H - Interlab - UFRJ

Electrophilic Aromatic Substitution – S E 2
G
E 1
+ E 2 +
G
E 2
+ E 1 +

G
Mechanisms of Reaction
� Ingold-Hughes (original idea)
� Advantage: aromaticity is mantained in the direct displacement
E +
� Melander
E
H
B
G
E
+ BH +
� Secondary kinetic isotopic effect for nitration and bromination of
aromatics
Reaction k H /k D
Benzene + HNO3 /H2SO4 0.89
Toluene + NO +
2 BF4 - 0.85

Energia
Do
Ponto
Zero
(EPZ)
E
Efeito Cinético Isotópico
C-H
C-D
N 1
EPZ = ∑ hν
i
2
i
ν =
1
2π
k
µ
C . + . H
C . + . D
ΔG D
ΔG H
r C-H(D)

“Accepted” Mechanism for Nitration
§� Ingold-Hughes (Polar) Mechanism
ArHNO 2 +
HNO 3 + HA H 2 NO 3 + + A - (1)
H 2 NO 3 +
k 1
k -1
NO 2 + + H2 O (2)
ArH + NO 2 + ArHNO2 + (3)
ArHNO 2 + + A -
k R
ArNO 2 + HA (4)
HNO 3 + ArH ArNO 2 + H 2 O
Wheland Intermediate
Arenium ion (Olah)
σ Complex (H. C. Brown)
Reaction Intermediate
Isolated or
detected

Modified Mechanisms
k1 ArH + NO +
2 ArH.NO2 +
π Complex
• Interaction between
reactants
• π system is involved
with the NO 2 + as a whole
(Olah)
Complex
k 2
Encounter Pair
• No interaction between
the reactants
• Random collision of
species leads
to the σ complex
• Reactants are trapped
into the solvent cage
G
(Schofield)
H
NO 2
Complex σ
-“H + ”
G
NO 2
SET
• Charge Transfer complex
• Formation of ArH + and NO 2
• Depends on ionization
potential of the aromatic
(Kerner, Weiss,
Perrin, Eberson,
Kochi)

SET Mechanism
§� Kenner (1945) and Weiss (1946)
§� Single Electron Transfer from ArH to NO 2 +
§� Perrin (1977)
§� Nitronaphthalene from naphthalene under NO 2 and electrolysis
§� Same product ratio for α and β (10:1) nitronaphthalene as that
found in HNO3 /H3CCN kSET ArH + NO +
2 ArH + + NO2
SET
(Single Electron Transfer)
k colapse
Oxidation potentials of aromatics more activated than
toluene are lower than oxidation potentials of NO 2
G
H
NO 2
σ Complex
-“H + ”
G
NO 2
SET is exothermic
Perrin, C. L.; J. Am. Chem. Soc. 1977, 99, 5516

SET Mechanism
§� Kochi, 1981
§� Nitration with NO 2 Y (Y= OH, OAc, NO 3 , Cl, Py, C(NO 2 ) 3 )
§� NO 2 Y + aromatics à� Observation of absorption
bands in the UV/Vis spectrum
Typical for Charge Transfer complexes
Intramolecular

Perrin and Kochi´s Mechanism
ArH + NO 2 Y [ArH, NO 2 Y] (CT)
[ArH, NO 2 Y] (CT)
[ArH + , NO 2 Y - ] (ET)
[ArH + , NO 2 Y - ] (ET) [ArH + , NO 2 ] Y -
[ArH + , NO 2 ] Y -
G
H
NO 2
hν
or Δ
- Y -
fast
+ Y- fast
G
H
NO 2
G
NO 2
(σ)
+ HY
Rate controlling: Single Electron Transfer (SET)
Spin density: Controls Regioselectivity
Problems: small k predicted for an outer sphere complex (Marcus Theory)
Explain low ipso substitution despite the high spin density on
this position

Ion-Molecule Reactions in the Gas Phase
§� Olah, Dunbar: ICR (Ion Cyclotron Resonance)
ArH + NO +
2 C6H6O + k1 . + NO
§� Cacace and col., ICR
ArH + NO 2 + .HOCH3
or
NO 2 + .O=CH2
Unknown
Intermediate
G
H
k H /k D = 1.0
NO 2
σ Complex
Gas phase results disfavor the mechanism of Schofield, since there is
complex formation and there is no solvent involved
Controversy: Nature of the intermediate
observed before the σ complex
B:
G
NO 2
+ HB +
Single electron transfer
π Complex
?

