Low-valent titanium reagent-promoted intramolecular reductive coupling reactions of ketomalononitriles: A facile synthesis of benzo[4,5]indene, acridine and quinoline derivatives

Article abstract of DOI:10.1055/s-2005-861820

The intramolecular reductive coupling reactions of ketomalononitriles induced by a low-valent titanium reagent were studied. Benzo[4,5]indene, acridine and quinoline derivatives are prepared in good yields under neutral and mild conditions.

Full text of DOI:10.1055/s-2005-861820

PAPER
717
Low-Valent Titanium Reagent-Promoted Intramolecular Reductive Coupling
Reactions of Ketomalononitriles: A Facile Synthesis of Benzo[4,5]indene, Acri-
dine and Quinoline Derivatives
F
acile Synthesis of
a
Benzo[4, 5
q
]indene,
A
cr
i
idine
a
n
n
d Quinoline
g
D
erivative
s
Shi,*a–c Liangce Rong,a Chunling Shi,a Qiya Zhuang,a,b Xiangshan Wang,a,b Shujiang Tu,a,b Hongwen Huc
a
b
c
Department of Chemistry, Xuzhou Normal University, Xuzhou 221116, P. R. China
The Key Laboratory of Biotechnology for Medical Plants of Jiangsu Province, Xuzhou 221116, P. R. China
Department of Chemistry, Nanjing University, Nanjing 210093, P. R. China
Fax +86(516)3403164; E-mail: dqshi@263.net
Received 3 September 2004; revised 26 November 2004
Abstract: The intramolecular reductive coupling reactions of ke-
tomalononitriles induced by a low-valent titanium reagent were
studied. Benzo[4,5]indene, acridine and quinoline derivatives are
prepared in good yields under neutral and mild conditions.
OH
H
H
H
NH2
CN
NH2
CN
TiCl4-Zn
THF, r.t.
O
+
CN
CN
Ar
Ar
Ar
Key words: low-valent titanium, benzo[4,5]indene, acridine, quin-
oline
1
2
3
Scheme 1
Low-valent titanium reagents have an exceedingly high
ability to promote reductive coupling of carbonyl com-
pounds and are attracting increasing interest in organic
synthesis.1 Many other functional groups can also be cou-
pled.2 Recently, we have reported the cyclodimerization
of a,b-unsaturated ketones and a,b-unsaturated nitriles
promoted by this reagent yielding functional
cyclopentanes3 and cyclopentenes,4 respectively. It is well
known that the carbonyl group can easily be reduced by
low-valent titanium. However, the cyano group is more
stable to low-valent titanium reagent than the carbonyl
group and could not be reduced unless the reaction mix-
ture was refluxed for a long time and even then only with
low reaction yield.5 In our previous work, we have report-
ed a novel cyclodimerzation of arylidenemalononitriles4
and arylidenecyanoacetates6 promoted by low-valent tita-
nium reagents. Herein, we wish to describe our prelimi-
nary results on a novel intramolecular reductive
cyclization of ketonemalononitrile promoted by low-va-
lent titanium reagent in THF.
The chloro, bromo and fluoro groups of the substrates
could not be reduced under the reaction conditions, but the
methoxy group was cleaved partly into hydroxyl group to
give 3i accompanied by 3h. A relevant ketone-nitrile cou-
pling by a Ti(III) reagent has already been reported by
Itoh et al.7 and Chen et al.,8 but this was different from
what were reported by Itoh7 and Chen et al.,8 where the d-
ketonenitriles could be converted into substituted cyclo-
pentanones under the same reaction conditions.
Although the detailed mechanism of the above reductive
coupling reaction has not been clarified yet, the formation
of tetrahydrobenzo[4,5]indenes may be explained by the
possible mechanism presented in Scheme 2.
TiCl4 is reduced by zinc dust to give low-valent titanium
species Ti(0).2h In the initial step, an electron is transferred
Table 1 The Intramolecular Reductive Coupling of g-Ketomalono-
nitriles
Entry
Ar
Isolated yield (%)
When racemate g-ketomalononitriles 1 were treated with
the low-valent titanium prepared from titanium tetrachlo-
ride and zinc powder in anhydrous THF at room tempera-
2
3
a
b
c
d
e
f
C6H5
31
32
33
30
32
21
43
–
40
49
38
36
41
61
39
36
43
ture under
a nitrogen atmosphere, the reductive
cyclization products 1-aryl-2-cyano-3-amino-3a,3b,6,7-
tetrahydrobenzo[4,5]indenes 2 and and 1-aryl-2-cyano-3-
amino-3a-hydroxy-3a,3b,6,7-tetrahydrobenzo[4,5]in-
denes 3 were obtained (Scheme 1).
4-CH3C6H4
4-ClC6H4
4-BrC6H4
4-FC6H4
Table 1 summarizes our results on the intramolecular cy-
clization of g-ketomalononitriles. All substrates were cy-
clized in good yields to afford two products 2 and 3. The
pinacol coupling products of ketones were not detected.
2,4-Cl2C6H3
2-ClC6H4
4-CH3OC6H4
4-HOC6H4
g
h
i
SYNTHESIS 2005, No. 5, pp 0717–0724
x
x
.
x
x
.2
0
0
5
Advanced online publication: 09.02.2005
DOI: 10.1055/s-2005-861820; Art ID: F12204SS
© Georg Thieme Verlag Stuttgart · New York
–

718
D. Shi et al.
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O
OTi(I)
Ti(0)
Ti(0)
C
N
OTi(I)
C
NTi(I)
CN
N
CN
CN
Ar
Ar
Ar
1
A
B
OTi(I)
H
H
NHTi(I)
CN
HCl
H2O
NHTi(I)
CN
NH2
CN
H
Ar
H
Ar
H
Ar
C
D
2
HCl H2O
OH
NH2
CN
H Ar
3
Scheme 2
from the low-valent titanium to g-ketomalononitriles 1 to
give a radical intermediate A, which was followed by the
attack of the radical on the nitrile group to form the car-
bon-carbon bond and generate intermediate B. Then the
carbon-nitrogen double bond is transformed to form a car-
bon-carbon double bond leading to intermediate C due to
stabilization by the cyano group. The deoxygenation of
the intermediate C gives a radical, which captures one hy-
drogen from the molecule of THF to form the intermedi-
ate D. Hydrolysis of the intermediates C and D give the
products 2 and 3, respectively.
The chemical structures of 2 and 3 have been established
using spectroscopic data. The protons of 2 and 3 could be
easily identified by 2D NMR spectra. The configurations
of the products 2 and 3 have been confirmed by X-ray
analysis. The X-ray diffraction studies on single crystal of
2a and 3h indicate that C1-H, C3b-H and C3a-H, C3b-OH
are in cis-form. The molecular structures of the products
2a, 3h, and 3i are shown in Figure 1, Figure 2, and
Figure 3, respectively.
