Homogeneous supported synthesis using ionic liquid supports: Tunable separation properties

Article abstract of DOI:10.1021/jo047807k

(Chemical Equation Presented) We report a homogeneous supported version of Koser's salt based on a room-temperature ionic liquid (RTIL) support. By altering the nature of the RTIL, a material was developed that was stable, recyclable, and readily separable from the tosyloxylated ketone products just by using variations in solvent polarity. A similar approach should be applicable to a wide range of supported catalysts and reagents.

Full text of DOI:10.1021/jo047807k

released by hydrogenolysis, resulting in a RTIL support
that could not be recycled, unlike the ester linkage
supports.6
Homogeneous Supported Synthesis Using
Ionic Liquid Supports: Tunable Separation
Properties
At the same time, far less effort has been spent on
RTIL-supported reagents. RTILs themselves have been
supported on silica or have been used as recyclable
reagents, but the idea of supporting a reagent on a RTIL
is far less studied. Most existing reports focus on the
support of metal catalysts, such as vanadyl salen com-
plexes7 and ruthenium metathesis catalysts.8 These
species were not only catalytically active, but were also
readily retained in RTIL layers and thereby recycled. In
terms of nonmetallic reagents, the only existing reports
all deal with either sulfonic acids9 or sulfonyl chlorides10
supported on RTILs, the former of which are recyclable
acid catalysts, while the later are consumed reagents for
Friedel-Crafts alkylations or Beckman rearrangements.
Our particular interest was in the preparation of
supported stoichiometric reagents, not catalysts. In par-
ticular, we viewed hypervalent iodine reagents such as
diacetoxyphenyliodane and Koser’s salt as appealing
challenges to the RTIL supported method.11 The reason-
ing behind this selection is 2-fold. First, reactions involv-
ing any of these reagents ultimately involve the separa-
tion of the iodobenzene byproduct from the desired
product. Although this can be accomplished via chroma-
tography, it does necessitate a chromatographic separa-
tion step and precludes the direct use of the reaction
products in subsequent reactions. This is particularly an
issue in cases where the reaction products are sensitive
and decompose on silica gel (vide infra). Second, these
hypervalent iodine reagents are generated from iodoben-
zene. Although this same material can, in theory, be
recovered at the end of the reaction, in practice it rarely
is due to the extra effort required for recovery, purifica-
tion, and regeneration.
Scott T. Handy* and Maurice Okello
Department of Chemistry, State University of New York at
Binghamton, Binghamton, New York 13902
shandy@binghamton.edu
Received December 15, 2004
We report a homogeneous supported version of Koser’s salt
based on a room-temperature ionic liquid (RTIL) support.
By altering the nature of the RTIL, a material was developed
that was stable, recyclable, and readily separable from the
tosyloxylated ketone products just by using variations in
solvent polarity. A similar approach should be applicable to
a wide range of supported catalysts and reagents.
Room-temperature ionic liquids (RTILs) are not only
gaining greater attention as solvents for organic synthe-
sis but also increasingly finding applications in other
areas as well.1 One of the more recent developments is
the use of RTILs as homogeneous supports. Much of this
interest has been in the area of homogeneous supported
synthesis.2,3 Bazureau and co-workers have been the most
active in this area and used ester linkages to tether
various small molecules to an ionic liquid core and then
employed condensation reactions to create compounds
such as thioxotetrahydropyrimidinones and thiazolidi-
nones.2 Other workers, including ourselves, have simi-
larly used ester linkages for the support of small mol-
ecules such as acrylates and iodobenzoates, which have
then be employed in further transformations.3-5 Only in
one case has a different linkage been used. In this case,
an amine linkage was formed and the final product
To address the issues associated with iodobenzene
recycling, various supported iodanes have been reported,
most typically using polystyrene as the support.12 These
supported reagents have been successfully applied in a
number of cases and can be recycled. At the same time,
(6) Miao, W.; Chan, T. H. Org. Lett. 2003, 5, 5003-5005.
(7) Baleizao, C.; Gigante, B.; Garcia, H.; Corma, A. Tetrahedron Lett.
2003, 44, 6813-6816.
