dr. wolf's chm 201 & 202 21-1 chapter 21 amines. dr. wolf's chm 201 & 202 21-2...

Dr. Wolf's CHM 201 & 202 21-1

Chapter 21Chapter 21AminesAmines

Dr. Wolf's CHM 201 & 202 21-2

Amine NomenclatureAmine Nomenclature

Dr. Wolf's CHM 201 & 202 21-3

AlkylamineAlkylamine

N attached to alkyl groupN attached to alkyl group

ArylamineArylamine

N attached to aryl groupN attached to aryl group

Primary, secondary, or tertiaryPrimary, secondary, or tertiary

determined by number of carbon atoms determined by number of carbon atoms directly attached to nitrogendirectly attached to nitrogen

Classification of AminesClassification of Amines

Dr. Wolf's CHM 201 & 202 21-4

Two IUPAC stylesTwo IUPAC styles

1)1) analogous to alcohols: replace -analogous to alcohols: replace -e e ending by -ending by -amineamine

2)2) name alkyl group and attach -name alkyl group and attach -amineamineas a suffixas a suffix

Nomenclature of Primary Alkylamines (RNHNomenclature of Primary Alkylamines (RNH22))

Dr. Wolf's CHM 201 & 202 21-5

Examples: some primary alkylaminesExamples: some primary alkylamines

CHCH33CHCHCHCH22CHCH22CHCH33

NNHH22

(RNH(RNH22: one carbon directly attached to N): one carbon directly attached to N)

CHCH33CHCH22NNHH22 NNHH22

ethylamineethylamine or or ethanamineethanamine

cyclohexylaminecyclohexylamine or orcyclohexanaminecyclohexanamine

1-methylbutylamine 1-methylbutylamine oror2-pentanamine2-pentanamine

Dr. Wolf's CHM 201 & 202 21-6

Name as derivatives of aniline.Name as derivatives of aniline.

Nomenclature of Primary Arylamines (ArNHNomenclature of Primary Arylamines (ArNH22))

pp-fluoroaniline-fluoroaniline 5-bromo-2-ethylaniline5-bromo-2-ethylaniline

NNHH22FF

NNHH22

BrBr CHCH22CHCH33

Dr. Wolf's CHM 201 & 202 21-7

Amino groups as substituentsAmino groups as substituents

pp-aminobenzaldehyde-aminobenzaldehyde

amino groups rank below OH groups and higher amino groups rank below OH groups and higher

oxidation states of carbonoxidation states of carbon

in such cases name the amino group as a in such cases name the amino group as a

substituentsubstituent NNHH22HHCC

OO

HHOOCHCH22CHCH22NNHH22

2-aminoethanol2-aminoethanol

Dr. Wolf's CHM 201 & 202 21-8

Name as Name as NN-substituted derivatives of parent -substituted derivatives of parent primary amine.primary amine.

(N is a locant-it is not alphabetized, but(N is a locant-it is not alphabetized, butis treated the same way as a numericalis treated the same way as a numericallocant)locant)

Parent amine is one with longest carbonParent amine is one with longest carbonchain.chain.

Secondary and Tertiary AminesSecondary and Tertiary Amines

Dr. Wolf's CHM 201 & 202 21-9

ExamplesExamples

CHCH33NNHCHHCH22CHCH33 NN-methylethylamine-methylethylamine NNHCHHCH22CHCH33

NONO22

ClCl

4-chloro-4-chloro-NN-ethyl-3-nitroaniline-ethyl-3-nitroaniline

CHCH33

NN

CHCH33

NN,,NN-dimethylcycloheptylamine-dimethylcycloheptylamine

Dr. Wolf's CHM 201 & 202 21-10

A nitrogen with four substituents is positivelyA nitrogen with four substituents is positivelycharged and is named as a derivative of charged and is named as a derivative of ammonium ammonium ion (NHion (NH44

++).).

Ammonium SaltsAmmonium Salts

CHCH33NHNH33

++ClCl

––

methylammoniummethylammonium

chloridechloride

NN

CHCH33

HH

CHCH22CHCH33

++CFCF33COCO22

––

NN-ethyl--ethyl-NN-methylcyclopentylammonium-methylcyclopentylammonium

trifluoroacetatetrifluoroacetate

Dr. Wolf's CHM 201 & 202 21-11

When all four atoms attached to N are carbon,When all four atoms attached to N are carbon,the ion is called a the ion is called a quaternary ammonium quaternary ammonium ion andion andsalts that contain it are called salts that contain it are called quaternaryquaternary ammoniumammonium salts. salts.

Ammonium SaltsAmmonium Salts

++

CHCH22 NN

CHCH33

CHCH33

CHCH33 II––

benzyltrimethylammonium iodidebenzyltrimethylammonium iodide

Dr. Wolf's CHM 201 & 202 21-12

Structure and BondingStructure and Bonding

Dr. Wolf's CHM 201 & 202 21-13

147 pm147 pm

106°106°112°112°

AlkylaminesAlkylamines

Dr. Wolf's CHM 201 & 202 21-14

Most prominent feature is high electrostaticMost prominent feature is high electrostaticpotential at nitrogen. Reactivity of nitrogen lonepotential at nitrogen. Reactivity of nitrogen lonepair dominates properties of amines. pair dominates properties of amines.

AlkylaminesAlkylamines

Dr. Wolf's CHM 201 & 202 21-15

Compare geometry at N of methylamine, aniline,Compare geometry at N of methylamine, aniline,and formamide.and formamide.

spsp33 spsp22

Geometry at NGeometry at N

Pyramidal geometry at Pyramidal geometry at spsp33-hybridized N in -hybridized N in

methylamine.methylamine.

Planar geometry at Planar geometry at spsp22-hybridized N in formamide.-hybridized N in formamide.

