High-yielding microwave assisted synthesis of quinoline and dihydroquinoline derivatives under solvent-free conditions

Article abstract of DOI:10.3987/COM-06-10668

A mild and efficient solvent-free method has been developed by two different approaches for the synthesis of quinoline and dihydroquinoline derivatives: (i) one-pot reaction of anilines with alkyl vinyl ketones (Skraup reaction) (ii) between various acetophenones and 2-aminoacetophenone (Friedlaender reaction) using stable and effective heterogeneous catalyst potassium dodecatangestocobaltate (25 mol %) (PDTC) under microwave irradiation in high yields.

Full text of DOI:10.3987/COM-06-10668

HETEROCYCLES, Vol. 68, No. 3, 2006
549
HETEROCYCLES, Vol. 68, No. 3, 2006, pp. 549 - 559. © The Japan Institute of Heterocyclic Chemistry
Received, 9th January, 2006, Accepted, 20th February, 2006, Published online, 21st February, 2006. COM-06-10668
HIGH-YIELDING MICROWAVE ASSISTED SYNTHESIS
OF
QUINOLINE
AND
DIHYDROQUINOLINE
DERIVATIVES UNDER SOLVENT-FREE CONDITIONS
D. Subhas Bose* and Racherla Kishore Kumar
Organic Chemistry Division III, Fine Chemicals Laboratory, Indian Institute of
Chemical Technology, Tarnaka, Hyderabad, 500 007, India, Fax: (040)
27160387; E-mail: dsb@iictnet.org; dsb@iict.res.in
Abstract- A mild and efficient solvent-free method has been developed by two
different approaches for the synthesis of quinoline and dihydroquinoline
derivatives: (i) one-pot reaction of anilines with alkyl vinyl ketones (Skraup
reaction) (ii) between various acetophenones and 2-aminoacetophenone
(Friedländer reaction) using stable and effective heterogeneous catalyst
potassium dodecatangestocobaltate (25 mol %) (PDTC) under microwave
irradiation in high yields.
INTRODUCTION
Quinolines and its derivatives display a wide spectrum of biological activities such as antimalarial,
antibacterial, antidiabetic, and anti-inflammatory behavior.1 Furthermore cytotoxic agents like
benzo[5,6]pyrrolizino[1,2-b]quinolines, antitumor agents like camptothecin also contain the quinoline ring
system.2 Recently quinolines are also shown for their formation of conjugated molecules and polymers
that combine enhanced electronic, optoelectronic, or nonlinear optical properties with excellent
mechanical properties.3,4 The structural core of quinolines has generally been synthesized by various
conventional routes such as Skraup, Döbner-von Miller, and Friedländer syntheses. Quinolines can be
prepared from aminoarenes and olefins using transition metal complexes as catalysts.5 The Skraup
reaction is venerable reaction and it is one of the most simple and straightforward methods for
synthesizing quinolines.6 Classically, the process involves a series of reactions brought about by heating a
primary aromatic amine, in which at least one position ortho to the amino group is unsubstituted, with
glycerol, sulfuric acid, and an oxidizing agent. However, it requires a large amount of sulfuric acid at
temperatures above 1500C and the reaction is often violent. Further, the disposal of acid waste leads to

