[()TD$FIG]
8
08
A. Khojastehnezhad et al. / Chinese Chemical Letters 22 (2011) 807–810
O
O
O
Ar
O
O
PPA-SiO2
2
OC H5
+
OC H5
2
+
+
NH OAc
4
Ar
H
Solvent-free
O
O
o
N
H
CH3
8
0 C
1
2a-j
3
4a-j
Scheme 1.
derivatives by one-pot four-component Hantzsch condensation reaction of aryl aldehydes, dimedone, ethyl
acetoacetate and ammonium acetate (Scheme 1).
1
. Experimental
Chemicals were either prepared in our laboratories or purchased from Merck, Fluka and Aldrich Chemical
Companies. All yields refer to isolated products. The products were characterized by comparing of their physical data
with those of known samples or by their spectral data. IR spectra were recorded on a4300 Shimadzu
spectrophotometer as KBr disks. Melting points were recorded on an electrothermal type 9100 melting point
1
apparatus. H NMR spectra were recorded on a Bruker DRX500 500-MHz spectrometer in CDCl as the solvent
3
relative to TMS. The catalyst was synthesized according to the literature [14].
1
.1. General procedure to synthesis of polyhydroquinoline derivatives using PPA-SiO as catalyst
2
A mixture of ethyl acetoacetate 1 (1 mmol), aromatic aldehyde 2a–j (1 mmol), dimedone 3 (1 mmol), ammonium
+
acetate (1 mmol) and PPA-SiO (0.03 g, 0.0150 mmol H ) [14] was heated on the oil bath at 80 8C for 40–60 min. The
2
reaction was monitored by TLC. After the completion of the reaction, the reaction mixture was cooled to room
temperature and hot ethanol was added. The solid residue was dissolved in hot ethanol and filtered off. The crude
product was collected from the filtrate after cooling to room temperature and recrystallized from ethanol to give
compounds 4a–j in high yields. All of the polyhydroquinoline derivatives are known and were identified by
comparison of their physical and spectroscopic data (IR, NMR) with those of authentic samples [8,10].
1
Representative H NMR spectral data for the selected products:
1
,7,7-Trimethyl-5-oxo-4-phenyl-1,4,5,6,7,8-hexahydroquinoline-3-carboxylic acid ethyl ester (entry 1): H NMR
2
(
500 MHz, CDCl ): d 7.27–7.32 (m, 2H), 7.17–7.22 (m, 2H), 7.07–7.12 (m, 1H), 6.63 (brs, 1H, NH), 5.06 (s, 1H),
3
4
.05 (q, 2H, J = 7.1 Hz), 2.34 (s, 3H), 2.12–2.28 (m, 4H), 1.20 (t, 3H, J = 7.1 Hz), 1.06 (s, 3H), 0.93 (s, 3H).
,7,7-Trimethyl-5-oxo-4-(4-chlorophenyl)-1,4,5,6,7,8-hexahydroquinoline-3-carboxylic acid ethyl ester (entry 3):
H NMR (500 MHz, CDCl ): d 0.94 (s, 3H), 1.08 (s, 3H), 1.18 (t, J = 7.1 Hz, 3H), 2.12–2.34 (m, 4H), 2.37 (s, 3H),
2
1
3
4
.06 (q, J = 7.1 Hz, 2H), 5.04 (s, 1H), 6.46 (brs, 1H, NH), 7.15–7.19 (d, J = 8 Hz, 2H), 7.24–7.26 (d, J = 8 Hz, 2H).
,7,7-Trimethyl-5-oxo-4-(3-nitrophenyl)-1,4,5,6,7,8-hexahydroquinoline-3-carboxylic acid ethyl ester (entry 7):
2
1
H NMR (500 MHz, CDCl ): d 0.89 (s, 3H), 1.09 (s, 3H), 1.2 (t, 3H, J = 7.3 Hz), 2.2–2.4 (m, 4H), 2.5 (s, 3H), 4.00
3
(
q, 2H, J = 7.3 Hz), 5.05 (s, 1H), 6.01 (br s, 1 H, NH), 7.5 (d, 2H, J = 9.2 Hz), 8.1 (d, 2H, J = 9.2 Hz).
2
. Result and discussion
To optimize the reaction conditions, the reaction of benzaldehyde (1 mmol), ethyl acetoacetate (1 mmol),
+
dimedone (1 mmol) and ammonium acetate (1 mmol) in the presence of PPA-SiO (0.03 g, 0.0150 mmol H ) [11] was
2
selected as a model. The reaction was carried out in various solvents and under solvent-free conditions. As shown in
Table 1, in comparison to conventional methods, the yields of the reaction under solvent-free conditions are greater
and the reaction time is shorter. The shortest time and best yield were achieved at 80 8C. Next, to found the optimum
quantity of PPA-SiO , the reaction of benzaldehyde, ethyl acetoacetate, dimedone and ammonium acetate was carried
out under the previously mentioned conditions using different quantities of catalyst at 80 8C. The use of 0.03 g of
catalyst resulted in the highest yield in 40 min.
2