CCOO

NNHH22

HH

CC NNHH22

HH

HH

HH

Dr. Wolf's CHM 201 & 202 21-16

Compare geometry at N of methylamine, aniline,Compare geometry at N of methylamine, aniline,and formamide.and formamide.

spsp33 spsp22


Pyramidal geometry at Pyramidal geometry at spsp33-hybridized N in -hybridized N in

methylamine.methylamine.

Planar geometry at Planar geometry at spsp22-hybridized N in formamide.-hybridized N in formamide.

Dr. Wolf's CHM 201 & 202 21-17

Angle that the C—N bond makes with bisector ofAngle that the C—N bond makes with bisector ofH—N—H angle is a measure of geometry at N.H—N—H angle is a measure of geometry at N.

spsp33 spsp22


~125°~125°180°180°

Note: this is not the same as the H—N—H bond angleNote: this is not the same as the H—N—H bond angle

Dr. Wolf's CHM 201 & 202 21-18

Angle that the C—N bond makes with bisector ofAngle that the C—N bond makes with bisector ofH—N—H angle is a measure of geometry at N.H—N—H angle is a measure of geometry at N.

spsp33 spsp22


~125°~125°180°180°

142.5°142.5°

Dr. Wolf's CHM 201 & 202 21-19

Geometry at N in aniline is pyramidal; closer toGeometry at N in aniline is pyramidal; closer tomethylamine than to formamide.methylamine than to formamide.


142.5°142.5°

Dr. Wolf's CHM 201 & 202 21-20


142.5°142.5°

Hybridization of N in aniline lies between Hybridization of N in aniline lies between spsp33 and and spsp22..

Lone pair of N can be delocalized into ring best if N is Lone pair of N can be delocalized into ring best if N is

spsp22 and lone pair is in a and lone pair is in a pp orbital. orbital.

Lone pair bound most strongly by N if pair is in an Lone pair bound most strongly by N if pair is in an spsp33

orbital of N, rather than orbital of N, rather than pp..

Actual hybridization is a compromise that maximizesActual hybridization is a compromise that maximizes

binding of lone pair.binding of lone pair.

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

Electrostatic Potential Maps of AnilineElectrostatic Potential Maps of Aniline

Nonplanar geometry at Nonplanar geometry at N. Region of highestN. Region of highestnegative potential is at N.negative potential is at N.

Planar geometry at N. Planar geometry at N. High negative potential High negative potential shared by N and ring.shared by N and ring.

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

Physical PropertiesPhysical Properties

Dr. Wolf's CHM 201 & 202 21-23

Amines are more polar and have higher boiling Amines are more polar and have higher boiling points than alkanes; but are less polar andpoints than alkanes; but are less polar andhave lower boiling points than alcohols.have lower boiling points than alcohols.


CHCH33CHCH22CHCH33 CHCH33CHCH22NNHH22 CHCH33CHCH22OOHH

dipoledipolemoment (moment ():):

boiling point:boiling point:

0 D0 D 1.2 D1.2 D 1.7 D1.7 D

-42°C-42°C 17°C17°C 78°C78°C

Dr. Wolf's CHM 201 & 202 21-24

Boiling points of isomeric amines decrease inBoiling points of isomeric amines decrease ingoing from primary to secondary to tertiary amines.going from primary to secondary to tertiary amines.

Primary amines have two hydrogens on N capable Primary amines have two hydrogens on N capable of being involved in intermolecular hydrogen of being involved in intermolecular hydrogen bonding. Secondary amines have one. Tertiary bonding. Secondary amines have one. Tertiary amines cannot be involved in intermolecular amines cannot be involved in intermolecular hydrogen bonds.hydrogen bonds.


CHCH33CHCH22NNHCHHCH33CHCH33CHCH22CHCH22NNHH22 (CH(CH33))33NN

boilingboilingpoint:point:

50°C50°C 34°C34°C 3°C3°C

Dr. Wolf's CHM 201 & 202 21-25

Basicity of AminesBasicity of Amines

Dr. Wolf's CHM 201 & 202 21-26

Effect of Structure on BasicityEffect of Structure on Basicity

1. Alkylamines are slightly stronger bases than 1. Alkylamines are slightly stronger bases than ammonia.ammonia.

Dr. Wolf's CHM 201 & 202 21-27

AmineAmine Conj. AcidConj. Acid pKpKaa

NHNH33 NHNH44++ 9.39.3

CHCH33CHCH22NHNH22 CHCH33CHCH22NHNH33++ 10.810.8

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

CHCH33CHCH22NHNH33++ is a weaker acid than NH is a weaker acid than NH44

++;;therefore, CHtherefore, CH33CHCH22NHNH22 is a stronger base is a stronger base than NHthan NH33..

Dr. Wolf's CHM 201 & 202 21-28



2. Alkylamines differ very little in basicity.2. Alkylamines differ very little in basicity.

Dr. Wolf's CHM 201 & 202 21-29


NHNH33 NHNH44++ 9.39.3


(CH(CH33CHCH22))22NHNH (CH(CH33CHCH22))22NHNH22++ 11.111.1

(CH(CH33CHCH22))33NN (CH(CH33CHCH22))33NHNH++ 10.810.8


Notice that the difference separating a primary,Notice that the difference separating a primary,secondary, and tertiary amine is only 0.3 pK units.secondary, and tertiary amine is only 0.3 pK units.

