Co2(CO)8 as novel and water-tolerant reagent for the conversion of azides to amines in aqueous media

Article abstract of DOI:10.1246/cl.2005.340

Azides are readily converted into their corresponding amines using a catalytic amount of Co₂(CO)₈ under mild conditions. The method is highly chemoselective and compatible with a variety of functionalities such as halides, esters, acids, ethers, nitro, cyano and olefinic double bonds present in the molecule. Copyright

Full text of DOI:10.1246/cl.2005.340

3
40
Chemistry Letters Vol.34, No.3 (2005)
Co (CO) as Novel and Water-tolerant Reagent
2
8
for the Conversion of Azides to Amines in Aqueous Media
Ã
J. S. Yadav, B. V. S. Reddy, G. Satheesh, and K. Raghavender Rao
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, India
(Received October 14, 2004; CL-041214)
Azides are readily converted into their corresponding
amines using a catalytic amount of Co2(CO)8 under mild condi-
tions. The method is highly chemoselective and compatible with
a variety of functionalities such as halides, esters, acids, ethers,
nitro, cyano and olefinic double bonds present in the molecule.
Table 1. Conversion of azides to amines using Co (CO) /H O
reagent system
2
Time/h
3.0
8
2
Entry
Azides
Producta
Yield/%
90
N3
NH
2
a
The conversion of aromatic azides to aryl amines is an im-
portant transformation in organic synthesis, used to construct a
variety of biologically active molecules, especially in heterocy-
N3
NH2
NH2
b
c
d
e
f
2.5
4.5
2.0
5.0
4.0
5.0
5.5
5.0
4.0
4.0
2.0
3.5
3.0
88
85
87
83
90
87
85
75
89
90
85
90
75
1
Me
Me
clic and medicinal chemistry. A number of reagents such as bo-
rohydrides, diborane, catalytic transfer hydrogenation, triphe-
nylphosphine, hydrogen sulfide, tri-n-butyltin hydride, zinc-hy-
drochloric acid, etc. have been reported to bring about this con-
N3
N3
N3
MeO
MeO
2
version under various reaction conditions. Among them LiAlH4
NH2
NH2
and Pd/C–H2 are the most commonly used reagents for this pur-
pose. But these reagents have one or more limitations regarding
to their general applicability, selectivity, commercial availabili-
ty, operational convenience and toxicity. For example, LiAlH4 is
not tolerable to many functionalities such as –CO2R, –NO2,
F
F
Cl
Cl
–COOH, etc., and on the other hand, diborane and catalytic
hydrogenation are not suitable to compounds having carbon–car-
N3
NH2
2
O N
2
O N
2
bon multiple bonds. Indeed, NaBH4 alone does not reduce
3
azides to amines except for arylsulfonyl azides. Subsequently,
N3
NH
2
zinc borohydride, samarium iodide, benzyl triethylammonium
tetrathiomolybdate, trimethylsilyl iodide, indium/ammonium
chloride, ferrous sulfate/ammonia and ferric chloride/sodium
g
h
i
CN
CN
N3
NH3
4
–7
iodide reagents, etc. have been employed for this conversion.
COOMe
COOMe
In spite of a large number of methods reported for this conver-
sion there is always considerable interest in exploring more
milder and selective reagents.
N3
NH2
COOH
COOH
Recently, a great deal of attention has been focussed on the
use of water as green solvent in organic synthesis. In addition to
its abundance and for economical and safety reasons, water has
naturally become as a substitute and an alternative environmen-
N3
Br
NH2
Br
j
Me
Cl
Me
Cl
8
tally benign solvent in organic synthesis. The use of aqueous
N3
NH2
Me
k
l
medium as solvent also reduces the harmful effects of organic
solvents on the environment. However, there are no precedents
on the use of metal carbonyls as catalysts for this transformation.
In this article, we describe a novel and efficient procedure
for the conversion of azides to amines using Co2(CO)8/H2O
reagent system under neutral conditions. Thus treatment of
phenyl azide with 0.15 equiv. of cobalt octacarbonyl [Co2(CO)8]
in water at room temperature gave the aniline in 90% yield
Me
N3
O
NH2
O
N3
NH2
m
n
(
Scheme 1).
SO N
SO NH
2
3
2
2
Me
Me
N3
Co
2
(CO)
8
NH2
H O
a
1
2
All products were characterized by H NMR, IR and mass spec-
troscopy.
Isolated and unoptimized yields.
1
2a
b
Scheme 1.
