Dr. Wolf's CHM 201 & 202 22-1

22.1522.15

Nitrosation of AlkylaminesNitrosation of Alkylamines

Dr. Wolf's CHM 201 & 202 22-2

Nitrite Ion, Nitrous Acid, and Nitrosyl CationNitrite Ion, Nitrous Acid, and Nitrosyl Cation

HH++

––OO••••••••

••••NN OO

•••• ••••••••

OO•••• ••••

NN OO•••• ••••

••••HH

HH++

OO••••NN OO

•••• ••••

HH

HH

++••••++

••••NN OO

•••• ••••++OO ••••

HH

HH

••••

Dr. Wolf's CHM 201 & 202 22-3

Nitrosyl Cation and NitrosationNitrosyl Cation and Nitrosation

++••••NN OO

•••• ••••

Dr. Wolf's CHM 201 & 202 22-4

Nitrosyl Cation and NitrosationNitrosyl Cation and Nitrosation

++••••NN OO

•••• ••••++••••NN

NN••••NN OO

•••• ••••++

Dr. Wolf's CHM 201 & 202 22-5

Nitrosation of Secondary AlkylaminesNitrosation of Secondary Alkylamines

++••••NN OO

•••• ••••••••NN

HH

++

NN••••NN OO

•••• ••••++

HH++

HH

++

NN••••NN OO

•••• •••••••• nitrosation of secondary nitrosation of secondary

amines gives an amines gives an NN--

nitroso aminenitroso amine

Dr. Wolf's CHM 201 & 202 22-6

ExampleExample

(CH(CH33))22NNHH•••• NaNONaNO22, HCl, HCl

HH22OO(88-90%)(88-90%)

••••(CH(CH33))22NN

••••NN OO

•••• ••••

Dr. Wolf's CHM 201 & 202 22-7

Some N-Nitroso AminesSome N-Nitroso Amines

NN-nitrosopyrrolidine-nitrosopyrrolidine(nitrite-cured bacon)(nitrite-cured bacon)

NN

NNOO

NN-nitrosonornicotine-nitrosonornicotine(tobacco smoke)(tobacco smoke)

NN

NNOONN

(CH(CH33))22NN NN OONN-nitrosodimethylamine-nitrosodimethylamine

(leather tanning)(leather tanning)

Dr. Wolf's CHM 201 & 202 22-8

Nitrosation of Primary AlkylaminesNitrosation of Primary Alkylamines

++ analogous to analogous to

nitrosation of nitrosation of

secondary amines to secondary amines to

this pointthis point

++••••NN OO

•••• ••••••••NN

HH

HHRR

NN••••NN OO

•••• ••••++

HH

HHRR

++HH

++

NN••••NN OO

•••• ••••••••

RR

HH

Dr. Wolf's CHM 201 & 202 22-9

Nitrosation of Primary AlkylaminesNitrosation of Primary Alkylamines

NN••••NN OO

•••• ••••••••

RR

HH

HH++

NN••••NN OO

••••••••

RR

HH HH

++

this species reacts furtherthis species reacts further

••••NN

••••NN OO

••••••••

RR

HHHH

++

++

HHHH

++••••NN

••••NN OO••••

RR

HH

Dr. Wolf's CHM 201 & 202 22-10

Nitrosation of Primary AlkylaminesNitrosation of Primary Alkylamines

++

HH

••••NN••••NN OO••••

RR

HH

++NN NN ••••RR

HH

••••OO

HH

••••++nitrosation of a nitrosation of a

primary alkylamine primary alkylamine

gives an alkyl gives an alkyl

diazonium iondiazonium ion

process is called process is called

diazotizationdiazotization

Dr. Wolf's CHM 201 & 202 22-11

Alkyl Diazonium Ions Alkyl Diazonium Ions

++NN NN ••••RR

alkyl diazonium ions alkyl diazonium ions

readily lose Nreadily lose N22 to to

give carbocationsgive carbocations

RR++ ++ NN NN ••••••••

Dr. Wolf's CHM 201 & 202 22-12

Example: Nitrosation of 1,1-DimethylpropylamineExample: Nitrosation of 1,1-Dimethylpropylamine NNHH22

NN NN++

HONOHONO

HH22OO

OOHH

(80%)(80%) ++

(2%)(2%)(3%)(3%)

