[Bmim]PF6: A novel and recyclable ionic liquid for conversion of oxiranes to thiiranes in aqueous media

Article abstract of DOI:10.1021/jo026544w

A variety of epoxides respond rapidly with potassium thiocyanate in [bmim]PF₆-H₂O (2:1) solvent system at room temperature under mild and convenient conditions to produce the corresponding thiiranes in high to quantitative yields. Enhanced rates, improved yields, and recyclability of ionic liquids are the remarkable features observed in ionic liquids (ILs). The use of ionic liquids for this transformation avoids the use of heavy metal halides as promoters and chlorinated hydrocarbons as solvents. The ionic liquid was recycled in five to six subsequent runs with gradual decrease in activity.

Full text of DOI:10.1021/jo026544w

SCHEME 1
[Bm im ]P F 6: A Novel a n d Recycla ble Ion ic
Liqu id for Con ver sion of Oxir a n es to
Th iir a n es in Aqu eou s Med ia
J . S. Yadav,* B. V. S. Reddy, Ch. Srinivas Reddy, and
K. Rajasekhar
and also entail undesirable side reactions due to the
rearrangement or polymerization of oxiranes, resulting
in low yields of thiiranes especially in case of cyclohexene
episulfide, styrene episulfide, and other higher thiiranes.
Furthermore, most of these methods are of limited
synthetic scope when applied to multifunctional com-
pounds. Since organic sulfur compounds have become
increasingly useful and important in organic synthesis,
the development of convenient and practical methods for
the preparation of thiiranes, especially those that carry
acid-labile functional groups, are desirable.
The toxic and volatile nature of many organic solvents,
particularly chlorinated hydrocarbons, that are widely
used in organic synthesis have posed a serious threat to
the environment. Consequently methods that successfully
minimize their use are the focus of much attention. In
this respect, ionic liquids are attracting growing interest
as alternative reaction media for various chemical and
biotransformations.8 Ionic liquids have emerged as a set
of green solvents with unique properties such as tunable
polarity, high thermal stability, immiscibility with a
number of organic solvents, negligible vapor pressure,
and recyclability. Their high polarity and ability to
solubilize both inorganic and organic compounds can
result in enhanced rates of chemical processes and can
provide higher selectivities compared to conventional
solvents. Room temperature ionic liquids, especially those
based on the 1-n-alkyl-3-methylimidazolium cation, have
shown great promise as an attractive alternative to
conventional solvents. One of several advantages of ionic
liquids is that they are environmentally benign since they
have no detectable vapor pressure. As a result of their
green credentials and potential to enhance rates and
selectivities, ionic liquids are finding increasing applica-
tions in organic synthesis.9,10 Furthermore, there are no
examples on the use of ionic liquids for the conversion of
epoxides to episulfides.
Division of Organic Chemistry, Indian Institute of Chemical
Technology, Hyderabad-500 007, India
yadav@iict.ap.nic.in
Received October 9, 2002
Abstr a ct: A variety of epoxides respond rapidly with
potassium thiocyanate in [bmim]PF6-H2O (2:1) solvent
system at room temperature under mild and convenient
conditions to produce the corresponding thiiranes in high
to quantitative yields. Enhanced rates, improved yields, and
recyclability of ionic liquids are the remarkable features
observed in ionic liquids (ILs). The use of ionic liquids for
this transformation avoids the use of heavy metal halides
as promoters and chlorinated hydrocarbons as solvents. The
ionic liquid was recycled in five to six subsequent runs with
gradual decrease in activity.
Epoxides are well-known carbon electrophiles capable
of reacting with various nucleophiles, and their ability
to undergo regioselective ring-opening reactions contrib-
utes largely to their synthetic value.1 The epoxide ring
opening with certain nucleophiles is generally carried out
using either acid or base catalysis to produce ring-opened
products. A variety of methods have been developed for
the preparation of thiiranes.2 One of the most straight-
forward synthetic procedures for the preparation of
thiiranes is the condensation of oxiranes with inorganic
thiocyanates such as potassium and ammonium thiocy-
anates3 or thiourea in water or in aqueous alcohols.4
Potassium thiocyanate has been the most widely used
reagent for this transformation. Other reagents such as
phosphine sulfide,5 3-methylbenzothiazol-2-thione,6 and
dimethylthioformamide7 in the presence of trifluoroacetic
acid have been reported to produce thiiranes from ox-
iranes. However, many of these methods often involve
the use of strongly acidic or oxidizing conditions, extended
reaction times, and high-temperature reaction conditions
We herein report the use of ionic liquids for the
synthesis of episulfides from oxiranes and potassium
thiocyanate under mild and neutral conditions. Initially,
we have carried out the experiment with 2-phenoxy-
methyloxirane and potassium thiocyanate for 2 h in
1-butyl-3-methylimidazolium hexafluorophosphate-wa-
ter (2:1) solvent system to afford the corresponding
episulfide in 95% yield (Scheme 1). The product was
obtained after simple extraction with ether. The remain-
ing ionic liquid was further washed with ether and
recycled in subsequent runs without further purification.
