Influence of Anionic and Cationic Reverse Micelles on Nucleophilic Aromatic Substitution Reaction between 1-Fluoro-2,4-dinitrobenzene and Piperidine

Article abstract of DOI:10.1021/jo000714s

The nucleophilic aromatic substitution (S_NAr) reaction between 1-fluoro-2,4-dinitrobenzene and piperidine (PIP) were studied in two different reverse micellar interfaces: benzene/sodium 1,4-bis(2-ethylhexyl) sulfosuccinate (AOT)/water and benze

Full text of DOI:10.1021/jo000714s

J . Org. Chem. 2000, 65, 6427-6433
6427
In flu en ce of An ion ic a n d Ca tion ic Rever se Micelles on
Nu cleop h ilic Ar om a tic Su bstitu tion Rea ction betw een
1
-F lu or o-2,4-d in itr oben zen e a n d P ip er id in e
N. Mariano Correa, Edgardo N. Durantini, and J uana J . Silber*
Departamento de Qu ı´ mica y F ı´ sica, Universidad Nacional de R ´ı o Cuarto, Agencia Postal No. 3,
R ı´ o Cuarto, 5800, Argentina
jsilber@exa.unrc.edu.ar
Received May 10, 2000
N
The nucleophilic aromatic substitution (S Ar) reaction between 1-fluoro-2,4-dinitrobenzene and
piperidine (PIP) were studied in two different reverse micellar interfaces: benzene/sodium 1,4-
bis(2-ethylhexyl) sulfosuccinate (AOT)/water and benzene/benzyl-n-hexadecyl dimethylammonium
chloride (BHDC)/water reverse micellar media. The kinetic profiles of the reactions were investigated
as a function of variables such as surfactant and amine concentration and the amount of water
dispersed in the reverse micelles, W
effect was observed and the reaction takes place almost entirely in the benzene pseudophase, at
every AOT and PIP concentration. At W ) 10, a slight increment of the reaction rate was observed
0
) [H
2 0
O]/[surfactant]. In the AOT system at W ) 0, no micellar
0
at low [PIP] with AOT concentration, probably due to the increase of micropolarity of the medium.
However, at [PIP] g 0.07 M the reaction rates are always higher in pure benzene than in the
micellar medium because the catalytic effect of the amine predominates in the organic solvent. In
the BHDC system the reaction is faster in the micellar medium than in the pure solvent. Increasing
the BHDC concentration accelerates the overall reaction, and the saturation of the micellar interface
is never reached. In addition, the reaction is not base-catalyzed in this micellar medium. Thus,
despite the partition of the reactants in both pseudophases the reactions effectively take place at
the interface of the aggregates. The kinetic behavior can be quantitatively explained taking into
account the distribution of the substrate and the nucleophile between the bulk solvent and the
micelle interface. The results were used to evaluate the amine distribution constant between the
micellar pseudophase and organic solvent and the second-order rate coefficient of S
N
Ar reaction in
the interface. A mechanism to rationalize the kinetic results in both interfaces is proposed.
In tr od u ction
Solubilization of a reactant in the same region of the
surfactant assembly can lead to significant acceleration
of reaction rates, while the rates of reactions of segre-
gated reactants are retarded. When both reactants are
in the water droplet, they are concentrated as in a
nanoreactor, and since the size of this reactor is easily
varied, the influence of the properties of the micellar
Reverse micellar systems are powerful models for
biological compartmentalization studies, enzymatic ca-
talysis, and separation of biomolecules.1-7 Also, these
micellar systems have been proven very useful to obtain
8
new inorganic materials such as nanocrystallites and
polymers under mild conditions.9
8,10
system is relatively easy to assess.
In previous works, we have been interested in bimo-
Two clearly differentiated phases (aqueous and or-
ganic) present in reversed micelles allow compartmen-
talization of solubilized species at the microscopic level.
lecular aromatic nucleophilic substitution (S
N
Ar) reac-
tions between several nitro-substituted aromatic sub-
1
1-13
strates and aliphatic amines in nonpolar
and polar
(
1) Fendler, J . H. Membrane Mimetic Chemistry; Wiley: New York,
982.
2) Pileni, M. P. Structure and Reactivity of Reverse Micelles;
Elsevier: New York, 1989.
14,15
aprotic solvents
and the sodium 1,4-bis(2-ethylhexyl)
1
sulfosuccinate (AOT)/n-hexane system.16
(
(
(
3) De, T. K.; Maitra, A. Adv. Colloid Interface Sci. 1995, 59, 95.
4) Moulik, S. P.; Paul, B. K. Adv. Colloid Interface Sci. 1998, 78,
(10) Garc ´ı a-R ´ı o, L.; Leis, J . R.; Iglesias, E. J . Phys. Chem. 1995, 99,
12318.
9
9.
(
(11) Chiacchiera, S. M.; Singh, J . O.; Anunziata, J . D.; Silber, J . J .
J . Chem. Soc., Perkin Trans. 2 1987, 987.
5) Luisi, P. L.; Straub, B. Reverse Micelles, 8th ed.; Plenum Press:
London, 1984.
