Palladium-catalyzed intramolecular N-arylation of heteroarenes: A novel and efficient route to benzimidazo[1,2-a]quinolines

Article abstract of DOI:10.1021/jo0522411

An efficient new route for the synthesis of benzimidazo-1,2-a]quinolines has been developed via the palladium-catalyzed intramolecular Buchwald-Harwtig aryl amination of newly synthesized 2-(2′-bromoanilino)quinolines.

Full text of DOI:10.1021/jo0522411

SCHEME 1
Palladium-Catalyzed Intramolecular N-Arylation
of Heteroarenes: A Novel and Efficient Route to
Benzimidazo[1,2-a]quinolines
C. Venkatesh, G. S. M. Sundaram, H. Ila,* and H. Junjappa
Department of Chemistry, Indian Institute of Technology,
Kanpur-208016, India
hila@iitk.ac.in
routes1,6-10 available for the synthesis of pyrido[1,2-a]benz-
imidazole and its condensed analogues, one of the approaches
involves formation of a five-membered heterocyclic ring via
intramolecular ring closure of an intermediate of the type 1
(usually a radical) containing an aryl group attached to a six-
membered heteroaromatic ring via nitrogen (Scheme 1). This
approach usually involves thermal or photochemical cyclization
and often affords systems such as 2 in low yields.11-13 Besides,
the precursors for the intermediate 1 (often a benzotriazole
derivative) are usually synthesized starting from o-chloro-
nitrobenzenes14 which further narrows the scope for diversifica-
tion in these fused target systems. During the course of our
continued interest in the development of new general synthetic
routes for substituted and condensed heteroaromatics,7,15-17 we
became interested in examining the ring closure of the systems
of the type 3 via palladium-catalyzed intramolecular N-arylation
of heteroarenes, analogous to the Buchwald-Hartwig aryl
ReceiVed October 27, 2005
An efficient new route for the synthesis of benzimidazo-
[1,2-a]quinolines has been developed via the palladium-
catalyzed intramolecular Buchwald-Harwtig aryl amination
of newly synthesized 2-(2′-bromoanilino)quinolines.
(7) Panda, K.; Suresh, J. R.; Ila, H.; Junjappa, H. J. Org. Chem. 2003,
68, 3498.
(8) (a) Popov, I. I. Khim. Geterotsikl. Soedin. 1989, 1695. (b) Kuzmenko,
V. V.; Komissarov, V. N.; Simonov, A. M. Khim. Geterotsikl. Soedin. 1981,
1497. (c) Bergerat, I.; Galous, H.; Rabaron, A.; Combet-Farnoux, C.;
Miocque, M. J. Heterocycl. Chem. 1985, 22, 369. (d) Toth, G.; Kovacs,
A.; Balogh, M.; Hermecz, J. J. Heterocycl. Chem. 1991, 28, 497.
(9) (a) Cooper, G.; Irwin, W. J. J. Chem. Soc., Perkin Trans. 1, 1976,
75. (b) Grimshaw, J.; Trocha-Grimshaw, J. Tetrahedron Lett. 1975, 2601.
(c) Benincori, T.; Sannicolo, F. J. Heterocycl. Chem. 1988, 25, 1029. (d)
Tkach, I. I.; Luk’yanets, E. A. Khim. Geterosikl. Soedin. 1992, 1053; Chem.
Abstr. 1993, 119, 28058z. (e) Knolker, H.-J.; Boese, R.; Hitzemann, R.
Chem. Ber. 1990, 123, 327. (f) Alajarin, M.; Vidal, A.; Tovar, F.
Tetrahedron Lett. 2000, 41, 7029. (g) Ohta, S.; Yuasa, T.; Narita, Y.;
Kawasaki, I.; Minamii, E.; Yamashita, M. Heterocycles 1991, 32, 1923.
(h) Alajarin, M.; Vidal, A.; Tovar, F.; Conesa, C. Tetrahedron Lett. 1999,
40, 6127.