Dr. Wolf's CHM 201 & 202 21-30



2. Alkylamines differ very little in basicity.2. Alkylamines differ very little in basicity.

3. Arylamines are much weaker bases than3. Arylamines are much weaker bases thanammonia.ammonia.

Dr. Wolf's CHM 201 & 202 21-31


NHNH33 NHNH44++ 9.39.3


(CH(CH33CHCH22))22NHNH (CH(CH33CHCH22))22NHNH22++ 11.111.1

(CH(CH33CHCH22))33NN (CH(CH33CHCH22))33NHNH++ 10.810.8

CC66HH55NHNH22 CC66HH55NHNH33++ 4.64.6


Dr. Wolf's CHM 201 & 202 21-32

HH22NN•••• Decreased basicity of arylaminesDecreased basicity of arylamines

++HH

NN

HH

HH

++ NNHH22 ++•••• ++

HH33NN

ppKKaa = 4.6 = 4.6

ppKKaa =10.6 =10.6

StrongerStrongeracidacid

WeakerWeakeracidacid

StrongerStrongerbasebase

WeakerWeakerbasebase

Dr. Wolf's CHM 201 & 202 21-33


++HH

NN

HH

HH

++ NNHH22 ++•••• ++

HH33NN

StrongerStrongeracidacid

WeakerWeakeracidacid

When anilinium ion loses a proton, theWhen anilinium ion loses a proton, theresulting lone pair is delocalized into the ring.resulting lone pair is delocalized into the ring.

Dr. Wolf's CHM 201 & 202 21-34


++HH

NN

HH

HH

++ NNHH22 ++•••• ++

HH33NN

Aniline is a weaker base because its Aniline is a weaker base because its lone pair is more strongly held.lone pair is more strongly held.

StrongerStrongerbasebase

WeakerWeakerbasebase

Dr. Wolf's CHM 201 & 202 21-35

Decreased basicity of arylaminesDecreased basicity of arylamines

CC66HH55NNHH22 (C(C66HH55))22NNHH (C(C66HH55))33NN

ppKKa a of conjugate acid:of conjugate acid:

4.64.6 0.80.8 ~-5~-5

Increasing delocalization makes diphenylamine a Increasing delocalization makes diphenylamine a

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

base than diphenylamine.base than diphenylamine.

Dr. Wolf's CHM 201 & 202 21-36

Effect of Substituents on Basicity of ArylaminesEffect of Substituents on Basicity of Arylamines

1. Alkyl groups on the ring increase basicity, but1. Alkyl groups on the ring increase basicity, butonly slightly (less than 1 ponly slightly (less than 1 pKK unit). unit).

XX NHNH22

XX ppKKa a of conjugate acidof conjugate acid

HH 4.64.6CHCH33 5.35.3

Dr. Wolf's CHM 201 & 202 21-37

Effect of Substituents on Basicity of ArylaminesEffect of Substituents on Basicity of Arylamines

2. Electron withdrawing groups, especially ortho2. Electron withdrawing groups, especially orthoand/or para to amine group, decrease basicityand/or para to amine group, decrease basicityand can have a large effect.and can have a large effect.

XX NHNH22

XX ppKKa a of conjugate acidof conjugate acid

HH 4.64.6CFCF33 3.53.5

OO22NN 1.01.0

Dr. Wolf's CHM 201 & 202 21-38

p-Nitroanilinep-Nitroaniline NNHH22

OO

NN

OO

–– ••••••••••••

••••

++

••••

••••

OO

NN

OO

–– ••••••••••••

•••• ••••••••––

NNHH22

++ ++

Lone pair on amine nitrogen is conjugated with Lone pair on amine nitrogen is conjugated with

pp-nitro group—more delocalized than in aniline -nitro group—more delocalized than in aniline

itself. Delocalization lost on protonation.itself. Delocalization lost on protonation.

Dr. Wolf's CHM 201 & 202 21-39

Effect is CumulativeEffect is Cumulative

Aniline is 3800 times more basic thanAniline is 3800 times more basic than

pp-nitroaniline.-nitroaniline.

Aniline is ~1,000,000,000 times more basic than Aniline is ~1,000,000,000 times more basic than

2,4-dinitroaniline.2,4-dinitroaniline.

Dr. Wolf's CHM 201 & 202 21-40

Heterocyclic Amines Heterocyclic Amines NN

HH

••••

NN••••

is more basic thanis more basic than

piperidinepiperidine pyridinepyridineppKKaa of conjugate acid: of conjugate acid:

11.211.2

ppKKaa of conjugate acid: of conjugate acid:

5.25.2

(an alkylamine)(an alkylamine)(resembles an(resembles anarylamine inarylamine in

basicity)basicity)

Dr. Wolf's CHM 201 & 202 21-41

Heterocyclic Amines Heterocyclic Amines NN••••

is more basic thanis more basic than

imidazoleimidazole pyridinepyridineppKKaa of conjugate acid: of conjugate acid:

7.07.0

ppKKaa of conjugate acid: of conjugate acid:

5.25.2

NN HHNN•••• ••••

Dr. Wolf's CHM 201 & 202 21-42

ImidazoleImidazole NN HHNN•••• ••••

Which nitrogen is protonated in imidazole?Which nitrogen is protonated in imidazole?

HH++ HH++ NN HHNN ••••HH

++

NN HHNN••••

HH

++

Dr. Wolf's CHM 201 & 202 21-43

ImidazoleImidazole NN HHNN•••• ••••

Protonation in the direction shown gives a Protonation in the direction shown gives a

stabilized ion.stabilized ion.

HH++ NN HHNNHH

++ ••••

NN HHNNHH

••••++

Dr. Wolf's CHM 201 & 202 21-44

Tetraalkylammonium SaltsTetraalkylammonium Salts

as Phase-Transfer Catalystsas Phase-Transfer Catalysts

Dr. Wolf's CHM 201 & 202 21-45

Phase-Transfer CatalysisPhase-Transfer Catalysis

Phase-transfer agents promote the solubility ofPhase-transfer agents promote the solubility ofionic substances in nonpolar solvents. Theyionic substances in nonpolar solvents. Theytransfer the ionic substance from an aqueoustransfer the ionic substance from an aqueousphase to a non-aqueous one.phase to a non-aqueous one.

