Efficient synthesis of various 4-tosyloxy-2-substituted phenols using pyridinium salt-supported [hydroxy(tosyloxy)iodo]benzene reagent

Article abstract of DOI:10.1246/cl.130229

A novel pyridinium salt-supported [hydroxy(tosyloxy)-iodo]benzene (HTIB) reagent (N-{4-[hydroxy(tosyloxy)iodo]-phenyl}pyridinium hexafluorophosphate) was prepared via Zincke's reaction. The conjugated HTIB was an effective reagent for tosyloxylation of phenolic aromatic rings with an electron-withdrawing substitute at the ortho-position. The reagent can be easily regenerated in high yield and reused three times without any decrease in activity.

Full text of DOI:10.1246/cl.130229

doi:10.1246/cl.130229
930
Published on the web May 31, 2013
Efficient Synthesis of Various 4-Tosyloxy-2-substituted Phenols
Using Pyridinium Salt-supported [Hydroxy(tosyloxy)iodo]benzene Reagent
Bing Yang,1,2 Jizhen Zhang,*1 Dejian Zhao,1 Yazhen Wang,1 and Hongbin Jia1
1School of Chemistry and Environmental Engineering, Jiangsu University of Technology,
1801 Zhongwu Road, Changzhou, Jiangsu 213001, P. R. China
2School of Petrochemical Engineering, Changzhou University, 1 Gehu Road, Changzhou, Jiangsu 213164, P. R. China
(Received March 16, 2013; CL-130229)
A novel pyridinium salt-supported [hydroxy(tosyloxy)-
Current existing ion-supported HTIB reagents are viscous
liquids and usually contain a functional linkage between the
RTIL and HTIB.4,5,9,11 which makes them inconvenient in
purification, storage, and regular use. In addition, the introduc-
tion of unstable functional linkage may limit their applications
in organic synthesis. For example, ester and amide bonds as
linkages are fairly stable in neutral aqueous media but are readily
cleaved in strong acid or base conditions. In attempting to
overcome these problems, symmetric cations (such as pyridinium
cation) can be used as a new linkage, which could generate novel
organic salt-supported HTIB reagents with superior properties. In
this paper, we report a novel pyridinium salt-supported HTIB
reagent, which is stable in all kinds of harsh conditions and
shows similar reactivity to original HTIB reagent.
iodo]benzene (HTIB) reagent (N-{4-[hydroxy(tosyloxy)iodo]-
phenyl}pyridinium hexafluorophosphate) was prepared via
Zincke’s reaction. The conjugated HTIB was an effective
reagent for tosyloxylation of phenolic aromatic rings with an
electron-withdrawing substitute at the ortho-position. The
reagent can be easily regenerated in high yield and reused three
times without any decrease in activity.
Hypervalent iodine reagents as versatile and environmen-
tally benign chemicals have attracted increasing interest in
recent years. Of great interest are organic iodine(III) compounds
(-3-iodanes), such as [hydroxy(tosyloxy)iodo]benzene (HTIB,
Koser’s reagent or Koser’s salt), (diacetoxyiodo)benzene (DIB),
[bis(trifluoroacetoxy)iodo]benzene (PIFA), and their analogues.
These selective oxidizing reagents are extensively used in
organic synthesis.1 However, one major drawback of these
iodine(III) reagents is that these reagents cannot be effectively
recovered as the reduced form iodobenzene remains intermin-
gled with the product. To overcome this problem, many efforts
have focused on developing polymer-supported HTIB reagents.2
Although these polymer-supported reagents can be easily
recovered, regenerated, and reused, some disadvantages, such
as lower reactivity, limited loading capacity, typical phase
transfer problems and inevitable polymer degradation during
repeated use, are still serious issues.3 Accordingly, recent
attention has been devoted to the development of nonpolymeric
and recyclable iodine(III) reagents with similar reactivity to their
original reagents by using organic salts as novel supporters. For
example, Qian’s and Okello’s groups reported the preparation of
room-temperature ionic liquid (RTIL)-supported DIB and HTIB
iodine(III) reagents and their applications in organic synthesis,
respectively.4,5 The cations of their iodine(III) reagents were
N-containing aromatic heterocycles, however, Togo’s group
reported aliphatic quaternary ammonium salt-supported DIB
reagents which were used in various oxidative reactions.6,7
Additionally, Zhdankin’s group prepared a convenient recycla-
ble bifunctional ionic liquid-supported hypervalent iodine
reagent for catalytic oxidation of alcohols.8
N-(4-Iodophenyl)pyridinium hexafluorophosphate, as the
precursor to synthesize pyridinium salt-supported HTIB reagent,
was prepared by using modified Zincke’s reaction in three
steps12 (Scheme 1).13 First, pyridine was transformed into N-
(2,4-dinitrophenyl)pyridinium salt in 80% yield. This pyridi-
nium salt was heated with 4-iodoaniline in ethanol to give N-(4-
iodophenyl)pyridinium chloride in excellent yield. After an
anion-exchange reaction, N-(4-iodophenyl)pyridinium hexa-
fluorophosphate was obtained as white solid in good yield.
Finally, a convenient one-pot procedure was used to prepare the
pyridinium salt-supported HTIB reagent by simply oxidizing N-
(4-iodophenyl)pyridinium salt 3 using m-CPBA in the presence
of p-toluenesulfonic acid monohydrate.14 The precipitated
product 4 was obtained in excellent yield by adding diethyl
ether to the reaction mixture followed by washing with ether.
This new pyridinium salt-supported reagent was fully charac-
1
terized by H NMR, 13C NMR, MS, and elemental analysis.13
Compared with previous RTIL-supported HTIB reagents, with
labile ester and amide bonds linkages under harsh condition,5,11
and highly hydroscopic reagents with methylene linkage
O2N
O2N
Cl
N
N
NO2
+
NO2
N
Cl
1
4-iodoaniline
KPF6
water
I
By changing the anion and cation of the RTIL, new RTIL-
supported reagents could be created, which may be highly
stable, easily separable, and readily recyclable. Thus, as an
extension of our study in the synthesis of novel RTIL-supported
HTIB reagents and their application in organic synthesis,9 we are
interested in developing pyridinium based RTIL supported
HTIB reagents. Herein we report the synthesis of pyridinium
salt-supported10 HTIB reagent and its application as an efficient
reagent for tosyloxylation of some 2-substituted phenols.
2,4-dinitroaniline
Cl
2
m-CPBA, TsOH
I
N
N
I(OH)OTs
CH3CN
PF6
PF6
3
4
Scheme 1. Preparation of N-{4-[hydroxy(tosyloxy)iodo]phen-
yl}pyridinium hexafluorophosphate.
Chem. Lett. 2013, 42, 930-932
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