6) Ballesteros, A.; Bornscheuer, U.; Capewel, A.; Combes, D.;
Condoret, J . S.; Koenig, K.; Kolisis, F. N.; Marty, A.; Mengue, U.;
(12) Cattana, R. I.; Singh, J . O.; Anunziata, J . D.; Silber, J . J . J .
Chem. Soc., Perkin Trans. 2 1987, 79.
(13) Chiacchiera, S. M.; Singh, J . O.; Anunziata, J . D.; Silber, J . J .
J . Chem. Soc., Perkin Trans. 2 1988, 1585.
(
Scheper, T.; Stamatis, H.; Xenakism, A. Biocatal. Biotransform. 1995,
1
3, 1.
7) Liu, J . Y.; Huang, T. M.; Chang, G. G. J . Chem. Soc., Perkin
Trans. 2 1999, 2171.
(14) Chiacchiera, S. M.; Cattana, R. I.; Singh, J . O.; Anunziata, J .
D.; Silber, J . J . J . Phys. Org. Chem. 1989, 2, 631.
(15) Durantini, E. N.; Zingaretti, L.; Anunziata, J . D.; Silber, J . J .
J . Phys. Org. Chem. 1992, 2, 557.
(
(8) Pileni, M. P. J . Phys. Chem. 1993, 97, 6961.
(
9) (a) Ichinohe, D.; Arai, T.; Kise, H. Synth. Metals 1997, 84, 75.
(16) Correa, N. M.; Durantini, E. N.; Silber, J . J . J . Org. Chem, 1999,
64, 5757.
(
b) Ichinohe, D.; Arai, T.; Kise, H. Synth. Metals 1997, 85, 1671.
1
0.1021/jo000714s CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/14/2000

6
428 J . Org. Chem., Vol. 65, No. 20, 2000
Diverse studies of S Ar reaction between haloaromatic
Correa et al.
surfactant in the micellar media was transferred into the cell.
The addition of water to the corresponding solution was
performed using a calibrated microsyringe. The amount of
water present in the system is expressed as the molar ratio
between water and the surfactant present in the reverse
N
derivatives and anionic nucleophiles in reverse micellar
media showed that the reactions were faster in the
cationic media than in the aqueous phase or anionic
micelles.7
,17-19
It has been proposed that the catalytic
micelle (W
called W ) 0, corresponds to a system with no addition of
water, and its presence corresponds to the intrinsic humidity
of the system (W = 0.3).
0
) [H
2 0
O]/[surfactant]). The lowest value of W ,
effect observed in the cationic systems could be explained
considering that the positively charged head of the
surfactant is capable of stabilizing the negatively charged
Meisenheimer intermediate.7 Moreover, the effective
0
0
,18
Kin etics. Reactions were followed spectrophotometrically
by the increase in the maximum absorption band of the
product, N-(2,4-dinitrophenyl)piperidine, at 25.0 ( 0.5 °C. To
start a kinetic run, a stock solution of FDNB was added (10
µL) into a thermostated cell containing the PIP and the reverse
micelle solution. The FDNB concentration in the reaction
concentration of the anionic nucleophiles at the cationic
interface is higher than in the anionic one.19 Thus, the
reactions are catalyzed relative to the homogeneous
solutions, whereas in the anionic micelles the reaction
is inhibited.7
,17-19
-5
media was 5 × 10 M. The kinetic runs were performed
Systematic studies using neutral nucleophiles in these
following the increase in the absorbance of the product of the
reaction (λmax ) 374 nm). When the reaction was very fast, a
High-Tech stopped flow instrument set at the λmax of the
product was used. In every case, pseudo-first-order plots were
obtained in excess of nucleophile. The pseudo-first-order rate
constants (kobs) were obtained by a nonlinear least-squares fit
of the experimental data absorbance vs time (r > 0.999) by
first-order rate equation. The value of the absorbance at
infinite reaction time was consistent with the value obtained
from authentic samples of the reaction product, within 3%.
The pooled standard deviation of the kinetic data, using
different prepared samples, was less than 5%.
1
6
kinds of systems are scarce. We have investigated the
Ar reaction of 1-fluoro-2,4-dinitrobenzene (FDNB) with
S
N
aliphatic amines in n-hexane and n-hexane/AOT/water.
The results showed that the reactions are faster in the
micellar media than in the pure solvent, being base-
catalyzed in n-hexane but not in the reverse micelles.
The aim of this work is to compare the influence of
anionic and cationic interfaces in this type of S
reaction. Therefore, we investigated the S Ar between
N
Ar
N
FDNB with piperidine (PIP) in the anionic system
benzene/AOT/water and in the cationic system benzene/
benzyl-n-hexadecyldimethylammoniumchloride (BHDC)/
water. It must be noted that benzene was elected because
is an oil phase where both surfactants can form reverse
micelles without the presence of cosurfactants.20 In
n-hexane cationic reverse micelles of three components
have not been yet characterized. The interface polarity
in both systems was studied and compared using 1-meth-
yl-8-oxyquinolinium betaine (QB) as molecular probe. The
results show that both interfaces are more polar than
the pure organic solvent.20
Resu lts
The reactions of FDNB with piperidine in benzene,
benzene/AOT/water, and benzene/BHDC/water reverse
micelles produce ipso-fluorine substitution, giving the
N-(2,4-dinitrophenyl)piperidine (eq 1) in quantitative
yields as shown by UV-visible spectroscopic analysis of
the reaction mixture.
