Zeolite-catalyzed environmentally friendly tetrahydropyranylation of alcohols and phenols

Article abstract of DOI:10.1081/SCC-200036596

A simple and environmentally friendly tetrahydropyranylation of various alcohols and phenols at room temperature was elaborated by using a small pore size zeolite. The material is also suitable for the deprotection but with less efficiency.

Full text of DOI:10.1081/SCC-200036596

This article was downloaded by: [University of Newcastle, Australia]
On: 31 December 2014, At: 01:58
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T
3JH, UK
Synthetic Communications:
An International Journal
for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Zeolite‐Catalyzed
Environmentally Friendly
Tetrahydropyranylation of
Alcohols and Phenols
Adrienn Hegedüs a , Ilona Vígh a & Zoltán Hell a
a Department of Organic Chemical Technology ,
Budapest University of Technology and
Economics , H‐1521, Budapest, Hungary
Published online: 10 Jan 2011.
To cite this article: Adrienn Hegedüs , Ilona Vígh & Zoltán Hell (2004)
Zeolite‐Catalyzed Environmentally Friendly Tetrahydropyranylation of Alcohols
and Phenols, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 34:22, 4145-4152, DOI: 10.1081/
SCC-200036596
To link to this article: http://dx.doi.org/10.1081/SCC-200036596
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all
the information (the “Content”) contained in the publications on our
platform. However, Taylor & Francis, our agents, and our licensors
make no representations or warranties whatsoever as to the accuracy,
completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of
the authors, and are not the views of or endorsed by Taylor & Francis.

The accuracy of the Content should not be relied upon and should be
independently verified with primary sources of information. Taylor and
Francis shall not be liable for any losses, actions, claims, proceedings,
demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in
relation to or arising out of the use of the Content.
This article may be used for research, teaching, and private study
purposes. Any substantial or systematic reproduction, redistribution,
reselling, loan, sub-licensing, systematic supply, or distribution in any form
to anyone is expressly forbidden. Terms & Conditions of access and use
can be found at http://www.tandfonline.com/page/terms-and-conditions

SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 22, pp. 4145–4152, 2004
Zeolite-Catalyzed Environmentally
Friendly Tetrahydropyranylation of
Alcohols and Phenols
*
´
´
Adrienn Hegedu¨s, Ilona Vıgh, and Zoltan Hell
Department of Organic Chemical Technology, Budapest University
of Technology and Economics, Budapest, Hungary
ABSTRACT
A simple and environmentally friendly tetrahydropyranylation of various
alcohols and phenols at room temperature was elaborated by using a small
pore size zeolite. The material is also suitable for the deprotection but
with less efficiency.
Key Words: Green chemistry; Tetrahydropyranylation; Zeolite.
*
´
Correspondence: Zoltan Hell, Department of Organic Chemical Technology,
Budapest University of Technology and Economics, H-1521 Budapest, Hungary;
Fax: þ36-1-463-3648; E-mail: zhell@mail.bme.hu.
4145
DOI: 10.1081/SCC-200036596
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

