A highly efficient and ecofriendly procedure for tetrahydropyranylation of alcohols and phenols in the presence of in-situ generated I2 under heterogeneous and neutral conditions

Article abstract of DOI:10.1007/s00706-009-0117-7

Molecular iodine generated in situ from Fe(NO₃) ₃?9H₂O/NaI acts as a highly efficient catalyst for tetrahydropyranylation of various alcohols and phenols with 3,4-dihydro-2H-pyran in almost quantitative yields. The reaction occurs rapidly in dichloromethane at room temperature, and use of toxic molecular iodine is avoided.

Full text of DOI:10.1007/s00706-009-0117-7

Monatsh Chem (2009) 140:663–667
DOI 10.1007/s00706-009-0117-7
ORIGINAL PAPER
A highly efficient and ecofriendly procedure for
tetrahydropyranylation of alcohols and phenols in the presence
of in-situ generated I under heterogeneous and neutral conditions
2
Amin Rostami Æ Sadegh Rahmati Æ Ardeshir Khazaei
Received: 14 August 2008 / Accepted: 17 December 2008 / Published online: 17 March 2009
Ó Springer-Verlag 2009
Abstract Molecular iodine generated in situ from
Fe(NO ) Á9H O/NaI acts as a highly efficient catalyst for
[7], NH Cl [8], acetonyltriphenylphosphonium bromide [9],
4
I [10, 11], LiBr [12], ZrCl [13], tetrabutylammonium tri-
2
3
3
2
4
tetrahydropyranylation of various alcohols and phenols
with 3,4-dihydro-2H-pyran in almost quantitative yields.
The reaction occurs rapidly in dichloromethane at room
temperature, and use of toxic molecular iodine is avoided.
bromide [14], Fe(ClO4)3 [15], K PW O Á3H O [16],
5
12 40
2
PdCl (CH CN) [17], trichloroisocyanuric acid [18], silica
2
3
2
sulfuric acid [19], Bi(NO ) Á5H O [20], aqueous zinc tet-
3
3
2
rafluoroborate [21], AlCl Á6H O [22], LiOTf [23],
3
2
VO(OAc) [24], CaCl [25], La(NO ) Á6H O [26], bismuth
2
2
3 3
2
Keywords Tetrahydropyranylation Á Alcohols Á
Phenols Á In-situ I Á Fe(NO ) Á9H O/NaI
triflate [27], H O [28], and copper(II) chloride–acetic acid
2
[29].
2
3 3
2
However, several of the reported methods are associated
with drawbacks, including long reaction times under reflux,
expensive reagents, and incompatibility with other func-
tionalities. Thus, there is still a need for a mild, neutral,
catalytically efficient alternative, preferably using a heter-
ogeneous catalyst, the protection of hydroxyl groups as
THP ethers.
Introduction
Protection of hydroxyl groups by conversion into the cor-
responding tetrahydropyranyl ethers (THP ethers) is a
common and extensively used transformation in organic
synthesis [1]. Tetrahydropyranyl (THP) is a very attractive
group for protection of hydroxyl groups, because of its low
cost and stability under many reaction conditions and its
compatibility with several reagents, for example metal
hydrides, Grignard, and organolithium reagents [2]. Con-
sequently, a variety of reagents have been introduced for
THP protection of alcohols and phenols, for example
p-toluenesulfonic acid (PTSA) [3, 4], pyridinium p-tolu-
enesulfonate (PPTS) [5], iodotrimethylsilane [6], acidic clay
Although molecular iodine is a versatile reagent in
organic synthesis [30], it is corrosive and toxic, making its
use somewhat unattractive. To overcome these disadvan-
tages with molecular iodine, Bailey et al. reported a
convenient method for in situ generation of I2 using
CuSO /NaI [31].
4
Results and discussion
As a part of our ongoing research program to develop new
synthetic methods for protection of hydroxyl functional
groups [32–35], we wish to describe a new procedure for
tetrahydropyranylation of a wide variety of alcohols and
phenols using 3,4-dihydro-2H-pyran (DHP) in the presence
of I generated in situ from Fe(NO ) Á9H O/NaI under mild
A. Rostami (&)
Department of Chemistry, Faculty of Science,
University of Kurdistan, 66177-15143 Sanandaj, Iran
e-mail: a_rostami372@yahoo.com
2
3 3
2
S. Rahmati Á A. Khazaei (&)
and heterogeneous conditions (Scheme 1).
Faculty of Chemistry, Bu-Ali Sina University,
65178-38683 Hamadan, Iran
e-mail: khazaei_1326@yahoo.com
It should be mentioned that molecular iodine is gener-
ated in situ by oxidation of NaI using Fe(NO ) Á9H O. We
3
3
2
123