Phase-transfer agents increase the rates ofPhase-transfer agents increase the rates ofreactions involving anions. The anion is relativelyreactions involving anions. The anion is relativelyunsolvated and very reactive in nonpolar mediaunsolvated and very reactive in nonpolar mediacompared to water or alcohols.compared to water or alcohols.

Dr. Wolf's CHM 201 & 202 21-46


Quaternary ammonium salts are phase-transferQuaternary ammonium salts are phase-transfercatalysts. They are soluble in nonpolar solvents.catalysts. They are soluble in nonpolar solvents.

NNHH33CC

CHCH22CHCH22CHCH22CHCH22CHCH22CHCH22CHCH22CHCH33



++ClCl––

Methyltrioctylammonium chlorideMethyltrioctylammonium chloride

Dr. Wolf's CHM 201 & 202 21-47


Quaternary ammonium salts are phase-transferQuaternary ammonium salts are phase-transfercatalysts. They are soluble in nonpolar solvents.catalysts. They are soluble in nonpolar solvents.

ClCl––

Benzyltriethylammonium chlorideBenzyltriethylammonium chloride

NN

CHCH22CHCH33

CHCH22CHCH33

CHCH22CHCH33

++

Dr. Wolf's CHM 201 & 202 21-48

ExampleExample

The SThe SNN2 reaction of sodium cyanide with butyl2 reaction of sodium cyanide with butyl

bromide occurs much faster when benzyl-bromide occurs much faster when benzyl-triethylammonium chloride is present than whentriethylammonium chloride is present than whenit is not.it is not.

CHCH33CHCH22CHCH22CHCH22BrBr ++ NaNaCNCN

CHCH33CHCH22CHCH22CHCH22CNCN ++ NaNaBrBr

benzyltriethylammonium chloridebenzyltriethylammonium chloride

Dr. Wolf's CHM 201 & 202 21-49

MechanismMechanismMechanismMechanism

ClCl––

(aqueous)(aqueous)

NN

CHCH22CHCH33

CHCH22CHCH33

CHCH22CHCH33

++

(aqueous)(aqueous)

CNCN––++

ClCl––NN

CHCH22CHCH33

CHCH22CHCH33

CHCH22CHCH33

++

++CNCN––

(aqueous)(aqueous)

(aqueous)(aqueous)

Dr. Wolf's CHM 201 & 202 21-50

NN

CHCH22CHCH33

CHCH22CHCH33

CHCH22CHCH33

++

CNCN––

(aqueous)(aqueous)

(in butyl bromide)(in butyl bromide)

NN

CHCH22CHCH33

CHCH22CHCH33

CHCH22CHCH33

++

CNCN––


Dr. Wolf's CHM 201 & 202 21-51


NN

CHCH22CHCH33

CHCH22CHCH33

CHCH22CHCH33

++

CNCN––


CHCH33CHCH22CHCH22CHCH22BrBr++

NN

CHCH22CHCH33

CHCH22CHCH33

CHCH22CHCH33

++

BrBr––


CHCH33CHCH22CHCH22CHCH22CNCN++

Dr. Wolf's CHM 201 & 202 21-52

Reactions of Amines:Reactions of Amines:

A Review and a PreviewA Review and a Preview

Dr. Wolf's CHM 201 & 202 21-53

Preparation of AminesPreparation of Amines

Two questions to answer:Two questions to answer:

1) 1) How is the C—N bond to be formed?How is the C—N bond to be formed?

2) 2) How do we obtain the correct oxidation How do we obtain the correct oxidation

state of nitrogen (and carbon)?state of nitrogen (and carbon)?

Dr. Wolf's CHM 201 & 202 21-54

Methods for C—N Bond FormationMethods for C—N Bond Formation

Nucleophilic substitution by azide ion (NNucleophilic substitution by azide ion (N33––) (Section 8.1, 8.13)) (Section 8.1, 8.13)

Nitration of arenes (Section 12.3)Nitration of arenes (Section 12.3)

Nucleophilic ring opening of epoxides by ammonia (Section Nucleophilic ring opening of epoxides by ammonia (Section

16.12)16.12)

Nucleophilic addition of amines to aldehydes and ketones Nucleophilic addition of amines to aldehydes and ketones

(Sections 17.10, 17.11)(Sections 17.10, 17.11)

Nucleophilic acyl substitution (Sections 19.4, 19.5, and 19.11)Nucleophilic acyl substitution (Sections 19.4, 19.5, and 19.11)

Nucleophilic substitution by ammonia on Nucleophilic substitution by ammonia on -halo acids -halo acids

(Section 20.15)(Section 20.15)

Dr. Wolf's CHM 201 & 202 21-55

Preparation of AminesPreparation of Amines

by Alkylation of Ammoniaby Alkylation of Ammonia

Dr. Wolf's CHM 201 & 202 21-56

Alkylation of AmmoniaAlkylation of Ammonia

Desired reaction is:Desired reaction is:

2 2 NNHH33 ++ R—R—XX R—R—NNHH22 ++ NNHH44XX

via:via:

HH33NN •••••••• ••••RR XX••••

HH33NN RR++ •••• ••••XX

••••••••

––++ ++

then:then:

HH33NN •••• ++

HH NN

HH

HH

RR++ HH33NN HH

++++ NN

HH

HH

RR••••

Dr. Wolf's CHM 201 & 202 21-57

Alkylation of AmmoniaAlkylation of Ammonia

But the method doesn't work well in practice.But the method doesn't work well in practice.Usually gives a mixture of primary, secondary,Usually gives a mixture of primary, secondary,and tertiary amines, plus the quaternary salt. and tertiary amines, plus the quaternary salt.

