Copper-exchanged bentonite: A reusable catalysis for the formation of alkoxycarbonyl nitrile ylides under microwave irradiation

Article abstract of DOI:10.3184/174751912X13298456741454

Ethyldiazoacetate reacts as a carbene precursor in presence of copper exchanged bentonite. Reaction with excess nitrile gave oxazole derivatives. Their formation is explained by intramolecular 1,5-cyclisation of alkoxycarbonyl substituted nitrile ylide intermediate.

Full text of DOI:10.3184/174751912X13298456741454

JOURNAL OF CHEMICAL RESEARCH 2012
RESEARCH PAPER 149
MARCH, 149–151
Copper-exchanged bentonite: a reusable catalysis for the formation of
alkoxycarbonyl nitrile ylides under microwave irradiation
Choukri Kamel Bendedouche and Hadj Benhaoua*
Laboratoire de Synthèse Organique Appliquée, Département de Chimie, Faculté des Sciences, Université d’Oran Es-Sénia, BP1524,
Oran, Algeria
Ethyldiazoacetate reacts as a carbene precursor in presence of copper exchanged bentonite. Reaction with excess
nitrile gave oxazole derivatives. Their formation is explained by intramolecular 1,5-cyclisation of alkoxycarbonyl
substituted nitrile ylide intermediate.
Keywords: ethyldiazoacetate, carbene, nitrile, copper exchanged bentonite, oxazole, nitrile ylide, microwave irradiation
Several methods are known for the formation of nitrile ylides.
The most important routes are the dehydrochlorination of
imidoyl chloride using triethylamine,1 the thermolysis of
The scope of the catalytic reaction was explored with a
range of aromatic and aliphatic nitriles. Under these condi-
tions, EDA give oxazoles in good yield and purity. However,
p-nitrobenzonitrile did not give the expected product. Analysis
3
∆ -oxazolinones,2 oxazaphospholes3 and the photolysis of
1
2H-azirines.4 Another useful method to generate nitrile ylides
is the carbene–nitrile reaction first suggested by Kende et al. in
1982.5
of the H NMR spectrum showed the formation of dimeric
products. The lack of reactivity of the p-nitrobenzonitrile was
probably due to the electron withdrawal caused by the nitro
group in the para position. With aliphatic nitriles it was best
to use the Synthewave 402® fitted with a reflux condenser.
Furthermore, in some cases (entries 7, 8) the formation of
an amide 6 as a side product was observed (Scheme 2). Its
The most common method for the generation of carbenes is
the catalytic decomposition of a diazocompound.6 However,
this method has various drawbacks such as the use of expen-
sive catalysts which are inaccessible and difficult to recycle
which limits their use in large-scale synthesis. Sometimes long
reaction times and tedious work-up are necessary. In the course
of our studies related to the use of inorganic solid supports
in heterocyclic synthesis,7 we have extended this work to
modified bentonite. Here, we report the catalytic effect of
copper exchanged bentonite (BCu) in the decomposition of
ethyl diazoacetate (EDA) in the presence of various nitriles as
a suitable route to alkoxycarbonyl-substituted nitrile ylides.
To the best of our knowledge the generation of a carbene
involving a combination of an exchanged clay and microwave
irradiation has not been explored. First of all, we demonstrated
the catalytic efficiency of BCu for the decomposition of EDA.
To study the role of the BCu in the formation of a carbene we
explored the decomposition of EDA under various conditions.
Benzonitrile was used as a model reaction. Reaction carried
out in the absence of the catalyst gave starting materials;
however, dimeric products were obtained in presence of BCu
(Scheme 1). As illustrated in Table 1 the decomposition of
EDA requires a catalyst, and the formation of oxazoles needs
an excess of nitrile. The reaction carried out in an excess of
benzonitrile (entry 7) leads exclusively to the 5-ethoxy-2-
phenyloxazole 5a in good yield. The results are reported in
Table 1.
1
structure was confirmed without ambiguity by the H NMR
and by comparison with a sample obtained by unambiguous
synthesis. It probably arises from the presence of water misci-
ble in acetonitrile. The results are summarised in Table 2.