931
OH
Table 1. Syntheses of 4-tosyloxy-2-substituted phenols by
using pyridinium salt-supported conjugated HTIB reagent 4
N
I
OH
PF6
TsO
X
m-CPBA
TsOH
3
5
N
I
OH
X
OH
X
OTs
PF6
OH
TsO
N
I(OH)OTs
CH3CN, 30 °C
5
PF6
X
X = NO2(5a), CHO(5b), COCH3(5c), COOCH3(5d)
4
Entry
Substrates
Products
Yield/%a
Scheme 2. The regeneration of the new pyridinium salt-
supported HTIB reagent 4.
1
2
3
4
5
6
7
8
o-O2NC6H4OH
o-HOC6H4CHO
o-HOC6H4COCH3
o-HOC6H4CO2CH3
o-HOC6H4CO2H
o-CH3C6H4OH
o-CH3OC6H4OH
C6H5OH
5a
5b
5c
5d
76
70
73
68
®
®
®
®
Table 2. Syntheses of 2-nitro-4-tosyloxyphenol by using
regenerative HTIB reagent 4
b
®
®
c
Sequence
Yield/% (2-nitro-4-tosyloxyphenol)
c
®
®
1
2
3
76.1
75.9
75.8
c
aIsolated yields after purification by preparative TLC. bNo
reaction. cCorresponding 4-tosyloxy-2-substituted phenols
were not obtained.
After demonstrating that this pyridinium salt-supported
HTIB reagent has similar reactivity to the original reagent, we
further investigated its recyclability in organic synthesis. In
these studies, once the tosyloxylation products were produced,
pyridinium salt-supported HTIB reagent 4 was reduced to the
pyridinium salt-supported iodobenzene [N-(4-iodophenyl)pyri-
dinium hexafluorophosphate (3)], which has very limited
solubility in chloroform. By taking advantage of this, regener-
ation of the reduced pyridinium salt-supported iodobenzene 3
can be easily realized by simple filtration and washing.
Therefore, after the reaction was completed, acetonitrile was
removed by evaporation and the solid residue was washed
several times with chloroform to afford filtrate which contained
the tosyloxyation products, while pyridinium salt-supported
iodobenzene 3 was recovered in greater than 90% yields
(Scheme 2). Then, recovered pyridinium salt-supported iodo-
benzene 3 can be reoxidized to HTIB reagent 4 and reused. It is
pleasing to find that this pyridinium salt-supported HTIB reagent
can be recycled three times without any loss of reactivity
(Table 2).
between the pyridinium salt and HTIB11 generated in our
laboratory, the current pyridinium salt-supported HTIB reagent 4
is quite stable and can be stored in air for several weeks without
any decomposition. This probably can be attributed to the
conjugation of the pyridine and benzene rings which stabilizes
the reagent by electron delocalization.
HTIB is a widely used oxidizing reagent in organic
transformations. Especially, this reagent is used to oxidize
monohydric phenols containing electron-withdrawing substitu-
ents at the ortho-position, leading to tosyloxylation product at
the para-position.15 These tosyloxylated products are difficult to
obtain by other methods and are highly useful intermediates with
potential for further transformation. Therefore, this reaction was
chosen as the model reaction to examine our pyridinium salt-
supported HTIB reagent. The reaction was performed by mixing
1.05 equiv of pyridinium salt-supported HTIB reagent 4 with
ortho-substituted phenols at 30 °C in acetonitrile. The tosyl-
oxylation reaction proceeded smoothly to give products 5a-5d
with yields ranging from 68 to 76% (Table 1). This means the
current pyridinium salt-supported HTIB reagent had the same
oxidation reactivity as the original HTIB reagent. In the case of
salicylic acid (Table 1, Entry 5), no oxidation product was
found. Besides, when phenol substrates with electron-rich
substituents or without substituents at the ortho-position
(Table 1, Entries 6-8) were used to explore this reaction, no
tosyloxylation products were formed. This was in accord with
the previous report.15 After the report, Gu’s group reported a
closely related reaction, in which PIFA was applied to the direct
tosyloxylation of anilides.16 Between these two kinds of
reactions, common ground lies in the reactive species formed
after nucleophilic attacks of iodine(III) reagents with anilides or
phenols. The reactive species existed in the forms of cations, this
In summary, a new solid pyridinium salt-supported HTIB
reagent was developed, which was prepared in four steps in
good yield. The reagent exhibited a similar reactivity to the
original HTIB reagent. Most importantly, the reagent can be
easily recycled several times without any loss of reactivity. It is
expected that this novel pyridinium salt-supported HTIB reagent
will have further applications in organic synthesis.
References and Notes
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¹
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© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/