Microwave accelerated tetrahydropyranylation and detetrahydropyranylation of alcohols, phenols, and thiols catalyzed by hydrated zirconia

Article abstract of DOI:10.1081/SCC-120004145

A solvent free and expeditious method for tetrahydropyranylation and detetrahydropyranylation of alcohols, phenols and thiols is described using hydrated zirconia and 3,4-dihydro-2H-pyran (DHP). A comparison of this microwave-accelerated reaction with conventional heating condition is also presented.

Full text of DOI:10.1081/SCC-120004145

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MICROWAVE ACCELERATED TETRAHYDROPYRANYLATION
AND DETETRAHYDROPYRANYLATION OF ALCOHOLS,
PHENOLS, AND THIOLS CATALYZED BY HYDRATED
ZIRCONIA
Anil S. Gajare a , Dhananjay P. Sabde a , Murlidhar S. Shingare b & Radhika D. Wakharkar c
a Organic Chemistry Technology Division , National Chemical Laboratory , Pune, 411 008,
India
b Department of chemistry , Dr. B. A. Marathwada University , Aurangabad, 431 004, India
c Organic Chemistry Technology Division , National Chemical Laboratory , Pune, 411 008,
India
Published online: 12 Dec 2006.
To cite this article: Anil S. Gajare , Dhananjay P. Sabde , Murlidhar S. Shingare & Radhika D. Wakharkar (2002) MICROWAVE
ACCELERATED TETRAHYDROPYRANYLATION AND DETETRAHYDROPYRANYLATION OF ALCOHOLS, PHENOLS, AND THIOLS
CATALYZED BY HYDRATED ZIRCONIA, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 32:10, 1549-1555, DOI: 10.1081/SCC-120004145
To link to this article: http://dx.doi.org/10.1081/SCC-120004145
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SYNTHETIC COMMUNICATIONS, 32(10), 1549–1555 (2002)
MICROWAVE ACCELERATED
TETRAHYDROPYRANYLATION AND
DETETRAHYDROPYRANYLATION OF
ALCOHOLS, PHENOLS, AND THIOLS
CATALYZED BY HYDRATED ZIRCONIA
Anil S. Gajare,1,2, Dhananjay P. Sabde,1
*
Murlidhar S. Shingare,2 and Radhika D. Wakharkar1,
*
1Organic Chemistry Technology Division, National
Chemical Laboratory, Pune 411 008, India
2Department of chemistry, Dr. B. A. Marathwada
University, Aurangabad431 004, India
ABSTRACT
A solvent free and expeditious method for tetrahydropyrany-
lation and detetrahydropyranylation of alcohols, phenols and
thiols is described using hydrated zirconia and 3,4-dihydro-
2H-pyran (DHP). A comparison of this microwave-accel-
eratedreaction with conventional heating condition is also
presented.
Key Words: Tetrahydropyranylation; Detetrahydropyranyl-
ation; Hydrated zirconia; Microwave accelerated; Alcohols;
Thiols
*Corresponding authors. Fax: 49-351-46337030; E-mail: agajre@yahoo.com or Fax:
þ91-20-5893614; E-mail: rdw@dalton.ncl.res.in
1549
Copyright & 2002 by Marcel Dekker, Inc.
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1550
GAJARE ET AL.
The tetrahydropyranylation is one of the most frequently used
methods for protection of hydroxyl groups1 because of the remarkable
stability of tetrahydropyranyl ethers towards a variety of reaction con-
ditions. Tetrahydropyranylation of alcohols is one of the methods of
choice to protect hydroxyl groups in a multi-step organic synthesis, and a
variety of reagents1 are reportedfor the same. Ongoing research in other
laboratories has disclosed the use of new reagents for the tetrahydropyra-
nylation of alcohols and their detetrahydropyranylation such as protic
acids2a (HCl andPTSA), Lewis acids andpyridinium
p-toluenesulfonate.2b
More recently, ion exchange resins (amberlyst H-152c andNafion 2d),
clay materials, (montmorillonite K-10,2e H-Y Zeolite2f) ZnCl2,2g tetra-n-
butylammonium peroxydisulfate,2h CuCl,2i zirconium sulfophenyl phospho-
2k
nate2j andH-Rho have also been employedfor the protection of alcohols
as THP ethers. Generally, aqueous acids such as acetic acid, HCl, boric acid
etc., are usedfor the cleavage of THP ethers. The weaker acids invariably
require higher temperatures. Other known reagents for hydrolysis of THP
ethers are Amberlyst H-15,3a MgBr2,3b Me2AlCl,3c (NCSBu2Sn)O,3d
MeOH/HCl,3e NaBH3CN/BF3ÁOEt2,3f PhPBr,3g DDQ3h andLiCl in H O-
2
DMSO3i etc. However, some of these procedures suffer from expensive
reagents, high temperature, and strongly acidic conditions. Heterogeneous
catalysts in the recent years have shown enormous potential in the synthesis
of fine chemicals because of their shape selectivity, thermal stability,4a
reusability,4b tailor made acidic and basic properties and environment
friendly nature.
Zirconia5 in its pure andmodifiedform has been employedin many
industrial processes. Recently we have reported the Friedel Crafts acylation
of aromatic compounds and reduction of azobenzenes by using hydrated
zirconia6. The preparation methods and pretreatment temperature are
foundto affect the activity of ZrO . The ZrO2 calcinedat relatively low
2
temperatures has been foundresponsible for the high selectivity andlonger
catalyst life for particular reactions. The high activity of ZrO2 is attributed
to its acidbase bifunctional properties.
Various microwave acceleratedorganic transformations under solvent
free conditions have been reported7 to date. Microwave assisted hetero-
geneous reactions8 coupledwith the various solidinorganic supports have
attractedresearchers because of the simplicity, greater stability andrapid
synthesis of variety of organic compounds.9 The enhancedreaction rates,
formation of pure products in high yields and the ease of manipulation are
the salient features of the microwave approach, along with the use of
mineral supportedreagents or catalysts. Recently solvent free microwave
10
assistedreactions have gainedmore popularity as they provide an oppor-
tunity to work with open vessels. This avoids the risk of development of