(8) Audic, N.; Clavier, H.; Mauduit, M.; Guillemin, J.-C. J. Am.
Chem. Soc. 2003, 125, 9248-9249. Geldbach, T. J.; Dyson, P. J. J. Am.
Chem. Soc. 2004, 126, 8114-8115.
(9) Cole, A. C.; Jensen, J. L.; Ntai, I.; Trans, K. L. T.; Weaver, K. J.;
Forbes, D. C.; Davis, Jr.; J. H. J. Am. Chem. Soc. 2002, 124, 5962-
5963. Gu, Y.; Shi, F.; Deng, Y. Catal. Commun. 2003, 4, 597-601.
(10) Qiao, K.; Yokoyama, C. Chem. Lett. 2004, 33, 472-473. Gui,
J.; Deng, Y.; Hu, Z.; Sun, Z. Tetrahedron Lett. 2004, 45, 2681-2683.
(11) For recent reviews of hypervalent iodine chemistry, see: Hy-
pervalent Iodine Chemistry: Modern Developments in Organic Syn-
thesis. Topics in Curr. Chem. Vol. 224; Springer-Verlag: Berlin, 2003.
Koser, G. F. Aldrichimica Acta 2001, 34, 89-102. Zhdankin, V. V.;
Stang, P. J. Chem. Rev. 2002, 102, 2523-2584. Varvolis, A. The
Organic Chemistry of Polycoordinated Iodine; VCH Publishers: New
York, 1992.
(12) For examples, see: Chen, J. M.; Lin, X. J.; Huang, X. A. J.
Chem. Res., Synop. 2004, 43-44. Lee, J. W.; Ko, K. Y. Bull. Korean
Chem. Soc. 2004, 25, 19-20. Togo, H.; Sakuratani, K. Synlett 2002,
1966-1975. Ficht, S.; Mulbaier, M.; Giannis, A. Tetrahedron 2001, 57,
4863-4866. Tohma, H.; Morioka, H.; Takizawa, S.; Arisawa, M.; Kita,
Y. Tetrahedron 2001, 57, 345-352. Ley, S. V.; Thomas, A. W.; Finch,
H. J. Chem. Soc., Perkin Trans. 1 1999, 669-671.
(1) Welton, T. Chem. Rev. 1999, 99, 2071-2083. Freemantle, M.
Chem. Eng. News 2000, 37-50. Wasserscheid, P.; Keim, W. Angew.
Chem., Int. Ed. 2000, 39, 3772-3789. Dupont, J.; de Souza, R. F.;
Suarez, P. A. Z. Chem. Rev. 2002, 102, 3667-3692. Ionic Liquids in
Synthesis; Wasserscheid, P., Welton, T., Eds.; Wiley-VCH: Weinheim,
2003.
(2) Hakkou, H.; Eynde, J. J. V.; Hamelin, J.; Bazureau, J. P.
Tetrahedron 2004, 60, 3745-3753. Hakkou, H.; Vanden Eynde, J. J.;
Hamelin, J.; Bazureau, J. P. Synthesis 2004, 1793-1798. Fraga-
Dubreuil, J.; Bazureau, J. P. Tetrahedron 2003, 59, 6121-6130. Fraga-
Dubreuil, J.; Bazureau, J. P. Tetrahedron Lett. 2001, 42, 6097-6100.
(3) Handy, S. T. Okello, M. Tetrahedron Lett. 2003, 44, 8399-8402.
(4) Anjaiah, S.; Chandrasekhar, S.; Gree, R. Tetrahedron Lett. 2004,
45, 569-571.
(5) de Kort, M.; Tuin, A. W.; Kuiper, S.; Overkleeft, H. S.; van der
Marel, G. A.; Buijsman, R. C. Tetrahedron Lett. 2004, 45, 2171-2175.
10.1021/jo047807k CCC: $30.25 © 2005 American Chemical Society
Published on Web 03/03/2005
2874
J. Org. Chem. 2005, 70, 2874-2877

TABLE 1. Tosyloxyketone Preparation with Koser’s
Salt 3
FIGURE 1. RTIL-supported hypervalent iodine reagents.