(10) Review: Tennant, G. In The Chemistry of Heterocyclic Compounds;
Weissberger, A., Taylor, E. C., Eds.; Interscience Publishers: NewYork,
1980; Vol. 40, Part 2, p 257.
(11) (a) Baklanov, M. V.; Frolov, A. N. Zh. Org. Khim. 1991, 27, 638.
(b) Prostakov, N. S.; Varlamov, A. V.; Shendrik, I. V.; Anisimov, B. N.;
Krapivko, A. P.; Lavani-Edogiaverie, S.; Fomichev, A. A. Khim. Geterotsikl.
Soedin. 1983, 1384; Chem. Abstr. 1984, 100, 51481y.
Substituted benzimidazoles and their azino fused variants such
as pyrido[1,2-a]benzimidazoles have attracted considerable
attention from medicinal and synthetic organic chemists because
of the wide range of biological activities1 (anxiolytic,2 antifungal/
antibacterial,3 antineoplastic,4 anticancer,5 DNA intercalator6)
displayed by this class of compounds. On the other hand, the
corresponding benzoannulated analogues such as benzimidazo-
[1,2-a]quinolines, benzimidazo[2,1-a]isoquinolines, and benz-
imidazo[1,2-f]phenanthridines have remained unexplored for
their biological activity which may be because of the lack of
general synthetic methods for these classes of heteroaromatics
from easily accessible precursors. A few of the pyrido[1,2-a]-
and pyridazino[1,6-a]benzoimidazolium salts with fused aro-
matic rings to the cationic heterocycles are reported to exhibit
enhanced DNA intercalation properties.6,7 Among the various
* Fax: 91-0512-2597436; 91-0512-2590260.
(1) Katritzky, A. R.; Tymoshenko, D. O.; Monteux, D.; Vvedensky, V.;
Nikonov, G.; Cooper, C. B.; Deshpande, M. J. Org. Chem. 2000, 65, 8059
and references therein.
(12) Hubert, A. J. J. Chem. Soc. C 1969, 1334.
(13) (a) Pipe, D. F.; Rees, C. W. J. Chem. Soc., Chem. Commun. 1982,
520. (b) Houghton, P. G.; Pipe, D. F.; Rees, C. W. J. Chem. Soc., Perkin
Trans. 1 1985, 1471.
(14) (a) Anderson, D. J.; Taylor, A. J. J. Heterocycl. Chem. 1986, 23,
1091. (b) Morgan, G. T.; Stewart, J. Chem. Ind. 1937, 670. (c) Stephensop,
L.; Warburton, W. K. J. Chem. Soc. C 1970, 1355.
(2) (a) Maryanoff, B. E.; McComsey, D. F.; Ho, W.; Shank, R. P.;
Dubinsky, B. Bioorg. Med. Chem. Lett. 1996, 6, 333. (b) Reitz, A. B.;
Gauthier, D. A.; Ho, W.; Maryanoff, B. E. Tetrahedron 2000, 56, 8809
and references therein.
(3) (a) Rida, S. M.; Soliman, F. S. G.; Badawey, E.; Kappe, T. J.
Heterocycl. Chem. 1988, 25, 1725. (b) Rida, S. M.; Soliman, F. S. G.;
Badawey, E.; El-Ghazzawi, E.; Kader, O.; Kappe, T. J. Heterocycl. Chem.
1988, 25, 1087.
(4) Badawey, E.; Kappe, T. Eur. J. Med. Chem. 1995, 30, 327.
(5) El-Hawash, S. A. M.; Badawey, E.; Kappe, T. Pharmazie 1999, 54,
341.
(6) Pastor, J.; Siro, J. G.; Garcio-Navio, J. L.; Vaquero, J. J.; Alvarez-
Builla, J.; Gago, F.; de Pascual-Teresa, B.; Pastor, M.; Melia Rodrigo, M.
J. Org. Chem. 1997, 62, 5476 and references therein.
(15) Review: Ila, H.; Junjappa, H.; Mohanta, P. K. Progress in
Heterocyclic Chemistry; Gribble, G. W., Gilchrist, T. L., Eds.; Pergamon:
New York, 2001; Vol. 13, Chapter 1, p 1.
