Functionalization of the Phenyl Ring
soluble in water and the other completely insoluble. Breslow
and co-workers used water in combination with antihydrophobic
additives as a mechanistic probe for elucidation of the structure
of the transition state.4 Mayr and co-workers found an important
influence of water on the reactivity of organic molecules,
enabling alkylation of aromatic molecules with benzyl halides
in a water/acetonitrile mixture without the use of a Friedel-
Crafts catalyst.5 Very recently Sharpless and co-workers6
reported the important observation that some organic molecules
can react on the surface of water and often a very strong
enhancement of reaction rates was noticed in this case,
particularly when at least one compound involved in these
reactions bears a polar group, enabling some degree of solubility
(carboxylic ether, amine, etc., ...) in water. The authors also
suggested that water could be a useful reaction medium for
reactions where no acceleration of the rate was observed,
especially in cases of exothermic reactions, due to the high heat
capacity of water. This concept of organic reactions on water
has been recently confirmed by Bose et al. as well.7
Water as a reaction medium has not been extensively used
in connection with introduction of halogens into organic
molecules. However, we recently reported that fluorination8 with
F-TEDA-BF4 and iodination9 with the I2/H2O2 tandem could
be effectively performed in water with various types of organic
compounds.10 To obtain some further information about the role
of water in these functionalizations, we decided to study the
reactions of methyl-substituted benzene derivatives which are
much more hydrophobic than previously studied substrates.
Hexamethylbenzene (HMB) was used several times as a
convenient structural probe for elucidation of several organic
reactions, because of the fact that various types of transforma-
tions strongly depending on the structure of the reagents and
the reaction conditions could be observed for this organic
molecule. Kochi and co-workers11 made an important contribu-
tion in the understanding of the transformations of alkylbenzene
derivatives with electron accepting reagents, while the impor-
tance of the formation of a π-complex and its further dual
transformation through single electron transfer (SET) to a cation
radical or a two-electron transfer to a Wheland σ-intermediate
was extensively discussed over the decades.12-15 On the other
hand, tetramethylbenzene derivatives, especially durene (DUR)
in relation to trimethyl-substituted benzenes (among them
mesitylene, MES), have also been suggested as effective
mechanistic probes for differentiation between SET or σ-ion
formation, and this was intensively discussed and documented
in the literature.14,15 In general it is expected that SET is the
dominant process with DUR since it is more reactive than MES.
Less reactive substrates such as MES are expected to proceed
by a two-electron transfer with formation of Wheland’s σ-in-
termediate as the rate determining step.
Various fluorinating reagents have been tested on HMB. Side
chain fluorinated products were formed by xenon difluoride in
dichloromethane solution in the presence of HF16 or by CsSO4F
in acetonitrile,17 while trifluoroacetic acid pentamethylphenyl-
methyl ester16 was formed by XeF2 in the presence in TFA as
a catalyst. Side chain methoxylation was achieved by methyl
hypofluorite (MeOF)18 and amidation by N-fluoropyridinium
salts,19 while side chain amides, alkoxides, or esters were formed
by F-TEDA-BF4.20 On the other hand, the DUR, MES tandem
has often been used as a convenient probe for the elucidation
of the role of the structure of reagents (XeF2,21 CsSO4F,22
F-TEDA,23 N-fluoropyridinium salts,19,24 HOF/MeCN,18 etc.),
solvent (MeCN, ionic liquid, etc.), catalyst, and various external
nucleophiles on the course of fluorination and its mechanistic
attributes.
Much valuable information about the mechanism of organic
reactions can be provided from relevant kinetic data (rate of
reactions, activation parameters, ...), but when dealing with
fluorination reagents such as CF3OF, CH3OF, CsSO4F, XeF2,
CF3COOF, AcOF, F2, etc. their high reactivity and high
sensitivity to reaction conditions often cause much experimental
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