These results prompted us to extend this process for
* To whom correspondence should be addressed. Fax: 91-40-
27160512.
(1) (a) Bonini, C.; Righi, G. Synthesis 1994, 225. (b) Shimizu, M.;
Yoshida, A.; Fujisawa, T. Synlett 1992, 204. (c) Smith, J . G. Synthesis
1984, 629.
(2) (a) Sander, M. Chem. Rev. 1966, 66, 297. (b) Vedejs, E.; Krafft,
G. A. Tetrahedron 1982, 38, 2857.
(3) (a) J ankowski, K.; Harvey, R. Synthesis 1972, 627. (b) Iranpoor,
N.; Kazemi, F. Synthesis 1996, 821. (c) Tamami, B.; Kiasat, A. R. Synth.
Commun. 1996, 26, 3953. (d) Brimeyer, M. O.; Mehrota, A.; Quici, S.;
Nigam, A.; Regen, S. L. J . Org. Chem. 1980, 45, 4254. (e) Sharghi, H.;
Nasseri, M. A.; Niknam, K. J . Org. Chem. 2001, 66, 7287.
(4) Doyle, F. P.; Holland, D. O.; Hunter, W. H.; Mayer, J . H. C.;
Queen, A. J . J . Chem. Soc. 1960, 2665.
(5) Chan, T. H.; Finkenbine, J . R. J . Am. Chem. Soc. 1972, 2880.
(6) Calo, V.; Lopez, L.; Marchese, L.; Pesce, G. J . Chem. Soc., Chem.
Commun. 1975, 62. (b) Cambie, R. C.; Mayer, G. D.; Rutledge, P. S.;
Woodgate, P. D. J . Chem. Soc., Perkin Trans. 1 1975, 52.
(7) Takido, T.; Kobayashi, Y.; Itabashi, K. Synthesis 1986, 779.
(8) (a) Welton, T. Chem. Rev. 1999, 99, 2071. (b) Wasserscheid, P.;
Keim, W. Angew. Chem., Int. Ed. 2000, 39, 3772.
(9) Sheldon, R. J . Chem. Soc., Chem. Commun. 2001, 2399.
(10) (a) Wheeler, C.; West, K. N.; Liotta, C. L.; Eckert, C. A. J . Chem.
Soc., Chem. Commun. 2001, 887. (b) Peng, J .; Deng, Y. Tetrahedron
Lett. 2001, 42, 5917. (c) Cole, A. C.; J ensen, J . L.; Ntai, I.; Tran, K. L.
T.; Weaver, K. J .; Forbes, D. C.; Davis, J . H., J r. J . Am. Chem. Soc.
2002, 124, 5962.
10.1021/jo026544w CCC: $25.00 © 2003 American Chemical Society
Published on Web 02/21/2003
J . Org. Chem. 2003, 68, 2525-2527
2525

SCHEME 2
efficiency of various quaternary ammonium salts was
tested. The reactions, however, did not take place at room
temperature either in n-tetrabutylammonium chloride
and water (2:1) or in 1-n-butyl-3-methylimidazolium
chloride and water (2:1) solvent system; they proceeded
at 85 °C under thermal conditions. The lowering of the
reaction temperature was detrimental to the efficiency
of this procedure. Furthermore, the epoxides did not react
with water to produce vic-diols under these reaction
conditions. The purity of the ionic liquids was determined
by comparing their 1H NMR spectra with commercial
samples obtained from Fluka. The purity of [bmim]PF6
ionic liquid is g97.0% (NMR). Although ionic liquids are
expensive commercially, they can easily be prepared from
an inexpensive and readily available N-methyl imidazole,
1-chlorobutane, and hexafluorophosphoric acid or sodium
tetrafluroborate.