SCHEME 1. Preparation of Supported Koser’s
Salt 3
R1
R2
conditions
time
% yielda
CH3
Et
H
CH3
H
55°C, ))))
RT
55°C, ))))
0°C
20 min
20 min
20 min
2 h
67
80
Ph
74
-(CH2)4-
65 (76)b
a Isolated yield. b Overnight reaction.
iodobenzene 4 from the reaction products. This salt
proved to be soluble in the same range of solvents as the
tosyloxyketone products (ether, ethyl acetate, acetone,
methylene chloride). Ultimately, the only effective method
for separating the products from iodobenzene 4 proved
to be chromatography. A quick separation using ethyl
acetate/hexanes to elute the tosyloxyketone, followed by
acetonitrile to elute salt 4 was reasonably effective and
did result in 76-80% recovery of salt 4. Still, the need
to use chromatography negated much of the potential
advantage of this supported reagent and the recovery of
4 was far from satisfactory.
At this point, we turned to one of the advantages of
RTIL materialsstunable physical properties. By varying
the anion and cation, RTILs can be prepared that vary
in polarity, viscosity, density, melting point, and miscibil-
ity/solubility properties.1 In particular, it is known that
for imidazolium cation based RTILs, harder anions such
as phosphate, tosylate, and chloride generally result in
RTILs that are miscible with polar solvents (water,
methanol) but not with less polar solvents (ether, ethyl
acetate, toluene). On the other hand, softer, more weakly
coordinating anions such as hexafluorophosphate and
triflimide result in RTILs that are immiscible with polar
solvents but miscible with less polar solvents including
toluene and ether. With this in mind, it appeared that
supported iodane reagents with a more coordinating
anion should be a method for obviating the product/
byproduct separation issue.
To that end, supported iodobenzene 5, which has a
toluenesulfonate anion, was prepared (Scheme 1). Oxida-
tion with peracetic acid, followed by treatment with tosic
acid in acetonitrile then afforded supported Koser’s salt
7 as before. During this sequence, it was noted that all
of the tosylate salts are more viscous than the triflimide
salts. Further, salt 5 is actually a solid at room temper-
ature.
With this second-generation supported Koser’s salt in
hand, the R-tosyloxyation of ketones was again examined
(Table 2). The reactions proceeded slightly slower than
with the triflimide salt version of the supported Koser’s
salt, but were still generally complete within 30 min. The
yields were comparable to those obtained before. The real
advantage came in the separation phase. With tosylate
salt 7, the byproduct was iodobenzene 5, which could be
readily separated by dilution of the reaction with ether.
This reduction in polarity was sufficient to precipitate
salt 5, which could then be recovered in >95% yield by
they do suffer from the typical phase transfer problems
that plague all hetereogeneous supports, thereby slowing
the progress of these reactions. Further, the long-term
stability of polystyrene to these oxidizing agents is a
concern as well.
Our alternative entry into supported iodane reagents
is based upon our previously reported fructose-derived
ionic liquid 1 (Figure 1).13 By attaching commercially
available p-iodobenzoic acid to this support, a family of
iodanes such as diacetoxy compound 2 and Koser’s salt
3 can be prepared.
In the event, salt 1 was acylated with p-iodobenzoyl
chloride to afford supported iodobenzene 4 in nearly
quantitative yield (Scheme 1). Oxidation of this com-
pound with peracetic acid under conditions similar to
those reported for the preparation of diacetoxyiodoben-
zene resulted in the preparation of diacetoxy compound
2.14 After the removal of all volatiles, the crude residue
was used directly to prepare supported Koser’s salt 3 by
treatment with tosic acid in acetonitrile, again paralleling
the procedure used for the parent, nonsupported com-
pound.15 Following removal of the volatiles, the resulting
viscous liquid was used as is in subsequent reactions. 1H
NMR indicated the absence of any of iodo compounds 4
or 2.
With the supported Koser’s salt in hand, the R-tosy-
loxyation of ketones was studied (Table 1). Much to our
delight, reagent 3 was effective for this transformation.
The R-tosyloxyketones were obtained in >60% isolated
yield. Further, the reactions themselves were faster than
those with Koser’s salt itself, likely due to the presence
of the electron-withdrawing ester group on the benzene
ring. The only problem was in the separation of supported
(13) Handy, S. T.; Okello, M.; Dickenson, G. Org. Lett. 2003, 5,
2513-2515.
