Efficient method for tetrahydropyranylation/depyranylation of phenols and alcohols using a solid acid catalyst with Wells-Dawson structure

Article abstract of DOI:10.1016/S0040-4039(02)01822-1

A simple and efficient procedure to form 2-tetrahydropyranyl acetals of phenols and alcohols is reported. Wells-Dawson heteropolyacid catalyst is used both in bulk form or supported on silica, reaction conditions include room temperature and toluene as solvent. Fast deprotection of THP-acetals can be attained by mere change of the solvent using THF-1% MeOH. In both reactions the supported catalyst is easily recoverable and reusable, and the yields are good to excellent.

Full text of DOI:10.1016/S0040-4039(02)01822-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7589–7591
Efficient method for tetrahydropyranylation/depyranylation of
phenols and alcohols using a solid acid catalyst with
Wells–Dawson structure
Gustavo P. Romanelli,a,b Graciela Baronetti,c Horacio J. Thomasb and Juan C. Autinoa,*
aLaboratorio de Estudio de Compuestos Orga´nicos (LADECOR), Departamento de Qu´ımica, Facultad de Ciencias Exactas,
Universidad Nacional de La Plata, Calles 47 y 115 (1900), La Plata, Argentina
bCentro de Investigacio´n y Desarrollo en Procesos Catal´ıticos (CINDECA), Departamento de Qu´ımica, Facultad de Ciencias
Exactas, Universidad Nacional de La Plata-CONICET, Calle 47 N° 257 (1900), La Plata, Argentina
cDepartamento de Ingenier´ıa Qu´ımica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad
Universitaria (1428), Buenos Aires, Argentina
Received 8 July 2002; revised 20 August 2002; accepted 21 August 2002
Abstract—A simple and efficient procedure to form 2-tetrahydropyranyl acetals of phenols and alcohols is reported. Wells–Daw-
son heteropolyacid catalyst is used both in bulk form or supported on silica, reaction conditions include room temperature and
toluene as solvent. Fast deprotection of THP-acetals can be attained by mere change of the solvent using THF–1% MeOH. In
both reactions the supported catalyst is easily recoverable and reusable, and the yields are good to excellent. © 2002 Elsevier
Science Ltd. All rights reserved.
Introduction and removal of protective groups is of
great significance in organic synthesis.1,2 Amongst vari-
ous procedures available for the protection of hydroxyl
groups, tetrahydropyranylation is the most frequently
used because of the remarkable stability of tetra-
hydropyranyl acetals under a variety of conditions.3 A
The problems associated with the handling and disposal
of the inorganic acids, and their environmental and
potential hazards have raised our interest in the devel-
opment of alternative procedures using solid acid cata-
lysts.9,14 Due to their superacidic properties, HPAs can
be used in reactions requiring electrophilic catalysis.
HPAs are applied both in bulk or supported form,
homogeneous and heterogeneous catalysis being possi-
ble. The structure of Wells–Dawson (WD) acid
(H6P2W18O62·24H2O) consists of a close-packed frame-
work of octahedra WO6 surrounding a central P atom,
two identical ‘half units’ PW9 are linked through the
oxygen atoms.15
number of
catalysts
have
been used
for
tetrahydropyranylation3 such as protic acids4 and Lewis
acids.5 Besides, tetrahydropyranylation has been carried
out using some heterogeneous catalysts, e.g. ion
exchange resins,6 zinc chloride on alumina, natural
kaolinite clay and sulfuric acid adsorbed on silica
gel;7 heteropolyoxometallates8 and heteropolyacids
(HPAs).9,10 Deprotection of tetrahydropyranyl deriva-
tives has involved catalysts such as mineral acids,11
organic acids, PPTS and Lewis acids,11 hetero-
polyoxometallates8 and HPAS;10 other compounds
have been recently used such as LiBr,3 CBr4/MeOH,12
Sc(OTf)3.13 Amongst the heterogeneous catalysts,
montmorillonite clays,2 Amberlyst H-1511 and sulfuric
acid adsorbed on silica gel7 have been used.
WD acid (H6P2W18O62(aq)) was prepared as described
elsewhere15 from an aqueous solution of a/b
K6P2W18O62·10H2O salt, which was treated with ether
and a concentrated (37%) HCl solution.
Silica-supported WD acid was obtained by wet impreg-
nation of Grace Davidson silica (Grade 59, specific
area=250 m2/g) with an aqueous solution of WD acid;
a catalyst containing 20% (weight) of WD acid was
prepared. After impregnation, catalyst samples were
dried at room temperature in a vacuum-dessicator for
8 h.
Keywords: protecting group; tetrahydropyranyl; heteropolyacids;
Wells–Dawson catalyst; alcohols; phenols.
* Corresponding author. Fax: +54221 4220288; e-mail: jautino@
quimica.unlp.edu.ar
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01822-1

