Tetrahydropyranylation of alcohols over modified zeolites

Article abstract of DOI:10.1007/s10562-009-0205-7

A catalytic amount of Moβ enables tetrahydropyranylation of various alcohols, phenols and naphthols under mild reaction conditions at room temperature in moderate to excellent yields within short reaction times is presented. The catalyst Moβ is reused without significant loss of activity. The product isolation is simple and environmentally benign.

Full text of DOI:10.1007/s10562-009-0205-7

Catal Lett (2010) 134:175–178
DOI 10.1007/s10562-009-0205-7
Tetrahydropyranylation of Alcohols over Modified Zeolites
•
N. Narender K. Suresh Kumar Reddy
•
•
M. Arun Kumar C. N. Rohitha S. J. Kulkarni
•
Received: 9 September 2009 / Accepted: 27 October 2009 / Published online: 10 November 2009
Ó Springer Science+Business Media, LLC 2009
Abstract A catalytic amount of Mob enables tetrahy-
dropyranylation of various alcohols, phenols and naphthols
under mild reaction conditions at room temperature in
moderate to excellent yields within short reaction times is
presented. The catalyst Mob is reused without significant
loss of activity. The product isolation is simple and envi-
ronmentally benign.
CuSO4Á5H2O [11], Fe2(SO4)3ÁXH2O [12], ferric perchlorate
[13], Ru(acac)3 [14], La(NO4)3Á6H2O [15], 2,4,6-Trichloro
[1,3,5] triazine [16], TBATB [17], In(OTf)3 [18], InCl3
immobilized on ionic liquids [19], bromodimethylsulfoni-
um bromide [20], tetrabutylammonium bromide [17],
CeCl3Á7H2O-NaI [21], PdCl2(CH3CN)2 [22]. On the other
hand, many methods have also been developed using het-
erogeneous catalysts and these have been reviewed recently
[23].
Keywords Tetrahydropyranylation Á Alcohols Á
Zeolites Á Protection
However, some of these procedures are associated with
drawbacks which include long reaction times under reflux
conditions, involvement of expensive, moisture sensitive
catalysts, some of these have to be prepared prior to use,
handling problem due to their environmental hazard, the use
of large amounts of solid support (which eventually results
in the generation of large amounts of toxic waste, harsh and
acidic conditions). Despite a number of procedures, there is
a need for greener catalytically efficient method, which
might work under mild and cheaper conditions.
1 Introduction
The choice of protection and deprotection strategies in a
synthetic sequence is inevitable, owing to chemoselective
transformations in the presence of various functional groups
[1]. The protection of hydroxyl group is a common event in
multistep organic synthesis. The tetrahydropyranyl (THP)
group is frequently used for the protection of alcohols and
phenols due to their ease of preparative and stability under
wide variety of reaction conditions such as with hydrides,
alkylating agents, Grignard reagents and organometallic
reagents [2]. In addition, they also serve as stable protecting
groups in peptide, nucleoside, nucleotide, carbohydrate and
steroid chemistry. Tetrahydropyranylation of alcohols can
be accompanied by using PTSA [3], BF3ÁOEt2 [4], PPTS [5]
and zeolites [6–9]. Some of the recently used reagents that
can catalyze tetrahydropyranylation are AlCl3Á6H2O [10],
In recent years considerable emphasis has been placed
on improvement in the environmental impact of industrial
chemical processes. Now a days there is a substantial
interest to design heterogeneous catalytic systems towards
ecofriendly, clean and shape selective reactions. In par-
ticular, microporous solids (zeolites), besides their natural
acidity and shape selective character can promote a specific
selectivity owing to their molecular sieving character and
ecofriendly nature. Catalysts based on zeolites posses
major importance both in petroleum and fine chemicals
industries. The large pore zeolites like Hb is reported to
have Bronsted acid sites in the micropores and on the
external surface and Lewis acid sites predominantly at the
internal surface due to the local defects [24]. Surprisingly,
the potential of zeolite Hb has not been yet widely
exploited as a solid catalyst in organic synthesis. In this
N. Narender (&) Á K. Suresh Kumar Reddy Á M. Arun Kumar Á
C. N. Rohitha Á S. J. Kulkarni
Catalysis Group, Indian Institute of Chemical Technology,
Hyderabad 500 007, India
e-mail: narendern33@yahoo.co.in
123

