Facile and selective deprotection of aryl acetates using sodium
perborate under mild and neutral conditions
Babasaheb P. Bandgar,* Lavkumar S. Uppalla, Vaibhav S. Sadavarte and Suresh V. Patil
Organic Chemistry Research Laboratory, School of Chemical Sciences,
Swami Ramanand Teerth Marathwada University, Nanded 431 606, India.
E-mail: bandgar_bp@yahoo.com; Fax: 91-2462-29245
L e t t e r
Received (in Montpellier, France) 17th April 2002, Accepted 1st August 2002
First published as an Advance Article on the web 16th September 2002
a bleaching and antiseptic agent. Applications of SPB in var-
ious organic functional group transformations is well docu-
mented.18 The development of a new method that allows
transformations under essentially neutral conditions should
heighten the synthetic potentiality of the deprotection of aryl
acetates. The useful common and cheap reagent, sodium per-
borate has not been studied so far for this transformation. This
communication deals with a study of the scope of sodium per-
borate for the selective removal of aryl acetates in the presence
of other sensitive functional groups under mild and neutral
conditions (Scheme 1).
A variety of aryl acetates are cleaved to the corresponding phe-
nols using sodium perborate in methanol under mild conditions
(25 ꢀC). The effectiveness of this protocol is manifested in its tol-
erance of different functional groups and selectivity of deprotec-
tion towards aryl acetates whereas alkyl acetates are found to be
unreactive under these reaction conditions.
Protection or deprotection of a functional group is one of the
important and widely carried out synthetic transformations in
preparative organic chemistry.1 In developing a synthesis of
any phenol-containing product, protection is often mandatory
to prevent reaction with oxidizing agents and electrophiles or
reaction of the nucleophilic phenoxide ion with even mild alky-
lating and acylating agents. The protection of phenol as O-acyl
derivatives has long played a key role in organic synthesis,
because of the ease with which they are formed and cleaved.
In the synthesis of multifunctional molecules, the problem
regularly arises that a given functional group has to be
deprotected in the presence of others. The methods available
for deprotection of aryl acetates involve treatment with
Zn–MeOH,1a LiBH4 ,1a p-TsOH–SiO2–H2O,1a bis(tributyltin)-
oxide,2 NaHTe,3 borohydride exchange resin,4 Al2O3/micro-
waves,5 metal complexes,6 enzymes,7 metalloenzymes,8
antibodies,9 cyclodextrin10 micelle-catalyzed saponification11
and [tBu2SnOH(Cl)]2 .12 Alkaline hydrolysis is most commonly
employed for deprotection of acetates, yet a number of other
functional groups are not tolerated in this procedure.1 In spite
of several efforts, the methods available for selective removal
of aryl acetates in the presence of other sensitive functional
groups are very few,12–14 not general14 and most involve homo-
geneous conditions. The recently reported ytterbium triflate,15
unlike hafnium triflate,16 cleaves aryl acetates without Fries
migration. However, it requires long reaction times, drastic con-
ditions,aqueouswork-upanddoesnotdiscriminatebetweenaryl
and alkyl acetates. More recently reported natural kaolinitic
clay17 and aromatic thiols in the presence of K2CO3 in dipolar
aprotic solvents13 constitute an efficient protocol for selective
cleavage of aryl acetates. However, the former method
involves mild but acidic conditions whereas the latter method
requires drastic reaction conditions and it does not discrimi-
nate between aryl acetates and aryl benzoates. The deacylation
of acetates is carried out using [tBu2SnOH(Cl)]2 as a highly effi-
cient catalyst under almost neutral conditions.12 Though a
variety of functional groups are tolerated and high selectivities
are obtained in competition between primary, secondary and
tertiary alcohol acetates, selective deprotection of acetates in
the presence of benzoates is not be achieved by this method.
The versatility of sodium perborate (SPB) in functional
group oxidations has been highlighted in the literature.18 It is
inexpensive and extensively used in the detergent industry as
A variety of aryl acetates were subjected to the deprotection
conditions with an equivalent amount of sodium perborate in
methanol at 25 ꢀC to give the corresponding phenols.19 Among
the various solvents studied methanol is the solvent of choice.
The results are presented in Table 1. It is important to note
that this economically attractive and manipulatively simple
protocol allows chemoselective deprotection of aryl acetates
in the presence of several other protecting groups such as oxi-
mes (entry 4), thioacetals (entry 7), THP ethers (entry 8) and
NH-acetyl (entry 9). Functional groups such as aldehyde
(entry 3), ketone (entry 6), imine (entry 5) and benzoate (entry
12) remain unaltered under these reaction conditions. Further-
more, it is noticed that the aryl acetate group is removed selec-
tively in the presence of benzyl acetate (entry 10) and no
deacylation was observed for alkyl acetates (entries 10, 16–
19). It is also noticed that aryl trifluoroacetates are cleaved
readily to the corresponding phenols (entry 13). It may be also
quite interesting that the presence of carbonyl groups (entries
3, 6), halogen atoms (entries 14, 15, 17–19) and ester groups
(entries 10, 16–19), which may show some reactivity under
the basic conditions of reported methods, did not disturb the
reaction under the present reaction conditions. THP ethers,
simple aryl ethers, anilides, oximes, thioacetals and benzoates
generally do not tolerate acidic conditions. However, these
protected groups remain intact under the present reaction con-
ditions. This is attributed to the fact that the reaction is carried
out under neutral conditions. The present reaction conditions
allow exclusive aryl deacetylation with no trace of Fries migra-
tion products.
Excellent selectivities were observed during inter- and intra-
molecular competition between aryl esters and alkyl esters
(Scheme 2). Thus, 4-methoxyphenyl acetate with ethyl benzo-
ate [Scheme 2, eqn. (1)] and 2-naphthyl acetate with cinnamyl
Scheme 1
DOI: 10.1039/b203766c
New J. Chem., 2002, 26, 1273–1276
1273
This journal is # The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2002