Silver phosphotungstate: A novel and recyclable heteropoly acid for Friedlaender quinoline synthesis

Article abstract of DOI:10.1055/s-2004-831185

o-Aminoaryl ketones undergo smooth condensation with α-methylene ketones on the surface of silver heteropoly acid (Ag₃PW ₁₂O₄₀) under mild reaction conditions to afford the corresponding polysubstituted quinolines in excel

Full text of DOI:10.1055/s-2004-831185

PAPER
2381
Silver Phosphotungstate: A Novel and Recyclable Heteropoly Acid for
Friedländer Quinoline Synthesis
F
J
riedlände
.
r
Q
uinoline
S
Synthesis Usin
.
g Heteropol
Yy Acid adav,* B. V. S. Reddy, P. Sreedhar, R. Srinivasa Rao, K. Nagaiah
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax +91(40)27160512; E-mail: yadav@iict.res.in
Received 26 March 2004; revised 9 June 2004
atives are increasingly useful and important in drugs and
pharmaceuticals, the development of simple, convenient
and environmentally benign approaches are desirable.
Abstract: o-Aminoaryl ketones undergo smooth condensation with
a-methylene ketones on the surface of silver heteropoly acid
(
Ag PW O ) under mild reaction conditions to afford the corre-
3 12 40
sponding polysubstituted quinolines in excellent yields with high
selectivity. The catalyst can be recovered by simple filtration and
can be recycled in subsequent reactions.
In recentyears, the use of solid acids as heterogeneous cat-
alysts has received considerable interest in different areas
11
of organic synthesis. Heterogeneous solid acids are ad-
vantageous over conventional homogeneous acid cata-
lysts as they can be easily recovered from the reaction
mixture by simple filtration and can be reused after acti-
vation or without activation, thereby making the process
economically viable. In many cases, heterogeneous cata-
lysts can be recovered with only minor change in activity
and selectivity so that they can be conveniently used in
continuous flow reactions. Among various heterogeneous
catalysts, heteropoly acids are most attractive, because of
their reusability, flexibility in modifying the acid strength,
ease of handling, environmental compatibility, nontoxici-
Keywords: heteropoly acids, o-aminoaryl ketones, a-methylene
ketones, quinolines
Quinoline nucleus is a back-bone of many natural prod-
ucts and pharmacologically significant compounds dis-
1
playing a broad range of biological activity. Many
functionalized quinolines are widely used as antimalarial,
anti-inflammatory agents, antiasthmatic, antibacterial, an-
tihypertensive and tyrokinase PDGF-RTK inhibiting
2
,3
agents.
In addition to the medicinal importance,
polyquinolines derived from quinolines, are found to un-
dergo hierarchical self-assembly into a variety of nano-
and mesostructures with enhanced electronic and photon-
12
ty and experimental simplicity. However, there are no
examples of the use of silver salt of heteropoly acid for the
preparation of quinolines. The use of heteropoly acid as a
recyclable catalyst makes the process convenient, eco-
nomic and environmentally benign.
4
ic functions. Consequently, various methods such as Sk-
raup, Doebner–von Miller, Friedlander and Combes
methods have been developed for the preparation of quin-
In view of the emerging importance of the use of hetero-
geneous solid acids as reusable catalysts in organic syn-
thesis, we wish to disclose a simple and efficient
procedure for the polysubstituted quinolines using het-
eropoly acid as a catalyst. Accordingly, treatment of 2-
aminobenzophenone (1) with ethyl acetoacetate (2) in the
5
,6
oline derivatives. Among them, Friedländer annulation
is of the most simple and straightforward approaches for
6
b
the synthesis of polysubstituted quinolines. Friedländer
reactions are generally carried out either by refluxing an
aqueous or alcoholic solution of reactants in the presence
of base or by heating a mixture of the reactants at high
temperatures ranging from 150–220 °C in the absence of
1
3
presence of silver salt of heteropoly acid (Ag PW O )
3
12 40
resulted in the formation of ethyl 2-methyl-4-phenyl-3-
quinolinecarboxylate (3a) in 92% yield (Scheme 1).
