LETTER
1777
Simple, Facile and Highly Selective Tetrahydropyranylation of Alcohols Using
Silica Chloride1
Simple
T
etrahydro
.
pyranylation
R
of Alcohols
U
si
a
ng
S
ilica
C
h
v
loride indranath, C. Ramesh, Biswanath Das*
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax +91(40)7173387, +91(40)7173757; E-mail: biswanathdas@yahoo.com
Received 4 July 2001
small quantity of catalyst. The catalyst can easily be
Abstract: A simple and efficient process for tetrahydropyranyla-
tion of alcohols has been developed by reacting with dihydropyran
at room temperature in presence of catalytic amount of silica chlo-
ride. The process is highly selective for monoprotection of the hy-
droxyl groups of symmetric diols.
prepared8 from the readily available reagents, thionyl
chloride and silica gel. When the reaction was carried out
with only thionyl chloride in absence of silica gel the
yields and the selectivity were diminished. The experi-
mental procedure is easy. After the reaction was complete
the product was isolated by simple elution of the solid
mass with CH2Cl2. The structures of all the products were
established from their spectral and analytical data.
Key words: alcohols, tetrahydropyranylation, silica chloride, sym-
metric diols, monoprotection
Tetrahydropyranylation is a versatile method for protec-
tion of hydroxyl groups.2 Due to the stability of the tet-
rahydropyranyl ethers under different conditions such as
alkaline media, reactions involving Grignard reagents and
lithium alkyls, oxidative reagents, metal hydrides and
alkylating and acylating reagents tetrahydropyranylation
is a general process to protect hydroxy groups in multistep
organic transformations.3 Tetrahydropyranyl derivatives
can be prepared by using a variety of reagents such as pro-
tic (HCl, p-toluenesulfonic acid) and Lewis acids
(BF3 OEt2, Al2(SO4)3 on silica gel, ZnCl2 on alumina),2,4
clay materials,3 ion exchange resins5 and DDQ.6 Howev-
er, several reported methods are associated with certain
drawbacks which include long reaction time, refluxing
condition and the uses of reagents which may effect the
other functionalities. They have also limitation in selectiv-
ity of monoprotection of the hydroxyl groups of symmet-
ric diols. Thus there is a need for suitable mild and
selective method for this purpose.
In conclusion, we have developed a simple, efficient and
highly selective process for tetrahydropyranylation of al-
cohols using combination of the solid surface of silica gel
and thionyl chloride. The mild reaction condition, high
yield, fast reaction time, less expensive and readily avail-
able reagents and easy experimental procedure are the ad-
vantages of the present method. We believe the present
process will find applications as a useful synthetic meth-
odology.
Typical experimental procedure:
To a solution of hexane-1,6-diol (118 mg, 1 mmol) and 3,4-dihydro-
2H-pyran (84 mg, 1 mmol) in CH2Cl2 (10 mL), silica chloride (10
mg) was added. The reaction was stirred at room temperature and
was monitored by TLC. After 30 min the mixture was filtered and
the filtrate was concentrated and purified by column chromatogra-
phy over silica gel to afford monotetrahydropyranyl ether of hex-
ane-1,6-diol (180 mg, 90%).
Acknowledgement
NR and CR thank UGC, New Delhi for financial assistance.
Scheme
References and Notes
In continuation of our recent work7 on solid supported re-
actions we have observed that silica chloride is a conve-
nient and efficient catalyst for tetrahydropyranylation of
alcohols. These compounds when treated with 3,4-dihy-
dro-2H-pyran at room temperature in presence of the
above mentioned catalyst produced the corresponding tet-
rahydropyranyl ethers in high yields (Scheme, Table).
The process was found to be highly selective for monotet-
rahydropyranylation of symmetric diols. The conversion
proceeded within a short time (30–40 min) and with a
(1) (a) Part 10 in series „Studies on Novel Synthetic
Methodology“, for part 9 see: Das B., Venkataiah B.,
Madhusudan P; Synth. Commun. 2001, in press. (b) IICT
Communication No: 4752.
(2) Green, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; John Wiley and Sons, Inc.: New York, 2000, 3rd
ed., 17–292; and reference cited therein.
(3) Hoyer, S.; Laazol, P. Synthesis 1986, 655; and reference
cited therein.
(4) (a) Ranu, B. C.; Saha, M. J. Org. Chem. 1994, 59, 8269; and
references cited therein. (b) Nishiguchi, T.; Kawamine, K. J.
Chem. Soc., Chem. Commun. 1990, 1766.
(5) (a) Bongini, A.; Cardillo, G.; Orena, M.; Sandri, S. Synthesis
1979, 618. (b) Olah, G. A.; Husain, A.; Singh, B. P.
Synthesis 1983, 892.
Synlett 2001, No. 11, 26 10 2001. Article Identifier:
1437-2096,E;2001,0,11,1777,1778,ftx,en;D15701ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214
Ravindranath
