The synthesis of 4-tosyloxy-2-substituted phenols using new solid pyridinium salt supported [hydroxyl(tosyloxy)iodo]benzene reagents

Article abstract of DOI:10.3184/174751912X13338131755814

Two new solid pyridinium salt supported HTIB reagents (N-{4- [hydroxyl(tosyloxy)iodo]benzyl}pyridinium tetrafluoroborate and N-{4-[hydroxyl(tosyloxy)iodo]phenylcarbamoylmethyl}pyridinium tetrafluoroborate) were synthesised using a pyridinium salt as a cat

Full text of DOI:10.3184/174751912X13338131755814

JOURNAL OF CHEMICAL RESEARCH 2012
RESEARCH PAPER 293
MAY, 293–295
The synthesis of 4-tosyloxy-2-substituted phenols using new solid
pyridinium salt supported [hydroxyl(tosyloxy)iodo]benzene reagents
Bing Yanga,b, Jizhen Zhanga*, Dejian Zhaoa and Hua Kuanga
aSchool of Chemistry and Environmental Engineering, JiangsuTeachers University ofTechnology,Changzhou, Jiangsu 213001, P. R. China
bSchool of Petrochemical Engineering, Changzhou University, Changzhou, Jiangsu 213164, P. R. China
Two new solid pyridinium salt supported HTIB reagents (N-{4-[hydroxyl(tosyloxy)iodo]benzyl}pyridinium tetrafluo-
roborate and N-{4-[hydroxyl(tosyloxy)iodo]phenylcarbamoylmethyl}pyridinium tetrafluoroborate) were synthesised
using a pyridinium salt as a cationic support. Although the former was hygroscopic the latter was stable in air and in
a highly humid atmosphere over a few weeks. The latter has an extra amide linkage. The structures of both com-
1
pounds were established by IR, H NMR, 13C NMR, MS and elemental analysis. Then, two 4-tosyloxy-2-substituted
phenols were successfully prepared using the new reagents. Both reagents were easily regenerated in high yields.
Keywords: [hydroxyl(tosyloxy)iodo]benzene, task-specific pyridinium salts, 4-tosyloxy-2-substituted phenols, synthesis
[Hydroxyl(tosyloxy)iodo]benzene (HTIB) is well known as a
very useful synthetic reagent,1 due to its moderate electrophi-
licity and its ability to bring about oxytosylation. The presence
of the hypervalent iodine in the molecule, HTIB facilitates
many oxidative transformations.2–4 However, the reaction of
HTIB usually generates an equimolar amount of iodobenzene
as a byproduct, which requires extra effort to remove from
the desired product. Although this can be accomplished by
chromatography, it is usually not cost-effective in larger scale
chemical synthesis or manufacture.
Traditionally, polymer-supported reagents have provided a
possible approach to the separation problem.5 However, they
are limited in application due to their loading capacity and
reactivity.6 Recently, attention has been focused on the use of
organic salts (such as room-temperature ionic liquids, RTILs)
as a novel support. The exploration of task-specific organic
salts has become an attractive research topic. Compared with
traditional polymer-supported reagents, organic salt supported
reagents have remarkable advantages, including high stability,
favourable solubility, high loading capacity, non-toxicity and
low vapor pressure. More importantly, organic salt supported
reagents can be easily regenerated and reused.
1-(4-Diacetoxyiodobenzyl)-3-methylimidazalium tetrafluo-
roborate, an ion-supported phenyliodine diacetate (PIDA)
reagent, has been prepared previously.7 The RTIL-supported
HTIB reagents {3–butyl-4(5)-[4-hydroxy(tosyloxy)iodobenz-
oyloxymethyl]-1-methyl-3H-imidazol-1-ium triflimide and
3–butyl-4(5)-[4-hydroxy(tosyloxy)iodobenzoyloxymethyl]-
1-methyl-3H-imidazol-1-ium 4-methylbenzenesulfonate} have
also been reported, which are viscous liquids with ester link-
ages.8 We previously reported a new RTIL-supported HTIB
reagent {1-[4-hydroxy(tosyloxy)iodobenzyl]-3-methylimid-
azalium tetrafluoroborate}9 which is also a liquid. The reactiv-
ity of the RTIL-supported HTIB was exemplified by the
α-tosyloxylation of ketones in an ionic liquid [emim]BF4 or
acetonitrile under microwave irradiation. The ion-supported
iodobenzene as a solid could be readily isolated and the HTIB
regenerated.9
cation was found to be a good candidate to form solid organic
salt supported HTIB reagents; (2) it was thought that the new
organic salt supported HTIB reagent may be converted to a
solid at room temperature by introducing an amide linkage
between the cation and HTIB. We now report the efficient
synthesis of two new solid pyridinium salt supported HTIB
reagents.