7
catalyst. Under thermal or base catalysis conditions, o-
aminobenzophenone fails to react with simple ketones
8
such as cyclohexanone, deoxybenzoin and b-keto esters.
Subsequent work showed that acid catalysts are more ef-
fective than base catalysts for the Friedländer annulation.8
Acid catalysts such as hydrochloric acid, sulfuric acid, p-
toluenesulfonic acid and phosphoric acids have been
7
a,9
widely used for this conversion.
However, many of
Scheme 1
these classical methods require high temperatures, pro-
longed reaction times and drastic conditions and the yields
reported are far from satisfactory due to the occurrence of
several side reactions. Therefore, new catalytic systems
are being continuously explored in search of improved ef-
Similarly, various ketones such as acetyl acetone, butan-
2
-one and acetophenone reacted smoothly with 2-ami-
nobenzophenone to give the corresponding substituted
quinolines. In most cases, the products were isolated by
simple filtration. The crude products were purified either
by recrystallization from a mixture of diethyl ether/n-hex-
ane or by silica gel column chromatography. Interesting-
ly, cyclic ketones such as cyclopentanone and
cyclohexanone also underwent smooth condensation with
1
0
ficiencies and cost effectiveness. Since quinoline deriv-
SYNTHESIS 2004, No. 14, pp 2381–2385
x
x.
x
x
.
2
0
0
4
Advanced online publication: 19.08.2004
DOI: 10.1055/s-2004-831185; Art ID: Z06404SS
Georg Thieme Verlag Stuttgart · New York
©

2
382
J. S. Yadav et al.
PAPER
did not proceed even after long reaction times (8–12 h).
The heteropoly acid (Ag PW O ) provides an ease sep-
3
12 40
aration of the catalyst and the product. The catalyst was
easily separated by simple filtration and reused after acti-
vation with gradual decrease in activity. For instance, the
reaction of 2-aminobenzophenone and acetyl acetone af-
forded the corresponding 3-acetyl-2-methyl-4-phe-
nylquinoline in 89%, 86%, 82%, and 80% yields over four
cycles. Furthermore, this method is clean and free from
side reactions such as self-condensation of ketones, which
was normally observed under basic conditions. Unlike re-
ported methods, present protocol does not require either
strong acids such as conc. HCl, conc. H SO , p-TSA and
Scheme 2
2
-aminoaryl ketones to afford respective tricyclic quino-
lines (Scheme 2).
This method is equally effective for both cyclic and acy-
clic ketones (Table 1). Various substituted 2-aminoaryl
ketones such as 2-aminoacetophenone, 2-aminoben-
zophenone, 2-amino-5-chlorobenzophenone and 2-ami-
no-5-chloro-2¢-chlorobenzophenone reacted smoothly
with a-methylene ketones to produce a range of quinoline
derivatives. As solvent, ethanol appears to be superior
giving the best results. The products were characterized
2
4
H PO or high temperature (190–250 °C) conditions to
3
4
produce quinoline derivatives. Thus, this procedure pro-
vides an easy access to the preparation of substituted quin-
olines with a wide range of substitution patterns. This
method offers several advantages such as high conver-
sions, short reaction times, cleaner reaction profiles and
simple experimental and workup procedures. The scope
and generality of this process is illustrated with respect to
various 2-aminoaryl ketones and a-methylene ketones
and the results are summarized in Table 1.
1
13
by H, C NMR, IR and mass spectroscopic data and also
7
a
by comparison with authentic samples. This method is
very useful for the preparation of quinolines from both 2-
aminoacetophenone and 2-aminobenzophenone. The effi-
cacy of other solid acids such as K10 clay, SiO , and H-
ZSM-5 was studied for this reaction and the results are
presented in Table 2. Among these catalysts, silver salt of
2
1
2-tungustophosphoric acid (Ag PW O ) was found to
3 12 40
be superior in terms of conversion and reaction rates.