++

– – NN22

Dr. Wolf's CHM 201 & 202 22-13

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

Nitrosation of Tertiary Alkylamines Nitrosation of Tertiary Alkylamines

••••NNRR

RR

RR

NN••••NN OO

•••• ••••++RR

RR

RR

Dr. Wolf's CHM 201 & 202 22-14

22.1622.16

Nitrosation of ArylaminesNitrosation of Arylamines

Dr. Wolf's CHM 201 & 202 22-15

reaction that occurs is reaction that occurs is electrophilic aromatic substitutionelectrophilic aromatic substitution

Nitrosation of Tertiary ArylaminesNitrosation of Tertiary Arylamines NN(CH(CH22CHCH33))22

(95%)(95%)

1. NaNO1. NaNO22, HCl,, HCl,

H H22O, 8°CO, 8°C

2. HO2. HO––

NN(CH(CH22CHCH33))22

NNOO

Dr. Wolf's CHM 201 & 202 22-16

similar to secondary alkylamines;similar to secondary alkylamines;

gives gives NN-nitroso amines-nitroso amines

Nitrosation of N-AlkylarylaminesNitrosation of N-Alkylarylamines

NaNONaNO22, HCl,, HCl,

HH22O, 10°CO, 10°C

NNHCHHCH33

(87-93%)(87-93%)

NNCHCH33

NN OO

Dr. Wolf's CHM 201 & 202 22-17

Nitrosation of Primary Nitrosation of Primary ArylaminesArylamines

gives aryl diazonium ionsgives aryl diazonium ions

aryl diazonium ions are much more stable thanaryl diazonium ions are much more stable than

alkyl diazonium ionsalkyl diazonium ions

most aryl diazonium ions are stable under the most aryl diazonium ions are stable under the

conditions of their formation (0-10°C) conditions of their formation (0-10°C)

ArArNN NN++

RRNN NN++ fastfast

slowslow

RR++ ++ NN22

ArAr++ ++ NN22

Dr. Wolf's CHM 201 & 202 22-18

Example:Example: (CH(CH33))22CHCH NNHH22

NaNONaNO22, H, H22SOSO44

HH22O, 0-5°CO, 0-5°C (CH(CH33))22CHCH NN NN

++HSOHSO44

––

Dr. Wolf's CHM 201 & 202 22-19

Synthetic Origin of Aryl Diazonium SaltsSynthetic Origin of Aryl Diazonium Salts

ArAr HH

ArAr NNOO22

ArAr NNHH22

ArAr NN NN++

Dr. Wolf's CHM 201 & 202 22-20

22.1722.17

Synthetic TransformationsSynthetic Transformations

ofAryl Diazonium SaltsofAryl Diazonium Salts

Dr. Wolf's CHM 201 & 202 22-21

Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts

ArAr NN NN++

ArAr HH

ArAr OOHH

ArAr II

ArAr FF

ArAr BrBrArAr ClCl

ArAr CNCN

Dr. Wolf's CHM 201 & 202 22-22

Preparation of PhenolsPreparation of Phenols

ArAr NN NN++

ArAr OOHH

HH22OO, heat, heat

Dr. Wolf's CHM 201 & 202 22-23

ExampleExample

2. H2. H22O, heatO, heat

(CH(CH33))22CHCH NNHH22

1. NaNO1. NaNO22, H, H22SOSO44

HH22O, 0-5°CO, 0-5°C (CH(CH33))22CHCH OOHH

(73%)(73%)

Dr. Wolf's CHM 201 & 202 22-24

Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts

ArAr NN NN++

ArAr HH

ArAr OOHH

ArAr II

ArAr FF

ArAr BrBrArAr ClCl

ArAr CNCN

Dr. Wolf's CHM 201 & 202 22-25

Preparation of Aryl IodidesPreparation of Aryl Iodides

ArAr NN NN++

ArAr II

reaction of an aryl diazonium salt with reaction of an aryl diazonium salt with

potassium iodidepotassium iodide

KKII

Dr. Wolf's CHM 201 & 202 22-26

ExampleExample

2. K2. KII, room temp., room temp.

1. NaNO1. NaNO22, HCl, HCl

HH22O, 0-5°CO, 0-5°C

(72-83%)(72-83%)

NNHH22

BrBr

II BrBr

Dr. Wolf's CHM 201 & 202 22-27

Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts

ArAr NN NN++

ArAr HH

ArAr OOHH

ArAr II

ArAr FF

ArAr BrBrArAr ClCl

ArAr CNCN

Dr. Wolf's CHM 201 & 202 22-28

Preparation of Aryl FluoridesPreparation of Aryl Fluorides

ArAr NN NN++

ArAr FF

heat the tetrafluoroborate salt of a diazonium ion;heat the tetrafluoroborate salt of a diazonium ion;

process is called the Schiemann reactionprocess is called the Schiemann reaction

Dr. Wolf's CHM 201 & 202 22-29

ExampleExample

(68%)(68%)