The formation of oxazole appears to proceed through a
nitrile ylide intermediate generated from EDA and nitrile. The
carbene generated by catalytic decomposition of diazoesters
in presence of exchanged bentonite reacts with nitrile to form
alkoxycarbonyl substituted nitrile ylide intermediate which
undergo 1,5 intramolecular cyclisation to give oxazoles
(Scheme 3). The formation of amide 6 which occurs only with
aliphatic nitriles, arises from the hydrolysis of the nitrile ylide
intermediate and is sensitive to experimental conditions8.
Experiments carried out in presence of water give exclusively
the amide, whereas under thermal or microwave irradiation, no
amide was formed with dry acetonitrile (distillation over P2O5).
We also found that acetonitrile alone was stable in presence of
water under the same conditions. Our experimental results
indicate that reaction pathway to oxazole proceeds stepwise
and the nitrile ylide exists as an intermediate. This suggestion
agrees with that previously reported by other authors9.
In conclusion, the Cu-exchanged bentonite catalysed decom-
position of diazoacetate in presence of various nitriles under
Scheme 1
* Correspondent. E-mail: hajben@hotmail.com

150 JOURNAL OF CHEMICAL RESEARCH 2012
Table 1 Effect of different conditions in the decomposition of EDA
Entry
Catalyst
Reagents
Exp. conditions
Products
1
2
3
4
5
6
7
Absence of BCu
Absence of BCu
Absence of BCu
Presence of BCu
Presence of BCu
Presence of BCu
Presence of BCu
EDA + benzonitrile
EDA + benzonitrile
EDA + benzonitrile
EDA + benzonitrile
EDA + benzonitrile
EDA + benzonitrile
EDA + benzonitrilea
Solventless, RT
∆ (135 °C)/20 min
MWI (20 min)
RT
∆ (135 °C)/20 min
MWI (20 min)
∆ or MWI
Starting materials
Starting materials
Starting materials
Dimers
Dimers
Dimers
Oxazole
a Excess of benzonitrile is used.
Scheme 2
(δ in ppm, J in Hz). Mass spectra (HRMS) were measured on a Varian
MAT 311 at the ionisation potential of 70 eV. IR spectra were mea-
sured with a JASCO 4200 FTIR spectrometer (range 4000–400 cm−1).
X-ray powder diffraction data were collected with monochromatic
CuKα radiation using Philips PW 3710 diffractometer. Microwave
assisted reactions were performed in a Synthewave 402 apparatus
(Merck Eurolab, France) using the stirring and refluxing option. The
microwave instrument consists of a continuous focused microwave
power output from 0 to 300 W. The target temperature was reached
with a ramp of 3 min and the chosen microwave power was constant
to maintain the temperature. The reaction temperature was monitored
using a calibrated IR sensor and the reaction time included the ramp
period.
microwave irradiation provides a clean, simple and rapid alter-
native for the synthesis of oxazole derivatives. This clay mate-
rial is shown to be a good substitute for many sophisticated
and inaccessible catalysts.
Experimental
1H NMR and 13C NMR spectra were recorded on Bruker AC 300 P
spectrometer using CDCl3 as solvent and TMS as internal standard
Table 2 Oxazoles synthesis with nitriles under MWI
Entry
R
Temperature % 5a
/ °C
% 6a
Yield/%
Procedure for the preparation of catalyst
5c
6d
Natural clay marketed under the name of bentonite has been the
subject of numerous studies that demonstrate that it belongs to the
smectite family, consisting mostly of montmorillonite.10 It was
purified using by sedimentation following by pretreatment with HCl
(0.01 mol L−1) to remove carbonates and sulfates.
1
2
Ph
o-MePh
p-MePh
p-MeOPh
p-ClPh
p-NO2Ph
Me
135
135
145
135
180
150
80
100
100
100
100
100
0
0
90
82
66
60
52
0
61
69
67
80
0
0
3
0
0
4
0
0
Specific treatments allow the introduction of metal cation Cu (II)11.