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HETEROCYCLES, Vol. 68, No. 3, 2006
environmental pollution. Since then, several methods have been developed for the synthesis of quinolines;
but most of these methods suffer from one or the other limitations such as drastic reaction conditions,7a,c,e,f
undesired side products, generality,7b,d,e low yield,7a,c,e,g and expensive transition metal-catalyzed
reagents.7h,i Consequently, there is scope for further renovation toward mild reaction conditions, increased
variation of the substituents in both components, and better yields.
In recent years, much attention has focused on microwave-assisted organic reactions8 in the absence of
solvent. Often, thermal demanding reactions take hours in solution, and may require repetitive treatments
with excess reagents to drive them to completion. However, with microwave irradiation these same
reactions may be completed in few minutes. In continuation of our ongoing efforts in this area,9 we
envisioned the applicability of potassium dodecatangestocobaltate trihydrate (K5CoW12O40.3H2O,
PDTC)10 was found to be the most suitable catalyst for the synthesis of substituted quinolines or
dihydroquinolines from readily available anilines and alkyl vinyl ketones under microwave irradiation
because of its availability, low cost and ease of recycling (Scheme 1). In a typical general experimental
procedure involves the irradiation of a mixture of the aniline and alkyl vinyl ketone by microwave in a
domestic microwave oven for a certain period of time as required to complete the reaction (TLC),
resulting in the formation of substituted quinolines (Scheme 1).
O
R3
R2
R2
R1
K5CoW12O40.3H2O
MW
R3
R
+
R
R
NH2
R1
O
N
CH3
K5CoW12O40.3H2O
MW
R
+
CH3
NH2
N
H
CH3
Scheme 1
The reaction mixture was then eluted with ethyl acetate and the extract was washed with brine, dried and
evaporated to obtain the crude material, which was purified by column chromatography over silica gel.
Preliminary optimization of reaction conditions was performed using 2,3,4-trimethoxyaniline and methyl
vinyl ketone (Entry 5 in Table 3). Optimal conditions for the synthesis were found to be 10 –15 min
reaction time using 500 W of microwave irradiation power. We first examined the reaction time and
temperature effects when 25 mol% of PDTC was used under microwave irradiation. As time increased,
the reaction temperature also increased and the maximum yield (88%) was obtained after 15 min as
illustrated in Table 1, Entry 3. The temperature was one of the key factors that improved the yields but a
longer time and a higher temperature did not increase the yield (Table 1, Entry 4).

HETEROCYCLES, Vol. 68, No. 3, 2006
551
Table 1. Optimization of the reaction time in the synthesis of substiuted quinoline (2e)
under microwave irradiation or conventional heating in a thermostated oil bath
( scale = 3 mmol, ratio of aniline:alkyl vinyl ketone:PDTC = 1:1.5:0.25 )
______________________________________________________________________
Yield (%)
Temp.(00C)a ______________________________
Entry
Time (min)
Microwaveb
Conventional
______________________________________________________________________
5
75
32
65
1
2
3
4
10
100
110
130
88
85
27c
15
20
______________________________________________________________________
a Temperature of reaction mixture was recorded after the microwave irradiation
at the given reaction time. b The reactions were carried out in a 2450 MHz commercial
microwave oven (BatliboiEddy, model # FR-5054-D). c Oil bath temperature = 1100C.
In order to evaluate the influence of PDTC, the reactions were carried out using different PDTC
equivalents. It should be pointed out that cyclization is enhanced by PDTC as shown in Table 2. In the
absence of PDTC, microwave irradiation effect was not observed in the synthesis of quinolines at 1100C
Table 2, Entry 1). However, when 25 mol % of PDTC was added, the yield was increased up to 88 %
Table 2, Entry 3). PDTC in excess of 25 mol % did not help to increase the yield Table 2, Entry 5).
Table 2. Optimization of the PDTC equivalents and reaction time in the synthesis of
substiuted quinoline (2e) under microwave irradiation
( scale = 3 mmol, ratio of aniline:alkyl vinyl ketone = 1 equiv.:1.5 equiv.)
______________________________________________________________________
Yield (%)
Entry
PDTC (mol %) Time (min)
______________________________
Conventional
Microwave
______________________________________________________________________
15
1
0
5
2a
_
15a
27a
5
2
3
5.0
32
65
88
15
10.0
25.0
4
5
6
15
50.00
75.0
25
360
85
83
38b
______________________________________________________________________
a Oil bath temperatre = 1100C. Oil bath temperature = 1300C.
b
To check the possibility of intervention of specific (non purely thermal) microwave effects, the reaction
has also been examined using a pre-heated oil bath for the same duration and at the same final
temperature as measured at the end of exposure during the microwave-assisted synthesis. It was found
that reaction proceeded slowly with 15-27 % yield in 15 min (Table 2, Entries 3 and 4) whereas 38 % of
diphenylquinolines was obtained after 360 min under conventional heating at 1300C (Table 2, Entry 6).
In an effort to optimize this process, a wide range of substituted anilines and structurally diverse alkyl
vinyl ketones were subjected to this procedure to produce the corresponding quinolines or
dihydroquinolines in moderate to high yields without side products (Table 3).

