Received: February 1, 2014 | Accepted: February 26, 2014 | Web Released: March 11, 2014
CL-140075
A New, Efficient, and Catalyst-free Microwave-assisted Approach
for Formation of O-tert-Butoxy Carbonates
Hacène K’tir, Aïcha Amira, Malika Berredjem, and Nour-Eddine Aouf*
Laboratory of Applied Organic Chemistry (LAOC), Bioorganic Chemistry Group, Sciences Faculty,
Chemistry Department, Badji Mokhtar-Annaba University, Box 12 23000, Algeria
(E-mail: noureddine.aouf@univ-annaba.dz)
13
A new simple, efficient, greener, and catalyst-free chemo-
selective protocol for the O-tert-butoxycarbonylation of various
structurally diverse hydroxy compounds was carried out with
(Boc)2O under microwave radiation. The corresponding O-tert-
butoxy carbonates were obtained in good to excellent yields in a
short reaction time without any side reactions.
(CBr4).12 The use of NaLaTiO4 as a heterogeneous reusable
catalyst is also reported.
Recently, Procopio et al.14 reported a new method for the
protection-cleavage of O-tert-butoxy carbonates of alcohols and
phenols using mesoporous silica-supported (ErIII-MCM-41).
Gawande et al.15 also reported an eco-friendly, chemoselective
O-tert-butoxycarbonylation of alcohols and phenols over
MgO-ZrO2 nanoparticles (NPs) under solvent-free conditions.
However, these methods have several drawbacks such as long
reaction times, formation of side-products during base-catalyzed
reactions, and excess reagents in the cases during solid acid-
catalyzed reactions.
In the last decade, organic synthesis in water under green
chemistry conditions has received great attention.1g,16 In the last
few years, our group reported a simple and eco-sustainable
method for O-Boc and N-Boc protection-deprotection under
various conditions.17
The replacement of conventional energy sources with other
alternative laboratory techniques has continued to attract a great
deal of attention over the last few years.18-20 Microwave and
ultrasound radiations have been proven to be better in terms
of its advantages such as reduced reaction times,21 enhanced
product yields,21 the elimination of undesirable side products,
and the ability to precisely control the temperature and pressure
profiles of the reaction.22 In this context, Dighe et al.23 and our
group24 are reported a new method for the N-tert-butoxycar-
bonylation of amines using microwave and ultrasound radiation,
respectively. It is a green chemistry approach for the synthesis of
Boc-protected amines, wherein the use of solvents and catalysts
is avoided.
Herein, we have reported a microwave-assisted effective,
simple, mild, rapid, and catalyst-free method for the chemo-
selective O-tert-butoxycarbonylation of hydroxy groups.
In our initial study, we reacted 1 mmol of phenol with
1.1 mmol of (Boc)2O in the absence of any catalyst with
minimum acetone as solvent under microwave irradiation; the
reaction was completed in just 30 min. We could also carry out
the reaction in the absence of solvent with similar yield.
(Scheme 1). Thus, we observed that microwave radiation played
an essential role, and the solvent did not affect the result of the
reaction.
To tackle serious pollution problems, scientists and chemists
have incorporated emerging approaches into the development of
new catalysts and energy systems for minimizing the negative
impact of chemicals on human health and environment;
this progressive development, known as “Green Chemistry” or
“sustainable technology,” has to take into account several
parameters such as the optimization of product yield, minimi-
zation of reaction time, avoiding the use of harmful organic
solvents, elimination of waste, and reduced use of toxic and/or
hazardous substances.1
In relation to organic transformations, the development of
mild, eco-friendly, and selective protocols for the protection-
deprotection of functional groups has received considerable
interest in the synthesis of the target molecule in the context of
green synthesis.2
Protection, one of the most significant methods in organic
chemistry, is based on the temporary blocking of one or more
functional groups to exploit maximum orthogonality; in other
words, the chemo- or/and the regioselectivity.3 The presence
of the hydroxy group in a wide range of biologically active
compounds make their protection an important step in synthetic
organic and medicinal chemistry, and the carbonates constitute
an important class of products having chemical interest.4
Among different methods, acylation is a commonly used
approach for the protection of the hydroxy group,5 but its
regeneration requires harsh reaction conditions,6 incompatible
with polyfunctional substrates. Furthermore, O-tert-butoxycar-
bonylation is suitable and is the preferred alternative process
to protect the hydroxy group. The tert-butoxycarbonyl group
(abbreviated as Boc or t-Boc) continues to attract a great deal
of attention due to both their resistance to nucleophilic reagents
and ease of regeneration under specific conditions.2a,2b Com-
mercially available di-tert-butyl pyrocarbonate (Boc)2O is a
better choice for preparing organic carbonates by direct coupling
with hydroxy compounds under various conditions.7
In order to optimize the reaction conditions, we conducted
the O-Boc protection of phenol (1 mmol) with (Boc)2O
(1.1 mmol) under various irradiations without solvent. The best
In general, the different strategies of O-tert-butoxycarbonyl-
ation of the hydroxy group available in literature were carried
out in the presence of a phase-transfer catalyst by using 4-
dimethylaminopyridine (DMAP) as catalyst8 and Lewis acid
O
O
MW, 100W
Neat
OH
OBoc
+
O
O
O
9
catalyst such as Zn(OAc)2 and BiCl3.10 Others methods use
Phenol
di-tert-butyl pyrocarbonate
tert-butyl phenyl carbonate
the organocatalyst such as 1-tert-butoxy-2-tert-butoxycarbonyl-
6,7-dihydroisoquinoline (BBDI),11 and carbon tetrabromide
Scheme 1. O-tert-Butoxycarbonylation of phenol.
© 2014 The Chemical Society of Japan | 851
K'tir, Hacene
