J. Chil. Chem. Soc., 58, Nº 1 (2013)
SOLVENT FREE N-BOC PROTECTION OF AMINES USING AMBERLYSTR A 21 SOLID BASE RESIN AS A
REUSABLE HETEROGENEOUS CATALYST
SUNIL U. TEKALE, SUSHAMA S. KAUTHALE AND RAJENDRA P. PAWAR*
Department of Chemistry, Deogiri College, Aurangabad, 431005 (MS) India.
(Received: May 22, 2012 - Accepted: October 22, 2012)
ABSTRACT
An efficient, environmentally benign, highly facile and convenient synthetic protocol for the selective t-butyl carboxylation of aliphatic, aromatic and
heterocyclic amines using AmberlystR A 21 catalyst; a mild basic solid resin under solvent free conditions is reported. This method explores several advantages
such as reusability of the heterogeneous catalyst, cleaner reaction profile, mild and solvent free system, short reaction time, operational simplicity, high
conversions , excellent product yields and low cost of the catalyst. Furthermore since the catalyst is mild basic, decomposition of the carbamate formed is not
observed if the reaction is continued for prolonged time as in the case of Lewis acid catalyzed N-Boc protection. This makes the present protocol a useful and
attractive for N-Boc protection of amines.
Key words: AmberlystR A 21, Amine, t-butyl dicarbonate, Carbamate, Heterogeneous catalyst.
INTRODUCTION
Technological progress with environmental safety is one of the key
challenges of this millennium. The basic idea of clean production is to increase
the production efficiency with minimization of wastes and emissions. Eco-
efficiency and Green chemistry are the new principles guiding the development
of next generation products and processes. Green chemistry is an essential
and comprehensive programme to protect human health and environment.
According to recent environmental considerations with safety concerns and
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economic views, the use of such reagents is undesirable. Hence there is still
Recently the application of heterogeneous catalysts like ion-exchange
need for the generation of more efficient processes for the protection and
resins, zeolites and clays have attracted much more attention in organic
deprotection strategies in chemo selective transformations.
synthesis due to their operational simplicity, reusability, environmental
Heterogeneous catalysis contributes more in synthetic organic chemistry
compatibility, high selectivity, non-corrosiveness and easy availability of the
as it provides not only an alternative to homogeneous catalysis but also an easy
reagents at low cost. Further the ion exchange resins facilitate the reaction
catalyst recovery, recycling ability, keeping the reaction conditions often mild,
profile quite simple, are environmentally friendly, economic and convenient.
simple and easy product-catalyst separation. The development of efficient
Hence they worked as the efficient catalysts for carrying out different organic
and versatile heterogeneous catalytic system has become an active ongoing
transformations.
research area recently due to the potential advantages of these materials over
Amberlyst RA21 is particularly used for the removal of acidic impurities
homogeneous systems.
from non-aqueous solutions and mainly available in water-moist free solid
Protection and deprotection strategy has emerged as a powerful tool in
basic bead form having surface area of about 25 m2g-1, and ion exchange
organic synthesis. Among the various protecting groups used for amines; di
capacity of 1.3 meq ml-1. It can sustain a maximum temperature of 383-393 K.
tertiary butyl dicarbonate i.e. (Boc) O 1-4 is the frequently employed protecting
group mainly due to high stability 2of corresponding carbamates to different
Due to its inexpensive and commercially available solid form; it can be used
for different organic transformations.
nucleophiles under alkaline conditions and their ease of labile nature under
Herein we wish to disclose AmberlystR A21 which is a bead form mild
mild acidic conditions such as TFA/DCM, ethanolic HCl , 10% H2SO4 in
solid base resin as the non toxic environmentally friendly, cheap, reusable
1,4-dioxane etc.
heterogeneous catalyst for N-Boc protection of amines under solvent free
Protection of amines with (Boc) O has been carried out with or
conditions and ambient temperature conditions.
without solvent using various catalytic s2ystems such as DMAP, NaOH,
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HClO4-SiO2, molecular iodine, sulfamic acid/ultrasound, yttria-zirconia,
EXPERIMENTAL
10 indion-190 resin, 11 saccharin sulfonic acid,
phosphomolybdic acid supported on silica gel, Bronsted acid ionic liquid
H3PW12O40,
LiClO4,
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All the chemicals were purchased from commercial source (Aldrich) and
used without further purification. Column chromatography was done using
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methylimidazoliumtetrafluoroborate,
ZrCl4,
organic solvents like
1,1,1,3,3,3-Hexafluoroisopropanol , 18 Thiourea , 19 10% aq. AcOH , 20 iodine-
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Merck silica gel (100-200 mesh). H and 13C NMR spectra were recorded on
CsF , 21 indium(III) halides etc. The protection strategy in aqueous23 medium
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Varian (400 MHz) spectrophotometer. IR spectra of the samples were recorded
with Bruker Vector 22 FT-IR spectrophotometer and the samples were ana-
lyzed for ESMS on Shimadzu mass analyzer.
has also been reported. Finally to avoid the use of hazardous organic solvents,
attempts are being made to develop solvent free protocols.
The previous reported methods are associated with several limitations such
as longer reaction time, use of costly reagents and limited scope. Further the
Lewis acid catalyzed N-Boc protection of amines is of little significance due
to strong affinity of the Lewis acid catalysts for amino groups which do not
allow regeneration of the catalysts after completion of the reaction and more
over they get decomposed or deactivated by the amines or their derivatives
when used in more than stoichiometric amounts. In acid catalyzed reactions,
the carbamate formed further decomposes if the reaction is continued for long
duration of time. Therefore there is a scope for improvement towards facile
and solvent free reaction conditions for N-Boc protection under mild and basic
conditions.
General experimental procedure for the N-Boc protection of amines using
Amberlyst R A21 catalyst
Amberlyst R A21 (20 wt %) was added to a mixture of amine (1 mmole)
and (Boc)2O (1 mmole) and the mixture was stirred for the appropriate reaction
time as specified in (Table 1). The progress of reaction was monitored by Thin
layer chromatography (10-20% ethyl acetate: hexane) on TLC plates (Merck)
precoated with silica. After completion of reaction, the reaction mass was di-
luted with methanol, filtered off the catalyst which was washed for several
times and then dried at 800 C under reduced pressure for 1 hour and subjected
to further recycle study (Table 4). It showed no much more decrease in the
product yield indicating high activity of the catalyst. The filtrate was concen-
trated on rotavacc and the product was purified by column chromatography to
afford pure products.
e-mail: rppawar@yahoo.com
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