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HETEROCYCLES, Vol. 68, No. 3, 2006
Table 3. K5CoW12O40.3H2O-catalyzed synthesis of quinolines under
solvent-free conditions
___________________________________________________________________
Time
Product (2)a
Yield (%)b
Entry
Substrate R (1)
R1
R2 R3
(min.)
___________________________________________________________________
CH3
1
2
H
H
CH3
CH3
8
75
78
H
H
NH2
NH2
N
a
a
CH3
CH3
CH3
10
N
b
c
b
c
CH3
CH3O
CH3O
CH3
CH3
H
H
3
4
H
H
10
12
85
81
NH2
NH2
N
CH3
N
d
OCH3
d
OCH3
OCH3
OCH3Ph
CH3O
CH3O
CH3O
CH3O
Ph
Ph
10
15
5
H
88
NH2
N
Ph
e
f
e
f
CH3
6
7
H
H
H
CH3
80
82
HO
NH2
HO
N
OCH3
CH3O
CH3O
CH3
CH3O
CH3O
CH3 12
Ph
NH2
CH3O
Cl
N
Ph
g
g
CH3
8
9
H
H
H
H
CH3
74
77
10
Cl
NH2
NH2
N
h
h
CH3
CH3 10
N
i
i
___________________________________________________________________
aAll the Products were characterized by IR, 1HNMR, 13CNMR and MS spectra.
b Yields refer to pure isolated products.
However, use of a β-substituted alkyl vinyl ketone such as mesityl oxide leads to the formation of a
dihydroquinoline ring. This may be because of the presence of two methyl groups at the carbon adjacent
to NH prevents aromatization to the quinoline ring. The results are depicted in Table 4. It is noteworthy to
mention here that the yield of this reaction strongly depends on the relative amount of the starting
materials used (a 2:1 molar ratio of the alkyl vinyl ketone versus aniline gave the optimal yield (65-88%)

HETEROCYCLES, Vol. 68, No. 3, 2006
553
of substituted quinoline). Furthermore, the reaction remains incomplete with lower amounts of the oxidant
even after extended exposure to microwaves. It is essential to work in an open vessel to enable the low
volatile formed either from the reaction mixture or excess alkyl vinyl ketones to escape from the reaction
Table 4. K5CoW12O40.3H2O-catalyzed synthesis of dihydroquinolines
______________________________________________________________________
Alkyl vinyl Time
Yield
Entry
Aniline R (1)
Product (2)
a
(min.)
ketone
______________________________________________________________________
(%)
CH3
O
78
65
1
2
15
20
N
H
a
NH2
NH2
a
CH3
O
CH3
CH3
N
H
b
b
OCH3 CH3
OCH3
O
O
CH3O
CH3O
CH3O
CH3O
15
25
3
4
80
68
N
NH2
NH2
c
H
c
CH3
N
H
d
COOCH3
COOCH3
d
CH3
O
O
Br
Br
72
67
5
20
15
N
NH2
e
f
H
e
CH3
t-C4H9
t-C4H9
6
NH2
N
H
f
CH3
O
7
15
75
N
H
g
g
NH2
_____________________________________________________________________
a Yeilds refer to those of pure isolated products fully characterized by
spectral (IR, 1H,13C NMR and MS spectra) and analytical data.
mixture. Synthesis of these compounds using analogue methodology, employing conventional heating,
requires a large excess of highly toxic anilines.
To investigate further the scope and limitations of the above optimal condition, quinoline and
dihydroquinoline derivatives was synthesized. The results from Table 3 reveal that the microwave-
assisted synthesis provides an efficient way to access a variety of 4-substituted quinolines under solvent-
free conditions. In general, the yields of quinolines are not affected by the nature of substituents on the