6
64
A. Rostami et al.
The substrates with multiple bonds (entries 10, 19, and
20) were tetrahydropyranylated without any addition
product of iodine as side products.
Fe(NO ) .9H O/NaI
3
3
2
R
OH
+
CH
2
Cl
2
, rt
O
R
O
O
To illustrate the catalytic activity of this system, we
compared our results for the tetrahydropyranylation of
benzyl alcohol on the basis of reaction conditions, molar
ratio of catalyst/DHP, time of reaction, and yield of prod-
uct, with the best of well known data from the literature
(Table 3). The notable features of this procedure are mild
reaction conditions, cleaner reactions, improved yields, and
enhanced reaction rates.
R = benzylic, linear, cyclic, aryl
Scheme 1
measured the amount of I generated in situ in CH Cl by
2
2
2
UV–visible spectrophotometry (NaI is the limiting
reagent). It was found that 0.142 mmol I is produced for
2
every mmol NaI.
Our initial efforts focused on identifying the optimum
conditions for the tetrahydropyranylation of benzyl alcohol
as model substrate in the presence of various salts and
solvents at room temperature. These results are summa-
rized in Table 1. Among the salts and solvents used, the
combination Fe(NO ) Á9H O/NaI in dichloromethane
Experimental
Determination of amount of I generated in situ
2
from Fe(NO ) Á9H O/NaI
3
3
2
3
3
2
delivered the best results (Table 1, Entry 1) and was then
used for all other substrates.
A series of standard solutions of I (0.0, 0.01, 0.02, 0.03,
2
3
and 0.04 mmol) in 25 cm CH Cl was prepared and a
2
2
Compounds that were tetrahydropyranylated in this way
are primary, allylic, benzylic, propargylic, hindered and
unhindered secondary, tertiary, acid-sensitive alcohols and
phenols (Table 2).
calibration plot (Beer’s Law plot) was obtained. The
unknown concentration of I2 solution [Fe(NO ) Á9H O
3 3
2
(0.1 mmol) and NaI (0.2 mmol)] was determined by
measuring UV absorbance.
Table 1 Tetrahydropyranylation of benzyl alcohol with DHP in the presence of various salts and solvents at room temperature
Catalyst
CH OH
+
CH2O
2
Solvent , rt
O
O
Entry
Mineral salt
Solvent
CH Cl
Time (h)
Yields (conversion) (%)
1
2
3
4
5
6
7
8
9
Fe(NO
Fe(NO
Fe(NO
Fe(NO
Fe(NO
Fe(NO
Fe(NO
Fe(NO
3
3
3
3
3
3
3
3
)
)
)
)
)
)
)
)
3
3
3
3
3
3
3
3
Á9H
Á9H
Á9H
Á9H
Á9H
Á9H
Á9H
Á9H
Á5H
O/NaI
O/NaI
ÁH
2
2
2
2
2
2
2
2
O/NaI
O/NaI
O/NaI
O/NaI
O/NaI
O/NaI
O/NaI
O/NaI
2
2
0.13
12
12
12
1
100
40
0
2
H O
Ethyl acetate
Et
2
O
50
100
40
0
n-Hexane
Acetone
Ethanol
12
12
12
0.44
12
10
10
2
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
3
2
2
2
2
2
2
2
2
2
2
2
CN
90
100
95
80
5
Fe
FeCl
CuCl
Cu(CH
CuSO
Á5H
Cu(NO
Á3H
CuCO
CrCl
ZnNO
Co(NO
Zr(NO
2
(SO
Á6H
Á2H
COO)
O/NaI
O/NaI
/NaI
4
)
3
2
O/NaI
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
2
2
2
2
2
2
2
2
2
2
2
1
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
9
3
2
2
2
3
2
2
O/NaI
4
2
100
100
0
3
)
2
2
0.4
10
0.5
24
14
1.5
3
ÁCu(OH)
2
3
Á6H
2
O/NaI
100
0
3
Á6H
2
O/NaI
3
)
6
/NaI
100
100
3 4
) /NaI
1
23

Highly efficient and ecofriendly protocol for the tetrahydropyranylation of alcohols and phenols
665
Table 2 Tetrahydropyranylation of alcohols and phenols (5 mmol) using 0.59 g DHP (7 mmol) catalyzed with I
8.3 mg Fe(NO
2
generated in situ from
2
3
)
3
Á9H
2
O (0.07 mmol) and 19.5 mg NaI (0.13 mmol) in CH
2
Cl
2
at room temperature
References for
spectroscopic data
of products
a
Entry
Substrate
Time/min
Product
Isolated yields/%
1
2
5
CH
2
OTHP
96
92
[7, 27]
2
CH OH
30
Cl
Cl
2
CH OTHP
[6, 7]
Cl
Cl
2
CH OH
CH
Cl
CH
2
OTHP
CH2OH
Cl
3
70
90
[28]
4
5
30
7
F
2
OTHP
94
91
[33]
F
CH2OH
MeO
CH
2
OTHP
[7, 28]
MeO
2
CH OH
6
7
15
7
CH CH
2 2
OTHP
OTHP
87
91
[20]
[7]
CH
2
CH
2
OH
OH
OTHP
OH
8
9
70
89
[29]
10
OTHP
83
78
[7]
OH
THPO
HO
OH
1
1
0
1
120
[6, 7]
OTHP
5
40
10
80
87
[33]
[6, 7]
[33]
1
2
OTHP
OH
OTHP
OH
1
1
3
4
84
180
60
85
80
[20]
OTHP
OTHP
OH
OH
H3C
H3C
1
5
[7, 28]
OH
OTHP
1
1
1
1
2
6
7
8
9
0
30
50
8
89
88
78
92
88
[33]
[6, 7]
[28]
CH
2
OH
CH2OTHP
O
O
O
O
OH
OTHP
15
90
[7]
OH
OTHP
O
O
OH
OTHP
[27, 28]
123

