Novel hydrophobic Bronsted acidic ionic-liquids as efficient and reusable catalysts for organic reactions in water

Article abstract of DOI:10.1246/cl.2006.1176

Novel Hydrophobic Bronsted acidic ionic liquids (HBAIL) were prepared and utilized as acid catalysts in organic reactions in water. HBAILs were demonstrated, for the first time, to be effective catalysts for Prins cyclization of styrene derivatives in water with a formaldehyde water solution. Many styrene derivatives could be successfully converted to the corresponding 1,3-dioxanes. Other dehydration reactions also proceeded well using HBAILs in water. After reactions, HBAILs could be easily recovered and reused without significant loss of activity. Copyright

Full text of DOI:10.1246/cl.2006.1176

1176
Chemistry Letters Vol.35, No.10 (2006)
Novel Hydrophobic Brønsted Acidic Ionic-liquids as Efficient
and Reusable Catalysts for Organic Reactions in Water
Yanlong Gu, Chikako Ogawa, and Shu¯ Kobayashiꢀ
Graduate School of Pharmaceutical Sciences, The University of Tokyo,
The HFRE Division, ERATO, Japan Science and Technology Agency (JST), Hongo, Bunkyo-ku, Tokyo 113-0033
(Received August 11, 2006; CL-060927; E-mail: skobayas@mol.f.u-tokyo.ac.jp)
Novel hydrophobic Brønsted acidic ionic liquids (HBAIL)
were prepared and utilized as acid catalysts in organic reactions
in water. HBAILs were demonstrated, for the first time, to be
effective catalysts for Prins cyclization of styrene derivatives
in water with a formaldehyde water solution. Many styrene de-
rivatives could be successfully converted to the corresponding
1,3-dioxanes. Other dehydration reactions also proceeded well
using HBAILs in water. After reactions, HBAILs could be easily
recovered and reused without significant loss of activity.
O
S
O
Neat condition
-
Oct3N
1a: n = 1
2a: n = 2
+
Oct3N
SO3
O
130 °C, 24 h
n
n
-
HNTf2
NTf2
Oct3N
SO3H 1b: n = 1
2b: n = 2
H2O, 80 °C
n
Scheme 1. Preparation of HBAILs.
nesultone were allowed to react with trioctylamine to prepare
sulfobetaines 1a and 2a. The sulfobetaines obtained were then
treated with trifluoromethanesulfonimide in water to afford hy-
drophobic products 1b and 2b. The compounds 1a, 2a, 1b, and
2b were well characterized by IR, 1H and 13C NMR and HRMS
(see Supporting Information).10 Compounds 1b (H0 = 1.23,
1 mmol/L in dichloromethane) and 2b (H0 = 1.27, 1 mmol/L
in dichloromethane) are highly viscous liquid at room tempera-
ture, and are stable to air and moisture. Solubility investigation
revealed that they are not soluble in water and hexane, but
dissolve in ethyl acetate. It should be noted that increases the
length of the alkyl group on the nitrogen atom from eight to
twelve carbon atoms suppressed the second step reaction, treat-
ment of sulfobetaine with trifluoromethanesulfonimide in water.
With the hydrophobic Brønsted acidic ionic liquids in hand,
some acid-catalyzed reactions were investigated in water. First,
we examined the activities of HBAILs in the Prins cyclization
reaction, which is an important carbon–carbon bond-forming re-
action and widely used in organic synthesis.6,7 Although there
have been many reports on the use of Lewis and Brønsted acids
as catalysts for this reaction, most of them include the use of
paraformaldehyde as a formaldehyde source, which is slowly
soluble in water. To dissolve paraformaldehyde, organic sol-
vents were consequently used in the reaction.8 From economical
and environmental points of view, an aqueous formaldehyde so-
lution should be a better substrate. However, only a few mineral
acids can work in water, and yields obtained are still far from sat-
isfactory (<60%).9 Thus, we decided to use an aqueous formal-
dehyde solution to investigate the Prins cyclization of styrene us-
ing HBAIL. Traditional mineral and organic aromatic sulfonic
acids were also examined to compare their efficiency of these
catalysts. A typical reaction of styrene with formaldehyde at
75 ꢁC using traditional acids such as H2SO4, H3PO4, HCl, and
TsOH showed low yields (<30%) even after 24 h (Table 1).
To our great delight, the reaction took place smoothly in the
presence of 10 mol % of 1b and 2b to afford 4-phenyl-1,3-diox-
ane in 92 and 95% yields after 12 h. The reaction also proceeded
well using DBSA (dodecylbenzenesulfonic acid) in water. An
advantage of HBAIL is the ease with which it can be recovered
and reused. With HBAIL 2b, the ionic liquid catalyst could be
easily recovered by removal of water after extraction of the
product with hexane. The recovered 2b showed an unchanged
Organic reactions in water without the use of any harmful
organic solvents are of great current interest, because water is
an easily available, economical, safe, and environmentally be-
nign solvent.1 Although various catalysts have been developed
to realize organic transformations in water, it is still difficult to
achieve recovery and reuse of the catalysts in many cases.
Brønsted acid catalysts are widely utilized in organic synthesis,
