Successive replacement of halogen atoms in 4,6-dihaloquinolines in cross-coupling reactions with arylboronic acids catalyzed by palladium and nickel complexes

Article abstract of DOI:10.1023/B:RUJO.0000013144.15578.2d

Conditions were found where in 6-halo-4-quinolines (halogen = iodine, bromine, or chlorine) the halogen atoms were replaced in succession by similar or different aryl groups in cross-coupling reactions with arylboric acids catalyzed by palladium and nickel complexes. Basing on successive Suzuki reaction a convenient procedure was developed for preparation of diarylquinolines that did not require isolation of the intermediate monoarylation product and afforded almost quantitative yields of diarylquinolines.

Full text of DOI:10.1023/B:RUJO.0000013144.15578.2d

Russian Journal of Organic Chemistry, Vol. 39, No. 11, 2003, pp. 1660 1667. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 11, 2003,
pp. 1729 1736.
Original Russian Text Copyright
2003 by Beletskaya, Tsvetkov, Latyshev, Lukashev.
Successive Replacement of Halogen Atoms
in 4,6-Dihaloquinolines in Cross-coupling Reactions
with Arylboronic Acids Catalyzed by Palladium
and Nickel Complexes
I. P. Beletskaya, A. V. Tsvetkov, G. V. Latyshev, and N. V. Lukashev
Lomonosov Moscow State University, Moscow, 119992 Russia
Received March 25, 2003
Abstract Conditions were found where in 6-halo-4-quinolines (halogen = iodine, bromine, or chlorine) the
halogen atoms were replaced in succession by similar or different aryl groups in cross-coupling reactions
with arylboric acids catalyzed by palladium and nickel complexes. Basing on successive Suzuki reaction a
convenient procedure was developed for preparation of diarylquinolines that did not require isolation of the
intermediate monoarylation product and afforded almost quantitative yields of diarylquinolines.
Cross-coupling reactions catalyzed by transition
metal complexes are nowadays a widely applied
instrument of building up a carbon-carbon bond in
versatile organic compounds. High yields of products,
the tolerance to a wide range of functional groups,
the opportunity to carry out the reaction under mild
conditions permits the use of the reactions in the
synthesis of pharmaceuticals, analogs of naturally
occurring molecules, and organic materials.
The possibility to perform successive introduction
of several substituents into a substrate by means of
compounds, taking into account that the chlorine in
the 4 position of the quinoline system is fairly active
in reactions of aromatic nucleophilic substitution,
whereas the C(sp2) I(Br) bond is more active in the
cross-coupling reactions. These substrates attract
additional interest because some functionally-sub-
stituted quinolines are known to possess a biological
activity [9 13]. In the organic synthesis the
opportunity to replace in succession halogenes in the
4,6-dihaloquinolines by cross-coupling reactions
opens a simple way to diaryl-substituted quinolines
with various functional groups in the aryl rings.
the cross-coupling reaction considerably extends the
prospects of the method and opens a simple synthetic
way to versatile classes of aromatic compounds. Such
approach was successfully applied to the synthesis of
polyaryl-substituted benzenes [1, 2], and also
pyridines [3, 4], quinolines [5], isoquinolines [6],
indoles [7], furans [8]. However the chemoselectivity
attained is essentially affected by the substrate struc-
ture, ligand surrounding of the catalyst, and external
conditions. Therefore the choice of conditions for a
selective succession of functionalization for each
definite substrate is a separate problem which not
always has a standard solution.
Preliminary experiments revealed that iodine in
the 6-iodo-4-chloroquinoline was selectively and
quantitatively substituted within 4 h at the use of a
stoichiometric amount of 4-anisylboric acid in the
presence of Pd(PPh3)4 and potassium carbonate in
dioxane. Regardless of the high yield of the mono-
arylation product the replacement of chlorine under
these conditions occurred very slowly, and the di-
arylated product was obtained in 48 h with an yield
To study the possibility of successive halogens
replacement in cross-coupling reactions we chose as
model Suzuki reaction with 6-halo-4-chloroquinolines
as substrate (where halogen was iodine, bromine, or
chlorine).
It is difficult to forecast the relative reactivity of
carbon halogen bonds in the cross-coupling for these
1070-4280/03/3911-1660$25.00 2003 MAIK Nauka/Interperiodica