6
66
A. Rostami et al.
Table 2 continued
Entry Substrate
References for
spectroscopic data
of products
a
Time/min
Product
Isolated yields/%
O
2
N
CH
2
OH
O
2
N
2
CH OTHP
2
2
1
2
150
20
89
80
[20, 27]
[7]
MeO
OH
MeO
OTHP
2
2
3
4
50
70
83
90
[33]
HO
Cl
THPO
Cl
[6, 7]
OH
OTHP
Table 3 Comparison of the activity of various catalysts in the tetrahydropyranylation of benzyl alcohol
Catalyst
CH2OH +
CH O
2
O
O
Entry
Reagent
Fe(NO
Conditions
Cat:DHP (mmol:mmol)
Time (h)
Yield (%)
Refs.
1
2
3
4
5
6
7
8
9
3
)
3
Á9H
2
O/NaI
CH
CH
2
Cl
Cl
2
, rt
, rt
0.014/0.026:1.4
0.01:1
0.08
0.5
2.5
0.08
2.5
1.5
5
96
90
95
97
96
98
92
91
95
89
93
72
89
This work
I
2
2
2
Kumar et al. [11]
Khazaei et al. [32]
Habibi et al. [16]
Karimi and Maleki [23]
Heravi et al. [15]
Firouzabadi et al. [18]
Pore et al. [19]
NBS
Solvent-free, rt
Acetone, H O, reflux
ClCH CH Cl, reflux
Et O, rt
Solvent-free, 60–70 °C
CH Cl , rt
CHCl , rt
CH Cl , rt
0.02:1.5
0.01:2
5
K PW12
O
40Á3H
2
O
2
LiOTf
Fe(ClO
TCCA
2
2
0.6:1.6
0.03:1
4
)
3
2
0.1:1.4
0.39:1.1
0.27:1.2
1:7
Silica sulfuric acid
2
2
0.5
1
VO(OAc)
CaCl
La(NO
PdCl
BNBBS
2
3
Choudary et al. [24]
Bandgar et al. [25]
Reddy et al. [26]
Wang et al. [17]
Khazaei et al. [33]
10
11
12
13
2
2
2
1.5
2.5
1
3
)
3
.6H
2
O
Solvent-free, rt
THF, rt
0.1:1
2
(CH
3
CN)
2
0.1:1.1
0.01:1.2
CH
2
Cl
2
, rt
1.83
3
filtered. The organic layer was washed with 25 cm water
General procedure for the tetrahydropyranylation
of alcohols and phenols using DHP catalyzed with I2
generated in situ from Fe(NO ) Á9H O/NaI in CH Cl
3
and 25 cm brine and dried over anhydrous Na SO . The
2
4
3
3
2
2
2
solvent was removed under reduced pressure and the crude
product was passed through a short column of silica gel using
n-hexane as eluent. After evaporation to dryness the pure
THP ethers were afforded. All products were characterized
In a typical experiment, the alcohol or phenol (5 mmol) and
.59 g DHP (7 mmol) were added to a mixture of 28.3 mg
Fe(NO ) Á9H O (0.07 mmol) and 19.5 mg NaI (0.13 mmol)
0
1
3
3
2
by comparison of their spectral data ( H NMR, IR) with those
3
in 5 cm CH Cl . The mixture was stirred at room temper-
of authentic samples [6, 7, 20, 27–29, 33].
2
2
ature for the specified time (Table 2). After completion of the
reaction (TLC), the mixture was filtered and the solids were
Acknowledgments The authors acknowledge to Bu-Ali Sina Uni-
versity Research Councils, University of Kurdistan Research
Councils, the Center of Excellence in Development of Chemistry
Methods (CEBCM) and National Foundation of Elites (NFE) for
support of this work.
3
washed with 5 cm CH Cl . Powdered Na S O (*2 g) was
2
2
2 2 3
added in portions to the combined filtrate, the mixture was
stirred for additional 5 min, and the resulting mixture was
1
23

Highly efficient and ecofriendly protocol for the tetrahydropyranylation of alcohols and phenols
667
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