Figure 2 Molecular structure of 3h showing the atom numbering
scheme
Figure 3 Molecular structure of 3i showing the atom numbering
scheme
To our surprise, the reduction racemate of a-(2-nitrophe-
nyl)-g-ketomalononitriles 4 with TiCl4-Zn in the THF un-
der the same reaction condition did not give us the
expected product 5, but we could isolate 5,6-dihydroben-
Figure 1 Molecular structure of 2a showing the atom numbering
scheme
Synthesis 2005, No. 5, 717–724 © Thieme Stuttgart · New York

PAPER
Facile Synthesis of Benzo[4,5]indene, Acridine and Quinoline Derivatives
719
O
O
TiCl4-Zn
THF
R1
R2
TiCl4-Zn
THF
N
CN
NH2
CN
NO2
N
R2
R1
R1
R2
5
4
6
Scheme 3
zo[c]a-cridines 6 (Scheme 3). The results are summarized Quinoline analogues have anti-inflammatory, analgesic,
in Table 2. These acridine derivatives are most probably antihypertensive, chloroquine, and antidepressive proper-
formed by the reductive coupling reaction of the nitro ties.9 It has been reported that quinine, primaquine, chlo-
group with carbonyl group followed by the elimination of roquine, piperaquine, hydroxypiperquine, chloroquine-
malononitrile. The driving force for this last step is the phosphate, primaquine phosphate and mefloquine have
possibility for aromatization of the acridine system.
antimalarial properties.10 Quinolines have attracted inter-
est due to their biological properties. There have been a
number of syntheses published,11 but most of these proce-
dures have some common disadvantageous features, such
as harsh reaction condition, laborious manipulation or low
yield. These observations promoted chemists to develop
novel and convenient synthetic methods for the prepara-
tion of these quinoline compounds. In this paper, we have
provided the novel and convenient synthesis of quino-
lines.
In literature,12 a plausible mechanistic pathway to quino-
lines is illustrated as depicted in Scheme 5, though the de-
tails are unclear as yet. TiCl4 is reduced by Zn dust to give
low-valent titanium. It is well known that nitro and carbo-
nyl groups can be more easily reduced by low-valent tita-
nium reagent than the cyano group. So in the initial steps,
electrons are transferred from low-valent titanium reagent
to nitro group and carbonyl group to give radical anion E;
the latter couples to form the carbon-nitrogen bond and
generates intermediate F. The intermediate (F) then un-
dergoes deoxygenation to form G, which loses malononi-
trile to give the product 8.
Table 2 The Synthesis of 5,6-Dihydrobenzo[c]acridines Promoted
by Low-Valent Titanium
Entry
6a
R1
R2
H
Isolated yield (%)
H
79
75
78
80
6b
H
Cl
6c
OCH2O
CH3O
6d
CH3O
Moreover, treatment of non-cyclic a-(2-nitrophenyl)-g-
ketomalononitriles 7 with low-valent titanium reagent un-
der the same reaction conditions gave the similar product,
2-arylquinolines 8 (Scheme 4). The results are summa-
rized in Table 3.
CH(CN)2
R2
R1
R2
R3
R1
CH CH2C
TiCl4-Zn
THF
O
R3
N
NO2
In conclusion, a series of 1-aryl-2-cyano-3-amino-
3a,3b,6,7-tetrahydrobenzo[4,5]indenes, 1-aryl-2-cyano-
3-amino-3a-hydroxy-3a,3b,6,7-tetrahydrobenzo[4,5]in-
denes, 5,6-dihydrobenzo[c]acridines and 2-arylquinolines
were synthesized via reductive cyclization of g-ketoma-
lononitriles induced by the TiCl4-Zn system. The advan-
tages of our method are the easily accessible starting
materials, convenient manipulation and moderate to high
yields.
7
8
Scheme 4
Table 3 The Synthesis of 2-Arylquinolines Promoted by Low-Va-
lent Titanium
Entry
8a
R1
H
R2
H
R3
H
H
H
H
Cl
H
H
Isolated yield (%)
78
85
88
79
91
90
78
8b
8c
H
Cl
Br
H
THF was distilled from sodium–benzophene immediately prior to
use. All reactions were conducted under N2 atmosphere. Melting
points are uncorrected. IR spectra were recorded on FTIR-8101
H
1
spectrometer in KBr with absorptions in cm–1. H NMR and 13C
8d
8e
Cl
Cl
Cl
Cl
NMR spectra were determined on Inova-400 MHz spectrometer in
CDCl3 or DMSO-d6 solution. J values are in Hz. Chemical shifts are
expressed in ppm downfield from internal standard, TMS. MS spec-
tra were carried out on HP 5973 GC-MS or VG-ZAB-HS instru-
ments. Microanalyses were carried out on Perkin-Elmer 2400 II
instruments. X-ray diffraction was recorded on a Siemens P4 dif-
fractometer. Zinc dust (100 mesh) was activated by being soaked in
H
8f
Cl
Br
8g
Synthesis 2005, No. 5, 717–724 © Thieme Stuttgart · New York

720
D. Shi et al.
PAPER
CH(CN)2
R3
R2
CH(CN)2
R3
R2
R1
CH CH2C
O
R1
CH CH2C
Ti(0)
O
N
O
O Ti(I)
NO2
7
CH(CN)2
CH(CN)2
R1
CH
R3
R2
R3
R2
E
CH2
R1
CH CH2C
O
Ti(0)
C
N
NO
O
O
Ti(I)
O
Ti(II)
Ti(I)
CH(CN)2
CH(CN)2
R3
R2
R1
R1
deoxygenation
coupling
R3
R2
N
O
N
Ti(I)
O
Ti(I)
G
F
R1
R3
R2
aromatisation
–CH(CN)2
N
8
Scheme 5
5% HCl, then washed with water, acetone, and Et2O successively
and dried in vacuo. TiCl4 was distilled before use. g-Ketomalononi-
triles were prepared according to the published literature.13 Other
chemicals were used as purchased.
Anal. Calcd for C20H18N2: C, 83.88; H, 6.34; N, 9.78. Found: C,
83.92; H, 6.19; N, 9.51.
Crystal Data and Structure Refinement for 2a
Crystal suitable for X-ray analysis was obtained by slow evapora-
tion of an EtOH solution of 2a. C20H18N2, M = 286.36, triclinic,
space group P-1, a = 9.169 (2), b = 9.520 (2), c = 10.276 (2) Å, a =
91.09 (2)°, b = 107.95 (1)°, g = 111.05 (2)°, V = 787.8 (3) Å3, Z =
2, rcalcd = 1.207 g·cm–3, F (000) = 304, m (MoKa) = 0.071 mm–1, col-
orless block crystals, crystal size 0.52 mm × 0.50 mm × 0.40 mm.
