Green preparation of quinoline derivatives through FeCl3· 6H2O Friedlander reaction in ionic liquids

Article abstract of DOI:10.1139/v04-066

The preparation of substituted quinoline derivatives through a Friedlander condensation reaction utilizing the ionic liquid [bmim][BF₄] as the reaction medium and iron chloride hexahydrate (FeCl₃·6H ₂O) as a catalyst is de

Full text of DOI:10.1139/v04-066

1
192
Green preparation of quinoline derivatives through
FeCl ·6H O catalyzed Friedlander reaction in ionic
3
2
liquids
Jianji Wang, Xuesen Fan, Xinying Zhang, and Lijun Han
Abstract: The preparation of substituted quinoline derivatives through a Friedlander condensation reaction utilizing the
ionic liquid [bmim][BF ] as the reaction medium and iron chloride hexahydrate (FeCl ·6H O) as a catalyst is described.
4
3
2
The advantages in using this method include its environmental friendliness, simple operating process in both mild and
neutral reaction conditions, and good yields.
Key words: ionic liquid, Friedlander reaction, quinoline derivatives, green chemistry.
Résumé : On décrit l’utilisation du [bmim][BF ], un liquide ionique, comme milieu réactionnel et de l’hexahydrate du
4
chlorure de fer (FeCl ·6H O) comme catalyseur pour la préparation de dérivés de quinoléines substituées par la réac-
3
2
tion de condensation de Friedlander. Cette méthode présente l’avantage d’être bénigne pour l’environnement,
d’impliquer un processus d’opération simple, de se faire dans des conditions douces et neutres et de donner de bons
rendements.
Mots clés : liquide ionique, réaction de Friedlander, dérivés de la quinoléine, chimie verte.
[
Traduit par la Rédaction] Wang et al. 1196
Introduction
tones appear to have met with very limited success. Subse-
quent studies showed that problems resulting from the clas-
sical Friedlander procedure can be overcome by using acid
catalysis. For example, it has been reported that drops of
concentrated sulfuric acid or 6 mol/L hydrochloric acid can
be used as efficient catalysts in the Friedlander condensation
procedure (4). With this method, various structurally varied
substrates, including 2-aminobenzophenone, can give the
corresponding quinolines in moderate to high yields. How-
ever, this method still has some drawbacks, notably use of
very strong acids as the catalyst, use of excessive glacial
acetic acid as the solvent, or even requiring the use of a
metal bath that can maintain a reaction temperature as high
as 200 °C, thus making this method unsuitable for scale up
in an environmentally benign and economical way.
For many years, the synthesis of quinoline and its deriva-
tives has been of considerable interest in organic and medici-
nal chemistry since a large number of natural products and
drugs contain this heterocyclic nucleus (1). While versatile
methods for the synthesis of the quinoline ring system have
been developed (2), many of them suffer from harsh reaction
conditions, poor yields, and (or) the use of expensive cata-
lysts. Thus, simple, general, and efficient procedures for the
synthesis of this important heterocycle are still in demand.
As one of the most frequently used pathways to prepare
quinoline derivatives, Friedlander synthesis involves a con-
densation of 2-aminobenzaldehyde with an aldehyde, ketone,
or polyfunctional carbonyl compound having a reactive α-
methylene group (3). This classical process is usually carried
out either by refluxing an aqueous or alcoholic solution of
the reactants in the presence of a base or by heating a mix-
ture of substrates at temperatures ranging from 150 to
Room temperature ionic liquids based on the 1,3-
dialkylimidazolium cation are attracting increasing interest
as alternative reaction media. The desirable advantages of
ionic liquids, include their lack of vapor pressure, wide liq-
uid range, and thermal stability, have made them exceptional
reaction media as well as environmentally benign solvents in
organic synthesis (5). In line with our research program of
using ionic liquids as novel reaction media in organic reac-
tions (6), we wish to report here a novel and efficient proce-
dure for the preparation of quinolines through a Friedlander
reaction catalyzed by FeCl ·6H O in an ionic liquid
2
20 °C in the absence of solvent and catalyst to produce the
corresponding 2- and 3-substituted quinolines in moderate
yields. Unfortunately, attempts to extend this method to the
preparation of 4-substituted quinolines from 2-aminoaryl ke-
Received 6 January 2004. Published on the NRC Research
Press Web site at http://canjchem.nrc.ca on 25 September
3
2
2
004.