Mechanistics Aspects
Initial approach: ab initio/DFT calculations

Initial Approach: π Complexes?
H
H H
H H
1.415
H
H
θ (ONO) = 180 o
1.129
O N O
3.486 3.486
1.406
H H
C 2v
1 (2)
1.376
O
1.185
H
H
C s
4 (0)
N
1.997
1.406
136.7 o
1.187
1.085
1.447
H
O
H
H
H
1.409
H
H
H
θ (ONO) = 145.0 o
1.390
θ (ONO) = 180 o
C s *
5 (1)
O
N
O 1.155
3.074 3.074
H
1.403
C 2v *
2 (2)
2.434
H
O
1.189
NO
H
1.419
H
H
1.387
H
H
1.403
O
H
H
1.173
142.2 o
N
1.428
1.429
2.607
C s
6 (2)
O
H
H
H
1.405
H
H
1.426
H
H
H
180.0 o
2.826
H
1.387
O
N
O
1.404
1.151
1.144
2.826
C 6v
3 (0)
O
C s
7 (1)
H
H
θ(ONO) = 141.1 o
1.175
N
2.331 2.331
H
H 1.404
H
1.086
1.178
1.442
H
O

B3LYP/6-311++G**//B3LYP/6-31++G** calculations
H
PhOH
+ NO +
4.3
-29.7
H
H
O
H
H
30.4
N
PhOH +.
+ NO .
17.3
H
H
O
O
N
H
H
16.5
H
20
O
17
H
22
≈
H
NO 2 + +
33.5
NO 2 +
-47.0
≈ ≈
18.9
H
21.8
11.7
-7.7
15
H H
H H
14.6
33
H
8.2
H
-6.0
O
O
N
N
H
32
H
0.5
O
H
H
H
O
N O
H H
14
O
H
O H
18
H H
H
16
36
2.2
13
N
H H
H H
[PhOH.NO] +
H H
21
H
H
H
H
N
H
O
O
H
H
H
H
2.6
O
2.2
6.6
H
H
O
O
31
34
N
12.0
H
H
H
3
14.3
O
N
O
H
H
π−complex
H
H
< 7 (estimated)
H
H
0.7
4
O
H
H
N
H
10
O
0.9
H
H
H H
H
H
O N O
7
8 1.1 8
σ−complex
O
N
O
H
28
10.8
4.4
H
12.7
O
H H
23
N
H
H
10.2
O
35
29
H
H
37
H
O
N
H
24
30
H
11.6
O
H
H
H H
H
H H
25
N
O
O
20.2
-32.8
H
H
H
O
N
H
26
O
5.1
H
H
H
O
≈
35.8
+ NO
H
H
O
H
27
N
H
O
H
H
C

Key intermediates
H
H
H
O
N
O
NO 2 + |ArH
π-complex /
Charge Transfer
Complex
H
H
H
H
H
H
NO 2 . |ArH +.
Cation radical molecule
Intimated pair
O
H
H
N
H
O
H
H
H
H H
Unoriented complex à� Electrostatic nature (π)
Oriented complex à� SET intimate pair
ArHNO 2
H
σ-complex
Avoided crossing between different electronic states
N
O
O

Ion-Molecule Reaction in the Gas Phase: Pentaquadrupole MS
Colaboration with Prof. Marcos N. Eberlin (State University of Campinas – Brazil)
Extrel Pentaquadrupole QqQqQ Mass Spectrometer (MS 3 )
Eberlin, M. N. Mass Spectrom. Reviews 1997, 16, 113

Extrel Pentaquadrupole QqQqQ Mass Spectrometer (MS 3 )
M 1
M 2
Fonte Q1 q2 Q3 q4 Q5 Det.
Eberlin, M. N. Mass Spectrom. Reviews 1997, 16, 113

Reaction of Benzene with NO 2 +
NO 2 +
SET is
dominant

Ion-Molecule Reaction: Solvent Effects
NO 2 + .CH3NO 2
(CI)

NO 2 + .CH3NO 2
(CI)
m/z 107
H
O
N O
H
m/z 185
124
m/z 78
NO 2
ou
NO 2.CH 3NO 2
SET
H
N O
O-
N O
O
+ CH 3NO 2*
OH
m/z 124 m/z 124 m/z 124 m/z 94
+ NO