Exp er im en ta l Section
Gen er a l. UV-visible spectra were recorded on a Hewlett-
Packard HP 8453 spectrophotometer or Hi-Tech Scientific
Stopped-Flow SHU SF-51 (SU-40 spectrophotometer unit) for
very fast reactions. The HPLC measurements were performed
on a Varian 5000 liquid chromatograph equipped with a UV-
visible variable λ detector (Varian 2550) operating at 250 nm
with a Varian MicroPak SI-5 (150 mm × 4 mm i.d.) column
and 1% 2-propanol in n-hexane as solvent.
Ma ter ia ls. FDNB from Aldrich and piperidine from Riedel-
deHa e¨ n were used without further purification. Sodium 1,4-
bis(2-ethylhexyl) sulfosuccinate (AOT) from Sigma purified by
the procedure described in ref 21 was dried under vacuum over
In every run, the UV-visible spectra taken at different
times show a clear isosbestic point, evidencing the
cleanness of the reaction and the fact that the rising
absorption is due to the absorbance of the product.
Moreover, considering that hydroxide ion may result from
amine hydrolysis in the water pool (see below), the
possibility of the reaction between FDNB and this ion
was searched. However, no reaction was detected under
the experimental condition. TLC and HPLC chromatog-
raphy analysis also show only one product at all times
of reaction. In every case a large excess of nucleophile
was used and the reactions follow pseudo-first-order
P
2
O
5
. Benzyl-n-hexadecyldimethylamonium chloride (BHDC)
from Sigma was recrystallized twice from ethyl acetate and
2
0
dried under vacuum over P
2
O
5
.
Benzene (Sintorgan, HPLC
quality) was used as received. Water was first distilled over
potassium permanganate and then bidistilled until a conduc-
-
1
-1
tivity of 0.3-0.5 µΩ
M
at 298 °K was reached.
P r oced u r es. Stock solutions of surfactants reverse micelle
were prepared by weighing and dilution in benzene. Stock
solutions of 1 M surfactant were agitated in a sonicating bath
until the reverse micelle was optically clear. The appropriate
amount of stock solution to obtain a given concentration of
N
kinetic. Trying to elucidate the mechanism of the S Ar
reaction in reverse micelles, influences of several vari-
ables were investigated as follows.
Effects of AOT Con cen tr a tion . Rea ction in Ben -
zen e/AOT/Wa ter Rever se Micelles. The kinetics of the
reaction was studied varying AOT concentrations be-
tween 0 and 0.5 M, keeping the other experimental
(
(
(
17) Fendler, J . P. H. Acc. Chem. Res. 1996, 9, 153.
18) Tang, S.-S.; Chang, G.-G. J . Org. Chem. 1995, 60, 6183.
19) Durantini, E. N.; Borsarelli, C. D. J . Chem. Soc,. Perkin Trans.
2
1996, 719.
20) Correa, N. M.; Biasutti, M. A.; Silber, J . J . J . Colloid Interface
Sci. 1996, 184, 570.
21) Maitra, A. N.; Eicke, H. F. J . Phys. Chem. 1981, 85, 2687.
conditions fixed. At W ) 0, no micellar effect was
0
(
observed. The kinetics results, at any AOT concentration,
(
were the same as that in benzene. A value of kobs ) 0.0148

Reverse Micelles and Nucleophilic Aromatic Substitution
J . Org. Chem., Vol. 65, No. 20, 2000 6429
F igu r e 3. Variation of pseudo-first-order rate constant (kobs
)
F igu r e 1. Dependence of the pseudo-first-order rate constant
with PIP concentration for the reaction of FDNB with PIP (0)
in benzene and (b) water/AOT/benzene reverse micelles at
(k
obs) with the AOT concentration for the reaction between
FDNB and PIP in water/AOT/benzene reverse micelles at
-
5
-
5
-3
W
0
) 10. [FDNB] ) 5.0 × 10 M, [AOT] ) 0.3 M.
W
0
) 10. [FDNB] ) 5.0 × 10 M, [PIP] ) 5.0 × 10 M. The
dotted lines show the fitting by eq 10.
F igu r e 4. Variation of pseudo-first-order rate constant (kobs
with BHDC concentration for the reaction of FDNB with PIP
in water/BHDC/benzene reverse micelles at (b) W ) 0 and
)
F igu r e 2. Variation of the pseudo-first-order rate constant
(k
obs) with the AOT concentration for the reaction between
0
-
5
-3
FDNB and PIP in water/AOT/benzene reverse micelles at
(9) W
0
) 10. [FDNB] ) 5.0 × 10 M, [PIP] ) 5.0 × 10 M.
