Direct synthesis of unsymmetrical ethers from alcohols catalyzed by titanium cation-exchanged montmorillonite

Article abstract of DOI:10.1039/c2gc16135d

Titanium-exchanged montmorillonite (Ti⁴⁺-mont) was found to act as an efficient heterogeneous catalyst for the etherification of a wide range of alcohols under mild reaction conditions. Ti⁴⁺-mont was reusable with retention of high efficiency and applicable to scale-up reaction conditions. The Royal Society of Chemistry 2012.

Full text of DOI:10.1039/c2gc16135d

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COMMUNICATION
Direct synthesis of unsymmetrical ethers from alcohols catalyzed by titanium
cation-exchanged montmorillonite†
Takato Mitsudome,a Tsuyoshi Matsuno,a Shoichiro Sueoka,a Tomoo Mizugaki,a Koichiro Jitsukawaa and
Kiyotomi Kaneda*a,b
Received 10th September 2011, Accepted 11th December 2011
DOI: 10.1039/c2gc16135d
Titanium-exchanged montmorillonite (Ti4+-mont) was found
catalytic activity for the acetalization of carbonyl compounds,
the deprotection of acetals and the esterification of carboxylic
acids.5 Herein, Ti4+-mont was also found to be effective as a reu-
sable catalyst in the direct synthesis of unsymmetrical ethers
from different classes of alcohols under mild reaction conditions.
This catalyst system provided several improvements over
reported solid acids in the scope of substrates and reaction
temperatures.
to act as an efficient heterogeneous catalyst for the etherifica-
tion of a wide range of alcohols under mild reaction con-
ditions. Ti4+-mont was reusable with retention of high
efficiency and applicable to scale-up reaction conditions.
Ethers are essential compounds in organic chemistry, serving as
solvents and important precursors for polymers and fragrances.1
The Williamson ether synthesis has been widely used for the
preparation of symmetrical and unsymmetrical ethers.2 However,
this method generally requires the preparation of organohalides
by the treatment of alcohols with environmentally harmful phos-
phorous halides, followed by their substitution with alkoxides
under strong basic conditions, which results in the generation of
large amounts of waste. Alternatively, the direct synthesis of
ethers through dehydrative etherification of alcohols has attracted
much attention because of its advantages, such as easy work-up
procedures, low costs and the formation of water as the only by-
product.3,4 Many homogeneous catalysts such as Brønsted acid
or Lewis acid based transition metals have been reported in the
etherification of alcohols.3 However, these systems have some
drawbacks including their deactivation through the decompo-
sition by water formed during the reaction, the necessity of neu-
tralization after the reaction, and difficulties in catalyst recovery
and reuse. Heterogeneous catalysts have been developed to over-
come these problems, but the reported heterogeneous catalysts
have been mostly applied to the synthesis of symmetrical ethers,
and heterogeneous catalysts for the synthesis of unsymmetrical
ethers are still rare.4 Therefore, the direct synthesis of a wide
range of unsymmetrical ethers derived from various combi-
nations of alcohols using heterogeneous catalysts is still a
challenge.
