2O

isocyanide

EXAMPLES
CH3CH2NH2 + CHCl3 + 3KOH CH3CH2NC + 3KCl + 3H2O

NH2 NC
+ CHCl3 + 3KOH + 3KCl + 3H2O
 ii. The reaction of primary amines with
dichlorocarbene (CCl2) and NaOH.

RNH2 + CCl2 + 2NaOH RNC + 2NaCl + 2H2O

isocyanide

EXAMPLE

CH3NH2 + CCl2 + 2NaOH CH3NC + 2NaCl + 2H2O

isocyanide
 REACTION OF AMINES WITH NITROUS ACID

• Nitrous acid (HNO2) is unstable and is prepared in situ by

the reaction of dilute HX (HCl, HBr, or H2SO4) with
sodium nitrite in the absence of heat.
• Example:
NaNO2 (s) + HCl (aq) → NaCl (aq) + O=N-OH (aq)
nitrous acid

• Nitrous acid can be used to differentiate primary,

secondary and tertiary aliphatic amines.
* PRIMARY ALIPHATIC AMINES *
Highly unstable diazonium salt, RN2+X- is formed when
primary amine is treated with a cold mixture of NaNO2 and
HX.

RNH2 + NaNO2 + 2HX → [RN2+X-] + NaX + 2H2O

Diazonium salt formed in the reaction dissociates into

carbocation, R+ with the release of N2 gas.

[RN2+X-] → R+ + X- + N2

The carbocation reacts to form mixtures of products

including alcohols, alkenes and alkyl halides.
Examples:
i) Ethylamine gives nitrogen and a mixture of ethanol (60%),
ethene and other products.

C2H5NH2 + O=N-OH → C2H5-OH + H2O + N2 (g) + other

products

ii) The reaction of propylamine with HNO2 produces nitrogen

and a mixture of 1-propanol (7%), 2-propanol (32%) and
propene (28%).

iii) The reaction of methylamine with HNO2 produces only a

little methanol, and the main products are methoxymethane
and nitrogen.
* SECONDARY ALIPHATIC AND AROMATIC
AMINES *
Aliphatic secondary amines react with HNO2 at room
temperature to form N-nitrosoamines / N-nitrosamines
(yellow oils).

R2N-H + NaNO2 + HCl → R2N-N=O + NaCl + H2O

or
R2N-H + HO-N=O → R2N-N=O + H2 O
nitrous acid N-nitrosoamine
Examples:

CH3 CH3
N H HO N=O N N=O H2O
CH3 CH3
dimethylamine N-nitroso-N,N-dimethylamine

CH3
NHCH3
HCl N
NaNO2 N=O NaCl + H2O
cold
* TERTIARY ALIPHATIC AMINES *
A tertiary aliphatic amines react with HNO2 will produced
ammonium salts which is dissolve readily in water as a clear
solution.
2R3N + NaNO2 + 2HX → R3NH+X- + R3N-N=O+X-

Example:

CH3 CH3
H3C N HNO2 H3C N H
CH3 nitrous acid CH3
trimethylamine trimethylammonium ion
 # PRIMARY AROMATIC AMINES #

• Aniline reacts with HNO2 (prepared in situ by

mixing NaNO2 and HCl, HBr or H2SO4) to form
very stable arenediazonium salt.
• The process is called as diazotization.

-
NH2 NaNO2 + 2HX N2+ X NaX + 2H2O

Example:

-
NH2 NaNO2 + 2HCl N2+ Cl NaCl + 2H2O

arenediazonium or benzenediazonium chloride

# TERTIARY AROMATIC AMINES #

Tertiary aromatic amines reacts with nitrous acid

by undergoing substitution at the para position of
the benzene ring to form nitrosoaniline which is a
yellow precipitate.

R R
N R HNO2
< 5oC ON N R

a nitosoamiline compound (yellow precipitate)

Reaction of nitrous acid with aliphatic amines in cold acidic
solution can be used to distinguish between primary,
secondary and tertiary amines.

RNH2 + HNO2 → N2 gas evolution from a clear solution.

(1° amines)

R2NH + HNO2 → An insoluble yellow oil formed

(2° amines) (N-nitrosoamine)

R3N + HNO2 → A clear solution (ammonium salt formation)

(3° amines)
SUBSTITUTION REACTIONS OF ARENEDIAZONIUM
SALTS

• Arenediazonium salts are formed by diazotizing a

primary aromatic amine.
• This salts are relatively stable in aqueous solutions
around 0-10°C.
• Above these temperatures, they will decomposed
and may be explode if they are isolated and
allowed to dry.
• Contain diazonium group:

N N or N2

• Example of diazonium ion is benzenediazonium

chloride.

N N Cl N2 Cl
or
• The –N2+ group can be replaced by many different
functional groups, including –H, -OH, -CN and
halogens.
• The nitrogen gas is released.
• Useful in synthesizing polysubstituted benzene
derivatives.
 H2O/H2SO4
OH
+ N2

CuCl Cl
+ N2

CuBr Br
+ N2

NH2 NaNO2/HCl N2 CN
CuCN
+ N2
0-5 oC
aniline arenediazonium salts
KI I
+ N2

HBF4, F
+ N2

H3PO2
H
+ N2
Examples:

NH2 NaNO2/HCl N2 Cl-

H2O/H2SO4
OH
0-5 oC + N2
H3C H3C
H3C

NH2 NaNO2/HCl N2 Cl-

o KI I
0-5 C + N2
Br Br
Br

NH2 NaNO2/HCl N2 Cl- Br

CuBr
+ N2
0-5 oC
H3C CH3 H3C CH3 H3C CH3
@nsmt2016