Microwave-assisted 1,3-dipolar cycloaddition reactions of nitrilimines and nitrile oxides

Article abstract of DOI:10.1039/a907010i

The 1,3-dipolar activity of hydrazonoyl chlorides and oxime chlorides over alumina with various alkenes and alkynes under microwave irradiation is studied; a comparative study between dry media conditions and the procedure in homogeneous solution under microwave and classical heating is described.

Full text of DOI:10.1039/a907010i

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7
18 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
Microwave-assisted 1,3-Dipolar Cycloaddition
1
999, 718^719y
Reactions of Nitrilimines and Nitrile Oxidesy
�
�
���
Ha¢da Kaddar, Jack Hamelin and Hadj Benhaoua*
a
Institut de Chimie, Universite
¨
d'Oran Es-senia, Alge
de Rennes I. Laboratoire de Synthese et Electrosynthe
Avenue du General Leclerc, F-35042 Rennes, France
¨
rie
b
Universite
¨
©
©
se organiques 3, UMR 6510,
¨
¨
The 1,3-dipolar activity of hydrazonoyl chlorides and oxime chlorides over alumina with various alkenes and
alkynes under microwave irradiation is studied; a comparative study between dry media conditions and the
procedure in homogeneous solution under microwave and classical heating is described.
In view of the synthetic importance of cycloaddition
reactions, there is an increasing interest in the development
of special methods and catalysts to enhance the selectivity
and shorten reaction times. Some studies related to
microwave-assisted cycloadditions in the presence of
solvents or under solvent-free conditions have been
We ¢rst studied the dehydrohalogenation of hydrazonoyl
chlorides and oxime chlorides over alumina under
microwave irradiation. The 1,3-dipoles generated in situ
4
were trapped with various alkenes and alkynes. Reactions
were carried out without solvent under microwave
irradiation using a monomode reactor over 30 min with
monitoring of temperature. Results and experimental con-
ditions are reported in Table 1.
1
described recently. Our current research programme
involving organic synthesis under microwave activation
led us to explore the possibility of performing 1,3-dipolar
cycloadditions under these conditions.
Experiments carried out under these conditions show that
reactions with alkynes and disubstituted alkenes give
moderate yields (40^60%) of the cycloadducts, whereas
no reaction of 1 and 2 with trisubtituted alkenes was
observed. These results are not surprising as trisubstituted
alkenes generally react more slowly than disubstitute
Recently, it was shown in our laboratory, that
dehydrohalogenation occurs over alumina under microwave
2
irradiation and in solvent-free conditions. According to
these results, we have extended this work to the 1,3-dipolar
activity of both hydrazonoyl chlorides and oxime chlorides
over alumina acting both as base and support with various
alkenes and alkynes. Here we report the results obtained
under various experimental conditions.
3
alkenes. Our experimental results show that generation
of the dipole can be achieved over alumina.
Manhas and coworkers have shown that the reaction
of imines with acid chlorides in the presence of
N-methylmorpholine (NMM) in chlorobenzene under
microwave irradiation provides a rapid access to b-lactams.
Unfortunately, however, a domestic oven was used without
accurate control of the temperature.
Table 1 Cycloaddition of 1,3-dipoles generated over alumina
under MW irradiation
Dipole
precursor
Ar
Dipolarophile
T/8C Yield(%)a
120c 40
120 60
140 50
110 40d
140 40
b
Table 2 Reactions with alkenes in xylene in the presence of
NMM under MW irradiation and classical heating
1a
1b
2a
2a
2b
1a
1b
2a
2b
1a
1b
Ph
p-ClC6H4
Ph
Ph
p-ClC6H4
Ph
p-ClC6H4
Ph
p-ClC6H4
Ph
ACꢀCE
ECꢀCE
ECꢀCE
3a(%)
MW
3a(%)
Heat
Dipole
precursor
HCꢀCCO2Et
(ECꢀCE
Ar
Alkene
b
b
PhCHˆCꢁCN†E
PhCHˆCꢁCN†E
PhCHˆCꢁCN†E
PhCHˆCꢁCN†E
120
120
120
140
0
0
0
0
1a
2a
1a
1b
2a
2b
1a
1b
Ph
Ph
Ph
p-ClC H
Ph
p-ClC H
Ph
p-ClC6H4
Ph
PhCHˆCꢁCN†E
PhCHˆCHE
ECHˆCHE
ECHˆCHE
ECHˆCHE
ECHˆCHE
Maleimide
0
0
0
0
65
85
80
75
55
75
80
30
40
40
40
22
42
40
6
4
b
ECHˆCHE
110 60
110 50
p-ClC6H4
Maleimide
6
4
aYields estimated by 1H NMR and not optimized, the remainder
b
c
Maleimide
Maleimide
being starting materials. E ˆ CO2Me. Maximum temperature
2
a
monitored by the oven in the cylindrical quartz reactor
diameter ˆ 4 cm). Yield of 4 + 5.
d
a
Yields estimated by 1H NMR are not optimized. bE ˆ CO Me
(
2
R
Y
Y
R
RC CY
+
+
Ar
Ar
C
N
X–
X–
Ar
Ar
X
Ar
X
N
4
N
5
Al2O3
MW
Ar
C
N
XH
Cl
+
N
RCH C(Y)(Z)
C
X
N
1
X = O; 2 X = NPh
a Ar = Ph; b p-ClC6H4
RC C(Y)(Z)
3
Scheme 1
In order to compare with the results of the above syn-
*
To receive any correspondence.
thesis over alumina, we applied the following procedure
for the cycloaddition of compounds 1 and 2 to alkenes
and alkynes.
y This is a Short Paper as de¢ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is
therefore no corresponding material in J. Chem. Research (M).