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TETRA- AND DETETRAHYDROPYRANYLATION
1551
high pressure with a possibility of upscaling the reaction on a preparative
scale and helps the induction of reaction under dry conditions.
RESULT AND DISCUSSION
In this communication we report the microwave-acceleratedtetra-
hydropyranylation of alcohols, phenols and thiols catalyzed by hydrated
zirconia (Scheme 1). This method has distinct advantages over the other
existing methods viz. mild reaction conditions, absence of solvent, shorter
reaction time, easy andquick isolation of the product andexcellent yields.
Scheme 1.
Generality of the present procedure of tetrahydropyranylation has been
exhibited by protection of a wide range of hydroxy compounds, such as
primary, secondary, tertiary, allylic, acetylenic alcohols, phenolic and poly
functional compounds with dihydropyran under mild conditions. The highly
acidic catalyst p-toluenesulfonic acid, Nafion-H is known to produce
polymeric byproducts.2d The hydrated zirconia does not exhibit the strong
acidic sites therefore the acid sensitive groups such as ketal and sillyl ethers
(Table 1, Entries 1 and 2) were found intact under the reaction conditions.
Allylic andacetylenic alcohols couldbe protectedwithout isomerization of
double or triple bonds under the reaction conditions, and the resulting ethers
were isolatedas the only products (Table 1, Entries 3 to 7). Reaction of
dihydropyran with bulky substrates (Entries 13–16) easily protected the
hydroxy group with quantitative yield. Thiols could be protected as tetra-
hydropyranyl thiol ethers without occurrence of dimerization of thiols
(Entries 17–22) in excellent yield. A selective protection of alcoholic function
(Entry 8) in case of 2-mercapto ethanol couldbe achievedwith one mole
DHP.
Table 2 demonstrates an equally efficient reversal of tetrahydro-
pyranylation reaction under similar conditions (Scheme 1). In the presence
of hydrated zirconia the removal of the THP group has been carried out
rapidly in methanol at reflux temperature (Table 2). As in the case of the

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1552GAJARE ET AL.
Table 1. Tetrahydropyranylation of Alcohols, Phenols, andThiols Catalyzedby
Hydrated Zirconia
Thermal
Microwave
Time
Time
Entry
Substrate
(min) Yielda (min) Yielda
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
4-(2-methyl-1,3-dioxolan-2-yl)phenol
4-hydroxy-1-phenyl-1-trimethylsilyl ether
Allyl alcohol
Dimethyl allyl alcohol
Propargyl alcohol
t-Butylanol
80
90
90
90
90
80
50
60
100
110
80
–
100
70
82
85
70
80
85
75
90
82
80
73
75
–
80
95
87
85
80
80
85
87
91
82
7
7
7
7
7
7
3
5
10
7
10
7
15
7
7
7
10
10
–
10
–
90
92
80
85
95
85
97
86
85
87
81
80
93
98
98
95
88
88
–
Chloro ethanol
2-Mercapto ethanol
Cinnamyl alcohol
Geraniol
(-)Menthol
Cyclohexanol
Phenyl ethyl alcohol
Cholesterol
Phenol
a-Naphthol
Thiophenol
4-Chloro thiophenol
4-Methyl thiophenol
4-Methoxy thiophenol
Benzyl mercaptan
Furfuryl mercaptan
60
80
90
90
80
100
100
100
90
–
89
10
aIsolatedby chromatographic purification andproducts were characterizedby IR,
1H, 13C NMR andMS.
protection study, the selectivity has been studied for the depyranylation of
ethers (Entries 1 and2). All the products were purifiedby column chroma-
tography andthe corresponding tetrahydropyranyl ethers andalcohols were
obtainedin goodto excellent yields.
EXPERIMENTAL
General procedure for the protection of alcohols: The alcohols, phenols
or thiols (10 mmol), 3,4-dihydro-2H-pyran (20 mmol) and hydrated zirconia