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HETEROCYCLES, Vol. 68, No. 3, 2006
aniline and alkyl vinyl ketone. In the case of m-substituted anilines, only one regioisomeric quinoline
corresponding to the p-cyclization is formed. Presumably, this process involves Michael addition of the
aniline to the vinyl ketone11 followed by subsequent cyclization and aromatization under the catalysis of
K5CoW12O40.3H2O.12 However, this reaction does not proceed with acrolein (or vinyl aldehyde in general)
yielding instead the corresponding imine. Another important aspect of this procedure is survival of
functional groups such as OCH3, CN under the reaction conditions. By conventional heating method (oil
bath) at 1100C in place of microwave activation induces considerable polymerization of vinyl ketones
reducing the yield of quinolines drastically.
We have also studied Friedländer13 coupling condensation reaction by using the same catalyst
K5CoW12O40.3H2O between various acetophenones and 2-aminoacetophenone or benzophenone under
microwave irradiation to obtain quinoline derivatives (Scheme 2). We first examined the reaction time
and temperature effects when 25mol % of catalyst K5CoW12O40.3H2O was used under microwave
irradiation. As time increased, the reaction temperature also increased and the maximum yield (78%) was
obtained after 10 min at 110oC as shown in Scheme 2 3b. The temperature was one of the important
factors that improved the yields but a longer time and a higher temperature did not increase the yield.
R2
R2
O
K5CoW12O40.3H2O
MW
O
CH3
+
H2N
N
R1
2
1
3
R1
a: R1 = Cl, R2 = Ph (65%)
b: R1 = CH3, R2 = Ph (78%)
Scheme 2
In summary, microwave-assisted solvent-free reactions were employed to synthesize quinoline derivatives.
The method not only offers substantial improvement in yield over conventional heating methods but also
eliminates the use of hazardous solvents and excess expensive acid catalyst. Advantages of this method
include the fact that it is environmentally benign, an economical procedure, has a short reaction time and
involves inexpensive reagents and can be effectively applied to large-scale synthesis of quinolines in high
yields.
ACKNOWLEDGEMENTS
One of the authors R. K. K thanks UGC, New Delhi, for financial support.
EXPERIMENTAL
Reagents and all solvents were analytically pure grade and were used without further purification.
Anhydrous conditions were not required for this reaction. 1H NMR spectra were recorded on Varian FT-
200 MHz (Gemini) in CDCl3. Chemicals shifts are reported in parts per million (δ) relative to