(16) (a) Venkatesh, C.; Singh, B.; Mahata, P. K.; Ila, H.; Junjappa, H.
Org. Lett. 2005, 7, 2169. (b) Mahata, P. K.; Venkatesh, C.; Syam Kumar,
U. K.; Ila, H.; Junjappa, H. J. Org. Chem. 2003, 68, 3966.
(17) (a) Panda, K.; Venkatesh, C.; Ila, H.; Junjappa, H. Eur. J. Org.
Chem. 2005, 2045. (b) Sundaram, G. S. M.; Venkatesh, C.; Syamkumar,
U. K.; Ila, H.; Junjappa, H. J. Org. Chem. 2004, 69, 5760. (c) Peruncher-
alathan, S.; Khan, T. A.; Ila, H.; Junjappa, H. Tetrahedron 2004, 60, 3457.
10.1021/jo0522411 CCC: $33.50 © 2006 American Chemical Society
Published on Web 01/04/2006
1280
J. Org. Chem. 2006, 71, 1280-1283

TABLE 1. Palladium-Catalyzed Intramolecular N-Arylation:
Catalyst, Ligand, Temperature, and Solvent Effects on the
Cyclization of 7a to 8a
SCHEME 2
mol
%
mol
%
%
entry catalyst
1
L
base
temp solvent yielda
K2CO3
K2CO3
K2CO3
K2CO3
130 °C DMF
130 °C DMF
130 °C DME
130 °C CH3CN
130 °C toluene
130 °C DMF
0
57
50
45
48
52
55
38
33
51
75
43
0
2
3
4
5
6
7
8
9
Pd(OAc)2 10 PPh3
Pd(OAc)2 10 PPh3
Pd(OAc)2 10 PPh3
Pd(OAc)2 10 P(o-tol)3 12.5 K2CO3
Pd(OAc)2 10 P(o-tol)3 12.5 K2CO3
40
40
40
Pd(OAc)2 10 PPh3
40
40
NaHCO3 130 °C DMFb
K2CO3 130 °C CH3CN
PdCl2
PdCl2
10 PPh3
10 dppp
10 Pd2(dba)3 10 PPh3
11 Pd(PPh3)4 10
12 Pd(PPh3)4 10
13 Pd(PPh3)4 10
12.5 Cs2CO3 130 °C DMF
40
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
130 °C DMF
130 °C DMF
80 °C DMF
rt
DMF
14 Pd(PPh3)4
5
130 °C DMF
40
a Isolated yields. b The indoloquinoline 9a (25%) was formed along with
8a.
amination.23 A recent report by Batey for the synthesis of
2-aminobenzimidazoles18 via intramolecular C-N bond forma-
tion between an aryl halide and a guanidine moiety in the
presence of a palladium (Buchwald-Hartwig coupling)19,20 or
copper catalyst further prompted us to attempt this type of
cyclization on 2-(2-bromoanilino)quinolines 7 with a view to
develop a novel approach for the synthesis of benzimidazo-
[1,2-a]quinolines. We have successfully achieved this goal and
report herein the results of our investigation.
The requisite cyclization precursors, i.e., 2-(2-bromoanilino)-
quinolines 7a-j, are readily synthesized by the methods
developed in our laboratory (Scheme 2).21 Thus, the substituted
2-(methylthio)quinolines 4a,b were obtained by the reported
procedure involving acid-induced cyclocondensation of anilines
with bis(methylthio)acrolein,21 whereas the 4-methyl-2-(meth-
ylthio)quinolines 4c,d were prepared in high yields by a
Combe’s-type cyclization22 of the respective R-acetyl-N,S-
anilinoacetals in the presence of PPA. The oxidation of
2-(methylthio)quinolines 4a-d with m-CPBA furnished the
respective 2-(methylsulfonyl)quinolines 5a-d (70-96%) which
underwent facile displacement of the methylsulfonyl group with
various 2-bromoanilines 6 under thermal conditions, affording
the desired 2-(2-bromoanilino)quinolines 7a-j in overall high
yields (Scheme 2).
