Sodium hydrogen sulfate in poly(ethylene glycol). An efficient recyclable system for the deprotection of 1,1-diacetates

Article abstract of DOI:10.1007/s00706-005-0298-7

Poly(ethylene glycol) was used as the solvent for selective deprotection of 1,1-diacetates (acylals) with easy recyclability of solvent and sodium hydrogen sulfate catalyst. This method is high yielding, fast, clean, safe, and therefore very suitable for practical organic synthesis. Springer-Verlag 2005.

Full text of DOI:10.1007/s00706-005-0298-7

Monatshefte f€ur Chemie 136, 1191–1195 (2005)
DOI 10.1007/s00706-005-0298-7
Sodium Hydrogen Sulfate in Poly(ethylene
glycol). An Efficient Recyclable System
for the Deprotection of 1,1-Diacetates
ꢀ
Zhan-Hui Zhang
College of Chemistry, Hebei Normal University, Shijiazhuang 050091, China
Received July 16, 2004; accepted (revised) October 28, 2004
Published online April 25, 2005 # Springer-Verlag 2005
Summary. Poly(ethylene glycol) was used as the solvent for selective deprotection of 1,1-diacetates
(acylals) with easy recyclability of solvent and sodium hydrogen sulfate catalyst. This method is high
yielding, fast, clean, safe, and therefore very suitable for practical organic synthesis.
Keywords. Sodium hydrogen sulfate; Poly(ethylene glycol); Deprotection; 1,1-Diacetates;
Aldehydes.
Introduction
The selective protection or deprotection of a functional group is one of the impor-
tant and widely carried out transformations in multistep synthesis of complex
organic molecules [1]. In recent years, 1,1-diacetates have been introduced as
suitable protection groups for aldehydes [2] owing to their stability in neutral
and basic medium and ease of preparation [3]. In addition, they can be converted
into other useful functional groups by reaction with appropriate nucleophiles [4]
and used as carbonyl surrogates for asymmetric synthesis [5]. The synthesis of
aldehyde enantiomers by lipase-catalysed resolution of the corresponding acylals
has been reported [6]. However, the final stages of chemical manipulation require
their cleavage so as to regenerate the parent aldehydes. Therefore, considerable
interest has been focused on mild and selective methods. Consequently, reagents
have been developed for this transformation, which include hydrochloric acid [7],
sulfuric acid [8], montmorillonite clays [9], expansive graphite [10], zeolite [11],
the boron triiodide-N,N-diethylaniline complex [12], ceric ammonium nitrate
coated on silica gel [13], neutral alumina under irradiation [14], CeCl3 ꢁ 7H2O=NaI
[15], CBr4 [16], NOþ ꢁ crown ꢁ HðNO3Þꢂ [17], AlCl3 [18], zirconium(IV) chlo-
2
ride [3f], BiCl3 [19a], 2,6-dicarboxypyridinium chlorochromate [19b], layered
ꢀ
E-mail: zhanhui@126.com

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Z.-H. Zhang
Scheme 1
zirconium sulfophenyl phosphonate [20], Sc(OTf)3 [21], base-catalysed cleavage
by sodium hydroxide or aqueous potassium carbonate [22], and potassium phen-
oxides [23]. Recently, ꢀ-cyclodextrin in aqueous medium has also been reported
for this conversion [24]. However, most of these methods are associated with
drawbacks including the use of harmful organic solvents and non-available, costly
reagents, harsh reaction conditions, low yields, and difficulties to separate and
recover the catalyst. Therefore, the development of an efficient and versatile cat-
alytic system for the deprotection of 1,1-diacetates is highly interesting.
In recent years, liquid polymers or low melting polymers have emerged as
alternative green reaction media with unique properties such as thermal stability,
commercial availability, nonvolatility, immiscibility with a number of organic sol-
vents, and recyclability. Poly(ethylene glycol)s are preferred over other polymers
because they are inexpensive, nonhalogenated, easily degradable, and of low toxic-
ity [25]. Many organic reactions have been carried out using PEGs as solvent or
co-solvent, such as the Heck reaction [26], asymmetric dihydroxylation [27],
Suzuki cross-coupling [28], oxydehydrogenation of alcohols and cyclic dienes,
oxidation of sulfides, the Wacker reaction [29], and partial reduction of alkynes
[30]. The use of PEG as a recyclable solvent system for the metal mediated radical
polymerisation of methyl methacrylate and styrene has also been reported [31]. In
view of the emerging importance of PEG as novel reaction media, we wish to
report a mild and highly efficient method for the selective deprotection of 1,1-
diacetates using sodium hydrogen sulfate as catalyst in PEG (MW 2000)
(Scheme 1).
Results and Discussion
As shown in Table 1, treatment of phenylmethanediol diacetate (1c) in PEG in the
presence of NaHSO4 at 70ꢃC afforded benzaldehyde in 95% yield. In a similar
reaction, various 1,1-diacetates 1 underwent deprotection smoothly to give the
corresponding aldehydes 2 in excellent yield. The reactions are mild and no side
products or decomposition are observed. In the absence of catalyst, the reaction did
not yield any product even after a long reaction time. Lower catalyst loading can be
used with only a marginal drop in reaction rate. In these cases, lower temperature
can also be applied but results in a longer reaction time. It should be mentioned that
the cleavage of (m-nitrophenyl)methanediol diacetate (1o) and (p-nitrophenyl)meth-
anediol diacetate (1p) require a little longer reaction time, possibly due to the
strongly electron-withdrawing nitro substituent, which is in agreement with the
reaction in an organic solvent.
The tolerance of various functional groups under the reaction conditions is
noteworthy. Thus acid sensitive or oxidizable groups, such as methoxy, benzyloxy,
methylenedioxy, nitro, chloro, and double bonds survive. The phenolic acetate
functions (1m and 1n) remain also unaffected under these reaction conditions.

