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N. Sun et al. / Tetrahedron 71 (2015) 4835e4841
a catalytic reaction, each pore could be considered as a typical
catalytic nanoreactor, where only the substrate with suitable size
could access these pores, and thus be activated for the reactions.
One of the most important properties of zeolites is the great variety
of topologies and pore architectures, together with the possibility
to adjust their acidity (type, concentration, and strength of acid
sites). As a result, the catalysis activity of zeolites could be tailored
for special chemical transformations. Additionally, their environ-
mentally benign nature, high surface area, and adsorption capacity,
as well as outstanding chemical and thermal stability, make them
ideal candidates for heterogeneous catalysis. Due to our continuous
interests in this area,10 we herein reported the first zeolite-
catalyzed intramolecular cyclization of 2-aryloxyacetaldehyde ac-
etals for the preparation of 2,3-unsubstituted benzo[b]furans.
the same as that of H-
improved to 93e96% (entries 5e8, Table 1). In particular, under the
catalysis of zeolite Sn- , the yield of benzo[b]furan 2a reached to
96% (entry 7, Table 1). With the Ga- zeolite as catalyst, moderate
yield improvement was observed (84%), and a relatively longer
reaction time (0.75 h) was needed for the completion of reaction
b, while the yields of 2a were significantly
b
b
(entry 9, Table 1). By contrast, In-
slower reaction rate, but also a lower selectivity than the parent H-
(entry 10, Table 1). Since Sn- zeolite exhibited best catalysis
b zeolite showed not only a much
b
b
performance in this transformation, it was selected as catalyst for
our further research.
Then, we tried to demonstrate the generality of Sn-b zeolite for
the synthesis of functionalized 2,3-unsubstituted benzo[b]furans
via the intramolecular cyclization of 2-aryloxyacetaldehyde acetals.
As shown in Table 2, a wide range of 2-aryloxyacetaldehyde diethyl
acetals 1ae1o can be smoothly converted to their corresponding
2,3-unsubstituted benzo[b]furans 2ae2o in the presence of Sn-
2. Results and discussion
b
zeolite catalyst. However, the reaction rate and selectivity were
Using the conversion of 2-phenyloxyacetaldehyde diethyl acetal
(1a) to benzo[b]furan (2a) as a model reaction, we initiated our
work by testing the catalytic activity of various commercially
remarkably dependent on the electronic property and position of
the substitute bearing on the substrates. Under identified reaction
conditions, the substrates 1be1f bearing electron-donating groups
(OMe, Me, t-Bu, Ph, and ethoxy-substituted naphthalenyl) at para-
position exhibited similar reactivity as non-substituted 1a, and the
corresponding cyclization products 2be2f were obtained in
86e95% yield. Noteworthy, substituents (t-Bu and Ph) with mod-
erate size showed no effects on both reaction rate and selectivity,
available zeolites, including H-ZSM-5, H-b
, and H-Y.11 The reaction
was also carried out in the absence of catalyst. The results are
summarized in Table 1. Without catalyst, the substrate 1a was inert
even after refluxing in trifluorotoluene for 6 h (entry 1, Table 1). The
reaction proceeded smoothly in the presence of each one of the
zeolites H-ZSM-5, H-b or H-Y, and the cyclization product benzo[b]
indicating that the pore size of zeolite Sn-b was large enough to
furan 2a was produced in moderate yields (58e77%) based on GC
accommodate these molecules. However, much larger substituent
(6-ethoxynaphthalen-2-yl) led to lower reaction rate, which was
ascribed to its much slower diffusion rate in the pores of zeolite Sn-
analysis (entries 2e4, Table 1). Zeolite H-
b
exhibited better catalytic
zeolite as catalyst and in
activity than H-Y and H-ZSM-5. With H-
b
refluxing trifluorotoluene, substrate 1a could be completely con-