-
4
W
0
) 10. [FDNB] ) 5.0 × 10 M, [PIP] ) 0.1 M. The dotted
The dotted lines show the fitting by eq 10.
line shows the fitting by eq 11.
at higher PIP concentration the reaction rate diminishes
with the amount of water dispersed.
Effect of Am in e Con cen tr a tion . To study the effect
of amine concentration, the reaction was carried using
0.0005 s-1 was obtained for [PIP] ) 5 × 10 M, which
-3
(
2
5
coincides with a value previously reported.
Two different types of profiles were obtained at W
0 depending on the amine concentration. A slight
0
)
0
)
.3 M AOT at W
0 the kinetic behavior was the same than the measured
in benzene. The results at W ) 10 are shown in Figure
. As can be seen, the kobs values are slightly higher or
0
) 0 and 10. As can be expected, at W
0
1
increment on kobs was found on increasing AOT concen-
tration at [PIP] lower than 0.07 M. A typical plot of kobs
0
3
-
3
vs [AOT] at [PIP] ) 5 × 10 M shows a downward
curvature (Figure 1). On the other hand, at higher PIP
concentration (i.e., g0.07 M), a decrease on kobs was
obtained as shown for [PIP] ) 0.1 M in Figure 2.
very similar to the observed reaction rate in benzene at
low nucleophile concentration (<0.07 M). At higher amine
concentration the values of kobs decrease in comparison
with the one found in the organic solvent. Because, as
will be discussed below, the reaction is occurring in both
benzene and interface pseudophases, it must be noted
that kobs has the contribution of both rate constants.
Effect of BHDC Con cen tr a tion . Rea ction in Ben -
zen e/BHDC/Wa ter Rever se Micelles. Typical kinetic
results with varying BHDC concentration are shown in
0
Moreover, at [PIP] e 0.07 M, kobs increases with W , while
(
22) Terrier, F. Nucleophilic Aromatic Displacement; VCH Publish-
ers Inc.: New York, 1991.
23) Nudelman, N. S. In The Chemistry of Amino, Nitroso, Nitro,
and Related Groups; Patai, S., Ed.; Wiley: New York, 1996; Chapter
(
2
6.
(
24) Bernasconi, C. F. MTP Int. Rev. Sci. Org. Chem., Ser. 1 1973,
, 33.
25) Bernasconi, C. F.; Rossi, R. H. J . Org. Chem. 1976, 41, 44.
Figure 4 at W
increases on increasing BHDC concentration in the whole
0
) 0 and 10. As can be observed kobs
3
(

6
430 J . Org. Chem., Vol. 65, No. 20, 2000
Correa et al.
ted2
2-24
for S
Ar reactions involving halogen or nitrite
N
as leaving groups can be represented by eq 2, where R′
could be H or an alkyl group, X is the leaving group ,and
G stands for electron-withdrawing substituents. B is the
i
nucleophile or any other base added to the reaction
medium. With application of the steady-state hypothesis
F igu r e 5. Variation of pseudo-first-order coefficient (kobs) with
PIP concentration for the reaction of FDNB with PIP in water/
to this mechanism and in the limiting situation when k-1
B
.
k
2
+ k
3
i
[B
i
], eq 3 is obtained, where k
A
is the second-
BHDC/benzene reverse micelles at (9) W
0
) 0 and (b) W
0
)
-
5
1
0. [FDNB] ) 5.0 × 10 M, [BHDC] ) 0.3 M.
k ) k′ + k′′[B ]
(3)
A
i
1 3
/ k-1, and k′′ ) k k .
Bi/k-1
order rate constant, k′ ) k
1
k
2
In this case the decomposition of Z is rate-limiting, and
base catalysis may be expected. A linear response to base
concentration such as depicted in eq 3 is characteristic
of the majority of base-catalyzed reactions. On the other
B
hand, if k-1 , k
2
+ k
3
i
[B
i
], or more precisely k
2
. k-1
,
the formation of the intermediate Z is rate-limiting and
consequently k . There are intermediate situations
A
) k
1
A
where curvilinear dependence of k with amine concen-
tration may be found.2
2-24
According to the results shown before and considering
that two pseudophases are mainly present at W
0
e 10,
the interface and the bulk organic solvent,2
,16,28
and both
reactants may be distributed between the two environ-
ments, a mechanism summarized as follows can be
F igu r e 6. Variation of pseudo-first-order rate constant (kobs
with W in water/BHDC/benzene reverse micelles for the
reaction of FDNB with PIP. [FDNB] ) 5.0 × 10 M, [PIP] )
)
0
-
5
-
3
5
.0 × 10 M, [BHDC] ) 0.3 M.
range. These results suggest that the saturation of the
substrate molecules in the micellar interface is not
reached in the range of surfactant concentrations used.