Contagem
MS/MS of m/z 124
2000
1500
1000
500
0
50 65 66
77
78
- CO
20 40 60 80 100 120 140
m/z
OH H O
94
ou
N O
H
O
e/ou
124
H
e/ou
N
O
O
H N
O
O

Does SET thermodynamically feasible?
Ionization Energy (Potential) for ionization in the Gas
Phase
. NO2 à� NO 2 + + e IE1
ArH à� ArH + + e IE 2
NO 2 + + e à� NO2 -IE 1
+ ArH à� ArH + + e IE 2
NO 2 + + ArH à� NO2 + ArH +
ΔH reaction ≈ IE 2 – IE 1 = ΔIE

Substrate Ionization Energy
(IE)
(eV) a
ΔIE for
Reaction with
NO 2 + (eV)
ΔIE for
Reaction with
NO 2 + (kcal/
mol)
NO 2 → NO 2 + + e 9.586 ± 0.002 0.000 0.00
Benzene → C 6 H 6 + + e 9.24378 ± 0.00007 -0.342 -7.89
Toluene → C 7 H 8 + + e 8.828 ± 0.001 -0.758 -17.48
mesitylene → C 9 H 12 + + e 8.40 ± 0.01 -1.186 -27.35
PhNH 2 → PhNH 2 + + e 7.720 ± 0.002 -1.866 -43.03
PhOMe → PhOMe + + e 8.20 ± 0.05 -1.386 -31.96
naphthalene → C 10 H 8 + + e 8.1442 ± 0.0009
8.141 ± 0.01
-1.442 -33.25
Nitrobenzene → C 6 H 5 NO 2 + + e 9.94 ± 0.08 +0.354 +8.16
1,3-dinitrobenzene → C 6 H 4 N 2 O 4 + + e 10.4 +0.814 +18.77
C 6 H 5 CN → C 6 H 5 CN + + e 9.73 ± 0.01 +0.144 +3.32
C 6 H 5 CF 3 → C 6 H 5 CF 3 + + e 9.685 ± 0.005 +0.099 +2.28
fluorbenzene → C 6 H 5 F + + e 9.20 ± 0.01 -0.386 -8.90
chlorobenzene → C 6 H 5 Cl + + e 9.07 ± 0.02 -0.516 -11.9
bromobenzene → C 6 H 5 Br + + e 9.00 ± 0.03 -0.586 -13.5
iodobenzene → C 6 H 5 I + + e 8.72 ± 0.04 -0.866 -20.0
Data from NIST database: http://webbook.nist.gov/chemistry

Nitration of Activated Aromatics
NO 2 + .CH3NO 2
(CI)
CH 3

Count
50000
40000
30000
20000
10000
Nitration of Activated Aromatics
0
NO +
2 .CH3NO2 107
NO 2 +
46
65
78
93
108
OCH 3
OH
OCH 3
124
0 50 100 150 200 250 300
m/z
NO 2 + .CH3NO 2
(CI)
OMe

Count
Nitration of Halo-Aromatics: PhF
35000
30000
25000
20000
15000
10000
5000
0
84
F
91
96
-CO
97
107
112
142
0 50 100 150 200 250
OH
F
m/z
NO 2 + .CH3NO 2
F
(CI)
NO 2
F

Count
2500
2000
1500
1000
500
0
MS/MS of m/z 142
62 75 84
96
112
125
142
0 20 40 60 80 100 120 140 160 180
m/z
- NO 2
- NO
- OH
N O
H
O
F

Count
2500
2000
1500
1000
500
0
MS/MS of m/z 112
20 40 60 80 100 120 140
m/z
84
- CO
112
OH
F

Nitration of Halo-Aromatics: PhCl
NO 2 + .CH3NO 2
(CI)
Cl

Count
Nitration of Halo-Aromatics: PhBr
12000
10000
8000
6000
4000
2000
0
46
68
72
85
106
92
100
107
156
158
0 50 100 150 200 250
m/z
Br
NO 2 + .CH3NO 2
(CI)
Br

Count
Nitration of Halo-Aromatics: PhI
30000
25000
20000
15000
10000
5000
0
107
204
0 50 100 150 200 250 300
m/z
NO 2 + .CH3NO 2
I
(CI)
I