SUCCESSIVE REPLACEMENT OF HALOGEN ATOMS
1661
of only 7%. This result demanded to carry out a
systematic search for optimum conditions for sub-
stitution of both halogens in the 6-halo-4-chloro-
quinolines (halogen was I, Br, Cl).
Table 1. Effect of the nature of palladium catalyst on the
rate of selective monoarylation of 6-iodo-4-chloroquinoline
Run no.
Catalyst
Time,
h
Yield, %
The effect of the catalyst nature on the rate of
substitution was studied in the mixture THF H2O in
the presence of K2CO3 (Table 1).
1
2
3
4
Pd(PPh3)4
15
5
4
100
100
100
100
Pd(PPh3)2Cl2
Pd(dppf)Cl2
Pd(OAc)2
4
Table 2. Effect of the nature of palladium catalyst on the
yield of arylation product of 6-(4-methoxyphenyl)-4-
chloroquinoline
Run no.
Catalyst
Yield, %
The best results were obtained at the use of
ligandless palladium Pd(OAc)2 and of the complex
Pd(dppf)Cl2. The reaction catalyzed by Pd(PPh3)4
was relatively slow but in all cases the yield was
quantitative. The position of the introduced aryl group
in these and also in all following experiments was
1
2
3
4
Pd(PPh3)4
82
21
11
4
Pd(PPh3)2Cl2
Pd(dppf)Cl2
Pd(OAc)2
confirmed by 1H NMR spectra and elemental analyses. Table 3. Effect of the catalyst nature on the yield of
successive diarylation product of 6-iodo-4-chloroquinoline
On the contrary, the highest yield of product
originating from chlorine substitution (82% in 48 h)
was obtained with Pd(PPh3)4 as catalyst. The other
palladium catalysts gave poor results (Table 2).
Time
Time of
Run
no.
Yield,
%
Catalyst
of 1st stage, h 2nd stage,
(yield 100%)
h
1
2
3
4
Pd(PPh3)4
15
5
4
48
48
48
48
82
19
3
Pd(PPh3)2Cl2
Pd(dppf)Cl2
Pd(OAc)2
4
<
1
boric acid into the reaction mixture after completion
of the first reaction (TLC monitoring) (Table 3). This
procedure rules out the use of additional amount of
palladium catalyst and the isolation and purification
of the intermediate product.
We found that the successive replacement of two
halogen atoms may be performed without isolation of
the intermediate product by adding the second aryl-
We studied the effect of the solvent nature on the
yield of diarylation product using as catalyst
Pd(PPh3)4. It turned out that the process in benzene
water mixture and in aqueous THF required long
boiling of the reaction mixture at both stages. The use
of aqueous acetonitrile and especially of aqueous
dioxane resulted in considerable acceleration of the
reaction (Table 4).
The observed acceleration is caused not only by
increased boiling point of the solvent but also by the
change in the solvent nature. The first stage in
aqueous dioxane at 64 C occurred faster than in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 11 2003

1662
BELETSKAYA et al.
THF water mixture at the same temperature (Table
4, runs nos. 1, 5); the second stage failed to proceed
in aqueous dioxane at 64 C (Table 4, run no. 5). It
should be noted that at room temperature even the
iodine substitution (first stage) is very slow (Table 4,
run no. 6).
yield of diarylation products was high in all cases. It
should be noted that the insignificant difference in the
reaction rate at the use of K3PO4 and K2CO3 permits
the application of the more accessible potassium
carbonate without a loss in the yield of the target
product.
The base nature is also a significant factor
(Table 5). The best results produced the application
as base of K3PO4. The activity of bases diminished in
the series K3PO4 K2CO3 > Ba(OH)2 > CsF but the
It turned out that the reaction selectivity under the
chosen optimum conditions [boiling in the dioxane
water mixture in the presence of Pd(PPh3)4 and
K2CO3] was not reduced at the use as substrate
of 6-bromo-4-chloroquinoline, and the yield of the
products was the same.
quinolines and arylboric acids is different from the
general mechanism of Suzuki reaction [14]. This
mechanism applied to the successive halogen substitu-
tion in the 4,6-dihaloquinolines is as follows.
There is no reason to believe that the reaction
mechanism of the cross-coupling between 4,6-dihalo-
The oxidative addition of Pd(0) occurs initially
exclusively to iodine or bromine in position 6 of the
quinoline ring. At the use of a stoichiometric amount
of arylboric acid the chlorine in position 4 remains
intact, and the reaction completed affording 6-aryl-4-
chloroquinoline (catalytic cycle A). On addition of
the second arylboric acid into the reaction mixture
occurred the chlorine substitution (catalytic cycle B).
To demonstrate the prospects of the method we
synthesized several diarylquinolines with identical
or different aryl groups in high preparative yields
(Table 6).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 11 2003

