CATALYTIC EFFECT OF NANOSIZED METAL OXIDES
567
1
tion products was studied using H NMR spectrosꢀ
copy and HPLC.
Product yield, %
90
1
80
70
60
50
40
30
20
10
EXPERIMENTAL
Methanol (98%), an aqueous ammonia solution
(30%), 2ꢀnitrobenzaldehyde (99%), 3ꢀnitrobenzaldeꢀ
hyde (99%), and methyl 3ꢀaminocrotonate (enamine)
(97%) from Lancaster and ethyl acetoacetate (99%)
and methyl acetoacetate (99%) from Acros Organics
were used in this study. Nanosized copper oxide (parꢀ
ticle size of 50–80 nm) and nanosized aluminum
oxide (particle size of 20–50 nm), which were preꢀ
pared using a gasꢀphase procedure at the Institute of
Metal Physics, Ural Division, Russian Academy of
Sciences (Laboratory of Prof. A.E. Ermakov), were
used as catalysts [4].
2
0
0.5
1.0
1.5
2.0
2.5
3.0
Reaction time, h
Fig. 1. Yields of nifedipine (according to HPLC data) (1)
The melting points measured on combined Boetius
plates were uncorrected. The diffuse reflectance specꢀ
tra were measured on a Spectrum One FTIR specꢀ
trometer (Perkin Elmer) using an automated diffuse
in the presence and (
nanooxide.
2) in the absence of aluminum
1
Ethyl 2ꢀAcetylꢀ3ꢀ(3ꢀNitrophenyl)ꢀAcrylate
(Chalcone) (2b
reflectance attachment. The H NMR spectra were
)
obtained on an AVANCE DRXꢀ400 spectrometer
(Bruker) with an operating frequency of 400 MHz.
3ꢀNitrobenzaldehyde (3.3 mmol, 0.5 g), ethyl aceꢀ
toacetate (9.9 mmol, 1.15 g), nanosized Al2O3
(1.1 mmol), morpholine (3.3 mmol), and acetonitrile
(5 ml) were mixed. The reaction mass was kept with
stirring at 60°С for 6 h with a reflux condenser; thereꢀ
after, crystallization from ethanol was performed. The
yield of the product with mp 109°С was 74%.
The Hantzsch reaction was performed by heating a
reaction mixture with an aldehyde : methyl acetoaceꢀ
tate : ammonia : metal nanooxide ratio of 1 : 2 : 1 : 0.1
(in the preparation of nifedipine) or an aldehyde :
ethyl acetoacetate : methyl acetoacetate : ammonia :
metal nanooxide ratio of 1 : 1 : 1 : 1 : 0.1 (in the prepꢀ
aration of nitrendipine) in methanol. Then, the reacꢀ
tion mixture was evaporated, and the resulting crude
For С13Н13О5N
anal. calcd. (%):
C 59.32;
C 59.11;
H 4.94;
H 4.97;
N 5.32.
N 5.29.
1
product was analyzed by H NMR spectroscopy and
Found (%)
:
HPLC (a normalꢀphase LiChrosorb Si 60 column;
mobile phase, a mixture of hexane with isopropanol in
a ratio of 9 : 1). The retention times (min) were the folꢀ
lowing: 18.70, nifedipine; 42.70, nitrendipine; 25.24, 7.16 Hz, С(О)CH2СН3); 2.45 (s, 3H, СН3); 4.38 (kv,
chalcone; and 16.12, enamine.
1H NMR spectrum (
, ppm): 1.31 (t, 3H, J =
δ
2H,
7.60 (t, H,
C(6)Ar); 8.26 (dd, H,
C(2)Ar).
J
= 7.16 Hz, С(О)CH2СН3); 7.59 (s, H, –СН=);
= 7.8 Hz, C(5)Ar); 7.76 (d, H, = 7.8 Hz,
= 7.8 Hz, C(4)Ar); 8.34 (s, H,
J
J
J
Dimethyl 2,6ꢀDimethylꢀ4ꢀ(2ꢀNitrophenyl)ꢀ1,4ꢀ
Dihydropyridineꢀ3,5ꢀDicarboxylate (Nifedipine) (1a
)
Methyl 3ꢀAminocrotonate (Enamine) (
3)
After recrystallization from ethanol, the yield of the
product with mp 165°С was 67%. 1H NMR spectrum
1H NMR spectrum (
δ
, ppm): 1.90 (s, 3H, ОСН3);
( , ppm): 2.25 (s, 6H, CH3); 3.51 (s, 6H, OCH3); 5.49
(s, H); 7.34–7.59 (m, 4H, Ar); 9.00 (s, H, NH).
δ
3.64 (s, 3H, СН3); 4.52 (s, H, CH=); 4.8 (br s, H, NH2);
7.9 (br s, H, NH2).
The sorption of starting compounds and Hantzsch
reaction intermediates on metal nanooxides was perꢀ
formed in methanol solutions at a sorbate : sorbent
molar ratio of 1 : 3 followed by the removal of the solꢀ
vent.
Methyl Ethyl 2,6ꢀDimethylꢀ4ꢀ(2ꢀNitrophenyl)ꢀ1,4ꢀ
Dihydropyridineꢀ3,5ꢀDicarboxylate (Nitrendipine) (1b
)
After extraction with chloroform and precipitation
with methanol, the yield of the product with mp 130–
132°С was 50%. 1H NMR spectrum (
δ
, ppm): 1.16 (t,
= 7.0 Hz); 2.25 (s, 6H, CH3); 3.51 (s,
3H, –OCH3); 3.98 (t, 2H, СН3СН2, = 7.0 Hz); 4.99
(s, H); 7.52–8.01 (m, 4H, Ar); 9.07 (s, H, NH).
RESULTS AND DISCUSSION
3H, СН3СН2,
J
J
The use of aluminum nanooxide allowed us to perꢀ
form a threeꢀcomponent version of the synthesis of
KINETICS AND CATALYSIS Vol. 51
No. 4
2010