Nitration of Deactivated Aromatics
NO 2 + .CH3NO 2
(CI)
NO 2
SET is not
detected

e
Proposal
� Aprotic polar solvent
O
N
O
O N
O
O
N
G
O
H
CH 3
G
N
O
O O N
O
+
G
(a) (b)
CH 3
Oxygen transfer Nitration
O
(c)
O
N
H
*
G
G
+ . NO 2
Electron Transfer

Solv
Solv
e
Proposal
� Protic polar solvent
H
O
N
H
O
H H
Solv
Solv-H
Solv
G
Solv
Solv
O
H H Solv
O
N
Solv-H*
H
O
H Solv
O
N
H
(a)
G
G
(b)
Nitration
G
+ . NO 2
Electron transfer

SET x Solvation
S
S
S
S
S S
S
S
S
S
S
S
S S
S
S
S
S
S
S
S S
S
S
S
S
S
S
S
S
O
S
O N O
S
S S
N O
S S
S S
S
S S
S
S
S
S
S
Electron
Transfer
S S
O
N
O
S
S
S
S
S
S
S
S
S
S S
S
O
N
O
S
S
S
S S S
S
S
S S S S
S
S
S
S
S
S
S
S
S
S S
S S
S
S S
Difusion Difusion
Non-oriented π complex
Electron
Transfer
S
S
S
S S
O
S
S
N O
S S
S
S
S
S
S
S
S
S
S
S
S
S
S S
O N O
S S
Interaction
S
S
S
S
S
Oriented π complex
S
S
S
S
S
S
S
Collapse
S
O N O
S S
S S
S
S
S
S
S
S
S
S
S
S
S
S
S
H
S
S
NO 2
S S
S S
S
S
S
S
S

18 O isotope study
H 3C NO 2
+ NO 2
O
O N
Detsina, Sidorova, Panova,
Malykhin, Shakirov
Zh. Org. Khim. 1979, 15, 1887

Proposal: Distinct Reaction Intermediates
NO 2 + +
33.5
NO 2 +
21.8
11.7
O
N
O
14.3
O
H
Avoided Crossing TS Step
(SET)?
N O
0.7
-7.7
O N O
O N O
H
NO 2
-11.0
O N O
7.5
O
H
NO 2
N
O
H
Three distinct
intermediates
before proton
elimination

LUMO
HOMO
Frontier MO and its relation to SET
LUMO
HOMO
LUMO
ΔE = hν
HOMO
Donor (D) Acceptor (A)
(b) Ground State: c 1 |NO 2 + ,C6 H 6 > + c 2 |NO 2 ,C 6 H 6 +. > + …
ΔE = 0
LUMO
HOMO
Donor (D) Acceptor (A)
LUMO
HOMO
ΔE = 0
LUMO
HOMO
Donor (D) Acceptor (A)
(a) Ground State: |NO 2 + ,C6 H 6 >
LUMO
HOMO
ΔE = 0
LUMO
HOMO
Donor (D) Acceptor (A)

θ = 180 o
O N O
LUMO
Angle
Distortion
LUMO energy of
NO 2 + as a function of
the ONO bond angle.
The LUMO of NO 2 +
becomes isoenergetic
with the HOMO of
benzene at 147 o ,
indicating an
approximate
geometry for the SET
process.
LUMO
θ
O N O
(a) (b)
LUMO energy of NO2+ (eV)
+
-0,20
-0,25
-0,30
-0,40
-0,45
LUMO in NO 2 + cation at (a) linear
and (b) bent geometries.
HOMO (ArH)-LUMO (NO 2 + )
Crossing point
(aproximate geometry where SET takes
place)
Energy of
the HOMO
of C6H6
(-0.336)
ONO angle in NO2+ (degrees)
-0,35120
125 130 135 140 145 150 155 160 165 170 175 180
E LUMO NO2+

Symmetric
HOMO of Benzene
Antisymmetric
E = -0,329 Hartrees E = -0,329 Hartrees
Jean, Y.; Volatron, F.; An introduction to molecular orbitals; Oxford University Press; New York, 213, 1993..

E
Z
C H Z C H
C H Y
6 5 6 6
6 5
Symmetric
Z Y
S , A
Antisymmetric
Y
Antisymmetric
Symmetric
Z=donor Y=acceptor
Fukuzumi, S.; Kochi, J.K.; J. Am. Chem. Soc., 103,7240, 1981.