(14) Ficht, S.; Mulbaier, M.; Giannis, A. Tetrahedron 2001, 57,
4863-4866.
(15) Koser, G. F.; Relenyi, A. G.; Kalo, A. N.; Rebrovic, L.; Wettach,
R. H. J. Org. Chem. 1982, 46, 2487-2489.
J. Org. Chem, Vol. 70, No. 7, 2005 2875

TABLE 2. Tosyloxyketone Preparation with Koser’s
Salt 7
mmol) of triethylamine. The resultant mixture was cooled to -20
°C, followed by the dropwise addition of a solution of 45 µL
(0.5589 mmol) of 4-iodobenzoyl chloride in 112 µL of dichlo-
romethane. The reaction mixture was left to stir for 30 min and
was then quenched using 5 N NaOH (200 µL) followed by
dilution with dichloromethane (5 mL) and water (2 mL). The
aqueous layer was extracted with dichloromethane (3 × 5 mL).
The combined organic extracts were dried (Na2CO3) and con-
centrated in vacuo to afford 0.2892 g (quantitative) of 5 as an
off-white solid (mp 164-166 °C): IR (CHCl3) νmax cm-1 3013.0,
2962.5, 2876.5, 1728.3, 1586.0, 1540.2, 1521.3, 1475.8, 1423.1,
1394.7, 1263.0, 1224.8, 1122.5, 1093.6, 1009.4, 928.5, 846.1,
R1
R2
conditions
time
% yielda
CH3
Et
H
CH3
H
55°C, ))))
55°C, ))))
55°C, ))))
0°C
30 min
30 min
30 min
6 h
60
57
74
79
74
1
734.1, 671.0, 626.5; H NMR (CDCl3, 360 MHz) δ 9.95 (s, 1H),
Ph
7.77 (d, J ) 11 Hz, 2H), 7.70 (d, J ) 11 Hz, 2H), 7.63 (d, J ) 7
Hz, 2H), 7.62 (s, 1H), 7.07 (d, 7 Hz, 2H), 5.31 (s, 2H), 4.11 (t, J
) 6 Hz, 2H), 3.97 (s, 3H), 2.27 (s, 6H), 1.74 (quint, J ) 6 Hz,
2H), 1.27 (quint, J ) 6 Hz, 2H), 0.84 (t, J ) 6 Hz, 3H); 13C NMR
(CDCl3, 90 MHz) δ 165.4, 143.4, 139.8, 138.1, 131.2, 129.7, 128.9,
128.3, 126.0, 122.8, 102.0, 54.6, 49.9, 34.4, 32.0, 21.4, 19.6, 13.5.
3-Butyl-4(5)-(4-diacetoxyiodobenzoyloxymethyl)-1-meth-
yl-3H-imidazol-1-ium Triflimide (2). Acetic anhydride and
hydrogen peroxide solution (35%) were mixed in a 4:1 ratio at 0
°C and stirred for 6 h. During this time, the solution was allowed
to slowly warm to room temperature. The resulting peracetic
acid solution was added to a flask containing 0.7659 g (1.1291
mmol) of the RTIL-supported 4-iodobenzoate salt 4 (about 10
mL per 0.66 mmol) at exactly 40 °C and stirred at this
temperature for 8 h. The reaction mixture was concentrated in
vacuo to remove all of the volatiles. The residual thick colorless
oily product 2 (0.8783 g) was used in the following experiments
as such without further purification: IR (CHCl3) νmax cm-1
3479.5, 3016.8, 2736.5, 2583.3, 2399.8, 1781.8, 1635.5, 1586.8,
1521.9, 1475.8, 1424.2, 1349.9, 1331.1, 1180.9, 1057.5, 1009.3,
-(CH2)4-
-(CH2)3-
55°C, ))))
30 min
a Isolated yield.
simple filtration. The tosyloxyketone product could be
isolated following an aqueous workup on the organic
layer. In most cases this afforded the pure product, but
in some cases a trace of unreacted ketone was observed,
which could be readily removed by trituration with cold
hexane.
