Short communication: Catalytic tetrahydropyranylation of phenols and alcohols using vanadium(V)-substituted polyoxomolybdates

Article abstract of DOI:10.2298/JSC110507176G

Alcohols and phenols were tetrahydropyranylated in the presence of H ₇[PMo₈V₄O₄₀] in good to excellent yields in acetonitrile and under solventfree reaction conditions. A mild and convenient method for the formation and deprotection of ethers (THP ethers) is described. The formation of THP ethers from the corresponding alcohols was accomplished in the presence of acid-sensitive functional groups.

Full text of DOI:10.2298/JSC110507176G

J. Serb. Chem. Soc. 77 (3) 287–296 (2012) UDC 547.43+547.56+546–328+66.095.253–927.7
JSCS–4268 Short communication
SHORT COMMUNICATION
Catalytic tetrahydropyranylation of phenols and alcohols using
vanadium(V)-substituted polyoxomolybdates
1
ALI GHARIB1,2 and MANOUCHEHR JAHANGIR
*
1Department of Chemistry, Islamic Azad University, Mashhad, Iran and
2Agricultural Research and Services Centre, Mashhad, Iran
(Received 7 May, revised 9 July 2011)
Abstract: Alcohols and phenols were tetrahydropyranylated in the presence of
H7[PMo8V4O40] in good to excellent yields in acetonitrile and under solvent-
free reaction conditions. A mild and convenient method for the formation and
deprotection of ethers (THP ethers) is described. The formation of THP ethers
from the corresponding alcohols was accomplished in the presence of acid-sen-
sitive functional groups.
Keywords: tetrahydropyranyl ethers; heteropolyacid; protecting group; tetra-
hydropyranylation.
INTRODUCTION
Due to the easy preparation and good stability of tetrahydropyranyl groups in
the presence of hydrides, alkylating agents, Grignard reagents, organometallic re-
1
agents, etc., they are frequently used for the protection of alcohols and phenols.
In addition, they serve as stable protecting groups in peptide, nucleoside, nucleo-
tide, carbohydrate and steroid chemistry. Tetrahydropyranylation of alcohols can
2
3
be accomplished using p-toluenesulfonic acid (p-TSA), BF ·OEt and pyridi-
3
2
4
nium ptoluenesulfonate (PPTS). Recently, some developed reagents have been
used for this purpose, such as ZrCl , I , LiBr, acetonyltriphenylphosphonium
bromide, tetrabutylammonium tribromide (TBATB), aluminium chloride hexa-
hydrate, indium(III) trifluoromethanesulfonate (In(OTf) ), alkylimidazolium
tetrachloroaluminates, InCl immobilized in ionic liquids, polystyrene-bound
tin(IV) porphyrin, Dowex 50WX4-100, pyridinium chloride, SiO2·p-TSA,
N,N’-bis[3,5-bis(trifluoromethyl)phenyl]thiourea and a polystyrene-bound ana-
logue, Al(OTf) , and bromodimethylsulphonium bromide. The employ-
ment of protective groups is an important procedure in organic synthesis.
5
6
7
4
2
8
9
10
11
3
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13
3
14
15
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3
21
*Corresponding author. E-mail: aligharib5@yahoo.com
doi: 10.2298/JSC110507176G
287
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GHARIB and JAHANGIR
Among numerous protecting groups of alcohols, the tetrahydropyranyl (THP)
group is one of the most frequently employed protecting groups due to its
stability towards most non-acidic reaction conditions, ease of preparation, and
facile removal under mild acidic conditions. Recent examples include stannous
22
chloride dihydrate, and heterogeneous catalysts such as sulphuric acid adsorbed
23
24
25
on silica gel, ionic liquids and polyoxometalate. For the deprotection of
tetrahydropyranyl ethers (THP ethers), reagents including tetrafluoroborate
26
27
28
29,30
anion, sodium bromate, CBr , and montmorillonite clays
have been
4
employed. Also, reductive reaction of tetrahydropyranyl ethers were reported in
31
the literature. Mild and chemoselective protection and deprotection of hydroxyl
functionality are essential parts in the synthetic operation of polyfunctional or-
21
ganic compounds, especially in the context of natural product and carbohydrate
chemistry. Furthermore, its precursor, 3,4-dihydro-2H-pyran (DHP) is relatively
32
inexpensive, rendering the process amenable to large-scale processes. A hetero-
polyacid is an oxide cluster that has a type of phosphorus/silicon oxo acid and
oxo acids with molybdenum, tungsten and other elements. The application of
heteropolyacid as catalytic materials is growing continuously in the field of cata-
33
lysis. These compounds possess unique properties, such as: well-defined struc-
ture, Brønsted acidity, possibility to modify their acid–base and redox properties
by changing their chemical composition (substituted HPAs), ability to accept and
34
release electrons, high proton mobility, etc. Acidity, basicity, and pseudo liquid
behaviour are the principal factors governing the acid catalysis by solid hetero-
polyacids. The acidic properties are mainly controlled by i) the structure and
composition of the heteropoly anion itself, ii) the counter cations and iii) the dis-
persion on supports. The acid strength can be controlled mainly by i), and the
number of acid sites is greatly influenced by ii) and iii). Besides, soft basicity of
the heteropoly anion itself sometimes plays an important role for high catalytic
activity in acid-catalyzed reactions. The acid strength of hydrogen forms in the
solid state reflects on the general the acidity in solution and it decreases when W
is replaced by Mo and when the central P atom is replaced by Si in Keggin hete-
ropolyacids, whereby Keggin heteropolyacids are stronger acids than Dawson
35
heteropolyacids.
