Nitrosation of Alkylamines

Nitrite Ion, Nitrous Acid, and Nitrosyl Cation

+
H

N
H

H
O

N
+

+
O

Nitrosyl Cation and Nitrosation

+
N

N
+

Nitrosation of Secondary Alkylamines

+

N
+

N
H

N
+

nitrosation of
secondary amines
gives an N-nitroso
amine

Example

(CH3)2NH

NaNO2, HCl
H2O

(CH3)2N

(88-90%)

Some N-Nitroso Amines

(CH3)2N

N-nitrosodimethylamine
(leather tanning)

N-nitrosopyrrolidine
(nitrite-cured bacon)

N-nitrosonornicotine
(tobacco smoke)

Nitrosation of Primary Alkylamines

R

H
H

N
+
H

N
H

N
+

analogous to
nitrosation of
secondary amines
to this point

Nitrosation of Primary Alkylamines

R

H
R
N

H
this species reacts further
R
H
N

O
+
H

Nitrosation of Primary Alkylamines

nitrosation of a
primary alkylamine
gives an alkyl
diazonium ion
process is called
diazotization

H
R

+
N

H
R

O
+
H

Alkyl Diazonium Ions

+ +
R
N

alkyl diazonium ions

readily lose N2 to
give carbocations

+
N

Example: Nitrosation of 1,1-Dimethylpropylamine

+
N

HONO

NH2

OH
(80%)

H2O

N2

+
(3%)

(2%)

Nitrosation of Tertiary Alkylamines

There is no useful chemistry associated with the
nitrosation of tertiary alkylamines.
R
R

N
R

R
R

+
N
R

Nitrosation of Arylamines

Nitrosation of Tertiary Arylamines

reaction that occurs is
electrophilic aromatic substitution

N(CH2CH3)2

1. NaNO2, HCl,
H2O, 8C

N(CH2CH3)2

2. HO
N
(95%)

Nitrosation of N-Alkylarylamines
similar to secondary alkylamines;
gives N-nitroso amines

NHCH3

NaNO2, HCl,
H2O, 10C

NCH3
(87-93%)

Nitrosation of Primary Arylamines

gives aryl diazonium ions
aryl diazonium ions are much more stable than
alkyl diazonium ions
most aryl diazonium ions are stable under the
conditions of their formation (0-10C)
+
RN
+
ArN

N
N

fast

+
R

+ N2

slow

+
Ar

+ N2

Example:

(CH3)2CH

NH2
NaNO2, H2SO4
H2O, 0-5C

(CH3)2CH

+
N

N HSO4

Synthetic Origin of Aryl Diazonium Salts

Ar

H
Ar

NO2
Ar

NH2

Ar

+
N

Synthetic Transformations
ofAryl Diazonium Salts

Transformations of Aryl Diazonium Salts

Ar
Ar

Cl

Ar

CN
+
N

Ar
Ar

Ar

Ar

H
Ar

Br

OH

Preparation of Phenols

+
N

Ar

N
H2O, heat

Ar

OH

Example

NH2

(CH3)2CH

1. NaNO2, H2SO4
H2O, 0-5C
2. H2O, heat

OH

(CH3)2CH
(73%)

Transformations of Aryl Diazonium Salts

Ar
Ar

Cl

Ar

CN
+
N

Ar
Ar

Ar

Ar

H
Ar

Br

OH

Preparation of Aryl Iodides

reaction of an aryl diazonium salt with
potassium iodide

Ar

+
N

KI
Ar

Example

NH2
Br

1. NaNO2, HCl
H2O, 0-5C

I
Br

2. KI, room temp.

(72-83%)

Transformations of Aryl Diazonium Salts

Ar
Ar

Cl

Ar

CN
+
N

Ar
Ar

Ar

Ar

H
Ar

Br

OH

Preparation of Aryl Fluorides

Ar
Ar

+
N

heat the tetrafluoroborate salt of a diazonium ion;

process is called the Schiemann reaction

Example

NH2

1. NaNO2, HCl,

H2O, 0-5C
CCH2CH3
O

2. HBF4
3. heat

CCH2CH3
O
(68%)

Transformations of Aryl Diazonium Salts

Ar
Ar

Cl

Ar

CN
+
N

Ar
Ar

Ar

Ar

H
Ar

Br

OH

Preparation of Aryl Chlorides and Bromides

Ar

Cl

Ar

Ar

+
N

Br

aryl chlorides and aryl bromides are prepared by

heating a diazonium salt with copper(I) chloride or
bromide
substitutions of diazonium salts that use copper(I)
halides are called Sandmeyer reactions

Example

NH2

1. NaNO2, HCl,

Cl

H2O, 0-5C
NO2

2. CuCl, heat

NO2
(68-71%)

Example

1. NaNO2, HBr,

NH2
Cl

H2O, 0-10C

Br
Cl

2. CuBr, heat
(89-95%)

Transformations of Aryl Diazonium Salts

Ar
Ar

Cl

Ar

CN
+
N

Ar
Ar

Ar

Ar

H
Ar

Br

OH

Preparation of Aryl Nitriles

Ar

CN
Ar

+
N

aryl nitriles are prepared by heating a diazonium

salt with copper(I) cyanide
this is another type of Sandmeyer reaction

Example

1. NaNO2, HCl,

NH2
CH3

H2O, 0C

CN
CH3

2. CuCN, heat
(64-70%)

Transformations of Aryl Diazonium Salts

Ar
Ar

Cl

Ar

CN
+
N

Ar
Ar

Ar

Ar

H
Ar

Br

OH

Transformations of Aryl Diazonium Salts

hypophosphorous acid (H3PO2) reduces diazonium
salts; ethanol does the same thing
this is called reductive deamination
Ar
Ar

+
N

Example

NaNO2, H2SO4,

NH2
CH3

H3PO2

CH3

(70-75%)

Value of Diazonium Salts

1) allows introduction of substituents such as
OH, F, I, and CN on the ring
2) allows preparation of otherwise difficultly
accessible substitution patterns

Example

NH2

Br2

NH2

Br

NaNO2, H2SO4,
Br
H2O, CH3CH2OH

H2O

Br

Br

Br

(100%)
Br
(74-77%)

Azo Coupling

Azo Coupling
Diazonium salts are weak electrophiles.
React with strongly activated aromatic
compounds by electrophilic aromatic
substitution.
Ar

+
N

N + Ar'

Ar

Ar'

an azo compound
Ar' must bear a strongly electron-releasing group
such as OH, OR, or NR2.

Example
OH

+
+ C6H5N

OH
N

NC6H5

Cl