SUCCESSIVE REPLACEMENT OF HALOGEN ATOMS
1663
Table 4. Effect of solvent on the yield of successive
Table 5. Effect of base on the yield of successive
diarylation product of 6-iodo-4-chloroquinolinea
diarylation product of 6-iodo-4-chloroquinolinea
Time of 1st Time of Yield,
Run
Run
no.
Time of 1st Time of 2nd Yield
Solvent
stage, h
2nd stage,
h
%
Base
stage
stage
%
no.
(yield, %)
completion, h completion, h
1
2
3
4
5
THF H2O
Benzene H2O
MeCN H2O
Dioxane H2O 0.5 (100)
Dioxane H2O
(64 C)
15 (100)
15 (100)
2 (100)
48
48
14
4
82
50
83
97
0
1
2
3
4
K2CO3
K3PO4
CsF
0.5
0.25
7
4
4
12
4
97
97
97
88
Ba(OH)2
0.25
5 (100)
48
a
2 mol% of Pd(PPh3)4, 6 equiv of base, dioxane H2O (3: 1),
heating at reflux. 1st stage: 1.0 equiv of 4-MeOC6H4B(OH)2;
2nd stage: 1.3 equiv of 4-MeC6H4B(OH)2.
6
Dioxane H2O
(20 C)
48 (44)
a
2 mol% of Pd(PPh3)4, 6 equiv of K2CO3, heating at reflux.
1st stage: 1.0 equiv of 4-MeOC6H4B(OH)2; 2nd stage:
1.3 equiv of 4-MeC6H4B(OH)2.
The character of substituent arising in the 6 posi-
tion of the quinoline ring in the first stage of reaction
affected the rate of the subsequent chlorine replace-
ment. For instance, the substitution of chlorine in
4-chloro-6-(4-chlorophenyl)quinoline proceeded faster
than in 4-chloro-6-(4-tolyl)quinoline or in 4-chloro-6-
(4-anisyl)quinoline. This results in some decrease in
selectivity, and with 6-(4-chlorophenyl)-4-chloro-
quinoline caused diminishing in the yield of the
successive diarylation product. It should be noted
that under the applied conditions the chlorine in
the 4-chlorophenyl moiety did not undergo substitu-
tion.
Table 6. Yield of successive diarylation products of 6-iodo-4-chloroquinolinea
Reaction product Time of completion, h
Run no.
Yield, %b
mp,
C
of 1st stage
of 2nd stage
R = 4-MeOC6H4
4-MeC6H4
4-MeC6H4
R = 4-ClC6H4
4-MeC6H4
4-ClC6H4
1
2
3
4
0.5
4
97 (96)c
97 (96)
127
R
R =
=
R
=
0.5
0.5
4
124
124
116
2.5
89 (87)
R
R =
=
R
=
3d
100 (99)
a
2 mol% of Pd(PPh3)4, 6 equiv of K2CO3, dioxane H2O (3: 1), heating at reflux. 1st stage: 1.0 equiv of
ArB(OH)2; 2nd stage: 1.3 equiv Ar B(OH)2.
Preparative yield given in parentheses.
The product was obtained in this yield both from 6-iodo-4-chloroquinoline and from 6-bromo-4-chloroquinoline.
2.3 equiv of 4-ClC6H4B(OH)2.
b
c
d
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 11 2003