NNHH33

RRXXRRNNHH22

RRXXRR22NNHH

RRXX

RR33NNRRXX

RR44NN++

XX––

Dr. Wolf's CHM 201 & 202 21-58

ExampleExample

CHCH33(CH(CH22))66CHCH22BrBrNHNH33

CHCH33(CH(CH22))66CHCH22NHNH22

(45%)(45%)

++

CHCH33(CH(CH22))66CHCH22NHNHCHCH22(CH(CH22))66CHCH33

(43%)(43%)As octylamine is formed, it competes with ammonia for As octylamine is formed, it competes with ammonia for

the remaining 1-bromooctane. Reaction of octylamine the remaining 1-bromooctane. Reaction of octylamine

with 1-bromooctane gives with 1-bromooctane gives NN,,NN-dioctylamine.-dioctylamine.

Dr. Wolf's CHM 201 & 202 21-59

The Gabriel Synthesis of The Gabriel Synthesis of

Primary AlkylaminesPrimary Alkylamines

Dr. Wolf's CHM 201 & 202 21-60

gives primary amines without formation ofgives primary amines without formation ofsecondary, etc. amines as byproductssecondary, etc. amines as byproducts

uses an Suses an SNN2 reaction on an alkyl halide to form2 reaction on an alkyl halide to form

the C—N bondthe C—N bond

the nitrogen-containing nucleophilethe nitrogen-containing nucleophileis is NN-potassiophthalimide-potassiophthalimide

Gabriel SynthesisGabriel Synthesis

Dr. Wolf's CHM 201 & 202 21-61

gives primary amines without formation ofgives primary amines without formation ofsecondary, etc. amines as byproductssecondary, etc. amines as byproducts

uses an Suses an SNN2 reaction on an alkyl halide to form2 reaction on an alkyl halide to form

the C—N bondthe C—N bond

the nitrogen-containing nucleophilethe nitrogen-containing nucleophileis is NN-potassiophthalimide-potassiophthalimide

Gabriel SynthesisGabriel Synthesis

OO

OO

NN•••• ••••––

KK++

Dr. Wolf's CHM 201 & 202 21-62

the pthe pKKa of phthalimide is 8.3a of phthalimide is 8.3

NN-potassiophthalimide is easily prepared by-potassiophthalimide is easily prepared bythe reaction of phthalimide with KOHthe reaction of phthalimide with KOH

N-PotassiophthalimideN-Potassiophthalimide OO

OO

NN•••• ••••––

KK++

OO

OO

NNHH••••

KOHKOH

Dr. Wolf's CHM 201 & 202 21-63

N-Potassiophthalimide as a nucleophileN-Potassiophthalimide as a nucleophile OO

OO

NN•••• ••••–– •••• ••••RR XX

••••++

OO

OO

NN RR••••

+ + •••• ••••XX••••

••••––

SSNN22

Dr. Wolf's CHM 201 & 202 21-64

Cleavage of Alkylated PhthalimideCleavage of Alkylated Phthalimide

OO

OO

NN RR•••• ++ HH22OO

HH22NN RR++

COCO22HH

COCO22HH

acid or baseacid or baseimide hydrolysis is imide hydrolysis is

nucleophilic acyl nucleophilic acyl

substitutionsubstitution

Dr. Wolf's CHM 201 & 202 21-65

Cleavage of Alkylated PhthalimideCleavage of Alkylated Phthalimide

hydrazinolysis is an alternative method of releasing the hydrazinolysis is an alternative method of releasing the

amine from its phthalimide derivativeamine from its phthalimide derivative

OO

OO

NN RR••••

HH22NN RR++

OO

OO

NHNH

NHNH

HH22NNHNNH22

Dr. Wolf's CHM 201 & 202 21-66

ExampleExample OO

OO

NN•••• ••••––

KK++ ++ CC66HH55CHCH22ClCl

DMFDMF

OO

OO

NN CHCH22CC66HH55

•••• (74%)(74%)

Dr. Wolf's CHM 201 & 202 21-67

ExampleExample

++ CC66HH55CHCH22NNHH22

OO

OO

NN CHCH22CC66HH55

••••

HH22NNHNNH22

(97%)(97%)

OO

OO

NHNH

NHNH

Dr. Wolf's CHM 201 & 202 21-68

Preparation of Amines by Preparation of Amines by

ReductionReduction

Dr. Wolf's CHM 201 & 202 21-69

almost any nitrogen-containing compound canalmost any nitrogen-containing compound canbe reduced to an amine, including:be reduced to an amine, including:

azidesazidesnitrilesnitrilesnitro-substituted benzene derivativesnitro-substituted benzene derivativesamidesamides

Preparation of Amines by ReductionPreparation of Amines by Reduction

Dr. Wolf's CHM 201 & 202 21-70

SSNN2 reaction, followed by reduction, gives a 2 reaction, followed by reduction, gives a

primary alkylamine.primary alkylamine.