(Scheme 1).
1
J. Wang, X. Fan, X. Zhang, and L. Han. School of
Chemical and Environmental Sciences, Key Laboratory of
Environmental Science and Engineering for Colleges and
Universities of Henan Province, Henan Normal University,
Xinxiang, Henan 453002, P. R. China.
Results and discussion
We set out to examine the Friedlander reaction in one
of the most widely used ionic liquids, 1-butyl-3-
methylimidazolium tetrafluoroborate ([bmim][BF ]), using
1Corresponding author (e-mail: jwang@henannu.edu.cn).
4
Can. J. Chem. 82: 1192–1196 (2004)
doi: 10.1139/V04-066
© 2004 NRC Canada

Wang et al.
Table 1. Friedlander reaction of 2-aminobenzophenone and acetophenone in different catalytic systems.
1193
Amount of
catalyst (mmol)
Reaction
temp. (°C)
Reaction
time (h)
Isolated
yield (%)
Entry
Solvent
Catalyst
1
2
3
4
5
6
7
8
9
0
1
[bmim][BF4]
[bmim][BF4]
[bmim][BF4]
[bmim][BF4]
[bmim][BF4]
[bmim][BF4]
[bmim][BF4]
Toluene
None
None
0
0
RT
100
10
10
10
10
10
6
0
9
FeCl ·6H O
0.1
0.3
0.5
0.5
0.5
0.5
0.5
0.5
0.5
100
41
65
78
75
74
62
68
8
3
2
FeCl ·6H O
100
3
2
FeCl ·6H O
100
3
2
FeCl ·6H O
100
3
2
FeCl3
100
6
FeCl ·6H O
100
6
3
2
EtOAc
FeCl ·6H O
reflux
reflux
reflux
6
3
2
1
1
THF
FeCl ·6H O
6
3
2
Ethanol
FeCl ·6H O
6
26
3
2
Note: Reaction conditions: 1 mL solvent, 1 mmol 2-aminobenzophenone, and 1 mmol acetophenone.
As for the possible mechanism of this catalytic reaction,
we believe that the Lewis acidity of Fe(III) ion in
FeCl ·6H O has played an important role in the promotion
Scheme 1.
3
2
of this condensation process. In order to clarify the role of
Fe(III) ion and the hydration water of FeCl ·6H O, anhy-
3
2
drous FeCl was also tried as the catalyst for this reaction,
3
and it gave similar results compared with FeCl ·6H O (Ta-
3
2
ble 1, entry 7). At this stage, it may be safe to say that it is
the Fe(III) ion rather than Fe(III) ion together with the
hydration water in FeCl ·6H O that acts as the real catalyst
3
2
Scheme 2.
in this condensation process. Of the two Fe(III) salts used,
although anhydrous FeCl exhibited a similar catalytic activ-
3
ity for this reaction when compared with FeCl ·6H O, the
3
2
latter is preferred because of its higher solubility in ionic liq-
uid, ease in handling, and lower price.
In addition, the use of several conventional organic sol-
vents, specifically toluene, tetrahydrofuran (THF), ethyl ace-
tate (EtOAc), and ethanol, in this catalytic process were also
studied for the sake of comparison with [bmim][BF ]. The
results are also shown in Table 1. It has been shown that of
2
-aminobenzophenone (Scheme 2, 1a) and acetophenone
4
(
2a) as the starting materials.
the five solvents used, [bmim][BF ] gave the highest yield
Firstly, the mixture of 1a (1 mmol) and 2a (1mmol) in
4
for the desired product under similar reaction conditions.