However, in the absence of heteropoly acid, the reaction
Table 1 Ag PW O -Catalyzed Friedlander Synthesis of Quinolines
3
12 40
b
Entry
2-Aminoketone
1
Ketone
2
Quinolinea
3
Time (h)
3.0
Yield (%)
a
92
b
c
d
e
f
4.5
3.5
3.0
6.0
4.5
5.0
89
87
90
81
83
80
g
Synthesis 2004, No. 14, 2381–2385 © Thieme Stuttgart · New York

PAPER
Friedländer Quinoline Synthesis Using Heteropoly Acid
2383
Table 1 Ag PW O -Catalyzed Friedlander Synthesis of Quinolines (continued)
3
12 40
b
Entry
2-Aminoketone
1
Ketone
2
Quinolinea
3
Time (h)
4.0
Yield (%)
h
87
89
82
i
3.5
5.5
j
k
l
4.5
4.0
5.5
3.5
86
83
80
85
m
n
a
All products were characterized by H NMR, 13C NMR, IR and mass spectroscopy.
Isolated and unoptimized yields.
1
b
Table 2 Comparative Study of Various Solid Acids in the Synthesis
of Ethyl 2-Methyl-4-phenyl-3-quinoline Carboxylate (3a)
more convenient and environmentally benign for the syn-
thesis of highly functionalized quinolines.
a
Entry
1
Catalyst
Quinoline Time (h)
Yield (%)
Melting points were recorded on Büchi R-535 apparatus and are un-
corrected. IR spectra were recorded on a Perkin-Elmer FT-IR
HZSM-5
3a
3.0
6.0
65
80
3
a
1
13
2
40-c spectrophotometer using KBr optics. H and C NMR spec-
tra were recorded on Gemini-200 and Varian Unity-500 spectrom-
2
3
KSF-Clay
3a
3.0
6.0
60
75
eter in CDCl using TMS as internal standard. Mass spectra were
3
a
3
recorded on a Finnigan MAT 1020 mass spectrometer operating at
70 eV. TLC was monitored on 0.25 mm precoated silica gel plates
(60F-254). All commercially available reagent grade chemicals
were purchased from Aldrich Chemical Company and used as re-
ceived without further purification unless otherwise stated. All the
Conc. H SO
3a
3.0
6.0
80
85
2
4
3
a
4
Ag PW O
3a
3.0
92
3
12 40
solvents distilled, dried and stored under N prior to use.
2
a
Isolated and unoptimized yields.
Polysubstituted Quinolines; General Procedure
A mixture of o-aminobenzophenone (1 mmol), ketone (1.5 mmol),
In summary, we have described a mild and efficient pro- and Ag PW O (0.2 mmol) in EtOH (10 mL) was stirred at reflux
3
12 40
tocol for the synthesis of quinolines and polycyclic quin- temperature for the appropriate time (Table 1). After completion of
the reaction, as indicated by TLC, the reaction mixture was filtered
olines via Friedländer condensation of 2-aminoaryl
and washed with EtOAc (2 × 10 mL). The combined organic ex-
ketones with a-methylene ketones using heteropoly acid
tracts were concentrated in vacuo and the resulting product was di-
as a recyclable heterogeneous catalyst. The simple exper-
rectly charged on small silica gel column and eluted with a mixture
of EtOAc–n-hexane (2:8) to afford pure trisubstituted quinoline.
imental procedure combined with ease of recovery and re-
use of this novel catalyst make this method quite simple,
Synthesis 2004, No. 14, 2381–2385 © Thieme Stuttgart · New York

2
384
J. S. Yadav et al.
PAPER
1
3
The recovered catalyst was washed with MeOH and activated at
20 °C for 3–4 h prior to reuse.
C NMR (proton decoupled, 75 MHz, CDCl ): d = 23.5, 31.6,
3
1
124.8, 125.8, 128.7, 129.0, 129.7, 130.8, 132.2, 134.5, 135.3, 142.8,
1
45.8, 153.7, 204.7.