Intensity data were collected at 296 K on a Siemens P4 diffractome-
ter with graphite-monochromated MoKa radiation (l = 0.71073 Å):
2922 independent reflections were collected using w scan mode in
the range of 2.11° to 25.50°, of which 2137 intensity data with [I >
2s (I)] were observed. The corrections for Lp factors were applied.
The structure was solved by direct methods and expanded using
Fourier techniques. Some non-hydrogen atoms were refined aniso-
tropically, while the rest were refined isotropically. Hydrogen at-
oms were induced in F value calculation but fixed during the
structure refinement. A full matrix least-squares refinement gave fi-
nal R1 = 0.0399 and wR2 = 0.1008, with w = 1/[s2Fo2 + (0.0595P)2]
where P = (Fo2 +2 Fc2)/3, S = 1.047. The maximum peak in the final
difference Fourier map was 0.184 e/Å3 and the minimum peak was
–0.145 e/Å3. In the final circle refinement the largest parameter shift
(D/s)max is 0.000. All calculations were performed using TEXSAN
program package.
Preparation of Tetrahydrobenzo[4,5]indenes; General Proce-
dure
TiCl4 (1.1 mL, 10 mmol) was added dropwise using a syringe to a
stirred suspension of zinc dust (1.3 g, 20 mmol) in freshly distilled
anhyd THF (15 mL) at r.t. under a dry N2 atmosphere. After com-
pletion of the addition, the mixture was refluxed for 3 h. The sus-
pension of the low-valent titanium reagent formed was cooled to r.t.
and a solution of g-ketomalononitriles (3 mmol) in THF (5 mL) was
added dropwise. The reaction mixture was then stirred at r.t. for
about 5 h. After this period, the TLC analysis of the mixture showed
the reaction to be complete. The reaction mixture was quenched
with 5% HCl (20 mL) and extracted with CH2Cl2 (3 × 30 mL). The
combined extracts were washed with water (3 × 50 mL) and dried
over anhyd Na2SO4. After evaporation of the solvent under reduced
pressure, the crude product was purified by column chromatogra-
phy on silica gel (200–300 mesh) using petroleum ether (bp 60–90
°C)–acetone (4:1) as eluent to give 2 and 3, respectively.
1-Phenyl-3-amino-2-cyano-3a,3b,6,7-tetrahydrobenzo[4,5]in-
dene (2a)
Solid; mp 196–198 °C.
IR (KBr): 3469, 3321, 2187, 1649, 1593, 1489, 1451, 783, 756, 708
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.40–7.13 (m, 9 H, ArH), 4.71 (s,
2 H, NH2), 4.40 (d, J = 10.0 Hz, 1 H, C1-H), 3.97 (d, J = 9.0 Hz, 1
H, C3a-H), 2.75–2.64 (m, 2 H, C6-H, C3b-H), 2.58–2.47 (m, 1 H, C6-
H), 1.48–1.34 (m, 1 H, C7-H), 1.06–0.98 (m, 1 H, C7-H).
13C NMR (400 MHz, CDCl3): d = 164.6, 138.5, 138.3, 131.9, 129.8,
128.6, 128.4, 128.3, 127.4, 126.9, 126.4, 119.1, 51.3, 48.8, 42.7,
28.4, 21.4.
1-Phenyl-3-amino-2-cyano-3a-hydroxy-3a,3b,6,7-tetrahydro-
benzo[4,5]indene (3a)
Solid; mp 200–201 °C.
IR (KBr): 3466, 3367, 2903, 2186, 1633, 1588, 1492, 1453, 1412,
1317, 1289, 1250, 1163, 1067, 1033, 1005, 917, 786, 763, 734, 707,
650 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 7.77–6.92 (m, 9 H, ArH), 6.37
(s, 2 H, NH2), 5.74 (s, 1 H, OH), 4.32 (d, J = 10.0 Hz, 1 H, C1-H),
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Facile Synthesis of Benzo[4,5]indene, Acridine and Quinoline Derivatives
721
2.68–2.60 (m, 1 H, C3b-H), 2.47–2.40 (m, 1 H, C6-H), 2.39–2.01 (m,
1 H, C6-H), 1.39–1.33 (m, 1 H, C7-H), 1.25–1.19 (m, 1 H, C7-H).
1-(4-Bromophenyl)-3-amino-2-cyano-3a,3b,6,7-tetrahydroben-
zo[4,5]indene (2d)
Solid; mp 220–222 °C.
13C NMR (400 MHz, DMSO-d6): d = 165.8, 140.3, 137.9, 137.1,
128.5, 127.9, 127.4, 127.1, 126.5, 125.9, 119.5, 79.9, 72.6, 49.1,
26.7, 22.2.
IR (KBr): 3466, 3320, 2939, 2922, 2192, 1649, 1594, 1486, 1451,
1433, 1407, 1217, 1007, 833, 784, 749 cm–1.
Anal. Calcd for C20H18N2O: C, 79.44; H, 6.00; N, 9.26. Found: C,
79.71; H, 5.84; N, 9.43.
1H NMR (400 MHz, DMSO-d6): d = 7.56–7.07 (m, 8 H, ArH), 6.29
(s, 2 H, NH2), 4.29 (d, J = 7.2 Hz, 1 H, C1-H), 3.93 (d, J = 7.6 Hz, 1
H, C3a-H), 2.76–2.69 (m, 1 H, C3b-H), 2.48–2.39 (m, 2 H, C6-H),
1.20–1.10 (m, 1 H, C7-H), 1.00–0.96 (m, 1 H, C7-H).
1-(4-Methylphenyl)-3-amino-2-cyano-3a,3b,6,7-tetrahydroben-
zo[4,5]indene (2b)
Solid; mp 202–203 °C.
Anal. Calcd for C20H17BrN2: C, 65.76; H, 4.69; N, 7.67. Found: C,
65.93; H, 4.48; N, 7.56.
IR (KBr): 3435, 3331, 2180, 1649, 1593, 1512, 1488, 1425, 851,
781, 754 cm–1.
1-(4-Bromophenyl)-3-amino-2-cyano-3a-hydroxy-3a,3b,6,7-tet-
rahydrobenzo[4,5]indene (3d)
Solid; mp 125–126 °C.
1H NMR (400 MHz, DMSO-d6): d = 7.38–7.05 (m, 8 H, ArH), 6.16
(s, 2 H, NH2), 4.25 (d, J = 6.4 Hz, 1 H, C1-H), 3.91 (d, J = 7.2 Hz, 1
H, C3a-H), 2.73–2.67 (m, 1 H, C3b-H), 2.55–2.38 (m, 2 H, C6-H),
2.28 (s, 3 H, CH3), 1.24–1.11 (m, 1 H, C7-H), 1.01–0.97 (m, 1 H,
C7-H).
IR (KBr): 3440, 3325, 3258, 3213, 2950, 2924, 2196, 1653, 1596,
1488, 1451, 1362, 1310, 1230, 1196, 1158, 1072, 1039, 1010, 829,
799, 768 cm–1.