1
1
mL of [bmim][BF ] was stirred at room temperature for
4
Thus, the use of [bmim][BF ] as the reaction medium not
0 h, but no reaction took place as indicated by TLC (Ta-
4
only avoids the disadvantages of conventional organic
solvents, such as volatility, inflammability, and potential pol-
lution hazards, but it also results in greatly enhanced reactiv-
ity.
ble 1, entry 1). Then, the mixture was heated at 100 °C. To
our delight, the desired condensation reaction eventually
took place but in a rather sluggish way. In fact, after being
stirred at 100 °C for more than 10 h, the mixture produced
the corresponding quinoline product in less than 10% yield
Based on the above results, this process was then ex-
tended to other structurally varied substrates to investigate
its scope and generality. The results collected are listed in
Table 2. It can be seen that under similar conditions, a wide
range of ketones containing a reactive α-methylene group
can undergo easy condensation with 2-aminobenzophenones
to give substituted quinolines with fast reaction times and in
reasonably high yields. It is worthwhile noting that both
aliphatic and aromatic-aliphatic ketones gave corresponding
quinoline products in almost equally fair yields. With un-
symmetrical ketone substrates of the type CH COCH R,
(
[
Table 1, entry 2). This means that while the ionic liquid
bmim][BF ] itself possesses some catalytic activity for this
4
condensation process, the activity is too low to give the
product in a reasonable yield. Bearing in mind that
FeCl ·6H O has been successfully used as an environmen-
tally benign and efficient Lewis acid catalyst for promoting
several kinds of reactions (7), we then added catalytic
amounts of FeCl ·6H O to the reaction mixture. Fortunately,
the expected product was obtained with a much improved
yield (Table 1, entry 3). Further studies showed that the
yield could be increased to as high as 75% within 6 h when
3
2
3
2
3
2
from which two different modes of cyclization are theoreti-
cally possible, condensation occurred predominantly at the
more highly substituted alpha position and thus only one
product was obtained (Table 2, entry 13). In addition, higher
0
.5 mmol of FeCl ·6H O was used (Table 1, entry 6). How-
3 2
ever, any excess use of FeCl ·6H O beyond this amount did
not show any further increase in yield.
3
2
©
2004 NRC Canada

1
194
Can. J. Chem. Vol. 82, 2004
Table 2. Preparation of quinoline derivatives through Friedlander reaction catalyzed by FeCl q6H O in
3
2
ionic liquid.
Reaction
temp. (°C)
Reaction
time (h)
Isolated
yield (%)
Entry
X
R1
R2
H
H
H
H
Products
3a
1
2
3
4
5
6
7
8
9
H
C H
100
100
100
40
6
6
6
8
5
5
6
6
6
6
6
8
8
8
5
5
75
84
89
75
74
75
82
85
85
80
92
78
73
74
70
72
6
5
H
4-BrC H4
3b
3c
6
H
4-NO C H
2 6 4
H
CH3
3d
3e
-(CH2)3–
-(CH2)4–
H
100
100
100
100
100
100
100
40
H
3f
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
C H
H
3g
6
5
4-BrC H4
H
3h
3i
6
4-ClC H4
H
6
1
1
1
1
1
1
1
0
1
2
3
4
5
6
4-CH C H
6 4
H
3j
3
4-NO C H
6 4
H
3k
3l
2
CH3
CH3
H
CH3
CH3
60
3m
3n
3o
C H
60
2
5
-(CH2)3–
-(CH2)4–
100
100
3p
yields were obtained using 4-nitroacetophone (Table 2, en-
tries 3 and 11), showing that the yields of quinolines are to
some extent affected by the nature of the substituents at-
tached to the aromatic ring of the ketone.
Our attention was then directed toward the possibility of
recycling the reaction media since recovery and reuse of the
catalyst and solvent are highly preferable for a greener pro-
cess. At completion, the reaction mixture was diluted with
water and extracted with diethyl ether to obtain the desired
product. Meanwhile, due to its much higher solubility in wa-
ter and ionic liquid than in diethyl ether, Fe(III) ion was left
Table 3. Reusability of both [bmim][BF ] and
catalyst.