1664
BELETSKAYA et al.
The coupling of 6-iodo-4-chloroquinoline with
dioxane in the presence of NiCl2(PPh3)2 did
not occur even at prolonged boiling, and the reaction
was likely to proceed only under anhydrous conditions.
arylboric acids on nickel catalysts in anhydrous
dioxane occurred with considerably lower selectivity
at the stage of iodine substitution. At the same time
the reaction carried out in a dioxane water mixture
resulted in exclusive replacement of iodine, and the
corresponding 6-aryl-4-chloroquinoline was obtained
in quantitative yield.
Thus the best way to carry out the successive di-
arylation of 6-iodo-4-chloroquinoline with the use of
NiCl2(PPh3)2 as catalyst is performing reaction in two
stages: the first stage should occur in aqueous dioxane
and provide the product of iodine substitution, the
second stage of chlorine replacement should be
However further substitution of chlorine in the
6-aryl-4-chloroquinoline by Suzuki reaction in aqueous carried out in anhydrous dioxane.
The nickel complexes used as catalysts provide a
possibility to carry out the cross-coupling of 4,6-di-
chloroquinoline with arylboric acids. However the
outcome of the reaction depended essentially on the
nature of phosphine ligands in the nickel complex.
For instance, NiCl2(PPh3)2, Ni(acac)2, and NiCl2
6H2O are inadequately efficient and selective and
afford mixtures of mono- and disubstituted products
(Table 7, runs nos. 1, 2, 3, 7, 9). Complexes
NiCl2(dppe), NiCl2(dppb), and NiCl2(dppf) turned
out to be more efficient, but also afforded mixtures
of products. Note however that in case both chlorine
atoms should be replaced by the same aryl the
applications of these catalysts is favorable.
We succeeded in selective replacement of chlorine
in the more active 4 position at the use as catalyst a
complex NiCl2(dppm). However this complex was
inefficient in the second stage of reaction (the sub-
stitution of chlorine in 6 position). We managed to
carry out the second stage by adding into the reaction
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 11 2003

SUCCESSIVE REPLACEMENT OF HALOGEN ATOMS
Table 7. Yield of diarylation products of 4,6-dichloroquinoline
1665
Run
no.
Composition of reaction mixture (%)
Catalyst
Time (h) Base
Solvent
1
2
3
4
1
2
3
NiCl2(PPh3)2
NiCl2(PPh3)2
NiCl2(PPh3)2/
butyllithium
NiCl2(dppb)
NiCl2(dppe)
NiCl2(dppm)
Ni(acac)2
1
1
1
K3PO4
K3PO4
K3PO4
Dioxane
Dioxane/water
Dioxane
67
100
57
22
-
29
-
-
-
11
14
-
-
4
5
6
7
8
9
1
1
1
1
1
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
34
29
23
98
48
38
33
34
69
2
11
45
-
33
37
6
Traces
2
-
-
NiCl2(dppf)
NiCl2 6H2O
41
10
20
7
mixture simultaneously with the second arylboric acid
also a more active catalyst, NiCl2(dppe).
Thus at the use of nickel-catalyzed coupling with
4,6-dichloroquinoline the assembling of the diaryl-
quinoline structure can be performed in a reverse
order as compared to reactions with 4-chloro-6-
iodoquinoline or 4-chloro-6-bromoquinoline.
complexes. In a flask equipped with a reflux
condenser was mixed in an argon atmosphere
50.0 mg (0.173 mmol) of 6-iodo-4-chloroquinoline,
26.2 mg (0.173 mmol) of 4-methoxyphenylboric acid,
71.6 mg (0.519 mmol) of K2CO3, 4 mg (3.5 mol)
of Pd(PPh3)4, 1.5 ml of THF, and 0.5 ml of water.
The reaction mixture was heated at reflux for an
appropriate time (TLC monitoring), then it was
cooled, diluted with dichloromethane, filtered
through a 3 cm bed of silica gel, the solvents were
evaporated at reduced pressure. The product was
purified by column chromatography on silica gel,
eluent petroleum ether ethyl ether (1: 1).
The yield of arylation products obtained from
4,6-dihaloquinolines was measured by means of
1H NMR spectroscopy (save the experiments with
preparative isolation of the products).
EXPERIMENTAL
The progress of reactions was monitored by TLC
1
on Silufol UV-254 plates and by H NMR spectro-
1
scopy. H NMR spectra were registered on spectro-
meter Varian VXR 400 at operating frequency
400 MHz. Chemical shifts are given in -scale with
respect to HMDS.
6-(4-Anisyl)-4-chloroquinoline. Yield 46.5 mg
(100 %). mp 113 C. H NMR spectrum, , ppm:
1
8.73 d (1H, J 4.7 Hz), 8.33 d (1H, J 2.1 Hz),
8.15 d (1H, J 8.8 Hz), 7.98 d.d (1H, J 8.8,
2.1 Hz), 7.66 m (2 H), 7.47 d (1H, J 4.7 Hz),
7.02 m (2H), 3.86 s (3H). Found, %: C 71.44;
H 4.39; N 4.98. C16H12ClNO. Calculated, %: C
71.25; H 4.48; Cl 13.14; N 5.19.
6-iodo-4-chloroquinoline [15], 6-bromo-4-chloro-
quinoline [16], and 4,6-dichloroquinoline [17] were
prepared by known procedures starting with the cor-
responding 4-haloaniline and diethyl (2-ethoxymethyl-
ene)malonate.
Cross-coupling of 6-(4-anisyl)-4-chloroquinoline
with 4-tolylboric acid catalyzed by palladium
Cross-coupling of 6-iodo-4-chloroquinoline with
4-anisylboric acid catalyzed with palladium
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 11 2003

