Sub Titution 1 Ho

8/11/2019 Sub Titution 1 Ho

1/41

WWU-ChemistryWWU-Chemistry

Aromatic SubstitutionAromatic Substitution


2/41


NomenclatureNomenclature

benzene

CH3

toluene

Cl

chlorobenzene

OH

phenol

NH2

O

OH

aniline benzoic acid

O

H

benzaldehyde

NO2

nitrobenzene


3/41


4/41


Nomenclature-- examplesNomenclature-- examples

O

OH

benzoic acid

O

H

&rouportho

meta or 3

para or 4

or 2

NO2

3-nitro ('PC)

m-nitrobenzoic acid (common)

Cl

4-chlorobenzaldehyde ('PC)

p-chlorobenzaldehyde (common)


5/41


Aromatic SubstitutionsAromatic Substitutions

Monosubstitution reactions on benzene

Electrophilic aromatic substitution mechanism

Nitration

Halogenation

Friedel-Crafts Reactions

Sulfonation Reactions


6/41


Electrophilic aromaticElectrophilic aromatic

substitutionsubstitution*

+SLOW

*

HH

*

H

*

H

resonance stabilized cation

*

H

,-

"base"

re-aromatize*

+ H-

delocalizedcation


7/41WWU-ChemistryWWU-Chemistry

NitrationNitration

! conc HN"#and H$S"%react to ma&e electrophile' N"$(

! nitro aromatics are important intermediates

! reduction of nitro groups gi)e anilines

N OO

nitronium ion

NO2

H

H.O4

NO2

H2.O4

HNO3

H2.O4

NO2

NO2 reduce NH2

reducing agents: /ilH4or H2 0 Pd(C)or .n 0 HClor 1e 0 HOc

+ H2O



Mechanism of Aromatic NitrationMechanism of Aromatic Nitration

Step *+ ,here does the electrophileStep *+ ,here does the electrophile

come fromcome from

HO N

O

O

+ H2SO4

O

H H

+N

Nitronium ion

O O

O N

O

OH

H

O N

O

OH

H

H.O4

Nitronium ion (NO2+) is the electrophile that reacts

with the benzene ring.



Mechanism of AromaticMechanism of Aromatic

Nitration .Step $/Nitration .Step $/H

+ NO2

slow

H

NO2

H

NO2

H

NO2

a resonance-stabilized arenium ion



Mechanism of AromaticMechanism of Aromatic

Nitration .Step #/Nitration .Step #/H

NO2 + HSO4

ast

NO2

+

this represents theresonance h!brido the arenium ion

H2SO4

H

NO2O -S

O

O

OH

NO2

S

O

O

OHH-O



HalogenationHalogenation! acti)e electrophile is a bromoniumor chloroniumion

! need 0e1is acid catal2st . Fe3#/ to acti)ate 3$

bomonium ion

-r

H

-r

-r

H-r

-r2

1e-r3

-r

+ H-r

-r

-r2+ 1e-r3

Cl2

1eCl3

Cl

+ HCl

(iodination requires special conditions)

mechanism:-r + 1e-r4



Friedel-Crafts Al&2lationFriedel-Crafts Al&2lation

! al&2l halide ( AlCl#--4carbocation ( AlCl#3-

! 1atch out for carbocation rearrangements5

! more than one al&2lation can occur --4 mixtures5

+ -r + H-rlCl3(cat)

CH2Cl2

+ + H-rlCl3(cat)

CH2Cl2-r



Friedel-Crafts Ac2lationFriedel-Crafts Ac2lation

! acid chloride ( AlCl#--4 ac2lium ion ( AlCl%-! cationrearrangements are NOT observed5

! ac2lation 1ill onl2 occur "NCE

! reactionVERYsensiti)e to substituents-- an ac2l group pre)ents

further reaction

+Cl

OlCl3(cat)

O

+ HCl

Cl

O

lCl4C OlCl3

O

an acylium ion



HO H

O

"o otherresonancestructures

H+

O



SulfonationSulfonation

Ar-H ( H$S"%' S"# Ar-S"#H ( H$"


16/41

Mechanism for sulfonation:



6irecting effects6irecting effects

! methox2 group releases electrons b2

resonance effect+ ortho and para director

! nitro group 1ithdra1s electrons b2

inducti)e and resonance effect+ meta

director



7hese are7hese are ortho and paraortho and para

directors5 All are electrondirectors5 All are electron

releasing55releasing55

-C8H9



All ortho/para directing groups have pairsofelectrons next to the benzene ring!

The only exception are alkyl groups. Theyare also ortho/para directors.



