Copper nitrate/acetic acid as an efficient synergistic catalytic system for the chemoselective tetrahydropyranylation of alcohols and phenols

Article abstract of DOI:10.1007/s00706-008-0051-0

Tetrahydropyranylation of alcohols and phenols was accomplished successfully using copper nitrate and acetic acid as a synergistic catalyst at room temperature under solvent-free condition. Compared with other synergistic catalytic systems, copper nitrate/acetic acid proved to be the most efficient. Both alcohols (primary, secondary, tertiary, benzylic, cyclic, allyl, cinnamyl, and furyl) and phenols reacted smoothly in high yields. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-008-0051-0

Monatsh Chem (2009) 140:177–179
DOI 10.1007/s00706-008-0051-0
ORIGINAL PAPER
Copper nitrate/acetic acid as an efficient synergistic catalytic
system for the chemoselective tetrahydropyranylation of alcohols
and phenols
Min Wang Æ Zhi-Guo Song Æ Hong Gong Æ
Heng Jiang
Received: 22 July 2008 / Accepted: 30 July 2008 / Published online: 27 September 2008
Ó Springer-Verlag 2008
Abstract Tetrahydropyranylation of alcohols and phenols
was accomplished successfully using copper nitrate and
acetic acid as a synergistic catalyst at room temperature
under solvent-free condition. Compared with other syner-
gistic catalytic systems, copper nitrate/acetic acid proved to
be the most efficient. Both alcohols (primary, secondary,
tertiary, benzylic, cyclic, allyl, cinnamyl, and furyl) and
phenols reacted smoothly in high yields.
p-TsOH [4], polyaniline salt [5], PdCl2(CH3CN)2 [6],
LiOTf [7], Fe(ClO4)3 [8], Bu4NBr3 [9], VO(OAc)2 [10],
CAN [11], Fe(HSO4)3 [12], K5CoW12O40Á3H2O [13],
Bi(NO3)3Á5H2O [14], Zeolite H-beta [15], and Al(HSO4)3
[16] have been reported. However, these procedures have
several drawbacks, such as elevated temperature, long
reaction time, inert atmosphere, harmful organic solvent,
and expensive catalysts. Therefore, an efficient and prac-
tical method for the tetrahydropyranylation of alcohols and
phenols under mild and economical reaction conditions is
desired.
Keywords Tetrahydropyranylation Á Alcohol Á
Phenol Á Synergistic catalysis Á Chemoselectivity
During our endeavours to explore the utility of ‘‘Brønsted
assisted Lewis acid catalysis,’’ we earlier reported that the
combinations of Cu(p-CH3C6H4SO3)2Á6H2O/HOAc and
CuCl2Á2H2O/HOAc are efficient and mild catalysts for the
tetrahydropyranylation [17, 18]. In further extension to our
work, we discovered that Cu(NO3)2Á3H2O/HOAc acts as a
synergistic catalytic system was more efficient than the
reports. In this paper, the details of the tetrahydropyranyla-
tion of alcohols and phenols in the presence of catalytic
amounts of Cu(NO3)2Á3H2O and HOAc are presented
(Scheme 1).
Introduction
Protection of alcohols and phenols in organic synthesis has
been paid much attention [1]. In particular, protection as
tetrahydropyranyl (THP) ether draws more attention due to
its stability towards a variety of reaction conditions such as
strongly basic media, Grignard reagents, acylating agents,
alkyllithiums, and metal hydrides [2]. THP ethers can be
synthesized from a variety of hydroxy-containing com-
pounds by acid-catalyzed reaction with 3,4-dihydro-2H-
pyran (DHP). Many catalysts, including H2NSO3H [3],
Results and discussion
The catalytic activity of several commonly used Lewis
copper salts (CuX) and CuX/HOAc was examined in a
model reaction of isopropyl alcohol (30 mmol) and DHP
(36 mmol) at room temperature; the results are shown in
Table 1. As can be seen from Table 1, CuX or HOAc used
separately is poorly active, and the catalytic activity of
CuX/HOAc is higher than that of CuX used alone. After
several trials, we found a powerful synergistic effect when
HOAc is mixed with Cu(NO3)2Á3H2O, which gave 94%
M. Wang (&)
College of Chemistry and Chemical Engineering,
Bohai University, Jinzhou, China
e-mail: minwangszg@yahoo.com.cn
Z.-G. Song
Center for Science and Technology Experiment,
Bohai University, Jinzhou, China
H. Gong Á H. Jiang
Liaoning Shihua University, Fushun, China
123