The insertion of copper was carried out by the slow addition
(12 hours) of a solution of copper chloride (500 mL 1N) to a suspen-
sion of sodium bentonite12 (50 g L−1). After removal of the superna-
tant, the operation was repeated three times. The cupric clay which
was obtained, was dried, crushed, and then analysed. Its structure was
confirmed by different spectral methods (FTIR, X-ray diffraction),
particularly the XRD spectra show the d001 decrease from 14.94 Å to
12.5 Å. This result is described in the literature.11
5
0
0
6
0b
0
0
7
85
90
100
100
15
10
0
10
5
8
Et
97
9
iPr
Bn
80
165
0
0
10
0
1
a Yields estimated by H NMR. b Dimerisation product of EDA.
c Yields of isolated oxazole based on EDA. d Yields of isolated
amide.
Scheme 3

JOURNAL OF CHEMICAL RESEARCH 2012 151
Preparation of oxazoles; general procedure
5-Ethoxy-2-isopropyl-1,3-oxazole (7c):17 Yield: 67%, translucent
1
liquid, b.p. 85 °C/20 mmHg. H NMR: δ = 1.30 (d,(CH3)2CH, 6H,
Experiments were performed in a Synthewave 402® oven equipped
with a stirring system and fitted with a refluxing condenser. A bipha-
sic mixture obtained from aromatic nitrile (5 mL), and BCu (0,1 g)
dried under domestic microwave oven (6 min, 650 watt) was placed in
a cylindrical quartz tube (reactor Ø = 2.8 cm). The irradiation was
performed at 135 °C obtained after 3 min (other irradiation tempera-
tures are given in Table 2). The reflux was maintained for 18 minutes
and during that time EDA (6.0 mmol) in nitrile (5 mL) was added
dropwise. When the reaction was complete the mixture was cooled
and extracted with CH2Cl2 (2 × 15 mL). After removal of the dichlo-
romethane and excess of nitrile under vacuum, the crude mixture
was analysed by 1H NMR and then the product is purified by short-path
distillation. To avoid formation of amides, aliphatic nitriles were
distilled over P2O5 before use and reactions were conducted under an
atmosphere of N2.
3JH-H = 7.0), 1.41 (t, OCH2–CH3, 3H, 3JH-H = 7.0), 2.94 (m, 1H), 4.08
(q, OCH2–CH3, 2H, 3JH-H = 7.0), 5.94 (s, 1H). 13C NMR: δ = 14.4, 20.1,
28.3, 67.6, 98.2, 159.25, 159.5; HRMS, m/z (found/calcd): 155.0943/
155. 0946 (M+., C8 H13 N O2).
2-Benzyl-5-ethoxy-1,3-oxazole (7d):18 Yield: 80%, white solid,
1
b.p. 65–70 °C/0.02 mmHg. H NMR: δ = 1.38 (t, OCH2–CH3, 3H,
3
3JH-H = 7.0), 3.97 (s, Ph-CH2, 2H), 4.05 (q, OCH2–CH3, 2H, JH-H
=
7.0), 5.97 (s, 1H), 7.22–7.35 (m, 5H). 13C NMR: δ = 14.4, 34.8, 67.8,
98.9, 126.9, 128.6, 128.7, 135.6, 153.6, 159.7; HRMS, m/z (found/
calcd): 203.0954 / 203.0946 (M+., C12 H13 N O2).
Ethyl acetamidoacetate (8a):19 Yield: 10%, hygroscopic white solid,
1
b.p. 65–70 °C/0.02 mmHg. H NMR: δ = 1.28 (t, OCH2–CH3, 3H,
3JH-H = 7.1), 2.04 (s, 3H), 3.99 (d, 2H, JH-H =5.5), 4.19 (q, 2H,
3
3JH-H = 7.1), 7.23 (br s, 1H, NH). 13C NMR: δ = 13.6, 22.5, 41.2, 61.2
171.0, 170.1.