Sodium Hydrogen Sulfate in Poly(ethylene glycol)
1193
Table 1. Selective cleavage of 1,1-diacetates using NaHSO4 in PEG at 70ꢃC
Substrate
Time=min
Yield=%a
1a
1b
1c
1d
1e
1f
CH3(CH2)4-CH(OAc)2
CH3(CH2)8-CH(OAc)2
Ph-CH(OAc)2
30
35
20
18
17
15
30
40
16
25
25
30
18
20
120
150
85
88
95
94
93
92
96
97
96
95
90
93
92
93
95
93
4-MePh-CH(OAc)2
2-MeOPh-CH(OAc)2
4-BnOPh-CH(OAc)2
2-ClPh-CH(OAc)2
1g
1h
1i
4-ClPh-CH(OAc)2
3,4-(OCH2O)Ph-CH(OAc)2
4-FPh-CH(OAc)2
1j
1k
1l
2-Furyl-CH(OAc)2
PhCH¼CHCH(OAc)2
4-AcOPh-CH(OAc)2
3-MeO-4-AcOPh-CH(OAc)2
2-NO2Ph-CH(OAc)2
4-NO2Ph-CH(OAc)2
1m
1n
1o
1p
a
Yields refer to isolated products
Therefore the present procedure is a selective deprotection of aryl aldehyde dia-
cetates to aryl aldehydes in the presence of the phenol acetates.
To check the reusability of solvent as well as the catalyst, the reaction mixture
was extracted with diethyl ether, and PEG and sodium hydrogen sulfate were
solidified and used in a further cleavage of 1 by charging with same substrate.
The product obtained was of the same purity and yield as in the first run. E.g., the
treatment of 1c in PEG in the presence of NaHSO4 at 70ꢃC afforded benzaldehyde
in 95%, 94%, 92%, 93%, and 91% yields over five cycles.
In conclusion, we have developed an alternative cleavage procedure for 1,1-
diacetates using PEG as the solvent. The simple procedure combined with ease of
recovery and reuse of this novel catalytic system is expected to contribute to the
development of a green strategy for the deprotection of 1,1-diacetates in protective
group chemistry.
Experimental
All products were characterized by comparison of their spectral and physical data with those of
authentic samples. Boiling points and melting points are uncorrected. 1H NMR spectra were recorded
on a BRUKER AC-P-200 spectrometer, using CDCl3 as solvent and TMS as internal standard. IR
spectra were obtained on a FTS-135 spectrometer. 1,1-diacetates 1 were prepared according to the
procedure reported in Ref. [32].
General Procedure for the Deprotection of 1,1-Diacetates 1
A mixture of 1 mmol 1, 0.12g NaHSO4 (1mmol), and 2 g PEG-2000 was placed in a 25-cm3 round-
bottomed flask and was stirred and heated at 70ꢃC. After completion of the reaction (monitored by
TLC), the reaction mixture was cooled, and extracted with 3ꢄ10 cm3 of diethyl ether. The combined

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Z.-H. Zhang
organic layers were washed with brine, dried over anhydrous Na2SO4, and the solvent was evaporated
under reduced pressure. The crude product was purified by column chromatography on silica gel to
afford pure 2. The remaining PEG and NaHSO4 were further washed with ether and would be recycled
for subsequent reactions.
Acknowledgement
The financial support for this work from Hebei Normal University and National Natural Science
Foundation of China (20477009) is gratefully acknowledged.
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