LETTER
771
Ultrasound Promoted ‘One Pot’ Conversion of Nitrocompounds to
Carbamates1
U
ltrasound Pr
o
.
m
oted
‘
One
C
pot’ Conversion
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of Nitrocom
a
pounds to
n
C
arbamates drasekhar,* Ch. Narsihmulu, V. Jagadeshwar
Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax +91(40)7160512; E-mail: srivaric@iict.ap.nic.in
Received 15 March 2002
Abstract: An efficient ultrasound promoted novel direct conver-
sion of nitro compounds to N-(tert-butoxycarbonyl) amines and N-
(ethoxycarbonylamines) is achieved using Sn-NH4Cl for the first
time.
Key words: ultrasound, nitrocompounds, N-(tert-butoxycarbonyl)
amines, N-(ethoxycarbonyl) amines, Sn-NH4Cl, one pot
Scheme
‘One pot’ reactions2 are gaining prominence due to their
environmental advantages and cost effectiveness. Simi-
larly, application of ultrasound3 in chemistry is reaching a
stage of importance because of its proven ability to accel-
erate even very robust transformations.
to reflux for 24 hours (in the absence of sonication) the
product yield was found to be only 50%. Encouraged by
this observation we investigated various other nitro com-
pounds to probe their behaviour under sonication. As
shown in the Table, this simple method can be applied to
a variety of nitro compounds such as simple and substitut-
ed aromatic nitro compounds. Selective reduction of the
nitro group in the presence of sensitive functional groups
such as halides (entry 5 and 6) and a carbonyl group (entry
8) is successfully achieved, conversions normally difficult
under catalytic hydrogenation methods. Conversion of ni-
trophenol (entry 7) proceeded smoothly to N-Boc protect-
ed hydroxy aniline. Nitroaniline (entry 9) yielded the
doubly protected derivative (with 2.6 equiv of Boc2O) un-
der the same reaction conditions. In addition nitropropane
(entry 10) yielded the corresponding N-Boc protected de-
rivative within 3 hours of reaction time. When all the sub-
strates were subjected to similar reaction conditions by
replacing (Boc)2O with ethyl chloroformate the corre-
sponding N-(ethoxycarbonyl) amines were isolated in
good yields (1b–10b).8
Our research group has been actively engaged in the de-
velopment of new methodologies directed towards reduc-
tion of functional groups.4 In this context, a direct
conversion of nitro group to a protected amino group was
desired as part of a solution phase library synthesis. Even
though numerous methods5 are described in the literature
for reduction of nitro groups to amino groups, no proce-
dure is documented describing nitro group conversion to
NHBoc or NHCOOEt in one pot.
Two papers however describe reductive carbonylation6 of
nitro functionality to NHCO2Me and reduction-reductive
amination protocol using B10H14-HOAc.7 The first meth-
od requires a high pressure carbonylation reactor and the
second method requires expensive decaborane for a two
stage reduction which is not applicable for large scale syn-
thesis. In this context, herein we disclose an ultrasound
promoted, novel and efficient method for the direct con-
version of nitro compounds to N-(tert-butyl carbonyl)
amines and N-(ethoxy carbonyl) amines with tin metal un-
der essentially neutral conditions (Scheme). As shown in
the Table a variety of nitro compounds could be reduced
and protected in one pot with ease and in high yields with
simple workup procedure.
In conclusion, we have demonstrated a novel and efficient
protocol for the direct conversion of nitro compounds to
N-Boc-protected primary amines and N-ethoxycarbonyl-
amines under neutral conditions for the first time. The one
pot conversion described here has tremendous application
in multi-step organic synthesis due to its high chemoselec-
tivity, simplicity and milder reaction conditions.
Initially nitrobenzene, Sn and NH4Cl in the presence of
(Boc)2O in MeOH as solvent was subjected to sonication.
After 3 hours the starting material was completely con-
sumed (monitored by TLC). The reaction mixture on fil-
tration and purification by column chromatography
afforded N-(tert-butoxycarbonyl) aniline in 92% yield.
However when the same reaction mixture was subjected
A Representative Procedure: A mixture of nitrobenzene (entry 1,
1 mmol), (Boc)2O (1.2 mmol), Sn granules (6 mmol) and NH4Cl (10
mmol) in MeOH (5 mL) was sonicated at 25 °C. The progress of the
reaction was monitored by TLC. At the end of the reaction the mix-
ture was filtered, washed with ethyl acetate (3 5 mL), the filtrate
was dried (sodium sulfate) the volatiles removed and the crude ma-
terial was chromatographed on silica gel to yield N-(tert-butoxycar-
bonyl) aniline 1a in 92% yield. In a similar manner, (Boc)2O was
replaced by ClCOOEt to furnish N-(ethoxycarbonyl) aniline 1b in
93% yield.
Synlett 2002, No. 5, 03 05 2002. Article Identifier:
1437-2096,E;2002,0,05,0771,0772,ftx,en;D03402ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214
Chandrasekhar