EI-MS: m/z (%) = 295 (M , 39), 281 (100), 252 (27), 217 (27), 176
12), 43 (41).
Ethyl 2-Methyl-4-phenylquinoline-3-carboxylate (3a)
Pale yellow solid; mp 97 °C.
+
(
IR (KBr): 3062, 2981, 2932, 1728, 1568, 1487, 1444, 1402, 1296,
–
1
1
229, 1066, 768 cm .
6-Chloro-2,3-dimethyl-4-phenylquinoline (3f)
1
Pale yellow solid; mp 117 °C.
H NMR (200 MHz, CDCl ): d = 0.95 (t, J = 6.9 Hz, 2 H), 2.78 (s,
3
–
1
3
H), 4.00–4.05 (q, J = 6.9 Hz, 2 H), 7.30–7.55 (m, 7 H), 7.65–7.70
IR (KBr): 3062, 2955, 1605, 1482, 1215, 754 cm .
(
1
m, 2 H), 8.05 (d, J = 8.1 Hz, 1 H).
1
H NMR (300 MHz, CDCl ): d = 2.18 (s, 3 H), 2.72 (s, 3 H), 7.20–
3
3
C NMR (proton decoupled, 50 MHz, CDCl ): d = 13.5, 23.5, 60.7,
7.24 (m, 3 H), 7.48–7.52 (m, 4 H), 7.92 (d, J = 8.2 Hz, 1 H).
13
3
9
1
6.0, 125.0, 126.0, 126.2, 127.9, 128.1, 129.0, 129.3, 129.7, 135.9,
C NMR (proton decoupled, 75 MHz, CDCl ): d = 16.7, 24.4,
3
45.7, 147.7, 154.2, 167.8.
1
24.8, 127.7, 128.0, 128.7, 128.9, 129.2, 130.2, 131.2, 136.7, 144.5,
+
EI-MS: m/z (%) = 291 (M , 80), 247 (100), 218 (46), 177 (21), 178
145.5, 159.0.
(
10), 75 (25), 43 (25).
+
EI-MS: m/z (%) = 267 (M , 100), 232 (25), 189 (12).
1
-(2-Methyl-4-phenylquinolin-3-yl)ethanone (3b)
6
-Chloro-2,4-diphenylquinoline (3g)
Pale yellow solid; mp 113 °C.
Pale yellow solid; mp 129 °C.
IR (KBr): 3062, 2961, 1699, 1567, 1439, 1393, 1214, 764, 706
cm .
IR (KBr): 3058, 1684, 1482, 910, 734 cm–1.
–
1
1
H NMR (300 MHz, CDCl ): d = 7.40–7.45 (m, 3 H), 7.55–7.70 (m,
1
3
H NMR (300 MHz, CDCl ): d = 1.96 (s, 3 H), 2.68 (s, 3 H), 7.35–
3
9
H), 7.94 (d, J = 8.0 Hz, 1 H).
7
.50 (m, 6 H), 7.60 (d, J = 7.9 Hz, 1 H), 7.68–7.70 (t, J = 7.9 Hz, 1
1
3
C NMR (proton decoupled, 75 MHz, CDCl ): d = 120.1, 124.4,
H), 8.05 (d, J = 8.0 Hz, 1 H).
3
1
1
26.5, 127.5, 128.6, 129.4, 130.3, 131.6, 132.7, 137.6, 139.0, 147.2,
48.4, 157.2.
1
3
C NMR (proton decoupled, 75 MHz, CDCl ): d = 23.7, 31.8,
3
1
1
25.0, 126.0, 126.4, 128.6, 128.8, 129.9, 134.7, 135.1, 143.8, 147.4,
53.4.
+
EI-MS: m/z (%) = 316 (M , 30), 288 (100), 125 (10), 89 (10), 77
(
45).
+
EI-MS: m/z (%) = 261 (M , 50), 246 (100), 218 (50), 178 (9), 176
(
22), 75 (20), 43 (35).
