lecture 22- amines

General

Organic ChemistryTwo 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. CareyThird Edition

Instructor: Rabih O. Al-Kaysi, PhD.

Chapter 14Chapter 14

AminesAmines

Lecture 22

Amine NomenclatureAmine Nomenclature

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

Two IUPAC stylesTwo IUPAC styles

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

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))

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

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

Amino groups as substituentsAmino groups as substituents

pp-aminobenzaldehyde-aminobenzaldehyde

amino groups rank amino groups rank belowbelow OH groups and higher 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

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

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

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

trifluoroacetatetrifluoroacetateJust for general knowledge, will not be tested on

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 iodideJust for general knowledge, will not be tested on

Structure and BondingStructure and Bonding

147 pm147 pm

106°106°112°112°

AlkylaminesAlkylamines

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

Just for general knowledge, will not be tested on

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.


Physical PropertiesPhysical Properties

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

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 of being involved in intermolecular hydrogen hydrogen bondingbonding. Secondary amines have one. Tertiary . 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

Basicity of AminesBasicity of Amines

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.

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..



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


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.



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.


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


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.

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

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

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.

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.

Reactions of Amines:Reactions of Amines:

A Review and a PreviewA Review and a Preview

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)?

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

Nucleophilic substitution by azide ion (NNucleophilic substitution by azide ion (N33––))

Nitration of arenes Nitration of arenes

Nucleophilic ring opening of epoxides by ammonia Nucleophilic ring opening of epoxides by ammonia

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

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

Nucleophilic acyl substitutionNucleophilic acyl substitution

Preparation of AminesPreparation of Amines

by Alkylation of Ammoniaby Alkylation of Ammonia

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••••

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––

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.

The Gabriel Synthesis of The Gabriel Synthesis of

Primary AlkylaminesPrimary Alkylamines


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

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++

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

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

OO

NN•••• ••••–– •••• ••••RR XX

••••++

OO

OO

NN RR••••

+ + •••• ••••XX••••

••••––

SSNN22

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

ExampleExample OO

OO

NN•••• ••••––

KK++ ++ CC66HH55CHCH22ClCl

DMFDMF

OO

OO

NN CHCH22CC66HH55

•••• (74%)(74%)

lecture 22- amines

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