Efficient tetrahydropyranylation of alcohols and detetrahydropyranylation reactions in the presence of catalytic amount of trichloroisocyanuric acid (TCCA) as a safe, cheap industrial chemical

Article abstract of DOI:10.1081/SCC-200031053

Preparation and cleavage of THP ethers of different hydroxy functional groups are easily and efficiently performed in the presence of trichloroisocyanuric acid (TCCA) in the absence of solvent with high yields.

Full text of DOI:10.1081/SCC-200031053

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Efficient
Tetrahydropyranylation
of Alcohols and
Detetrahydropyranylation
Reactions in the Presence
of Catalytic Amount of
Trichloroisocyanuric Acid
(TCCA) as a Safe, Cheap
Industrial Chemical
Habib Firouzabadi a , Nasser Iranpoor a & Hassan
Hazarkhani a
a Department of Chemistry, College of Sciences ,
Shiraz University , Shiraz, 71454, Iran
Published online: 10 Jan 2011.
To cite this article: Habib Firouzabadi , Nasser Iranpoor & Hassan Hazarkhani
(2004) Efficient Tetrahydropyranylation of Alcohols and Detetrahydropyranylation
Reactions in the Presence of Catalytic Amount of Trichloroisocyanuric Acid (TCCA)
as a Safe, Cheap Industrial Chemical, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 34:19, 3623-3630,
DOI: 10.1081/SCC-200031053
To link to this article: http://dx.doi.org/10.1081/SCC-200031053

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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 19, pp. 3623–3630, 2004
Efficient Tetrahydropyranylation of Alcohols
and Detetrahydropyranylation Reactions in
the Presence of Catalytic Amount of
Trichloroisocyanuric Acid (TCCA)
as a Safe, Cheap Industrial Chemical
*
Habib Firouzabadi, Nasser Iranpoor,
and Hassan Hazarkhani
*
Department of Chemistry, College of Sciences,
Shiraz University, Shiraz, 71454, Iran
ABSTRACT
Preparation and cleavage of THP ethers of different hydroxy functional
groups are easily and efficiently performed in the presence of trichloro-
isocyanuric acid (TCCA) in the absence of solvent with high yields.
Key Words: Trichloroisocyanuric acid; Tetrahydropyranylation;
Detetrahydropyranylation; Solvent-free.
*
Correspondence: Habib Firouzabadi and Nasser Iranpoor, Department of Chemistry,
College of Sciences, Shiraz University, Shiraz, 71454, Iran; Fax: þ98-711-2280926;
E-mail: firouzabadi@chem.susc.ac.ir or iranpoor@chem.susc.ac.ir.
3623
DOI: 10.1081/SCC-200031053
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

3624
Firouzabadi, Iranpoor, and Hazarkhani
INTRODUCTION
The worldwide production of trichloroisocyanuric acid, 1, 3, 5-2, 4,
6-(1H, 3H, 5H)trione (TCCA) and its monosodium salt (DCCA) is about
100,000 t/year and the demand is increasing by 8–10% per year for swim-
ming pools and 3–5% for food processing. This safe chemical has never
had a real breakthrough in organic laboratories and its uses in organic chem-
istry are mostly limited to chlorination and oxidation reactions.[1] Recently,
dehydrogenation of indolines,[2] urazoles,[3a] and N-nitrosation of secondary
amines[3b] have been achieved in the presence of TCCA.
The first catalytic application of trichloroisocyanuric acid was reported by
our research group for efficient thioacetalization and transthioacetalization
reactions.[4]
Tetrahydropyranylation of alcohols and phenols is a useful tool for masking
hydroxy functional groups for further manipulation in organic synthesis. This
transformation has found important synthetic applications because of the stab-
ility of the tetrahydropyranyl derivatives towards basic media, Grignard
reagents, and reactions involving oxidation and reduction by inorganic hydride
transfer agents.[5] In this article we have presented another catalytic application
of TCCA in tetrahydropyranylation and detetrahydropyranylation reactions.
RESULTS AND DISCUSSION
In continuation of our interest in functional group transformation under mild
reaction conditions, we now report that TCCA can be employed as an efficient
catalyst for the protection of primary, secondary, and tertiary alcohols and
phenols with 3,4-dihydro-2-H-pyran (DHP) at 60–808C under solvent-free con-
ditions. In this study, we have shown that primary and secondary benzylic alco-
hols substituted with electron-donating and electron-withdrawing groups can be
effectively protected in the presence of 0.1 molar ratio of TCCA to their corre-
sponding tetrahydropyranyl ethers in high yields (Sch. 1, Table 1, entries 1–11).
Scheme 1.

