Amberlyst-15-catalyzed one-pot synthesis of 2-aryltetrahydrofurans from tetrahydrofuran

Article abstract of DOI:10.1055/s-0032-1317195

A simple one-step route for the conversion of naphthols and phenols with tetrahydrofuran into corresponding 2-aryltetrahydrofurans using Amberlyst-15 as a catalyst is reported. This is the first example of the acid-mediated formation and rearrangement reactions of tetrahydrofuranyl ethers prepared from the tetrahydrofuran and aromatic/aliphatic hydroxy compounds.

Full text of DOI:10.1055/s-0032-1317195

LETTER
▌2473
lAettmer berlyst-15-Catalyzed One-Pot Synthesis of 2-Aryltetrahydrofurans from
Tetrahydrofuran
One-Pot Synthesis of 2-Aryltetrahydrofurans
Hande Gunduz, Volkan Kumbaraci, Naciye Talinli*
Department of Chemistry, Istanbul Technical University, Maslak, 34469 Istanbul, Turkey
Fax +90(212)2856386; E-mail: talinlin@itu.edu.tr
Received: 14.07.2012; Accepted after revision: 14.08.2012
(ON+)(salen)ruthenium(II)2 complex, Al(OTf)3,1 or pyri-
Abstract: A simple one-step route for the conversion of naphthols
dinium p-toluenesulfonate (PPTS).3 The second method is
and phenols with tetrahydrofuran into corresponding 2-aryltetrahy-
based on the use of THF, in the presence of one-electron
drofurans using Amberlyst-15 as a catalyst is reported. This is the
oxidants progressing via a radical pathway. CrCl2–CCl4,4
first example of the acid-mediated formation and rearrangement re-
actions of tetrahydrofuranyl ethers prepared from the tetrahydrofu- BrCl3,5 Mn(0) powder,6 alkylperoxy-λ3-iodane7/carbon
8
ran and aromatic/aliphatic hydroxy compounds.
tetrachloride, and VCl3 were used effectively for tetrahy-
drofuranylation reaction as oxidants (Scheme 1). Alterna-
tively, Troisi and co-workers9 reported that the
tetrahydrofuranyl radical, generated by heating distilled
tetrahydrofuran in the presence of CO, Pd(OAc)2, Ph3P,
air, and allyl/benzyl chloride, becomes a useful tool to
transform the hydroxyl functions into tetrahydrofuranyl
ethers. However, when they performed the reactions using
undistilled THF, the products were not observed or were
only present in trace amounts. If stabilized THF is used,
an oxidant should be added to the reaction medium to let
the reaction progress.
Key words: 2-aryltetrahydrofurans, tetrahydrofuranyl ethers, Am-
berlyst-15, rearrangement reactions, naphthols
The conversion into tetrahydropyranyl (THP) or tetrahy-
drofuranyl (THF) ethers is part of an important method for
protecting alcohol functional groups. It is well-known
that, in comparison with THP ethers, THF ethers have the
advantage that they can be hydrolyzed under even milder
acidic conditions and also they can be selectively cleaved
in the presence of THP1 ethers.
On the other hand, it is also reported that the tetrahydrofu-
ranyl ether of 1-naphthol synthesized using one of these
methods afforded 2-aryltetrahydrofuran (Table 1, entry 4)
via rearrangement under acidic conditions.3 Additionaly,
Pinhey and Xuan10 reported that pyrolysis of phenol and
DHF at 150–180 °C in a Paar autoclave resulted directly
in the formation of 2-tetrahydrofuran-2-yl phenol with
37% yield within 17 hours. However, there is no report in
the literature on the protection of phenolic compounds
with THF in acidic media and also rearrangement product
being formed directly from the reaction between hydroxy
aromatic compounds and THF under acidic conditions.
O
OH
PPTS
O
O
or
+
oxidant
O
BF3⋅OEt2, 0 °C
or heat
OH
O
We disclose herein an operatively simple, inexpensive,
single-step procedure for the preparation of 2-aryltetrahy-
drofurans using commercial reagents and Amberlyst-15
strongly acidic resin (Scheme 2).
Scheme 1 Literature synthesis of 2-aryltetrahydrofurans
There are mainly two methods for the preparation of tet-
rahydrofuranyl ethers; the first one uses 2,3-dihydrofuran
(DHF) in the presence of various acid catalysts, including
In our previous studies, we have synthesized naphthofuro-
furan and naphthopyranopyran11 derivatives starting from
O
O
OH
OH
Amberlyst-15
+
+
O
heat
O
2
1
Scheme 2 Synthesis of 2-(2-hydroxynaphthyl)tetrahydrofuran using Amberlyst-15 as catalyst
SYNLETT 2012, 23, 2473–2476
Advanced online publication: 21.09.2012
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0032-1317195; Art ID: ST-2012-D0512-L
© Georg Thieme Verlag Stuttgart · New York

