Nitrosation of Alkylamines

Nitrite Ion, Nitrous Acid, and Nitrosyl Cation

+
–• •• •• •• • H •• •• •• •
•O N O• H O N O•
•• ••
+
H

H H
•• •• • + •• •• •
• O •• + N O• •• O N O•
•
+
H H
 Nitrosyl Cation and Nitrosation

+ •• •• •
N N O•

•• •• •
N •• + N O•
+
 Nitrosation of Secondary Alkylamines

+ •• •• • •• •• •
N N O• •• N N O•

H +
+
H

•• •• • nitrosation of
N •• + N O•
+ secondary amines
gives an N-nitroso
H amine
Example

•• NaNO2, HCl •• •• •• •
(CH3)2NH (CH3)2N N O•
H2O
(88-90%)
 Some N-Nitroso Amines

N-nitrosodimethylamine
(CH3)2N N O
(leather tanning)

N N

N N
N
O O

N-nitrosopyrrolidine N-nitrosonornicotine
(nitrite-cured bacon) (tobacco smoke)
 Nitrosation of Primary Alkylamines

R R
H + •• •• • •• •• •
N N O• •• N N O•

H H +
+
R H
H
•• •• • analogous to
N •• + N O•
+ nitrosation of
secondary amines
H to this point
 Nitrosation of Primary Alkylamines

R R
+
•• •• + H •• •• •
•• N N O •• N N O•

H H H
this species reacts further
R R H
+
•• •• • H ••
•• N N O• •• N N O ••
+
+ H H
H
 Nitrosation of Primary Alkylamines

nitrosation of a H
+
primary alkylamine •• O ••
R N N •• +
gives an alkyl
diazonium ion H
process is called
diazotization R H
••
•• N N O ••
+
H
 Alkyl Diazonium Ions

+
+ + • N ••
R •N N •• R N

alkyl diazonium ions

readily lose N2 to
give carbocations
 Example: Nitrosation of 1,1-
Dimethylpropylamine
+
NH2 HONO N N

OH H2O – N2
+

(80%)
+

(3%) (2%)
 Nitrosation of Tertiary Alkylamines

There is no useful chemistry associated with the

nitrosation of tertiary alkylamines.

R R
R R + •• •• •
N •• N N O•

R R
Nitrosation of Arylamines
 Nitrosation of Tertiary Arylamines

reaction that occurs is

electrophilic aromatic substitution

N(CH2CH3)2 N(CH2CH3)2
1. NaNO2, HCl,
H2O, 8°C
2. HO–

N
O
(95%)
Nitrosation of N-Alkylarylamines

similar to secondary alkylamines;

gives N-nitroso amines

NaNO2, HCl, N O
H2O, 10°C
NHCH3 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 (0-10°C)
+ fast +
RN N R + N2

+ slow +
ArN N Ar + N2
Example:

(CH3)2CH NH2

NaNO2, H2SO4
H2O, 0-5°C

+
(CH3)2CH N NHSO4–
Synthetic Origin of Aryl Diazonium Salts

Ar H

Ar NO2

Ar NH2

+
Ar N N
Synthetic Transformations
ofAryl Diazonium Salts
 Transformations of Aryl Diazonium Salts

Ar Cl Ar Br

Ar CN Ar F
+
Ar N N

Ar H Ar I

Ar OH
Preparation of Phenols

+
Ar N N

H2O, heat

Ar OH
Example

(CH3)2CH NH2

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

(CH3)2CH OH

(73%)
 Transformations of Aryl Diazonium Salts

Ar Cl Ar Br

Ar CN Ar F
+
Ar N N

Ar H Ar I

Ar OH
 Preparation of Aryl Iodides

reaction of an aryl diazonium salt with

potassium iodide

+
Ar N N
KI
Ar I
Example

NH2 I
1. NaNO2, HCl
Br H2O, 0-5°C Br

2. KI, room temp.

(72-83%)
 Transformations of Aryl Diazonium Salts

Ar Cl Ar Br

Ar CN Ar F
+
Ar N N

Ar H Ar I

Ar OH
 Preparation of Aryl Fluorides

Ar F
+
Ar N N

heat the tetrafluoroborate salt of a diazonium ion;

process is called the Schiemann reaction
 Example

NH2 1. NaNO2, HCl, F

H2O, 0-5°C

2. HBF4
CCH2CH3 CCH2CH3
3. heat
O O
(68%)
 Transformations of Aryl Diazonium Salts

Ar Cl Ar Br

Ar CN Ar F
+
Ar N N

Ar H Ar I

Ar OH
 Preparation of Aryl Chlorides and Bromides

Ar Cl Ar Br

+
Ar N N

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, 0-5°C

2. CuCl, heat
NO2 NO2

(68-71%)
 Example

NH2 1. NaNO2, HBr, Br

H2O, 0-10°C
Cl Cl

2. CuBr, heat

(89-95%)
 Transformations of Aryl Diazonium Salts

Ar Cl Ar Br

Ar CN Ar F
+
Ar N N

Ar H Ar I

Ar OH
 Preparation of Aryl Nitriles

Ar CN
+
Ar N N

aryl nitriles are prepared by heating a diazonium

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

NH2 1. NaNO2, HCl, CN

H2O, 0°C
CH3 CH3

2. CuCN, heat

(64-70%)
 Transformations of Aryl Diazonium Salts

Ar Cl Ar Br

Ar CN Ar F
+
Ar N N

Ar H Ar I

Ar OH
 Transformations of Aryl Diazonium Salts

hypophosphorous acid (H3PO2) reduces diazonium

salts; ethanol does the same thing
this is called reductive deamination
+
Ar N N

Ar H
 Example

NH2 NaNO2, H2SO4,

H3PO2
CH3 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 NH2
NaNO2, H2SO4,
Br Br
Br2 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' H Ar N N Ar'

an azo compound

Ar' must bear a strongly electron-releasing group

such as OH, OR, or NR2.
Example
OH

+
+ C6H5N N Cl–

OH

N NC6H5