A Simple and Efficient Procedure for Deprotection of Tetrahydropyranyl Ethers Catalysed by Expansive Graphite

Article abstract of DOI:10.1039/a707188d

A variety of tetrahydropyranyl ethers of alcohols and phenols are easily deprotected in excellent yield under catalysis by expansive graphite.

Full text of DOI:10.1039/a707188d

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152 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 152±153$
A Simple and Efficient Procedure for Deprotection
of Tetrahydropyranyl Ethers Catalysed by Expansive
Graphite$
Zhan-Hui Zhang, Tong-Shuang Li,* Tong-Shou Jin and
Jian-Xin Wang
Department of Chemistry, Hebei University, Baoding 071002, Hebei Province, P.R. China
A variety of tetrahydropyranyl ethers of alcohols and phenols are easily deprotected in excellent yield under catalysis by
expansive graphite.
Selective introduction and removal of protective groups is
of great signi®cance in organic synthesis.1 The tetrahydro-
pyran-2-yl ether (THPE) functions are one of the most
common protecting groups for hydroxy functions owing
to their easy installation and remarkable stability towards
basic media, Grignard reagents and reactions involving
oxidation and reduction by inorganic hydrides.2
methoxymethyl ethers18 catalysed by expansive graphite. In
connection with our ongoing work on expansive graphite
catalysis, herein we wish to report an ecient deprotection
of THPEs under catalysis by expansive graphite under mild
conditions (Scheme 1).
Tetrahydropyran-2-yl ethers are usually transformed
into their parent alcohols or phenols under acid-catalysed
conditions. A wide variety of catalysts have been already
used for this conversion, including the use of protic acids3
(acetic acid, toluene-p-sulfonic acid, boric acid), Lewis
acids4 (magnesium bromide in diethyl ether, dimethylalumi-
nium chloride), electrogenerated acid,5 pyridinium toluene-
p-sulfonate,6 ion-exchange resins7 (amberlyst H-15, Dowex
50W-X8, Na®on-H), bis(trimethylsilyl)sulfate,8 distann-
oxane,9 organotin phosphate condensates10 and triphenyl-
phosphine dibromide (PPh3Br2).11 More recently, 2,3-
dichloro-5,6-dicyano-p-benzoquinone (DDQ),12 mesoporous
H-MCM-41 molecular sieve13 and heteropoly acid14 have
been applied to this reaction. However, some of these
procedures su€er from using expensive reagents, strongly
acidic conditions and/or necessitate aqueous work-up.
Consequently, there is still a demand to develop a mild and
ecient alternative procedure for this conversion.
Scheme 1
As summarised in Table 1, in the presence of expansive
graphite the deprotection of THPEs could be carried out
rapidly in methanol to a€ord the corresponding parent
hydroxy compounds (2) at 40±50; 8C in high yields. The
present procedure for deprotection of THPEs is quite
general as a wide range of THPEs of primary (1a±c and
1 h), secondary (1d±i) and benzylic alcohols (1c, 1 g and 1i)
as well as phenols and naphthols (1j±1q) were cleaved in
excellent yield. The acid-sensitive functionalities such as
methoxy (11) are safe in this procedure. Betulin (1 h) was
not converted into allobetulin under these conditions.
The reaction proceeds cleanly and the work-up is simple,
involving only the ®ltration of the catalyst and the removal
of solvent to obtain the product in high purity.
The surface acid character of expansive graphite has
been used as an ecient catalyst for organic reactions.15
Previously we have developed ecient and convenient
methods for the preparation16 and cleavage17 of 1,1-di-
acetates and the protection of alcohols by formation of
The reaction rate is markedly dependent on temperature.
We found that at room temperature the reaction proceeds
much more slowly; for example, complete conversion of
Table 1 Deprotection of THPE of alcohols and phenols catalysed by expansive graphite
Substrate
Product
Time (t/h)
Yield (%)a
n-C8H17-OTHP (1a)
n-C10H21-OTHP (1b)
PhCH2-OTHP (1c)
n-C6H13CH(OTHP)CH3 (1d)
Cholesteryl-OTHP (1e)
b-Sitosteryl-OTHP (1f)
Ph2CH-OTHP (1g)
Lup-20(29)-ene-3b,28-diyl-diOTHP (1h)
PhCH(OTHP)COPh (1i)
PhOTHP (1j)
p-CH3C6H4OTHP (1k)
p-CH3OC6H4OTHP (1l)
Resorcinyl-(OTHP)2 (m)
a-Naphthyl-OTHP (1n)
b-Naphthyl-OTHP (1o)
m-O2NC6H4OTHP (1p)
p-O2NC6H4OTHP (1q)
n-C8H17OH (2a)
n-C10H21OH (2b)
PhCH2OH (2c)
n-C6H13CH(OH)CH3 (2d)
Cholesterol(2e)
b-Sitosterol (2f)
PhCHOH (2g)
Betulin (2h)
Benzoin (2i)
PhOH (2j)
p-CH3C6H4OTHP (2k)
p-CH3OC6H4OH (2l)
Resorcinol (2m)
a-Naphthol (2n)
b-Naphthol (2o)
m-O2NC6H4OH (2p)
p-O2NC6H4OH (2q)
0.70
0.80
0.50
1.0
0.60
0.50
0.70
1.0
0.50
0.35
0.50
0.50
0.50
0.30
0.65
0.35
0.35
94
96
96
97
95
97
92
95
94
96
96
96
96
97
92
98
97
aYields refer to isolated pure products.
cholesteryl THPE (1e) into cholesterol (2e) needed 6 h in
methanol under catalysis of expansive graphite. The catalyst
was easily regenerated by washing with ethanol followed by
drying at 120 8C for 1 h. The catalyst could be reused four
*To receive any correspondence (e-mail: orgsyn@hbu.edu.cn).
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).

