A novel and efficient method for the synthesis of α-azidoketones and α-ketothiocyanates

Article abstract of DOI:10.1246/cl.2004.882

α-Diazoketones underwent insertion smoothly with sodium azide and potassium thiocyanate in the presence of CeCl₃ ·7H ₂O under mild reaction conditions to afford the corresponding α-azidoketones and α-ketothiocyanates in excellent yields.

Full text of DOI:10.1246/cl.2004.882

882
Chemistry Letters Vol.33, No.7 (2004)
A Novel and Efficient Method for the Synthesis of ꢀ-Azidoketones and ꢀ-Ketothiocyanates
J. S. Yadav,ꢀ B. V. Subba Reddy, and M. Srinivas
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, India
(Received April 1, 2004; CL-040353)
ꢀ-Diazoketones underwent insertion smoothly with sodium
.
Table 1. CeCl3 7H2O-Promoted Synthesis of ꢀ-Azidoketones
and ꢀ-Ketothiocyanates
.
azide and potassium thiocyanate in the presence of CeCl3 7H2O
under mild reaction conditions to afford the corresponding ꢀ-
azidoketones and ꢀ-ketothiocyanates in excellent yields.
Producta
Yield /%b
Time/h
Entry
Nucleophile
Diazoketone
1
2
3
O
O
N3
N2
a
5.0(6.5)
91(86)
85(79)
89(81)
NaN3
ꢀ-Azidoketones are useful intermediates in organic synthe-
sis especially for the synthesis of a variety of heterocyclic com-
pounds such as oxazoles, pyrazines, 2-acylimidazoles, substitut-
ed pyrroles, and many others.1 In particular, ꢀ-azidoketones are
important intermediates for ꢁ-aminoalcohols which are, in turn,
useful as chiral ligands in asymmetric synthesis2 and as ꢁ-block-
ers in pharmaceuticals.3 The ready availability, relative stability,
and facile decomposition of ꢀ-diazocarbonyl compounds under
acid or thermal or photochemical conditions make them useful
intermediates in organic synthesis.4 Furthermore, ꢀ-diazoke-
tones undergo a variety of transformations such as cyclopropa-
nation, aziridine formation, ylide formation, C–H, X–H (X =
O, S, NH) insertion reactions and cyclization reactions.5 Lantha-
nide salts are unique Lewis acids that are currently of great re-
search interest.6 In particular, cerium reagents are relatively
non-toxic, readily available at low cost and are fairly stable to
air or moisture. Owing to its unique properties, CeCl3 has been
extensively used for a variety of organic transformations.7
In continuation of our interest on the use of cerium(III) chlo-
ride heptahydrate for various transformations,8 we herein report
a novel protocol for the preparation of ꢀ-azidoketones and ꢀ-ke-
O
O
6.0(7.0)
6.5(7.5)
SCN
b
c
KSCN
NaN3
"
O
N2
N3
F
F
O
O
4.5(6.0)
87(75)
N3
d
N2
NaN3
Me
Me
O
O
SCN
N3
6.5(7.0)
5.0(6.0)
84(71)
89(80)
e
f
KSCN
NaN3
"
Me
O
N2
MeO
MeO
O
O
SCN
N3
5.0(6.5)
6.0(7.0)
7.0(8.5)
86(78)
88(75)
82(70)
g
KSCN
NaN3
"
O
MeO
F
N2
h
i
F
O
SCN
N3
KSCN
NaN3
"
F
O
O
j
6.5(8.0)
7.0(9.0)
90(85)
87(81)
N2
( )9
.
( )9
tothiocyanates using CeCl3 7H2O as an efficient reagent
(Scheme 1).
O
SCN
KSCN
NaN3
k
( )9
"
"
O
O
.
CeCl3 7H2O
N2
X
+
R
R
MX
CF3
Cl
CF3
Cl
CH3CN
N3
N2
3
2
l
5.5(6.5)
6.0(7.5)
85(70)
80(75)
1
O
O
O
R = aryl, alkyl, cyclopropyl
MX = NaN3 or KSCN
CF3
Cl
Scheme 1.
m
KSCN
SCN
Thus treatment of ꢀ-diazoacetophenone with sodium azide
in the presence of cerium(III) chloride heptahydrate in acetoni-
trile afforded 2-azido-1-phenyl-1-ethanone in 91% yield. The re-
markable catalytic activity of cerium(III) chloride encouraged us
for further study of reactions with other ꢀ-diazocarbonyl com-
pounds. Interestingly, various ꢀ-diazoketones reacted smoothly
aAll products were characterized by 1H NMR, IR and mass spec-
troscopy.
bIsolated and unoptimized yields.
cYield and time shown in parenthesis obtained by Ce(OTf)3.
diazoketones failed to give the corresponding ꢀ-haloketones un-
der similar conditions. No side product arising from a Wolff re-
arrangement was observed under these reaction conditions. Oth-
er side products such as ꢀ-chloro- and ꢀ-hydroxy ketones (the
ꢁ
.
with sodium azide in the presence of CeCl3 7H2O at 80 C to
give the corresponding 2-azidoaryl and 2-azidoalkylketones.
Both aromatic and aliphatic ꢀ-diazoketones afforded the respec-
tive ꢀ-azidoketones in high yields (Table 1). The diazoketone
derived from cis-cyhalothric acid also gave similar results. In
a similar manner, potassium thiocyanate also reacted efficiently
with ꢀ-diazoketones to furnish 1-aryl-2-thiocyanato-1-etha-
nones or 1-alkyl-2-thiocyanato-1-ethanones in high yields. The
method is clean and the products are obtained in high yields.9
However, treatment of sodium bromide and sodium iodide with
.
products of chloride or OH insertion) arising from CeCl3 7H2O
were not detected under these reaction conditions. To know the
efficiency of this procedure, we have also carried out the reac-
tions with other cerium salts such as cerium(III) triflate and ceric
ammonium nitrate. Among these catalysts, cerium(III) chloride
was found to be the most effective reagent and giving the best
.
results. The reaction proceeded smoothly by CeCl3 7H2O in
Copyright Ó 2004 The Chemical Society of Japan