N-[4-Hydroxyl(tosyloxy)iodobenzyl]pyridinium tetrafluo-
roborate 3 was obtained in high yield via two methods
(Scheme 1), while N-{[4- hydroxyl(tosyloxy)iodo]phenylcarb-
amoylmethyl} pyridinium tetrafluoroborate 7 was synthesised
by a one-pot procedure (Scheme 2). We made one attempt to
prepare the ion-supported PIDA reagent from 6 with an amide
linkage in the structure, but the yield of this reaction was very
low (<30%). Since compound 6 could be easily transformed
into 7, the one-pot method was used to give a high yield.
We found that compound 5 was not stable in air due to its
hygroscopicity. On the other hand, compound 5 was highly
soluble in water. 1-(4-Iodobenzyl)-3- methylimidazolium
tetrafluoroborate was prepared using 1-(4-iodobenzyl)-3-
methylimidazolium chloride by anion exchange in acetone.7
Because of the low solubility of the reactants in acetone, the
reaction was very slow (60 h). However, 1,1-dimethylpyrro-
lidinium bis(trifluoromethanesulfonyl)imide salt was obtained
in distilled water in 3 h.10 Since 6 is insoluble in water, the
transformation from compound 5 to 6 was completed in water
in a few minutes in high yield.
Pyridinium based organic salts appear to absorb moisture,
and compound 3, was found to completely liquefy in air. How-
ever, 7 was stable under atmospheric conditions. In our view,
the introduction of the amide linkage changed its properties.
Because of the asymmetry of the imidazole structure, these
imidazolium salt supported reagents have a lower melting
point and exist in a liquid phase.9 This study demonstrates that
solid pyridinium salt supported HTIB reagents can be success-
fully prepared by the introduction of the amide linkage or
by the application of the symmetry of pyridinium cation.
Introducing the amide linkage confers a high stability to the
The RTIL-supported HTIB reagents which have been
reported are usually viscous liquids, which are inconvenient
to purify. Therefore, we are interested in exploring the solid
ion-supported HTIB reagents. The properties of organic salts
are changed by varying the structure of anions or/and cations.
In designing the novel solid organic salt supported HTIB
reagents, we considered the following facts: (1) it was found
that the melting points of organic salt supported reagents is
increased by using symmetric cations. The symmetric pyridine
Scheme 1 (a) m-CPMA/p-TsOH; (b) p-TsOH.
* Correspondent. E-mail: zhangjizhen999999@yahoo.com.cn

294 JOURNAL OF CHEMICAL RESEARCH 2012
Scheme 2
and then this solution was added to flask. A white precipitate appeared
after 10 min by stirring with increasing amounts of NaBF4 solution.
The precipitate was filtered, washed with a little water, and then dried
under vacuum to afford a white solid (4.40 g, 92%). M.p. 176.0–
178.0 °C. IR (KBr): ν 3365, 3098, 3076, 3057, 2927, 2853, 1705,
new solid reagent in air, which had previously restricted the
application to other syntheses.
Monohydric phenols, which contain some electron-with-
drawing substituents at the ortho position, on treatment with
HTIB in dichloromethane underwent tosyloxylation to the
corresponding 4-tosyloxy-2-substituted phenols.11 We now
reported the syntheses of two 4-tosyloxy-2-substituted phenols
using new solid pyridinium salt supported HTIB reagents 3
and 7 (Scheme 3).
The most important feature is that 3 and 7 can be regener-
ated and reused for the same reaction, and consequently they
have several advantages over the conventional HTIB reagents
in their ability to be recycled.