EXPERIMENTAL
Materials and methods
All chemical materials were purchased from Merck and used without further purify-
cation.
Instruments
The 1H-NMR spectra were recorded on a FT NMR Bruker 300 MHz spectrometer at 298
K. Chemical shifts were reported in ppm (δ-scale) relative to the internal standard TMS (0.00
ppm); the solvent was used as a reference. Melting points (m.p.) were recorded on an Electro-
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TETRAHYDROPYRANYLATION OF PHENOLS AND ALCOHOLS
289
thermal type 9100 melting point apparatus and are uncorrected. The products were identified
by comparison of their m.p., IR and NMR spectra with those of authentic samples.
Catalyst preparation
The catalysts H4[PMo11VO40], H5[PMo10V2O40], H6[PMo9V3O40], H7[PMo8V4O40] and
Wells–Dawson, H6[P2W18O62] were prepared in accordance to literature methods.36–41
General procedure for the protection of alcohols using the heteropolyacid catalysts in the
presence of solvents
To a mixture of benzyl alcohol (1.0 mmol) and DHP (1.0 mmol) in dry CH3CN (5 mL)
was added a heteropolyacid catalyst (1.2 mol), and the resulting mixture was stirred at room
temperature for the appropriate time until the complete disappearance of the starting alcohol
was confirmed by thin layer chromatography (TLC). After completion of the reaction, the
solid catalyst was removed by simple filtration. Evaporation of the solvent under reduced
pressure gave the almost pure THP ether. Column chromatography of the filtrate on silica gel
using n-hexane:EtOAc (6:1) as eluent gave benzyl tetrahydropyranyl ether in high yield.
General procedure for the solvent-free protection of alcohols using heteropolyacid catalysts
To a mixture of benzyl alcohol (1.0 mmol) and DHP (1.0 mmol) was added a heteropoly-
acid catalyst (1.2 mol), and the resulting mixture was stirred at room temperature for the ap-
propriate time until the complete disappearance of the starting alcohol (as monitored by TLC).
After completion of the reaction, reaction, CHCl3 (5 ml) was added and the organic phase was
obtained by simple filtration. Evaporation of the solvent under reduced pressure gave the al-
most pure THP ether. Column chromatography of the filtrate on silica gel using n-hexane:EtOAc
(6:1) as eluent gave benzyl tetrahydropyranyl ether in high yield.
RESULTS AND DISCUSSION
Alcohols, phenols, 3,4-dihydro-2H-pyran (DHP), and H [PMo V O ] and
7
8 4 40
other heteropolyacid catalysts were stirred in CH CN at room temperature to
3
yield the corresponding THP ethers. The tetrahydropyranylation of alcohols and
phenols in the presence of H [PMo V O ] was investigated and herein, a mild
7
8 4 40
and efficient method for the conversion of alcohols to THP compounds is re-
ported. First, the protection of benzyl alcohol in the presence of H [PMo V O ]
7
8 4 40
and other heteropolyacid catalysts was studied. Benzyl tetrahydropyranyl ether
was formed after appropriate times. Then, these conditions were applied for the
protection of structurally different alcohols and phenols (Scheme 1).
Scheme 1. Tetrahydropyranylation of phenols and alcohols using heteropolyacid catalysts.
Various aromatic and aliphatic alcohols were tetrahydropyranylated to THP
compounds using H [PMo V O ] heteropolyacid catalyst in good to high yields
7
8 4 40
under ambient conditions without any by-products. Employing the ratios shown
in Table I, the best results were obtained and THP ethers were produced in good
to excellent yields. The results of tetrahydropyranylation of alcohols to THP
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GHARIB and JAHANGIR
ethers are presented in Table I. As can be seen in Table I, primary, secondary and
tertiary alcohols and phenols were all protected under the employed conditions.
