O. D'Alessandro et al. / Catalysis Communications 60 (2015) 65–69
67
Table 2
Selectivity in the Hantzsch reaction at 25 °C using the four synthesized catalysts.
Table 4
Selectivity in the Hantzsch reaction at 60 °C using the four synthesized catalysts.
Entry
Catalyst
Time (h)
Selectivity 4 (%)
Selectivity 7 (%)
Entry
Catalyst
Time (h)
Selectivity 4 (%)
Selectivity 7 (%)
1
2
3
4
5
None
MnOx
CeO2
MnOx(Cu)
CeO2 (Cu)
60
6
6
6
6
13
8
3
9
12
87
92
97
91
88
1
2
3
4
5
None
MnOx
CeO2
Cu/MnOx
Cu/CeO2
16
1
1
1
1
32
24
42
28
35
68
76
58
72
65
Reaction conditions: Benzaldehyde, 1 mmol; methyl acetoacetate, 2 mmol; ammonium
acetate, 1.2 mmol; catalyst, 50 mg; solvent-free, 25 °C; stirring. The conversion of benzal-
dehyde was 100% (1 h). Conversion and selectivity were estimated by GC analysis. Selec-
tivities of 5 and 6 were 0%.
Reaction conditions: Benzaldehyde, 1 mmol; methyl acetoacetate, 2 mmol; ammonium
acetate, 1.2 mmol; catalyst, 50 mg; solvent-free, 60 °C; stirring. The conversion of benzal-
dehyde was 100% (1 h). Conversion and selectivity were estimated by GC analysis. Selec-
tivities of 5 and 6 were 0%.
compare the conversion and selectivity of the synthesized catalysts.
Table 3 shows the results obtained at 40 °C and Table 4 the ones corre-
sponding to 60 °C.
production. In this case, an increase of the catalyst basicity could im-
prove 1,4-dihydropyridine selectivity.
The catalysts synthesized in the present article have Lewis acid sites
Table 3, entry 3, shows that the 4/7 product selectivity of the reac-
tion using 50 mg CeO2 was excellent (ratio 4/7 4/96%). Similar to the re-
sult obtained at 25 °C, the selectivity is slightly dependent on the
catalyst type tested. The more selective catalyst was CeO2, which pre-
sents a 2-phenylpyridine 7 selectivity of 96% (Table 3, entry 3). In all
cases, the reaction is complete in 2 h; therefore the CeO2 catalyst and
this condition represent an excellent alternative for the selective syn-
thesis of 2-phenylpyridine 7.
Table 4 lists the obtained results, using the initial reaction conditions
at a temperature of 60 °C. Also, an increase in 1,4-dihydropyridine 4
selectivity, with respect to the results obtained at 25 and 40 °C, was
observed. In this case, the reaction proceeds via 1,4-addition (Michael-
type), and 1,4-dihydropyrimidine 4 is the most thermodynamically
favorable compound.
Another notable difference at 60 °C is that the reaction selectivity in
product 4 or 7 changes and begins to be dependent on the catalyst used.
For example, when we used the CeO2 catalyst, the selectivity of 1,4-
dihydropyridine 4 was 42% (Table 4, entry 3) and using MnOx the selec-
tivity of 4 was only 24% and the selectivity of 2-phenylpyridine 7 76%
(Table 4, entry 2). It is remarkable that CeO2 starts to favor the forma-
tion of 1,4-dihydropyridine 4.
Table 5 lists the obtained results, using the initial reaction conditions
at a temperature of 80 °C. The catalysts were tested, and in all cases 1 h is
the time required to obtain an aldehyde conversion of 100%. Also, an in-
crease in 1,4-dihydropyridine 4 selectivity with respect to the results
obtained at 25, 40 °C, and 60 °C was observed. For example, when
the CeO2 catalyst was used, a very good selectivity of 75% of 1,4-
dihydropyridine 4 was obtained (Table 5, entry 3). For this reason, 80
° C is an excellent temperature for performing the selective synthesis
of 1,4-dihydropyridine 4.
M
+n, Bronsted acid hydroxyl groups, and Lewis basic sites O−2 and O−.