Ti4+-mont was prepared according to our previous report.5a
The loading of Ti in Ti4+-mont was 3.25 wt% from elemental
analysis. A mixture of p-methoxybenzyl alcohol (1a) and n-
butanol (2a) was stirred in the presence of Ti4+-mont at 30 °C in
an Ar atmosphere for 4 h. 1a was converted to the desired
unsymmetrical ether 3a in 90% yield with >99% selectivity
without the production of symmetric ethers. Among the various
acid catalysts tested, Ti4+-mont showed the highest catalytic
activity. Commercially available acid catalysts of montmorillo-
nite K-10, H-USY and H-Y resulted in low yields of 3a (Table 1,
entries 2–4), and other solid acids and a homogeneous Brønsted
acid of p-toluenesulfonic acid barely worked as catalysts
(Table 1, entries 5–8). The use of parent Na+-mont in place of
Ti4+-mont did not promote the etherification, suggesting that the
titanium species within layers of the montmorillonite was an
active Brønsted acid species (Table 1, entry 9).6 At 50%
Table 1 Etherification of p-methoxybenzyl alcohol and n-butanola
Entry
Catalyst
Yield (%)b
Recently, we demonstrated that titanium cation-exchanged
montmorillonite (Ti4+-mont) acted as an efficient solid acid cata-
lyst for many environmentally benign reactions where the tita-
nium oxide species sandwiched in the layers exhibited high
1
2
3
4
5
6
7
8
9
Ti4+-mont
Montmorillonite K-10
H-USY
H-Y
Nafion-H NR50
H-ZSM-5
H-mordenite
p-Toluenesulfonic acidc
Na+-mont
90
38
20
15
5
4
2
aDepartment of Materials Engineering Science, Graduate School of
Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka,
Osaka 560-8531, Japan. E-mail: kaneda@cheng.es.osaka-u.ac.jp; Fax:
+81 6-6850-6260; Tel: +81 6-6850-6260
4
0
bResearch Center for Solar Energy Chemistry, Osaka University, 1-3
Machikaneyama, Toyonaka, Osaka 560-8531, Japan
a Reaction conditions: catalyst (0.1 g), p-methoxybenzyl alcohol
(1 mmol), n-butanol (3 mL), 30 °C, Ar atmosphere, 4 h. b Determined
by GC using an internal standard technique. c 10 mol%.
†Electronic supplementary information (ESI) available: See DOI:
10.1039/c2gc16135d
610 | Green Chem., 2012, 14, 610–613
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Table 2 Etherification of different classes of alcohols by Ti4+-monta
Entry
R–OH
R′–OH
R–O–R′
Time (h)
Yield (%)b
1
6
6
6
6
99 (92)
97
97
2c
3d
4e
3a
96
5f
3b
3c
3d
8
98 (95)
80 (65)
74 (61)
6
20
30
7
8g
9
3e
10
5
99 (91)
99 (98)
3h
10g
11f
3j
3f
30
15
98 (95)
91 (85)
12
3g
20
98 (98)
13f
14f
3i
8
99 (97)
87 (81)
3k
10
15f
3l
10
10
82
73
16h
3m
17i
18j
3n
3o
1.5
12
96
98
a Reaction conditions: Ti4+-mont (0.1 g), 1 (1 mmol), 2 (3 mL), 30 °C, Ar atmosphere. b Determined by GC using an internal standard technique.
f
i
Values in parentheses are isolated yields. c Reuse 1. d Reuse 2. e Reuse 3. 60 °C. g 120 °C. h 100 °C. Ti4+-mont (0.05 g), CH2CI2 (5 mL), 120 °C.
j Ti4+-mont (0.05 g), CH2CI2 (5 mL), 140 °C.
conversion of 1a, Ti4+-mont was removed from the reaction
mixture by filtration, and further treatment of the resulting filtrate
under similar reaction conditions did not afford any products.
This confirmed that Ti4+-mont performed as a heterogeneous cat-
alyst in the etherification.
unsymmetrical ethers in high yields (Table 2, entries 1 and
5–7).8 The etherification of various primary benzylic alcohols
with 2a afforded excellent yields of unsymmetrical ethers
(Table 2, entries 8–10), even in the case of chlorobenzyl alcohol
with an electron-withdrawing group at the para-position which
is known to be less reactive (Table 2, entry 10).4a Ti4+-mont was
also effective in the etherification of secondary benzylic alco-
hols. For example, 1-phenylethanol (1e) was selectively con-
verted to the corresponding ether without any formation of
The substrate scope of Ti4+-mont for the synthesis of unsym-
metrical ethers derived from diverse combinations of alcohols is
exemplified in Table 2. 1a could react with secondary and ter-
tiary alcohols, as well as primary ones, giving the corresponding
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Scheme 1 Etherifications using Ti4+-mont under scale-up reaction conditions.
Table 3 NH3-TPD measurement of Ti4+-mont
Temp. range of NH3 desorption
25–100 °C
0.06
100–200 °C
0.02
200–300 °C
0.10
300–400 °C
0.05
400–500 °C
0.03
Amounts of partial acid sites (mmol g−1
)
Ti4+-mont (treatment temp.)