2474
H. Gunduz et al.
LETTER
structure of the byproduct, it was isolated in low yield by
preparative thin-layer chromatography. After the GC–MS
and NMR analysis, we were surprised to find out that the
byproduct was formed from 2-naphthol and THF, that is,
it was an unusual THF-involved reaction. In order to con-
firm this interesting result we treated 2-naphthol with
THF in the presence of Amberlyst-15 under reflux tem-
perature.12 Corresponding THF ether 21 was formed in 3%
yield but it was accompanied by the rearrangement prod-
uct 1 in 40% yield (Scheme 2).
Table 1 Synthesized 2-Aryltetrahydrofurans
Entry Substrate
Product
Yield
(%)b
O
OH
OH
1
40
1
Different from the earlier reported studies, in our study,
we have directly obtained compound 1 as the main prod-
uct starting with 2-naphthol and commercially supplied
THF in acidic conditions.
O
MeO
OH
MeO
3
OH
2
30
20
Treatment of various aromatic compounds which have a
free OH group gave ortho-substituted rearrangement
products (Table 1) accompanied by a small amount of tet-
rahydrofuranyl ethers. Phenol derivatives yielded the cor-
responding tetrahydrofuranyl compounds in lower yield
than naphthols (Table 1, entries 6 and 7). A protected phe-
nolic compound (Table 1, entry 5) did not give any prod-
uct. This result showed that 2-aryltetrahydrofurans
probably were not formed via an ortho-alkylation reac-
tion. These interesting results raised a question: How have
the protection and rearrangement reactions been realized
under these reaction conditions?
O
OH
Br
OH
Br
3
4
5
OH
O
OH
43,10
15a
As mentioned before, there is no report in the literature for
tetrahydrofuranylation of a hydroxyl group using THF in
the presence of acid catalyst alone. However, it is reported
that THF can be oxidized to 2-hydroperoxytetrahydrofu-
ran with hydrogen peroxide to give 2-hydroxy-THF, γ-bu-
tyrolactone.13 Furthermore, autoxidation of THF also
generates 2-hydroperoxytetrahydrofuran which decom-
poses to 2-hydroxy-THF and γ-butyrolactone.5,14
OMe
Br
5
–
–
OH
O
In addition to these studies, a series of tetrahyrofuranyl
ethers are synthesized using 2-hydroxy-THF and alco-
hols.15 In the conditions of our study, the oxidant could be
the air. Therefore, in order to investigate the role of air, we
repeated the reaction of 2-naphthol and THF under three
different conditions; (i) without catalyst in air, (ii) with
catalyst under inert atmosphere, and (iii) with catalyst us-
ing distilled THF. Without catalyst, only compound 2 was
detected by chromatographic analysis in trace amount.
However, under inert atmosphere neither 1 nor 2 were
formed even in traces. Using distilled THF did not much
affect the conversion rate. These results clearly showed
that the tetrahydrofuranylation reaction needed O2 as oxi-
dant. Based on these observations, a plausible reaction
mechanism for the tetrahydrofuranylation of the hydroxyl
group is proposed as follows: In the first step, 2-hydroxy-
THF formed from 2-hydroperoxytetrahydrofuran reacted
with 2-naphthol to give tetrahydrofuranyl ether and then
in the presence of acid catalyst the tetrahydrofuranyl
group was transferred to the α-position of the OH goup,
and the ortho-alkylated product was obtained (Scheme 3).
OH
6
7
13
15
6
OH
O
OH
O
O
O
Ph
Ph
7
a Product yields determined by GC–MS analysis.
b Isolated product yields.
2-naphthol and carbonyl compounds. In the continuation
of this study, 2-naphthol and derivatives were reacted
with different carbonyl compounds in THF using Amber-
lyst-15 as catalyst. Together with the desired product, a
small amount of unknown byproduct was observed by
thin-layer chromatography. In order to determine the
These unusual findings provoked our interest to further
explore these reactions. In order to prevent the rearrange-
Synlett 2012, 23, 2473–2476
© Georg Thieme Verlag Stuttgart · New York

