Chemistry 125: Lecture 62March 29, 2010

Electrophilic Aromatic Substitution

This

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Electrophilic Aromatic

Substitution

Electrophilic Aromatic Substitution

H

HH

H

H

H

D2SO4

H

HH

H

D

H

Sec. 14.4

H

HH

H

H

H

D

A/D via intermediate

+

D2SO4C6D6

etc.

Observable!

Or other electrophiles in place of D+

e.g. NO2+, Br+, HOSO2 , R+, R-C=O R-C=O+HOSO2

+

In electrophilic addition to alkenes, a nucleophile would add in the next step, but here it is easier to lose H+ and recover aromatic stabilization.

H3C CH3

H3C

H3C

CH3

CH3

CH3

+

A

C C

B

D

B

1H vs. 1Hcorrelation in time

H3C CH3

H3C

H3C

CH3

CH3

CH3

+

CH3

CH3

H3C

H3C

CH3

CH3

CH3

+

A

A

C C

B

D

B

C

C

B

D

B

0.3 sec 40°C

CA

DB

Remember

+

+

+

SHMo2 (Simple Hückel Molecular Orbital Program)

Benzene Pentadienyl

Cation addition converts ring to chain.

H

HH

H

H

H

D+

H

HH

H

H

H

D

+

Locus ofodd electron in radical,

+ charge(LUMO)

in cation.

- charge (HOMO)

in anion,SOMO

(nonbonding)

+

+

+

Cf.

Sec. 14.4b

LUMO

X

NO2

++

+ +

HO2N

X

+++

+

H

O2N

X

+

+ +

H

Substituent Effects on Rate (sec. 14.9-14.10)

X

O2N

X

O2N

X X

NO2

+ +NO2

+

(from HONO2/H2SO4)

X Relative Rate (overall)

H [1] Cl 0.03 NO2 6 10-

8

CH3 25 OH 1000

(CH3)3N+ 1 10-

8

donation / withdrawal

(or ) e-donation eases formation of cation intermediates

(or ) e-withdrawal retards formation of cation intermediates

HOH

+

Note: +NO2 is O=C=O with an extra proton in the center

productsintermediates

Cf. Table 14.2

Why is -NO2 e-Withdrawing when -OH is e-Donating?

-NO2 6 10-

8

e-withdrawal retards formation of cation intermediates

-OH 1000 e-donation eases

N

O O

O

HpC

C=C pO-1

0

High HOMO; Good Overlap with Phenyl

Low OMO;Good Overlapwith Phenyl

(but poor E-match)

High HOMO;

Low LUMO;Good Overlapwith Phenyl

OH is a Donor

NO2 is a Acceptor

No Overlap with Phenyl

NO2 isallylic

(willing but not able)

Substituent Effects on Orientation (sec. 14.9-14.10)

X

NO2

+

(from HONO2/H2SO4)

X- Relative Rate (per replaceable H)

H- [1] [1] [1] Cl- 0.0008 0.03 0.13

O2N- 9 10-

8

0.6 10-8 0.03 10-8

H3C- 1 39 46 (CH3)3C- 4 6 72

DirectingActivating

Deactivating

Act

Deact

Deact

(CH3)3N- 3 10-

8

0.6 10-8 + _

ortho meta para

EtOC=O 0.006 0.0006

- 0.003

o/p

m

o/p

“e-donating”

“e-withdrawing”

(steric hindrance)?

X

NO2

++

+ +

HO2N

X

+++

+

H

O2N

X

+

+ +

H intermediates

Activate the ElectrophileHalogenation (sec. 14.4f)

“Cl+”

H

+29 +38

AlCl3 “Lewis acid”catalyst

AlCl5Cl2 vs.

LUMOsSurface Potentials

(Al, like B, has an empty valence AO)AlCl4

leaving group

Activate the Nucleophile

H

OH

C

O

O

OH

H

NH2

100 atm125°C

Self-Igniting Rocket Fuel(1944)

C

OH3C

N

O

O

+

Salicylic AcidKolbe (1860)

OH

CO

OH

H+

Aspirin

loweredHOMO

raisedHOMO

Acetylation of anilinemakes its nitration

controllable.

Taming Aniline Nitration

Friedel-Crafts Alkylation (sec. 14.5)

Friedel-Crafts Acylation (sec. 14.6)

Synthetic Accessibility (sec. 14.7)

End of Lecture 62March 29, 2010

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