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TETRA- AND DETETRAHYDROPYRANYLATION
1553
Table 2. Detetrahydropyranylation of Alcohols, Phenols, andThiols Catalyzedby
Hydrated Zirconia
Thermal
Microwave
Time
Time
Entry
Substrate
(min) Yielda (min) Yielda
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
4-(2-methyl-1,3-dioxolan-2-yl)phenol
4-hydroxy-1-phenyl-1-trimethylsilyl ether
Allyl alcohol
Dimethyl allyl alcohol
Propargyl alcohol
t-Butylanol
80
90
90
90
90
80
80
70
65
50
50
90
85
75
75
95
80
90
100
60
75
80
75
70
70
75
80
82
80
85
85
70
75
85
70
90
90
87
85
85
82
80
70
70
7
7
7
7
7
8
7
10
10
7
80
87
80
80
85
85
90
92
75
80
90
78
92
95
90
90
85
85
82
85
75
75
Chloro ethanol
2-Mercapto ethanol
Cinnamyl alcohol
Geraniol
(-)Menthol
Cyclohexanol
Phenyl ethyl alcohol
Cholesterol
Phenol
a-Naphthol
Thiophenol
4-Chloro thiophenol
4-Methyl thiophenol
4-Methoxy thiophenol
Benzyl mercaptan
Furfuryl mercaptan
7
10
10
10
10
8
8
8
7
8
8
8
aIsolatedby chromatographic purification andproducts were characterizedby IR,
1H, 13C NMR andMS.
(20% w/w) were added in a glass test tube and the reaction mixture was
placedinside a householdmicrowave oven andirradiated[14] for the spe-
cifiedtime or heatedin an oil bath at 80–100 ꢀC (see Table 1). On completion
of the reaction as indicated by TLC, the reaction mixture was diluted with
dichloromethane (10 ml). The catalyst was removed by filtration and washed
with dichloromethane (2 Â 10 ml). Removal of the solvent under reduced
pressure followed by chromatographic purification afforded products in
goodto excellent yields.
General procedure for the deprotection of alcohols: A solution of THP
ether (10 mmol) with hydrated zirconia (20% w/w) in methanol (5–10 ml)
were added in a glass test tube and the reaction mixture was placed inside a