LETTER
One-Pot Synthesis of 2-Aryltetrahydrofurans
2475
OH
O
OH
air
+
O
Δ
O
H
O
O
O
HO
H
H+
– H2O
O
O
O
OH
H+
Scheme 3 Proposed mechanism of Amberlyst-15-catalyzed rearrangement reactions
ment reaction, we included a number of aliphatic alcohols
in our study. In our first attempt, we treated 1-octanol with
THF and Amberlyst-15 under the same reaction condi-
tions. The corresponding THF ether7,16,17 (Table 2, entry
1) was formed in low yield. Similarly, 1-pentanol,7 cyclo-
hexanol,5,7,9,17 isobutanol,9 and tert-butanol14 also gave the
corresponding THF ethers (Table 2). The tetrahydrofura-
nylation of aliphatic alcohols with THF without additional
oxidants supports the plausible reaction mechanism pro-
posed before.
Acknowledgment
We thank the Istanbul Technical University Research Fund for fi-
nancial support.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SupInpfioomgrattr
o
nSupprigI
o
tnnofrmat
References and Notes
(1) Williams, G. B. D.; Simelane, S. B.; Lawton, M.; Kinfe,
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J. R. Org. Lett. 2000, 2, 485.
(5) Barks, J. M.; Gilbert, B. C.; Parsons, A. F.; Upeadran, B.
Tetrahedron Lett. 2000, 41, 6249.
Table 2 Tetrahydrofuranylation of Aliphatic Alcohols
Entry
Substrate
Product
Yield (%)a
25
1
H15C7
OH
O
H15C7
O
(6) Falck, J. R.; Li, D. R.; Bejot, R.; Mioskowski, C.
Tetrahedron Lett. 2006, 47, 5111.
(7) Ochiai, M.; Sueda, T. Tetrahedron Lett. 2004, 45, 3557.
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Bu
OH
OH
2
3
40
15
O
Bu
O
O
O
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i-Pr
O
O
i-Pr
OH
(10) Pinhey, J. T.; Xuan, P. T. Aust. J. Chem. 1988, 41, 69.
(11) Talinli, N.; Karliga, B. J. Heterocycl. Chem. 2004, 41, 205.
(12) General Procedure for Tetrahydrofuranylation of
Aromatic and Aliphatic Hydroxy Compounds
THF, aromatic or aliphatic hydroxy compounds, and
Amberlyst-15 was stirred for 5–8 h. At the end of the
reaction, the mixture was filtered to remove the Amberlyst-
15 resins. The organic layer was dried over Na2SO4, filtered,
and the solvent was evaporated under reduced pressure, and
the products were purified by chromatographic methods.
1-(Tetrahydrofuran-2-yl)naphthalen-2-ol (1)
1H NMR (300 MHz, CDCl3): δ = 9.75 (s, 1 H), 7.67–7.65(d,
J = 8.1 Hz, 1 H), 7.64–7.58 (dd, J = 8.19, 3.2 Hz, 1 H), 7.36
(td, J = 7.2, 7.0, 1.0 Hz, 1 H), 7.36–7.34 (dd, J = 6.8, 1.0 Hz,
1 H), 7.34–7.32 (dd, J = 7.2, 1.1 Hz, 1 H), 7.11–7.08 (d,
J = 8.8 Hz, 1 H), 5.73 (t, J = 6.5 Hz, 1 H), 4.21–4.28 (dd,
J = 7.0, 8.3 Hz, 1 H), 3.94–3.86 (dd, J = 7.2, 8.4 Hz, 1 H),
2.56–2.50 (m, 1 H), 2.07–2.00 (m, 2 H), 1.85–1.80 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 153.80, 131.70, 129.45,
128.96, 128.77, 126.61, 122.91, 121.49, 120.1, 114.75,
81.14, 68.71, 33.77, 25.92. IR (neat): 3240, 3053, 2946,
2879, 1623, 1467, 1262, 1041, 816 cm–1. MS (EI): m/z (%)
= 213.8 (100) [M+], 182.8 (46), 164.8 (64), 152.9 (20), 114.8
(30), 62.9 (6).
4
5
30
10
O
t-BuOH
t-BuO
a Product yields determined by 1H NMR analysis.
In conclusion, we proposed an unusual THF-involved re-
action of aromatic hydroxyl compounds in the presence of
acid catalyst, but without additional oxidants. Products
are 2-aryltetrahydrofurans, and the yields are comparable
with or are higher than the results reported before. The
features of this procedure are mild reaction conditions,
short reaction time, commercially available inexpensive
starting materials, and one-step reaction. Aliphatic alco-
hols gave corresponding tetrahydrofuranyl ethers in low
yield expectedly, but supported the proposed reaction
pathway. We are currently working on this process to im-
prove the yields under different conditions.
© Georg Thieme Verlag Stuttgart · New York
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H. Gunduz et al.
LETTER
(13) Salavati-Niasari, M. Inorg. Chem. Commun. 2006, 628.
2,4-Dimethyl-6-(tetrahydrofuran-2-yl)phenol (6)
1H NMR (250 MHz, CDCl3): δ = 8.45 (br, s, 1 H), 6.91 (s, 1
H), 6.61 (s, 1 H), 4.93 (t, J = 8.4 Hz, 1 H), 4.10 (m, 1 H), 3.92
(m, 1 H), 2.27 (m, 2 H), 2.18 (s, 3 H), 2.01 (s, 3 H), 1.95 (m,
2 H). 13C NMR (75 MHz, CDCl3): δ = 151.36, 130.63,
130.02, 128.04, 124.91, 123.78, 82.45, 68.40, 33.17, 25.45,
20.45, 15.77. IR (neat): 3300, 2922, 2870, 1613, 1486, 1228,
1049 cm–1. MS (EI): m/z (%) = 191.9 (80) [M+], 160.9 (100),
159.0 (42), 146.0 (34), 91.0 (34), 77.0 (30), 41.0 (20).
(14) Liang, G.; Gannett, P.; Shi, X.; Zhang, Y.; Chen, F.; Gold,
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3815.
(17) Kruse, C. G.; Broekhof, N. L. J. M.; Gen, A. Tetrahedron
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Synlett 2012, 23, 2473–2476
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