Metal benzenesulfonates/acetic acid mixtures as novel catalytic systems: Application to the protection of a hydroxyl group

Article abstract of DOI:10.1515/znb-2010-1109

A surprising synergistic effect has been discovered in mixtures of metal benzenesulfonates (Co, Al, Ni, Zn, Cd, Pr, La, Cu, Mn) and acetic acid, leading to active catalytic systems for the tetrahydropyranylation of alcohols and phenols to produce tetrahydropyranyl ethers. All reactions proceed mildly and efficiently with moderate to high yields at room temperature without solvent. After the reaction, the metal benzenesulfonate can be easily recovered and reused many times. The efficiency of these systems might result from the "double activation" by Bronsted and Lewis acid catalysis.

Full text of DOI:10.1515/znb-2010-1109

Metal Benzenesulfonates/Acetic Acid Mixtures as Novel Catalytic
Systems: Application to the Protection of a Hydroxyl Group
Min Wanga, Jingjing Gaoa, and Zhiguo Songb
a College of Chemistry and Chemical Engineering, Bohai University, Jinzhou 121000, P. R. China
b Center for Science & Technology Experiment, Bohai University, Jinzhou 121000, P. R. China
Reprint requests to Dr. Min Wang. E-mail: minwangszg@yahoo.com.cn
Z. Naturforsch. 2010, 65b, 1349 – 1352; received July 6, 2010
A surprising synergistic effect has been discovered in mixtures of metal benzenesulfonates (Co,
Al, Ni, Zn, Cd, Pr, La, Cu, Mn) and acetic acid, leading to active catalytic systems for the tetrahy-
dropyranylation of alcohols and phenols to produce tetrahydropyranyl ethers. All reactions proceed
mildly and efficiently with moderate to high yields at room temperature without solvent. After the
reaction, the metal benzenesulfonate can be easily recovered and reused many times. The efficiency
of these systems might result from the “double activation” by Brønsted and Lewis acid catalysis.
Key words: Tetrahydropyranylation, Metal Benzenesulfonate, Alcohol, Phenol, Protection
Introduction
much attention [15 – 17]. Properties such as low tox-
icity, moisture tolerance, and reusability make them
attractive alternatives to conventional Lewis acids. In
addition, a most remarkable characteristic of metal sul-
fonates is the ability to form superacidic systems by
mixing an appropriate metal sulfonate and a Brønsted
acid. Such complexation (ideally between an inactive
Lewis acid and an inactive organic acid toward a spe-
cific reaction) has been used efficiently in many types
of electrophilic substitutions. For example, Mouhtady
and co-workers combined Sc(OTf)3 with CH3SO3H
in a 1 : 2 ratio to produce a very active catalyst for
the Fries rearrangement [18]. Aspinall et al. reported
a successful acceleration in a La(OTf)3-PhCO2H-
catalyzed allylation reaction [19]. We also reported
that Cu(CH3SO3)2·4H2O/HOAc can efficiently cat-
alyze the diacetylation of aldehydes and the tetrahy-
dropyranylation of alcohols and phenols [20, 21]. Both
Lewis acid and Brønsted acid are indispensable for
these conversions. For protecting functional groups, 2
mol-% of Cu(CH3SO3)2·4H2O and 12 mmol of HOAc
were used as catalysts. During our further endeavors to
explore the utility of metal sulfonates, we found that
the combination of a metal benzenesulfonate (MBS)
and HOAc, acting as a synergistic catalytic system,
can catalyze efficiently the tetrahydropyranylation of
alcohols or phenols with 3,4-dihydro-2H-pyran(DHP)
(Scheme 1). The amount of MBS is only 1 mol-%,
and benzenesulfonates are significantly cheaper than
methanesulfonates. The new catalytic system enlarges
The protection of a hydroxyl group is a common
process in multistep organic synthesis. The tetrahy-
dropyranyl (THP) group is frequently used for the pro-
tection of alcohols and phenols due to the remark-
able stability of the resulting acetals (THP ethers)
under a variety of conditions such as strongly basic
media, or the presence of Grignard reagents, acyl-
ating agents, lithium alkyls, and metal hydrides [1].
Some of the recently reported reagents that can cat-
alyze tetrahydropyranylation are LiOTf [2], polyani-
line salts [3], PdCl2(CH3CN)2 [4], Fe(HSO4)3 [5],
H14[NaP5W30O110] [6], Bi(NO3)3·5H2O [7], NbCl5
[8], pyridinium chloride [9], Ru(acac)3 [10], Moβ
zeolite [11], activated carbon-supported H2SO4 [12],
2,4,6-trichloro-[1,3, 5]triazine [13], Dowex 50WX4-
100 [14], etc. Most of them proved to be efficient
for this reaction. However, some of these have several
drawbacks such as elevated temperature, long reaction
time, harmful organic solvents, and expensive cata-
lysts. In addition, some catalysts have to be prepared
prior to use, and/or require by using large amounts of
solid support that eventually results in the generation
of large amounts of toxic waste, under harsh and acidic
conditions. Thus, there is still a demand for the intro-
duction of cheap, green and efficient methods for this
transformation.