Yield of 3a (%)a
TONb
Ti4+-mont (100)
trace
<1
Ti4+-mont (200)
3
4
Ti4+-mont (300)
71
66
Ti4+-mont (400)
84
26
Ti4+-mont (500)
90
17
a Reaction conditions: Ti4+-mont (0.1 g), p-methoxybenzyl alcohol (1 mmol), n-butanol (3 mL), 30 °C, Ar atmosphere, 4 h. b TON of Ti4+-mont(X) =
[the amount of 3a using Ti4+-mont(X) − the amount of 3a using Ti4+-mont(X − 100)]/the amount of partial acid sites of Ti4+-mont(X).
styrene as a by-product through the intramolecular dehydration
of 1e (Table 2, entry 11). The present Ti4+-mont-catalyzed ether-
ification could be extended to the preparation of aliphatic unsym-
metrical ethers from non-activated aliphatic alcohols (Table 2,
entries 14–16). For example, ethyl tert-butyl ether, which is an
effective fuel additive in gasoline reforming, was obtained in
high yield from tert-butanol and ethanol (Table 2, entry 16). The
catalytic activity of Ti4+-mont in the synthesis of aliphatic ethers
was found to be outstanding compared to other solid acids which
showed low activity under similar reaction conditions.9 More-
over, Ti4+-mont was applicable to the intramolecular etherifica-
tion of diols. 1,4-Butanediol and 1,5-pentanediol were
successfully converted into the corresponding cyclic ethers with
excellent selectivity (Table 2, entries 17 and 18). The high
efficiency of Ti4+-mont was also demonstrated under preparative-
scale reaction conditions in these inter- and intra-molecular
etherifications of alcohols. For example, 7.7 g of vanillyl alcohol
(50 mmol) smoothly reacted with 1-butanol at 30 °C to give
10.3 g (96% isolated yield) of vanillyl butyl ether, commonly
used in fragrances and warming agents (Scheme 1). These above
etherifications were achieved without requiring the removal of
water, indicating that Ti4+-mont was water-compatible. A further
advantage of this solid catalytic system was its reusability. The
Ti4+-mont catalyst was easily recoverable and reusable without
loss of its high activity (Table 2, entries 2–4).
extremely low yields,12 revealing that the acid sites of Ti4+-mont
generated during the desorption of NH3 in the range of 200 °C
to 300 °C were extremely effective in the etherification. The cal-
culation of turnover numbers also showed the high efficiency of
the acid sites generated during the above treatment (Table 3).
From these results, the high catalytic activity of Ti4+-mont may
be due to having the largest amount of acid sites with suitable
acid strengths for the etherification. Similar phenomena of
proper acid strengths were observed in other solid acids.13
In conclusion, Ti4+-mont acted as a highly efficient hetero-
geneous Brønsted acid catalyst in the etherification of various
unsymmetrical ethers from different classes of alcohols under
mild conditions. Moreover, Ti4+-mont was also separable and
reusable and maintained its high activity and selectivity without
requiring the removal of water. We also found that the acid sites
generated during desorption of NH3 in the range of 200 °C to
300 °C were quite effective in the etherification.
Acknowledgements
This investigation was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science, and Technology of Japan. This work was supported by
a Grant-in-Aid for Young Scientists (A) (no. 23686116) from the
Japan Society for the Promotion of Science (JSPS).
To investigate the high catalytic activity of Ti4+-mont, the
acidity of Ti4+-mont was measured by NH3-TPD (temperature
programmed desorption) at different temperatures (Table 3).10
The maximum number of acid sites was present in the range of
200–300 °C.11 The acid sites of Ti4+-mont were poisoned by the
adsorption of NH3 and then the acid sites were partially regener-
ated by the desorption of NH3 at different temperatures. As
shown in Table 3, Ti4+-mont treated at 300 °C [Ti4+-mont(300)]
could promote the etherification of 1a with 2a to give 3a in 71%
yield, while use of Ti4+-mont(100) and Ti4+-mont(200) gave
Notes and references
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Mechanism and Structure, Wiley, New York, 4th edn, 1992, pp. 386–387.