Importantly, the recovered iodobenzene 5 could be
converted once again into the supported Koser’s salt 7
as before. This material was again capable of carrying
out the tosyloxyation reaction and afforded results in-
distinguishable from the initially prepared material. This
recovery/reoxidation sequence could be carried out again
and again, with no detectable degradation of the support.
In conclusion, we have reported the application of a
RTIL support for recyclable hypervalent iodine reagents.
The ability to tune the solubility/miscibility properties
of the support by changing the anion greatly facilitates
its recovery and demonstrates another method whereby
RTIL supports exhibit potential advantages over other
supports. Further studies and applications of this concept
are underway and will be reported in due course.
1
928.6, 849.3, 778.9, 673.0, 625.8; H NMR (CDCl3, 360 MHz) δ
8.80 (s, 1H), 8.16 (d, J ) 11 Hz, 2H), 8.10 (d, J ) 11 Hz, 2H),
7.48 (s, 1H), 5.43 (s, 2H), 4.16 (t, J ) 6 Hz, 2H), 3.99 (s, 3H),
1.99 (s, 6H), 1.83 (quint, J ) 6 Hz, 2H), 1.35 (quint, J ) 6 Hz,
2H), 0.95 (t, J ) 6 Hz, 3H); 13C NMR (CDCl3, 90 MHz) δ 179.7,
161.0 (q, J ) 41 Hz), 138.5, 137.2, 135.5, 133.8, 131.9, 131.2,
114.4 (q, JC,F ) 315 Hz, NTf2), 54.7, 50.4, 34.5, 31.9, 20.8, 19.5,
16.8, 13.2.
3-Butyl-4(5)-(4-diacetoxyiodobenzoyloxymethyl)-1-meth-
yl-3H-imidazol-1-ium 4-methylbenzenesulfonate (6). Acetic
anhydride and hydrogen peroxide solution (35%) were mixed in
a 4:1 ratio at 0 °C and stirred for 6 h. During this time, the
solution was allowed to slowly warm to room temperature. The
resulting peracetic acid solution was added to a flask containing
0.7659 g (1.1291 mmol) of the RTIL-supported 4-iodobenzoate
salt 5 (about 10 mL per 0.66 mmol) at exactly 40 °C and stirred
at this temperature for 8 h. The reaction mixture was concen-
trated in vacuo to remove all of the volatiles. The residual thick
colorless oily product 6 (0.8783 g) was used in the following
experiments as such without further purification: IR (CHCl3)
νmax cm-1 3384.1, 3010.2, 2681.4, 2585.2, 2436.8, 2400.5, 2336.5,
2255.7, 2218.1, 2068.5, 1778.2, 1692.0, 1586.0, 1521.5, 1477.1,
1423.6, 1231.8, 1121.3, 1086.1, 1030.1, 972.4, 928.4, 888.7, 849.7,
727.8, 671.0, 627.3; 1H NMR (acetone-d6, 360 MHz) δ (C2 not
observed due to facile deuterium exchange in this sample), 8.25
(d, 7 Hz, 2H), 8.17 (d, H ) 7 Hz, 2H), 7.98 (s, 1H), 7.68 (d, J )
7 Hz, 2H), 7.15 (d, J ) 7 Hz, 2H), 5.60 (s, 2H), 4.31 (t, J ) 6 Hz,
2H), 4.12 (s, 3H), 2.30 (s, 3H), 2.09 (s, 6H), 1.85 (obs quint, 2H),
1.35 (quint, J ) 6 Hz, 2H), 0.91 (t, J ) 6 Hz, 3H); 13C NMR
(CDCl3, 90 MHz) δ 179.8, 160.8 (q, J ) 43.2 Hz), 143.2, 138.6,
135.6, 133.3, 131.2, 130.2, 129.7, 126.01 123.2, 119.9 (q, NTf2),
103.0, 55.0, 54.7, 50.4, 34.6, 31.9, 21.5, 20.8, 19.5, 13.2.
