Potassium triiodide. A new and efficient catalyst for carbon-carbon bond formation in aqueous media

Article abstract of DOI:10.1246/cl.2003.258

Potassium triiodide catalyses the condensation of carbonyl compounds with active methylene compounds in aqueous media to afford E olefinic products in high yields.

Full text of DOI:10.1246/cl.2003.258

258
Chemistry Letters Vol.32, No.3 (2003)
Potassium Triiodide. A New and Efficient Catalyst for Carbon–Carbon
Bond Formation in Aqueous Media
Ashim J. Thakur, Dipak Prajapati,Ã Baikuntha J. Gogoi, and Jagir S. SandhuÃ
Regional Research Laboratory, Jorhat 785006, Assam, India
(Received November 22, 2002; CL-020997)
Potassium triiodide catalyses the condensation of carbonyl
compounds with active methylene compounds in aqueous media
to afford E olefinic products in high yields.
can be seen from the table that all reactions proceeded selectively
to the dehydrated products without any side reaction. The reaction
between benzaldehyde and ethyl cyanoacetate in the presence of
KI3 (entry 3g) gave selectively the Knoevenagel adduct while the
same reaction promoted by an alkali metal containing MCM-41
yielded a mixture of hydrated and dehydrated products.12 The
aromatic a; b-unsaturated aldehydes gave the corresponding
olefinic products without the formation of any Michael-type
addition products. Thus, cinnamaldehyde with malononitrile
gave 1,1-dicyano-4-phenylbuta-1,3-diene (90% conversion after
20 min) exclusively. In the reaction of o-hydroxybenzaldehyde
with active methylene compounds the first-formed Knoevenagel
condensation products underwent further transformations as a
result of nucleophilic attack by the phenolate ion on the cyano
group, which is held in a stereochemically favourable position by
the olefinic bond. Thus 2-imino-2H-1-benzopyran-3-carbonitrile
and 2-imino-2H-1-benzopyran-3-carboxylate were formed ex-
clusively in 82 and 85% yields. The reaction13 was carried out by
mixing carbonyl compound, active methylene compound and
potassium triiodide14 at room temperature and heating them at
70 ꢀC for a specified time period, to give after usual work-up
excellent yields of the corresponding Knoevenagel products.
Some yields (e.g. 3a, 98%) were much higher than reactions
carried out in boiling benzene (74%). Furthermore, the rate of the
There has been growing interest in the use of metallic
elements1 in aqueous media, as they offer significant advantages
over conventional reactions using dry organic solvents. The
development of such reactions is of interest because they also
offer the possibility of obtaining environmentally benign reaction
conditions by reducing the burden of organic solvent disposal.2
The study and application of Knoevenagel condensation in water
is still in its infancy. Since their century old history the full
synthetic potential of such reactions is still waiting to be explored
and they need to be expanded.3 In recent years there has been
increasing emphasis on the use of environment friendly condi-
tions to reduce the amount of toxic waste and by-products arising
from the chemical processes. The challenge is to develop catalytic
conditions leading to carbon–carbon bond formation which are
widely employed in organic synthesis. The Knoevenagel con-
densation, have numerous applications in the elegant synthesis of
fine chemicals,4 in hetero Diels–Alder reactions,5 in the synthesis
of carbocycles and heterocycles6 and are usually catalysed by
organic bases (primary, secondary and tertiary amines, ammonia
and ammonium salts). With piperidine base, the by-products
formed are difficult to remove.7 However, in recent years, new
catalysts8 including silica gel functionalised with amine groups
(Al2O3, AlPO4–Al2O3, TiCl4/base and doped xonontlite), solid
phase resin,9 CdI2 in solid9 state, MS 5A/ethylenediammonium
diacetate10 and MW11 have been employed. But these methods
have their own merits as well as limitations. The main hurdle with
the Knoevenagel condensation is the reactivity of ketones with
the competitive Michael addition occuring in the reaction of some
active methylene compounds and there is also problem with the
stereocontrol in the synthesis of Knoevenagel products from
unsymmetrical carbonyl compounds. Here we wish to report the
first example of a new catalyst Kl3, for carbon–carbon bond
formation in aqueous condition. It can perform the reaction to
produce the E olefinic products in good purity and high yields, and
eliminates the piperidine based by-products and reduces trans-
esterification.
Table 1. Reaction time and yield of Knoevenagel product 3
R3
Prod-
ucts
R1
R2
Reaction Yield
time/min /%
3a
3b(
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
Ph
CN
E)-PhCH=CH CN
CN
15
20
20
22
21
16
15
20
16
20
18
16
15
15
20
22
20
22
20
22
98
88
80
80
85
83
86
85
87
82
83
89
85
90
90
90
85
80
82
80
CN
CN
CN
CN
CN
Me
2-Furyl
4-Quinolyl
p-NO2C6H4
Ph
(E)-PhCH=CH CO2Et CN
p-NO2C6H4
2-Furyl
4-Quinolyl
Ph
(E)-PhCH=CH CO2H
Ph
(E)-PhCH=CH CONH2 CN
p-MeOC6H4
Ph
Ph
o-OHC6H4
o-OHC6H4
CN
CN
CN
CN
CO2Et CN
CO2Et CN
CO2Et CN
CO2Et CN
The results obtained with different aliphatic, aromatic and
heterocyclic aldehydes and different active methylene com-
pounds, according to scheme 1 are recorded in the table. Also it
CO2H
CN
CN
CONH2 CN
CONH2 CN
CO2Et CO2Et
MeCO CO2Et
CN
CN
R1
H
R1
H
R2
R3
R2
R3
KI3
O
+
3s
3t
CN
CO2Et
Scheme 1.
Copyright ꢀ 2003 The Chemical Society of Japan

