8
16
Chemistry Letters 2000
A Novel and Chemoselective Protocol for the Reduction of Azides
Using FeCl –Zn System
3
Diganta Pathak, Dhrubojyoti D Laskar, Dipak Prajapati, and Jagir S Sandhu*
Regional Research Laboratory, Jorhat 785006, Assam, India
(Received April 11, 2000; CL-000337)
Chemoselective reduction of alkyl, aryl, aroyl and arylsul-
fonyl azides to the parent amines or amides, respectively,
occurs in excellent yields upon treatment with a novel inexpen-
it exercises unique selectivity, is chemoselective, nonhazardous,
readily available and inexpensive
In a typical case, to a mixture of ferric chloride (0.270 g, 1
mmol) and zinc powder (0.065 g, 1 mmol) in a round bottom
flask was added a solution of phenyl azide (0.109 g, 1 mmol) in
ethanol (25 mL) dropwise with constant stirring at 0 °C. It was
then brought to room temperature and the stirring was contin-
ued for 4 h. (The progress of the reaction was monitored by
tlc). After completion of the reaction, metal was filtered off
and the filtrate was evaporated and extracted with chloroform
(2 × 30 mL). The extract was washed with water and brine and
dried over anhydrous Na SO . The organic layers were dis-
sive reduction system consisting of FeCl –Zn at room tempera-
3
ture.
Reduction of azides to amines is an important reaction in
organic synthesis, especially in carbohydrate and nucleoside
1
2
chemistry. A number of methods have been reported for this
reductive process describing the use of, for example, lithium
3
2
aluminium hydride, catalytic hydrogenation , zinc boro-
hydride, borohydride exchange resin (BER)–nickel acetate,
lithium aminoborohydrides, sodium borohydride, benzyl tri-
ethylammonium tetrathiomolybdate and bakers’ yeast etc.
But most of these methods have one or more drawbacks with
regard to general applicability, selectivity, ready availability,
2
4
4
5
tilled off under reduced pressure to get the crude amine which
was further purified by column chromatography using chloro-
form as eluent. Evaporation of the organic layers gave the cor-
responding crude aniline in virtually quantitative yield. Similar
treatment of other organic azides gave the corresponding
amines or amides in 80–98% yields.
6
7
8
9
operational convenience or toxicity. For instance, LiAlH is not
4
tolerable to many functionalities, such as –COOR, –NO etc.
The excellent yields of the reduction products demonstrate
the efficiency of this new method. Table summarizes our
results on the reduction of a number of aryl, alkyl, aroyl and
arylsulfonyl azides. In all the reactions, the cleavage takes
place between the N–N bond, rather than the C–N or S–N bond.
At the same time, azides are selectively reduced in the presence
of a double bond (entries 11 and 12), an aromatic methoxyl
group, acetonide and carboxyl groups. In case of nitro substi-
tuted aromatic azides, the corresponding nitro aniline was selec-
tively obtained without any further reduction of nitro group
(entry 4). Furthermore, haloaromatic azides showed remark-
able selectivity to give the amine without any dehalogenation
(entries 2, 3 and 7). Also the amides are not reduced further to
the corresponding amines. In addition, it was worth commenting
that 4-acetylphenylazide was converted to the 4-aminoaceto-
phenone and the sensitive carbonyl group remains intact.
Similar to aryl azides, p-toluenesulfonylazide also undergoes
fast and clean reduction with this novel reduction system. The
use of a lesser amount of the reagent normally results in signifi-
cant recovery of the starting azide. To include an example of
aliphatic azide we have carried out the reduction of 1-hexyl
azide under same conditions and the corresponding 1-hexyl-
amine was obtained in 80% yield (entry 9).
2
and on the other hand, catalytic hydrogenation and diborane
reduction have limitations for being applied to unsaturated
compounds containing a double or a triple bond. Also sodium
borohydride does not usually convert azides to amines in good
yield at ambient conditions in homogeneous systems, except in
1
0
the case of arylsulfonyl azides. Recently reduction of azides
1
1
12
by rare earths namely samarium iodide and samarium met-
als appeared in the literature. But the main drawbacks with
these methods, the metals used were comparatively expensive
and not readily available. As a result, there is always consider-
able interest in finding a simple and efficient reducing agent of
general applicability to all types of azides with tolerance to
1
3
other sensitive functionalities. Our interest in metal catalyst
prompted us to initiate systematic investigation on reduction of
organic azides including aroyl, arylsulfonyl, aryl and alkyl
azides. Herein we report a novel reduction system consisting of
inexpensive FeCl –Zn in ethanol for the chemoselective reduc-
3
tion of various organic azides. The reaction generally proceed-
ed with excellent yields at room temperature. The main advan-
tage of this new combination system over other methods is that
In conclusion, the present results demonstrate the novelty
of zinc–ferric chloride combination system which shows unique
selectivity and constitue a useful alternative to the commonly
accepted procedure for the synthesis of various primary amines
or amides. Moreover, this simple, readily available and cheap
metal affords various amines or amides in excellent yields with-
out the formation of any undesirable side products than the
classical methods.
Copyright © 2000 The Chemical Society of Japan
Pathak, Diganta