Anal. Calcd for C21H20N2: C, 83.93; H, 6.71; N, 9.33. Found: C,
83.43; H, 6.55; N, 9.57.
1H NMR (400 MHz, DMSO-d6): d = 7.89–7.13 (m, 8 H, ArH), 6.79
(s, 2 H, NH2), 5.87 (s, 1 H, OH), 4.31 (d, J = 6.8 Hz, 1 H, C1-H),
3.10–3.04 (m, 1 H, C3b-H), 2.69–2.65 (m, 1 H, C6-H), 2.28–2.26 (m,
1 H, C6-H), 1.83–1.76 (m, 1 H, C7-H), 1.60–1.57 (m, 1 H, C7-H).
1-(4-Methylphenyl)-3-amino-2-cyano-3a-hydroxy-3a,3b,6,7-
tetrahydrobenzo[4,5]indene (3b)
Solid; mp 189–190 °C.
Anal. Calcd for C20H17BrN2O: C, 63.10; H, 4.49; N, 7.35. Found: C,
63.27; H, 4.36; N, 7.47.
IR (KBr): 3443, 3326, 3261, 3215, 3048, 2922, 2859, 2197, 1654,
1599, 1514, 1488, 1452, 1363, 1353, 1232, 1196, 1159, 1038, 1007,
807, 768 cm–1.
1-(4-Fluorophenyl)-3-amino-2-cyano-3a,3b,6,7-tetrahydroben-
zo[4,5]indene (2e)
Solid; mp 199–200 °C.
1H NMR (400 MHz, DMSO-d6): d = 8.01 (d, J = 7.2 Hz, 1 H, ArH),
7.49 (dd, J1 = 7.2 Hz, J2 = 7.2 Hz, 1 H, ArH), 7.42 (dd, J1 = 7.2 Hz,
J2 = 7.2 Hz, 1 H, ArH), 7.27 (d, J = 7.2 Hz, 2 H, ArH), 7.22 (d, J =
7.2 Hz, 1 H, ArH), 7.12 (d, J = 7.2 Hz, 2 H, ArH), 6.56 (s, 2 H, NH2),
5.96 (s, 1 H, OH), 4.54 (d, J = 7.2 Hz, 1 H, C1-H), 2.91–2.86 (m, 1
H, C3b-H), 2.73–2.68 (m, 1 H, C6-H), 2.48 (s, 3 H, CH3), 2.40–2.35
(m, 1 H, C6-H), 1.66–1.60 (m, 1 H, C7-H), 1.49–1.40 (m, 1 H, C7-
H).
IR (KBr): 3467, 3330, 3066, 2955, 2192, 1675, 1600, 1510, 1480,
1454, 1228, 1158, 964, 790, 774, 737 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 7.39–7.07 (m, 8 H, ArH), 6.26
(s, 2 H, NH2), 4.31 (d, J = 6.0 Hz, 1 H, C1-H), 3.92 (d, J = 7.6 Hz, 1
H, C3a-H), 2.74–2.67 (m, 1 H, C3b-H), 2.47–2.39 (m, 2 H, C6-H),
1.21–1.11 (m, 1 H, C7-H), 0.99–0.95 (m, 1 H, C7-H).
Anal. Calcd for C20H17FN2: C, 78.92; H, 5.63; N, 9.20. Found: C,
79.08; H, 5.44; N, 9.35.
Anal. Calcd for C21H20N2O: C, 79.72; H, 6.37; N, 8.85. Found: C,
79.89; H, 6.13; N, 8.65.
1-(4-Fluorophenyl)-3-amino-2-cyano-3a-hydroxy-3a,3b,6,7-tet-
rahydrobenzo[4,5]indene (3e)
Solid; mp 204–205 °C.
1-(4-Chlorophenyl)-3-amino-2-cyano-3a,3b,6,7-tetrahydroben-
zo[4,5]indene (2c)
Solid; mp 158–160 °C.
IR (KBr): 3507, 3474, 3351, 2944, 2920, 2870, 2185, 1650, 1603,
1591, 1508, 1389, 1361, 1341, 1305, 1213, 1161, 1027, 1001, 838,
817, 769 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 7.77–6.94 (m, 8 H, ArH), 6.40
(s, 2 H, NH2), 5.71 (s, 1 H, OH), 4.33 (d, J = 7.6 Hz, 1 H, C1-H),
2.67–2.62 (m, 1 H, C3b-H), 2.47–2.44 (m, 1 H, C6-H), 2.09–2.03 (m,
1 H, C6-H), 1.42–1.38 (m, 1 H, C7-H), 1.24–1.21 (m, 1 H, C7-H).
IR (KBr): 3467, 3326, 2962, 2941, 2193, 1671, 1599, 1491, 1456,
1297, 1229, 1213, 1096, 1014, 942, 795, 758, 733 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 7.85–7.19 (m, 8 H, ArH), 6.29
(s, 2 H, NH2), 5.80 (d, J = 7.2 Hz, 1 H, C1-H), 4.06–4.02 (m, 1 H,
C3a-H), 3.30–3.28 (m, 1 H, C3b-H), 3.14–3.08 (m, 1 H, C6-H), 2.99–
2.94 (m, 1 H, C6-H), 2.24–2.21 (m, 1 H, C7-H), 1.74–1.65 (m, 1 H,
C7-H).
Anal. Calcd for C20H17FN2O: C, 74.98; H, 5.35; N, 8.74. Found: C,
75.08; H, 5.47; N, 8.53.
Anal. Calcd for C20H17ClN2: C, 74.88; H, 5.34; N, 8.73. Found: C,
75.02; H, 5.08; N, 8.81.
1-(2,4-Dichlorophenyl)-3-amino-2-cyano-3a,3b,6,7-tetrahydro-
benzo[4,5]indene (2f)
Solid; mp 189–190 °C.
1-(4-Chlorophenyl)-3-amino-2-cyano-3a-hydroxy-3a,3b,6,7-
tetrahydrobenzo[4,5]indene (3c)
Solid; mp 195–196 °C.
IR (KBr): 3462, 3328, 2926, 2875, 2834, 2179, 1671, 1599, 1560,
1476, 1456, 1383, 1232, 1213, 1202, 1158, 1119, 1050, 1019, 826,
813, 735 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 7.84–7.06 (m, 7 H, ArH), 6.41
(s, 2 H, NH2), 5.70 (d, J = 8.4 Hz, 1 H, C1-H), 4.64 (d, J = 8.8 Hz, 1
H, C3a-H), 3.38–3.31 (m, 1 H, C3b-H), 3.15–2.95 (m, 2 H, C6-H),
2.27–2.23 (m, 1 H, C7-H), 1.90–1.82 (m, 1 H, C7-H).