4
Recycle
no.
Ionic liquid
recovered (%)
Isolated yield
of 3a (%)a
1
2
3
4
5
6
a
99
98
99
99
98
97
75
78
77
75
73
69
and immobilized in [bmim][BF ]. After removal of water
4
Reaction conditions: reaction time 6 h at 100 °C.
under reduced pressure, [bmim][BF ] together with the cata-
4
lyst could be recovered almost quantitatively. Then, their re-
usability was investigated by using 2-aminobenzophenone
and acetophenone as model substrates. It was observed that
even in the sixth recycle, reuse of the ionic liquid and the
catalyst recovered from the fifth recycle still gave the corre-
sponding product in fairly good yield (Table 3, Recycle no.
recorded for KBr pellets on a Bruker Vector 22 spectrometer
with absorptions given in cm . H NMR spectra were ob-
–
1 1
tained with a Bruker AC 400 spectrometer using CDCl as
3
the solvent. Chemical shifts (δ) were expressed in ppm
downfield from an internal tetramethylsilane standard and
coupling constants (J) were given in Hz. Mass spectra were
recorded on a HP-5989B mass spectrometer. Elemental anal-
yses were performed on an EA-1110 (CE Instruments) in-
strument.
6
).
In conclusion, [bmim][BF ] was proved to be a useful and
4
alternative reaction medium, and FeCl ·6H O was found to
3
2
be an efficient catalyst for the preparation of quinolines. The
simple experimental and product isolation procedures, com-
bined with ease of recovery and reuse of the catalyst and the
reaction media, are expected to contribute to the develop-
ment of greener and waste free chemical processes for the
preparation of quinolines with biological activity. Further
studies to develop other new uses for ionic liquid in the
preparation of heterocyclic compounds are now in progress
in our laboratory.
The ionic liquid [bmim][BF ] was prepared and purified
4
according to a literature procedure (8). All other reagents
were reagent grade and were used without further purifica-
tion.
General procedure for the preparation of quinoline
derivatives
2
-Aminobenzophenone (1, 1 mmol), ketone (2, 1 mmol)
and FeCl ·6H O (0.5 mmol) were added to a 10-mL round-
3
2
bottom flask containing 1 mL of [bmim][BF ]. The mixture
4
Experimental
was then stirred at 100 °C for a certain period of time to en-
sure complete reaction (monitored by TLC). At completion,
the reaction mixture was diluted with water (5 mL) and ex-
Melting points were measured using a Kofler micro melt-
ing point apparatus and were uncorrected. IR spectra were
©
2004 NRC Canada

Wang et al.
1195
tracted with ethyl ether (3 × 10 mL). After drying, the com-
bined ether layers were concentrated under reduced pressure
and the resulting residue was charged on a silica gel column
and eluted with a mixture of ethyl acetate/n-hexane (1:8) to
obtain product 3. All products were fully characterized by
C H N: C 87.99, H 6.61, and N 5.40; found: C 88.07, H
6.52, and N 5.48.
1
8
17
6-Chloro-2,4-diphenylquinoline (3g)
–
1
mp 130–132 °C (lit. (11) 130–131 °C). IR ν (cm ): 3050,
1
1
IR, H NMR, MS, and elemental analysis. The aqueous so-
1610, and 1589. H NMR (400 MHz, CDCl3) δ: 8.11–8.15
lution of ionic liquid and catalyst was concentrated at re-
duced pressure to recover the ionic liquid and catalyst for
subsequent reuse.