View Article Online
J. CHEM. RESEARCH (S), 1999 719
R
Y
H
R
Y
Table 3 Reactions with alkynes in xylene in presence of NMM
under MW irradiationa
NMM
MW
H
Y
1, 2 + RC CY
4 + 5 +
N
+
O
Dipole
b
b
b
precursor Ar
Alkyne
4/5 (%) 6 (%) 7 (%)
O
R
H
1ac
Ph
p-ClC6H4
Ph
p-ClC6H4
Ph
p-ClC6H4
Ph
p-ClC6H4
ECꢀCE
ECꢀCE
ECꢀCE
ECꢀCE
d
41/0
73/0
50/0
44/0
25/13 50
52/22 26
32/12 35
38/13 38
59
27
50
56
0
0
0
0
12
0
6
7
1
b
Scheme 2
2a
2b
1a
1b
HCꢀCCO2Et
HCꢀCCO2Et
Me
1
N
O
2a
HCꢀCCO Et
21
11
Ar
Cl
Ar
2
2
b
HCꢀCCO2Et
1
C
N
XH
+
C
N
XMe + H
N
O
30 ˚C
a
Yields estimated by H NMR are nearly quantitative. bRelative
Cl
c
proportions. In this case the selectivity is the same under classical
RC CY
Y
d
heating. E ˆ CO2Me.
R
H
N
reactions were run with monitoring of the temperature. All com-
1
13
pounds were analyzed by H and C NMR (200 MHz) spectroscopy,
the data are identical to those from the literature.
O
6
Scheme 3
Received, 25th August 1999
Paper F/9/07010I
Compounds 1 and 2 were reacted with a variety of
alkenes in the presence of NMM in xylene at 130 8C during
0 min under focused microwave irradiation. A comparison
with classical heating shows the superiority of the
microwave procedure. The same products are obtained
and the yields are better than for the reactions in dry
media (Table 1). Results are summarized in Table 2.
Reactions with alkynes under the same conditions
References
3
1
A. Loupy, A. Petit, J. Hamelin, F. Texier-Boullet, P. Jacquault
and D. Mathe, Synthesis, 1998, 9, 1213; A. Boruah, D.
¨
Prajapaty, J. S. Sandhu and A. C. Ghosh, Tetrahedron Lett.,
1996, 37, 4203; A. Diaz-Ortiz, E. Diez-Barra, A. de la Hoz,
A. Loupy, A. Petit and L. Sanchez, Heterocycles, 1994, 38,
7
85; A. Diaz-Ortiz, E. Diez-Barra, A. de la Hoz, A. Moreno,
M. J. Gomez-Escalonilla and A. Loupy, Heterocycles, 1996,
3, 1021.
(
30 min, 130 8C) gave the desired cyclized products 4
4
and 5 together with enamine 6 and the compound 7.
The formation of 6 is not unexpected as it is well known
2
3
B. Touaux, B. Klein, F. Texier-Boullet and J. Hamelin, J.
Chem. Res. (S), 1994, 116; B. Touaux, B. Klein, F.
Texier-Boullet and J. Hamelin, J. Heteroatom. Chem., 1998,
7
that tertiary amines react with alkynes to give enamines.
3
, 351; A. Saoudi, J. Hamelin and H. Benhaoua, Tetrahedron
Results collected in Table 3 show that the course of the
reaction is the same as when applying classical methods.
Scheme 3 accounts for the formation of the enamine 6.
Product 7 results from the transformation of ethyl
propiolate in the presence of water, as already mentioned
Lett., 1998, 39, 4033; S. Kasmi, J. Hamelin and H. Benhaoua,
Tetrahedron Lett., 1998, 39 8093.
Nitrile Oxides, Nitrones and Nitronates in Organic Synthesis,
ed B. G. Kurt Torssell, VCH Publishers, Inc. New York, 1988;
M. H. Hassaneen, H. A. Moussa, S. T. Ezmirly and A. S.
Shawali, Can. J. Chem., 1988, 66, 1386.
6
in the literature.
4
5
K. Bougrin, M. Sou¢aoui, A. Loupy and P. Jacquault, New. J.
Chem., 1995, 19, 213.
In summary, microwave heating accelerates the
cycloaddition processus when performed in a non-polar sol-
vent but the yields depend on the experimental conditions.
It is obvious that the use of NMM as a base is not a better
way to generate 1,3-dipoles in the presence of alkynes.
A. K. Bose, B. K. Banik and M. S. Manhas, Tetrahedron Lett.,
1
995, 32 213.
6
7
Winterfeldt, Chem Ber., 1964, 97, 1952.
1
We used a focused microwave oven Synthewave 402 from
Prolabo. This oven was ¢tted with an open reactor vessel
and a stirring device. R. Commarmsot, R. Didenot, J. F.
Gardais, Rhone-Poulenc/Prolabo (Pat. No. 84/03496. October
27th, 1986). The temperature was measured using an IR
captor, Prolabo (Pat. No. 62241D, 14669 FR. December 23rd
1991).
Experimental
ꢀ
R†
from
Experiments were performed in
a
Synthewave 402
Prolabo. The reactions were run in a quartz reactor of 4 cm diameter,
tted with a re£uxing condenser for the reactions in solution. All the
7
¢