Chemistry Letters Vol.32, No.3 (2003)
259
reaction is quite impressive and comparable with the recently
reported Knoevenagel condensation under microwave
irradiation15 employing phosphorous pentoxide as dehydrating
agent and chlorobenzene as an energy transfer medium for the
removal of water. All the compounds obtained were characterized
by spectroscopic methods and finally by comparison with
authentic samples. Here the role of KI3 is as a mild base and the
reaction is probably similar to that of the reactions promoted by
haomogeneous bases.16 It proceeded by the abstraction of a
proton from active methylene compound, which gets stabilized
by the cationic charge. This stabilized carbanion attacks the
electrophilic carbonyl carbon to form an intermediate which in
turn, abstracts a proton from in situ generated HI. Dehydration
then takes place to form the Knoevenagel product.
in ‘‘Comprehensive Organic Synthesis,’’ ed. by B. M. Trost,
Pergamon Press, Oxford (1991), Vol. 2, p 341.
8
9
a) E. Angeletti, C. Canepa, G. Martinetti, and P. Venturello,
Tetrahedron Lett., 29, 2261 (1988). b) F. Texier-Boulleet and
A. Foucaud, Tetrahedron Lett., 23, 4927 (1982). c) J. A.
Cabello, J. M. Campelo, A. Garcia, D. Luna, and J. M.
Marinas, J. Org. Chem., 49, 5195 (1984). d) W. Lehnert,
Tetrahedron Lett., 19, 4723 (1978). e) S. Chalais, P. Laszlo,
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J. Simpson, D. L. Rathbone, and D. C. Billington, Tetra-
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10 Y. Hayashi, Y. Miyamoto, and M. Shoji, Tetrahedron Lett.,
43, 4079 (2002).
In conclusion, the present investigation in aqueous condition
offers a convenient and alternative method for the stereospecific
preparation of E olefins where the reaction is rapid, the yields are
excellent, the procedure is simple, the method is devoid of side
reactions such as self-condensation, bis-addition, dimerisation or
rearrangements and the use of nontoxic and inexpensive catalysts.
11 S. A. Ayoubi, F. Texier-Boullet, and J. Hamelin, Synthesis,
1994, 258; S. A. Ayoubi, and F. Texier-Boullet, J. Chem. Res.,
Synop., 1995, 208.
12 K. R. Kloetstra and H. V. Bekkum, J. Chem. Soc., Chem.
Commun., 1995, 1005.
13 General procedure for the Knoevenagel condensations in the
presence of potassium triiodide. In a typical case, to a solution
of potassium triiodide (0.04 gm, 0.1 mmol), benzaldehyde
(0.21 g, 2 mmol) and malononitrile (0.13 g, 2 mmol) were
added at room temperature. After stirring for 2 min, the
resulting mixture was heated at 70 ꢀC for 15 min (monitored
vide tlc). The reaction was then cooled to room temperature,
quenched with cold water, washed with sodium thiosulphate
and extracted with chloroform (2 Â 20 ml). The organic
extract was washed with water (20 ml), dried (Na2SO4) and
evaporated under reduced pressure to furnish a residue which
was purified by column chromatography (silica gel:CHCl3).
The product benzylidene malononitrile was obtained as a
crystalline solid mp 82 ꢀC (Lit17. mp 83 ꢀC) yield 98%. Other
Knoevenagel products were (entry 2 to 18) prepared similarly
and their characteristics are recorded in the table. Reaction of
o-hydroxybenzaldehyde with active methylene compounds,
carried out in the same way which gave the imino lactones in
80 to 82% yields.
We thank the Department of Science and Technology (DST)
New Delhi, for financial assistance and one of us AJT thanks
CSIR, New Delhi for the award of a senior research fellowship.
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