3-Butyl-4(5)-(4-hydroxy(tosyloxy)iodobenzoyloxymethyl)-
1-methyl-3H-imidazol-1-ium Triflimide (3). 4-(Diacetoxy-
iodo)benzoate derivative 2 (0.3380 g, 0.4243 mmol) was dissolved
in 500 µL of acetonitrile. To this solution was added 0.0807 g
(0.42430 mmol) of p-toluenesulfonic acid monohydrate in 1 mL
of acetonitrile. After the mixture was stirred for 1 h, the solvent
was removed in vacuo to afford 0.3847 g (100%) of 3 as a pale
yellow, viscous liquid. No further purification was attempted and
this was used in the tosyloxylation reactions as obtained: IR
Experimental
3-Butyl-4(5)-(4-iodobenzoyloxymethyl)-1-methyl-3H-imi-
dazol-1-ium triflimide (4). To a vial containing 0.2590 g of
dried ionic liquid 1 (0.5589 mmol) was added 671 µL of
dichloromethane followed by 117 µL (0.8383 mmol) of triethy-
lamine. The resultant mixture was cooled to -20 °C, followed
by the dropwise addition of a solution of 45 µL (0.5589 mmol) of
4-iodobenzoyl chloride in 112 µL of dichloromethane. The
reaction mixture was left to stir for 30 min and then was
quenched using 5 N NaOH (200 µL) followed by dilution with
dichloromethane (5 mL) and water (2 mL). The aqueous layer
was extracted with dichloromethane (3 × 5 mL). The combined
organic extracts were dried (Na2CO3) and concentrated in vacuo
to afford 0.2892 g (quantitative) of 4 as a orange reddish viscous
thick liquid which crystallized on standing (mp 71-75 °C): IR
(CHCl3) νmax cm-1 3139.2, 3023.0, 2877.4, 1791.7, 1729.9, 1585.6,
1521.1, 1476.7, 1423.2, 1394.8, 1350.0, 1262.0, 1203.5, 1134.0,
1091.4, 1057.7, 1008.9, 996.4, 928.8, 909.7, 848.7, 787.4, 666.8,
625.8; 1H NMR (CDCl3, 360 MHz) δ 8.71 (s, 1H), 7.79 (d, J ) 11
Hz, 2H), 7.68 (d, J ) 11 Hz, 2H), 7.48 (s, 1H), 5.37 (s, 2H), 4.14
(t, J ) 6 Hz, 2H), 3.94 (s, 3H), 1.83 (quint, J ) 6 Hz, 2H), 1.35
(quint, J ) 6 Hz, 2H), 0.93 (t, J ) 6 Hz, 3H); 13C NMR (CDCl3,
90 MHz) δ 165.5, 138.6, 138.3, 137.5, 131.9, 131.3, 124.7, 120.4
(q, JC,F ) 315 Hz, NTf2), 102.2, 54.3, 50.4, 34.5, 32.0, 19.6, 13.4.
3-Butyl-4(5)-(4-iodobenzoyloxymethyl)-1-methyl-3H-imi-
dazol-1-ium Toluene-4-sulfonate (5). To a vial containing
0.2590 g of dried ionic liquid 1 (X - OTs) (0.5589 mmol) was
added 671 µL of dichloromethane followed by 117 µL (0.8383
2876 J. Org. Chem., Vol. 70, No. 7, 2005

(CHCl3) νmax cm-1 3472.0, 3017.7, 2584.9, 2400.0, 1776.7, 1599.9,
ethyl acetate/hexanes (20:80) as eluent to afford 164 mg (67%)
of 2-tosyloxyacetone. Further elution with acetonitrile afford
288.3 mg (40%) of recovered salt 4.
1522.0, 1462.8, 1424.3, 1349.8, 1331.2, 1156.0, 1057.0, 1034.8,
1
1009.2, 928.5, 894.6, 849.6, 793.9, 625.9; H NMR (CDCl3, 360
MHz) δ 8.63 (s, 1H), 8.32 (d, J ) 7 Hz, 2H), 8.21 (d, J ) 7 Hz,
2H), 7.70 (d, J ) 10 Hz, 2H), 7.50 (s, 1H), 7.28 (d, J ) 10 Hz,
2H), 5.49 (s, 2H), 4.15 (t, J ) 7 Hz, 2H), 4.01 (s, 3H), 2.20 (s,
3H), 1.85 (quint, J ) 6 Hz, 2H), 1.35 (quint, J ) 6 Hz, 2H), 0.95
(t, J ) 6 Hz, 3H); 13C NMR (CDCl3, 90 MHz) δ 170.7, 161.6 (q,
43.2 Hz), 145.3, 138.6, 137.2, 135.7, 133.9, 132.0, 130.2, 126.7,
123.7, 114.4 (q, JC,F ) 315 Hz, NTf2), 55.3, 50.7, 34.5, 31.9, 21.5,
19.5, 13.0.
