LiBr-catalyzed simple and efficient synthesis of some novel substituted quinolines via Friedlander heteroannulation reaction

Article abstract of DOI:10.1080/00397910701575871

A simple and efficient method has been developed for the condensation of o-aminoaryl ketones with α-methylene ketones in the presence of catalytic amounts of LiBr to afford the corresponding fused cyclic quinolines in high yield using the Friedlander hete

Full text of DOI:10.1080/00397910701575871

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LiBr‐Catalyzed Simple and Efficient Synthesis
of Some Novel Substituted Quinolines via
Friedlander Heteroannulation Reaction
M. A. Päsha a , K. A. Mahammed a & V. P. Jayäshankara a
a Department of Studies in Chemistry, Central College Campus, Bangalore
University, Bangalore, India
Published online: 14 Dec 2007.
To cite this article: M. A. Päsha , K. A. Mahammed & V. P. Jayäshankara (2007) LiBr‐Catalyzed Simple and
Efficient Synthesis of Some Novel Substituted Quinolines via Friedlander Heteroannulation Reaction, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:24,
4319-4326, DOI: 10.1080/00397910701575871
To link to this article: http://dx.doi.org/10.1080/00397910701575871
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Synthetic Communicationsw, 37: 4319–4326, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701575871
LiBr-Catalyzed Simple and Efficient
Synthesis of Some Novel Substituted
Quinolines via Friedlander
Heteroannulation Reaction
¨
¨
M. A. Pasha, K. A. Mahammed, and V. P. Jayashankara
Department of Studies in Chemistry, Central College Campus, Bangalore
University, Bangalore, India
Abstract: A simple and efficient method has been developed for the condensation of
o-aminoaryl ketones with a-methylene ketones in the presence of catalytic amounts
of LiBr to afford the corresponding fused cyclic quinolines in high yield using the
Friedlander heteroannulation reaction. The reaction works at ambient temperature to
give the products within 1.5–2 h.
Keywords: o-aminoaryl ketones, Friedlander heteroannulation, a-methylene ketones,
quinolines
INTRODUCTION
The fused polycyclic quinoline moiety is a ubiquitous subunit in many natural
products with remarkable pharmacological activity such as antimalarial, anti-
inflammatory, anti-asthmatic, antibacterial, and antihypertensive activi-
ties.[1,2] Tyrosine kinase PDGF-RTK inhibiting properties[3] continue to
spur synthetic efforts.[4] In addition, quinolines are valuable synthons for
the preparation of nano-meso structures and polymers that combine
enhanced electronic, optoelectronic, or nonlinear optical properties with
excellent mechanical properties.[5] A number of catalysts have been
Received in India May 10, 2007
Address correspondence to M. A. Pasha, Department of Studies in Chemistry, Central
¨
College Campus, Bangalore University, Bangalore, India. E-mail: m_af_pasha@yahoo.
co.in
4319

¨ ¨
M. A. Pasha, K. A. Mahammed, and V. P. Jayashankara
4320
Scheme 1.
.
developed for the synthesis of quinolines such as AuCl3 3H2O, FeCl3, ZnCl2,
.
Mg(ClO4)2, SnCl2, Bi(OTf)3, Sc(OTf)3, Y(OTf)3, NaAuCl4 2H2O, silver
phosphotungstate,[6] diphosgene/acetonitrile,[7] and ZnCl2/triethylamine,[8]
and different methodologies have been used for the Friedlander reaction.[9]
Ruthenium, palladium, and iron complexes have been shown to affect the
formation of 2,3-disubstiuted quinolines from nitrobenzene and aldehydes
or alcohols in the presence of CO.[10] Aniline was shown to undergo N-hetero-
cyclization to generate quinolines with aliphatic aldehydes in the presence of
transition-metal complexes.[11] The Friedlander reaction is also effected in the
absence of catalysts by refluxing an aqueous or alcoholic solution at tempera-
tures ranging from 150 to 2208C.[12]
Herein we report the synthesis of some known and novel quinolines and
cyclic quinolines using LiBr as a catalyst. Accordingly, a mixture of 2-amino-
benzophenone (1), tetrahydro-4H-pyran-4-one (2), and catalytic amount of
LiBr in acetonitrile were stirred at 508C to get 10-phenyl-3,4-dihydro-1H-
pyrano [4,3-b] quinoline (3b) in 94% yield (Scheme 1). We have synthesized
five novel compounds using various type of heterocyclic ketones and dicarbo-
nyl ketones such as tetrahydro-4H-pyran-4-one, N-methyl-4-pyperidone,
indane-1,3-one, and benzyl acetoacetate. These ketones smoothly react with
o-aminobenzophenone to give corresponding products in excellent yields.
Other cyclic ketones such cyclopentanone and cyclohexanone also
underwent smooth condensation with o-aminoaryl ketones (Scheme 2). The
method is equally effective for both cyclic and acyclic ketones (Table 1);
thus is very useful for the preparation of quinolines from both o-aminobenzo-
phenones and o-aminoacetophenones. All the products were characterized by
1
IR, H, 13C NMR, and mass spectral analysis.
In conclusion, we have developed a rapid and efficient method for the
synthesis of substituted quinolines under ambient conditions.
Scheme 2.

