General

Organic Chemistry
Two credits
Second Semester 2009

King Saud bin Abdulaziz University for Health Science

Reference Book: Organic Chemistry: A Brief Course,

by Robert C. Atkins and Francis A. Carey
Third Edition

Instructor: Rabih O. Al-Kaysi, PhD.

 Lecture 22

Chapter 14

Amines
Amine Nomenclature
 Classification of Amines

Alkylamine
N attached to alkyl group
Arylamine
N attached to aryl group
Primary, secondary, or tertiary
determined by number of carbon atoms
directly attached to nitrogen
 Nomenclature of Primary Alkylamines (RNH2)

Two IUPAC styles

1) analogous to alcohols: replace -e

ending by -anamine
2) name alkyl group and attach -amine
as a suffix
 Examples: some primary alkylamines

(RNH2: one carbon directly attached to N)

CH3CH2NH2 ethylamine or ethanamine

NH2 cyclohexylamine or
cyclohexanamine

CH3CHCH2CH2CH3 1-methylbutylamine or
NH2 2-pentanamine
 Nomenclature of Primary Arylamines (ArNH2)

Name as derivatives of aniline.

NH2

F NH2 Br CH2CH3

p-fluoroaniline 5-bromo-2-ethylaniline
 Amino groups as substituents

amino groups rank below OH groups and higher

oxidation states of carbon
in such cases name the amino group as a substituent

O
HOCH2CH2NH2 HC NH2

2-aminoethanol p-aminobenzaldehyde
 Secondary and Tertiary Amines

Name as N-substituted derivatives of parent

primary amine.
(N is a locant-it is not alphabetized, but
is treated the same way as a numerical
locant)
Parent amine is one with longest carbon
chain.
 Examples

CH3NHCH2CH3 N-methylethylamine
NHCH2CH3

4-chloro-N-ethyl-3-nitroaniline
NO2

Cl CH3

N
CH3
N,N-dimethylcycloheptylamine
 Ammonium Salts

A nitrogen with four substituents is positively

charged and is named as a derivative of
ammonium ion (NH4+).

CH3
+
CH3NH3 Cl– +
CH CH CF CO –
N 2 3 3 2

methylammonium H
chloride N-ethyl-N-methylcyclopentylammonium
trifluoroacetate
Just for general knowledge, will not be tested on
 Ammonium Salts

When all four atoms attached to N are carbon,

the ion is called a quaternary ammonium ion and
salts that contain it are called quaternary
ammonium salts.
CH3
+
CH2 N CH3 I –

CH3

benzyltrimethylammonium iodide
Just for general knowledge, will not be tested on
Structure and Bonding
Alkylamines

147 pm

112°
106°
 Geometry at N

Compare geometry at N of methylamine, aniline,

and formamide.
H H
H sp3 sp2
C NH2 C NH2
O

H
Pyramidal geometry at sp3-hybridized N in
methylamine.
Planar geometry at sp2-hybridized N in formamide.

Just for general knowledge, will not be tested on

 Geometry at N

Compare geometry at N of methylamine, aniline,

and formamide.

sp3 sp2

Pyramidal geometry at sp3-hybridized N in

methylamine.
Planar geometry at sp2-hybridized N in formamide.

Just for general knowledge, will not be tested on

Physical Properties
 Physical Properties

Amines are more polar and have higher boiling

points than alkanes; but are less polar and
have lower boiling points than alcohols.

CH3CH2CH3 CH3CH2NH2 CH3CH2OH

dipole
moment (µ ): 0D 1.2 D 1.7 D

boiling point: -42°C 17°C 78°C

 Physical Properties

CH3CH2CH2NH2 CH3CH2NHCH3 (CH3)3N

boiling 50°C 34°C 3°C
point:
Boiling points of isomeric amines decrease in
going from primary to secondary to tertiary amines.

Primary amines have two hydrogens on N capable

of being involved in intermolecular hydrogen
bonding. Secondary amines have one. Tertiary
amines cannot be involved in intermolecular
hydrogen bonds.
Basicity of Amines
 Effect of Structure on Basicity

1. Alkylamines are slightly stronger bases than

ammonia.
 Table 22.1 (page 920)
Basicity of Amines in Aqueous Solution

Amine Conj. Acid pKa

NH3 NH4+ 9.3

CH3CH2NH2 CH3CH2NH3+ 10.8

CH3CH2NH3+ is a weaker acid than NH4+;

therefore, CH3CH2NH2 is a stronger base
than NH3.
 Effect of Structure on Basicity

1. Alkylamines are slightly stronger bases than

ammonia.