temperatures, and bases were undertaken (Table 1). Intramo-
lecular cyclization of 7a using Pd(OAc)2 (10 mol %) and PPh3
(40 mol %) with base-like K2CO3 was first investigated with
various solvents (DMF, DME, and CH3CN) which gave only
moderate yields of benzimidazo[1,2-a]quinoline 8a (Table 1,
entries 2-4). Use of the tris(o-tolyl)phosphine ligand also led
to only a moderate conversion at 130 °C (Table 1, entries 5
and 6). Interestingly, the use of sodium bicarbonate as base in
DMF gave 8a (55%) along with the formation of indolo[2,3-
b]quinoline17b 9a (25%) via intramolecular Pd-catalyzed C-
arylation on the 3-position of the quinoline ring of 7a (Table 1,
entry 7). Use of PdCl2 or Pd2(dba)3 also resulted in only lower
conversion to 8a (Table 1, entries 8-10). On the other hand,
use of Pd(PPh3)4 (10 mol %) in DMF with K2CO3 as base
showed maximum conversion of 7a to 8a (75%) at 130 °C
(Table 1, entry 11). Reaction at a lower temperature with a Pd-
(PPh3)4 catalyst resulted in a decreased yield of 8a (entry 12)
or failure of the reaction (entry 13), as did lowering the amount
of Pd(PPh3)4 catalyst (Table 1, entry 14).
The intramolecular, heteroarene N-arylation was applied to
various substituted 2-(2-bromoanilino)quinolines 7b-j using
optimized reaction conditions with the goal to examine the scope
and generality of this novel cyclization reaction. In general,
excellent yields (70-93%) of substituted benzimidazo[1,2-a]-
quinolines 8b-j are obtained from the substrates 7b-j bearing
various substitutents (methyl, isopropyl, or methoxy groups) in
different positions of either the quinoline ring or the anilino
moiety (Table 2).
The 2-(2-bromoanilino)quinoline 7a was chosen as a repre-
sentative substrate for the synthesis of 8a, and optimization
studies with various palladium sources, ligands, solvents,
(18) Evindar, G.; Batey, R. A. Org. Lett. 2003, 5, 133.
(19) Reviews: (a) Muci, A. R.; Buchwald, S. L. Top. Curr. Chem. 2002,
219, 131. (b) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L.
Acc. Chem. Res. 1998, 31, 805. (c) Hartwig, J. F. Acc. Chem. Res. 1998,
31, 852.
(20) Recent papers: (a) Ferreira, I. C. F. R.; Queiroz, M.-J. R. P.; Kirsch,
G. Tetrahedron 2003, 59, 975. (b) Jonckers, T. H. M.; Maes, B. U. W.;
Lemiere, G. L. F.; Rombouts, G.; Pieters, L.; Haemers, A.; Dommisse, R.
A. Synlett 2003, 615. (c) Bedford, R. B.; Cazin, C. S. J. Chem. Commun.
2002, 2310.
(21) Panda, K.; Siddiqui, I.; Mahata, P. K.; Ila, H.; Junjappa, H. Synlett
2004, 449.
(22) Jones, G. In ComprehensiVe Heterocyclic Chemistry II; Katritzky,
A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon Press: Oxford, 1996;
Vol. 5, Chapter 5.05, p 167.
The probable mechanism for the formation of benzimidazo-
[1,2-a]quinolines 8a-j from 7a-j under palladium catalysis is
shown in Scheme 3. The intermediate 10 formed by the
oxidative addition of palladium(0) to 7 undergoes intramolecular
nucleophilic attack by basic quinoline nitrogen with elimination
J. Org. Chem, Vol. 71, No. 3, 2006 1281

TABLE 2. Synthesis of Benzimidazo[1,2-a]quinolines 8
Experimental Section
General. 1H NMR (400 MHz) and 13C NMR (100 MHz) spectra
were recorded in CDCl3. TMS was used as an internal reference.