Preparation of THP Ethers in Presence of Trichloroisocyanuric Acid
3625
Table 1. Tetrahydropyranylation of alcohols and phenols catalyzed by TCCA under
solvent-free conditions.
Time (h)
Yield (%)a,c,d
Prot. Deprot.
92 95
Entry
Subs.
Prot.
Deprot.
1
2
5
5
3
4
92
96
3
4
5
3.5
3
93
95
5.5
94
95
5
6
5
4
4
94
91
94
95
5.5
7
8
9
5
8
6
4
6
4
92
87
92
94
92
94
10
11
12
6
7
5
4
4
3
90
90
92
92
90
95
(continued)

3626
Firouzabadi, Iranpoor, and Hazarkhani
Table 1. Continued.
Time (h)
Yield (%)a,c,d
Prot. Deprot.
88 95
Entry
13
Subs.
Prot.
8
Deprot.
5
14
15
8
6
6
87
89
92
91
10
16
17
8
6
7
5
92b
95
95b
96
18
19
5.5
7
5
6
94
90
94
95
20
21
6
7
6
6
89
94
87b
92b
22
23
5
6
4
5
92
90
95
94
24
25
5
6
4
4
91
90
93
94
26
5
4
90
92
(continued)

Preparation of THP Ethers in Presence of Trichloroisocyanuric Acid
3627
Table 1. Continued.
Time (h)
Yield (%)a,c,d
Entry
27
Subs.
Prot.
Deprot.
7
Prot.
75b
Deprot.
91b
24
24
28
8
80b
90b
29
30
31
32
33
1-adamantanol
phenol
8
36
38
5
5
6
7
4
7
89
85
87
88
85
90
92
90
90
91
4-bromo phenol
cholesterol
4-hydroxybenzaldehyde
36
aIsolated yields.
bGC yields using internal standard.
cThe amount of DHP was 1.2–1.6 mmol per 1 mmol of the substrate.
1
dStructures were confirmed by IR, H-NMR, 13C-NMR, mp/bp.
Cinnamyl, primary and secondary allylic and propargylic alcohols were
also efficiently converted to their tetrahydropyranyl ethers in excellent
yields without isomerization of the C-C double and triple bonds (Table1,
entries 12–16). Primary and secondary acyclic and cyclic saturated alcohols
were also effectively transformed to their tetrahydropyranyl ethers with
high yields (Table 1, entries 17–25). Preparation of tertiary ethers is not an
easy task and is usually accompanied by the formation of olefins and
usually with low yields. Therefore, we applied this method for the preparation
of tetrahydropyranyl ethers from tertiary benzylic alcohols such as 1-methyl-
cyclohexanol, 2-methyl-2-hexanol, and 1-adamantol in good yields (Table 1,
entries 27–29). Protection of phenolic hydroxy groups has been achieved in
the presence of this catalyst. Phenol, 4-bromophenol and 4-hydroxy benzal-
dehyde were converted to their corresponding ethers in high yields (Table 1,
entries 30, 31, and 33). The hydroxy functional group of cholesterol was also
efficiently converted to its THP ether under solvent-free conditions in the pre-
sence of this catalyst in 88% yield (Table 1, entry 34). When the method is
applied for the synthesis of multifunctional organic molecules, selectivity of
the method shows its importance. We have observed that reactions conducted
in the presence of this catalyst proceeded with high selectivity in excellent
yields. As we have observed, steric hindrance and nucleophilicity of hydroxyl
groups are important for differentiation between different hydroxyl groups.