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J. CHEM. RESEARCH (S), 1998 153
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times for the deprotection of cholesteryl THPE (1e) without
any loss of catalytic activity.
In conclusion, the present procedure provides a general
methodology for the deprotection of THPE from a variety
of primary, secondary and benzylic alcohols and phenols.
The operational simplicity, use of an inexpensive, non-
corrosive and reusable catalyst, high yields and short reac-
tion time can make this procedure a useful and attractive
alternative to the currently available methods.
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Experimental
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The expansive graphite catalyst was prepared according to the
literature.16,19 THPEs were synthesised according to our recent
report.20 The products were characterised by IR and 1H NMR
spectra and by comparison of their TLC and mps or bps with
authentic samples.
General Procedure for Deprotection of THPE.ÐA mixture of
THPE (2 mmol), methanol (5 ml) and expansive graphite (100 mg)
was stirred at 40±50 8C for the length of time indicated in Table 1.
The progress of the reaction was monitored by TLC. After
completion of the reaction, the catalyst was removed by ®ltration
and washed with CH2Cl2 (5 ml). Evaporation of the solvent gave,
essentially pure, the corresponding parent hydroxy compound (2).
Further puri®cation was performed by ¯ash column chromatog-
raphy on silica gel with light petroleum±diethyl ether as eluent
wherever necessary.
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The project was supported by NSFC (29572039),
Education Commission of Hebei Province and Science and
Technology Commission of Hebei Province.
14 A. Molnar and T. Beregszaszi, Tetrahedron Lett., 1996, 37, 8597.
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H. Imamara, Bull. Chem. Soc. Jpn., 1991, 64, 1011; (b) J. Bertin,
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Received, 6th October 1997; Accepted, 3rd November 1997
Paper E/7/07188D
16 T.-S. Jin, G.-Y. Du, Z.-H. Zhang and T.-S. Li, Synth. Commun.,
1997, 27, 2261.
17 T.-S. Jin, Y.-R. Ma, Z.-H. Zhang and T.-S. Li, Synth. Commun.,
1997, 27, 3379.
References
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