3-Butyl-4(5)-(4-hydroxy(tosyloxy)iodobenzoyloxymethyl)-
1-methyl-3H-imidazol-1-ium 4-methylbenzenesulfonate (7).
4-(Diacetoxyiodo)benzoate derivative 6 (0.2774 g, 0.4028 mmol)
was dissolved in 500 µL of acetonitrile. To this solution was
added 77 mg (0.4028 mmol) of p-toluenesulfonic acid monohy-
drate in 1 mL of acetonitrile. After the mixture was stirred for
1 h, the solvent was removed in vacuo to afford 0.290 g (95%) of
7 as a pale yellow, viscous liquid. No further purification was
attempted, and this was used in the tosyloxylation reactions as
obtained: IR (CHCl3) νmax cm-1 3473.1, 3013.8, 2578.9, 2400.0,
1981.3, 1793.1, 1599.6, 1588.3, 1521.9, 1462.2, 1424.5, 1313.8,
1228.9, 1058.7, 1034.8, 1009.0, 928.2, 895.4, 849.3, 733.1, 626.1;
1H NMR (CDCl3, 360 MHz) δ 8.75 (s, 1H), 8.0-7.3 (m, 13H),
5.40 (s, 2H), 4.16 (t, J ) 6 Hz, 2H), 3.98 (s, 3H), 2.66 (s, 6H),
1.85 (quint, J ) 6 Hz, 2H), 1.35 (quint, J ) 6 Hz, 2H), 0.94 (t, J
) 6 Hz, 3H); 13C NMR (CDCl3, 90 MHz) δ 166.9, 160.3 (q, J )
43.2 Hz), 144.4, 138.4, 137.41, 135.9, 131.2, 130.2, 130.1, 129.9,
127.7, 126.7, 126.6, 123.1, 119.32, 102.8, 54.8, 50.4, 34.6, 31.9,
21.6, 19.5, 13.2.
1-Tosyloxyacetone (toluene-4-sulfonic acid 2-oxopropyl
ester): 1H NMR (CDCl3, 360 MHz) δ 7.77 (d, J ) 6 Hz, 2H),
7.34 (d, J ) 6 Hz, 2H), 4.47 (s, 2H), 2.42 (s, 3H), 2.16 (s, 3H);
13C NMR (CDCl3, 90 MHz) δ201.2, 145.7, 132.4, 130.2, 128.2,
72.2, 26.7, 21.8.
2-Tosyloxycyclopentanone (toluene-4-sulfonic acid 2-oxo-
1
cyclopentyl ester): H NMR (CDCl3) 360 MHz δ 7.84 (d, J )
6 Hz, 2H), 7.35 (d, J ) 6 Hz, 2H), 4.71 (dd, J ) 6 Hz, 10 Hz,
1H), 2.42 (s, 3H), 2.44-1.92 (m, 6H); 13C NMR (CDCl3) δ 209.6,
145.2, 133.5, 130.0, 128.2, 80.4, 34.5, 29.6, 21.8, 17.0.
2-Tosyloxycyclohexanone (toluene-4-sulfonic acid 2-oxo-
1
cyclohexyl ester): H NMR (CDCl3) 360 MHz δ 7.83 (d, 2H),
7.33 (d, 2H), 4.91-4.87 (m, 1H), 2.55-2.27 (m, 3H), 2.43 (s, 3H),
1.99-1.68 (m, 5H); 13C NMR (CDCl3) δ 202.9, 145.1, 133.4, 129.9,
128.1, 82.0, 40.7, 34.8, 27.1, 23.3, 21.8.