Chemistry Letters Vol.33, No.7 (2004)
883
acetonitrile at 80 ꢁC. Furthermore, we have examined the possi-
.
bility of CeCl3 7H2O functioning catalytically or at least, in less
than stoichiometric amounts. But best results were obtained with
8
9
a) J. S. Yadav, B. V. S. Reddy, K. B. Reddy, and M.
Satyanarayana, Tetrahedron Lett., 43, 7009 (2002). b) J. S.
Yadav, B. V. S. Reddy, M. S. K. Reddy, and G. Sabitha,
Synlett, 2001, 1134. c) J. S. Yadav and B. V. S. Reddy,
Synlett, 2000, 1275.
.
an equimolar ratio of CeCl3 7H2O. There are many advantages
in the use of cerium(III) chloride for this transformation, which
avoids the use of strongly acidic or basic conditions. The method
does not require the use of expensive or corrosive reagents and
no precautions need to be taken to exclude moisture from the re-
action medium. The scope and generality of this procedure is il-
lustrated with respect to various diazoketones and the results are
summerized in the Table 1.
Experimental procedure: A mixture of ꢀ-diazoketone (5
mmol), sodium azide or potassium thiocyanate (6 mmol)
.
CeCl3 7H2O (5 mmol) in acetonitrile (10 mL) was stirred at
80 ꢁC for a specified time as required to complete the reaction
(Table 1). After complete conversion, as indicated by TLC,
the reaction mixture was diluted with water (15 mL) and ex-
tracted with ethyl acetate (2 ꢂ 15 mL). The combined organic
layers were dried over anhydrous Na2SO4, concentrated in
vacuo and purified by column chromatography on silica gel
(Merck, 100–200 mesh, ethyl acetate-hexane, 1:9) to afford
pure 2-azidoketone or 2-ketothiocyanate. Spectral data for
the compounds 3e: Yellow solid, mp 102–103 ꢁC, IR
(KBr): ꢂ 2930, 2854, 2100, 1685, 1606, 1598, 1451, 1389,
1249, 981, 922, 772, 550 cmꢃ1. 1H NMR (200 MHz, CDCl3):
ꢃ 2.45 (s, 3H), 4.78 (s, 2H), 7.38 (d, 2H, J ¼ 8:0 Hz), 7.85 (d,
2H, J ¼ 8:0 Hz). 13C NMR (Proton decoupled, 75 MHz,
CDCl3): ꢃ 21.6, 44.6, 111.8, 126, 129.4, 131.7, 132.5,
133.3, 140.0, 193.0. EI–MS: m=z: 191 Mþ, 155, 141, 119,
105, 91, 77, 65, 39. 3j: Colourless solid, mp 41–42 ꢁC, IR
In summary, we disclose a new procedure for the prepara-
tion of 2-azidoketones and 2-ketothiocyanates using CeCl3
.
7H2O as a novel catalyst under mild conditions. The notable fea-
tures of this procedure are high conversions, simplicity in oper-
ation, cleaner reaction profiles, and ready availability of reagents
at low cost which make it a useful and attractive strategy for the
synthesis of 2-azidoketones and 2-ketothiocyanates of synthetic
importance.
BVS thank CSIR, New Delhi for the award of fellowship.
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.
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2
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770, 671 cmꢃ1. H NMR (200 MHz, CDCl3): ꢃ 1.25 (s, 3H,
3
4
5
–CH3), 1.35 (s, 3H, –CH3), 2.23 (dd, 1H, J ¼ 8:0, 8.6 Hz,
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.
6
7
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Published on the web (Advance View) June 14, 2004; DOI 10.1246/cl.2004.882