Indium-mediated efficient conversion of azides to carbamates¤
Jhillu S. Yadav,* Basi V. Subba Reddy and Garudammagari S. Kiran Kumar Reddy
Organic Chemistry Division-I, Indian Institute of Chemical T echnology, Hyderabad-500 007,
India. Fax: ]91 40 717 0512; E-mail: yadav=uct.ap.nic.in
L e t t e r
Received (in Montpellier, France) 4th April 2000, Accepted 8th June 2000
Published on the Web 13th July 2000
A novel and efficient method for the high yield preparation of
carbamates by the reaction of azides with several chlorofor-
mates using indium metal in DMF at ambient temperature is
described for the Ðrst time.
tion. The reaction proceeds smoothly at room temperature
and does not require any promoter, stringent conditions or
anhydrous solvent. The reaction of azides with chloroformates
in the presence of indium is rapid and a†ords high yields of
carbamates in a short time. All the products were character-
ized by 1H NMR, IR and mass spectra. A variety of functional
groups like esters, ethers, oleÐns, nitros and cyanos present in
the substrate are una†ected under the reaction conditions. It
should be emphasized that in the absence of indium, the reac-
tion did not proceed and mainly resulted in the recovery of
the starting materials. Similarly, the reaction of azides with
Azides are an important class of compounds, particularly for
producing primary amines via reductive transformation. Pro-
tection of amines with appropriate groups plays an important
role in multistep synthesis of complex natural products and
also in peptide synthesis. Among the various amine-protecting
groups,1 carbamates are commonly used due to their chemical
stability towards acids, bases and hydrogenation. In addition
to this, carbamates are well-known in the Ðeld of medicine
and agrochemicals.2 The most commonly used procedures for
the conversion of azides to carbamates are based on the azide
catalytic reduction, followed by in situ protection with
Boc O in the presence of metals did not yield the product,
2
even after a long reaction time at room temperature. The
failure of this reaction with Boc O in the presence of indium
2
metal clearly indicates that the chloroformate activates the
metal, allowing the reaction to proceed rapidly at room tem-
perature. Even though we have not studied the reaction
mechanism in detail we presume that indium metal quickly
reacts with chloroformates to generate an In(III)
Boc O.3 However, in spite of its potential utility, catalytic
2
hydrogenation4 is generally incompatible with carbonÈcarbon
multiple bonds, benzyloxycarbonyl (CBz) and related protect-
ing groups present in the substrate. An alternative method for
catalytic hydrogenation is the treatment of the azide with
organometallic species that attacks the azide with loss of N
gas to a†ord an RÈN(In)ÈCOOR1 intermediate, which on
2
phosphines, followed by the reaction with Boc O5 or chloro-
hydrolysis gave the desired carbamate. In the blank experi-
ment the azides were not reduced by indium metal under the
reaction conditions. The reaction was successful only with
chloroformates in the presence of metals. Furthermore, high
yields of products were isolated when the reactions were
carried out in DMF. Among various metals like Mg, Zn and
Sn used for this transformation, indium is found to be more
e†ective than the others. The comparative yields of car-
bamates with zinc have also been summarized in the table.
In conclusion, this letter describes a novel, efficient and
practical methodology for the high yield preparation of car-
bamates from azides using indium metal under mild condi-
tions. The adopted procedure is very simple, rapid and
convenient, and is a useful addition to the existing methods.
2
formates.6 Some of these methods su†er from drawbacks like
unsatisfactory yields with secondary/aromatic azides7 and
require tedious isolation procedures to remove by-products.8
Even though catalytic hydrogenation and Staudinger methods
have been employed for the direct conversion of azides to car-
bamates, such an organometallic reaction has not been
hitherto applied for the preparation of carbamates. In recent
years, indium-mediated reactions9 have received considerable
attention due to its exceptional stability to air and water,
compared to other metals. Since indium has special properties
in organometallic chemistry, the application of indium for the
one-pot conversion of azides to carbamates is of interest.
In continuation of our work on the applications10 of
indium, zinc and magnesium for various transformations,
herein we report a novel, convenient and practical method for
the direct conversion of azides to carbamates using indium
metal under mild reaction conditions (see Scheme 1). Thus,
several aryl and alkyl azides (see Table 1) were converted into
the corresponding carbamates by the reaction of the azide
with equimolar quantities of the chloroformate and indium
metal in DMF at room temperature. The application of this
method to a variety of azides indicates the scope of the reac-
Experimental
A mixture of chloroformate (6 mmol) and activated indium or
zinc powder (6 mmol) was stirred in commercial dimethyl for-
mamide (10 ml) for 5 min at 0 ¡C. A solution of azide (5 mmol)
in commercial DMF (5 ml) was then slowly added and the
mixture stirred for an appropriate length of time at room tem-
perature. After complete conversion, as indicated by TLC, the
reaction was quenched with aqueous ammonium chloride
(20%, 20 ml) and extracted with ether (2 ] 25 ml). The com-
bined organic layer was washed with brine (20 ml), dried over
anhydrous Na SO and concentrated in vacuo to yield crude
2
4
product, which was puriÐed by column chromatography on
silica gel (Aldrich, 100È200 mesh, ethyl acetateÈhexane 1 : 9),
to a†ord pure carbamate.
2c: 1H NMR (CDCl ): d 1.4 (t, 3H, J \ 7.8 Hz), 2.3 (s, 3H),
Scheme 1
3
4.3 (q, 2H, J \ 7.8 Hz), 6.4 (br s, NH), 7.4È7.65 (m, 3H).
¤ IICT Communication No. 4465
IR (KBr): l
3288 (NH), 1690 (CO), 2982, 1577, 1528, 1479,
max
DOI: 10.1039/b002660n
New J. Chem., 2000, 24, 571È573
571
This journal is ( The Royal Society of Chemistry and the Centre National de la Recherche ScientiÐque 2000
Yadav