however, traditional Brønsted acid catalysts are hydrophilic and
generally less active for organic reactions in water because of the
fact that most substrates are not soluble in water. Recently, we
have addressed this issue by constructing hydrophobic reaction
environments in water utilizing surfactant-type Brønsted acid2
or styrene-based hydrophobic polymer-supported sulfonic acid
catalysts.3 In these cases, however, substrate scope is rather
limited for hydrophobic substrates, and the efficiency of reuse
of catalysts are not yet satisfactory.
Ionic liquids constitute a class of solvent entirely composed
of ions. Their use as an environmentally friendly alternative for
conventional solvents has received much attention recently.4
Our specific interest in ionic liquids centers on their designabil-
ity, which allows easy manipulate of their structure and their
properties. As a typical example of functionalized ionic liquids,
non-chloroaluminate acidic ionic liquids have exhibited great
potential in replacement of conventional homogeneous and het-
erogeneous acidic catalysts, because they are air- and moisture-
stable, less volatile and non-corrosive.5 However, non-chloro-
aluminate acidic ionic liquids developed to date are all hydro-
philic despite the fact that hydrophobic non-functionalized ionic
liquids have been widely used in some processes. In the course
of our investigations to develop efficient catalysts in water, we
reasoned that hydrophobic Brønsted acidic ionic liquids might
act as hydrophobic acid catalysts in water. Herein, we describe
a novel hydrophobic Brønsted acidic ionic liquid catalyst
(HBAIL), which works very efficiently in several acid-catalyzed
organic reactions in water. In contract to our previous systems,
HBAIL can work well for reactions with hydrophilic substrates
in water.
The structures and the synthetic procedures of two HBAILs
are shown in Scheme 1. First, 1,3-propanesultone and 1,4-buta-
Copyright Ó 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.10 (2006)
1177
Table 1. Screening of catalyst for Prins cyclization of styrene
in water
OMe
NH
O
OMe
NH2
HBAIL 2b (15 mol %)
H2O, 25 °C, 4 h
O
PhCHO
+
+
Entry
Catalyst
Time/h
Yield/%
Ph
1
2
3
4
5
6
7
8aÞ
H2SO4
H3PO4
HCl
TsOH
1b
2b
24
24
24
24
12
12
12
12
23
trace
11
trace
92
95
82
95
93% yield, syn/anti = 44/66
OMe
OH
HBAIL 2b (10 mol %)
H2O, 90 °C, 24 h
Ph
Ph
Ph
+ MeOH
OH
O
O
80% yield
Ph O
OH
HBAIL 2b (10 mol %)
H2O, 75 °C, 24 h
+
Ph
Ph 84% yield
DBSA
2b
Scheme 2. Dehydrative reactions over HBAIL system in water.
aThe catalyst was reused in the second run.10
for Prins cyclization of styrene derivatives in water using an
aqueous formaldehyde solution. Many styrene derivatives can
be successfully converted to the corresponding 1,3-dioxanes in
water. Some other dehydrative reactions in water also proceeded
well using HBAIL systems. In addition, HBAIL could be easily
recovered after reactions and reused in the next run without loss
of activity.
Table 2. Substrate scope for Prins cyclization
O
O
2b, 10 mol %
+
2 HCHO
Ar
Ar
H2O
Entry
1
Styrene
Temp./°C
Time/h
12
Yield/%
93
References and Notes
75
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3
4
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60
12
12
81
94
Cl
MeO
2
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4
activity in the Prins cyclization of styrene with an aqueous
formaldehyde solution. DBSA is soluble in hexane, and it would
be leached into organic phase during the extraction.
Many styrene derivatives can be used in this Prins cycliza-
tion, and good to excellent yields were obtained as shown in
Table 2. For highly active substrates, such as 4-methoxystyrene
and indene, lower temperature was better for the formation of the
desired Prins cyclization products, as high temperatures caused
polymerization of the olefins. When the ꢀ-position of styrene
was substituted by one or two methyl groups, the yield of the
reaction decreases presumably due to steric hindrance.
We then tested some dehydrative reactions with HBAIL in
water. As shown in Scheme 2, the direct three-component Man-
nich reaction of benzaldehyde, o-anisidine, and cyclohexanone
proceeded smoothly in water in the presence of a catalytic
amount of HBAIL 2b. 6-Phenylhexaoic acid was esterified by
methanol in water in 80% yield using HBAIL 2b. Etherification
reaction between benzhydrol and n-butanol also proceeded well
with HBAIL 2b in water. These results demonstrate that HBAIL
can be widely used as a Brønsted acid catalyst in many acid-
catalyzed reactions in water.
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10 Supporting Information is available electronically on the
In summary, novel hydrophobic Brønsted acidic ionic
liquids (HBAIL) have been developed and utilized as acid
catalysts in organic reactions in water. Furthermore, HBAILs
were demonstrated for the first time to be effective catalysts
CSJ-Journal web site, http://www.csj/jounals/chem-lett.
Published on the web (Advance View) September 16, 2006; doi:10.1246/cl.2006.1176