Energy (a.u.) of MO´s for the aromatic substrates
Substrate HOMO HOMO - 1
Benzene
-0,329 (S) -0,329 (A)
Toluene
Aniline
Phenol
Fluorbenzene
Clorobenzene
Bromobenzene
Nitrobenzene
Benzaldehyde
(Trifluormethyl)benzene
-0,317 (S)
-0,290 (S)
-0,310 (S)
-0,334 (S)
-0,333 (S)
-0,330 (S)
-0,365 (A)
-0,346 (A)
-0,352 (A)
-0,328 (A)
-0,330 (A)
-0,338 (A)
Analysis of symmetry and energy of selected MOs
-0,347 (A)
-0,347 (A)
-0,348 (A)
-0,374 (S)
-0,350 (S)
-0,357 (S)
Donors: CH 3 , NH 2 , OH, F, Cl and Br.
Acceptors: NO 2 , CHO and CF 3 .

Regioselectivity: SET pair for PhCl
2,396Å 146 o
145 o 40’
q(NO 2 )= +0.34 e –
q(ArH)= +0.66 e –
2,327Å
q(NO 2 )= +0.30 e –
q(ArH)= +0.70 e –
Directing groups ortho and para
SET complex is only formed at ipso and para positions

MO’s for the complex between PhNO 2 and NO 2 +
ortho
HOMO HOMO - 1
para
HOMO
HOMO - 1

E LUMO (hartrees)
-0,260
-0,300
-0,340
-0,380
-0,420
o
o
NO
2
o
E LUMO of NO 2 + versus θONO
CHO
CF
3
o
Br
Cl
F
CH
H
o
o
3
OH
o
NH
130 150 170
190
o
2
o
o
o
Ângulo O-N-O
θ = 180 o
O N O
LUMO
Angle
Distortion
LUMO
θ
O N O
(a) (b)
+

E (Kcal/mol)
40,00
30,00
20,00
10,00
E rel of NO 2 + (λMarcus ) versus θ ONO
o
o
o
λ NO2+
o
NO
2
o
CF
3
CHO
o
λ NO2+
F
Cl
Br
H
CH3
OH
0,00
o o
130 150 170
190
o
o
Reactivity order for the substrates:
C 6 H 5 NH 2 > C 6 H 5 OH > C 6 H 5 CH 3 > C 6 H 6 >
C 6 H 5 Br > C 6 H 5 Cl > C 6 H 5 F > C 6 H 5 CHO >
C 6 H 5 CF 3 and C 6 H 5 NO 2 .
o
Crossing curve model
E a = f(λ NO2+ +λ ArH )
NH
2
Angle ONO
λ ArH ≈ 0
E a = f(λ NO2+ )

R
NH
Rearrangement of N-Nitroanilines
R NO2 N
"H + "
R
NH
R NO2 N H
+ NO 2 +
Fissão
homolítica
SET
R
NH
. NO2
R
NH
NO 2

SET in aniline nitration?
Reação
Energia de
Ionização (IE)
(eV) a
ΔEI para a
reação com
NO 2 + (kcal/mol)
NO 2 → NO 2 + + e 9.586 ± 0.002 0.00
PhNH 2 → PhNH 2 + + e 7.72 ± 0.002 -43.0
p-MeOC 6 H 4 NH 2 → p-MeOC 6 H 4 NH 2 + + e 7.58 ± 0.01 -46.3
p-MeSC 6 H 4 NH 2 → p-MeSC 6 H 4 NH 2 + + e 7.60 ± 0.01 -45.8
p-MeC 6 H 4 NH 2 → p-MeC 6 H 4 NH 2 + + e 7.85 ± 0.05 -40.0
m-MeC 6 H 4 NH 2 → m-MeC 6 H 4 NH 2 + + e 7.50 ± 0.02 -40.7
p-FC 6 H 4 NH 2 → p-FC 6 H 4 NH 2 + + e 8.18 -32.4
p-ClC 6 H 4 NH 2 → p-ClC 6 H 4 NH 2 + + e 7.8 -41.2
m-FC 6 H 4 NH 2 → m-FC 6 H 4 NH 2 + + e 8.33 -29.0
m-ClC 6 H 4 NH 2 → m-ClC 6 H 4 NH 2 + + e 8.1 ± 0.1 -34.3
m-BrC 6 H 4 NH 2 → m-BrC 6 H 4 NH 2 + + e 7.7 ± 0.1 -43.5
p-NCC 6 H 4 NH 2 → p-NCC 6 H 4 NH 2 + + e 8.64 ± 0.04 -21.8
p-O 2 NC 6 H 4 NH 2 → p-O 2 NC 6 H 4 NH 2 + + e 8.34 ± 0.01 -28.7