Synthesis of Amines via AzidesSynthesis of Amines via Azides CHCH22CHCH22BrBr

CHCH22CHCH22NN33

NaNaNN33

(74%)(74%) CHCH22CHCH22NNHH22

(89%)(89%)

1. LiAlH1. LiAlH44

2. H2. H22OO

azides may also bereduced by catalytichydrogenation

Dr. Wolf's CHM 201 & 202 21-71



Synthesis of Amines via NitrilesSynthesis of Amines via Nitriles

CHCH33CHCH22CHCH22CHCH22BrBrNaNaCCNN

(69%)(69%)

CHCH33CHCH22CHCH22CHCH22CCNN

CHCH33CHCH22CHCH22CHCH22CCHH22NNHH22

(56%)(56%)

HH22 (100 atm), Ni (100 atm), Ni

nitriles may also bereduced by lithiumaluminum hydride

Dr. Wolf's CHM 201 & 202 21-72



Synthesis of Amines via NitrilesSynthesis of Amines via Nitriles

CHCH33CHCH22CHCH22CHCH22BrBrNaNaCCNN

(69%)(69%)

CHCH33CHCH22CHCH22CHCH22CCNN

CHCH33CHCH22CHCH22CHCH22CCHH22NNHH22

(56%)(56%)

HH22 (100 atm), Ni (100 atm), Ni

the reduction alsothe reduction alsoworks with cyanohydrinsworks with cyanohydrins

Dr. Wolf's CHM 201 & 202 21-73

Synthesis of Amines via NitroarenesSynthesis of Amines via Nitroarenes

HHNNOO33

(88-95%)(88-95%)

ClCl

ClCl NNOO22

HH22SOSO44

(95%)(95%)

1. Fe, HCl1. Fe, HCl

2. NaOH2. NaOH ClCl NNHH22

nitro groups may alsobe reduced with tin (Sn)+ HCl or by catalytichydrogenation

Dr. Wolf's CHM 201 & 202 21-74

Synthesis of Amines via AmidesSynthesis of Amines via Amides

(86-89%)(86-89%)

COHCOH

OO1. SOCl1. SOCl22

2. (CH2. (CH33))22NNHH

CCNN(CH(CH33))22

OO

(88%)(88%)

1. LiAlH1. LiAlH44

2. H2. H22OO CHCH22NN(CH(CH33))22

only LiAlH4 is an

appropriate reducingagent for this reaction

Dr. Wolf's CHM 201 & 202 21-75

Reductive AminationReductive Amination

Dr. Wolf's CHM 201 & 202 21-76

The aldehyde or ketone equilibrates with theThe aldehyde or ketone equilibrates with theimine faster than imine faster than hydrogenationhydrogenation occurs. occurs.

Synthesis of Amines via Reductive AminationSynthesis of Amines via Reductive Amination

OOCC

RR

R'R'

++ NNHH33

fastfast

NNHHCC

RR

R'R'

++ HH22OO

In reductive amination, an aldehyde or ketoneIn reductive amination, an aldehyde or ketoneis subjected to catalytic hydrogenation in theis subjected to catalytic hydrogenation in thepresence of ammonia or an amine.presence of ammonia or an amine.

Dr. Wolf's CHM 201 & 202 21-77

Synthesis of Amines via Reductive AminationSynthesis of Amines via Reductive Amination

OOCC

RR

R'R'

++ NNHH33

fastfast

NNHHCC

RR

R'R'

++ HH22OO

HH22, Ni, Ni

NNHH22

RR

R'R' CC

HH

The imine undergoes hydrogenation fasterThe imine undergoes hydrogenation fasterthan the aldehyde or ketone. An amine is than the aldehyde or ketone. An amine is the product.the product.

Dr. Wolf's CHM 201 & 202 21-78

Example: Ammonia gives a primary amine.Example: Ammonia gives a primary amine. OO ++ NNHH33

HH

NNHH22

HH22, Ni, Ni

ethanolethanol

(80%)(80%)

via:via:

NNHH

Dr. Wolf's CHM 201 & 202 21-79

Example: Primary amines give secondary aminesExample: Primary amines give secondary amines

HH22, Ni, Ni ethanolethanol

(65%)(65%)

CHCH33(CH(CH22))55CHCH22NNHH

++ HH22NN

CHCH33(CH(CH22))55CHCH

OO

via:via: NN

CHCH33(CH(CH22))55CHCH

Dr. Wolf's CHM 201 & 202 21-80

Example: Secondary amines give tertiary aminesExample: Secondary amines give tertiary amines

HH22, Ni, ethanol, Ni, ethanol

(93%)(93%)

++CHCH33CHCH22CHCH22CHCH

OO

NN

HH NN

CHCH22CHCH22CHCH22CHCH33

Dr. Wolf's CHM 201 & 202 21-81

Example: Secondary amines give tertiary aminesExample: Secondary amines give tertiary amines

CHCHCHCH22CHCH22CHCH33

NN++

possible intermediates include:possible intermediates include: NN

CHCH CHCHCHCH22CHCH33

CHCHCHCH22CHCH22CHCH33

NN

HOHO

Dr. Wolf's CHM 201 & 202 21-82

Reactions of Amines:Reactions of Amines:

A Review and a PreviewA Review and a Preview

Dr. Wolf's CHM 201 & 202 21-83

Reactions of AminesReactions of Amines

Reactions of amines almost always involve theReactions of amines almost always involve thenitrogen lone pair.nitrogen lone pair.

••••NN HH XX

as a base:as a base:

••••NN

CC OOas a nucleophile:as a nucleophile:

Dr. Wolf's CHM 201 & 202 21-84

Reactions of AminesReactions of Amines

basicity (Section 21.4)basicity (Section 21.4)

reaction with aldehydes and ketones (Chapter 17)reaction with aldehydes and ketones (Chapter 17)

reaction with acyl chlorides, reaction with acyl chlorides, anhydrides, and estersanhydrides, and esters

Reactions already discussedReactions already discussed

Dr. Wolf's CHM 201 & 202 21-85

Reactions of Amines with Alkyl Reactions of Amines with Alkyl

HalidesHalides

Dr. Wolf's CHM 201 & 202 21-86

Reaction with Alkyl HalidesReaction with Alkyl Halides

Amines act as nucleophiles toward alkyl halides.Amines act as nucleophiles toward alkyl halides.