Tosyloxyacetophenone (toluene-4-sulfonic acid 2-oxo-
2-phenylethyl ester): 1H NMR (CDCl3, 360 MHz) δ 7.84-7.80
(m, 4H), 7.59 (t, J ) 6 Hz, 1H), 7.44 (t, J ) 6 Hz, 2H), 7.31 (d,
J ) 6 Hz, 2H), 5.26 (s, 2H), 2.42 (s, 3H); 13C NMR (CDCl3, 90
MHz) δ 190.4, 145.4, 134.3, 133.8, 132.6, 130.0, 129.0, 128.2,
128.0, 70.12, 21.8.
2-Tosyloxy-3-pentanone (toluene-4-sulfonic acid 1-meth-
1
yl-2-oxobutyl ester): H NMR (CDCl3, 360 MHz) δ 7.84 (d, J
) 6 Hz, 2H), 7.35 (d, J ) 6 Hz, 2H), 4.71 (q, J ) 6 Hz, 1H), 2.60
(q, 6 Hz, 2H), 2.45 (s, 3H), 1.34 (d, J - 6 Hz, 3H), 1.01 (t, J ) 6
Hz, 3H); 13C NMR (CDCl3, 90 MHz) δ 209.6, 145.2, 133.5, 130.0,
128.2, 80.4, 34.5, 29.6, 21.8, 17.04.
General Procedure for the Tosyloxylation Reaction. To
a chilled solution of 0.3390 g (0.3912 mmol) of supported Koser’s
salt 3 in a dry round-bottom flask under argon was added 660
µL (0.6373 mmol) of cyclohexanone and 3.5 mL of acetonitrile.
The reaction mixture was then stirred for 2 h at 0 °C, during
which time the cloudy reaction mixture became a clear pale
yellow solution. The reaction was quenched by the addition of
20 mL of water followed by extraction with dichloromethane (3
× 15 mL). The combined organic extracts were dried (Na2SO4)
and concentrated in vacuo to yield the crude product mixture.
Purification on silica gel using ethyl acetate/hexanes (20: 80)
as eluent yielded 80 mg (76%) of 2-tosyloxycyclohexanone.
Further elution with acetonitrile afforded 200 mg (75%) of
recovered salt 4.
Procedure for Tosyloxylation Using Sonication. To
0.9232 g (1.0654 mmol) of supported Koser’s salt 3 in a dry
round-bottom flask under argon was added 1.0 mL (13.6157
mmol) of acetone and 5.0 mL of acetonitrile. The flask was then
lowered into an ultrasound cleaning bath filled with warm (55
°C) water to a depth of 2 in.. The reaction mixture was sonicated
for 20 min, during which time the cloudy reaction mixture
cleared into a yellowish-brown solution. The reaction was
quenched by the addition of 20 mL of water followed by
extraction with dichloromethane (3 × 15 mL). The combined
organic extracts were dried (Na2SO4) and concentrated in vacuo
to afford the crude product which was purified on silica gel using
General Procedure Using Tosylate Salt. To a chilled
solution of 0.2996 g (0.3949 mmol) of the tosylate salt 7 in a dry
round-bottom flask under argon was added 660 µL (0.6373
mmol) of cyclohexanone and 3.5 mL of acetonitrile. The reaction
mixture was then stirred for 6 h at 0 °C, during which time the
cloudy reaction mixture became a clear pale yellow solution. The
reaction mixture was then diluted with ether (50 mL) precipitat-
ing the insoluble RTIL-4-iodobenzoate salt 5. Vacuum filtration
and further washing with ether afforded the recovery of 248 mg
(100%) of this salt. The ether washes were then washed with
saturated aqueous NaHCO3 (20 mL) and water (20 mL) to
removed residual toluenesulfonic acid. The organic layer was
then dried with Na2SO4, filtered, and concentrated in vacuo. The
residual crude was triturated with cold hexanes to afford 83 mg
(79%) of 2-tosyloxycyclohexanone.
Acknowledgment. We thank the New York State
Energy Research Development Agency (NYSERDA) and
the Research Foundation for support of this research.
Supporting Information Available: Spectra for salts
2-7 and the R-tosyloxyketone products. This material is
available free of charge via the Internet at http://pubs.acs.org.
JO047807K
J. Org. Chem, Vol. 70, No. 7, 2005 2877