´
Hegedu¨s, Vıgh, and Hell
4146
INTRODUCTION
Tetrahydropyranylation (THP) is a common and widely used method to
protect alcoholic and phenolic hydroxyl groups. The THP ethers are resistant
to oxidizing and reducing agents, unreactive under neutral and basic con-
ditions, and the THP-group is easy to remove.[1]
Numerous catalysts have been developed for tetrahydropyranylation of
hydroxy groups, such as the classical concentrated hydrochloric acid[2] and
p-toluenesulfonic acid[3] as well as trimethyliodosilane,[4] zirconium sulfo-
phenyl phosphonate,[5] bis[trimethylsilyl]sulfate,[6] lithium perchlorate–
diethyl ether,[7] vanadyl(IV)acetate,[8] polyaniline salts,[9] lithium triflate,[10]
and tributylammonium bromide.[11] Because most of these catalysts are
dangerous or harmful for the environment, cleaner and safer methods were
also developed by using, for example, ionic liquids[12] and some hetero-
geneous catalysts: heteropolyacids,[13] K10 montmorillonite,[14] sulfonated
charcoal,[15] HY zeolite,[16] HSZ zeolite,[17] Envirocat EPZG,[18] etc. Simi-
larly, a lot of methods were described for the cleavage of the THP group,
thus pyridinium p-toluenesulfonate (PPTS) in ethanol,[19] p-toluenesulfonic
acid,[20] zinc chloride,[21] and also environmentally friendly catalysts (e.g.,
bentonitic clay[22] and heteropolyacid[13]).
In this article we report that Ersorb-4 (E4) is also an excellent and effec-
tive catalyst to tetrahydropyranylation of alcohols and phenols under mild
˚
conditions. E4 is a weakly acidic zeolite-type adsorbent with 4 A pore size.
It can adsorb small molecules such as water, hydrochloric acid, ammonia,
methanol, etc. It has several advantages—it is environmentally friendly,
nontoxic, recoverable, reusable, and inexpensive. Recently we found that E4
showed good activity in different condensation reactions such as acylation of
aminoacids with aromatic acid chlorides,[23] cyclization of b-aminoalcohols
with carboxylic acids into oxazoline derivatives,[24] and synthesis of
2-arylimidazoline derivatives and 2-arylbenzoxazole derivatives.[25]

Zeolite-Catalyzed THP of Alcohols and Phenols
EXPERIMENTAL
4147
All tetrahydropyranyl ethers are known compounds and were character-
1
ized by H NMR spectroscopy. Spectra were made on Bruker Avanche 300
spectrometer in CDCl3 using TMS as internal standard. Gas chromatography
was performed on Agilent 4890D instrument.
The commercial chemicals were purchased from Merck-Hungary Ltd.
´´ ´
except E4, which is the product of Erdokemia-ker Ltd., Hungary.
Pretreatment of the Catalyst
Before the experiments, a sample of E4 was powdered and heated at
1208C for 2 hr.
General Method for Tetrahydropyranylation of Alcohols
A mixture of alcohol (20 mmol), 3,4-dihydro-2H-pyran (26 mmol), and
1g E4 was stirred at room temperature for 30 min. The solid was then filtered
out, the product was obtained by simple distillation and was characterized by
1H NMR.
General Method for Tetrahydropyranylation of Phenols
A mixture of phenol (20 mmol), 3,4-dihydro-2H-pyran (26 mmol), and 1g
E4 in toluene was stirred at room temperature for 3 hr. The solid was then fil-
tered out, the filtrate was evaporated, and the residue was characterized.
General Method for Deprotection of Tetrahydropyranyl
Ethers
A mixture of THP ether (20 mmol), 1g E4, and 15mL methanol was stirred
at room temperature, and the progress of the reaction was monitored by GC.
RESULTS AND DISCUSSION
Several types of alcohols (primary, secondary, tertiary, benzylic, and
allylic) and phenols with different substituents were converted to the corre-
sponding THP ethers in high yields (see Tables 1 and 2). The zeolite can be

´
Hegedu¨s, Vıgh, and Hell
4148
Table 1. Tetrahydropyranylation of alcohols in the presence of E4.
Reaction
time (min)
Entry
Alcohol
Yield (%)a
83 (100)
1
2
30
30
81 (100)b
80 (100)c
85 (100)
3
4
30
30
76 (97)
71 (89)
77 (93)
5
6
30
30
7
8
9
30
30
30
80 (100)
76 (98)
84 (95)
10
60
73 (87)
11
12
60
60
(79)
(74)
13
14
60
90
82 (100)
(98)
15
90
(96)
aIsolated yield; the values in parentheses refer to the conversion estimated by the
1H NMR spectra.
bRecycled E4.
cThird use of the catalyst.