Recently, the synthesis, characterization, and use of
metal sulfonates in organic synthesis have received
c
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M. Wang et al. · Metal Benzenesulfonates/Acetic Acid Mixtures as Novel Catalytic Systems
Table 1. Screening of MBSs for the tetrahydropyranylation
of benzyl alcohol.
Yield (%)a
Entry
MBS
MBS
0
2
33
0
0
9
5
7
0
MBS-HOAcb
Scheme 1. Tetrahydropyranylation of alcohol or phenol cat-
alyzed by a metal benzenesulfonate (MBS) and HOAc.
1
2
3
4
5
6
7
8
Co(C6H5SO3)2·6H2O
Al(C6H5SO3)2·6H2O
Ni(C6H5SO3)2·6H2O
Zn(C6H5SO3)2·6H2O
Cd(C6H5SO3)2·5H2O
Pr(C6H5SO3)3·2H2O
La(C6H5SO3)3·2H2O
Cu(C6H5SO3)2·6H2O
98, 95, 91, 85c
91
83
83
80
66
56
41
36
the scope of reactants. After reaction, the MBS can be
easily recovered by simple phase-separation and can
be reused many times. The details of our studies are
presented herein.
9
Mn(C6H5SO3)2·6H2O
Results and Discussion
a
b
Isolated yield;
Co(C6H5SO3)2·6H2O was reused four times.
2 mol-% of MBS and 12 mmol of HOAc;
c
First, nine MBSs including Co, Al, Ni, Zn, Cd, Pr,
La, Cu, and Mn benzenesulfonates were screened for
their ability to catalyze the protection of a hydroxyl
group using benzyl alcohol as a model hydroxyl com-
pound for 1 h (Table 1). It appeared that all MBSs used
alone were inactive or poorly active. However, pow-
erful synergistic effects were observed when the MBS
was mixed with HOAc. In the investigation of various
catalysts, the combination of Co(C6H5SO3)2·6H2O
with HOAc was the most efficient and gave the cor-
responding THP ether in 98 % yield. The recycling of
Co(C6H5SO3)2·6H2O was realized easily. It could be
recovered by simple phase-separation because it was
slightly soluble in the reaction system. After being
washed with acetone and dried at ambient temperature,
Co(C6H5SO3)2·6H2O was reused for the next reaction
run. It could be recycled four times without significant
loss of catalytic activity (entry 1).
Next, the optimization of the amount of
Co(C6H5SO3)2·6H2O and HOAc was investigated in a
model reaction of benzyl alcohol with DHP (Table 2).
The control experiment showed that no product was
obtained in the absence of catalyst even after one
day (entry 1). Co(C6H5SO3)2·6H2O or HOAc, when
applied alone, did not catalyze the conversion either
(entries 2 and 8). A surprising synergistic effect
occurred when Co(C6H5SO3)2·6H2O was mixed with
HOAc. The yields improved greatly when the amount
of HOAc increased from 3 mmol to 12 mmol (entries
3 – 5). When 2 mol-% of Co(C6H5SO3)2·6H2O and
12 mmol of HOAc were used together, a 98 % yield
of the product resulted. Moreover, it was found that
1 mol-% of Co(C6H5SO3)2·6H2O was also efficient
to drive the transformation (entry 6). However, the
reaction proceeded incompletely when the amount of
Co(C6H5SO3)2·6H2O was less than 1 mol-% (entry 7).
Therefore, the optimal catalyst consists of 1 mol-% of
Co(C6H5SO3)2·6H2O and 12 mmol of HOAc.
Table 2. Effect of the amounts of Co(C6H5SO3)2·6H2O and
HOAc on the yields.
Entry
Co(C6H5SO3)2·6H2O
HOAc
(mmol)
Time
(h)
24
1
1
1
1
1
1
1
Yielda
(%)
0
(mol-%)
1
2
3
4
5
6
7
0
2
2
2
2
1
0.5
0
0
0
3
0
31
72
98
97
84
0
6
12
12
12
12
8
a
Isolated yields.
Table 3. Tetrahydropyranylation of alcohols and phenols cat-
alyzed by Co(C6H5SO3)2·6H2O-HOAc.
Entry
Alcohol/phenol
Time (h)
Yield (%)a
Refs.b
1
2
3
4
5
6
7
8
PhCH2OH
PhCH2CH2OH
CH3OH
C2H5OH
n-C3H7OH
i-C3H7OH
1
5
97
90
97
97
92
95
93
98
60
0
91
84
92
74
24
85
95
90
73
57
95+0
[22, 23]
[7]
1.0
1.5
2.0
2.5
2.5
1.5
5
9
3.5
6
4
6
6
1
[22]
[22]
[22]
[23]
[22]
[23]
[23]
–
[24]
[23]
[23]
[23]
[23]
[22, 23]
[24, 25]
[25]
[23, 25]
[7]
n-C4H9OH
i-C4H9OH
9
s-C4H9OH
t-C4H9OH
n-C5H11OH
i-C5H11OH
n-C8H17OH
n-C12H25OH
c-C6H11OH
PhOH
4-CH3C6H4OH
4-ClC6H4OH
4-NO2C6H4OH
2-naphthol
10
11
12
13
14
15
16
17
18
19
20
1
2.5
2
5.5
1
21
PhCH2OH+PhOH
–
a
Isolated yield; the purity and the identity of the products were de-
termined by GC, IR, 1H NMR, and elemental analysis; b references
for spectroscopic data of products.