1666
BELETSKAYA et al.
complexes. In a flask equipped with a reflux con-
denser was mixed in an argon atmosphere 50.0 mg
(0.186 mmol) of 6-(4-anisyl)-4-chloroquinoline,
30.5 mg (0.223 mmol) of 4-methylphenylboric acid,
77.0 mg (0.558 mmol) of K2CO3, 4.3 mg (3.7 mol)
of Pd(PPh3)4, 1.5 ml of THF, and 0.5 ml of water.
The reaction mixture was heated at reflux for an
appropriate time (TLC monitoring), then it was cool-
ed, diluted with dichloromethane, filtered through a
3 cm bed of silica gel, the solvents were evaporated
at reduced pressure. The product was purified by
column chromatography on silica gel, eluent petrol-
eum ether ethyl ether (1: 1).
(1H, J 2.1 Hz), 7.93 d.d (1H, J 8.8, 2.1 Hz), 7.47 m
(2H), 7.42 m (2H), 7.29 (3H), 7.21 m (2H), 3.81 s
(3H), 2.44 s (3H). Found, %: C 89.18; H 6.49;
N 4.22. C23H19N. Calculated, %: C 89.28; H 6.19;
N 4.53.
4-(4-Tolyl)-6-(4-chlorophenyl)quinoline was pre-
pared from 50 mg of 6-iodo-4-chloroquinoline in
1
49.7 mg (87%) yield. mp 124 C. H NMR spectrum,
, ppm: 8.91 d (1H, J 4.4 Hz), 8.21 d (1H, J 8.8 Hz),
8.07 d (1H, J 2.1 Hz), 7.90 d.d (1H, J 8.8, 2.1 Hz),
7.50 m (2H), 7.36 (7H), 2.46 s (3H). Found, %:
C 79.94; H 4.95; N 4.13; C22H16ClN. Calculated,
%: C 80.11; H 4.89; N 4.25.
6-(4-Anisyl)-4-(4-tolyl)quinoline. Yield 49.6 mg
(82%). mp 127 C. H NMR spectrum, , ppm: 8.87
d (1H, J 4.7 Hz), 8.20 d (1H, J 8.8 Hz), 8.06 d (1H,
J 2.1 Hz), 7.92 d.d (1H, J 8.8, 2.1 Hz), 7.52 m (2H),
7.42 m (2H), 7.31 (3H), 6.95 m (2H), 3.81 s (3H),
2.44 s (3H).
4,6-Bis(4-chlorophenyl)quinoline was prepared
from 50 mg of 6-iodo-4-chloroquinoline and 62.1 mg
of 4-chlorophenylboric acid in 60.0 mg (99%) yield.
(99%). mp 116 C. 1H NMR spectrum, , ppm:
8.92 d (1H, J 4.4 Hz), 8.24 d (1H, J 8.8 Hz), 7.96 d
(1H, J 2.1 Hz), 7.91 d.d (1H, J 8.8, 2.1 Hz), 7.48
(4H), 7.43m(2H), 7.36m(2H), 7.29 d (1H, J 4.4 Hz).
Found, %: C 72.26; H 3.90; N 3.86. C21H13Cl2N.
Calculated, %: C 72.01; H 3.74; N 4.00.
1
Successive cross-coupling of 6-iodo-4-chloro-
quinoline and 6-bromo-4-chloroquinoline with
arylboric acids catalyzed by palladium complexes.
In a flask equipped with a reflux condenser was mix-
ed in an argon atmosphere 0.173 mmol of 6-halo-4-
chloroquinoline, 0.173 mmol of the first arylboric
acid, 143.2 mg (1.04 mmol) of K2CO3, 3.5 mol of
palladium catalyst, 1.5 ml of dioxane, and 0.5 ml of
water. The reaction mixture was heated at reflux till
complete consumption of 6-halo-4-chloroquinoline
(TLC monitoring), then 0.225 mmol of the second
arylboric acid was added, and the heating was
continued till the full completion of the reaction (TLC
monitoring). Then the reaction mixture was cooled,
diluted with dichloromethane, filtered through a 3 cm
bed of silica gel, the solvents were evaporated at
reduced pressure. The product was purified by
column chromatography on silica gel, eluent petrol-
eum ether ethyl ether (1: 1).
Cross-coupling of 4,6-dichloroquinoline with