IR (KBr): 3443, 3327, 3258, 3214, 2927, 2863, 2195, 1652, 1595,
1490, 1451, 1410, 1361, 1229, 1071, 1039, 1012, 831, 768 cm– 1
.
1H NMR (400 MHz, DMSO-d6): d = 7.77–6.95 (m, 8 H, ArH), 6.42
(s, 2 H, NH2), 5.76 (s, 1 H, OH), 4.33 (d, J = 7.2 Hz, 1 H, C1-H),
2.69–2.64 (m, 1 H, C3b-H), 2.47–2.44 (m, 1 H, C6-H), 2.09–2.05 (m,
1 H, C6-H), 1.43–1.38 (m, 1 H, C7-H), 1.25–1.18 (m, 1 H, C7-H).
Anal. Calcd for C20H17ClN2O: C, 71.32; H, 5.09; N, 8.32. Found: C,
71.48; H, 4.80; N, 8.51.
Anal. Calcd for C20H16Cl2N2: C, 67.62; H, 4.54; N, 7.89. Found: C,
67.83; H, 4.37; N, 7.96.
Synthesis 2005, No. 5, 717–724 © Thieme Stuttgart · New York

722
D. Shi et al.
PAPER
1-(2,4-Dichlorophenyl)-3-amino-2-cyano-3a-hydroxy-
3a,3b,6,7-tetrahydrobenzo[4,5]indene (3f)
Solid; mp 210–211 °C.
The structure was solved by direct methods and expanded using
Fourier techniques. Some non-hydrogen atoms were refined aniso-
tropically, while the rest were refined isotropically. Hydrogen at-
oms were induced in F value calculation but fixed during the
structure refinement. A full matrix least-squares refinement gave fi-
nal R1 = 0.0379 and wR2 = 0.0789, with w = 1/[s2Fo2 +(0.0417P)2]
where P = (Fo2 +2 Fc2)/3, S = 0.879. The maximum peak in the final
difference Fourier map was 0.151 e/Å3 and the minimum peak was
–0.154 e/Å3. In the final circle refinement the largest parameter shift
(D/s)max was 0.000. All calculations were performed using TEX-
SAN program package.
IR (KBr): 3458, 3328, 3265, 3221, 2937, 2854, 2196, 1653, 1597,
1557, 1468, 1385, 1364, 1103, 1049, 1036, 1006, 814, 767, 760
cm–1.
1H NMR (400 MHz, DMSO-d6): d = 7.77–6.94 (m, 7 H, ArH), 6.45
(s, 2 H, NH2), 5.88 (s, 1 H, OH), 4.72 (d, J = 7.2 Hz, 1 H, C1-H),
2.85–2.79 (m, 1 H, C3b-H), 2.56–2.51 (m, 1 H, C6-H), 2.22–2.18 (m,
1 H, C6-H), 1.36–1.31 (m, 1 H, C7-H), 1.21–1.12 (m, 1 H, C7-H).
Anal. Calcd for C20H16Cl2N2O: C, 64.70; H, 4.34; N, 7.55. Found:
C, 64.93; H, 4.15; N, 7.60.
1-(4-Hydroxyphenyl)-3-amino-2-cyano-3a-hydroxy-3a,3b,6,7-
tetrahydrobenzo[4,5]indene (3i)
Solid; mp 213–214 °C.
1-(2-Chlorophenyl)-3-amino-2-cyano-3a,3b,6,7-tetrahydroben-
zo[4,5]indene (2g)
Solid; mp 193–195 °C.
IR (KBr): 3466, 3373, 3344, 2938, 2908, 2832, 2192, 1644, 1596,
1511, 1432, 1250, 1236, 1177, 1073, 1008, 830, 809, 770 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 7.75 (d, J = 7.6 Hz, 1 H, ArH),
7.25–7.15 (m, 2 H, ArH), 6.96 (d, J = 7.2 Hz, 1 H, ArH), 6.89 (d,
J = 8.8 Hz, 2 H, ArH), 6.77 (d, J = 8.8 Hz, 2 H, ArH), 6.30 (s, 2 H,
NH2), 5.94 (s, 1 H, OH), 5.70 (s, 1 H, OH), 4.28 (d, J = 7.2 Hz, 1 H,
C1-H), 2.63–2.58 (m, 1 H, C3b-H), 2.47–2.44 (m, 1 H, C6-H), 2.12–
2.09 (m, 1 H, C6-H), 1.41–1.36 (m, 1 H, C7-H), 1.24–1.20 (m, 1 H,
C7-H).
IR (KBr): 3477, 3378, 2953, 2930, 2901, 2187, 1633, 1586, 1471,
1445, 1405, 1340, 1245, 1198, 1035, 1004, 763, 743 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 7.78–6.96 (m, 8 H, ArH), 6.38
(s, 2 H, NH2), 4.77 (d, J = 7.2 Hz, 1 H, C1-H), 3.44 (d, J = 7.2 Hz, 1
H, C3a-H), 2.85–2.80 (m, 1 H, C3b-H), 2.51–2.45 (m, 1 H, C6-H),
2.20–2.16 (m, 1 H, C6-H), 1.34–1.29 (m, 1 H, C7-H), 1.23–1.17 (m,
1 H, C7-H).
Anal. Calcd for C20H18N2O2: C, 75.45; H, 5.70; N, 8.80. Found: C,
75.57; H, 5.59; N, 8.74.
Anal. Calcd for C20H17ClN2: C, 74.88; H, 5.34; N, 8.73. Found: C,
75.07; H, 5.16; N, 8.92.
Crystal Data and Structure Refinement for 3i
1-(2-Chlorophenyl)-3-amino-2-cyano-3a-hydroxy-3a,3b,6,7-
tetrahydrobenzo[4,5]indene (3g)
Solid; mp 158–159 °C.
Crystal suitable for X-ray analysis was obtained by slow evapora-
tion of an EtOH solution of 3i. C20H18N2O2, M = 318.36, monoclin-
ic, space group P21/n, a = 7.701 (1), b = 9.841 (1), c = 20.768 (3) Å,
IR (KBr): 3448, 3350, 3224, 2927, 2855, 2189, 1646, 1594, 1490,
1474, 1439, 1339, 1214, 1181, 1088, 1050, 1035, 755, 737 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 7.91–7.16 (m, 8 H, ArH), 6.83
(s, 2 H, NH2), 5.91 (s, 1 H, OH), 4.19 (d, J = 8.8 Hz, 1 H, C1-H),
3.12–3.05 (m, 1 H, C3b-H), 2.75–2.72 (m, 1 H, C6-H), 2.40–2.38 (m,
1 H, C6-H), 1.87–1.81 (m, 1 H, C7-H), 1.65–1.61 (m, 1 H, C7-H).
a = 90°, b = 92.40 (1)°, g = 90°, V = 1572.4 (3) Å3, Z = 4, rcalcd
=
1.345 g·cm–3, F (000) = 672, m (MoKa) = 0.088 mm–1, colorless
block crystals, crystal size 0.58 mm × 0.50 mm × 0.26 mm. Inten-
sity data were collected at 291 K on a Siemens P4 diffractometer
with graphite-monochromated MoKa radiation (l = 0.71073 Å):
2767 independent reflections were collected using w scan mode in
the range of 1.96° to 25.00°, of which 2008 intensity data with [I >
2s (I)] were observed. The structure was solved by direct methods
and expanded using Fourier techniques. All non-hydrogen atoms
were refined anisotropically. The hydrogen atoms were included
but not refined. The final cycle of full-matrix least-squares refine-
ment give R1 = 0.0439 and wR2 = 0.0608, with w = 1/[s2Fo2 +
(0.0693P)2 + 0.1228P], S = 1.069. The maximum and minimum
peak on the final difference Fourier map corresponded to 0.306 and
–0.348 e/Å3, respectively. All calculations were performed using
TEXSAN program package.