•••• XX++ ••••••••

••••

••••NN RR

HH

++ XX ••••••••

••••NN RR

HH

++ ––

++NN RR••••

HH++

Dr. Wolf's CHM 201 & 202 21-87

Example: excess amineExample: excess amine NNHH22 ++ ClClCHCH22

NNHCHHCH22

(85-87%)(85-87%)

NaHCONaHCO33 90°C90°C

(4 mol)(4 mol) (1 mol)(1 mol)

Dr. Wolf's CHM 201 & 202 21-88

Example: excess alkyl halideExample: excess alkyl halide

++ 3CH3CH33II

(99%)(99%)

methanolmethanol heatheat

CHCH22NN (CH (CH33))33

CHCH22NNHH22

++

II––

Dr. Wolf's CHM 201 & 202 21-89

The Hofmann EliminationThe Hofmann Elimination

Dr. Wolf's CHM 201 & 202 21-90


a quaternary ammonium hydroxide is the reactanta quaternary ammonium hydroxide is the reactantand an alkene is the productand an alkene is the product

is an anti eliminationis an anti elimination

the leaving group is a trialkylaminethe leaving group is a trialkylamine

the regioselectivity is opposite to the Zaitsev rule.the regioselectivity is opposite to the Zaitsev rule.

Dr. Wolf's CHM 201 & 202 21-91

Quaternary Ammonium HydroxidesQuaternary Ammonium Hydroxides

AgAg22OO HH22O, CHO, CH33OHOH

CHCH22N N (CH(CH33))33

++

HOHO––

are prepared by treating quaternary ammmoniumare prepared by treating quaternary ammmoniumhalides with moist silver oxidehalides with moist silver oxide


II––

Dr. Wolf's CHM 201 & 202 21-92


160°C160°C


++

HOHO––

on being heated, quaternary ammonium on being heated, quaternary ammonium hydroxides undergo eliminationhydroxides undergo elimination

CHCH22

(69%)(69%)

++ NN(CH(CH33))33 ++ HH22OO

Dr. Wolf's CHM 201 & 202 21-93

MechanismMechanismMechanismMechanism HH

CCHH22

++NN(CH(CH33))33

––OO•••••••• HH••••

OO••••

HH••••

HH

NN(CH(CH33))33••••

CCHH22

Dr. Wolf's CHM 201 & 202 21-94

RegioselectivityRegioselectivity

heatheat

Elimination occurs in the direction that gives Elimination occurs in the direction that gives the less-substituted double bond. This is called the less-substituted double bond. This is called the the Hofmann rule.Hofmann rule.

NN(CH(CH33))33++

HOHO––

CHCH33CHCHCHCH22CHCH33HH22CC CHCHCHCH22CHCH33

CHCH33CHCH CHCHCHCH33

++

(95%)(95%)

(5%)(5%)

Dr. Wolf's CHM 201 & 202 21-95


Steric factors seem to control the regioselectivity.Steric factors seem to control the regioselectivity.The transition state that leads to 1-butene isThe transition state that leads to 1-butene isless crowded than the one leading to cisless crowded than the one leading to cisor trans-2-butene.or trans-2-butene.

Dr. Wolf's CHM 201 & 202 21-96


NN(CH(CH33))33++

HH

HH

HH HH

CHCH33CHCH22

largest group is between two H atomslargest group is between two H atoms

CC

HHCC

HHHH

CHCH33CHCH22

major productmajor product

Dr. Wolf's CHM 201 & 202 21-97


NN(CH(CH33))33++

HH

HH

HH

CHCH33

largest group is between anlargest group is between anH atom and a methyl groupH atom and a methyl group

CC

HHCC

CHCH33 HH

CHCH33

minor productminor product

CHCH33

Dr. Wolf's CHM 201 & 202 21-98

Electrophilic Aromatic Electrophilic Aromatic

SubstitutionSubstitution

in Arylaminesin Arylamines

Dr. Wolf's CHM 201 & 202 21-99

Nitration of AnililneNitration of Anililne

NHNH22 is a very strongly activating group is a very strongly activating group

NHNH22 not only activates the ring toward not only activates the ring toward

electrophilic aromatic substitution, it also electrophilic aromatic substitution, it also makes it more easily oxidizedmakes it more easily oxidized

attemped nitration of aniline fails because attemped nitration of aniline fails because nitric acid oxidizes aniline to a black tarnitric acid oxidizes aniline to a black tar

Dr. Wolf's CHM 201 & 202 21-100


Strategy: decrease the reactivity of aniline by Strategy: decrease the reactivity of aniline by

converting the NHconverting the NH22 group to an amide group to an amide CH(CHCH(CH33))22

NNHH22 CH(CHCH(CH33))22

NNHCCHHCCH33

OO

OO

CHCH33COCCHCOCCH33

OO

(98%)(98%)

(acetyl chloride may be used instead of acetic anhydride)(acetyl chloride may be used instead of acetic anhydride)

Dr. Wolf's CHM 201 & 202 21-101


Strategy: nitrate the amide formed in the first Strategy: nitrate the amide formed in the first

stepstep CH(CHCH(CH33))22

NNHCCHHCCH33

OO

HNOHNO33

CH(CHCH(CH33))22

NNHCCHHCCH33

OO NONO22

(94%)(94%)

Dr. Wolf's CHM 201 & 202 21-102


Strategy: remove the acyl group from the amide Strategy: remove the acyl group from the amide

by hydrolysisby hydrolysis

CH(CHCH(CH33))22

NNHCCHHCCH33

OO NONO22

KOHKOH

ethanol,ethanol,heatheat

CH(CHCH(CH33))22

NNHH22 NONO22

(100%)(100%)

Dr. Wolf's CHM 201 & 202 21-103

occurs readily without necessity of protecting occurs readily without necessity of protecting

amino group, but difficult to limit it to amino group, but difficult to limit it to

monohalogenationmonohalogenation

Halogenation of ArylaminesHalogenation of Arylamines COCO22HH

NNHH22

BrBr22

acetic acidacetic acid

(82%)(82%)