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1554
GAJARE ET AL.
householdmicrowave oven andirradiated 11 for the specifiedtime or heated
in an oil bath at 80–100ꢀC (see Table 2). On completion of the reaction as
indicated by TLC, the catalyst was removed by filtration and washed with
methanol (2 Â 10 ml). Removal of the solvent under reduced pressure
followed by chromatographic purification afforded products in good to
excellent yields.
Thus, a simple andefficient methodfor tetrahydropyranylation and
its cleavage of a variety of alcohols, phenols andthiols has been explored
using hydrated zirconia as a catalyst, thermally as well as under microwave
irradiation.
ACKNOWLEDGMENTS
We wish to thank CSIR New Delhi for the awardof Research
Associateship to ASG andsenior research fellowship to DPS.
REFERENCES
1. (a) Green, T.W.; Wuts, P.G.M. Protecting Groups in Organic Synthesis,
2ndEd.; John Wiley & Sons, Inc.: New York, 1991; (b) Kocienski, P.J.
Protecting Groups; Enders, D., Noyori, R., Trost, B.M., Eds.;
New York, 1994 George Thieme; andreferences citedtherein.
2. (a) Bernady, K.F.; Weiss, M.J. J. Org. Chem. 1979, 44, 1438; (b)
Miyashita, M.; Yoshikoshi, A.; Grieco, P.A. J. Org. Chem. 1977, 42,
3772; (c) Bongini, A.; Cardillo, G.; Orena, M.; Sandri, S. Synthesis 1979,
618; (d) Olah, G.A.; Husain, A.; Sigh, B.P. Synthesis 1983, 892; (e)
Hoyer, S.; Laszlo, P.; Synthesis 1986, 655, andreferences citedtherein;
(f ) Kumar, P.; Dinesh, C.V.; Reddy, R.S.; Pandey, B. Synthesis 1993,
1069; (g) Ranu, B.C.; Saha, M.J. J. Org. Chem. 1994, 59, 8269; (h) Choi,
H.C.; Cho, K.H.; Kim, Y.H. Synlett. 1995, 207; (i) Bhalerao, U.T.;
Davis, K.J.; Rao, B.V. Synth. Commun. 1996, 26, 3081; (j) Curini,
M.; Epifano, F.; Marcotullio, M.C.; Rosati, O. Tetrahedron Lett.
1998, 39, 8159; (k) Sabde, D.P.; Naik, B.C.; Hegde, V.R.; Hegde,
S.G. J. Chem. Res.(s) 1996, 494.
3. (a) Johnston, R.D.; Marston, C.R.; Krieger, P.E.; Goe, G.L. Synthesis
1988, 393; (b) Kim, S.; Park, J.H. Tetrahedron Lett. 1987, 28, 439; (c)
Ogawa, Y.; Shibasaki, M. Tetrahedron Lett. 1984, 25, 663; (d) Otera, J.;
Nozaki, H. Tetrahedron Lett. 1986, 27, 5743; (e) Zimmarmann, K.
Synth. Commun. 1995, 25, 2559; (f ) Srikrishna, A.; Sattigeri, J.A.;
Viswajanani, R.; Yelamgged, C.V. J. Org. Chem. 1995, 60, 2260;

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TETRA- AND DETETRAHYDROPYRANYLATION
1555
(g) Wagner, A.; Heitz, M.P.; Mioskowski, C. J. Chem. Soc., Chem.
Commun. 1989, 1619; (h) Raina, S.; Shingh, V.K. Synth. Commun.
1995, 25, 2395; i) Maiti, G.; Roy, S.C. J. Org. Chem. 1996, 61, 6038.
4. (a) Balogh, M.; Laszlo, P. Organic Chemistry Using Clays. Springer-
Verlag: Berline, 1993; (b) Laszlo, P. Preparative Chemistry Using
Supported Reagents. Academic Press: San Diego, California, 1987.
5. (a) Shibagaki, M.; Takahashi, K.; Hideyuki, K.; Matsushita, H. Bull.
Chem. Soc. Jpn. 1990, 63, 1258; (b) Ibid 1988, 61, 3283; (c) Takashashi,
K.; Shibagaki, M.; Matsyshita, H. Bull. Chem. Soc. Jpn. 1989, 62,
2353; (d) Takashashi, K.; Shibagaki, M.; Kuno, H.; Kawakami, H.;
Matsashita, H. Bull. Chem. Soc. Jpn. 1989, 62, 1333.
6. Patil, M.L.; Jnaneshwara, G.K.; Sabde, D.P.; Dongare, M.K.;
Sudalai, A.; Deshpande, V.H. Tetrahedron Lett. 1997, 38, 2137.
7. Varma, R.S.; Dahiya, R. Tetrahedron 1998, 54, 6298, andreferences
cites therein.
8. (a) Caddick, S. Tetrahedron 1995, 51, 10403, andthe references cited
therein; (b) Anil, S. Gajare; Nadim, S. Shaikh; Bhusan, K. Bonde;
Vishnu, H. Deshpande. J. Chem. Soc., Perkin Trans. 1 2000, 639.
9. (a) Varma, R.S.; Naicker, K.P.; Liesen, P.J. Tetrahedron Lett. 1998,
39, 8437; (b) Varma, R.S.; Chatterjee, A.K.; Varma, M. Tetrahedron
Lett. 1993, 34, 4603, andreferences citedtherein.
10. (a) Varma, R.S.; Chatterjee, A.K. J. Chem. Soc., Perkin Trans. 1 1993,
999; (b) Vellemin, D.; Alloum, A.B. Synth. Commun. 1991, 21, 63; (c)
Varma, R.S.; Meshram, H.M. Tetrahedron Lett. 1997, 38, 5427, and
references citedtherein.
11. Microwave reactions were carried out in a Battliboi Eddy domestic
microwave oven operating at 2450 MHz (model no. ER5054D). It
was operatedat 45% of its full power for the specifiedtime.
Receivedin the UK March 5, 2001

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