Copper p-toluenesulfonate/acetic acid: A recyclable synergistic catalytic system for the tetrahydropyranylation of alcohols and phenols

Article abstract of DOI:10.1007/s00706-007-0821-0

Copper p-toluenesulfonate/acetic acid was found to be an efficient, chemoselective synergistic catalytic system, with catalyst loading as low as 0.3 mol% leading to clean, high-yielding tetrahydropyranylation of a variety of alcohols and phenols. By simple phase-separation, copper p-toluenesulfonate can be easily recovered and reused for several times without deterioration in catalytic activity.

Full text of DOI:10.1007/s00706-007-0821-0

Monatsh Chem 139, 601–604 (2008)
DOI 10.1007/s00706-007-0821-0
Printed in The Netherlands
Copper p-toluenesulfonate=acetic acid: a recyclable synergistic catalytic system
for the tetrahydropyranylation of alcohols and phenols
Min Wang1, Zhi-Guo Song2, Heng Jiang3, Hong Gong3
1
College of Chemistry and Chemical Engineering, Bohai University, Jinzhou, China
2
Center for Science and Technology Experiment, Bohai University, Jinzhou, China
3
Liaoning Shihua University, Fushun, China
Received 30 September 2007; Accepted 2 October 2007; Published online 19 May 2008
# Springer-Verlag 2008
Abstract Copper p-toluenesulfonate=acetic acid was
found to be an efficient, chemoselective synergistic
catalytic system, with catalyst loading as low as
0.3 mol% leading to clean, high-yielding tetrahydro-
pyranylation of a variety of alcohols and phenols. By
simple phase-separation, copper p-toluenesulfonate
can be easily recovered and reused for several times
without deterioration in catalytic activity.
SAC-13 [8], PdCl2(CH3CN)2 [9], Bi(NO3)3 ꢀ 5H2O
[10], and In(OTf)3 [11], etc. However, these proce-
dures have several drawbacks including elevated re-
action temperature, long reaction times, harmful
organic solvents, and expensive reagents. Despite a
number of precedents, an efficient and practical
method for tetrahydropyranylation is desired.
Over recent years, sulfonate mediated Lewis acid
catalysis has attracted tremendous interest through-
out scientific communities. The low toxicity, ease
of handling, recyclable nature, and low cost make
sulfonate species attractive alternatives to classical
Lewis acids, particularly in large-scale industrial
processes. During our endeavors to explore the utili-
ty of sulfonates, we have reported that the combina-
tion of copper methanesulfonate (CMS) and acetic
acid was an efficient catalyst for diacetylation of al-
dehydes [12]. In further extension to our work, we
discovered that copper p-toluenesulfonate (CPTS)=
HOAc, which acts as synergistic catalytic system can
catalyze tetrahydropyranylation efficiently at room
temperature under solvent-free condition. It is im-
portant to mention that the procedure used only
0.3 mol% CPTS but reached the same yields as high
as those provided by the procedure with 2 mol%
Lewis acid catalyst reported recently [13]. After re-
action, CPTS can be easily recovered by simple
phase-separation and can be reused for many times.
The details of our studies are presented herein.
Keywords Tetrahydropyranylation; Alcohols and phenols;
Synergistic catalysis; Chemoselectivity; Reusability.
Introduction
Protection and deprotection strategy in organic syn-
thesis is inevitable, owing to chemoselective trans-
formations in the presence of various functional
groups. Tetrahydropyran is an attractive protecting
group that is often used for protection of alcohol
moieties due to its stability and compatibility under
various reaction conditions and reagents, such as
metal hydrides, alkylithiums, Grignard reagents, and
catalytic hydrogenation [1]. There are several known
catalysts for the tetrahydropyranylation of alcohols,
the most commonly used are Li(OTf) [2], MgBr2 [3],
LiBF4 [4], VO(OAc)2 [5], CaCl2 [6], Ps-AlCl3 [7],
Correspondence: Min Wang, College of Chemistry and
Chemical Engineering, Bohai University, Jinzhou, China.
E-mail: minwangszg@yahoo.com.cn