Moreover, from Figure 4 it can be inferred that the
proposed, where subscripts f and b indicate the organic
phase and the micellar pseudophase, respectively. Surf
represents the micellized surfactant molecules. The rate
coefficients of the reaction k
1 2 3
, k-1, k , and k were defined
reaction is slower at W
0
) 10 than W
0
) 0.
above (eq 1). K and K are the distribution constants
s
A
Effect of th e Am in e Con cen tr a tion . Figure 5 shows
the variation of the kobs with the PIP concentration in
for FDNB and PIP between the organic phase and
micellar pseudophase, respectively.
the micelle at [BHDC] ) 0.3 M, W
0
) 10 and in pure
) 0. As
It is known that this reaction is wholly base-catalyzed
benzene. Similar profiles were obtained at W
0
in benzene and the decomposition of the intermediate Z
b
2
5
can be seen, the rate of reaction is higher in the reverse
micelle than in the pure solvent, at any PIP concentra-
tion.
N
is rate-limiting. However, these S Ar reactions are not
base-catalyzed in polar solvents.24 The micropolarity of
the interface in reversed micelles of benzene/AOT or
2
0,26
Effect of th e Wa ter Disp er sed . The effects of chang-
BHDC/water is always higher than in benzene.
Thus,
ing the value of W
concentrations constant, is shown in Figure 6. As can be
observed, the value of kobs decreases with W
0
on kobs, keeping BHDC and PIP
it can be assumed that the reactions of FDNB with PIP
are not base-catalyzed in the anionic micellar interface
0
.
(
26) Correa, N. M.; Biasutti, M. A.; Silber, J . J . J . Colloid Interface
Sci. 1995, 172, 71.
27) Garc ´ı a-R ´ı o, L.; Leis, J . R.; Pe n˜ a, E.; Iglesias, E. J . Phys. Chem.
993, 97, 3437.
28) Silber, J . J .; Biasutti, M. A.; Abuin, E.; Lissi, E. Adv. Colloid.
Interface Sci. 1999, 82, 189.
Discu ssion
(
1
Mech a n ism of Rea ction . For primary or secondary
amines as nucleophiles the general mechanism accep-
(

Reverse Micelles and Nucleophilic Aromatic Substitution
or in the cationic one. Consequently, the formation of the
J . Org. Chem., Vol. 65, No. 20, 2000 6431
Rea ction in th e AOT/Ben zen e System . Considering
that the kinetic response of the system at PIP concentra-
tion <0.07 M is different than at higher amine concen-
trations, the possibility of PIP protonation at this micellar
interface was analyzed.
intermediate Z
b
is assumed to be rate-limiting.
The rate of the reaction can be expressed by eq 4 where
d[P]
dt
[Am
b
][FDNB
]
b
)
k [Am ][FDNB ] + k′
b
(4)
f
f
f
The importance of the hydrolysis basic-equilibrium of
PIP in water was demonstrated for nitrosation reactions
involving PIP in anionic direct micelles, albeit this effect
vj [Surf]
k
f
represents the second-order rate constant in the
3
0
organic solvent (k ) k′′[Am ]). For absolute comparison
f
f
was not important in cationic micellar systems. Also,
it was found31 that the absorption and emission behavior
of â-carbolines in cyclohexane/AOT/water reverse mi-
celles is highly influenced by protonation at the interface.
On the other hand, for nitrosation reactions carried out
in isooctane/AOT/water microemulsions,27 the effect of
the protonation of aliphatic amines was not detected.
Likewise, when the charge-transfer interaction between
hexylamine and 7,7,8,8-tetracyanoquinodimethane in
cyclohexane/AOT/water reverse micelles was studied,
of reactivity in different media, the molar reaction volume
at the interface, vj , should be known. This can be
estimated from the molar volume of AOT and BHDC in
the reverse micelles, which can be taken as vj .19,27 Thus,
b
k′ is the conventional second-order rate constant in the
interface. The concentrations in square brackets refer to
the total volume of reverse micelle.
The distribution constant of FDNB can be expressed
by eq 5:28
there was no evidence of the amine protonation even at
[
FDNBb]
32
W ) 10.
0
K )
(5)
s
[
FDNB ][Surf]
Previous studies of S
PIP performed in n-hexane/AOT/water reverse micelles
showed no PIP hydrolysis. The effect of the amine
concentration on kobs at [AOT] ) 0.2 M, W ) 0 and 10,
N
Ar reaction between FDNB and
f
1
6
A simple mass balance using the distribution constant
and the analytical concentration of FDNB, [FDNB ],
allows one to calculate the [FDNB ] (eq 6):
K
s
T
0
b
shows a linear relationship expected for a non-base-
catalyzed reaction, while an upward curvature would be
K [Surf][FDNB ]
s
T
obtained if the hydrolysis equilibrium of the PIP is
[
FDNB ] )
(6)
30
b
present. Moreover, the reaction is faster at W ) 10
0
(
1 + K [Surf])
s
than W ) 0, indicating that, even when the water pool
0
is formed, the protonation of the amine is not detected.