NNHH22 CCHCCH22CHCH33

OO

2. HBF2. HBF44

1. NaNO1. NaNO22, HCl,, HCl,

HH22O, 0-5°CO, 0-5°C

3. heat3. heat

FF CCHCCH22CHCH33

OO

Dr. Wolf's CHM 201 & 202 22-30

Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts

ArAr NN NN++

ArAr HH

ArAr OOHH

ArAr II

ArAr FF

ArAr BrBrArAr ClCl

ArAr CNCN

Dr. Wolf's CHM 201 & 202 22-31

Preparation of Aryl Chlorides and Preparation of Aryl Chlorides and BromidesBromides

ArAr NN NN++

ArAr BrBrArAr ClCl

aryl chlorides and aryl bromides are prepared by heating aryl chlorides and aryl bromides are prepared by heating

a diazonium salt with copper(I) chloride or bromidea diazonium salt with copper(I) chloride or bromide

substitutions of diazonium salts that use copper(I) substitutions of diazonium salts that use copper(I)

halides are called halides are called SandmeyerSandmeyer reactionsreactions

Dr. Wolf's CHM 201 & 202 22-32

ExampleExample

(68-71%)(68-71%)

NNHH22 NONO22

2. Cu2. CuClCl, heat, heat

1. NaNO1. NaNO22, HCl,, HCl,

HH22O, 0-5°CO, 0-5°C

ClCl NONO22

Dr. Wolf's CHM 201 & 202 22-33

ExampleExample

(89-95%)(89-95%)

2. Cu2. CuBrBr, heat, heat

1. NaNO1. NaNO22, HBr,, HBr,

HH22O, 0-10°CO, 0-10°CNNHH22

ClCl

BrBr ClCl

Dr. Wolf's CHM 201 & 202 22-34

Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts

ArAr NN NN++

ArAr HH

ArAr OOHH

ArAr II

ArAr FF

ArAr BrBrArAr ClCl

ArAr CNCN

Dr. Wolf's CHM 201 & 202 22-35

Preparation of Aryl NitrilesPreparation of Aryl Nitriles

ArAr NN NN++

ArAr CNCN

aryl nitriles are prepared by heating a diazonium aryl nitriles are prepared by heating a diazonium

salt with copper(I) cyanidesalt with copper(I) cyanide

this is another type of Sandmeyer reactionthis is another type of Sandmeyer reaction

Dr. Wolf's CHM 201 & 202 22-36

ExampleExample

(64-70%)(64-70%)

2. CuCN, heat2. CuCN, heat

1. NaNO1. NaNO22, HCl,, HCl,

HH22O, 0°CO, 0°CNNHH22

CHCH33

CNCN CHCH33

Dr. Wolf's CHM 201 & 202 22-37

Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts

ArAr NN NN++

ArAr HH

ArAr OOHH

ArAr II

ArAr FF

ArAr BrBrArAr ClCl

ArAr CNCN

Dr. Wolf's CHM 201 & 202 22-38

Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts

ArAr NN NN++

ArAr HH

hypophosphorous acid (Hhypophosphorous acid (H33POPO22) reduces diazonium ) reduces diazonium

salts; ethanol does the same thingsalts; ethanol does the same thing

this is called this is called reductive deaminationreductive deamination

Dr. Wolf's CHM 201 & 202 22-39

ExampleExample

(70-75%)(70-75%)

NaNONaNO22, H, H22SOSO44,,

HH33POPO22

NNHH22

CHCH33 CHCH33

Dr. Wolf's CHM 201 & 202 22-40

Value of Diazonium SaltsValue of Diazonium Salts

1) 1) allows introduction of substituents such as OH, F, allows introduction of substituents such as OH, F,

I, and CN on the ringI, and CN on the ring

2) 2) allows preparation of otherwise difficultly allows preparation of otherwise difficultly

accessible substitution patternsaccessible substitution patterns

Dr. Wolf's CHM 201 & 202 22-41

ExampleExample BrBr

BrBrBrBr

NNHH22

BrBr

BrBr

BrBr

(74-77%)(74-77%)

NaNONaNO22, H, H22SOSO44,,

HH22O, CHO, CH33CHCH22OHOH

NNHH22 BrBr22

HH22OO

(100%)(100%)

Dr. Wolf's CHM 201 & 202 22-42

22.1822.18

Azo CouplingAzo Coupling

Dr. Wolf's CHM 201 & 202 22-43

Azo CouplingAzo Coupling

Diazonium salts are weak electrophiles.Diazonium salts are weak electrophiles.