Anal. Calcd for C20H17ClN2O: C, 71.32; H, 5.09; N, 8.32. Found: C,
71.35; H, 4.84; N, 8.09.
1-(4-Methoxyphenyl)-3-amino-2-cyano-3a-hydroxy-3a,3b,6,7-
tetrahydrobenzo[4,5]indene (3h)
Solid; mp 197–198 °C.
IR (KBr): 3460, 3369, 3257, 2948, 2833, 2177, 1642, 1632, 1577,
1510, 1489, 1235, 1175, 1028, 836, 781, 757 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 7.38–6.84 (m, 8 H, ArH), 6.23
(s, 2 H, NH2), 5.99 (s, 1 H, OH), 4.24 (d, J = 6.8 Hz, 1 H, C1-H),
3.91–3.87 (m, 1 H, C3b-H), 3.74 (s, 3 H, CH3O), 2.70–2.62 (m, 1 H,
C6-H), 2.46–2.38 (m, 1 H, C6-H), 1.22–1.12 (m, 1 H, C7-H), 1.01–
0.97 (m, 1 H, C7-H).
Synthesis of 5,6-Dihydrobenzo[c]acridines (6) and 2-Arylquino-
lines (8); General Procedure
TiCl4 (2.2 mL, 20 mmol) was added dropwise using a syringe to a
stirred suspension of zinc dust (2.6 g, 40 mmol) in freshly distilled
anhyd THF (20 mL) at r.t. under a dry N2 atmosphere. After com-
pletion of the addition, the mixture was refluxed for 3 h. The sus-
pension of the low-valent titanium reagent formed was cooled to r.t.
and a solution of a-(2-nitrophenyl)-g-ketomalononitriles (4 or 7) (5
mmol) in anhyd THF (10 mL) was added carefully at r.t. The reac-
tion mixture was then stirred at r.t. for 4 h. The reaction mixture was
quenched with 5% HCl (50 mL) and extracted with CHCl3 (3 × 50
mL). The combined organic layers were washed with water (3 × 50
mL), dried (Na2SO4), and the solvent was removed in vacuo to give
the crude product that was recrystallized from EtOH to give the pure
product 6 or 8.
Anal. Calcd for C21H20N2O2: C, 75.88; H, 6.06; N, 8.43. Found: C,
76.02; H, 5.84; N, 8.35.
Crystal Data and Structure Refinement for 3h
Crystal suitable for X-ray analysis was obtained by slow evapora-
tion of an EtOH solution of 3h. C21H18N2O2, M = 332.39, orthor-
hombic, space group P2(1)2(1)2(1), a = 7.820 (2), b = 7.911(2), c =
28.766 (7) Å, a = 90°, b = 90°, g = 90°, V = 1779.4 (7) Å3, Z = 4,
r
calcd = 1.241 g·cm–3, F (000) = 704, m (MoKa) = 0.081 mm–1, col-
orless block crystals, crystal size 0.58 mm × 0.46 mm × 0.24 mm.
Intensity data were collected at 291 K on a Siemens P4 diffractome-
ter with graphite-monochromated MoKa radiation (l = 0.71073 Å):
2361 independent reflections were collected using w scan mode in
the range of 1.42° to 27.30°, of which 1575 intensity data with [I >
2s (I)] were observed. The corrections for Lp factors were applied.
5,6-Dihydrobenzo[c]acridine (6a)
Solid; mp 61–63 °C.
Synthesis 2005, No. 5, 717–724 © Thieme Stuttgart · New York

PAPER
Facile Synthesis of Benzo[4,5]indene, Acridine and Quinoline Derivatives
723
IR (KBr): 3031, 2928, 1621, 1609, 1551, 1493, 1459, 1432, 1400,
1284, 1015, 946, 912, 860, 770, 737 cm–1.
2-Phenylquinoline (8a)
Solid; mp 79–81 °C (lit.14 83 °C).
1H NMR (400 MHz, CDCl3): d = 8.58 (d, J = 6.8 Hz, 1 H, ArH),
8.14 (d, J = 8.4 Hz, 1 H, ArH), 7.93 (s, 1 H, ArH), 7.75 (d, J = 7.2
Hz, 1 H, ArH), 7.65 (t, J = 8.4 Hz, 1 H, ArH), 7.49–7.36 (m, 3 H,
ArH), 7.29–7.25 (m, 1 H, ArH), 3.13 (t, J = 7.2 Hz, 2 H, CH2), 3.01
(t, J = 7.2 Hz, 2 H, CH2).
13C NMR (400 MHz, DMSO-d6): d = 153.0, 147.3, 139.9, 134.5,
134.4, 130.9, 130.3, 129.4, 129.3, 128.7, 128.0, 127.7, 127.5, 126.7,
125.9, 28.4, 28.0.
IR (KBr): 3055, 1622, 1596, 1546, 1496, 1442, 1321, 1204, 1128,
1026, 830, 792, 772, 691 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.24 (d, J = 8.4 Hz, 1 H, ArH),
8.20–8.16 (m, 3 H, ArH), 7.89 (d, J = 8.4 Hz, 1 H, ArH), 7.84 (d,
J = 7.2 Hz, 1 H, ArH), 7.74 (t, J = 7.2 Hz, 1 H, ArH), 7.56–7.45 (m,
4 H, ArH).
13C NMR (400 MHz, CDCl3): d = 157.3, 147.9, 139.3, 137.1, 129.9,
129.5, 128.9, 127.7, 127.5, 127.2, 126.5, 119.1.
MS (%): m/z = 205 (100) [M+], 204 (96) [M – 1].
MS (%): m/z = 232 (16.2) [M + 1], 231 (96) [M+], 230 (100) [M – 1].
Anal. Calcd for C17H13N: C, 88.28; H, 5.66; N, 6.06. Found: C,
88.43; H, 5.48; N, 6.25.
2-(4-Chlorophenyl)quinoline (8b)
Solid; mp 112–114 °C.