Acti)ation during substitutionActi)ation during substitutionAll ortho and paradirecting groups are activatingrelati)e to benzene' except halogen substituents

Halogens are 1ea&l2 deacti)ating but are still o' p-

directors&

H *

(

Electron releasing groups .:/ help stabilize

the ( in the ring introduced b2 the electrophile7his increases the rate of substitution5


21/41


,h2 do ortho;para groups direct as,h2 do ortho;para groups direct as

the2 do Resonance55the2 do Resonance55

O CH3

H3C

O

CllCl3

H3C

O

lCl4

O

CH3H

H

O

CH3

OCH3

H

O

CH3

OCH3

H

O

CH3

OCH3

H

O

CH3

OCH3 *%tra resonancestructure $rom lonepair on o%y#en!Ortho "ould "ortoo5

6eta "on7t "or!can7t put + ne%tto O-CH3


22/41


7hese are7hese are metameta directors5 All aredirectors5 All are

electron 1ithdra1ing55electron 1ithdra1ing55


23/41


6eacti)ation during substitution6eacti)ation during substitution

! All metadirectors arestrongl2deactivating

relati)e to benzene

&

H *

(

Electron 1ithdra1ing groups .:/ intensif2

the ( in the ring introduced b2 the electrophile7his slo1s the substitution reaction5


24/41


No1 let


25/41


,h2 does the nitration reaction ta&e,h2 does the nitration reaction ta&e

place preferentiall2 at theplace preferentiall2 at the metametapositionposition

Lets ask a what if question.


26/41


ortho

meta

para

BAD!

BAD!

H

NO2

"

O O"H#

H

NO2

"

O O"H#

H

NO2

"

O O"H#

"

O O"H#"

O O"H#"

O O"H#

H

NO2

H

NO2

H

NO2

"

O O"H#

"

O O"H#

"

O O"H#

H NO2 H NO2 H NO2


27/41


meta substitution preferred becausemeta substitution preferred because

the ( charge is ne)er next to thethe ( charge is ne)er next to the

C"C"$$R groupR group


28/41


7hird substitution7hird substitution


29/41


! ortho/paradirectors can 1or& together 1ith

metadirectors 7he2 reinforce each other

O-CH3HNO3

O-CH3

NO2

HNO3

O-CH3

NO2

NO2

H2.O4 H2.O4

ortho0 para director ortho0para

meta


30/41


Strongo/ pdirectors 1in o)er 1ea& o, p

and meta directors

OH

CH3

r2

er3

OH

CH3

r


31/41


Substitution RARELY occurs in-between two

substituents--too hindered!

CH3

CH3

H3C

O

Cl

)lCl3

CH3

CH3

OCH3

nothin# here!


32/41


Some groups can be modifiedto change their

directing effects

CH3

ortho0paradirector

86nO4

O OH

meta directorr2

er3

CH3

r

CH3

r

r2

er3

O OH

r86nO4 86nO4

r

O OH OOH

r

3-bromobenzoic acid

2-bromobenzoic acid 4-bromobenzoic acid


33/41


H3C

O

Cl

lCl3

O CH3

r2

er3r

O CH3

O CH3

r

r2

er3

r

H3C

O

Cl

lCl3

meta director

ortho0para director

Some more good stuff5Some more good stuff5


34/41


An explosi)e5An explosi)e5

CH3

NO2

NO2

O2N

$'%'8-trinitrotoluene .7N7/


35/41


CH3HNO3

H2.O4

CH3

NO2

CH3

NO2

*asy!

HNO3

H2.O4

CH3

NO2

NO2

more di$$icultHeat it!

HNO3

H2.O4

*en more di$$icultso really heat it!

CH3

NO2

NO2O2N

2,4,Trinitrotoluene "T#T


36/41

"""A #$%LE&'()L)% AR&MA*)% S$+S*)*$*) +Y

A,,)*) EL)M)#A*): *(E S#Ar ME%(A#)SM

Nucleophilic substitution can occur 1hen strong electron-1ithdra1ing groups

are ortho or para to the halogen atom

Cl

N"$

"H

N"$

( "H-a= NaHC"#

*#>?@

H(

Cl

N"$

N"$

"H

N"$

N"$

( "H-a= NaHC"#

*>>?@

H(

Cl

N"$

N"$

"$N

"H

N"$

N"$

"$N

( "H-a= NaHC"#

#9?@

H(

7he temperatureis related to thenumber of ortho orpara nitro groups


37/41

ut the meta-nitro group does not produce a similar acti)ating effect

Mechanism:

Cl

N"$

( "H-addition

slo1

"HCl

N"$

elimination

fast"H-( Cl-

"-

N"$

"H

N"$

( Cl-

H" Cl

N" "

H" Cl

N" "

H" Cl

N" "

H" Cl

N" "

7he delocalized carbanion is stabilized b2 electron-1ithdra1ing groups in the

positions ortho and para to the halogen atom


38/41

"""+ #$%LE&'()L)% AR&MA*)% S$+S*)*$*) *(R&$.( A#

EL)M)#A*)-A,,)*) ME%(A#)SM: +E#/Y#E

Chlorobenzene can be con)erted to phenol b2 heating it 1ith a=ueous sodium

h2droxide in a pressurized reactor

Cl

#9>?@ .high pressure/

"NaNa"H HCl

"H

romobenzene reacts 1ith the )er2 po1erful base' in li=uid ammonia


39/41

Mechanism:

CF#

NH

NH#

CF#

NH2

CF#

Cl

H

NaNH$

NH#.-HCl/

CF#

( NH$

CF#

NH2

NH#

X

" !

0

1

0ess stable

carbanion

More stable

cabanion

Carbanion # is more stable than % because the carbon atom bearing

the negati)e charge is closer to the highl2 electronegati)e trifluoro-

meth2l group


40/41



41/41

Documents

Sub Titution 1 Ho