602
M. Wang et al.
Results and discussion
CPTS for 0.5 h in Table 2. As can be seen from
Table 2, excess DHP facilitates the reaction (entries
1–3). The optimum molar ratio of DHP to benzolic
alcohol was found to be 1.2:1. In the presence of
0.045 mmol CPTS, the increasing the amount of
HOAc greatly increased the yields (entries 3–6).
When 12 mmol HOAc was used, 96% yield of prod-
uct was resulted. We believe what we were observ-
ing was a Brønsted assisted Lewis acid catalysis. In
the complex, the copper cation and proton coopera-
tively act as a combined catalyst in the step of
nucleophilic addition of alkoxy to DHP. It is impos-
sible to form p-toluenesulfonic acid because the pKa
value of HOAc is higher than that of p-toluenesul-
fonic acid. We also determined that the yield of 2-
phenylmethyl tetrahydropyranyl ether was only 45%
in the presence of 0.045 mmol p-toluenesulfonic acid
in this study. Similar examples closely relates to
our situation were reported by Deaton et al. [14],
Aspinall et al. [15], and Mouhtady et al. [16].
A series of CuX or CuX=HOAc were used as catalysts
in a model reaction of benzoic alcohol (15 mmol)
and 3,4-dihydro-2H-pyran (DHP, 18 mmol) at room
temperature, the results were shown in Table 1. As
can be seen from Table 1, only 0.3 mol% CuX
or 12 mmol HOAc used separately is poorly active.
Some CuX combined with HOAc showed much higher
catalytic activity than CuX used alone (entries 6–8).
CPTS=HOAc showed the best results, which gave
96% yield of product within 0.5 h. A powerful syn-
ergistic effect was observed when CPTS was mixed
with HOAc. Both CPTS and HOAc are indispensable
for the rate acceleration of the reaction. It is an exo-
thermic reaction and an increase of temperature indi-
cates the reaction happened.
Encouraged by this result, we investigated the
optimal conditions for tetrahydropyranlyation of
benzoic alcohol using CPTS=HOAc as catalyst. The
amounts of DHP and HOAc were investigated in the
presence of 15mmol benzoic alcohol and 0.045 mmol
Under the optimal condition, a series of alcohols
and phenols were subjected to tetrahydropyranyla-
tion in the presence of CPTS=HOAc at room temper-
ature to give corresponding tetrahydropyranyl ethers
in high yields (Table 3). All the reactions proceeded
efficiently and smoothly. The procedure works with
a variety of primary, secondary, tertiary alcohols, a
cyclic saturated alcohol (entry 15), and phenols
(entries 18–21). It is noteworthy that in the case
of tertiary alcohols (entry 10) no dehydration pro-
ducts were observed (determined by GC). The recy-
cling of CPTS was investigated in the model reaction
of benzoic alcohol and DHP (entry 1). After reaction,
the organic phase was extracted by CH2Cl2. CPTS
could be recovered by filtration and washed with
CH2Cl2, then reused for its next run. Compared with
the fresh catalyst, no obvious decrease of catalytic
activity was detected after four runs. The selectivity
in protection of this process was demonstrated using
equimolar benzoic alcohol and phenol (entry 22).
Smooth conversion of the benzoic alcohol to the cor-
responding 2-phenylmethyl tetrahydropyranyl ether
was observed while the phenol remained unaffected.
In conclusion, we present an efficient catalytic
system under which tetrahydropyranylation of alco-
hols and phenols can be carried out in good to high
yields. The Lewis acid catalyst can be easily recov-
ered and recycled providing an atom economic pro-
cedure. A series of experiments confirmed that the
Brønsted acid or Lewis acid was not simply regen-
Table 1 Tetrahydropyranylation of benzoic alcohol and DHP
catalyzed by CuX or CuX=HOAc
Entry CuX
Time=h
Yield=%a
CuX CuX=HOAc
1
2
3
4
5
6
7
8
–
10
1
1
0.5
0.6
0.7
0.5
0.5
–
0
0
0
0
6
0
5
0b
0
0
0
Cu(OAc)2 ꢀ H2O
Cu(acac)2
CuSO4 ꢀ 5H2O
Cu(NO3)2 ꢀ 3H2O
CuCl2 ꢀ 2H2O
CMS
7
44
45
96
CPTS
a
Isolated yields
Only 12 mmol HOAc was used
b
Table 2 Tetrahydropyranylation of benzoic alcohol and DHP
under different conditiona
Entry
nbenzoic alcohol:nDHP
nHOAc=mmol
Yield=%b
1
2
3
4
5
6
7
1:1
12
12
12
9
6
3
84
92
96
91
79
17
5
1:1.1
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
0
a
Benzoic alcohol 15 mmol, CPTS 0.045 mmol, 0.5 h
Isolated yields
b

A recyclable synergistic catalytic system for the tetrahydropyranylation of alcohols and phenols
603
Table 3 Tetrahydropyranylation of alcohols and phenols using a catalytic amount of CPTS and HOAc
Entry
Alcohol
Time=h
Yield=%a
Refs.b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
PhCH2OH
0.5
1
96, 94, 93, 89
[17, 18]
[17, 18]
[17, 18]
[17, 18]
[17, 18]
[17, 18]
[17, 18]
[17, 18]
[17, 18]
[17, 18]
[17, 18]
[17, 18]
[17, 18]
[17, 18]
[17, 18]
[17, 18]
[13]
PhCH2CH2OH
CH3OH
C2H5OH
n-C3H7OH
i-C3H7OH
n-C4H9OH
i-C4H9OH
s-C4H9OH
t-C4H9OH
(CH3)2CHCH2CH2OH
n-C8H17OH
i-C8H17OH
n-C12H25OH
c-C6H11OH
CH2¼CHCH2OH
n-BuOCH2CH2OH
PhOH
4-CH3C6H4OH
4-CH3OC6H4OH
4-ClC6H4OH
PhCH2OH þ PhOH
93
96
92
91
94
92
93
85
77
91
91
89
87
96
91
90
91
94
93
76
96 þ 0
0.5
0.5
0.5
1.5
1
3
3
3
2.5
4
3
6
2
2
5
0.5
0.5
0.7
2
[17, 18]
[17, 18]
[17, 18]
[17, 18]
[17, 18]
4
a
1
Isolated yields, the purity, and the identity of the products were determined by H NMR and GC
Reference for spectroscopic data of products
b
temperature for an appropriate time (monitored by GC). After
reaction, the organic layer was washed twice with 10cm3 sa-
turated NaHCO3 solution, dried (Na2SO4), and evaporated to
yield the almost pure product. The product was purified fur-
ther by column chromatography on silica gel (ethyl acetate:n-
hexane, 1:9 as the eluent). All the tetrahydropyranyl ethers
erating the catalyst and that the Brønsted acid and
Lewis acid were acting together as a combined cata-
lyst for the reaction. A number of synthetic applica-
tions about synergistic catalysis are currently under
study, and further results in this area will be de-
scribed in due course.
1
were characterized by IR, H NMR, and elemental analysis.
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