176
N. Narender et al.
communication we wish to report that Mob is an excellent
and efficient catalyst to perform tetrahydropyranylation of
alcohols in acetic acid at room temperature.
Table 1 Tetrahydropyranylation of benzyl alcohol: variation of
catalysta
Entry
Catalyst
Yield(%)b
1
2
3
4
5
6
7
8
9
a
Hb
86
60
33
27
28
70
78
72
75
HZSM-5(40)
HY
2 Experimental
NaY
2.1 Preparation of Modified b-Zeolite
HX
Mordenite
HMCM-41
NaMCM-41
Montmorillonite-K10
All the catalysts were prepared by impregnation method,
4 g of the Hb zeolite added to 40 mL of 5% aqueous
solution (metal precursor salt corresponding to 200 mg of
metal dissolved in 40 mL of water) of corresponding
inorganic precursor salts and stirred at 80 °C for 24 h.
After impregnation, the catalyst was dried at 100 °C for
overnight and calcined at 450 °C for 6 h.
Benzyl alcohol (2 mmol), DHP (2 mmol), acetic acid (4 mL),
catalyst (100 mg), RT, time = 30 min
b
The products were characterized by 1HNMR, Mass spectra and
quantified by GC
2.2 General Procedure for the Tetrahydropyranylation
of Alcohols
Table 1. It shows that Hb zeolite gives higher yield
towards the corresponding product compared to other
catalysts.
A 25 mL two-necked round-bottomed flask was charged
with 10 mg of 5 wt%Mob, alcohol (2 mmol) in acetic acid
(4 mL). 3,4-Dihydro-2H-pyran (2 mmol) was added drop
wise to the reaction mixture and the contents allowed to stir
at room temperature. The reaction mixture was monitored
by thin layer chromatography (TLC). After completion of
the reaction, the catalyst was filtered and solid was washed
with ethyl acetate. The combined filtrates were washed
with saturated sodium bicarbonate solution. The organic
extract was dried over anhydrous sodium sulfate and sol-
vent evaporated under reduced pressure. The products were
purified by column chromatography and confirmed by
1HNMR and mass spectra. The catalyst was calcined at
450 °C for 5 h under air flow before reuse.
A wide range of solvents have been employed in these
reaction including, acetic acid, acetonitrile, dichlorometh-
ane, carbon tetrachloride and hexane (Table 2). The best
results were obtained when acetic acid was used as a sol-
vent compared to others.
Table 3 summarizes the results of tetrahydropyranyla-
tion of benzyl alcohol with 3,4-dihydro-2H-pyran (DHP)
over different amounts of Hb zeolite. It can be seen from
this table that 10 mg of Hb zeolite has given highest yield
toward the desired product and in absence of catalyst
showed lower yield. Thus confirming the role of catalyst in
the reaction.
Next, our efforts focused on achieving the highest yield
at shorter reaction time. Then we investigated tetrahydro-
pyranylation of benzyl alcohol using Hb zeolite modified
with various transition metal cations and results are pre-
sented in Table 4. It is, however, clear from this table that
the reaction with Mob exhibits much higher activity than
3 Results and Discussion
As a part of our ongoing research program to develop novel
synthetic methodologies using zeolites, herein we report
tetrahydropyranylation of alcohols and phenols using zeo-
lites (Scheme 1). In order to choose the best catalyst first,
the reaction was carried out with equimolar amounts of
benzyl alcohol (2 mmol) and 3,4-dihydro-2H-pyran in the
presence of zeolites, MCM-41 and Montmorillonite-K10
(100 mg) in acetic acid. The results are presented in
Table 2 Tetrahydropyranylation of benzyl alcohol: effect of solventa
Entry
Solvent
Yield(%)c
1
2
3
4
5
a
Acetic acidb
86
69
51
41
54
Acetonitrile
Dichloromethane
Carbon tetrachloride
Hexane
Zeolite, AcOH
ROH
Benzyl alcohol (2 mmol), DHP (2 mmol), solvent (10 mL), Hb
zeolite (100 mg), RT, time = 30 min
+
R
RT
O
O
O
b
Acetic acid (4 mL)
c
The products were characterized by 1HNMR, Mass spectra and
quantified by GC
Scheme 1 Tetrahydropyranylation of alcohols with DHP using
modified zeolites
123