Melting points are uncorrected. Chromatographic purification was
conducted by column chromatography using 100-200 mesh silica
gel obtained from a commercial supplier. DMF and CH2Cl2 were
distilled over CaH2 and stored over molecular sieves. THF and
toluene were distilled over sodium/benzophenone prior to use.
n-BuLi (1.6 M solution in hexane) and substituted 2-bromoanilines
were purchased from standard firms and used directly. m-CPBA
(50-55% suspension in water) was diluted with CH2Cl2 and dried
over anhydrous Na2SO4. Pd(PPh3)4 was freshly prepared according
to the reported procedure.26a All the known21 (4a-c) and unknown
quinoline (4d) was prepared according to our previously reported
method.
General Procedure for the Synthesis of 2-(2′-Bromoanilino)-
quinolines 7a-j. A mixture of 2-(methylsulfonyl)quinolines 5a-d
(2.0 mmol) and the corresponding 2-bromoanilines (8.0 mmol) was
heated at 160-170 °C in a sealed tube for 5-6 h (monitored by
TLC) with constant stirring. It was then cooled, diluted with CHCl3
(25 mL), and washed with water (2 × 25 mL) followed by brine
(25 mL). The organic layer was dried over anhydrous Na2SO4, and
the solvent was evaporated under reduced pressure to afford the
crude products 7a-j, which were purified by column chromatog-
raphy over silica gel using hexanes-EtOAc as eluent.
% yielda
entry
8
R1
R2
R3
R4
8
1
2
3
4
5
6
7
8
9
8b
8c
8d
8e
8f
8g
8h
8i
H
H
H
OMe
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
Me
Me
Me
Me
Me
Me
i-Pr
OMe
H
70
82
88
91
93
88
87
92
92
H
Me
i-Pr
OMe
Me
8j
a Isolated yields.
SCHEME 3
2-(2′-Bromoanilino)quinoline (7a): yield 75% (0.45 g); colorless
crystals; mp 69-70 °C; Rf 0.82 (10:1 hexanes/EtOAc); IR (KBr)
3388, 1621, 1525, 1316, 1019, 808, 749 cm-1; 1H NMR (400 MHz,
CDCl3) δ 6.90 (dt, J ) 7.70, 1.72 Hz, 1H), 6.94 (d, J ) 9.00 Hz,
1H), 7.12 (brs, 1H), 7.33 (dd, J ) 8.04, 8.42 Hz, 2H), 7.57 (dd, J
) 8.06, 1.48 Hz, 1H), 7.60 (dt, J ) 7.82, 1.48 Hz, 1H), 7.65 (dd,
J ) 8.06, 1.24 Hz, 1H), 7.83 (d, J ) 8.56 Hz, 1H), 7.94 (d, J )
9.04 Hz, 1H), 8.62 (dd, J ) 8.18, 1.68 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 112.8, 113.7, 120.4, 123.1, 123.6, 124.3, 127.0,
127.3, 128.1, 129.8, 132.5, 137.7, 138.0, 147.3, 153.2; MS (m/z,
%) 299 (M + 1, 100), 301 (M + 1, 80). Anal. Calcd for C15H11N2-
Br (299.17): C, 60.22; H, 3.71; N, 9.36. Found: C, 60.11; H, 3.84;
N, 9.48.
2-(2′-Bromoanilino)-7-methoxyquinoline (7e): yield 75% (0.49
g); colorless crystals; mp 108-109 °C; Rf 0.75 (10:1 hexanes-
EtOAc); IR (KBr) 3402, 2363, 1625, 1593, 1526, 1451, 1413, 1370,
1312, 1215, 1022, 826, 752 cm-1; 1H NMR (400 MHz, CDCl3) δ
3.86 (s, 3H), 6.74 (d, J ) 8.80 Hz, 1H), 6.85 (dt, J ) 7.58, 1.48
Hz, 1H), 6.91 (dd, J ) 8.76, 2.44 Hz, 1H), 7.12 (d, J ) 2.44 Hz,
1H), 7.28 (dt, J ) 8.54, 1.44 Hz, 1H), 7.47 (d, J ) 8.80 Hz, 1H),
7.51 (dd, J ) 7.92, 1.24 Hz, 1H), 7.81 (d, J ) 8.80 Hz, 1H), 8.41
(dd, J ) 7.68, 1.20 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 55.4,
105.8, 109.9, 114.1, 116.0, 119.0, 120.8, 123.4, 128.1, 128.4, 132.6,
137.6, 137.9, 148.6, 153.7, 161.3; MS (m/z, %) 329 (M+, 75), 331
(M + 1, 73). Anal. Calcd for C16H13N2OBr (329.19): C, 58.38; H,
3.98; N, 8.51. Found: C, 58.14; H, 3.76; N, 8.69.