3-Chloro-5,6-dihydrobenzo[c]acridine (6b)
Solid; mp 101–103 °C.
IR (KBr): 3043, 1623, 1588, 1552, 1486, 1430, 1127, 1090, 1008,
817, 787, 752, 714 cm–1.
IR (KBr): 3028, 2943, 1632, 1598, 1484, 1395, 1342, 1289, 1251,
1178, 1074, 1013, 914, 835, 760, 742, 725, 695 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.56 (d, J = 4.4 Hz, 1 H, ArH),
8.09 (s, 1 H, ArH), 7.85 (s, 1 H, ArH), 7.73 (s, 1 H, ArH), 7.59 (d,
J = 8.8 Hz, 1 H, ArH), 7.45–7.37 (m, 2 H, ArH), 7.29–7.26 (m, 1 H,
ArH), 3.13(t, J = 6.8 Hz, 2 H, CH2), 3.02 (t, J = 6.8 Hz, 2 H, CH2).
13C NMR (400 MHz, CDCl3): d = 153.7, 145.9, 139.4, 134.3, 132.8,
131.7, 131.6, 130.9, 130.0, 129.6, 128.4, 128.0, 127.4, 126.1, 125.6,
28.8, 28.2.
1H NMR (400 MHz, CDCl3): d = 8.24 (d, J = 8.4 Hz, 1 H, ArH),
8.18–8.12 (m, 3 H, ArH), 7.85 (dd, J1 = 8.4 Hz, J2 = 4.4 Hz, 2 H,
ArH), 7.74 (t, J = 7.2 Hz, 1 H, ArH), 7.57–7.49 (m, 3 H, ArH).
13C NMR (400 MHz, CDCl3): d = 156.0, 148.1, 137.9, 137.1, 135.6,
129.9, 129.6, 129.1, 128.9, 127.5, 127.2, 126.6, 118.6.
MS (%): m/z = 241 (31.4) [M + 2], 239 (100) [M+], 238 (36) [M – 1].
Anal. Calcd for C15H10ClN: C, 75.16; H, 4.20; N, 5.84. Found: C,
75.23; H, 4.09; N, 5.62.
MS (%): m/z = 267 (31.3) [M + 2], 266 (40) [M + 1], 265 (100)
2-(4-Bromophenyl)quinoline (8c)
Solid; mp 114–116 °C.
[M+], 264 (80.1) [M – 1].
Anal. Calcd for C17H12ClN: C, 76.84; H, 4.55; N, 5.27. Found: C,
77.07; H, 4.38; N, 5.09.
IR (KBr): 3034, 1623, 1594, 1485, 1429, 1126, 1070, 1005, 815,
787, 751, 713 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.25 (d, J = 8.4 Hz, 1 H, ArH),
8.18 (d, J = 8.4 Hz, 1 H, ArH), 8.07 (d, J = 7.2 Hz, 2 H, ArH), 7.85
(dd, J1 = 8.4 Hz, J2 = 4.4 Hz, 2 H, ArH), 7.77 (t, J = 7.2 Hz, 1 H,
ArH), 7.66 (d, J = 8.4 Hz, 2 H, ArH), 7.55 (t, J = 7.2 Hz, 1 H, ArH).
13C NMR (400 MHz, CDCl3): d = 156.0, 148.5, 138.6, 137.1, 132.0,
130.0, 129.6, 129.1, 127.5, 127.3, 126.6, 124.0, 118.6.
2,3-Methylenedioxy-5,6-dihydrobenzo[c]acridine (6c)
Solid; mp 206–208 °C.
IR (KBr): 3050, 2990, 1652, 1618, 1547, 1471, 1377, 1314, 1267,
1200, 1030, 964, 925, 865, 845, 784, 757, 682 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.43 (d, J = 6.0 Hz, 1 H, ArH),
8.33 (s, 1 H, ArH), 7.66 (s, 1 H, ArH), 7.48–7.43 (m, 4 H, ArH),
6.29 (s, 2 H, OCH2O), 3.08 (t, J = 7.2 Hz, 2 H, CH2), 2.98 (t, J = 7.2
Hz, 2 H, CH2).
13C NMR (400 MHz, DMSO-d6): d = 153.2, 149.4, 147.6, 141.0,
139.7, 132.3, 132.1, 130.2, 129.1, 127.7, 127.2, 125.8, 103.8, 103.3,
27.6, 27.3.
MS: (%): m/z = 285 (96) [M + 2], 283 (100) [M+], 204 (87) [M – Br].
Anal. Calcd for C15H10BrN: C, 63.40; H, 3.55; N, 4.93. Found: C,
63.69; H, 3.38; N, 4.77.
6-Chloro-2-phenylquinoline (8d)
Solid; mp 109–110 °C.
MS (%): m/z = 275 (100) [M+], 274 (92.9) [M – 1].
IR (KBr): 3050, 1618, 1595, 1546, 1483, 1318, 1191, 1129, 1073,
1022, 944, 876, 833, 782, 754, 715, 694 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.17–8.11 (m, 4 H, ArH), 7.91 (d,
J = 8.4 Hz, 1 H, ArH), 7.82 (s, 1 H, ArH), 7.66 (d, J = 8.4 Hz, 1 H,
ArH), 7.54 (t, J = 7.2 Hz, 2 H, ArH), 7.50–7.47 (m, 1 H, ArH).
13C NMR (400 MHz, CDCl3): d = 157.6, 146.6, 139.1, 135.9, 132.0,
131.3, 130.6, 129.6, 128.9, 127.7, 127.6, 126.2, 119.8.
Anal. Calcd for C18H13NO2: C, 78.53; H, 4.76; N, 5.09. Found: C,
78.73; H, 4.54; N, 5.21%
2,3-Dimethoxy-5,6-dihydrobenzo[c]acridine (6d)
Solid; mp 175–176 °C.
IR (KBr): 3050, 2990, 1621, 1585, 1503, 1453, 1426, 1386, 1320,
1291, 1239, 1145, 1009, 911, 843, 792, 760, 735 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.38 (d, J = 5.6 Hz, 1 H, ArH),
7.98 (s, 1 H, ArH), 7.40–7.31 (m, 4 H, ArH), 7.27 (s, 1 H, ArH),
3.94 (s, 3 H, CH3O), 3.90 (s, 3 H, CH3O), 3.04 (t, J = 7.2 Hz, 2 H,
CH2), 2.94 (t, J = 7.2 Hz, 2 H, CH2).
MS (%): m/z = 241 (32) [M + 2], 239 (100) [M+], 238 (48) [M – 1],
204 (30.5) [M – Cl].
Anal. Calcd for C15H10ClN: C, 75.16; H, 4.20; N, 5.84. Found: C,
75.32; H, 4.09; N, 5.92.