7
-Chloro-9-phenyl-2,3-dihydro-1H-cyclopenta[b]quinoline (3h)
Pale yellow solid; mp 95 °C.
9
-Phenyl-1,2,3,4-tetrahydroacridine (3c)
–
1
IR (KBr): 3062, 2958, 1605, 1485, 827, 714 cm .
Pale yellow solid; mp 137 °C.
1
H NMR (300 MHz, CDCl ): d = 2.18–2.28 (m, 2 H), 2.98 (s,
IR (KBr): 3060, 2935, 2862, 1571, 1487, 1443, 1219, 764, 703
cm .
3
–
1
J = 7.0 Hz, 2 H), 3.28 (t, J = 7.2 Hz, 2 H), 7.35 (m, 2 H), 7.50–7.60
(
m, 5 H), 8.24 (d, J = 8.2 Hz, 1 H).
1
H NMR (200 MHz, CDCl ): d = 1.75–1.85 (m, 2 H), 1.95–2.00 (m,
3
1
3
C NMR (proton decoupled, 75 MHz, CDCl ): d = 23.2, 30.2, 35.0,
2
H), 2.60 (t, J = 6.7 Hz, 2 H), 3.18 (t, J = 7.0 Hz, 2 H), 7.20–7.30
3
1
1
24.2, 126.8, 128.2, 128.7, 129.1, 130.2, 131.2, 134.3, 135.7, 141.8,
46.2, 167.6.
(
m, 4 H), 7.40–7.60 (m, 4 H), 7.98 (d, J = 8.0 Hz, 1 H).
1
3
C NMR (proton decoupled, 50 MHz, CDCl ): d = 22.9, 23.1, 27.9,
4.0, 96.1, 125.1, 125.5, 126.5, 127.5, 127.8, 128.0, 128.4, 128.6,
29.1, 137.3, 146.0, 146.4, 158.5.
3
+
EI-MS: m/z (%) = 279 (M , 80), 244 (100), 202 (20), 167 (20), 121
3
1
(50), 114 (17), 94 (10), 75 (15), 63 (5).
+
EI-MS: m/z (%) = 259 (M , 100), 230 (12), 183 (9).
7
-Chloro-9-phenyl-1,2,3,4-tetrahydroacridine (3i)
Pale yellow solid; mp 162 °C.
Ethyl 6-Chloro-2-methyl-4-phenylquinoline-3-carboxylate (3d)
Pale yellow solid; mp 99 °C.
–
1
IR (KBr): 3061, 2945, 1604, 1570, 1482, 1215, 704 cm .
1
–
1
H NMR (300 MHz, CDCl ): d = 1.75–1.80 (m, 2 H), 1.95–2.00 (m,
3
IR (KBr): 3065, 2984, 1725, 1605, 1225, 908, 734 cm .
2
H), 2.58 (t, J = 6.7 Hz, 2 H), 3.15 (t, J = 7.0 Hz, 2 H), 7.18–7.22
1
H NMR (300 MHz, CDCl ): d = 0.90–0.95 (t, J = 6.9 Hz, 3 H), 2.74
3
(m, 3 H), 7.45–7.55 (m, 4 H), 7.90 (d, J = 8.1 Hz, 1 H).
(
s, 3 H), 4.00–4.06 (q, J = 6.9 Hz, 2 H), 7.30–7.34 (m, 2 H), 7.48–
1
3
C NMR (proton decoupled, 75 MHz, CDCl ): d = 23.1, 28.2, 34.4,
7
.51 (m, 4 H), 7.62 (d, J = 8.0 Hz, 1 H), 8.00 (d, J = 8.0 Hz, 1 H).
3
1
1
24.5, 127.5, 128.2, 128.8, 129.1, 129.3, 129.5, 130.3, 131.3, 136.7,
44.8, 145.7, 159.5.
