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R. Pagadala et al. / Tetrahedron Letters xxx (2014) xxx–xxx
Preparation of Au(III) stock solution
With continuous stirring, HAuCl4 (3 ml) was added to H2O
(50 ml) in a pre-weighed beaker containing a stir bar. The beaker
equipped with a thermometer, was then placed on a hot-plate
and was heated to a temperature of 90 °C. The solution was left
to stir for 6 h at a constant temperature to concentrate the solu-
tion. Evaporation of the solution resulted in orange microcrystals
(2.053 g) and the wet crystals were then dissolved in H2O/EtOH
mixture (9:1) and made up to 50 ml to attain a stock solution with
a concentration of 0.0873 M.
Catalyst preparation
The preparation of gold on magnesium oxide (MgO) support was
undertaken via a wet impregnation method.10 To achieve a 5% Au/
MgO loading, 5 ml of the Au(III) stock solution containing 0.133 g
of gold was added to a beaker containing MgO (2.525 g) in
double-distilled H2O (10 ml). The mixture was allowed to stir for a
period of 3 h with continual analysis. The resultant mixture was
then filtered under vacuum and washed with H2O (3 Â 5 ml). The
purple powder was collected and dried at 130–140 °C overnight. It
was then calcined in the presence of air, at 450 °C for 5 h which
yielded the pink-colored 5% Au/MgO catalyst.
Figure 5. BET surface area and pore size of Au/MgO.
Typical procedure for the synthesis of multisubstituted pyridine
derivatives catalyzed by Au/MgO (5a–g/7a–d)
Freshly distilled benzaldehyde (2.0 mmol) in EtOH (3 ml) at
room temperature, malononitrile (2.0 mmol), cycloheptanone/
ethyl methyl ketone (4.0 mmol), ammonium acetate (3.0 mmol),
and Au/MgO (20.0 mg) were added to a round-bottomed flask
equipped with a magnetic stir bar and a condenser. The mixture
was heated at 70 °C for the time specified in Table 2. The reaction
progress was monitored by TLC (EtOAc/hexane = 3:7). After com-
pletion of the reaction, the mixture was cooled to room tempera-
ture and extracted with EtOAc. After filtering the Au/MgO solid,
the solvent layer was washed with H2O, dried over anhydrous Na2-
SO4, and the solvent was removed to obtain a precipitate which
was recrystallized from EtOH to give the pure target compound 5
or 7. The recovered Au/MgO solid was washed with CH2Cl2, dried
under reduced pressure, and reused.
Figure 6. Powder X-ray diffractogram of Au/MgO.
nature of the catalyst (Fig. 5). Data show that the surface area is clo-
sely related to the Au molar fraction. The surface area for the cata-
lyst was found to be 87.8 m2/g, which is double the surface area for
a catalyst previously synthesized using a similar method.10 The
pore volume was found to be 0.51 cm3/g.
Compound 5a
The XRD spectrum of 5% Au loaded on MgO is shown in Figure 6.
The powder XRD diffraction patterns of the prepared catalyst show
d-spacing values of 3.27, 2.31, 1.88, 1.63, and 1.46 Å for 2h angles of
19, 38.9, 46.2, 53.2, and 63.6°, respectively. The d-spacing phases
correlated with the ICDD file numbers are 01-078-0430,
01-076-0667, and 4-0796 for Au-MgO phases respectively. The
support phases, that is, Au and MgO, correlate well with reported
values.11
In summary, we have synthesized highly substituted pyridines
in excellent yields, with the use of Au loaded on MgO as a catalyst
in a one-pot, multicomponent system by employing simple start-
ing materials. The present protocol offers advantages in terms of
higher yields, short reaction times, and no column chromatography
is needed. Paramount is the use of the heterogeneous catalyst
which can be easily recovered and reused. The proposed method
should be a valuable addition to methods for synthesizing polysub-
stituted pyridines. Further studies on the sustainable applications
of this catalyst to other chemical reactions are underway in our
laboratory.
Off-white solid: mp 227–228 °C (lit.,6 225–226 °C); 1H NMR
(400 MHz, CDCl3): d = 1.47–1.52 (2H, m), 1.69–1.82 (4H, m), 2.46
(2H, t, J = 5.4 Hz), 2.92 (2H, t, J = 5.5 Hz), 5.11 (2H, s, NH2),
7.21–7.49 (5H, m); 13C NMR (100 MHz, CDCl3): d 26.18, 28.03,
28.97, 31.98, 39.67, 89.33, 116.94, 126.42, 128.38, 128.60, 128.68,
136.85, 153.11, 157.22, 167.96; IR (KBr, cmÀ1): 3316 (NH2), 2212
(CN); MS (ESI), m/z = 286 (M+Na, 100%); Anal. Calcd (C17H17N3):
C, 77.54; H, 6.51; N, 15.96. Found: C, 77.62 H 6.49, N 15.98.
Compound 7a
Off-white solid: mp 240–241 °C (lit.,12 243–244 °C); 1H NMR
(400 MHz, CDCl3): d = 1.95 (3H, s, –CH3), 2.44 (3H, s, –CH3), 5.05
(2H, s, NH2), 7.23–7.50 (5H, m); 13C NMR (100 MHz, CDCl3): d
15.30, 23.72, 89.72, 116.80, 119.69, 128.33, 128.64, 128.77,
136.79, 153.86, 157.23, 161.57; IR (KBr, cmÀ1): 3330 (NH2), 2211
(CN); MS (ESI), m/z = 224 (M+1, 100%); Anal. Calcd (C14H13N3): C,
75.31; H, 5.87; N, 18.82. Found: C, 75.37; H, 5.89; N, 18.78.