In this paper, [bmim]PF6-H2O or [bmim]BF4-H2O
solvent system was proved to be a useful and alternative
reaction medium for the synthesis of episulfides from
epoxides, avoiding the use of environmentally unfavor-
able volatile chlorinated hydrocarbons by playing a dual
role of solvent as well as catalyst. The substrates show
significant increase in reactivity, reducing the reaction
times and improving the yields substantially. The simple
experimental and product isolation procedures combined
with ease of recovery and reuse of this novel reaction
media is expected to contribute to the development of
green strategy for the preparation of episulfides from
epoxides. The use of ionic liquids as reaction media for
this transformation avoids the use of moisture-sensitive
and heavy metal Lewis acids and also eliminates routine
aqueous workup procedures for the isolation of products.
various epoxides. Interestingly, aryl, alkyl, and sterically
hindered epoxides reacted smoothly with potassium
thiocyanate under these reaction conditions to produce
corresponding thiiranes in excellent yields. Similarly,
cycloalkyl oxiranes such cyclopentyl, cyclohexyl, and
cyclooctyl oxiranes were converted into the corresponding
cycloalkyl thiiranes in high to quantitative yields by
using this procedure (Scheme 2). The reaction conditions
are mild enough not to induce isomerization of C-C
multiple bonds during the preparation of thiiranes bear-
ing allylic and propagylic functionalities and are selective
enough to convert oxiranes to thiiranes in the presence
of acid-sensitive groups, which are difficult to achieve
under conventional conditions where protic acids such
as trifluoroacetic acid or strong Lewis acids are employed.
Moreover, the reactions are clean and high yielding while
no side products or decomposition of the products are
observed. Ammonium thiocyanate also works equally well
for this conversion. The scope and generality of this
process is illustrated with respect to various epoxides and
potassium thiocyanate, and the results are presented in
the Table 1. Compared to conventional methods, en-
hanced reaction rates, improved yields, and high selectiv-
ity are the remarkable features observed in these ionic
liquids. However, in the absence of either ionic liquid or
water, the reaction did not yield any product even after
a long reaction time. Addition of 1 equiv of water
dramatically improved the reaction rates as well as
yields. This is probably due to the higher solubility of
potassium thiocyanate in water. The solubility of potas-
sium thiocyanate in ionic liquid is very poor, and hence
the addition of water increases the solubility of potassium
thiocyanate. The reaction, however, was unsuccessful in
water alone. Thus, the combination of ionic liquid and
water was found to be an efficient reaction media for this
transformation. Furthermore, we have performed the
reactions in DMF/H2O and HPF6/H2O solvent systems
to compare the efficiency of ionic liquids. Although, the
reactions did not occur in DMF/H2O solvent system even
under heating conditions, they worked well in HPF6/H2O
solvent system to produce thiiranes. In this reaction, the
efficiency of the ionic liquid was strongly influenced by
the nature of the anion. The reactions of various epoxides
with thiocyanates were examined in hydrophilic [bmim]-
BF4 and hydrophobic [bmim]PF6 ionic liquids. Among
these ionic liquids, [bmim]PF6 was found to be superior
in terms of conversion. Since the ionic liquids were
insoluble in diethyl ether, the products were easily
isolated by simple extraction with ether. The rest of the
ionic liquid was further washed with diethyl ether and
recycled in five to six subsequent runs with gradual
decrease in activity. For example, the treatment of
styrene oxide with potassium thiocyanate in [bmim]PF6
ionic liquid afforded 2-phenylthiirane in 93%, 89%, 85%,
81%, and 78% yields over five cycles.11 Even though yields
were gradually decreased in runs carried out using
recovered ionic liquid, the products obtained were of the
same purity as in the first run. In further reactions, the
Exp er im en ta l Section
Gen er a l Meth od s. Melting points are uncorrected. TLC was
performed using precoated silica gel 60 F254 (0.25 mm) glass
plates. Chromatography was performed using silica gel (100-
200 mesh). IR spectra were recorded neat on a refractive
spectrophotometer. 1H NMR spectra were recorded in CDCl3 at
200 MHz. Chemical shifts are given in ppm with respect to
internal TMS, and J values are quoted in Hz. Mass spectra were
recorded at 70 eV. Epoxides were either purchased commercially
or synthesized as reported in the literature.12 1-Butyl-3-meth-
ylimidazolium tetrafluoroborate ([bmim]BF4) and 1-butyl-3-
methylimidazolium hexafluorophosphate ([bmim]PF6) ionic liq-
uids were prepared according to the procedures reported
previously in the literature.13
Gen er al P r ocedu r e for Con ver sion of Epoxide to Episu l-
fid e. Epoxide (1 mmol) and potassium thiocyanate (1 mmol) in
1-butyl-3-methylimidazolium hexafluorophosphate (2 mL) and
water (1 mL) were stirred at room temperature for an appropri-
ate time (see Table 1). After completion of the reaction, as
indicated by TLC, the reaction mixture was washed with diethyl
ether (3 × 10 mL). The combined ether extracts were concen-
(11) The continual reuse of [bmim]BF4 and [bmim]PF6 ionic liquids
may cause the liberation of most hazardous HF. Therefore, these BF4
and PF6 ionic liquids should be recycled with the utmost care. After
three to four subsequent runs, the ionic liquid was diluted with water
and extracted with ethyl acetate and the extracts were dried at 80 °C
under reduced pressure for reuse in further reactions.