1
3
C NMR (proton decoupled, 75 MHz, CDCl ): d = 13.4, 23.6, 61.2,
3
1
1
25.0, 125.8, 128.4, 128.7, 129.1, 130.4, 131.0, 132.2, 135.1, 145.2,
46.0, 154.2, 168.0.
+
EI-MS: m/z (%) = 293 (M , 100), 258 (41), 242 (12), 230 (20), 176
(
5), 150 (12), 89 (7), 77 (45).
+
EI-MS: m/z (%) = 325 (M , 77), 280 (100), 252 (35), 217 (37), 189
(
(
10), 176 (38), 149 (53), 123 (13), 109 (20), 88 (20), 71 (20), 57
33).
Ethyl 6-Chloro-4-(2-chlorophenyl)-2-methyl-3-quinolinecar-
boxylate (3j)
Pale yellow solid; mp 110 °C.
1
-(6-Chloro-2-methyl-4-phenylquinolin-3-yl)ethanone (3e)
IR (KBr): 3062, 2981, 1727, 1573, 1471, 1390, 1222, 1077, 759
Pale yellow solid; mp 151 °C.
–
1
cm .
–
1
IR (KBr): 3026, 2960, 1700, 1605, 1565, 1481, 908, 692 cm .
1
H NMR (200 MHz, CDCl ): d = 0.90–0.98 (t, J = 7.0 Hz, 3 H), 2.78
1
3
H NMR (300 MHz, CDCl ): d = 1.99 (s, 3 H), 2.68 (s, 3 H), 7.30–
3
(
s, 3 H), 4.00–4.10 (q, J = 7.0 Hz, 2 H), 7.20–7.65 (m, 6 H), 8.00 (d,
7
.40 (m, 2 H), 7.50–7.60 (m, 4 H), 7.65 (d, J = 7.6 Hz, 4 H), 8.00
J = 8.2 Hz, 1 H).
(
d, J = 8.0 Hz, 1 H).
Synthesis 2004, No. 14, 2381–2385 © Thieme Stuttgart · New York

PAPER
Friedländer Quinoline Synthesis Using Heteropoly Acid
2385
1
3
C NMR (proton decoupled, 75 MHz, CDCl ): d = 23.1, 28.2, 34.4, Acknowledgment
3
1
1
24.5, 127.5, 128.2, 128.8, 129.1, 129.3, 129.5, 130.3, 131.3, 136.7,
44.8, 145.7, 159.5.
BVS, PS, RSR thank CSIR, New Delhi, for the award of fel-
lowships.
+
EI-MS: m/z (%) = 361 (M , 80), 315 (100), 287 (37), 252 (39), 217
(
30), 76 (9), 43 (35).
References
1
-[6-Chloro-4-(2-chlorophenyl)-2-methyl-3-quinolyl]-1-etha-
(
1) (a) Larsen, R. D.; Corley, E. G.; King, A. O.; Carrol, J. D.;
Davis, P.; Verhoeven, T. R.; Reider, P. J.; Labelle, M.;
Gauthier, J. Y.; Xiang, Y. B.; Zamboni, R. J. J. Org. Chem.
none (3k)
Pale yellow solid; mp 104 °C.
–
1
IR (KBr): 2925, 1702, 1568, 1471, 1386, 1202, 1055, 768 cm .
1996, 61, 3398. (b) Chen, Y. L.; Fang, K. C.; Sheu, J.-Y.;
1
H NMR (200 MHz, CDCl ): d = 2.10 (s, 3 H), 2.68 (s, 3 H), 7.20–
Hsu, S. L.; Tzeng, C. C. J. Med. Chem. 2001, 44, 2374.
(c) Roma, G.; Braccio, M. D.; Grossi, G.; Mattioli, F.; Ghia,
M. Eur. J. Med. Chem. 2000, 35, 1021.
3
7
.25 (m, 2 H), 7.40–7.50 (m, 2 H), 7.55–7.65 (m, 2 H), 8.00 (d,
J = 8.0 Hz, 1 H).