(m, 3H), 7.82 (d, 1H, J = 2.2 Hz), 7.76 (s, 1H), 7.59–7.60
+
(m, 2H), and 7.45–7.50 (m, 7H). MS m/z (%): 317 (M + 2,
+
33), 315 (M , 100), and 280 (32). Anal. calcd. for
C H ClN: C 79.87, H 4.47, and N 4.44; found: C 79.95, H
2
1
14
2
,4-Diphenylquinoline (3a)
4.43, and N 4.35.
mp 110–111 °C (lit. (9) 112–113 °C). 1H NMR
6
-Chloro-2-(4-bromophenyl)-4-phenylquinoline (3h)
(
(
400 MHz, CDCl ) δ: 8.26 (d, 1H, J = 8.4 Hz), 8.19–8.22
m, 2H), 7.91 (dd, 1H, J = 8.4 Hz, J = 1.2 Hz), 7.83 (s,
3
–
1
mp 174–176 °C (lit. (11) 174–175 °C). IR ν (cm ): 3061,
1
2
1
1
600, and 1590. H NMR (400 MHz, CDCl ) δ: 8.14 (d, 1H,
1
H), 7.72–7.76 (m, 1H), and 7.47–7.59 (m, 9H). MS m/z
3
+
+
J = 8.8 Hz), 8.07 (d, 2H, J = 8.8 Hz), 7.85 (d, 1H, J =
(
%): 281 (M , 70), 280 (M – 1, 100), 202 (9), and 139 (8).
2
5
.2 Hz), 7.79 (s, 1H), 7.64–7.68 (m, 3H), and 7.54–7.58 (m,
+
+
H). MS m/z (%): 397 (M + 4, 26), 395 (M + 2, 100), 393
2
-(4-Bromophenyl)-4-phenylquinoline (3b)
mp 128–129 °C. IR ν (cm ) : 3050, 1610, and 1590. H
+
–
1
1
(M , 79), and 358 (18). Anal. calcd. for C H BrClN: C
21 13
6
3
3.90, H 3.32, and N 3.55; found: C 63.85, H 3.21, and N
.53.
NMR (400 MHz, CDCl ) δ: 8.23 (d, 1H, J = 8.0 Hz), 8.08–
3
8
7
.11 (m, 2H), 7.90 (d, 1H, J = 8.0 Hz), 7.72–7.78 (m, 2H),
.64–7.67 (m, 2H), and 7.47–7.59 (m, 6H). MS m/z (%): 361
+
+
6-Chloro-2-(4-chlorophenyl)-4-phenylquinoline (3i)
(
M +2, 89), 359 (M , 100), 278 (40), 202 (17), and 139
25). Anal. calcd. for C H BrN: C 70.01, H 3.92, and N
–
1
mp 164–166 °C (lit.(11) 159–160 °C). IR ν (cm ): 3058,
(
2
1
14
1
1
605, and 1587. H NMR (400 MHz, CDCl ) δ: 8.26 (d, 1H,
3
3
.89; found: C 69.85, H 3.88, and N 3.73.
J = 8.4 Hz), 8.15 (d, 2H, J = 8 Hz), 7.87 (d, 1H, J = 2.2 Hz),
7
.80 (s, 1H), 7.68–7.71 (m, 1H), and 7.50–7.59 (m, 7H).
2
-(4-Nitrophenyl)-4-phenylquinoline (3c)
+
+
+
–
1
MS m/z (%): 353 (M + 4, 12), 351 (M + 2, 65), 349 (M ,
100), and 314 (34). Anal. calcd. for C21H13Cl2N: C 72.02, H
3
mp 162–163 °C (lit. (9) 156–161 °C). IR ν (cm ): 3061,
1
1
620, and 1595. H NMR (400 MHz, CDCl ) δ: 8.37–8.42
3
.74, and N 4.00; found: C 72.07, H 3.71, and N 4.03.
(
m, 4H), 8.31 (d, 1H, J = 8.0 Hz), 7.96 (d, 1H, J = 8.0 Hz),
7
6
.87 (s, 1H), 7.80 (t, 1H, J = 8.0 Hz), and 7.54 –7.59 (m,
H). MS m/z (%): 326 (M , 100) and 202 (23). Anal. calcd.