Table 1. LiBr-catalyzed synthesis of 2,3,4-trisubstituted quinolines
Entry
o-Aminoketone (1)
Ketone (2)
Quinolinea (3)
Time (h)
1.5
Yieldb (%)
85
Mp (lit.) (8C)
a
98–100c
b
c
d
e
f
—
—
—
—
—
1.5
1
80
92
82
85
80
135–136c
140 (138)d
82c
1
1
115 (115)d
98 (99–100)d
1
(continued)

Table 1. Continued
Entry
o-Aminoketone (1)
Ketone (2)
Quinolinea (3)
Time (h)
1
Yieldb (%)
78
Mp (lit.) (8C)
g
—
95–96 (96)d
h
i
—
—
1
80
82
144 (147)d
172c
1.5
j
—
1
1
85
84
132 (132–134)d
k
89c
l
—
1.5
90
132 (131)d
aProducts c, e, f, g, h, j, and l are known and compared with the authentic samples (Refs. [9–11]).
bIsolated yields.
1
cNovel compounds a, b, d, i, and k are characterized by IR, H NMR, and GC mass spectral analysis.
dReported melting points.

Substituted Quinolines
EXPERIMENTAL
4323
Melting points were determined on a Bu¨chi melting-point apparatus and are
uncorrected. IR, 1H NMR, 13C NMR, and gas chromatograph-mass spec-
trometer (GC-MS) were recorded on a Nicolet 400D FT-IR spectropho-
tometer, 400-MHz Brucker spectrometer, and Shimadzu GC-MS QP 5050A,
respectively. o-Aminoaryl ketone, ketones, and LiBr were all commercial
products and were used without further purification.
General Procedure for the Preparation of Quinolines
A mixture of the o-aminoaryl ketone (1, 0.5 mmol), a-methylene ketone (2,
1.2 equiv.), and LiBr (5 mol%) in CH3CN (1.0 mL) was stirred at 508C.
After completion of the reaction as indicated by thin-layer chromatography
(TLC), The concentrated reaction mixture is taken into ethyl acetate
(2 ꢀ 10 mL) and washed with a water and brine solution. Evaporation of
the solvent gave the crude product; recrystallization from hexane or by puri-
fication on a silica-gel column afforded pure quinoline.
Spectral Data for Novel Compounds
2-Methyl-10-phenyl 1,2,3,4-Tetrahydrobenzo[b]1,6-napthhydrine (3a)
IR (KBr): 3059, 2950, 2841, 2764, 1584, 1491, 1409, 1362, 1264, 1171, 948,
768 cm21
.
1H NMR (400 MHz, CDCl3): d ¼ 2.41 (s, 3H), 2.87–2.90
(t, J ¼ 4.0 Hz, 2H), 3.35–3.38 (t, J ¼ 4.0 Hz, 2H), 3.48 (s, 2H), 7.25–7.27
(m, 2H), 7.34–7.35 (d, J ¼ 4.0 Hz, 2H), 7.53–7.57 (m, 3H), 7.6–7.65 (m,
1H), 8.03–8.05 (d, J ¼ 8.0 Hz, 1H). 13C NMR (400 MHz, CDCl3): 33.69,
46.07, 52.87, 56.65, 125.9, 125.69, 125.82, 126.4, 128.1, 128.4, 128.7,
128.81, 128.95, 135.93, 145.06, 146.7, 155.72; MS: m/z (%) ¼ 275 (Mþ).
10-Phenyl-3,4-dihydro-1H-pyrano[4,3-b]quinoline (3b)
IR (KBr): 3053, 2976, 2940, 2872, 1590, 1491, 1403, 1238, 1109, 772 cm21
.
1H NMR (400 MHz, CDCl3): d ¼ 3.3–3.4 (t, J ¼ 6.0 Hz, 2H), 4.15–4.18
(t, J ¼ 6.0 Hz, 2H), 4.63 (s, 2H), 7.2–7.41 (m, 2H), 7.4–7.49 (m, 2H),
7.52–7.66 (m, 3H), 7.66–7.7 (t, J ¼ 2.0 Hz, 2H), 8.1 (d, J ¼ 8.0 Hz, 1H).
13C NMR (400 MHz, CDCl3): 33.67, 46.00, 52.87, 56.65, 125.9, 125.69,
125.82, 126.4, 128.2, 128.5, 128.8, 129.83, 128.87, 135.91, 146.08, 147.2,
156.5; MS: m/z (%) ¼ 261.9 (Mþ).