5-Ethoxy-2-phenyl-1,3-oxazole (5a):9 Yield: 90%, translucent
Ethyl 2-(propionamido)acetate (8b):Yield: 5%, light yellow liquid,
1
solid, m.p. < 50 °C, b.p. 90–100 °C/0.2 mmHg. H NMR: δ = 1.24
1
3
b.p. 100 °C/0,1 mmHg. H NMR: δ = 1.14 (t, CH3–CH2, 3H, JH-H
=
(t, OCH2–CH3, 3H, 3JH-H = 7.1), 4.13 (q, OCH2–CH3, 2H, 3JH-H = 7.1),
6.19 (s, 1H), 7.27–7.92 (m, 5H). 13C NMR: δ = 14.5, 68.0, 100.6,
125.2, 127.6, 128.6, 132.6, 152.4, 159.8; HRMS, m/z (found/calcd):
189.0823 / 189.0790 (M+., C11H11NO2).
3
3
7.2), 1.29 (t, OCH2–CH3, 3H, JH-H = 7.1), 2.34 (q, 2H, JH-H = 7.3),
3
3
4.02 (d, 2H, JH-H =5.2), 4.19 (q, OCH2–CH3, 2H, JH-H = 7.1), 6.28
(br s, 1H, NH). 13C NMR: δ = 9.0, 14.1, 26.0, 48.0, 61.2, 169.5, 174.3.
HRMS, m/z (found/calcd): 159.0902 / 159.0895 (M+., C7 H13 N O3).
5-Ethoxy-2-o-tolyl-1,3-oxazole (5b): Yield: 82%, white solid, b.p.
45 °C/0.03 mmHg. 1H NMR: δ = 1.40 (t, OCH2–CH3, 3H, 3JH-H = 7.1),
Received 12 November 2012; accepted 3 February 2012
Paper 1100981 doi: 10.3184/174751912X13298456741454
Published online: 22 March 2012
3
2.65 (s, o-CH3Ph, 3H), 4.10 (q, OCH2–CH3, 2H, JH-H = 7.1), 6.21
(s, 1H), 7.18–7.87 (m, 4H). 13C NMR: δ = 14.5, 21.9, 67.8, 100.3,
125.8, 126.5, 127.8, 129.1, 131.5, 136.6, 152.7, 159.5; HRMS, m/z
(found/calcd): 203.0940 / 203.0946 (M+., C12H13NO2).
5-Ethoxy-2-p-tolyl-1,3-oxazole (5c):13 Yield: 66%, white solid, b.p.
References
50 °C/0.02 mmHg. 1H NMR: δ = 1.42 (t, OCH2–CH3, 3H, 3JH-H = 7.0),
1
R. Huisgen, H. Stangl, H.J. Sturm and H. Wagenhofer, Angew. Chem., Int.
Ed., 1962, 1, 50.
W. Steglich, P. Gruber, H.H. Ulrich and F. Kneidl, Chem. Ber., 1971, 104,
3816.
K. Burger, J. Fehn and E. Moll, Chem. Ber., 1971, 104, 1826.
A. Padwa and S.I. Jr. Wetmore, J. Org. Chem., 1974, 39, 1396.
A.S. Kende, P. Hebeisen, P.J. Sanfilippo, and B.H. Toder, J. Am. Chem.
Soc., 1982, 104, 4244.
3
2.34 (s, p-CH3Ph, 3H), 4.12 (q, OCH2–CH3, 2H, JH-H = 7.0), 6.16
(s, 1H), 7.18–7.81 (syst. aa’, bb’, 4H). 13C NMR: δ = 14.5, 21.3,
67.9, 100.4, 124.9, 125.2, 129.3, 139.6, 152.7, 159.5; HRMS, m/z
(found/calcd): 203.0940 / 203.0946 (M+., C12H13NO2).
2
3
4
5
5-Ethoxy-2-(4-methoxyphenyl)-1,3-oxazole (5d):14 Yield: 60%,
white solid, b.p. 50 °C/0.04 mmHg. 1H NMR: δ = 1.42 (t, OCH2–CH3,
3
3
3H, JH-H = 7.1), 3.79 (s, 3H), 4.12 (q, OCH2–CH3, 2H, JH-H = 7.1),
6.14 (s, 1H), 6.89–7.86 (syst. aa’,bb’, 4H). 13C NMR: δ = 14.5, 55.2,
68.0, 100.3, 144.1, 120.5, 126.9, 152.6, 159.5, 160.7; HRMS, m/z
(found/calcd): 219.0870 / 219.0895 (M+., C12 H13 N O3).
