1
98
S. Abdolmohammadi · Zr(HPO ) in the Synthesis of Hexahydroquinolines
4
2
that Zr(HPO ) catalyzes the formation of carbocation 2.21 (d, 2 H, 2JHH = 16.7 Hz, 2 CH), 4.45 (s, 1 H, H-4), 5.40
4
2
3
6
which then undergoes a Knoevenagel condensation (s, 2 H, NH2), 7.24 (d, 2 H, JHH = 8.1 Hz, HAr), 7.39 (d, 2
3
3
H, J = 6.5 Hz, HAr), 7.52 (d, 2 H, J = 8.1 Hz, HAr),
.61 (m, 3 H, HAr). – Anal. for C H BrN O (448.36):
calcd. C 64.29, H 4.95, N 9.37; found C 64.17, H 5.13, N
.50%.
with malononitrile (2), which produces alkene 8 via
intermediate 7. The enamine 9, which is obtained from
the reaction of dimedone (3) and aryl amine 4, adds to
alkene 8 to produce the Michael adduct 10. Intramolec-
HH
HH
7
24 22 3
9
ular cyclization of 10 gives product 5 after tautomer- 2-Amino-1,4-bis(4-bromophenyl)-7,7-dimethyl-5-oxo-
ization.
1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (5b)
Pale-yellow solid, yield: 0.511 g (97%). – 1H NMR:
δ = 0.74 (s, 3 H, CH ), 0.87 (s, 3 H, CH ), 1.70 (d, 1
Conclusion
3
3
2
2
H, JHH = 17.2 Hz, CH), 2.00 (d, 1 H, JHH = 16.0 Hz,
In summary, we have reported a novel green method
for the synthesis of 2-amino-1,4-diaryl-7,7-dimethyl-
2
CH), 2.20 (d, 1 H, JHH = 16.0 Hz, CH), 2.22 (d, 1 H,
2
JHH = 17.2 Hz, CH), 4.43 (s, 1 H, H-4), 5.58 (s, 2 H,
3
5
-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carbonitriles
NH ), 7.24 (t, 2 H, JHH = 8.2 Hz, HAr), 7.37 (t, 2 H,
2
3
3
via a one-pot four-component reaction of aromatic
JHH = 8.2 Hz, HAr), 7.50 (d, 2 H, JHH = 8.2 Hz, HAr), 7.75
3
aldehydes, malononitrile, dimedone and arylamines, (d, 2 H, JHH = 8.2 Hz, HAr). – Anal. for C24H21Br2N3O
(527.26): calcd. C 54.67, H 4.01, N 7.97; found C 54.61, H
catalyzed by α-ZrP. Compared to known methods, this
procedure provides noteworthy features and benefits,
3
.93, N 8.06%.
as Zr(HPO ) is not toxic or expensive, and work-up
is simple. High yields and an improvement of the bond
4
2
2-Amino-4-(4-bromophenyl)-7,7-dimethyl-1-(4-
methylphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
forming efficiency (BFE) and atom economy are other carbonitrile (5c)
major advantages.
Pale-yellow solid, yield: 0.453 g (98%). – 1H NMR:
δ = 0.73 (s, 3 H, CH ), 0.87 (s, 3 H, CH ), 1.72 (d, 1 H,
3
3
Experimental Section
2
2
JHH = 17.4 Hz, CH), 1.99 (d, 1 H, JHH = 16.2 Hz, CH),
2
5
2
7
.19 (m, 2 H, 2 CH), 2.40 (s, 3 H, CH ), 4.44 (s, 1 H, H-4),
Materials and methods
3
3
.37 (s, 2 H, NH ), 7.24 (t, 2 H, J = 8.2 Hz, HAr), 7.27 (t,
2
HH
All of the chemical materials used in this work were
purchased from Merck and used without further purifica-
tion. Melting points were determined on an Electrother-
mal 9100 apparatus and are uncorrected. H NMR spectra
were recorded on a Bruker DRX-500 Avance instrument at
3
3
H, J = 8.2 Hz, H ), 7.41 (d, 2 H, J = 8.2 Hz, HAr),
HH
Ar
HH
3
.51 (d, 2 H, J = 8.2 Hz, HAr). – Anal. for C H BrN O
HH
25 24
3
(462.39): calcd. C 64.94, H 5.23, N 9.09; found C 64.99, H
1
5
.28, N 9.16%.
2
-Amino-1-(4-bromophenyl)-4-(3,4-dichlorophenyl)-7,7-
5
00 MHz, using TMS as internal standard and [D ]DMSO
6
dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
carbonitrile (5d)
as solvent. Elemental analyses were carried out using a Her-
aeus CHN rapid analyzer.
Pale-yellow solid, yield: 0.497 g (96%). – 1H NMR:
δ = 0.73 (s, 3 H, CH ), 0.88 (s, 3 H, CH ), 1.74 (d, 1 H,
General procedure for preparation of compounds 5a – g
A mixture of aromatic aldehyde (1, 1 mmol), malono-
3
3
2
2
JHH = 17.0 Hz, CH), 2.01 (d, 1 H, JHH = 16.1 Hz, CH),
2
nitrile (2, 1 mmol), dimedone (3, 1 mmol), arylamine (4, 2.19 (d, 2 H, J = 16.2 Hz, 2 CH), 4.50 (s, 1 H, H-4), 5.63
HH
3
4
1
8
mmol), and α-ZrP (30.1 mg, 10 mol-%) was stirred at (s, 2 H, NH ), 7.28 (dd, 1 H, J = 8.2 Hz, J = 2.0 Hz,
2 HH HH
◦
3
0 C for 2 h. After completion of the reaction (TLC), H O
HAr), 7.36 (t, 2 H, JHH = 8.2 Hz, HAr), 7.42 (d, 1 H,
2
4
3
(20 mL) was added and the mixture and filtered. The residue
JHH = 2.0 Hz, H ), 7.59 (d, 1 H, J = 8.2 Hz, HAr), 7.77
Ar HH
3
was washed with aqueous ethanol to generate the pure prod- (d, 2 H, J = 8.2 Hz, HAr). – Anal. for C H BrCl N O
HH
24 20
2 3
◦
uct. The filtrate was recovered for reuse by drying at 80 C (517.25): calcd. C 55.73, H 3.90, N 8.12; found C 55.81, H
for several hours in a vacuum.
3.97, N 8.21%.
2
1
-Amino-4-(4-bromophenyl)-7,7-dimethyl-5-oxo-1-phenyl-
,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (5a)
2-Amino-4-(3,4-dichlorophenyl)-7,7-dimethyl-1-(4-
methylphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-
carbonitrile (5e)
1
Yellow solid, yield: 0.439 g (98%). – H NMR: δ = 0.74
(
s, 3 H, CH ), 0.87 (s, 3 H, CH ), 1.68 (d, 1 H,
Pale-yellow solid, yield: 0.443 g (98%). – 1H NMR:
3
3
2
2
JHH = 17.4 Hz, CH), 2.01 (d, 1 H, JHH = 16.0 Hz, CH), δ = 0.73 (s, 3 H, CH ), 0.87 (s, 3 H, CH ), 1.74 (d, 1
3
3