6
-Chloro-2-(4-methylphenyl)-4-phenylquinoline (3j)
+
1
–1
mp 132–134 °C (lit. 1 132–133). IR ν (cm ): 3048, 1600,
for C H N O : C 77.29, H 4.32, and N 8.58; found: C
1
2
1
14
2
2
and 1580. H NMR (400 MHz, CDCl ) δ: 8.20 (d, 1H, J =
3
7
2
2
7.15, H 4.48, and N 8.63.
8
7
2
3
.4 Hz), 8.09 (d, 2H, J = 8.0 Hz), 7.85 (d, 1H, J = 3.5 Hz),
.82 (s, 1H), 7.67–7.64 (m, 1H), 7.57–7.52 (m, 5H), 7.33 (d,
-Methyl-4-phenylquinoline (3d)
+
H, J = 8.0 Hz), and 2.43 (s, 3H). MS m/z (%): 331 (M + 2,
–
1
mp 93–95 °C (lit. (10) 92–94 °C). IR ν (cm ): 3057,
+
4), 329 (M , 100), and 294 (23). Anal. calcd. for
.
1
971, 1617, and 1485 H NMR (400 MHz, CDCl ) δ: 8.09
3
C H ClN: C 80.11, H 4.89, and N 4.25; found: C 80.25, H
2
2
16
(
d, 1H, J = 8.4 Hz), 7.85 (dd, 1H, J = 8.4 Hz, J = 0.8 Hz),
1 2
4
.78, and N 4.33.
7
7
2
.66–7.70 (m, 1H), 7.45–7.55 (m, 5H), 7.40–7.45 (m, 1H),
+
.22 (s, 1H), and 2.77 (s, 3H). MS m/z (%): 219 (M , 100),
6
-Chloro-2-(4-nitrophenyl)-4-phenylquinoline (3k)
04 (14), and 176 (10). Anal. calcd. for C H N: C 87.64,
–1
1
1
6
13
mp 218–220 °C. IR ν (cm ): 3038, 1610, and 1525. H
H 5.98, and N 6.39; found: C 87.48, H 6.12, and N 6.46.
NMR (400 MHz, CDCl ) δ: 8.34–8.38 (m, 4H), 8.20 (d, 1H,
J = 8.0 Hz), 7.90 (d, 1H, J = 2.4 Hz), 7.88 (s, 1H), 7.23 (dd,
3
2
,3-Dihydro-9-phenyl-1H-cyclopenta[b]-quinoline (3e)
1
H, J = 9.2 Hz, J = 2.4 Hz), and 7.54–7.60 (m, 5H).
1 2
–
1
mp 104–105.5 °C (lit. (4) 134– 135 °C). IR ν (cm ) :
+
+
MS m/z (%): 362 (M + 2, 34), 360 (M , 100), 314 (40), 278
1
3
8
7
8
1
8
5
011, 2968, 1610, and 1455. H NMR (400 MHz, CDCl ) δ:
3
(32), and 139 (20). Anal. calcd. for C H ClN O : C 69.91,
H 3.63, and N 7.76; found: C 69.94, H 3.68, and N 7.59.
2
1
13
2
2
.06–8.08 (m, 1H), 7.60–7.64 (m, 2H), 7.45–7.55 (m, 3H),
.35–7.40 (m, 3H), 3.24 (t, 2H, J = 8.0 Hz), 2.91 (t, 2H, J =
+
.0 Hz), and 2.13–2.21 (m, 2H). MS m/z (%): 245 (M ,
6
-Chloro-2-methyl-4-phenylquinoline (3l)
–
1
00), 217 (9), and 168 (14). Anal. calcd. for C H N: C
1
8
15
mp 88–90 °C. IR ν (cm ): 3050, 2978, 1610, and 1496.
1
8.13, H 6.16, and N 5.71; found: C 88.18, H 6.02, and N
.86.
H NMR (400 MHz, CDCl ) δ: 8.02 (d, 1H, J = 9.2 Hz),
3
7
.82 (d, 1H, J = 2.4 Hz), 7.62 (dd, 1H, J = 9.2 Hz, J =
1 2
2
.4 Hz), 7.46–7.57 (m, 5H), 7.24 (s, 1H), and 2.77 (s, 3H).