7590
G. P. Romanelli et al. / Tetrahedron Letters 43 (2002) 7589–7591
Table 1. Tetrahydropyranylation of phenols and alcoholsa
In general, the experiments involving catalyst supported
on silica afforded similar yields to those obtained using
bulk catalyst. However, use of the supported one allows
for the easy separation and recovery of the catalyst for
its immediate reutilization, without any lowering of its
activity. For the checked examples, yields were practi-
cally unchanged over three reaction cycles. All yields
were calculated from isolated products. Their purity was
established by GLC, being better than 97% in all the
cases.
Phenol or
alcohol
ROH:DHP
molar ratio
% Yield
Bulk WD
Supported WDb
1
2
3
4
5
6
7
8
1:2
1:5
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
98
61
91
95
76
99 (98)
61
90
92 (92)
70
80
100 (98)
98
97
100 (99)
99
98
81
The protection reaction was studied using phenols 1–8
and alcohols 9–13 as the substrates,† structure and
substitution pattern are showed in Scheme 1. Different
reaction conditions were checked: temperature, time and
concentration of the solutions. The reaction was carried
out using both bulk and supported WD catalysts; molar
ratio of the WD acid to substrate was also varied.
100
100
99
100
98
9
10
11
12
13
97
96
95
To a mixture of phenol or alcohol (0.5 mmol) and DHP
(1 mmol) in toluene (2 ml) WD catalyst (1% mmol) was
added and stirred at room temperature for 2 h, see Table
1. The reaction mixture was filtered, washed (1 M NaOH
and then H2O but only for phenol substrates) and the
solution was dried over anhydrous Na2SO4. Filtration
and concentration followed by flash column chromatog-
raphy on silica (hexanes–toluene) afforded THP-acetals.
They were identified via comparison with authentic
samples (TLC, GC).
a Reactions were performed at 20°C in toluene, using 1% (mmol) of
WD acid; reaction time 2 h.
b Yields in parentheses correspond to the second reutilization of the
catalyst.
Removal of the THP group can be performed under
mild reaction conditions, and the reaction proceeds in a
few minutes. Hydrolysis of 1-THP using 1% of bulk or
supported catalyst in different solvents give the results
shown in Table 2. When toluene was used, the reaction
was slow and a maximum yield of 78% in 5 h was
reached. Using THF, 94% yield was obtained in 2 h.
Methanol dissolves the catalyst, yielding 100% after 15
min, therefore is a good solvent for the homogeneous
reaction, but it is disadvantageous when supported
catalyst is used because it dissolves the WD acid off the
silica. Therefore, and taking into account recent
results,14 we examined the use of a THF plus 1% MeOH
mixture, obtaining excellent yields. Besides, the use of
supported WD acid afforded similar yields to those
obtained with bulk catalyst. Deprotection of THP-
acetals of compounds 2–13 was performed using stan-
dardized reaction conditions, see Table 3, giving clean
reactions and yields better than 95% in all the examples.
Shorter reaction times cause lower yields of THP-acetal
of 1 (1-THP), longer times also cause a lowering of the
yields. When there is a nitro group at the phenyl ring,
moderate yields are obtained, unmodified by prolonged
reaction times; however, yields are at least good in the
presence of other electron withdrawing groups.
Table 2. Deprotection of THP-acetal of phenol 1a
Solvent
t (min)
% Yield
Supported WD
Bulk WD
MeOH
PhMe
THF
15
300
60
100
78
88
–
78
90
THF
120
5
10
94
91
100
100
94
71
1% MeOH/THF
1% MeOH/THF
1% MeOH/THF
94
15
99 (98)b
Scheme 1. Phenol and alcohol substrates.
a Reactions were performed at 20°C using 1% (mmol) of WD acid
and molar ratio ROH:DHP, 1:2.
† Starting phenols and alcohols 1–13 were commercial, they were
initially purified to match the reported physical data.
b Yields in parentheses correspond to the second reutilization of the
catalyst.

G. P. Romanelli et al. / Tetrahedron Letters 43 (2002) 7589–7591
7591
Table 3. Deprotection of THP-acetals of phenols and
Acknowledgements
alcoholsa
THP-acetal of
% Yield
Supported WDb
Financial support from CONICET (Argentina), and
Universidad Nacional de La Plata is gratefully
acknowledged. G.P.R., G.B. and H.J.T. are members
of CONICET.
Bulk WD
2
3
99
98
94
97
4
5
100
96
98 (97)
95
References
6
95
95
7
8
9
10
11
12
13
98
96
98
99
100
100
98
96 (96)
95
98
97 (95)
99
98
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The THP-acetal (0.5 mmol) was dissolved in THF–1%
MeOH (2 ml), 1% WD catalyst was added and the
mixture was stirred at room temperature for the stated
time (Tables 2 and 3). The suspension was filtered, the
solution was dried over anhydrous Na2SO4, filtered and
concentrated, and the crude product was subjected to
column chromatography (toluene–EtOAc) to yield the
alcohol or phenol.
Conclusions
These procedures provide a useful alternative for the
preparation of THP-acetals, as well as for their cleav-
age to the corresponding phenols or alcohols. Advan-
tages of this methodology are: operational simplicity,
no corrosive and reusable catalyst, mild conditions,
short reaction times and excellent yields. The use of the
solid catalyst allows replacement of the usual soluble
inorganic acids, contributing to a reduction of waste.
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