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Published on the web February 25, 2012
Environmentally Friendly Tetrahydrofuranylation of Alcohols
Using NaHSO4-SiO2 under Solvent-free Conditions
Henok H. Kinfe,* Sullivan Terblanche, Konanani D. Tshivhase, and Livhuwani Ravhura
Research Centre in Synthesis and Catalysis, Department of Chemistry, University of Johannesburg,
P. O. Box 524, Auckland Park 2006, South Africa
(Received December 10, 2011; CL-111179; E-mail: hhkinfe@uj.ac.za)
A simple, environmentally friendly, and efficient tetra-
hydrofuranylation of alcohols has been developed using NaH-
SO4-SiO2 (0.5 mol %) as a catalyst under solvent-free condi-
tions to yield corresponding THF ethers in good to excellent
yields.
OH NaHSO4-SiO2 (0.5 mol%)
O
O
O
(1.5 equiv)
Scheme 1. Tetrahydrofuranylation of benzyl alcohol.
The protection of alcohols as 2-tetrahydrofuranyl (THF) ether
is a well-established protocol in organic synthesis.1,2 THF ethers
like their homologues relative and extensively studied 2-tetra-
hydropyranyl (THP) ethers are tolerant to a range of alkaline and
organometallic reagents.3,4 THF ethers are more preferable
protecting groups than THP ethers since they can be deprotected
under very mild acidic conditions.3 This difference in labiality to
acidic conditions allows selective deprotection of THF ethers in
the presence of THP ethers in organic synthesis strategies.1,3,5,6
However, the wide application of THF ethers as orthogonal
protecting groups is hampered by the limited number of tetra-
hydrofuranylation protocols reported in the literature. This is
mainly due to the reagents employed being expensive, toxic,
commercially unavailable, corrosive, incompatible with sensitive
functional groups as well as the need for chlorinated solvents.7,8
The reagent systems reported include: BrCCl3/2,4,6-collidine/
THF,3 Al(OTf)3/DHF/DCM,4 2-chlorotetrahydrofuran/Et3N,5
the catalyst loading to 0.2 mol % resulted in a sluggish reaction
and low yields.
Variation in the total amount of DHF revealed that 1.5
equivalents were sufficient to fully convert the alcohol into the
desired THF ether. Treatment of various primary and secondary
alcohols in this way provided efficient access to the desired THF
ethers.27 While tertiary alcohols were difficult to protect, the
reactions proceeded remarkably well with the other alcohols.
In all cases, complete conversion of the starting alcohol was
achieved in a short reaction time, and good to excellent yields
(67-91%) of the ethers were obtained (Table 1). Products were
identified by 1H and 13C NMR spectroscopy after chromato-
graphic purification. Interestingly, no aqueous workup was
required as reaction mixtures were directly loaded onto silica
gel for chromatographic purification. The reaction conditions are
tolerant of a range of acid-sensitive groups such as allyl (Table 1,
Entry 6), propargyl (Table 1, Entry 7), and ether linkages
(Table 1, Entry 2).
CrCl2/CCl4/THF,6
VCl3/THF/CCl4,7
Mn(0)/THF/CCl4,8
(ON+)(Salen)ruthenium(II) complex/2,3-dihydrofuran (DHF)/
DCM,9 Ph2CHCO2-DHF/TsOH/CCl4,10 CAN/THF,11 PhI(OAc)2/
Investigation of the recovery and reusability of the catalyst
was carried out using benzyl alcohol as a model substrate. The
catalyst was recovered quantitatively by simple filtration, washed
with diethyl ether, and then reactivated at 100 °C for 30 min in an
oven. The catalyst was reused at least three times without lose of
activity (1st use 90%, 2nd use 90%, and 3rd use 92%).
THF,12 (n-Bu4N+)2S2O8 /THF,13 tert-butylperoxy--3-iodane/
¹
CCl4/THF,14 acetonyltriphenylphosphonium bromide (ATPB)/
CH2Cl2,15 p-TsCl/NaH/THF,16 and FeCl3/THF/UV.17 Unlike in
the tetrahydropyranylation of alcohols, the use of efficient acid
catalysts for tetrahydrofuranylation has received very little
attention in the literature.4 Herein, we report a novel, inexpensive,
solvent-free, high yielding, and simple protocol using NaHSO4
supported on silica gel as a catalyst in order to address some of the
tetrahydrofuranylation issues.
Since SiO2 is a well-known Lewis acid catalyst,28 it was
important to investigate whether the activity of the NaHSO4-SiO2
was the result of SiO2 alone or a combination of the two. Thus,
attempts were made to effect tetrahydrofuranylation of benzyl
alcohol using SiO2. However, formation of a new product was not
detected from TLC analysis. The importance of SiO2 was then
tested by trying to effect tetrahydrofuranylation of benzyl alcohol
in the presence of unsupported NaHSO4 (0.5 mol %). The reaction
provided the desired THF ether but at a relatively slower rate,
50 min (compared to less than 5 min in the case of supported
NaHSO4) proving it was the combination of NaHSO4 and SiO2
that contributed to the efficiency of the catalyst. This difference in
the rate of the reaction is in accordance with results reported in the
literature.29 Nishiguchi and Taya reported that the silica gel serves
as a “reaction field” increasing the surface area where the reagents
and substances get adsorbed to react at a relatively faster rate.29
The protocol is superior to reported methods in terms of
yield, catalyst loading, and reaction rate as can be seen from the
results shown in Table 2. All the reported methods require an
organic solvent, longer reaction time, and in most cases elevated
NaHSO4 supported on silica gel has gained interest in organic
synthesis as a viable and alternative acid catalyst for a number of
transformations due to its low cost, ease of preparation, mildness,
recoverability, reusability, and insensitivity to moisture. It has
been applied as a catalyst in the opening of epoxides into ¢-
hydroperoxy alcohols;18 synthesis of trisubstituted quinolines,19
¢-enaminones,20 N-acylsulfonamides,21 aryl-14H-dibenzo[a.j]-
xanthenes,22 amidoalkylnaphthols,23 and coumarins;24 selective
monoacetylation of unsymmetrical diols;25 and the Ferrier rear-
rangement of glycals.26
In our first attempt in developing a solvent-free NaHSO4-
catalyzed tetrahydrofuranylation, a solvent-free solution of benzyl
alcohol and DHF was treated with 0.5 mol % of NaHSO4-SiO2
(3.0 mmol NaHSO4/g)25 to afford the corresponding THF ether in
90% yield in 5 min at room temperature (Scheme 1). Reducing
Chem. Lett. 2012, 41, 272-273
© 2012 The Chemical Society of Japan
Kinfe, Henok H.