From the results in the present work, it seems that
the protonation effect, if any, is negligible. When the
[PIP] is low (Figure 1) there is micellar catalytic effect,
In the same way, using the distribution constant
defined by eq 7, [PIP ] can be expressed by eq 8:
b
[
PIPb]
K )
(7)
(8)
A
while at higher PIP concentration there is not (Figure
(
[PIP ][Surf])
f
30
2
a
). Considering that PIP’s pK ) 2.88 in pure water it
could be expected that the percentage of molecules
K [Surf][PIP ]
A
T
-3
ionized at [PIP] ) 5 × 10 M would be nearly 40% of
[
PIP ] )
b
(
1 + K [Surf])
the total PIP concentration and that in the presence of
AOT this percentage increase significantly as found for
A
If [PIP
T
] . [FDNB
T
] a pseudo-first-order behavior for the
30
aqueous micelles. In addition at [PIP] ) 0.1 M, the
kinetics of the reaction is assumed. Then, replacing
concentration of protonated amine would be just 10% of
the total concentration, i.e., it is negligible. Therefore, if
PIP would be protonated at the micellar interface kobs
should decrease with [AOT] preferentially at low amine
concentration. Quite the opposite, this trend was found
at high PIP concentration (compare Figures 1 and 2).
Moreover no evidence was found of hydroxide ion in the
media, an ion that will react with FDNB giving the
b b
[FDNB ] and [PIP ] in eq 4, we can obtain the final
expression for the rate (eq 9) and the observed pseudo-
first-order rate constant kobs (eq 10). with
d[P]
)
kobs[FDNBT]
(9)
dt
k + (k ′K K [PIP ][Surf]/ vj )
19
f
b
S
A
T
corresponding phenol derivative. These results could be
kobs
)
(10)
(
1 + K [Surf])(1 + K [Surf])
indicating that in the AOT reverse micellar systems
studied the proton concentration at the interface is
actually much lower than could be expected by comparing
S
A
The variation of kobs with the [Surf] can now be
explained from eq 10. It shows that when the values of
the products between the distribution constants and
2
0
with direct micelles. In fact in previous studies working
with QB as molecular probe, which is a very sensitive
molecule to acids, no evidence of acidic interface in the
benzene/AOT/water reverse micelles was found. Finally
[
Surf] are not negligible with respect to unity, kobs would
exhibit a nonlinear relationship with the surfactant
concentration.16 However, if K
and K are small enough,
it must be noted that PIP has low affinity for the
A
S
microemulsion aqueous phase1
6,27
(see Table 1), a fact
this product are almost negligible with respect to unity
and micellar interface saturation is not reached. The
second-order rate constant of the reaction in the organic
that may contribute to preventing protonation.
The lack of micellar effect observed at W
0
) 0 working
solvent, k
f
, is known from the studies of these reactions
with different concentrations of AOT shows that the
in benzene.25 The molar volume of BHDC and AOT to be
-
1
taken as vj was estimated in values of 0.44 M and 0.38
(30) Iglesias, E.; Leis, J . R.; Pe n˜ a, M. E. Langmuir 1994, 10, 662.
(31) Varela, A. P.; Miguel, M. Da G.; Ma c¸ anita, A. L.; Burrows, H.
D.; Becker, R. S. J . Phys. Chem. 1995, 99, 16093.
-
1 19,27,29
M
.
(
32) Paul, B. K.; Mukherjee, D. C.; Moulik, S. P. J . Photochem.
(29) Lang, J .; J ada, A.; Malliaris, A. J . Phys. Chem. 1988, 92, 1946.
Photobiol., A 1996, 94, 53.

6
432 J . Org. Chem., Vol. 65, No. 20, 2000
Correa et al.
Ta ble 1. Kin etic P a r a m eter s a n d Distr ibu tion Con sta n ts for th e Rea ction betw een F DNB a n d P IP in Differ en t Med ia
k′ (M- s-1
1
)
k′′ (M-2 s-1
)
k′b (M-1 s-1
)
KS (M-1
)
KA (M-1
)
benzenea
0.72
609
b
AOT-benzene W0 ) 10
113 ( 10
1.0 ( 0.2
0.90 ( 0.20
0.10 ( 0.04
0.11 ( 0.05
0.09 ( 0.04
0.10 ( 0.04
0.30 ( 0.10
0.30 ( 0.10
c
AOT-benzene W0 ) 10
d
BHDC-benzene W0 ) 0
1670 ( 200
1060 ( 200
1950 ( 300
1100 ( 300
d
BHDC-benzene W0 ) 10
e
BHDC-benzene W0 ) 0
e
BHDC-benzene W0 ) 10
a
From ref 25. b From fitting Figure 1 by eq 10. c From fitting Figure 2 by eq 11. d From fitting Figure 4 by eq 10. e From fitting Figure
7
by eq 10. Parameter values calculated using 0.995 confidence level in nonlinear regression.
reaction takes place mainly in the organic pseudophase,
probably as a result of the very low values of K . In fact,
in the micellar system it is not kinetically distinguish-
able. Also, the attempts to calculate the value of K using
These reactant distributions also explain the decrease of
obs in the micelles compared to the organic medium,
shown in Figure 3 at high PIP concentration. By fitting
Figure 2 by eq 11 the values of K and K are obtained
S
k
S
A
s
Encinas-Lissi’s33 fluorescence quenching method varying
AOT concentration between 0.05 and 0.3 M failed,
probably because the value is in the limit of sensitivity
of the method. Thus, it is assumed that FDNB resides
mainly in the organic phase of the micellar solution,
which seems quite reasonable as a result of the aromatic
character of both the solute and the organic solvent.