verted in 0.5 h and benzo[b]furan 2a was obtained in 77% yield
b. Nevertheless, the corresponding cyclization product 2f could still
be obtained in 88% yield. Both the reaction rate and yield were
dramatically affected by the electron-withdrawing groups attached
on the substrates. For instance, the substrates 1ge1j, bearing F, Cl,
Br, and ethoxycarboxyl group at para-position, exhibited slower
reaction rate (1.5e4 h) and lower product yield (71e82%). As for
substrate 1k, bearing two chloro groups on the 2 and 4-positions of
phenyl ring, it took 10 h for the complete conversion, and the cy-
clization product 2k was obtained in only 30% yield. The substrates
with strong electron-withdrawing groups (such as CN and NO2) in
phenyl ring could not afford the desired cyclization products. The
above results were consistent with the basic electronic effect of
FriedeleCrafts type reactions. It was noteworthy to point out that
the main by-products detected by GCeMS in the reaction of those
electron-deficient substrates were phenols, which undoubtedly
resulted from the decomposition of these substrates under the
reaction conditions. We are convinced that this competitive de-
composition side-reaction led to the decreased yields of these 2,3-
unsubstituted benzo[b]furans. Moreover, the cyclization reaction
rate was also affected by the position of substituent on the phenyl
ring. The substrates 1l and 1m bearing substituent at ortho-position
required relatively longer reaction time than their analogs (1b and
1h) with substituent at para-position. But the yields of 2l and 2m
were similar with those of 2b and 2h. In addition, under the ca-
(entry 4, Table 1). The better performance of H-b zeolite on this
FriedeleCrafts type reaction could be attributed to its higher con-
centration of Bronsted acid sites and special three-dimensional
large size porous structure.12 Unfortunately, with H-
b zeolite as
catalyst, simply optimizing the reaction conditions, such as the
solvent, reaction temperature, and the amount of catalyst, could not
further improve the selectivity. Next, we turned our efforts to the
metal-exchanged H-
and In-
13 The various salts of these metal ions are widely used as
Lewis acid catalyst in numerous acid-promoted organic trans-
formations. To our delight, the zeolites Fe- , Zn- , Sn- , and Zr-
exhibited significantly better catalysis performance than parent
b zeolites, such as Fe-b, Zn-b, Sn-b, Zr-b, Ga-b,
b
.
b
b
b
b
H-b. With each one of these metal-exchanged zeolites as catalyst,
and under the identified reaction conditions, the reaction rate was
Table 1
The cyclization of 2-phenyloxyacetaldehyde diethyl acetal under the catalysis of
different kinds of zeolitesa
Entry
Catalyst
T (h)
Conv.b (%)
Yieldb (%)
talysis of Sn-b, the 2,3-unsubstituted benzo[b]furans with multiple
1
2
3
4
5
6
7
8
9
10
None
H-ZSM-5
H-Y
6
6
2
0.5
0.5
0.5
0.5
0.5
0.75
1
d
d
substituents on phenyl ring and fused ring could also be prepared
in excellent yields (2n and 2o). The isolation yields of benzo[b]furan
2a and 5-flourobenzo[b]furan 2g were much lower than their GC
assay yields due to their highly volatile character.
Considering that shape selectivity is a distinctive property of
zeolites over other acid catalysts, we furthermore studied the cy-
clization reactions of meta-substituted 2-aryloxyacetaldehyde
>99
>99
>99
>99
>99
>99
>99
>99
>99
75
58
77
93
92
96
93
84
52
H-
Fe-
Zn-
Sn-
Zr-
Ga-
In-
b
b
b
b
b
b
b
diethyl acetals under the catalysis of Sn-b zeolite, and the results
were listed in Table 3. Under the identified reaction conditions, the
substrates (1pe1t) bearing OMe, Me, Ph, Cl, and Br groups at meta-
position exhibited similar reactivity as their para-substituted
a
Reaction conditions: 1a (1 mmol), catalyst (0.10 g), and trifluorotoluene (10 mL)
at refluxing temperature.
b
GC yields by internal standard method with naphthalene as internal standard.