(12) (a) Moreau, S. P.; Morissseau, C.; Zylber, J .; Archelas, A.;
Baratti, J .; Furstoss, R. J . Org. Chem. 1996, 61, 7402. (b) Stephenson,
O. J . Chem. Soc. 1954, 1571.
(13) Preparation of ionic liquids: (a) Park, S.; Kazlauskas, R. J . J .
Org. Chem. 2001, 66, 8395. (b) BonhOte, P.; Dias, A. P.; Papageorgiou,
N.; Kalyanasundaram, K.; Gratzel, M. Inorg. Chem. 1996, 35, 1168.
2526 J . Org. Chem., Vol. 68, No. 6, 2003

TABLE 1. Con ver sion of Oxir a n es to Th iir a n es in 1-Bu tyl-3-m eth ylim id a zoliu m Ion ic Liqu id s
a
b
All products were reported previsiously in the literature.14 Conversions were determined by GC analysis. c Yield refers to the isolated
pure products after column chromatography.
trated in vacuo, and the resulting product was directly charged
on a small silica gel column and eluted with a mixture of ethyl
acetate and n-hexane (2:8) to afford pure episulfide. The rest of
the ionic liquid was further washed with ether and recycled in
subsequent runs. The products were characterized by compari-
son of their NMR, IR, MS, TLC, mixed TLC analysis, and
physical data with authentic samples. The spectral data of all
products other than 2n were identical with those of authentic
samples.14 Spectroscopic data for the product 2-phenylcarbonyl-
oxymethylthiirane (2n ): liquid; IR (KBr) ν 2927, 1720, 1606,
68.8, 128.4, 129.8, 133.1, 165.9; EIMS m/z 194 M+, 170, 154,
139, 133, 117, 103, 80, 69, 56, 44. Anal. Calcd for C10H10O2S
(194.25): C, 61.83; H, 5.19; S, 16.50. Found: C, 61.85; H, 5.20;
S, 16.51.
Ack n ow led gm en t. B.V.S. and Ch.S.R. thank CSIR
New Delhi for the award of fellowships.
J O026544W
1450, 1316, 1271, 1160, 1109, 1027, 711 cm-1 1H NMR (200
;
(14) (a) Takido, T.; Kobayashi, Y.; Itabashi, K. Synthesis 1986, 779.
(b) Brimeyer, M. O.; Mehrota, A.; Quici, S.; Nigam, A.; Regen, S. L. J .
Org. Chem. 1980, 45, 4254. (c) Iranpoor, N.; Kazemi, F. Synthesis 1996,
821.
MHz, CDCl3) δ 2.38 (d, 1H, J ) 6.5 Hz), 2.58 (d, 1H, J ) 6.5
Hz), 3.20-3.29 (m, 1H), 4.29-4.50 (m, 2H), 7.40-7.60 (m, 3H),
8.10 (d, 2H, J ) 8.0 Hz); 13C NMR (50 MHz, CDCl3) δ 23.8, 30.8,
J . Org. Chem, Vol. 68, No. 6, 2003 2527