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M. Wang et al. · Metal Benzenesulfonates/Acetic Acid Mixtures as Novel Catalytic Systems
1351
From a mechanistic point of view, we can specu- Conclusion
late that the observed catalytic effects arise as follows:
In conclusion, we have demonstrated that mixing an
appropriate MBS with HOAc leads to a strong syner-
gistic effect, which can be employed in a new set of
active catalysts for the protection of a hydroxyl group.
This method has notable advantages over the existing
ones owing to its features of environmental friendli-
ness, low cost, and easy operation. On the other hand,
this protocol supplies a good further example of cat-
alytic applications of metal sulfonates towards organic
synthesis. The extension of this work to other reactions
is currently under investigation in our laboratory.
(i) a pure Lewis acid or Brønsted acid catalysis could
be ruled out according to the results in entries 2 and 8;
(ii) a ligand exchange between MBS and HOAc, gen-
erating acetate and benzene sulfonic acid, is impossi-
ble because the pKa value of benzene sulfonic acid is
lower than that of HOAc. Moreover, the peak of ben-
zenesulfonic acid was not detected through GC; (iii) a
Brønsted-Lewis acid catalysis resulting in the double
activation of reactants. Based on the above results and
previous reports, it seems that the real catalyst might be
HOAc-assisted Co(C6H5SO3)2·6H2O, which produces
a “double activation” of DHP. Then, nucleophilic at-
tack of alcohol to DHP occurs, followed by proton
transfer and formation of the final product. A similar
example of Brønsted-assisted Lewis acid catalysis was
reported by Mouhtady [18] and Aspinall [19] et al.
In order to ascertain the scope and limitation of
this catalyzed tetrahydropyranylation, the use of the
catalytic system was extended to the reaction of var-
ious alcohols and phenols (Table 3). Under the opti-
mized experimental conditions, benzylic, primary, iso-
merical, secondary alcohols as well as phenols undergo
tetrahydropyranylation in moderate to excellent yields.
In the case of linear-chain aliphatic alcohols, the pro-
tection of short-chain alcohols proceeds faster than in
case of the long-chain ones. However, the catalyst sys-
tem appears to show no catalytic activity for the protec-
tion of acid-sensitive and sterically hindered alcohols
such as tert-butyl alcohol (entry 10). In addition, cy-
clohexanol gave generally very low yields (entry 15).
With the present methodology, tetrahydropyrany-
lation of phenolic hydroxyl groups was also investi-
gated. Phenol was conveniently protected as the cor-
Experimental Section
Melting points were determined using an RY-1 micromelt-
ing point apparatus. GC analysis was carried out on a Perkin
Elmer Auto System XL gas chromatograph. Infrared spectra
were recorded on a Spectrum GX series Fourier Transform
instrument of Perkin Elmer. 1H NMR spectra were recorded
on a Bruker ARX-300 spectrometer in CDCl3 using TMS
as an internal standard. Elemental analyses were carried out
on an EA 2400II elemental analyzer (Perkin Elmer), and the
results agreed favorably with the calculated values.
General procedure for the tetrahydropyranylation of alco-
hols and phenols
A mixture of alcohol or phenol (15 mmol), DHP
(18 mmol, 1.514 g), Co(C6H5SO3)2·6H2O (0.15 mmol,
0.072 g), and HOAc (12 mmol, 0.721 g) was stirred magnet-
ically at ambient temperature for an appropriate time (mon-
itored by GC). After the reaction, the organic layer was
washed twice with saturated NaHCO3 solution (10 mL),
dried (Na2SO4), and evaporated to yield the almost pure
product. The products were purified further by column chro-
matography on silica gel (ethyl acetate-n-hexane 1 : 9 as the
responding THP ether no matter whether the ben- eluent). All the THP ethers were characterized by m. p./b. p.,
IR, 1H NMR, and elemental analysis. The data were com-
zene ring was substituted with electron-donating or
pared with literature data and found to be identical with those
of authentic samples.
-withdrawing substituents (entries 16 – 19). A bulky
phenol like 2-naphthol was also smoothly tetrahy-
dropyranylated in moderate yield when reacted with
DHP (entry 20). Furthermore, chemoselective protec-
tion of an alcohol in the presence of phenol was ex-
plored under similar reaction conditions. The results
show that an alcohol can be protected selectively and
efficiently while the phenol remains unaffected (en-
try 21).
Acknowledgement
This research work was financially supported by the Ed-
ucation Committee of Liaoning Province of China (No.
2009A033) and the Committee of Science and Technology
of Liaoning Province of China (No. 20091001).
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1352
M. Wang et al. · Metal Benzenesulfonates/Acetic Acid Mixtures as Novel Catalytic Systems
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