1
1605, 1587, 1488, 815, 496 cm−1. H NMR (500 MHz, DMSO-d6):
δ (ppm) 2.29 (s, 3 H, CH3), 5.63 (s, 2 H, CH2), 7.42 (d, J = 8.7 Hz, 2
H, ArH), 7.70 (d, J = 8.7 Hz, 2 H, ArH), 8.23 (t, J = 7.4 Hz, 2 H, PyH),
8.70 (t, J = 7.8 Hz, 1 H, PyH), 9.03 (d, J = 5.6 Hz, 2 H, PyH), 10.79
(s, 1 H, NH). (Py = pyridinium) 13C NMR (125 MHz, DMSO-d6): δ
(ppm) 62.1, 87.6, 121.3, 127.4, 137.8, 137.9, 146.2, 146.4, 163.6. MS
(Agilent 5975I) (EI, 70eV): m/z (%) 339.0 (9) [M+–BF4−], 261.0 (19)
[M+–BF4−–C5H4N], 246.0 (17) [p-IC6H4NHC≡O+], 245.0 (100)
[p-IC6H4N=C=O·+], 219.0 (100) [p-IC6H4NH2]+·, 79.1 (94) [C5H5N]+·.
Anal. Calcd for C13H12BF4IN2O: C, 36.64; H, 2.84; N 6.58. Found: C,
36.68; H, 2.85; N, 6.57%.
Experimental
N-{[4-Hydroxyl(tosyloxy)iodo]phenylcarbamoylmethyl}pyridin-
ium tetrafluoroborate (7): Compound 6 (3.83 g, 9.0 mmol) and p-
TsOH•H2O (1.71 g, 9.0 mmol) were dissolved in acetonitrile (25 mL),
and then m-CPBA (2.16 g, 80%, 10.0 mmol) was added and the
mixture was stirred under a nitrogen atmosphere. After the reaction,
Et2O was added, and a yellow solid was filtered out from the resulting
mixture. The solid was washed with Et2O to provide 7 (4.36 g, 79%).
M.p. 136.0–138.0 °C. IR (KBr): ν 3276, 3060, 1696, 1607, 1587,
1543, 1488, 1197, 1034, 810, 501 cm−1. 1H NMR(500 MHz, DMSO-
d6): δ (ppm) 2.29 (s, 3 H, CH3), 5.64 (s, 2 H, CH2), 7.11 (d, J = 8.0 Hz,
2 H, ArH), 7.42 (d, J = 8.8 Hz, 2 H, ArH), 7.49 (d, J = 8.0 Hz, 2 H,
ArH), 7.69 (d, J = 8.8 Hz, 2 H, ArH), 8.20–8.25 (m, 2 H, PyH),
8.69 (t, J = 7.8 Hz, 1 H, PyH), 9.03 (d, J = 5.5 Hz, 2 H, PyH), 10.78
(s, 1 H, NH). 13C NMR (125 MHz, DMSO-d6): δ (ppm) 20.9,
62.2, 87.9, 121.4, 121.5, 125.6, 127.6, 127.9, 137.8, 137.9, 145.4,
146.4, 146.5, 163.4. MS (HP 5989B) (EI, 70eV): m/z (%) 261 (25)
[M+–BF4−-C5H4N–OH–OTs], 245 (14) [p-IC6H4N=C=O·+], 219 (80)
[p-IC6H4NH2]+·, 93 (37) [PhNH2]+·, 79 (60) [C5H5N]+·. Anal. Calcd for
C20H20BF4IN2O5S: C, 39.09; H, 3.28; N 4.56. Found: C, 39.06; H,
3.29; N, 4.57%.
Melting points were determined using a WBS-1B digital thermometer,
1
and were uncorrected. H NMR and 13C NMR were recorded on a
Bruker DRX-500AVANCE spectrometer using TMS as the internal
standard. IR spectra were recorded on a Nicolet Protege 460 IR spec-
trometer. Mass spectra were obtained on a HP5989B and an Agilent
5975I instrument. Elemental analyses were performed using an
EA2400 II instrument.
N-(4-Iodobenzyl)pyridinium tetrafluoroborate
1 and N-[4–bis
(diacetoxy)iodobenzyl] pyridinium tetrafluoroborate 2 were prepared
according to literature methods.12 All other reagents were of analytical
or chemical grade purchased commercially and used as received
unless noted otherwise.