Zeolite-Catalyzed THP of Alcohols and Phenols
4149
Table 2. Tetrahydropyranylation of phenols in the presence of E4 in toluene.
Reaction
time (hr)
Entry
1
Phenol
Yield (%)a
3
58 (71)
2
3
4
3
3
3
55 (67)
51 (69)
51 (61)
5
6
4
4
44 (53)
57 (65)b
aIsolated yield; the values in parentheses refer to the conversion estimated by the
1H NMR spectra.
b
In dioxane.
reused without significant loss of activity (see Table 1, Entry 2). In the phenols
without solvent, vigorous reaction and the formation of tarry product was
observed. Thus, the reaction was performed in toluene. The reaction time
was longer than in the case of the aliphatic alcohols, and the yield was
lower, especially at the ortho-substituted derivatives, probably due to a
steric hindrance of the substituents.
The removal of the tetrahydropyranyl group can be carried out under
similar mild reaction conditions, but the reaction was significantly longer
and the conversions are moderate, as it shown in Table 3.

´
Hegedu¨s, Vıgh, and Hell
4150
Table 3. Deprotection of tetrahydropyranyl ethers in methanol in the presence of E4.
Reaction
time (hr)
Yield
(%)a
Entry
1
THP ether
4
52
2
3
7
6
73
55
4
6
61
aGC yield.
CONCLUSION
The modified zeolite-type adsorbent E4 is a suitable agent for tetrahydro-
pyranylation of alcohols and phenols. The method is simple, convenient,
cheap, and environmentally friendly, and the catalyst can be recycled
without any loss of activity.
ACKNOWLEDGMENTS
This work was supported by Hungarian Research Fund Programs (OTKA
Grant No. T 037757).
REFERENCES
1. Greene, T.W.; Wuts, P.G.M. Protective Groups in Organic Synthesis, 3rd
Ed.; Wiley: New York, 1999; 49.
2. Forrest Woods, G.; Kramer, D.N. Dihydropyrane addition products.
J. Am. Chem. Soc. 1947, 69, 2246.

Zeolite-Catalyzed THP of Alcohols and Phenols
4151
3. Bernady, K.F.; Floyd, M.B.; Poletto, J.E.; Weiss, M.J. Prostaglandins and
congeners. 20. Synthesis of prostaglandins via conjugate addition of
lithium trans-1-alkenyltrialkilalanate reagents. A novel reagent for conju-
gate 1,4-additions. J. Org. Chem. 1979, 44, 1438.
4. Olah, G.A.; Husain, A.; Sigh, B.P. Iodotrimethylsilane-catalyzed prep-
aration of 2-tetrahydropyranyl derivatives of primary and secondary alco-
hols with dihydropyran. Synthesis 1985, 7, 703.
5. Curini, M.; Epifano, F.; Marcotullio, M.C.; Rosati, O. Zirconium sulfo-
phenyl phosphonate as a heterogeneous catalyst in tetrahydropyranylation
of alcohols and phenols. Tetrahedron Lett. 1998, 39, 8159.
6. Yoshitomi, M.; Ichiro, M.; Tamejiro, H.; Hitosi, N. Bis[trimethylsilyl]
sulfate-catalyzed alcohol protection with dihydropyran, deprotection
and transesterification. Synthesis 1981, 11, 899.
7. Babu, B.S.; Balasubramanian, K.K. Mild and efficient tetrahyropyranyla-
tion of alcohols-catalysis by lithium perchlorate in diethyl ether. Tetra-
hedron Lett. 1998, 39, 9287.
8. Choudary, B.M.; Neeraja, V.; Kantam, M.L. Vanadyl(IV)acetate: a mild
and efficient heterogeneous catalyst for the tetrahydropyranylation of
alcohols, thiols and phenols. J. Mol. Catal. A 2001, 175, 169.
9. Palaniappan, S.; Ram Sai, M.; Amarnath, C.A. Tetrahydropyranylation of
alcohols catalyzed by polyaniline salts. Green Chem. 2002, 4, 369.
10. Karimi, B.; Maleki, J. Lithium triflate (LiOTf) catalyzed efficient and che-
moselective tetrahydropyranylation of alcohols and phenols under mild
and neutral reaction conditions. Tetrahedron Lett. 2002, 43, 5353.
11. Naik, S.; Gopinath, R.; Patel, B.K. Tetrabutylammonium tribromide
(TBATB)-promoted tetrahydropyranylation/depyranylation of alcohols.
Tetrahedron Lett. 2001, 42, 7679.
12. Branco, L.C.; Afonso, C.A.M. Ionic liquids as recyclabe reaction media
for the terahydropyranylation of alcohols. Tetrahedron 2001, 57, 4405.
´
´
´
13. Molnar, A.; Beregszaszi, T. Mild and efficient tetrahydropyranylation and
deprotection of alcohols catalyzed by heteropoly acids. Tetrahedron Lett.
1996, 37, 8597.
14. Hoyer, S.; Laszlo, P.; Orlovri, M.; Polla, E. Catalysis by acidic clay of the
protective tetrahydropyranylation of alcohols and phenols. Synthesis
1986, 8, 655.
15. Patney, H.K. Sulfonated charcoal, a mild and efficient reagent for the
terahydropyranylation of alcohols and phenols. Synth. Commun.
1991, 21, 2329.
16. Kumar, P.; Dinesh, C.U.; Reddy, R.S.; Pandey, B. HY Zeolite: a mild and
efficient catalyst for the tertahydropyranylation of alcohols. Synthesis
1993, 11, 1069.