of HBr to give six-membered palladacycle intermediate 11
which subsequently yields the benzimidazo[1,2-a]quinolines
8a-j via reductive elimination accompanied by N-C bond
formation.
In conclusion, we have developed a new high-yielding route
for benzimidazo[1,2-a]quinolines via palladium-catalyzed in-
tramolecular heterocyclization of readily accessible 2-(2-bro-
moanilino)quinolines. The overall process involves Buchwald-
Hartwig intramolecular aryl amination in which a heteroarene
ring nitrogen participates in N-C bond formation.23,24 We are
currently investigating the construction of other biologically
important azino-fused heteroaromatics such as pyrido[1,2-a]-
benzimidazoles, benzothiazoles, benzimidazo[2,1-a]isoquino-
lines, benzimidazo[1,2-f]phenanthridines, imidazo[1,2-a]py-
ridines, and other related ring systems25 following this approach
with a hope to expand the scope of this methodology.
2-(2′-Bromo-4′-methylanilino)-4,6-dimethylquinoline (7j): yield
71% (0.48 g); colorless crystals; mp 105-106 °C; Rf 0.78 (10:1
hexanes-EtOAc); IR (CH2Cl2) 3408, 2923, 1604, 1523, 1264, 739
1
cm-1; H NMR (400 MHz, CDCl3) δ 2.30 (s, 3H), 2.48 (s, 3H),
2.55 (s, 3H), 6.73 (s, 1H), 7.13 (dd, J ) 8.30, 1.68 Hz, 1H), 7.39
(d, J ) 1.20 Hz, 1H), 7.41 (dd, J ) 8.56, 1.96 Hz, 1H), 7.56 (s,
1H), 7.71 (d, J ) 8.52 Hz, 1H), 8.28 (d, J ) 8.28 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 18.8, 20.4, 21.5, 112.5, 114.2, 121.0,
122.8, 124.3, 126.8, 128.7, 131.4, 132.7, 132.8, 133.2, 135.5, 145.1,
145.3, 152.8; MS (m/z, %) 341 (M + 1, 100), 343 (M + 1, 96).
(23) Only one report has recently appeared for this kind of cyclization
involving Pd-catalyzed one-pot tandem inter- and intramolecular Buchwald-
Hartwig amination of 2-chloro-3-iodopyridine with aminoazines and diazines
to give dipyrido[1,2-a:3′,2′-d]imidazole and its benzo and aza analogues:
Loones, K. T. J.; Maes, B. U. W.; Dommisse, R. A.; Lemiere, G. L. F.
Chem. Commun. 2004, 2466.
(25) Chezal, J. M.; Moreau, E.; Delmas, G.; Gueiffier, A.; Blache, Y.;
Grassy, G.; Lartigue, C.; Chavignon, O.; Teulade, J. C. J. Org. Chem. 2001,
66, 6576.
(26) (a) Coulson, D. R. Inorg. Synth. 1972, 13, 121. (b) Darnault, G.;
Saquet, M.; Thuillier, A. Chim. Ind. 1983, 10, 391. (c) Taylor, E. C.;
Chittenden, M. L.; Martin, S. F. Heterocycles 1973, 1, 59.
(24) Iwaki, T.; Yashuhara, A.; Sakamoto, T. J. Chem. Soc., Perkin Trans.
1 1999, 1505.
1282 J. Org. Chem., Vol. 71, No. 3, 2006

Anal. Calcd for C18H17N2Br (341.25): C, 63.35; H, 5.02; N, 8.21.