3628
Firouzabadi, Iranpoor, and Hazarkhani
In order to show the selectivity of the method, we have performed several
competitive reactions. The results are shown in Sch. 2, which presents the
high selectivity of the catalyst under reaction conditions.
Deprotection of THP ethers is important in organic synthesis and there
are many reported methods for this purpose.[5,6] TCCA can be employed
very easily for the highly efficient catalytic detetrahydropyranylation reac-
tions in the presence of CH3OH (5 mmol) at room temperature in excellent
yields (Sch. 1, Table 1). We have also proposed a mechanism in which
the role of TCCA for the protection of hydroxyl functional groups by
DHP ether by the in situ generation of catalytic amounts of HCl is clarified
(Sch. 3).
In conclusion, we have introduced a new selective and efficient catalytic
system for tetrahydropyranylation and detetrahydropyranylation reactions
under mild and neat conditions. TCCA is a safe, commercially available,
cheap industrial chemical.
Scheme 2.

Preparation of THP Ethers in Presence of Trichloroisocyanuric Acid
3629
Scheme 3.
EXPERIMENTAL
All the products are known and commercially available compounds.
Therefore, their physical data are not given. The products were purified by
column or plate chromatography on silica gel; when necessary, the purity
determination of the products was accomplished by GC on a Shimadzu
model GC-14A instrument or by TLC on silica gel polygram SIL G/UV
254 plates. The IR spectra were recorded on a Perkin Elmer 781 spectropho-
tometer. The NMR spectra were recorded on a Bruker advance DPX 250 MHz
spectrometer.
General procedure for tetrahydropyranylation of alcohols and phenols
catalyzed by TCCA:
To a mixture of an alcohol or a phenol (5 mmol), DHP (0.51–0.67 g, 6–
8 mmol), TCCA (0.12 g, 0.5 mmol) was added. The mixture was stirred at
60–808C for the appropriate reaction time (Table 1). After completion of
the reaction (GC or TLC), the resulting mixture was applied on a silica gel
pad (5-cm thick) and was washed with a mixture of petroleum ether (bp
60–808C)/EtOAc (10 : 1, 100 mL). Evaporation of the solvent under
reduced pressure gave the desired compound in high purity. Spectroscopic
data (IR, NMR) of the isolated ethers were in agreement with those reported
for the authentic samples.
General procedure for detetrahydropyranylation reactions catalyzed by
TCCA:
To a mixture of tetrahydropyranyl ether (5 mmol) in CH3OH (25 mmol),
TCCA (0.12 g, 0.5 mmol) was added. The mixture was stirred at room temp-
erature for the appropriate reaction time (Table 1). After completion of the

3630
Firouzabadi, Iranpoor, and Hazarkhani
reaction (GC or TLC), CH2Cl2 (50 mL) was added to the reaction mixture. The
resulting mixture was washed with aqueous solution of Na2S2O3 (10%,
10 mL), decanted, and the organic phase was dried over anhydrous MgSO4.
Evaporation of the solvent under reduced pressure gave the hydroxy com-
pound in high yields. Spectral data (IR, NMR) of the isolated products were
identical with those reported for the authentic samples.
ACKNOWLEDGMENT
The authors are grateful for the partial support of this work by the Shiraz
University Research Council. The valuable help of K. Amani and
S. Ghassamipour for repeating some of the reactions is gratefully
acknowledged.
REFERENCES
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2002, 1633; (b) Zolfigol, M.A.; Ghorbani-Choghamarani, A.;
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Received in the UK July 7, 2003