4-tolylboric acid catalyzed with nickel complexes.
In a flask equipped with a reflux condenser was mix-
ed in an argon atmosphere 50 mg (0.254 mmol) of
4,6-dichloroquinoline, 34.5 mg (0.254) mmol of the
4-tolylboric acid, 164 mg (0.762 mmol) of K3PO4,
12.7 mol (6.5 mg, 5 mol%) of NiCl2(dppm), and
2 ml of dioxane. The reaction mixture was heated at
reflux for 1 h, then cooled, diluted with dichloro-
methane, filtered through a 3 cm bed of silica gel, the
solvents were evaporated at reduced pressure. The
product was purified by column chromatography on
silica gel, eluent petroleum ether ethyl ether (1: 1).
4-(4-Tolyl)-6-chloroquinoline. Yield 38.4 mg
1
(60%). Yield 69% according to H NMR spectrum.
1
mp 125 C. H NMR spectrum, , ppm: 8.89 d (1H,
4-(4-Tolyl)-6-(4-anisyl)quinoline was prepared
from 50 mg of 6-iodo-4-chloroquinoline in 54.0 mg
(96%) yield, or from 41.7 mg of 6-bromo-4-chloro-
quinoline in 54.0 mg (96%) yield. mp 127 C.
1H NMR spectrum, , ppm: 8.87 d (1H, J 4.7 Hz),
8.20 d (1H, J 8.8 Hz), 8.06 d (1H, J 2.1 Hz),
7.92 d.d (1H, J 8.8, 2.1 Hz), 7.52 m (2H), 7.42 m
(2H), 7.31 (3H), 6.95 m (2H), 3.81 s (3H), 2.44 s
(3H). Found, %: C 84.56; H 9.67; N 4.19. C23H19N.
Calculated, %: C 84.89; H 9.89; N 4.30.
J 4.4 Hz), 8.09 d (1H, J 9.1 Hz), 7.89 d (1H,
J 2.4 Hz), 7.63 d.d (1H, J 9.1, 2.4 Hz), 7.35m (4H),
7.33 d (1H, J 4.4 Hz), 2.46 s (3H). Found, %:
C 75.24; H 4.23; N 5.49. C16H12ClN. Calculated,
%: C 75.74; H 4.77; N 5.52.
Successive cross-coupling of 4,6-dichloroquino-
line with arylboric acids catalyzed by nickel
complexes. The reaction was carried out in keeping
with the general procedure of palladium-catalyzed
cross-coupling of 6-iodo-4-chloroquinoline in an-
hydrous dioxane using K3PO4 instead of K2CO3 and
NiCl2(dppm) (5 mol%) as catalyst. After completion
of the first reaction stage (TLC monitoring) into the
4,6-Bis(4-tolyl)quinoline was prepared from
50.0 mg of 6-iodo-4-chloroquinoline in 51.1 mg
1
(98%) yield. mp 124 C. H NMR spectrum, , ppm:
8.86 d (1H, J 4.7 Hz), 8.19 d (1H, J 8.8 Hz), 8.09 d
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 11 2003

SUCCESSIVE REPLACEMENT OF HALOGEN ATOMS
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1667
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11. Gershon, H., Clarke, D.D., and Gershon, M.,
Monatsh. Chem., 1994, vol. 125, p. 51.
4-(4-Tolyl)-6-(4-anisyl)quinoline was prepared
from 50 mg of 4,6-dichloroquinoline in 84 mg (78%)
1
yield. mp 127 C. H NMR spectrum, , ppm: 8.87 d
(1H, J 4.7 Hz), 8.20 d (1H, J 8.8 Hz), 8.06 d (1H,
J 2.1 Hz), 7.92 d.d (1H, J 8.8, 2.1 Hz), 7.52 m (2H),
7.42 m (2H), 7.31 (3H), 6.95 m (2H), 3.81 s (3H),
2.44 s (3H).
The study was carried out under financial support
of the Russian Foundation for Basic Research (grant
no. 01-03-33144).
12. Hino, K., Kawashima, K., Oka, M., Nagai, Y.,
Uno, H., and Matsumoto, M., J. Chem. Farm. Bull.,
1989, vol. 37, p. 110.
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