Tetrahydropyranylation of Alcohols over Modified Zeolites
177
Table 3 Tetrahydropyranylation of benzyl alcohol with Hb zeolite:
Table 5 Tetrahydropyranylation of alcohols over 5 wt%Mob
variation of amount of catalysta
zeolitea
Entry
Amount of
catalyst (mg)
Time (min)
Yield(%)b
Time (min)
Entry
1
Substrate
Yieldb(%)
91
OH
OH
15
1
2
3
4
5
6
a
100
50
25
10
10
–
30
30
30
30
15
30
86
77
80
90
63
23
2
120
80
H CO
3
OCH
3
OH
3
4
5
30
30
90
88
82
79
OH
Benzyl alcohol (2 mmol), DHP (2 mmol), acetic acid (4 mL), Hb
zeolite, RT
b
The products were characterized by 1HNMR, Mass spectra and
quantified by GC
OH
OH
OH
6
7
30
40
99
80
4
Table 4 Tetrahydropyranylation of benzyl alcohol—Effect of mod-
ified Hb zeolitea
8
Entry
Catalyst
Yield(%)b
OH
1
5 wt%Feb
5 wt%Crb
5 wt%Mob
5 wt%Zrb
5 wt%Wb
5 wt%Cob
5 wt%Pbb
5 wt%Cub
5 wt%Nib
5 wt%Znb
5 wt%Ceb
44
45
91
29
65
33
53
39
48
57
25
40
57
8
2
HO
3
9
60
30
65
79
63
4
5
OH
10
11
6
O
7
8
180
OH
N
9
OH
10
11
a
12
13
14
120
45
Benzyl alcohol (2 mmol), DHP (2 mmol), acetic acid (4 mL),
OH
OH
CH
3
catalyst (10 mg), RT, Time = 15 min
b
120
120
67
56
The products were characterized by 1HNMR, Mass spectra and
quantified by GC
CH
that with other transition metal modified Hb zeolites and
the reaction time decreased to half when compare to
unmodified Hb-zeolite.
3
OH
15
16
360
180
-
This novel method for tetrahydropyranylation is applied
to a variety of alcohols, phenols and naphthols. As shown
in Table 5 with a catalytic amount of 5 wt%Mob, a wide
range of alcohols, including primary, secondary, benzylic,
heterocyclic and allylic alcohols as well as phenols and
naphthol undergo tetrahydropyranylation in moderate to
excellent yields. Benzyl alcohol gave high yields at room
temperature whereas phenols gave moderate yields. The
bulkiness of the reagents represents a crucial factor in the
present process: for example 3,4-dimethoxybenzyl alcohol
undergoes reaction relatively slower than benzyl alcohol.
In this case bulkiness of the reagent inhibits its diffusion
into the pores of the catalyst and the reaction probably
OH
95
a
Substrate (2 mmol), DHP (2 mmol), acetic acid (4 ml), 5wt% Mob
(10 mg), RT
The products were characterized by 1HNMR, Mass spectra and
quantified by GC
b
occurs only on the external surface or on the external acidic
sites. Cyclic aliphatic alcohols (Table 5, entries 8 and 9)
gave less yields compared to acyclic aliphatic alcohols
(Table 5, entries 6 and 7). Among the heterocylic alcohols
123

178
N. Narender et al.
the reaction is slower for 2-pyridyl alcohol when compared
to furfuryl alcohol. 1-Naphthol (Table 5, entries 15) does
not react even after longer time (360 min), whereas 2-
naphthol (Table 5, entries 16) gave 95% yield (180 min).
2-Naphthol is more reactive than 1-naphthol due to its high
nucleophilicity and acidity. As can be seen from Table 5
the application of this method to a variety of different
substrates shows the generality and versatility of this
method. Among the different transition metals, molybde-
num incorporated systems are having highest catalytic
activity in tetrahydropyranylation of alcohols with DHP.
This can be attributed to the enhanced amount of acidic
sites present in the catalyst systems. Molybdenum incor-
porated systems are having comparatively high abundance
of Bronsted acid sites [25]. The catalyst was easily sepa-
rated from the reaction mixture by simple filtration. Fur-
ther, catalyst was reused for the tetrahydropyranylation of
benzyl alcohol. The recovered catalyst showed consistent
activity even after third reuse (Table 6).
4 Conclusions
In conclusion, the present methodology demonstrates Mob
zeolite as an effective catalyst for protection of structurally
varied alcohols and phenols as tetrahydropyranyl ethers.
The significant advantages of this methodology are mild
reaction conditions, faster reaction rates, high substrate to
catalyst ratios, reusability of catalyst and environmentally
benign process. We believe that this work will find useful
application for the protection of alcohols in modern syn-
thetic methodologies.
Acknowledgments K. Suresh Kumar Reddy and M. Arun Kumar
thank the CSIR, New Delhi, for the award of SRF-GATE and JRF-
CSIR, respectively.
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Scheme 2 Plausible reaction mechanism for the tetrahydropyranyla-
tion of alcohols using modified zeolites
123