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.3 (2005)
341
Co(CO)4
HCo(CO)4
Co (CO)
Chap. 6. b) E. F. V. Scriven, ‘‘Azides and Nitrenes Reactivity
and Utility,’’ Academic Press, Inc., New York (1984).
a) E. F. V. Scriven and K. Turnbull, Chem. Rev., 88, 297
+
HCo(CO)4
Ph
N
N
N
Ph
N
N
N
H
2
-
2
8
(
1988). b) R. C. Larock, ‘‘Comprehensive Organic Transfor-
mations: A Guide to Functional Group Preparations,’’ VCH,
New York (1989), p 409.
M. Hedayatullah and A. Guy, Synthesis, 1978, 357.
a) B. C. Ranu, A. Sarkar, and R. Chakraborty, J. Org. Chem.,
H
H
Ph NH
N
N
H
PhNH2
Ph
N
N
N
-
N2
3
4
Scheme 2.
5
9, 4114 (1994). b) A. R. Ramesha, S. Bhat, and S.
Chandrasekaran, J. Org. Chem., 60, 7682 (1995). c) C.
Goulaouic-Dubois and M. Hesse, Tetrahedron Lett., 36,
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(1999). b) F. Fringuelli, F. Pizzo, and L. Vaccaro, Synthesis,
2000, 646. c) A. Kamal, K. V. Ramana, H. A. Babu, and
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a) C. J. Li and T. H. Chan, ‘‘Organic Reactions in Aqueous
Media,’’ John Wiley and Sons, New York (1997), p 159.
b) P. A. Grieco, ‘‘Organic Synthesis in Water,’’ Blackie
Academic and Professional, London (1998).
Encouraged by the results obtained with phenyl azide, we
turned our attention to various substituted azides. Interestingly,
a variety of aryl azides underwent reduction under similar con-
ditions to give the corresponding aryl amines. This method
was equally effective for the reducion of both electron rich as
well as electron-deficient azides. Aryl azides bearing nitro,
cyano and ester functionalities on the aromatic ring are remained
intact under the reaction conditions. In cases, the reactions
proceeded smoothly at room temperature and the products were
obtained in excellent yields. In the absence of catalyst, the reac-
tions did not take place even after long reaction times (8–12 h).
Among various solvents such as water, 1,2-dimethoxy ethane,
tetrahydrofuran, acetonitrile, and methanol tested for conver-
sion, water was found to give the best results. Further, we have
carried out the experiments using various metal carbonyls such
as Co2(CO)8, Cr(CO)6, and Fe(CO)5. Among them, cobalt octa-
carbonyl gave higher yields than others. The scope and general-
ity of this process was illustrated with respect to various aryl
5
6
7
8
9
azides and the results were presented in the Table 1.
The possible mechanism is expected to be the initial attack
9
Experimental procedure: A mixture of aryl azide (1 mmol)
and Co2(CO)8 (0.15 mmol) in water (10 mL) was stirred at
room temperature. After complete conversion, as indicated
by TLC, the reaction mixture was extracted with ethyl ace-
tate (2 Â 10 mL). The organic layers were dried over anhy-
drous Na2SO4 and purified by column chromatography on
silica gel (Merck, 100–200 mesh, ethyl acetate–hexane,
2:8) to afford pure aryl amine. All the products were fully
1
0
of hydro carbonyl [(HCo(CO)4] on the azide nitrogen atom fol-
lowd by formation of amine and release of nitrogen. (Scheme 2)
In summary, we have described a mild and efficient ap-
proach for the conversion of azides to amines using Co2(CO)8/
H2O as the novel reagent system. The use of water as solvent
makes this method simple and convenient. This method is very
useful especially for the chemoselective reduction of azides to
amines in the presence of other reducible functionalities such
as nitro, cyano, esters, and halides.
1
characterized by H NMR, IR and mass spectroscopy and al-
so by the comparison with known products. The spectral data
of all the products were identical with data reported in the lit-
3
–7
erature.
References and Notes
1
10 a) R. W. Goetz and M. Orchin, J. Org. Chem., 27, 3698
(1962). b) H. Y. Lee and M. An, Tetrahedron Lett., 44,
2775 (2003). c) L. Marco, Proc. Chem. Soc., 1962, 67.
a) T. Sheradsky, ‘‘The Chemistry of the Azido Group,’’ ed.
by S. Patai, Interscience Publishers, New York (1971),
Published on the web (Advance View) February 5, 2005; DOI 10.1246/cl.2005.340