1438
Lanthanide Nitrates as Lewis Acids in the One-Pot Synthesis of 1,2,4-Oxadiazole Derivatives
J. Braz. Chem. Soc.
column of fused silica, Supelco Simplicity 1TM.All reactions
were monitored by TLC. Flash column chromatography
was carried out using 200-300 mesh silica gel at increased
pressure.
(1), 159.1 (5), 147.1 (4), 136.1 (2), 119.1 (100), 105.1 (51),
91.0 (27), 77.0 (23), 65.0 (10), 51.0 (6).
3-(4-Methoxybenzoyl)-5-phenyl-1,2,4-oxadiazole (6)
1H NMR (300 MHz, CDCl3) d 8.36 (dd, 2H, J 6.5
Hz), 7.64 (t, 1H, J 6.5 Hz), 7.58 (t, 2H, J 6.5 Hz), 7.03 (d,
Representative experimental procedure for synthesis of
3,5-substituted-1,2,4-oxadiazole compounds by use of
lanthanide oxides
13
2H, J 7.0 Hz), 3.92 (s, 3H). C NMR (75 MHz, CDCl3)
d 181.3, 176.3, 166.4, 164, 9, 133.3, 133.3, 129.2, 128.5,
128.2, 123.5, 114.1, 55.6. MS (EI): m/z (%) 280 (22) [M+],
206.9 (4), 174.9 (12), 160.9 (5), 146.9 (10), 135.1 (100),
121.1 (3), 105.1 (54), 92 (10), 77.0 (44), 63.0 (9), 51.0 (11).
In a typical procedure, the lanthanide oxides (0.3 mmol)
and nitric acid (0.3 mmol) were stirred at 50 oC and then was
added the ketone (3 mmol). After 10 min the appropriated
nitrile (1 mL) was added and the result mixture stirred
3-(4-Nitrobenzoyl)-5-phenyl-1,2,4-oxadiazole (7)
1H NMR (300 MHz, CDCl3): d 8.55 (d, 2H, J 7 Hz), 8.40
(d, 2H, J 9 Hz), 8.27 (d, 2H, J 7 Hz), 7.69 (t, 1H, J 7 Hz),
7.60 ( t, 2H, J 7.50 Hz). 13C NMR (75 MHz, CDCl3):
d 181.4, 177.1, 165.9, 151.1, 139.5, 133.8, 131.8, 129.4,
129.3, 128.61, 123.0. MS (EI): m/z (%) 295.1 (17) [M+],
149.9 (40), 120.1 (8) 105.1 (100), 92.0 (14), 77.0 (35),
76.0 (16), 51.0 (10).
o
at 80 C for the appropriate time (Table 3). The reaction
mixture was quenched with NaHCO3 and the product was
repeatedly extracted with ethyl acetate. The combined
organic phases were dried over anhydrous MgSO4, followed
by evaporation of the solvent under reduced pressure.
The purification of the residue was performed using flash
column chromatography (silica gel, EtOAc-cyclohexane
10:90). All the products were identified by comparison of
their spectral data and physical properties with authentic
sample. The compounds 1, 2, 8 and 9 were characterized
by comparison with spectral date reported in the literature
date.17,18
3-(4-Methylbenzoyl)-5-methyl-1,2,4-oxadiazole (10)
1H NMR (300 MHz, CDCl3) d 8.14 (d, 2H, J 6.5 Hz),
7.34 (d, 2H, J 8 Hz), 2.73 (s, 3H), 2.46 (s, 3H). 13C NMR
(75 MHz, CDCl3): d 182.4, 177.4, 165.8, 145.8, 132.6,
130.7, 129.5, 21.8, 12.3. MS (EI): m/z (%) 202.1 (9) [M+],
177.1 (1), 160.1 (10), 145.1 (2), 132.1 (10), 119.1 (100),
104.1 (2), 91.0 (32), 77.0 (3), 65.0 (12), 51.0 (3).
Characterization data for representative compounds
3-(4-Bromobenzoyl)-5-phenyl-1,2,4-oxadiazole (3)
1H NMR (300 MHz, CDCl3) d 8.26 (dd, 2H, J 7.5,
2.5 Hz), 8.24 (dd, 2H, J 7.6, 2.5 Hz), 7.71 (d, 2H, J 8.5 Hz),
Results and Discussion
13
7.67 (t, 1H, J 7.0 Hz), 7.57 (t, 2H, J 7.5 Hz). C NMR
In a preliminary screening, we carried out the reaction
of benzonitrile, using europium nitrate prepared in situ
from europium oxide or from europium dithiocarbamate
with nitric acid and 4-chloroacetophenone at 80 C. The
results are compared with those obtained from the europium
triflate and were shown in Table 1.
(75 MHz, CDCl3) d 181.9, 176.7, 166.0, 133.8, 133.6,
132.1, 132.1, 130.3, 129.3, 128.5, 123.2. MS (EI): m/z (%)
329.9 (17) [M+], 280.9 (46), 206.9 (100), 182.8 (71), 154.8
(34), 104.9 (71), 76.9 (37), 51.0 (17).
o
3-Benzoyl-5-phenyl-1,2,4-oxadiazole (4)
All of the three europium compounds gave similar
yields; however, the reactions with europium nitrate and
europium ditiocarbamate were faster than those with
europium triflate. The similarity between the results for
the three Lewis acids indicates that same intermediate is
formed in all of the three reactions. Probably the europium
nitrate formed in situ acts as Lewis acid in the enolization
of the ketones in all of the cases.
1H NMR (300 MHz, CDCl3) d 8.34 (d, 1H, J 8.5 Hz),
8.27 (d, 1H, J 8.5 Hz), 7.71 (t, 2H, J 7.5 Hz), 7.65 (t, 2H,
J 7.5), 7.51 (q, 2H, J 7.5 Hz). 13 C NMR (75 MHz, CDCl3)
d 123.4, 128.5, 128.7, 129.2, 130.7, 133.4, 134.6, 135.1,
166.2, 176.5, 183.1. MS (EI): m/z (%) 250.1 (3) [M+], 145.1
(9), 105.1 (100), 77.0 (37), 51 (10).
3-(4-Methylbenzoyl)-5-phenyl-1,2,4-oxadiazole (5)
The lanthanide nitrates is a salt of easy preparation from
available lanthanide oxides, cheaper and more stable than
others salts and lanthanide compounds. We have prepared
and applied on the reaction described above nitrates of
different metals, in order to investigate their role upon the
reaction. The results are summarized on Table 2.
1H NMR (300 MHz, CDCl3) d 8.26 (dd, 2H, J 8.5,
1.5 Hz), 7.65 (t, 1H, J 7.0 Hz), 7.59 ( t, 2H, J 8.0 Hz), 7.36
(d, 2H, J 8.5 Hz), 2.46 (s, 3H). 13C NMR (75 MHz, CDCl3)
d 182.6, 176.4, 166.3, 145.9, 133.4, 132.7, 130.8, 129.5,
128.5, 123.4, 21.8. MS (EI): m/z (%) 264.1 (8) [M+], 239.1