HETEROCYCLES, Vol. 68, No. 3, 2006
555
tetramethylsilane (δ 0.0) as an internal standard. Mass spectra were recorded under electron impact at
70eV on Finnigan Mat 1020B mass spectrometer. Melting points were recorded on Büchi 535 and are
uncorrected. Elemental analyses were performed on elemental analyzer Vario EL. Column
chromatography was carried out using 60-120 mesh silica gel. Thin-layer chromatography was performed
on Merck 60 F-254 silica gel plates.
A typical procedure for 2,4,-diphenyl-5,6,7-trimethoxyquinoline synthesis is as follows: A mixture of
3,4,5-trimethoxyaniline (3.66 g, 20 mmol) and 1,3-diphenylprop-2-en-1-one (6.24 g, 30 mmol) was added
to potassium dodecatangestocobaltate (80 mg, 0.01 mmol) and the whole mixture was stirred for few
minutes for uniform mixing. This mass was then irradiated by microwave in a domestic microwave oven
(BatliboiEddy, model # FR-5054-D) at 500W for 2 min intervals. After this heating, a period of 30 sec
was allowed for cooling to prevent excess heating. This process was repeated 5-8 times (i.e. total of 10-15
min). The reaction mixture is allowed to attain room temperature, the solid mass was dissolved in ethyl
acetate (2x15 mL), filtered to separate the catalyst and the crude product quinoline (2e, Table 3) isolated
in pure form by passing through a silica gel column chromatography (petroleum ether-ethyl acetate 9:1) as
1
a yellow oil (6.52 g, 88%). IR 3024, 1616, 1519 cm-1; HNMR (CDCl3): δ 3.22 (s, 3H), 3.91(s, 3H),
4.06(s, 3H), 7.38-7.55(m, 11H), 8.12(d, J = 4.4 Hz, 1H). 13CNMR (CDCl3): δ 56.0, 60.6, 61.0, 96.2, 105.5,
119.7, 126.9, 127.1, 127.4, 128.4, 128.7, 129.1, 139.5, 142.3, 147.2, 147.6, 148.7, 155.7; EIMS: m/z (%)
371 (M+, 62), 324(8), 117(100), 84(44), 47(21). Anal. Calcd for C24H21NO3: C, 77.60; H. 5.70; N, 3.77.
Found: C, 77.45; H, 5.59; N, 3.73.
4,6-Dimethylquinoline (2b, Table 3). Yellow oil (85%); 3000, 1625, 1500 cm-1; 1HNMR δ 2.58 (s, 3H),
2.67 (s, 3H), 7.12 (d, J = 4.1 Hz, 1H), 7.58 (d, J = 8.5 Hz, 1H), 7.78 (s, 1H), 8.02 (d, J = 8.5 Hz, 1H), 8.73
(d, J = 4.1 Hz, 1H). 13CNMR (CDCl3): δ 18.4, 21.6, 121.8, 122.6, 128.5, 128.9, 131.3, 136.2, 144.0, 145.6,
148.8; EIMS: m/z (%) 157 (M+, 38), 117(100), 106 (12), 84(100), 77 (10), 51 (28), 49 (93). Anal. Calcd
for C11H11N: C, 84.04; H. 7.05; N, 8.91. Found: C, 83.93; H, 7.02; N, 8.85.
1
6-Methoxy-4-methylquinoline (2c, Table 3). Yellow oil (85%); IR 3017, 1615, 1500 cm-1; HNMR δ
2.45 (s, 3H), 3.88 (s, 3H), 7.15-7.19 (m, 2H), 7.36 (d, J = 9.0 Hz, 1H), 8.02 (d, J = 9.0 Hz, 1H), 8.61 (d, J
13
= 4.4Hz). CNMR δ 17.4, 53.6, 110.0, 112.0, 120.2, 127.5, 127.7, 141.2, 142.0, 146.2, 156.0. Anal.
Calcd for C11H11NO: C, 76.28; H. 6.40; N, 8.09. Found: C, 76.23; H, 6.32; N, 8.01.
1
8-Methoxy-4-methylquinoline (2d, Table 3). Yellow oil (81%); IR 3085, 1620, 1520 cm-1; HNMR δ
2.69 (s, 3H), 3.90 (s, 3H), 7.18-7.22 (m, 2H), 7.45 (t, J = 6.0 Hz, 1H), 8.02 (d, J = 6.0 Hz, 1H), 8.75 (d, J