178
M. Wang et al.
Table 2 Tetrahydropyranylation of alcohols and phenols catalyzed
by Cu(NO3)2Á3H2O/HOAc
Cu(NO3)2 3H2O/HOAc
solvent free, r. t.
+
R
OH
Time (h) Yield (%)a Referencesb
O
O
Entry Alcohol/phenol
R
O
1
CH3OH
0.16
0.3
0.4
0.5
0.35
1.5
1.5
0.4
0.5
94
97
96
92
94
90
85
96
93
94
96
93
92
92
90
93
94
96
91
89
95
85
86
94
95
92
44
62
99
[19]
Scheme 1
2
C2H5OH
[19]
3
n-C3H7OH
i-C3H7OH
n-C4H9OH
s-C4H9OH
t-C4H9OH
i-C4H9OH
n-C5H11OH
[19]
Table 1 Screening of catalysts for the tetrahydropyranylation of
isopropyl alcohol
4
[20]
5
[19]
CuX
Time (h)
Yield (%)a
6
[20]
CuX
CuX/HOAcb
7
[21, 22]
[20]
8
None
10
7
–
1
0
0
9
2
3
1
1
3c
13
3
9
[22]
CuSO4Á5H2O
Cu(OAc)2ÁH2O
Cu(acac)2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
a
(CH3)2CHCH2CH2OH 0.8
[20]
8
n-C7H15OH
1
[23]
7
2
n-C8H17OH
1
[20]
Cu(CH3SO3)2Á4H2O
Cu(p-CH3C6H4SO3)2Á6H2O
Cu(o-CH3C6H4SO3)2Á4H2O
CuCl2Á2H2O
5
87
72
75
91
94
i-C8H17OH
1
[20]
0.5
0.5
0.5
0.5
n-C12H25OH
n-C16H33OH
PhCH2OH
1.7
5
[20]
[24]
0.1
0.1
0.7
0.8
1
[19, 20]
[14]
Cu(NO3)2Á3H2O
PhCH2CH2OH
c-C6H11OH
a
Isolated yield
[20]
b
0.6 mmol CuX, 12 mmol HOAc
Only 12 mmol HOAc was used
CH2=CHCH2OH
PhCH=CHCH2OH
Furfuryl alcohol
PhOH
[20]
c
[22]
0.6
0.1
0.5
0.1
0.1
0.1
5
[19, 20]
[19, 20]
[22, 25]
[25]
yield of the product within 0.5 h. The yields improved
greatly when the amount of HOAc was increased, while a
decrease of the amount of Cu(NO3)2Á3H2O would retard
the reaction. All the results stated above suggest that the
copper cation and proton cooperatively act as a synergistic
catalyst in the step of the nucleophilic addition of alkoxy to
DHP.
4-CH3C6H4OH
4-ClC6H4OH
4-BrC6H4OH
4-NO2C6H4OH
1-Nathphol
[26]
[20, 25]
[22]
2-Nathphol
5
[14]
Under the conditions of alcohol/phenol (30 mmol) and
DHP (36 mmol), we then examined other substrates using
0.6 mmol Cu(NO3)2Á3H2O and 12 mmol HOAc as cata-
lysts to give corresponding THP ether at room temperature
(Table 2). As evident from Table 2, all the reaction pro-
ceeded smoothly and efficiently. No polymeric by-product
of DHP was observed, and the THP ether was isolated as
the only product. It is worth mentioning that our procedure
is more efficient than some of the recently reported pro-
cedures in terms of reaction times and yields. Most
protections were completed within 0.1–1 h in almost
quantitative yields. A wide range of hydroxy compounds,
such as primary, secondary, tertiary alcohols, benzyl
alcohol (entry 16), cyclic saturated alcohol (entry 18),
allyl alcohol (entry 19), cinnamyl alcohol (entry 20), furyl
alcohol (entry 21), and phenols (entries 22–28), could be
protected by using the new synergistic catalytic system. In
the case of tertiary alcohols (entry 7), no dehydration
products were observed (as determined by GC). For linear
chain aliphatic alcohols, the protection of short-chain
alcohols proceeds faster than in case of the long-chain ones.
PhCH2OH ? PhOH
0.2
–
Isolated yield, the purity and the identity of the products were
1
determined by GC, IR, H NMR, and elemental analysis
b
Reference for spectroscopic data of products
We were then interested in whether the same catalytic
system could be employed for the tetrahydropyranylation of
phenolic compounds. By following identical reaction con-
ditions, various phenols except bulky phenols (entries 27
and 28) were converted into the corresponding THP ethers
quickly in high yields (entries 22–26). Reactions of
1-nathphol and 2-nathphol were slow, and long reaction
time was required. In addition to these results, we also
investigated the selectivity in protection of this process
using equimolar benzoic alcohol and phenol (entry 29). The
results show that alcohol can be protected selectively and
efficiently while the phenol remained unaffected.
In conclusion, tetrahydropyranylation of alcohols and
phenols has been carried out successfully using the new
synergistic catalyst system, Cu(NO3)2Á3H2O and HOAc.
123

Copper nitrate/acetic acid as an efficient synergistic catalytic system
179
The significant advantages of this methodology are high
yields, short reaction time, cheap and readily available
catalysts, and mild reaction conditions. The most important
is that the amount of HOAc of the new catalytic system
was decreased to one half of the reported [17, 18]. This
improvement can avoid environmental pollution especially
in large-scale industrial processes. It can be predicted that
this method will find useful application for tetrahydropyr-
anylation in modern synthetic chemistry.
elemental analysis with those reported for the authentic
samples.
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General procedure for the tetrahydropyranylation
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To a mixture of 30 mmol alcohol or phenol and 3.028 g
DHP (36 mmol) was added 0.145 g Cu(NO3)2Á3H2O
(0.6 mmol) and 0.721 g HOAc (12 mmol) at room tem-
perature. The mixture was stirred until completion of the
reaction (monitored by GC). After reaction, the organic
layer was washed twice with 20 cm3 saturated NaHCO3
solution, dried (Na2SO4), and evaporated to yield the
almost pure product. The product was purified further by
column chromatography on silica gel (ethyl acetate/
n-hexane = 1/9 as the eluent). Then the pure products were
1
identified by comparing their m.p./b.p., IR, H NMR, and
123