React with strongly activated aromatic compounds React with strongly activated aromatic compounds

by electrophilic aromatic substitution.by electrophilic aromatic substitution.

ArAr NN NN++

Ar'Ar' HH++ ArAr NN NN Ar'Ar'

an azo compoundan azo compound

Ar'Ar' must bear a strongly electron-releasing group must bear a strongly electron-releasing group such as OH, OR, or NR such as OH, OR, or NR22..

Dr. Wolf's CHM 201 & 202 22-44

ExampleExample OHOH

++ CC66HH55NN NN++ OHOH

NN NCNC66HH55

ClCl––

Dr. Wolf's CHM 201 & 202 22-45

Section 22.19Section 22.19

Spectroscopic Analysis of AminesSpectroscopic Analysis of Amines

Dr. Wolf's CHM 201 & 202 22-46

the N—H stretching band appears in the rangethe N—H stretching band appears in the range3000-3500 cm3000-3500 cm-1-1

primary amines give two peaks in this region, oneprimary amines give two peaks in this region, onefor a symmetrical stretching vibration, the other forfor a symmetrical stretching vibration, the other foran antisymmetrical stretchan antisymmetrical stretch

Infrared SpectroscopyInfrared Spectroscopy

RR NN

HH

HH

symmetricsymmetric

RR NN

HH

HH

antisymmetricantisymmetric

Dr. Wolf's CHM 201 & 202 22-47

Infrared SpectroscopyInfrared Spectroscopy

RNHRNH22 RR22NHNH

primary amines give two N—H stretching peaks, primary amines give two N—H stretching peaks,

secondary amines give onesecondary amines give one

Dr. Wolf's CHM 201 & 202 22-48

compare chemical shifts in:compare chemical shifts in:

11H NMRH NMR HH33CC CHCH22NNHH22

HH33CC CHCH22OOHH

NN CC HH is more shielded than is more shielded than

3.9 ppm3.9 ppm 4.7 ppm4.7 ppm

OO CC HH

Dr. Wolf's CHM 201 & 202 22-49

1313C NMRC NMR

Carbons bonded to N are more shielded than Carbons bonded to N are more shielded than

those bonded to O.those bonded to O.

CHCH33NNHH22 CHCH33OHOH

26.9 ppm26.9 ppm 48.0 ppm48.0 ppm

Dr. Wolf's CHM 201 & 202 22-50

maxmax

204 nm204 nm256 nm256 nm

maxmax

230 nm230 nm280 nm280 nm

maxmax

203 nm203 nm254 nm254 nm

An amino group on a benzene ring shifts An amino group on a benzene ring shifts maxmax

to longer wavelength. Protonation of N causesto longer wavelength. Protonation of N causesUV spectrum to resemble that of benzene.UV spectrum to resemble that of benzene.

UV-VISUV-VIS NHNH22

NHNH33

++

Dr. Wolf's CHM 201 & 202 22-51

Mass SpectrometryMass Spectrometry

Compounds that contain only C, H, and O have Compounds that contain only C, H, and O have

even molecular weights. If an odd number of N even molecular weights. If an odd number of N

atoms is present, the molecular weight is odd.atoms is present, the molecular weight is odd.

A molecular-ion peak with an odd A molecular-ion peak with an odd mm//zz value value

suggests that the sample being analyzed contains suggests that the sample being analyzed contains

N.N.

Dr. Wolf's CHM 201 & 202 22-52

Mass SpectrometryMass Spectrometry

Nitrogen stabilizes Nitrogen stabilizes

carbocations, which carbocations, which

drives the fragmentation drives the fragmentation

pathways.pathways.

(CH(CH33))22NCHNCH22CHCH22CHCH22CHCH33••••

ee––

(CH(CH33))22NCHNCH22CHCH22CHCH22CHCH33

••++

••CHCH22CHCH22CHCH33++(CH(CH33))22NN CHCH22

++

Dr. Wolf's CHM 201 & 202 22-53

Mass SpectrometryMass Spectrometry

Nitrogen stabilizes Nitrogen stabilizes

carbocations, which carbocations, which

drives the fragmentation drives the fragmentation

pathways.pathways.

CHCH33NHCHNHCH22CHCH22CH(CHCH(CH33))22••••

ee––

CHCH33NHCHNHCH22CHCH22CH(CHCH(CH33))22

••++

••CHCH22CH(CHCH(CH33))22++CHCH33NHNH CHCH22

++

Dr. Wolf's CHM 201 & 202 22-54

End of Chapter 22End of Chapter 22