Thus, this method is very suitable for the protection of various types of alcohols
and phenols, providing a novel application of H [PMo V O ] heteropolyacid
7
8 4 40
catalyst in organic synthesis.
TABLE I. Preparation of THP ethers in the presence of H7[PMo8V4O40] catalyst in MeCN
and under solvent-free conditions (The products were characterized by their physical proper-
ties, comparison with authentic samples, and by spectroscopic methods. The reaction was
performed at room temperature. Molar ratios for ROH/DHP/H7[PMo8V4O40], (HPAs) ca-
talysts were 1:1:1.2)
CH3CN
Solvent-free
Entry
1
ROH
meTi, min Isolated yield, % Time, min Isolated yield, %
OH
32
33
65.5
80
20
23
69
82
OH
2
3
OH
23
91
21
80.5
O2N
Cl
OH
4
5
25
8
95
96
24
10
93.4
94.4
OH
H3C
OH
6
7
9
90
98
9
8
90
CH3
OH
10
95.5
H3C
O
OH
8
9
9
7
96
89
10
6
97
88
H3C
H3C
H3C
OH
OH
10
11
12
15
18
8
91
98
16
20
11
93
99
98
CH3
OH
96.3
OH
H3C
O
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TETRAHYDROPYRANYLATION OF PHENOLS AND ALCOHOLS
291
TABLE I. Continued
CH3CN
Solvent-free
Entry
13
ROH
Time, min Isolated yield, % Time, min Isolated yield, %
OH
OH
5
97.5
7
95
O
H3C
14
15
11
16
98
10
19
97
93
90.6
OH
Cl
16
17
17
23
86
15
25
88
98
OH
OH
O2N
OH
97.5
18
19
20
30
31
7
98.5
97.5
98
30
29
11
96
96
98
OH
OH
21
6
97
9
97
OH
22
23
9
9.5
91.5
93.5
10
9
94
91
OH
OH
CH2
24
14
94.5
17
95
OH
Br
OH
25
26
27
8
7
92
94
93
12
9
94
90.5
93
H3C
CH3
OH
Cl
Cl
OH
16
15
O
O
28
29
11
93.2
87
12
18
95.5
89.5
OH
OH
Ph
19.5
30
8.5
91.2
11.5
93
OH
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GHARIB and JAHANGIR
TABLE I. Continued
CH3CN
Solvent-free
Entry
31
ROH
Time, min Isolated yield, % eTim, min Isolated yield, %
OH
27.5
94.5
29
91.6
OH
32
21
92.4
20
90.5
HO
This method was found to be highly selective for primary alcohols. In a bi-
nary mixture of 3-phenyl-1-propanol and 2-octanol, the primary alcohol was
completely converted to corresponding THP ether, while only 8 % of 2-octanol
reacted. Similarly, excellent selectivity was observed for tetrahydropyranylation
of benzyl alcohol in the presence of 1-phenylethanol (Table II, entry 2). Primary
and secondary alcohols were selectively converted to THP ethers in the presence
of a tertiary alcohol (Table II, entries 5 and 6). Furthermore, this method showed
excellent selectivity in the tetrahydropyranylation of alcohols in the presence of
phenols (Table II, entry 7).
TABLE II. Selectivity of the reactions of different binary mixtures with DHP/H7[PMo8V4O40]
Entry
1
Binary mixture
Product
Time, min Yielda, %
11
91.5
OH
OTHP
OTHP
8
OH
OH
2
18
93.2
OTHP
CH3
OTHP
CH3
6
OH
3
4
22
14
83
16
OH
OTHP
OTHP
OH
100
0
OH
OTHP
OTHP
OH
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TETRAHYDROPYRANYLATION OF PHENOLS AND ALCOHOLS
293
TABLE II. Continued
Entry
5
Binary mixture
Product
Time, min Yielda, %
23
91
OH
OTHP
OH
OTHP
9
OH
OH
OTHP
OTHP
6
21
82
18
7
18
92
8
OH
OH
OTHP
OTHP
a
GC yield using internal standard; ROH:DHP:H7[PMo8V4O40] = 1:1:1.2; the reaction was performed at room
temperature
Effect of the catalyst type
In order to compare the kinds of vanadium(V)-substituted polyoxomolyb-
dates, i.e., H [PMo VO ], H [PMo V O ], H [PMo V O ], and Wells–Daw-
4
11
40
5
10 2 40
6
9 3 40
son catalysts, with the H [PMo V O ] catalyst in the tetrahydropyranylation of
7
8 4 40
alcohols and phenols, these catalysts were used for the tetrahydropyranylation of
alcohols and phenols. The results are shown in Table III. The yield of product
decreased in the following order: H [PMo V O ] > H [P W O ] >
7
8
4
40
6
2
18 62
H [PMo V O ] > H [PMo V O ] > H [PMo VO ]. The results showed
6
9 3 40
5
10
2
40
4
11
40
that H [PMo V O ] was the most efficient catalyst for THP with a higher acti-
7
8 4 40
vity than the Keggin and Dawson heteropolyacids. The larger number of protons
in its structure may lower the activation barrier for the alkylation reaction. In
addition, the large anion also provides many “sites” on the molecule that are li-
kely to contribute to the effectiveness of the catalyst. Comparison of the results
obtained using vanadium (V)-substituted polyoxomolybdates types of hetero-
polyacids and Wells–Dawson catalysts with those reported for H [PMo V O ]
7
8 4 40
and Dawson type catalysts shows some advantages of the former catalysts in
these reactions (Table III).