4-Iodochloroacetanilide (4): Et3N (2 mL) was added to a chloro-
form solution (10 mL) of 4-iodoaniline (2.62 g, 12.0 mmol). Then the
solution was cooled to 0 °C, and 2-chloroacetyl chloride (1.34 g,
12.0 mmol) was added dropwise to this solution. The resulting
solution was warmed to room temperature and stirred for 2 h. The
precipitated product was collected by vacuum filtration, washed with
distilled water and dried under reduced pressure to afford an off-white
solid (2.90 g, 82%). M.p. 192–194 °C (194.0–195.0 °C).13 IR (KBr):
ν 3307, 3076, 2949, 2852, 1672, 1611, 1586, 1484, 818, 495 cm−1.
1H NMR (500 MHz, CDCl3): δ (ppm) 4.19 (s, 2 H, CH2), 7.34 (d,
J = 8.7 Hz, 2 H, ArH), 7.67 (d, J = 8.7 Hz, 2 H, ArH), 8.20 (s, 1 H,
NH). (Ar = benzene).
N-(4-Iodophenylcarbamoylmethyl) pyridinium tetrafluoroborate
(6): Compound 4 (3.32 g, 18.0 mmol) was dissolved in anhydrous
acetonitrile (20 mL), and anhydrous pyridine (3.56 g, 45.0 mmol) was
added to this solution. The resulting mixture was heated at reflux for
5 h with magnetic stirring and protected from moisture by using an
anhydrous CaCl2 drying tube. The solvent and excess pyridine were
then evaporated and the residue was cooled to room temperature.
Water (10 mL) was added to the reaction and the residual solid was
dissolved. NaBF4 (1.98 g, 18 mmol) was dissolved in water (10 mL),
N-[4-Hydroxyl(tosyloxy)iodobenzyl]pyridinium tetrafluoroborate (3)
Method a: Compound 3 was prepared under the similar condition of
compound 7.
Method b: A mixture of 2 (3.0 g, 6.0 mmol) and p-TsOH•H2O (1.14 g,
6.0 mmol) in acetonitrile (20 mL) was stirred at room temperature.
After the reaction, the solvent was then evaporated and the residue
was washed with Et2O. The residual solid was further dried vacuum at
50 °C to afford 3 as a yellow solid (3.25 g, 95%). M.p. 52.0–54.0 °C.
IR (KBr): ν 3428, 3072, 1570, 1486, 1449, 1182, 1043, 816, 522 cm−1.
1H NMR (500 MHz, DMSO-d6): δ (ppm) 2.28 (s, 3 H, CH3), 5.80
Table 1 Syntheses of two 4-tosyloxy-2-substituted phenols
with pyridinium salt supported HTIB reagents in acetonitrile
and regeneration of new reagents
Reagent
Yield (8,%)
64
61
91
62
60
78
Yield (9,%)
Yield (3 or 7,%)a
a The yields of regenerated reagents after a single reaction.
Scheme 3

JOURNAL OF CHEMICAL RESEARCH 2012 295
(s, 2 H, CH2), 7.14 (d, J = 8.0 Hz, 2 H, ArH), 7.33 (t, J = 8.0 Hz, 2 H,
ArH), 7.47 (d, J = 8.0 Hz, 2 H, ArH), 7.82 (t, J = 8.0 Hz, 2 H, ArH),
8.16–8.20 (m, 2 H, PyH), 8.63 (d, J = 7.5 Hz, 1 H, PyH), 9.17 (d,
J = 5.5 Hz, 2 H, PyH). 13C NMR (125 MHz, DMSO-d6): δ (ppm) 20.8,
62.7, 96.4, 125.5, 128.1, 128.6, 131.1, 133.9, 137.8, 138.0, 144.9,
145.5, 146.1. MS (HP 5989B) (EI, 70eV): m/z (%) 296 (1) [M+–BF4−
–OH–OTs], 295 (1) [M+–BF4––OH–TsOH], 217 (35) [I–C6H4CH2+],
169 (5) [M+–BF4––OH–OTs–I], 91 (93) [C6H5CH2+], 79 (100)
[C5H5N]+·. Anal. Calcd for C19H19BF4INO4S: C, 39.94; H, 3.35; N,
2.45. Found: C, 39.97; H, 3.34; N, 2.45%.
2.38 (s, 3 H, CH3), 6.81 (d, J = 9.0 Hz, 1 H), 6.98 (dd, J = 9.0, 3.0 Hz,
1 H), 7.21 (d, J = 3.0 Hz, 1 H), 7.27 (d, J = 8.0 Hz, 2 H), 7.64 (d,
J = 8.0 Hz, 2 H), 9.72 (s, 1 H, –CHO), 10.90 (s, 1 H, OH).