COCO22HH

NNHH22

BrBr BrBr

Dr. Wolf's CHM 201 & 202 21-104

Monohalogenation of ArylaminesMonohalogenation of Arylamines

ClCl

NNHCCHHCCH33

OO CHCH33

(74%)(74%)

ClCl22

acetic acidacetic acid

NNHCCHHCCH33

OO

CHCH33

Decreasing the reactivity of the arylamine by converting Decreasing the reactivity of the arylamine by converting

the NHthe NH22 group to an amide allows halogenation to be group to an amide allows halogenation to be

limited to monosubstitutionlimited to monosubstitution

Dr. Wolf's CHM 201 & 202 21-105

Friedel-Crafts ReactionsFriedel-Crafts Reactions

The amino group of an arylamine must be protected The amino group of an arylamine must be protected

as an amide when carrying out a Friedel-Crafts as an amide when carrying out a Friedel-Crafts

reaction.reaction. NNHCCHHCCH33

OO

CHCH33 CHCH33CClCCl

OO

AlClAlCl33

(57%)(57%)

NNHCCHHCCH33

OO CHCH33

CCHCCH33OO

Dr. Wolf's CHM 201 & 202 21-106

Nitrosation of AlkylaminesNitrosation of Alkylamines

Dr. Wolf's CHM 201 & 202 21-107

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 21-108

Nitrosyl Cation and NitrosationNitrosyl Cation and Nitrosation

++••••NN OO

•••• ••••

Dr. Wolf's CHM 201 & 202 21-109

Nitrosyl Cation and NitrosationNitrosyl Cation and Nitrosation

++••••NN OO

•••• ••••++••••NN

NN••••NN OO

•••• ••••++

Dr. Wolf's CHM 201 & 202 21-110

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 21-111

ExampleExample

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

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

••••(CH(CH33))22NN

••••NN OO

•••• ••••

Dr. Wolf's CHM 201 & 202 21-112

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 21-113

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 21-114


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 21-115


++

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 21-116

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 21-117

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 21-118

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 21-119

Nitrosation of ArylaminesNitrosation of Arylamines

Dr. Wolf's CHM 201 & 202 21-120

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 21-121

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 21-122

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 21-123

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 21-124

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 21-125

Synthetic TransformationsSynthetic Transformations

of Aryl Diazonium Saltsof Aryl Diazonium Salts

Dr. Wolf's CHM 201 & 202 21-126

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 21-127

Preparation of PhenolsPreparation of Phenols

ArAr NN NN++

ArAr OOHH

HH22OO, heat, heat

Dr. Wolf's CHM 201 & 202 21-128

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 21-129


ArAr NN NN++

ArAr HH

ArAr OOHH

ArAr II

ArAr FF

ArAr BrBrArAr ClCl

ArAr CNCN

Dr. Wolf's CHM 201 & 202 21-130

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 21-131

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 21-132


ArAr NN NN++

ArAr HH

ArAr OOHH

ArAr II

ArAr FF

ArAr BrBrArAr ClCl

ArAr CNCN

Dr. Wolf's CHM 201 & 202 21-133

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 21-134

ExampleExample

(68%)(68%)

NNHH22 CCHCCH22CHCH33

OO

2. HBF2. HBF44


HH22O, 0-5°CO, 0-5°C

3. heat3. heat

FF CCHCCH22CHCH33

OO

Dr. Wolf's CHM 201 & 202 21-135


ArAr NN NN++

ArAr HH

ArAr OOHH

ArAr II

ArAr FF

ArAr BrBrArAr ClCl

ArAr CNCN

Dr. Wolf's CHM 201 & 202 21-136

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 21-137

ExampleExample

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

NNHH22 NONO22

2. Cu2. CuClCl, heat, heat


HH22O, 0-5°CO, 0-5°C

ClCl NONO22

Dr. Wolf's CHM 201 & 202 21-138

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 21-139


ArAr NN NN++

ArAr HH

ArAr OOHH

ArAr II

ArAr FF

ArAr BrBrArAr ClCl

ArAr CNCN

Dr. Wolf's CHM 201 & 202 21-140

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 21-141

ExampleExample

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

2. CuCN, heat2. CuCN, heat


HH22O, 0°CO, 0°CNNHH22

CHCH33

CNCN CHCH33

Dr. Wolf's CHM 201 & 202 21-142


ArAr NN NN++

ArAr HH

ArAr OOHH

ArAr II

ArAr FF

ArAr BrBrArAr ClCl

ArAr CNCN

Dr. Wolf's CHM 201 & 202 21-143


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 21-144

ExampleExample

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

NaNONaNO22, H, H22SOSO44,,

HH33POPO22

NNHH22

CHCH33 CHCH33

Dr. Wolf's CHM 201 & 202 21-145

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 21-146

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 21-147

Azo CouplingAzo Coupling

Dr. Wolf's CHM 201 & 202 21-148

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 21-149

ExampleExample OHOH

++ CC66HH55NN NN++ OHOH

NN NCNC66HH55

ClCl––

Dr. Wolf's CHM 201 & 202 21-150

Spectroscopic Analysis of AminesSpectroscopic Analysis of Amines

Dr. Wolf's CHM 201 & 202 21-151

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 21-152

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 21-153

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 21-154

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 CHCH33OOHH

26.9 ppm26.9 ppm 48.0 ppm48.0 ppm

Dr. Wolf's CHM 201 & 202 21-155

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 21-156

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 21-157


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 21-158


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 21-159

End of Chapter 21End of Chapter 21

dr. wolf's chm 201 & 202 21-1 chapter 21 amines. dr. wolf's chm 201 & 202 21-2...

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