2. Alkylamines differ very little in basicity.

 Table 22.1 (page 920)
Basicity of Amines in Aqueous Solution

Amine Conj. Acid pKa

NH3 NH4+ 9.3

CH3CH2NH2 CH3CH2NH3+ 10.8

(CH3CH2)2NH (CH3CH2)2NH2+ 11.1

(CH3CH2)3N (CH3CH2)3NH+ 10.8

Notice that the difference separating a primary,

secondary, and tertiary amine is only 0.3 pK units.
 Effect of Structure on Basicity

1. Alkylamines are slightly stronger bases than

ammonia.

2. Alkylamines differ very little in basicity.

3. Arylamines are much weaker bases than

ammonia.
 Table 22.1 (page 920)
Basicity of Amines in Aqueous Solution

Amine Conj. Acid pKa

NH3 NH4+ 9.3

CH3CH2NH2 CH3CH2NH3+ 10.8

(CH3CH2)2NH (CH3CH2)2NH2+ 11.1

(CH3CH2)3N (CH3CH2)3NH+ 10.8

C6H5NH2 C6H5NH3+ 4.6
 Decreased basicity of arylamines

Increasing delocalization makes diphenylamine a weaker

base than aniline, and triphenylamine a weaker base than
diphenylamine.

C6H5NH2 (C6H5)2NH (C6H5)3N

pKa of conjugate acid:
4.6 0.8 ~-5
 Effect of Substituents on Basicity of Arylamines

1. Alkyl groups on the ring increase basicity, but

only slightly (less than 1 pK unit).

X NH2

X pKa of conjugate acid

H 4.6
CH3 5.3
 Effect of Substituents on Basicity of Arylamines

2. Electron withdrawing groups, especially ortho

and/or para to amine group, decrease basicity
and can have a large effect.

X NH2

X pKa of conjugate acid

H 4.6
CF3 3.5
O2N 1.0
 p-Nitroaniline

•• • –• •• •
O• •O•
+ •• + +
N NH2 N NH2
•• O •• •• O ••
– •• – ••

Lone pair on amine nitrogen is conjugated with

p-nitro group—more delocalized than in aniline
itself. Delocalization lost on protonation.
 Effect is Cumulative

Aniline is 3800 times more basic than

p-nitroaniline.
Aniline is ~1,000,000,000 times more basic than
2,4-dinitroaniline.
 Reactions of Amines:
A Review and a Preview
 Preparation of Amines

Two questions to answer:

1) How is the C—N bond to be formed?
2) How do we obtain the correct oxidation
state of nitrogen (and carbon)?
 Methods for C—N Bond Formation

Nucleophilic substitution by azide ion (N3–)

Nitration of arenes

Nucleophilic ring opening of epoxides by ammonia

Nucleophilic addition of amines to aldehydes and ketones

Nucleophilic substitution by ammonia on α -halo acids

Nucleophilic acyl substitution

 Preparation of Amines
by Alkylation of Ammonia
 Alkylation of Ammonia

Desired reaction is:

2 NH3 + R—X R—NH2 + NH4X

via:
•• • + •• –
H3N •• + R X• H3N R + •• ••
X
•• ••
then: H H
+ +
H3N •• + H N R H3N H + •• N R

H H
 Alkylation of Ammonia

But the method doesn't work well in practice.

Usually gives a mixture of primary, secondary,
and tertiary amines, plus the quaternary salt.

RX RX
NH3 RNH2 R2NH

RX
+ – RX
R4N X R3N
 Example

NH3
CH3(CH2)6CH2Br CH3(CH2)6CH2NH2
(45%)
+
CH3(CH2)6CH2NHCH2(CH2)6CH3
(43%)
As octylamine is formed, it competes with ammonia for
the remaining 1-bromooctane. Reaction of octylamine
with 1-bromooctane gives N,N-dioctylamine.
 The Gabriel Synthesis of
Primary Alkylamines

Just for general knowledge, will not be tested on

 Gabriel Synthesis

gives primary amines without formation of

secondary, etc. amines as byproducts
uses an SN2 reaction on an alkyl halide to form
the C—N bond
the nitrogen-containing nucleophile
is N-potassiophthalimide
 Gabriel Synthesis

gives primary amines without formation of

secondary, etc. amines as byproducts
uses an SN2 reaction on an alkyl halide to form
the C—N bond
the nitrogen-containing nucleophile
O
is N-potassiophthalimide
–
•• N–• +
• K

O
 N-Potassiophthalimide

the pKa of phthalimide is 8.3

N-potassiophthalimide is easily prepared by

the reaction of phthalimide with KOH

O O
KOH –
•• N • +
•• NH • K

O O
N-Potassiophthalimide as a nucleophile

O O
SN2
–
•• N–• •• •
• + R X• •• N R
••

O O

•• •
–
+ •• X •
••
 Cleavage of Alkylated Phthalimide

•• N R + H2O

O imide hydrolysis is
acid or base nucleophilic acyl
substitution
CO2H
+ H2N R
CO2H
Example

O
–
•• N–• +
• K + C6H5CH2Cl

O DMF

•• N CH2C6H5 (74%)