+
+
1
,2,3,4-Tetrahydro-9-phenylacridine (3f)
MS m/z (%): 255 (M + 2, 32), 253 (M , 100), 218 (40), and
176 (11). Anal. calcd. for C H ClN: C 75.74, H 4.77, and
N 5.52; found: C 75.88, H 4.62, and N 5.63.
–
1
mp 131–133 °C (lit. (4) 142–143 °C). IR ν (cm ) : 3020,
1
6
12
1
2
978, 1600, and 1495. H NMR (400 MHz, CDCl ) δ: 8.06
3
(
d, 1H, J = 8.0 Hz), 7.59–7.64 (m, 1H), 7.43–7.55 (m, 3H),
7
8
.28–7.34 (m, 4H), 3.23 (t, 2H, J = 8.0 Hz), 2.59 (t, 2H, J =
6-Chloro-2,3-dimethyl-4-phenylquinoline (3m)
–
1
.0 Hz), 1.94–2.00 (m, 2H), and 1.76–1.83 (m, 2H). MS m/z
mp 121–124 °C. IR ν (cm ): 3035, 2959, 1610, and 1459.
+
1
(
%): 259 (M , 100), 230 (12), and 182 (6). Anal. calcd. for
H NMR (400 MHz, CDCl ) δ: 7.95 (d, 1H, J = 9.2 Hz),
3
©
2004 NRC Canada

1
196
Can. J. Chem. Vol. 82, 2004
7
2
2
.47–7.56 (m, 4H), 7.27 (d, 1H, J = 2.4 Hz), 7.20–7.23 (m,
No. 20273019 and the Research Foundation of Henan Nor-
mal University (No. 200303).
+
H), 2.74 (s, 3H), and 2.17 (s, 3H). MS m/z (%): 269 (M +
+
, 33), 267 (M , 100), 232 (32), 217 (15), 189 (18), and 94
(
6). Anal. calcd. for C H ClN: C 76.26, H 5.27, and N
References
1
7
14
5
.23; found: C 76.38, H 5.32, and N 5.16.
1
. (a) A.R. Katritzky and C.N. Rees. In Comprehensive hetero-
cyclic chemistry. Edited by A.J. Boulton and A. McKillop.
Vol. 2. Pergamon Press, Oxford. 1984; (b) T.L. Gilchist.
Heterocyclic chemistry. Longmans, London. 1997.
6
-Chloro-2-ethyl-3-methyl-4-phenylquinoline (3n)
–
1
mp 139–141 °C. IR ν (cm ): 3025, 2950, 1621, and 1493.
1
H NMR (400 MHz, CDCl ) δ: 7.99 (d, 1H, J = 8.8 Hz),
3
2
. (a) G. Jones. In Comprehensive heterocyclic chemistry. Edited
by A.R. Katritzky, C.W. Rees, and R.F.V. Scriven. Vol. 5.
Pergamon Press, Oxford. 1996. Chap. 5.05. p. 167; (b) H.
Tokuyama, M. Sato, T. Ueda, and T. Fukuyama. Heterocycles,
54, 105 (2001); (c) N.J. Ton and E.M. Ruel. Synthesis, 1351
7
.46–7.55 (m, 4H), 7.22–7.26 (m, 3H), 3.05 (q, 2H, J =
.2 Hz), 2.20 (s, 3H), and 1.41 (t, 3H, J = 7.2 Hz). MS m/z
7
+
+
(
%): 283 (M + 2, 34), 281 (M , 100), 217 (9), 189 (7), and
1
4
15 (5). Anal. calcd. for C H ClN: C 76.72, H 5.72, and N
18 16
.97; found: C 76.74, H 5.80, and N 4.88.
(
2001).
3
. (a) P. Friedlander. Ber. 15, 2572 (1882); (b) R.C. Elderfield. In
The chemistry of heterocyclic compounds. Edited by R.C.