612 | Green Chem., 2012, 14, 610–613
This journal is © The Royal Society of Chemistry 2012

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3 For representative examples of homogeneous catalysts for etherification
of alcohols, see: (a) S. Kim, K. N. Chung and S. Yang, J. Org. Chem.,
1987, 52, 3917; (b) L. Karas and W. J. Piel, in Kirk-Othmer Encyclopedia
of Chemical Technology, Wiley, New York, 4th edn, 1992, vol. 9
pp. 860–876; (c) P. Salehi, N. Iranpoor and F. K. Behbahani, Tetrahedron,
1998, 54, 943; (d) G. V. M. Sharma and A. K. Mahalingam,
J. Org. Chem., 1999, 64, 8943; (e) A. Kawada, K. Yasuda, H. Abe and
T. Harayama, Chem. Pharm. Bull., 2002, 50, 380; (f) K. J. Miller and
M. M. Abu-Omar, Eur. J. Org. Chem., 2003, 1294; (g) Y. Liu, R. Hua,
H.-B. Sun and X. Qiu, Organometallics, 2005, 24, 2819; (h) T. Shibata,
R. Fujiwara and Y. Ueno, Synlett, 2005, 1, 152; (i) A. Prades,
R. Corberán, M. Poyatos and E. Peris, Chem.–Eur. J., 2008, 14, 11474.
4 Reported solid catalysts act not as Brønsted acids but as Lewis acids. See
AlPW12O40: Reactions of benzylic or allylic alcohols with primary or
secondary alcohols under reflux conditions: (a) H. Firouzabadi,
N. Iranpoor and A. A. Jafari, J. Mol. Catal. A: Chem., 2005, 227, 97; .
Sn- and Zr-containing silicate molecular sieve: Reaction of benzylic alco-
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Lett., 2003, 44, 9205; (e) K. Kaneda, Synlett, 2007, 999;
(f) T. Mitsudome, T. Matsuno, S. Sueoka, T. Mizugaki, K Jitsukawa and
K. Kaneda, Heterocycles, 2012, 84, 371.
6 It is known that 2,6-lutidine can interact with Brønsted acid sites but
cannot react with Lewis acid sites due to steric hindrance.7 The Ti4+
-
mont-catalyzed etherification of alcohols was inhibited by the addition of
2,6-lutidine, showing that the active species of Ti4+-mont were Brønsted
acid sites in the etherification.
7 A. Corma, Chem. Rev., 1995, 95, 559.
8 In the Ti4+-mont-catalyzed etherifications, trace amounts of symmetrical
ethers from aliphaticalcohols (2) were formed as by-products.
9 The yields of 3m in the etherification of 1h with 2a were as
follows: montmorillonite K-10, 36%; p-toluenesulfonic acid, 18%;
H-Y, 5%.
10 The measurement of desorbed NH3 was carried out at different tempera-
tures where higher NH3 desorption temperatures corresponded to stronger
acid sites; see the following reference: P. Berteau and B. Delmon, Catal.
Today, 1989, 5, 121.
M. Renz, Angew. Chem., Int. Ed., 2007, 46, 298; . Cs2.5H0.5PW12O40
/
ZrO2: The synthesis of ethers derived from combinations of p-methoxy-
benzyl alcohols with aliphatic alcohols at 65 °C and diphenyl methanol
with aliphatic alcohols at 120 °C, respectively: (c) K. T. V. Rao,
P. S. N. Rao, P. S. Sai Prasad and N. Lingaiah, Catal. Commun., 2009,
10, 1394.
5 (a) K. Ebitani, T. Kawabata, K. Nagashima, T. Mizugaki and K. Kaneda,
Green Chem., 2000, 2, 157; (b) T. Kawabata, T. Mizugaki, K. Ebitani and
K. Kaneda, Tetrahedron Lett., 2001, 42, 8329; (c) T. Kawabata, M. Kato,
11 The total amount of acid sites in Ti4+-mont was 0.26 mmol g−1, which
corresponded to the amount of NH3 in the whole range of NH3 desorption
temperatures (25–500 °C).
12 The catalytic activity of Ti4+-mont(500) was very similar to that of the
fresh Ti4+-mont catalyst, showing that the total active acid sites of fresh
Ti4+-mont in the etherification corresponded to that of Ti4+-mont(500).
13 See ESI†.
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