´
Hegedu¨s, Vıgh, and Hell
4152
17. Ballini, R.; Bigi, F.; Carloni, S.; Maggi, R.; Sartori, G. Solvent-free terta-
hydropyranylation of phenols and alcohols over zeolites HSZ as reusable
catalysts. Tetrahedron Lett. 1997, 38, 4169.
18. Bandgar, B.P.; Jagtap, S.R.; Aghade, B.B.; Wadgaonkar, P.P. Solid sup-
ported reagents and reactions. 7. Environcat EZPG as a new hetero-
geneous catalyst for the solvent-free terahydropyranylation of alcohols
and phenols. Synth. Commun. 1995, 25, 2211.
19. Miyashita, M.; Yoshikoshi, A.; Grieco, P.A. Pyridinium p-toluenesulfonate.
A mild and efficient catalyst for the terahydropyranylation of alcohols.
J. Org. Chem. 1977, 42, 3772.
20. Corey, E.J.; Niwa, H.; Knolle, J. Total synthesis of (S)-12-hydroxy-
5,8,14-cis-10-trans-eicosatetraenoic acid (Samuelsson’s HETE). J. Am.
Chem. Soc. 1978, 100, 1942.
21. Parham, W.E.; Gordon, I.; Swalen, J.D. Heterocyclic vinyl ethers I.
p-Oxathiene. J. Am. Chem. Soc. 1952, 74, 1824.
22. Cruz-Almanza, R.; Perez-Flores, F.J.; Avila, M. Deprotection of tetrahy-
dropyranyl ethers with a Mexican bentonite. Synthesis of farnesylhydro-
quinone. Synth. Commun. 1990, 20, 1125.
´
23. Hell, Z.; Cwik, A.; Finta, Z.; Horvath, Z. A new and convenient method
for the acylation of amino acids in the presence of a modified zeolite:
Ersorbw. J. Mol. Catal. A: Chemical 2002, 184, 191.
´
24. Cwik, A.; Hell, Z.; Hegedu¨s, A.; Finta, Z.; Horvath, Z. A simple synthesis
of 2-substituted oxazolines and oxazines. Tetrahedron Lett. 2002, 43,
3985.
´
25. Hegedu¨s, A.; Vıgh, I.; Hell, Z. Zeolite-catalyzed simple synthesis of
different heterocyclic rings. Heteroatom Chemistry, in press.
Received in the UK May 11, 2004