The principal difference between cerium and manganese catalysts is
that the cerium catalyst presents basic sites of greater strength than
the manganese catalyst. This characteristic was confirmed by a qualita-
tive determination of the strongest basic sites by Hammett indicators
and XPS techniques. The pH range obtained for the four catalysts
were: CeO2, 9.6 b pH b 11.4; MnOx, 6 b pH b 6.8; CeO2(Cu), 6 b
pH b 6.8; and MnOx(Cu), 5.4 b pH b 6, respectively. Thus, CeO2 is the
most basic catalyst of the series, and it showed high selectivity to 1,4-
dihydropyridine 4.
Finally, to increase 1,4-dihydropyridine 4 selectivity, we performed
the next experiment at 100 °C. In all experiments, and using the four
catalysts, the selectivity of 1,4-dihydropyridine 4 was less than 70%,
and some unidentified side products were detected by TLC. Particularly,
in the catalyst CeO2(Cu), where Cu was used as dopant agent, a second-
ary product 6 was detected, with a selectivity of 9%. Product 6 is the re-
sult of the subsequent oxidation of 1,4-dihydropyridine 4 in the
corresponding pyridine 6. In this case Cu incorporation in the CeO2 cat-
alyst improves its oxidant capacity. Several papers have reported that
Cu-doped CeO2 improves the oxidant capacity. The increased catalytic
activity of Cu-doped CeO2 is explained by the enhanced concentration
and mobility of oxygen vacancies and the enhanced redox pair Cu+
/
Cu2+ in the CeO2: Cu system [20]. In addition, Prasad and Rattan report-
ed that the high activity of CuO–CeO2 is attributed to the quick revers-
ible Cu2+/Cu+ redox couples assisted by Ce4+/Ce3+ cycles [21].
In all the experiments, the CeO2 catalyst showed to be the most
selective for obtaining 2-phenylpyridine 7 and 1,4-dihydropyridine
4. For this reason, it was used in two additional experiments for per-
forming the preparative synthesis of both compounds using the opti-
mized reaction conditions. When an appropriate mixture of three
substrates and the catalyst was stirred at 40 °C under solvent-free con-
ditions, the corresponding 2-phenylpyridine 7 was formed with 91%
yield, in a reaction time of 6 h. Under the same condition and at a tem-
perature of 80 °C, the corresponding 1,4-dihydropyridine 4 was obtain-
ed with 74% yield in 1 h, indicating that the CeO2 catalyst is effective to
The change of reaction selectivity observed at 80 °C using the differ-
ent synthesized catalysts could be interpreted comparing the acid–base
properties. It is well known from the literature that an increase in the
acidity or basicity of the catalyst and the reaction temperature improve
the efficiency of the Hantzsch reaction for 1,4-dihydropyridine 4
Table 5
Table 3
Conversion and selectivity in the Hantzsch reaction at 80 °C using the four synthesized
catalysts.
Selectivity in the Hantzsch reaction at 40 °C using the four synthesized catalysts.
Entry
Catalyst
Time (h)
Selectivity 4 (%)
Selectivity 7 (%)
Entry
Catalyst
Time (h)
Selectivity 4 (%)
Selectivity 7 (%)
1
2
3
4
5
None
MnOx
CeO2
MnOx(Cu)
CeO2 (Cu)
30
2
2
2
2
23
16
4
7
5
77
84
96
93
95
1
2
3
4
5
None
MnOx
CeO2
MnOx(Cu)
CeO2(Cu)
12
1
1
1
1
30
44
75
48
66
70
56
25
52
34
Reaction conditions: Benzaldehyde, 1 mmol; methyl acetoacetate, 2 mmol; ammonium
acetate, 1.2 mmol; catalyst, 50 mg; solvent-free, 40 °C; stirring. The conversion of benzal-
dehyde was 100% (2 h). Conversion and selectivity were estimated by GC analysis. Selec-
tivities of 5 and 6 were 0%.
Reaction conditions: Benzaldehyde, 1 mmol; methyl acetoacetate, 2 mmol; ammonium
acetate, 1.2 mmol; catalyst, 50 mg; solvent-free, 80 °C; stirring. The conversion of benzal-
dehyde was 100% (1 h). Conversion and selectivity were estimated by GC analysis. Selec-
tivities of 5 and 6 were 0%.