6
7
8
M.P. Doyle, Chem. Rev., 1986, 86, 919.
A. Saoudi, J. Hamelin and H. Benhaoua, J. Chem. Res., 1996, 492.
H.-J. Hansen and H. Heimgartner, 1,3-Dipolar cycloaddition chemistry,
eds A. Padwa, John Wiley & Sons, New York, 1984, Vol. 1, pp. 177–279.
K. Fukushima and T. Ibata, Bull. Chem. Soc. Jpn., 1995, 68, 3469.
9
2-(4-Chlorophenyl)-5-ethoxy-1,3-oxazole (5e):13 Yield: 52%, light
10 S. Caillère, S. Henin and M. Rautureau, Minéralogie des argiles, Ed.
Masson, Paris, 1982, Part 2, pp. 49-56.
11 J.M. Adams, J.A. Ballantine, S.H. Graham, R.J. Laub, J.H. Purnell,
P.I. Reid, W.Y.M. Shaman and J.M. Thomas, J. Catal., 1979, 58, 238.
12 A. Elaziouti, Z. Derriche, Z. Bouberka and N. Laouedj, J. Korean Chem.
Soc., 2010, 54, 110.
13 R.D. Connell, M. Tebbe, A.R. Gangloff, P. Helquist and B. Åkkermark,
Tetrahedron, 1993, 49, 5445.
14 N.Y. Huang, Y.B. Nie and M.W. Ding, Synlett, 2009, 611.
15 W.R. McKay and G.R. Proctor, J. Chem. Soc., Perkin Trans. 1, 1981,
2443.
16 G.Y. Kondratèwa and K. Tschshi-Chen, Russ. J. Gen. Chem., 1962, 32,
2315.
17 E. Zbiral, E. Bauer and J. Stroh, Monatsh. Chem., 1971, 102, 168.
18 B. Shi, A.J. Blake, I.B. Campbell, B.D. Judkins and C.J. Moody, Chem.
Commun., 2009, 3291.
1
yellow solid, b.p. 100 °C/0.04 mmHg. H NMR: δ = 1.47 (t, OCH2–
3
3
CH3, 3H, JH-H = 7.1), 4.18 (q, OCH2–CH3, 2H, JH-H = 7.1), 6.20
(s, 1H), 7.36–7.85 (syst. aa’, bb’, 4H). 13C NMR: δ =14.5, 68.1, 100.7,
126.0, 128.5, 128.8, 135.4, 151.6, 159.9; HRMS, m/z (found/calcd):
223.0412 / 223.0400 (M+., C11 H10 N O2 35Cl).
5-Ethoxy-2-methyl-1,3-oxazole (7a):15 Yield = 73%, translucent
1
liquid, b.p. 70 °C/20 mmHg. H NMR: δ = 1.40 (t, OCH2–CH3, 3H,
3JH-H = 7.1), 2.32 (s, 3H), 4.07 (q, OCH2–CH3, 2H, JH-H = 7.1), 5.92
3
(s, 1H). 13C NMR: δ = 14.0, 14.5, 67.9, 98.9, 152.1, 159.4; HRMS,
m/z (found/calcd): 127.0632 / 127.0633 (M+. C6 H9 N O2).
5-Ethoxy-2-ethyl-1,3-oxazole (7b):16 Yield: 69%, yellow liquid, b.p.
1
3
85 °C/20 mmHg. H NMR: δ = 1.28 (t, CH2–CH3, 3H, JH-H = 7.6),
3
3
1.41 (t, OCH2–CH3, 3H, JH-H = 7.1), 2.66 (q, CH2–CH3, 2H, JH-H
=
3
7.6), 4.08 (q, OCH2–CH3, 2H, JH-H = 7.1), 5.95 (s, 1H). 13C NMR:
19 T.P. Andersen, A.G. Ghattas and S.O. Lawesson, Tetrahedron, 1983, 39,
3419.
δ = 10.9, 14.5, 21.7, 67.8, 98.6, 156.5, 159.4.

Copyright of Journal of Chemical Research is the property of Science Reviews 2000 Ltd. and its content may
not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written
permission. However, users may print, download, or email articles for individual use.