¨ ¨
M. A. Pasha, K. A. Mahammed, and V. P. Jayashankara
4324
Benzyl-2-methyl-4-phenylquinoline-3-carboxylate (3d)
IR (KBr): 3064, 3022, 2955, 1724, 1574, 1486, 1414, 1300, 1238, 1176, 1083,
767 cm21. 1H NMR (400 MHz, CDCl3): d ¼ 2.83 (s, 3H), 5.04 (s, 2H), 7.06–
7.08 (t, J ¼ 4.0 Hz, 1H), 7.27–7.30 (t, J ¼ 8.0 Hz, 3H), 7.31–7.32 (dd,
J ¼ 8.0 Hz, 2H), 7.4 (m, 4H), 7.61–7.63 (d, J ¼ 8.0 Hz, 1H), 7.75–7.79
(t, J ¼ 8.0 Hz, 1H), 8.23 (s, 1H). 13C NMR (400 MHz, CDCl3): 23.62,
67.47, 125.15, 126.54, 126.60, 127.16, 128.07, 128.35, 128.38, 128.48,
128.61, 129.11, 129.33, 130.51, 134.78, 135.40, 146.64, 147.35, 154.54,
168.22, 170.34; MS: m/z (%) ¼ 354.1 (Mþ).
6-Phenyl-7H-indeno[1,2-b]pyridine-7-one (3i)
1
IR (KBr): 3074, 2929, 1621, 1455, 1326, 964, 778, 695 cm21; H NMR
(400 MHz, CDCl3): d ¼ 7.46 (t, J ¼ Hz, 2H), 7.5–7.6 (m, 4H), 7.6–7.7
(t, J ¼ 8.0 Hz, 3H), 7.8–7.84 (t, J ¼ 8.0 Hz, 1H), 8.5 (s, 2H). 13C NMR
(400 MHz, CDCl3): 29.69, 122.82, 123.89, 127.23, 127.82, 128.17, 128.65,
129.04, 129.40, 131.79, 131.93, 132.76, 135.35, 137.58, 162.00; MS: m/z
(%) ¼ 307.9 (Mþ).
Benzyl-2,4-dimethylquinoline-3-carboxylate (3k)
1
IR (KBr): 3069, 2960, 1724, 1569, 1409, 1300, 1238, 1078, 767 cm21. H
NMR (400 MHz, CDCl3): d ¼ 2.25 (s, 3H), 2.69 (s, 3H), 5.49 (s, 2H),
7.27–7.37 (m, 4H), 7.4–7.5 (m, 2H), 7.5–7.58 (t, J ¼ 8.0 Hz, 1H), 7.75–
7.8 (t, J ¼ 8.0 Hz, 1H), 8.0–8.1 (d, J ¼ 8.0 Hz, 1H). 13C NMR (400 MHz,
CDCl3): 15.83, 67.66, 124.03, 125.81, 126.68, 126.97, 128.55, 128.75,
128.83, 135.05, 154.05; MS: m/z (%) ¼ 291.9 (Mþ).
ACKNOWLEDGMENT
¨
K. A. Mahammed and V. P. Jayashankara thank P. N. Arunachalam, senior
scientific manager, Syngene Intel Ltd., India for the encouragement.
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