Hammett correlation
log(kx/kh)
4
3
2
1
0
-0.4 -0.2 0 0.2 0.4 0.6 0.8 1
σ +
-1
-2
-3
-4
R
NH
R NO2 N
"H + "
R
NH
R NO2 N H
+ NO 2 +
y = -3.0643x + 0.2259
R 2 = 0.9213
Fissão
homolítica
SET
R
NH
. NO2
White, W. N.; e Klink, J. R. J. Org. Chem. 1970, 35(4), 965-9.
R
NH
NO 2

Rearrangement
of
N-Nitrosoanilines
X
Log(k X /k H )
CH3 N
NO
..
+ "H + "
X
δ-
Polar
CH3 N
H
..
+ NO +
SET Polar
X
CH3 N
NO
H
X
SET
δ+
CH3 N
H
+ NO
σ

ArH + NO 2 + ArH.NO 2 +
ArH.NO 2 +
ArH + fast
.NO2 (SET)
G
Mechanistic Proposal
H
NO 2
- “H + ”
ArH + .NO 2 (SET)
G
Rate controlling step: Depends on the ionization potential of ArH
G
H
NO 2
NO 2
(σ)
Unoriented
electrostatic complex
SET intimate complex

Conclusions: Nitration
§� Reaction of NO 2 + with ArH à� SET
§� Solvation makes
§� Deactivated aromatics à� Aducts formed
§� Activated aromatics à� SET is favored
§� SET mechanism is surely involved in nitration of activated
aromatics
§� Mechanistic continuum between polar mechanism (Ingold-
Hughes) and SET: Depends on ArH and on solvation
§� The higher the HOMO of ArH, lower the “barrier” for the SET
and aromatic is more easily undergo oxidation.

Nitration: Mechanistic Continuum
Polar
Mechanism
(Ingold-Hughes)
• Substrates with high PI (meta
directing substituents)
• Non oxidant electrophiles
• Solvents with high ε (H 2 SO 4 ,
polar protic solvents, etc)
SET
Mechanism
• Substrates with low PI (orthopara
directing substituents)
• Oxidant electrophiles
• Solvents with low ε (aprotic
polar solvents, SO 2 , CH 2 Cl 2 ,
etc)

Other Typical Electrophilic Aromatic
Substitution
� Friedel-Crafts Alkylation
� Friedel-Crafts Acylation
� Halogenation
� Sulfonation
� Nitrosation
� Metalation

49,4
16,3
2,4
2,1
1,6
1,5
0,0
Acetilação do tolueno
ΔH (kcal/mol)
33,1
0,3
0,5
13,9
14,2
14,7
0,1
+ 180,0o
SET
0,8
+
(e)
128,6 o
(a)
(d)
(c)
(b)
127,0 o
1,80
137,2 o
2,05 (e)
128,0 o
1,77 (d)
130,3 o
130,9 o
1,83 (c)
1,68
0,3 kcal/mol
0,5 kcal/mol
0,1 kcal/mol
(b)
1,5 kcal/mol
(a)
Eletrófilo X Oxidante
Ativação pelo CH 3
Permite a formação de
um complexo σ em para,
porém menos estável
que o complexo π
correspondente.
Complexo σ em orto não
foi encontrado.
Pequenas diferenças de
Energia X efeito estérico?
Parâmetros geométricos
Ângulo do grupo acílio
nos complexos é muito
semelhante ao do radical
acila
Complexo π X complexo
SET

85,5
24,6
4,4
0,0
Acetilação do nitrobenzeno
ΔH (kcal/mol)
180,0 o
20,2
+
81,2
+
1,79
178 o
128,6 o
135,9 o
1,57
Desativação pelo grupo nitro
Processo SET muito desfavorecido
Complexos π não foram encontrados
Dois mínimos encontrados:
ambos de interação do íon
acetílio com a base n do grupo
nitro (átomo de oxigênio), mais
forte do que a base π do anel.

