C O M M U N I C A T I O N S
Table 1. Oxychlorination of Arene with HCl/H2O2 in
system or the one coordinated by EtOH by ∼6 kcal/mol. The bottom
geometries and charge distribution (NBO charges) in the three TS’s
show that TFE stabilizes the polar TS by acting as a charge template
with charges complementary to those in the TS. Thus, the OH group
stabilizes the departing Cl- by an OH- - -Cl- hydrogen bond, while
the negative fluorine stabilizes the positively charged Clδ+ that
attacks the benzene ring. This charge complementarity can be
contrasted with the adverse effect of ethanol. Here, while EtOH
can stabilize the departing Cl-, its interaction with the attacking
Clδ+ is repulsive due to the positive charges on the hydrogen atoms
of the CH3 group. Thus, TFE catalyzes the chlorination by providing
a complementary charge template to the TS, thereby enabling
oxychlorination of less activate arenes.13
Trifluoroethanola
substrate
yield, mol %
product
benzene
toluene
73
>99
chlorobenzene (100)
2-chlorotoluene (36)
4-chlorotoluene (64)
ethylbenzene
cumene
>99
>99
98
2-chloroethylbenzene (33)
4-chloroethylbenzene (67)
2-chlorocumene (21)
4-chlorocumene (79)
i-butylbenzene
t-butylbenzene
2-chloro-iso-butylbenzene (25)
4-chloro-iso-butylbenzene (75)
2-chloro-tert-butylbenzene (15)
4-chloro-tert-butylbenzene (85)
2-chloro-p-xylene (100)
chloromesitylene
>99
p-xylene
mesitylene
chlorobenzene
98
>99
23
1,4-dichlorobenzene (67)
1,2-dichlorobenzene (33)
Acknowledgment. The research was supported by the Israeli
Ministry of Science. R.N. is the Rebecca and Israel Sieff Professor
of Organic Chemistry.
a Reaction conditions: 1 M ArH, 1.5 M HCl, 3 M H2O2, 8.1 M H2O in
TFE, 25 °C, 15 h.
Supporting Information Available: Details of the B3LYP/6-
311+G* results (PDF). This material is available free of charge via
but rather it is because of low H+ concentrations. Therefore, the
polyfluorinated alcohol has a dual function in the nonmetal-
catalyzed oxychlorination of arenes; it catalyzes electrophilic
chlorination of less reactive arenes and oxidation of chloride at
lower H+ concentrations. In practice, TFE can be used as solvent
to oxychlorinate a series of normally nonreactive arenes, Table 1.
It may be observed that benzene and its alkylated derivatives react
in high yields at room temperature. Even deactivated substrates
such as chlorobenzene were somewhat reactive, although nitroben-
zene did not react.10
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(10) The reactivity trends as a function of the electronic properties of the sub-
stituents as well as the para directing effects of bulky substituents are clearly
consistent with electrophilic substitution. The substrates, for example,
p-xylene or mesitylene, are not isomerized under the reaction conditions.
(11) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M.
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(12) To ascertain that the trends in the barriers do not arise from global solvent
polarity effects, we calculated(Jaguar 4.1, Schro¨dinger, Inc., Portland, OR,
2001} all of the processes in two dielectric constants (ꢀ ) 10.65, nonpolar
solvent, and ꢀ ) 33.65, methanol). We used RB3LYP hybrid functional
and the 6-311+G* basis set after benchmarking (Table S1). The critical
species passed the stability test and did not reveal a lower unrestricted
solution. The bare system led to the expected cationic σ-complex
coordinated to Cl- (see Supporting Information). The surface around this
intermediate is extremely flat, and our geometry scans show that it
collapses either to the addition product or the substitution product. This
collapse is not the rate determining step (verified experimentally - no
deuterium isotope effect in the oxychlorination of toluene/toluene-d8).
Therefore, in all reactions, we focused on the bond activation step which
is rate determining.
Figure 2. Bond activation barriers (kcal/mol) for the chlorination of
benzene: out of parentheses, in the gas phase; in parentheses, a solvent
with a dielectric constant ꢀ ) 10.65; in square brackets, a solvent with ꢀ )
33.65. X is EtOH or TFE.
To understand the catalytic effect of TFE on the electrophilic
chlorination of arenes, we used DFT11 to study the chlorination of
benzene by one of the conceivable active chlorinating species, Cl2.
Figure 2 shows the energy profiles for chlorination in the bare
system, and with EtOH and TFE.12 It is seen that, irrespective of
the dielectric constant, TFE lowers the barrier relative to the bare
(13) Similar effects on the TS and similar experimental rate constants were
observed using hexafluoro-2-propanol instead of TFE as solvent.
JA0364524
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J. AM. CHEM. SOC. VOL. 125, NO. 40, 2003 12117