1
3
(2) (a) Kalluraya, B.; Sreenivasa, S. Farmaco 1998, 53, 399.
b) Doube, D.; Blouin, M.; Brideau, C.; Chan, C.;
C NMR (proton decoupled, 50 MHz, CDCl ): d = 23.8, 30.4,
3
(
1
1
24.5, 125.4, 127.3, 128.7, 130.0, 130.6, 130.8, 131.1, 132.0, 132.5,
32.8, 133.4, 140.4, 145.6, 154.0, 167.6.
Desmarais, S.; Eithier, D.; Falgueyret, J. P.; Friesen, R. W.;
Girard, M.; Girard, Y.; Guay, J.; Tagari, P.; Young, R. N.
Bioorg. Med. Chem. Lett. 1998, 8, 1255.
+
EI-MS: m/z (%) = 331 (M , 70), 293 (100), 286 (43), 251 (28), 216
(
9), 75 (7), 43 (37).
(
(
3) Maguire, M. P.; Sheets, K. R.; McVety, K.; Spada, A. P.;
Zilberstein, A. J. Med. Chem. 1994, 37, 2129.
4) (a) Agarwal, A. K.; Jenekhe, S. A. Macromolecules 1991,
7
-Chloro-9-(2-chlorophenyl)-2,3-dihydro-1H-cyclopen-
ta[b]quinoline (3l)
Pale yellow solid; mp 141 °C.
24, 6806. (b) Zhang, X.; Shetty, A. S.; Jenekhe, S. A.
Macromolecules 1999, 32, 7422. (c) Zhang, X.; Shetty, A.
S.; Jenekhe, S. A. Macromolecules 2000, 33, 2069.
–
1
IR (KBr): 3058, 2961, 1608, 1477, 1386, 1212, 954, 756 cm .
1
(
2
d) Jenekhe, S. A.; Lu, L.; Alam, M. M. Macromolecules
001, 34, 7315.
H NMR (200 MHz, CDCl ): d = 2.10–2.30 (m, 2 H), 2.70–3.00 (m,
3
2
7
H), 3.20–3.30 (m, 2 H), 7.20–7.30 (m, 2 H), 7.40–7.50 (m, 2 H),
(
5) (a) Jones, G. In Comprehensive Heterocyclic Chemistry II,
Vol. 5; Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V., Eds.;
Pergamon: New York, 1996, 167. (b) Cho, C. S.; Oh, B. H.;
Kim, T. J.; Shim, S. C. Chem. Commun. 2000, 1885; and
references cited therein. (c) Jiang, B.; Si, Y.-C. J. Org.
Chem. 2002, 67, 9449.
.55–7.65 (m, 2 H), 8.00 (d, J = 8.2 Hz, 1 H).
3
1
C NMR (proton decoupled, 50 MHz, CDCl ): d = 23.0, 29.9, 34.9,
3
1
1
24.0, 126.8, 127.0, 129.1, 129.8, 130.0, 130.4, 130.7, 131.5, 133.1,
34.9, 135.5, 139.2, 146.2, 167.8.
+
EI-MS: m/z (%) = 313 (25) M , 279 (30), 261 (7), 122 (30), 97 (16),
7
(
(
6) (a) Skraup, H. Ber. 1880, 13, 2086. (b) Friedländer, P. Ber.
5 (100), 43 (15).
1882, 15, 2572. (c) Mansake, R. H. F.; Kulka, M. Org.
React. 1953, 7, 59. (d) Linderman, R. J.; Kirollos, S. K.
Tetrahedron Lett. 1990, 31, 2689. (e) Theoclitou, M.-E.;
Robinson, L. A. Tetrahedron Lett. 2002, 43, 3907.
7) (a) Cheng, C.-C.; Yan, S.-J. Org. React. 1982, 28, 37.
(b) Thummel, R. P. Synlett 1992, 1. (c) Eckert, H. Angew.
Chem., Int. Ed. Engl. 1981, 20, 208. (d) Gladiali, S.;
Chelucci, G.; Mudadu, M. S.; Gastaut, M. A.; Thummel, R.