13C NMR (400 MHz, DMSO-d6): d = 152.2, 150.4, 149.9, 144.2,
139.3, 134.9, 132.9, 129.5, 128.6, 128.5, 127.3, 125.4, 123.5, 108.1,
105.6, 56.1, 56.0, 28.2.
6-Chloro-2-(3-chlorophenyl)quinoline (8e)
Solid; mp 96–98 °C.
IR (KBr): 3043, 1625, 1596, 1548, 1474, 1328, 1190, 1131, 1099,
1079, 947, 898, 870, 831, 811, 785, 757, 697 cm–1.
MS (%): m/z = 291 (100) [M+], 289 (29) [M – 2].
Anal. Calcd for C19H17NO2: C, 78.33; H, 5.88; N, 4.81. Found: C,
78.47; H, 5.64; N, 4.75.
1H NMR (400 MHz, CDCl3): d = 8.19–8.13 (m, 3 H, ArH), 8.03 (d,
J = 5.6 Hz, 1 H, ArH), 7.88 (d, J = 8.8 Hz, 1 H, ArH), 7.83 (s, 1 H,
ArH), 7.69 (d, J = 10.0 Hz, 1 H, ArH), 7.49–7.46 (m, 2 H, ArH).
Synthesis 2005, No. 5, 717–724 © Thieme Stuttgart · New York

724
D. Shi et al.
PAPER
13C NMR (400 MHz, CDCl3): d = 155.9, 146.5, 140.8, 136.2, 135.1,
References
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H. W. Tetrahedron Lett. 2003, 44, 3199. (g) Shi, D. Q.;
Wang, J. X.; Shi, C. L.; Rong, L. C.; Zhuang, Q. Y.; Hu, H.
W. Synlett 2004, 1098. (h) Li, J.; Shi, D. Q.; Chen, W. X.
Heterocycles 1997, 45, 2381. (i) Shi, D. Q.; Shi, C. L.;
Wang, X. S.; Zhuang, Q. Y.; Tu, S. J.; Hu, H. W. Synlett
2004, 2239.
(3) Zhou, L. H.; Shi, D. Q.; Gao, Y.; Shen, W. B.; Dai, G. Y.;
Chen, W. X. Tetrahedron Lett. 1997, 38, 2729.
(4) Zhou, L. H.; Tu, S. J.; Shi, D. Q.; Dai, G. Y.; Chen, W. X.
Synthesis 1998, 851.
(5) (a) Chen, W. X.; Zhang, J. H.; Hu, M. Y.; Wang, X. C.
Synthesis 1990, 701. (b) Chen, J. X.; Jiang, J. P.; Chen, W.
X.; Kao, T. Y. Chin. Chem. Lett. 1991, 2, 351. (c) Chen, J.
X.; Jiang, J. P.; Chen, W. X.; Kao, T. Y. Heterocycles 1990,
701.
238 (57) [M – Cl].
Anal. Calcd for C15H9Cl2N: C, 65.72; H, 3.31; N, 5.11. Found: C,
65.83; H, 3.06; N, 4.92.
6-Chloro-2-(4-chlorophenyl)quinoline (8f)
Solid; mp 162–164 °C.
IR (KBr): 3040, 1623, 1596, 1484, 1407, 1180, 1092, 1073, 1012,
886, 847, 823, 804, 665 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.16–8.09 (m, 4 H, ArH), 7.87 (d,
J = 10.0 Hz, 1 H, ArH), 7.82 (s, 1 H, ArH), 7.67 (d, J = 8.4 Hz, 1 H,
ArH), 7.50 (d, J = 8.8 Hz, 2 H, ArH).
13C NMR (400 MHz, DMSO-d6): d = 155.8, 146.4, 137.5, 137.3,
135.3, 131.7, 131.4, 131.1, 129.5, 129.4, 128.3, 127.1, 120.1.
MS (%): m/z = 277 (7.3) [M + 4], 275 (51.3) [M + 2], 273 (100)
[M+], 238 (54.4) [M – Cl].
Anal. Calcd for C15H9Cl2N: C, 65.72; H, 3.31; N, 5.11. Found: C,
65.81; H, 2.94; N, 5.25.
6-Chloro-2-(4-bromophenyl)quinoline (8g)
Solid; mp 174–175 °C.
(6) Shi, D. Q.; Zhao, H.; Wang, X. S.; Yao, C. S.; Zhou, L. H. J.
Chem. Res., Synop. 2002, 452.
(7) Yamamoto, Y.; Matsumi, D.; Itoh, K. Chem. Commun.
1998, 875.
IR (KBr): 3040, 1617, 1596, 1546, 1482, 1403, 1314, 1179, 1072,
886, 844, 823, 803, 657 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.19 (d, J = 8.4 Hz, 2 H, ArH),
8.06 (d, J = 8.4 Hz, 2 H, ArH), 7.88 (d, J = 8.8 Hz, 1 H, ArH), 7.83
(s, 1 H, ArH), 7.70–7.66 (m, 3 H, ArH).
13C NMR (400 MHz, CDCl3): d = 156.2, 146.7, 138.0, 136.2, 132.3,
132.1, 131.2, 130.9, 129.1, 127.8, 126.2, 124.4, 119.4.
(8) Chen, J. X.; Chen, W. X.; Zhang, J. H. Chin. J. Org. Chem.
1992, 12, 26.
(9) Huang, L. S. Acta Pharm. Simica 1983, 18, 553.
(10) (a) Huang, L. S. Acta Pharm. Simica 1983, 18, 633.
(b) Akira, Y.; Kazuo, K. Radioisotopes 1979, 28, 687.
(11) Claret, P. A. In Comprehensive Organic Chemistry, Vol. 4;
Barton, D. H. R.; Ollis, W. D., Eds.; Pergamon Press:
Oxford, 1979, 155.
MS (%): m/z = 321 (9.4) [M + 4], 319 (100) [M + 2], 317 (95.2)
[M+], 238 (43) [M – Br], 203 (22.1) [M – Br – Cl].
Anal. Calcd for C15H9BrClN: C, 56.55; H, 2.85; N, 4.40. Found: C,
56.71; H, 2.62; N, 4.28.
(12) Jiang, J. P.; Gao, J.; Shen, W. B.; Chen, W. X. Acta Chimica
Sinica 1992, 50, 1134.
(13) Shi, D. Q.; Lu, Z. S.; Wang, S. H.; Tu, S. J.; Dai, G. Y. Synth.
Commun. 1998, 28, 4003.
(14) Kundu, N. G.; Mahanty, J. S.; Das, B. Tetrahedron Lett.
Acknowledgment
1993, 34, 1625.
We are grateful to the Natural Science Foundation of Jiangsu Edu-
cation Department (No. 03KJB150136) and Foundation of the Key
Laboratory of Biotechnology for Medical Plants of Jiangsu Pro-
vince (No. 02AXL13) for financial support.
Synthesis 2005, No. 5, 717–724 © Thieme Stuttgart · New York