Spectroscopic data for the new compound 16
Compound 16 (Table I). Yellowish oil (eluted with n-hexane: EtOAc, 6:1).
1
H-NMR (300 MHz, CDCl , δ / ppm): 1.48–1.90 (6H, m), 3.52 (1H, m), 3.89
3
(1H, m), 4.42 (1H, d, J = 11.6 Hz), 4.70 (1H, m), 4.80 (1H, d, J = 12.0 Hz), 7.25
13
(4H, m); C-NMR (75 MHz, CDCl , δ / ppm): 147.6, 146.6, 128.1, 123.9, 98.7,
3
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GHARIB and JAHANGIR
+
68.0, 62.6, 30.8, 25.7, 19.6; HRMS (EI): Calcd. for C H O N [M] , 237.1001.
12 15
4
Found: 237.1003.
TABLE III. The role of the heteropolyacid on the tetrahydropyranylation under solvent-free
reaction conditions
Entry
1
Substrate
Catalyst
H7[PMo8V4O40]
Time, min
10
Yielda, %
97.3
OH
2
3
4
5
6
A
A
A
A
H6[P2W18O62]
H6[PMo9V3O40]
H5[PMo10V2O40]
H4[PMo11VO40]
H7[PMo8V4O40]
10
10
10
10
10
94.5
92.2
91.5
88.6
97
OH
7
8
9
10
11
B
B
B
B
H6[P2W18O62]
H6[PMo9V3O40]
H5[PMo10V2O40]
H4[PMo11VO40]
H7[PMo8V4O40]
10
10
10
10
22
94
91.5
90
88.5
99
CH3
OH
12
13
14
15
a
C
H6[P2W18O62]
H6[PMo9V3O40]
H5[PMo10V2O40]
H4[PMo11VO40]
22
22
22
22
96.5
94.3
91.5
90.4
C
C
C
Isolated yield determined by GC. The reaction was performed at room temperature. Substrate of entry 1: com-
pound A, substrate of entry 6: compound B and substrate of entry 11: compound C
CONCLUSIONS
In summary, a novel method using different vanadium(V)-substituted poly-
oxomolybdates and Wells–Dawson heteropolyacids as inexpensive, non-corro-
sive and environmentally benign catalysts for protection of phenols and alcohols
as THP ethers was developed. The advantages of the presented procedure are
simplicity of operation and work-up and good yields of products, mild condi-
tions, short reaction times and high yields (> 90 %).
И З В О Д
КАТАЛИТИЧКА ТЕТРАХИДРОПИРАНИЛАЦИЈА ФЕНОЛА И АЛКОХОЛА
ВАНАДИЈУМ(V)-СУПСТИТУИСАНИМ ПОЛИОКСОМОЛИБДАТИМА
ALI GHARIB1,2 и MANOUCHEHR JAHANGIR1
1Department of Chemistry, Islamic Azad University, Mashhad и 2Agricultural Research
and Services Center, Mashhad, Iran
Успешно је извршена реакција алкохола и фенола са тетрахидропираном у присуству
H7[PMo8V4O40] у добром до одличном приносу, без присустног растварача. Описани су бла-
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TETRAHYDROPYRANYLATION OF PHENOLS AND ALCOHOLS
295
ги реакциони услови за формирање и депротекцију тетрахидропиранил етара (THP етри).
Грађење THP етара са одговарајућим алкохолима извршено је у присуству функционалних
група које су осетљиве на киселе реакционе услове.
(Примљено 7. маја, ревидирано 9. јула 2011)
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