P. J. Org. Chem. 2001, 66, 400.
7
-Chloro-9-(2-chlorophenyl)-1,2,3,4-tetrahydroacridine (3m)
Pale yellow solid; mp 153 °C.
–
1
IR (KBr): 3060, 2962, 1615, 1478, 1390, 1225, 1067, 758 cm .
1
H NMR (300 MHz, CDCl ): d = 1.78–1.84 (m, 2 H), 1.95–2.02 (m,
H), 2.45–2.55 (m, 2 H), 3.10–3.20 (m, 2 H), 7.05 (m, 1 H), 7.15–
.20 (m, 1 H), 7.40–7.45 (m, 2 H), 7.50–7.60 (m, 2 H), 7.94 (d,
3
2
7
J = 8.0 Hz, 1 H).
(
(
8) Fehnel, E. A. J. Heterocycl. Chem. 1967, 4, 565.
9) (a) Strekowski, L.; Czamy, A. J. Fluorine Chem. 2000, 104,
1
3
C NMR (proton decoupled, 75 MHz, CDCl ): d = 21.8, 26.6, 28.8,
3
3
1
3.2, 125.9, 126.5, 127.5, 128.6, 129.0, 129.2, 129.3, 130.7, 129.8,
32.2, 134.3, 138.2, 149.1, 158.8.
281. (b) Hu, Y.-Z.; Zang, G.; Thummel, R. P. Org. Lett.
2003, 5, 2251.
+
EI-MS: m/z (%) = 329 (M , 98), 292 (100), 265 (22), 256 (15), 230
(
(10) (a) Kwon, T. W.; Song, S. J.; Cho, S. J. Tetrahedron Lett.
2003, 44, 255. (b) McNaughton, B. R.; Miller, B. L. Org.
Lett. 2003, 5, 4257. (c) Yadav, J. S.; Reddy, B. V. S.; Rao,
R. S.; Kumar, V. N.; Nagaiah, K. Synthesis 2003, 1610.
(d) Arkadi, A.; Chiarini, M.; Di Giuseppe, S.; Marinelli, F.
Synlett 2003, 203. (e) Palimkar, S. S.; Siddiqui, S. A.;
Daniel, T.; Lahoti, R. J.; Srinivasan, K. V. J. Org. Chem.
003, 68, 9371.
(11) Clark, J. H. Acc. Chem. Res. 2002, 35, 791.
12) (a) Okuhara, T.; Mizuno, N.; Misono, M. Appl. Catal. A
001, 222, 63. (b) Kozhevnikov, I. V. Chem. Rev. 1998, 98,
171.
(13) Preparation of Ag
Matachowski, L.; Napruszewska, B.; Poltowicz, J. J. Catal.
002, 207, 296.
27), 201 (8), 154 (10), 127 (12), 111 (9), 71 (30), 57 (52), 43 (60).
Ethyl 2,4-Dimethylquinoline-3-carboxylate (3n)
Pale yellow oil.
IR (KBr): 3068, 2930, 2872, 1723, 1615, 1587, 1212, 1082, 758
cm .
–
1
2
1
H NMR (300 MHz, CDCl ): d = 1.79 (t, J = 6.9 Hz, 3 H), 2.98 (s,
3
3
H), 3.10 (s, 3 H), 4.75–4.80 (q, J = 6.9 Hz, 2 H), 7.85–8.05 (m, 3
(
H), 8.40 (d, J = 8.1 Hz, 1 H).
1
2
3
C NMR (proton decoupled, 75 MHz, CDCl ): d = 14.0, 15.4, 23.5,
3
6
1
1.2, 123.7, 125.7, 126.0, 127.9, 129.3, 129.8, 141.1, 147.0, 154.1,
68.8.
PW12O40: Haber, J.; Pamin, K.;
3
2
+
EI-MS: m/z (%) = 229 (M , 100), 186 (70), 158 (20), 125 (12).
Synthesis 2004, No. 14, 2381–2385 © Thieme Stuttgart · New York