and gathered in the Table. It must be pointed out that
the small deviation observed in this fitting (Figure 2)
could be due to the fact that the contribution to kobs
coming from the micelle interface was not taken into
account in eq 11; however, similar values for K
A s
and K ,
within experimental error, as those calculated by eq 10
A
are found. The K value in this system is smaller than
At W
0
) 10 and [PIP] e 0.07 M acceleration of the
that obtained in n-hexane/AOT/water.16 This seems quite
reaction rate is observed. In this case the increased
reasonable because benzene, a more polar and polarizable
polarity of the interface1
6,20
may favor the reaction by
solvent, will better solubilize the amine. Moreover, the
35
b
stabilizing the Z intermediate, increasing k
b
1
. The
hydrogen bond interactions between AOT and PIP are
weaker in benzene. Similar effects were observed in the
interaction of aromatic amines with AOT in which a
solvent more polar than n-hexane, such as carbon tetra-
chloride, increases the solubility of the amine and
characteristic base catalysis observed in benzene is lost.
By fitting the experimental data with eq 10, the value of
k′ and the distribution constants were calculated (see
b
Table 1). As can be seen, the reaction in the micellar
medium is more than 2 orders of magnitude faster than
in benzene. This can be observed in Figure 3 at low amine
concentration where kobs is higher in the micelle system
3
6
weakens the interaction with the surfactant.
Rea ction s in BHDC/Ben zen e System . The increase
of kobs values while increasing BHDC concentration
than in the organic solvent. It must be noted that k′
b
in
(Figure 4) at both W studied could be due to the gradual
0
this system is 1 order of magnitude faster than in
incorporation of the reactants into the micellar ag-
1
6
n-hexane/AOT/water reverse micelles at the same W
0
.
gregates. However, the micellar interface saturation
Considering the studies with zwitterionic probes,20 one
can assume that the Z intermediate should be located in
the “oil side” of the micellar interface in the benzene/
AOT/water system. On the other hand, in the n-hexane/
AOT/water system Z may be forced to reside more in the
aqueous side of the interface. The later would be a
hydrogen bond donor environment, which decreases the
rate constant, as is observed when this reaction takes
place in protic solvents.2
16
observed in the n-hexane/AOT/water system is never
reached. By fitting Figure 4 by eq 10, the values of KS,
K , and k′ can be obtained (Table 1). As can be inferred,
A
b
k′b is several orders of magnitude faster than that
observed in pure benzene. Also, as was shown in Figure
6, the value of k′ is lower at W ) 10 than at W ) 0.
b
0
0
This result suggests a decrease in the PIP nucleophilicity
due to the hydration of the amine, as has been observed
for other systems where the reaction takes place at the
interface.16
4,34
On the other hand, at [PIP] > 0.07 M, the reaction
rates are retarded in the micellar medium with a typical
behavior of segregated reactants. A possible explanation
could be that, at high [PIP] the reaction in the organic
pseudophase, where it is strongly base-catalyzed, pre-
dominates.
The greater catalytic effects of cationic interfaces over
the anionic ones have been previously detected with
7,17-19
anionic nucleophiles
and are explained by the
cationic surfactant’s stabilization of the amines Z inter-
mediate. In this reaction, which involves a neutral
nucleophile and no neat charge is expected for Z, a
In this condition the second term of eq 4 is negligible
and kobs has the expression given in eq 11. This equation
similar effect is found. Thus, at W
reaction in BHDC is about 10 times faster than in AOT,
while at W ) 0 in the last system there is no micellar
0
) 10 the rate of
2
k′′[PIPT]
0
kobs
)
(11)
2
catalytic effect. A possible explanation for the cationic
micellar catalysis is that it could be due to specific
(
1 + K [AOT]) (1 + K [AOT])
A
S
interaction between the ammonium head of BHDC and
predicts the results observed in Figure 2. Since most of
the reaction occurs in the organic phase, kobs diminishes
with [AOT] as a result of the reactants’ distribution
between the organic phase and the micellar interface.
20,37
the zwitterionic intermediate Z
responsible for the additional stabilization of Z
b
.
This effect could be
with the
b
(
(
35) Marcus, Y. Chem. Soc. Rev. 1993, 409.
36) Correa, N. M.; Durantini, E. N.; Silber, J . J . J . Colloid Interface
(
(
33) Encinas, M. V.; Lissi, E. A. Chem. Phys. Lett. 1982, 82, 155.
34) Mancini, P. M. E.; Terenzani, A.; Gasparri, M. G.; Vottero, L.
Sci. 1998, 208, 96.
(37) Bacaloglu, R.; Bunton, C. A.; Cerichelli, G.; Ortega, F. J . Phys.
Chem. 1989, 93, 1490.