Kinetic Isotope Effect for Propionilation and
Benzoylation of Aromatics
CH 3 CH 2 CO + SbF 6 -
Toluene-benzene-d 6
Toluene-benzene-d 6
Tolueno-d 5 -benzeno
C 6 H 5 CO + SbF 6 -
p-Xilene-benzene
p-Xileno-benzeno-d 6
Toluene-d 5 -benzene
Toluene-d 5 -benzene
k H :k D = 2.84
Benzeno-d 6
k H :k D = 3.06
Toluene-d 5
k H :k D = 1.80
Benzene-d 5
k H :k D = 1.65
Toluene-d 5
G. A. Olah, J. Lukas, E. Lukas; JACS 1969, 91(19), 5319

Other kinetic isotopic effects:
Reaction Type k H /k D
PhNMe 2 + Br 2 Halogenation 2.6
PhOMe + ICl Halogenation 3.8
PhBr + H 2 SO 4 (oleum) Sulfonation 1.5
PhOH + NO + Nitrosation 4.1
PhH + Hg(OAc) 2 Metalation 6.0

New Reactions: New paradigms
G
G
X
ATCIC (oxidante)
NaNO 2,SiO 2/H 2O
ATCIC (oxidante)
NaNO 2,SiO 2/H 2O
Yields
G = OH, X = H 98%
G = OH, X= F 99%
G = OH, X = CN, 95%
G = OH, X = NHAc 33%
O 2N
G
NO 2
G
X
NO 2
NO 2
Zolfigol, Madrakian e Ghaemi
Synlett, 2003, 14, 2222-2224

E
Reaction Profiles: States and Electronic Configurations
[E
ΨC + Ar . . H] [E . . Ar H + ] [E . Ar + . H]
Ψ A
S 1
Case 1: Ψ c of high energy
E a
Ψ B
Transition State is due to the
Crossing of the electronic
configurations
r Ar-E

E
Reaction Profiles: States and Electronic Configurations
Ψ A
S 1
Case 2: Ψ c of low energy
[E + Ar . . H] [E . . Ar H + ] [E . Ar + . H]
Ψ C
Ψ B
2 Transition States
1 Reaction intermediate
r Ar-E

Conclusion
� The electrophilic aromatic substitution mechanism
can be a spectrum of possibilities between the SET
or Polar (Ingold-Hughes) mechanism,
dependending on the oxidative character of the
electrophile and the ionization potential of the
aromatic substrate.
� Solvent/medium effects can influence the
reactional pathway

Perspectives
§� Reinvestigation of other electrophilic aromatic and alifatic
substitution under the SET paradigm
§� Electrophiles, Superelectrophiles or Superoxidants?
§� The single electron transfer process and theories of
reactivity
§� Development of new reaction under the new paradigm.

Team
§� Coworkers
§� José Walkimar de M. Carneiro (IQ/UFF)
§� Marcos N. Eberlin (IQ/UNICAMP)
§� Regina Sparapan (IQ/UNICAMP)
§� Adão A. Sabino (IQ/UNICAMP)
§� Liliane (IQ/UNICAMP)
§� Márcio Contrucci de Mattos (IQ/UFRJ)
§� Students
§� Students (Cont.)
§� Fabio Luis Rodrigues (IC/UFRJ)
§� Leonardo Almeida (PG/DQO/UFRJ)
§� Gabriela Fonseca (PG/DQO/UFRJ)
§� Felipe Fleming Pereira (PG/DQO/UFRJ)
§� Jorge Freitas (IQ/UFF)
§� Rachel Moraes (IC/UFRJ)
§� Leandro (IC/UFRJ)
§� Ana Cristina Paes Leme (IC/UFRJ)
§� Vivian Mazzei (IC/UFRJ)
§� Thiago Muza (IC/UFRJ)
§� Rejane Magalhães Ramos (IC/UFRJ)
§� Carolina Leite Araujo (IC/UFRJ)

Acknowledgements
§� CNPq
§� CNPq (PROFIX)
§� FAPERJ (Cientista Jovem do Nosso Estado)

Instituto de Química
Universidade Federal do Rio de Janeiro
Prof. Pierre M. Esteves
(pesteves@iq.ufrj.br)
www.iq.ufrj.br/~pesteves