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B. S. Samant, S. S. Bhagwat
Iodination and bromination of phenol
Synthetic methods involving a source of positive iodine as
the reactive species [28–30] seem to be the most convenient
method for the direct halogenation of aromatics. However,
the use of iodine for the synthesis of this important class of
compounds is not extensively applied because of the weaker
electrophilic nature of iodine than chlorine and bromine.
These limitations in generating haloaromatics and their
important applications in various fields have increased
research interest in finding methodologies of aromatic halo-
genation that are suitable in later stages of total synthesis and
with substrates containing complex functionalities. Selec-
tivity improvement towards a particular product in total
synthesis of bioactive compounds is the key factor to affect
the overall yield and consequently implementation of such a
process in industry. Halogenation reactions in micellar or
aqueous systems proved to be very useful [31–36].
In continuation of this approach for halogenation reactions
in micellar media, iodination and bromination of phenol
using potassium iodide/sodium bromide, sulfuric acid, and
hydrogen peroxide was performed. However, to our sur-
prise, in both cases enhancement in selectivity towards the
para-halogenated product was observed. The conversion in
the case of bromination was higher; however, enhancement
in para selectivity was less as compared with the iodination
(Table 1). The change in the selectivity of the reaction is
clearly attributed to the effect of micelles on these halo-
genation reactions. In the case of chlorination of phenol
using potassium chloride, sulfuric acid, and hydrogen
peroxide a change in ortho selectivity was observed
(Table 2). It was anticipated that the selectivity towards a
particular product in halogenation reaction in micellar
media depends on the nature of reagents used for
halogenation.
In that regard, we intend to present our study of the
halogenation of aromatic compounds in micellar media.
The objective of the present work is to study the effect of
micellar media on the regioselectivity of iodination and
bromination and to observe the effect of halogenating
reagents on the orientation of an aromatic compound in a
micelle with the help of proton NMR spectroscopy. The
use of micellar interface as reaction site is well known;
however, mechanistic studies of this micellar catalyst
system for particular reactions are limited. Although fluo-
rination, chlorination, bromination, and iodination are all
halogenation reactions, the different properties (e.g., size,
charge, electrophilicity, etc.) of the attacking species in the
corresponding reactions mean that the selectivity and
conversion vary for each reaction. Hence, the complete
study for each halogenation reaction in micellar media for
various aromatic compounds (activated as well as deacti-
vated) will serve as an important contribution to the study
of electrophilic substitution reaction pathways. Each
halogenation reaction produces different products depend-
ing on the polarity of substrates used, reactivity of
attacking species, and ionic environment in which this
micellar interface acts as reaction site.
Orientation of phenol in micelle
To know the reason for this change in selectivity of halo-
genation with respect to the reagents used, solubilization
1
studies of phenol in micelles were carried out using H
NMR spectroscopy (Fig. 1). To study the effect of various
ionic species on the orientation of phenol, a similar ionic
atmosphere was maintained with the same ionic strength of
solution as the initial ionic strength of halogenation
reactions.
Table 3 shows the change in the chemical shifts of the
aromatic proton resonance of phenol due to the addition of
sodium dodecyl sulfate (SDS). The aromatic proton reso-
nance of the phenol molecule shifts to lower d values in the
presence of SDS. This shift is highest for H3–H5 and
smallest for H2 and H6 protons (Table 3, entry 1). This
indicates that the H3–H5 protons experience a more non-
polar environment in the presence of SDS micelles,
whereas H2 and H6 protons have essentially the same polar
environment in both the presence and absence of SDS
micelles. This suggests that the ortho-substituted hydro-
gens of phenol are present in the bulk water. On the other
hand, meta- and para-substituted hydrogens are present
inside the micellar interface. Thus the phenol molecule is
not fully inside the micelle, but adsorbed on the micellar
surface. The increase in the ionic strength of media also
failed to cause any shift in aromatic proton resonance of the
phenol molecule (Table 3, entries 2 and 3). This may be
because the complete phenol molecule is in contact with
bulk water. This indicates the presence of ionic species
disturbing the spatial orientation of phenol in micelles.
Though the exact model for this loose assemblage of sur-
factant monomers in highly ionic media is not yet clear,
Results and discussion
In chlorination of phenol using hydrogen peroxide and
hydrochloric acid it was observed that the nature of the
substituent on the aromatic ring affects the balance of
hydrophobicity of the molecule [4]. The solute molecule
exists in a preferred average orientation in the domain of
the surfactant micelle. Substituted aromatic compounds
show orientation in micelles depending on the polarity of
the substituent group, and due to this spatial orientation,
increases in the conversion and the selectivity towards a
particular product were observed [4].
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