2-Methoxyformyl-4-tosyloxyphenol (9):Yellow crystals. M.p. 88.3–
1
90.2 °C; lit.11 91–92 °C. H NMR (500 MHz, CDCl3): δ (ppm) 2.38
(s, 3 H, CH3), 3.85 (s, 3 H, –OCH3), 6.77 (d, J = 9.0 Hz, 1 H), 6.87
(dd, J = 9.0, 3.0Hz, 1 H), 7.25 (d, J = 8.0 Hz, 2 H), 7.50 (d, J = 3.0 Hz,
1 H), 7.63 (d, J = 8.0 Hz, 2 H), 10.65 (s, 1 H, OH).
Received 2 February 2012; accepted 9 March 2012
Paper 1201144 doi: 10.3184/174751912X13338131755814
Published online: 10 May 2012
Synthesis of 4-tosyloxy-2-substituted phenols using reagent 3; general
procedure
Substituted monohydric phenols (2 mmol) were added to a solution of
reagent 3 (2.1 mmol) in acetonitrile (20 mL), the mixture was stirred
inat30°C.Aftercompletionofreaction[asmonitoredbyTLC(EtOAc–
petroleum=1:10)], the product was purified as follows: the solvent
was evaporated under reduced pressure to give a solid residue, which
was washed with EtOAc or CHCl3 (10 mL × 3) to afford the pyridin-
ium salt supported iodobenzene 1 as a white solid. At the same time,
the washings were combined and concentrated under reduced pres-
sure to give a product which was further purified by preparative TLC
on silica gel using 1:10 EtOAc-petroleum as developing solvent.
References
1
2
3
4
5
6
G.F. Koser, Aldrichim. Acta, 2001, 34, 89.
V.V. Zhdankin and P.J. Stang, Chem. Rev., 2008, 108, 5299.
V.V. Zhdankin and P.J. Stang, Chem. Rev., 2002, 102, 2523.
P.J. Stang and V.V. Zhdankin, Chem. Rev., 1996, 96, 1123.
S. Abe, K. Sakuratani and H.Togo, Synlett., 2001, 22.
S.V. Ley, A.W. Thomas and H. Finch, J. Chem. Soc., Perkin Trans. 1, 1999,
667.
7
W.X. Qian, E.L. Jin, W.L. Bao and Y.M. Zhang, Angew. Chem. Int. Ed.,
2005, 44, 952.
8
9
S.T. Handy and M. Okello, J. Org. Chem., 2005, 70, 2874.
F. Su, J.Z. Zhang, G.Y. Jin, T. Qiu, D.J. Zhao and H.B. Jia, J. Chem. Res.,
2009, 741.
Regeneration of reagent 3; general procedure
After extraction with EtOAc, the pyridinium salt supported iodoben-
zene 1 was used to prepare reagent 3 under the similar condition of
compound 7.
The syntheses of 4-tosyloxy-2-substituted phenols using reagent 7
and the regeneration of reagent 7 were similar to reagent 3. The results
are listed in Table 1.
10 D.R. Macfarlane, P. Meakin, J. Sun, N. Amini and M. Forsyth, J. Phys.
Chem. B, 1999, 103, 4164.
11 O. Prakash, M. Kumar and R. Kumar, Tetrahedron, 2010, 66, 5827.
12 J.Z. Zhang, D.J. Zhao, Y.Z. Wang, H. Kuang and H.B. Jia, J. Chem. Res.,
2011, 35, 333.
13 P.G. Baraldi, D. Preti, M.A. Tabrizi, F. Fruttarolo, G. Saponaro, S. Baraldi,
R. Romagnoli, A.R. Moorman, S. Gessi, K. Varani and P.A. Borea, Bioorg.
Med. Chem., 2007, 15, 2514.
2-Formyl-4-tosyloxyphenol (8): Yellow crystals. M.p. 216.7–
1
217.5 °C; lit.11 219–220 °C. H NMR (500 MHz, CDCl3): δ (ppm)

Copyright of Journal of Chemical Research is the property of Science Reviews 2000 Ltd. and its content may
not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written
permission. However, users may print, download, or email articles for individual use.