Found: C, 63.14; H, 5.21; N, 8.43.
(218.25): C, 82.55; H, 4.62; N, 12.84. Found: C, 82.41; H, 4.80;
N, 12.70.
2-Methoxybenzo[4,5]imidazo[1,2-a]quinoline (8e): yield 91%
(0.45 g); colorless crystals; mp 142-143 °C; Rf 0.25 (3:1 hexanes-
EtOAc); IR (KBr) 2838, 1623, 1543, 1486, 1452, 1387, 1328, 1277,
1257, 1236, 1169, 1143, 1024, 819, 741 cm-1; 1H NMR (400 MHz,
CDCl3) δ 4.01 (s, 3H), 7.04 (dd, J ) 8.68, 2.44 Hz, 1H), 7.44 (d,
J ) 7.08 Hz, 1H), 7.47 (t, J ) 8.28 Hz, 1H), 7.52 (t, J ) 7.32 Hz,
1H), 7.62 (d, J ) 9.52 Hz, 1H), 7.71 (d, J ) 8.56 Hz, 1H), 7.97
(d, J ) 2.20 Hz, 1H), 7.99 (d, J ) 9.28 Hz, 1H), 8.29 (d, J ) 8.04
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 55.8, 100.2, 111.6, 113.8,
114.3, 117.3, 120.0, 122.4, 124.6, 130.5, 130.7, 131.4, 136.7, 148.3,
161.0; MS (m/z, %) 249 (M + 1, 100). Anal. Calcd for C16H12N2O
(248.28): C, 77.40; H, 4.87; N, 11.28. Found: C, 77.27; H, 4.71;
N, 11.12.
General Procedure for the Palladium-Catalyzed Intramo-
lecular N-C Coupling: Synthesis of Benzimidazo[1,2-a]quino-
lines 8a-j. A mixture of 2-(2′-bromoanilino)quinolines 7a-j (2.0
mmol), freshly prepared Pd(PPh3)4 (10 mol %), and anhydrous K2-
CO3 (4.4 mmol) in 5 mL of DMF was heated at 130-140 °C in a
pressure tube for 10-12 h with constant stirring. The reaction
mixture was cooled and filtered, and the filtrate was diluted with
CHCl3 (25 mL) and washed with water (2 × 25 mL) followed by
brine (20 mL). The organic layer was dried over anhydrous Na2-
SO4 and concentrated in a vacuum to give crude benzimidazo[1,2-
a]quinolines 8a-j which were purified by silica gel column
chromatography using hexanes-EtOAc (3:1) as eluent.
Benzo[4,5]imidazo[1,2-a]quinoline (8a):9a yield 75% (0.33 g);
colorless crystals; mp 98-99 °C; Rf 0.30 (4:1 hexanes-EtOAc);
Acknowledgment. C.V. and G.S.M.S. thank CSIR, New
Delhi, and IIT Kanpur, respectively, for senior research fel-
lowships. Financial assistance under the DST project is also
acknowledged.
IR (KBr) 2364, 1610, 1539, 1451, 1392, 1329, 1017, 813, 739 cm-1
;
1H NMR (400 MHz, CDCl3) δ 7.40-7.47 (m, 2H), 7.51 (t, J )
7.60 Hz, 1H), 7.57 (d, J ) 9.52 Hz, 1H), 7.63 (d, J ) 9.28 Hz,
1H), 7.69 (t, J ) 7.56 Hz, 1H), 7.77 (d, J ) 7.32 Hz, 1H), 7.99 (d,
J ) 8.08 Hz, 1H), 8.33 (d, J ) 8.08 Hz, 1H), 8.50 (d, J ) 8.08
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 114.0, 115.2, 117.4, 120.2,
122.7, 123.3, 124.2, 124.5, 129.5, 129.7, 130.7, 131.4, 135.5, 144.1,
147.9; MS (m/z, %) 219 (M + 1, 100). Anal. Calcd for C15H10N2
Supporting Information Available: 1H and 13C NMR spectral
data of all compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
JO0522411
J. Org. Chem, Vol. 71, No. 3, 2006 1283