R. J . Phys. Org. Chem. 1996, 9, 459.

Reverse Micelles and Nucleophilic Aromatic Substitution
J . Org. Chem., Vol. 65, No. 20, 2000 6433
k
1
) and the formation of Z intermediate is rate-determin-
ing. Hence, it can be concluded that the reactions takes
place mainly in the interface, which is more polar than
the organic medium.20 The values of K
S A
and K are low
and very similar to those calculated for the anionic
system, showing that the solubilization of the reactants
in the organic phase prevails. Nevertheless, the stabiliza-
tion of the intermediate achieved at the cationic interface
overcomes this effect, and neat micellar catalysis is
observed.
Con clu sion s
In benzene/AOT/water reverse micelle medium at W
0, the reaction between FDNB and PIP takes place
0
)
mainly in the organic pseudophase. In this system, the
reactants’ distribution toward the micelle interface is
negligible and kinetically undetectable. However, at W
10, a slight catalytic micellar effect is observed when
PIP] e 0.03 M is used, probably as a result of the
increase in the interface micropolarity. At higher amine
concentration (g0.07 M), the base-catalyzed reaction in
the benzene pseudophase predominates over the interface
0
F igu r e 7. Variation of pseudo-first-order coefficient in the
micelle (kobs ) with PIP concentration for the reaction of FDNB
)
[
M
with PIP in water/BHDC/benzene reverse micelles at (b)
-
5
W
0
0
) 0 and (9) W
0
) 10. [FDNB] ) 5.0 × 10 M, [BHDC] )
.3 M. The dotted lines show the fitting by eq 10.
corresponding increase on k b
. Moreover, although Z
is
reaction, producing a very large increment on k
f
. Thus,
2
b
a dipolar compound, Coulombic attraction between the
cationic surfactant and the negative pole of the interme-
diate could be stronger than the attraction between the
kobs decreases with [AOT] because of the reactant distri-
butions. The fact that the overall rate of the reaction is
accelerated at least 3 orders of magnitude in benzene/
BHDC/water reverse micelle medium with respect to the
pure solvent suggests that the reactions occur in the
positive pole and anionic surfactant; consequently Z
b
resides more in the oil side of the benzene/BHDC reverse
micelle interface. In the anionic interface, the intermedi-
ate resides in a more hydrogen bond donor environment
because it is located in the aqueous side of the interface.
In this way, in the last medium the rate constants are
slower than in the cationic ones, as was observed when
the same reaction takes place in protic solvents.24,34 In
fact, that type of interactions seems to be responsible for
the anomalous behavior of the zwitterionic compound QB
with BHDC in benzene/BHDC/water system.20
N
micelle interface. A change in mechanism for the S Ar
reaction is observed. The reactions, which are wholly
base-catalyzed in benzene, in the reverse micelles are not.
The formation of the Z intermediate is rate-determining
as a result of the higher polarity in the micelle interface
as compared with the bulk solvent. The kinetic behavior
can be quantitatively explained taking into account the
distribution of the substrate and amines. For both media,
the interface micellar saturation is never reached prob-
The values of the pseudo-first-order coefficient in the
A S
ably due to the small K and K values. Comparisons
M
micelles (kobs ) were estimated from Figure 5 at different
between anionic and cationic interfaces shows that even
nonionic nucleophile the cationic ones exert a greater
catalytic effect. A possible specific interaction between
the ammonium head of BHDC and the zwitterionic
bz
PIP concentration, taking into account eq 12 where kobs
M
bz
kobs ) kobs + kobs
(12)
intermediate (Z
b
) could be responsible for the additional
, with the corresponding increase on
stabilization of Z
b
is the pseudo-first-order coefficient in the benzene
2
bz
kb The results in this study can be used as a good model
pseudophase. The kobs values can be calculated from the
.
kinetic law in benzene25 and the value of K
to predict micellar catalysis for reaction between nonionic
substrates, which give a zwitterionic-type intermediate.
A
(Table 1).
Figure 7 shows the variation of kobsM with the PIP
concentration at [BHDC] ) 0.3 M at W ) 0 and 10.
0
M
Ack n ow led gm en t. We gratefully acknowledge fi-
nancial support for this work by the Consejo Nacional
de Investigaciones Cient ´ı ficas (CONICET), Consejo de
Investigaciones Cient ´ı ficas y Tecnol o´ gicas de la Provin-
cia de C o´ rdoba (CONICOR), Secretar ´ı a de Ciencia y
T e´ cnica de la Universidad Nacional de R ´ı o Cuarto,
Fundaci o´ n Antorchas and Agencia Nacional de Promo-
ci o´ n Cient ´ı fica y Tecnol o´ gica. E.N.D. and J .J .S. hold a
research position at CONICET. N.M.C thanks CONICET
for a research fellowship.
Linear relationships between kobs and the nucleophile
concentration are always obtained. By introduction of the
proper values of K
with varying [BHDC], the values of k′
at W ) 0 and 10 by fitting the new set of experimental
data (Figure 7) by eq 10. The results are shown in the
table. As can be seen, good estimates for k′ within
A
and K
S
obtained in the experiments
b
were recalculated
0
b
experimental error are obtained by two independent
methods. Thus, the kinetic results are consistent with
the assumption that in benzene/BHDC/water reverse
micelles the reaction is not base-catalyzed (k
A
) k′
b
)
J O000714S