Elderfield. Vol. 4. John Wiley & Sons, New York. 1952.
6
-Chloro-2,3-Dihydro-9-phenyl-1H-cyclopenta[b]-
quinoline (3o)
–
1
mp 94–96 °C. IR ν (cm ): 3035, 2970, 1610, and 1486.
4. E.A. Fehnel. J. Org. Chem. 31, 2899 (1966).
1
H NMR (400 MHz, CDCl ) δ: 7.99 (d, 1H, J = 8.8 Hz),
5. (a) J. Dupont, R.F. de Souza, and P.A.Z. Suarez. Chem. Rev.
102, 3667 (2002); (b) D.B. Zhao, M. Wu, Y. Kou, and E.Z.
Min. Catal. Today, 74, 157 (2002); (c) H. Olivier-Bourbigou
and L. Magna. J. Mol. Catal. A, 182–183, 419 (2002); (d) T.
Welton. Chem. Rev. 99, 2071 (1999); (e) Z. Li and C.G. Xia.
Tetrahedron Lett. 44, 2069 (2003); (f) J.S. Yadav, B.V.B.
Reddy, A.K. Basak, and A. Venkat Narsaiah. Tetrahedron Lett.
3
7
8
.46–7.58 (m, 5H), 7.32–7.35 (m, 2H), 3.20 (t, 2H, J =
.0 Hz), 2.90 (t, 2H, J = 8.0 Hz), and 2.13–2.20 (m, 2H).
+
+
MS m/z (%): 281 (M + 2, 33), 279 (M , 100), 244 (95), 202
(
11), and 120 (12). Anal. calcd. for C H ClN: C 77.28, H
18 14
5
.04, and N 5.01; found: C 77.40, H 5.02, and N 4.96.
4
4, 1047 (2003).
6
-Chloro-1,2,3,4-tetrahydro-9-phenylacridine (3p)
–
1
6. (a) X. Zhang, H. Niu, and J. Wang. J. Chem. Res. (S) 33
(2003); (b) X. Zhang, X. Fan, H. Niu, and J. Wang. Green
Chem. 5, 267 (2003).
mp 163.5–165 °C. IR ν (cm ): 3038, 2975, 1605, and
1
1
8
7
6
488. H NMR (400 MHz, CDCl ) δ: 7.95 (1H, d, J =
3
.8 Hz), 7.48–7.56 (m, 4H), 7.28 (1H, d, J = 2.4 Hz), 7.20–
.22 (m, 2H), 3.18 (t, 2H, J = 6.4 Hz), 2.59 (t, 2H, J =
.4 Hz), 1.93–1.98 (m, 2H), and 1.77–1.82 (m, 2H). MS m/z
7
. (a) J. Christoffers. J. Chem. Soc., Perkin Trans. 1, 3141
1997); (b) J. Lu, H.R. Ma, and W.H. Li. Chin. J. Org. Chem.
0, 815 (2000).
(
2
+
+
(
%): 295 (M + 2, 35), 293 (M , 100), 258 (59), 230 (9), and
8
9
. J.D. Holbrey and K.R. Seddon. J. Chem. Soc., Dalton Trans.
2133 (1999).
. R. Leardini, D. Nanni, A. Tundo, G. Zanardi, and F. Ruggieri.
J. Org. Chem. 57, 1842 (1992).
1
4
21 (8). Anal. calcd. for C H ClN: C 77.68, H 5.49, and N
19 16
.77; found: C 77.55, H 5.42, and N 4.68.
1
1
0. M. Al-Talib, J.C. Jochims, Q. Wang, A. Hamed, and A.E.
Ismail. Synthesis, 875 (1992).
1. Y. Toi, K. Isagawa, Y. Fushizaki. Nippon Kagaku Zasshi, 89,
Acknowledgement
This work was financially supported by the National Nat-
ural Science Foundation of China under NSFC grant
1
096 (1968); Chem. Abstr. 70, 87508 (1969).
©
2004 NRC Canada