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HETEROCYCLES, Vol. 68, No. 3, 2006
13
= 4.5Hz, 1H); CNMR (CDCl3): δ 17.9, 54.0, 109.3, 118.0, 122.5, 125.4, 128.1, 135.8, 140.2, 148.0,
155.2. Anal. Calcd for C11H11NO: C, 76.28; H. 6.40; N, 8.09. Found: C, 76.18; H, 6.33; N, 8.04.
1
7-Hydroxy-4-methylquinoline (2f, Table 3). Yellow oil (65%); IR 3380, 1610, 1505cm-1; HNMR δ
2.72 (s, 3H), 7.28 (m, 2H), 7.52 (d, J = 9.0 Hz, 1H), 7.95 (d, J = 9.0 Hz, 1H), 8.11 (d, J = 1.2 Hz, 1H),
8.76 (d, J = 6.0 Hz, 1H). 13CNMR (CDCl3): δ 8.76 (d, J = 6.0 Hz, 1H). 13CNMR (CDCl3): δ 17.4, 110.0,
121.5, 122.0, 127.2, 131.8, 140.0, 142.2, 150.0, 155.4. Anal. Calcd for C10H9NO: C, 75.45; H. 5.70; N,
8.80. Found: C, 75.36; H, 5.67; N, 8.72.
2-Phenyl-4-methyl-5,6,7-trimethoxyquinoline (2g, Table 3). Yellow oil (82%); IR 3020, 1615, 1525
cm-1; 1HNMR (CDCl3): δ 2.75 (s, 3H), 3.21 (s, 3H), 3.89 (s, 3H), 4.02 (s, 3H), 7.38-7.55 (m, 6H), 8.12 (d,
J = 4.4 Hz, 1H). EIMS: m/z (%) 309 (M+, 100), 294(45), 266(100), 84(38), 251(27), 180(26), 141(35),
71(48), 57(81), 43(78). Anal. Calcd for C19H19NO3: C, 73.76; H. 6.19; N, 4.53. Found: C, 73.69; H, 6.14;
N, 4.50.
7-Chloro-4-methylquinoline (2h, Table 3). Yellow oil (74%); IR 3020, 1600, 1510 cm-1; 1HNMR δ 2.70
(s, 3H), 7.28 (d, J = 4.2 Hz, 1H), 7.55 (dd, J = 9.0, 1.8 Hz, 1H), 7.95 (d, J = 9.0 Hz, 1H), 8.14 (d, J = 1.8
Hz, 1H), 8.75 (d, J = 4.2 Hz, 1H). 13CNMR (CDCl3): δ 18.5, 121.0, 125.5, 127.4, 128.0, 129.2, 135.4,
145.0, 147.2, 150.4. Anal. Calcd for C10H8NCl: C, 67.62; H. 4.54; N, 7.89. Found: C, 67.58; H, 4.51; N,
7.82.
4-Methyl-7,8-benzoquinoline (2i, Table 3). Yellow oil (77%); IR 3040, 1600, 1510 cm-1; 1HNMR δ 2.75
(s, 3H), 7.31 (d, J = 4.5 Hz, 1H), 7.68-7.85 (m, 5H), 8.82 (d, J = 4.5 Hz, 1H), 9.28 (d, J = 8.1 Hz, 1H);
13CNMR (CDCl3): δ 19.5, 121.9, 122.7, 123.9, 125.0, 125.5, 126.4, 126.6, 127.5, 128.0, 133.0, 138.0,
147.0, 147.8. Anal. Calcd for C14H11N: C, 87.01; H. 5.74; N, 7.25. Found: C, 86.96; H, 5.68; N, 7.23.
2,2,4-Trimethyl-1,2-dihydroquinoline (2a, Table 4). colorless oil (78%); IR 3355 cm-1; 1HNMR δ 1.25
(s, 6H), 1.98 (d, J = 1.3 Hz, 3H), 5.25 (s, 1H), 6.45 (dt, J = 1.1, 7.5 Hz, 1H), 6.65 (dt, J = 1.1, 7.5 Hz, 1H),
13
7.01 (dt, J = 1.4, 7.6 Hz, 1H), 7.08 (dd, J = 1.4, 7.6 Hz, 1H); CNMR (CDCl3): δ 19.1, 31.0 (2C), 52.2,
113.3, 117.5, 122.0, 123.8, 128.5 (2C), 129.1, 130.2, 141.6. Anal. Calcd for C12H15N: C, 83.19; H. 8.73;
N, 8.08. Found: C, 83.06; H, 8.62; N, 7.98.
2,2,3,6-Tetramethyl-1,2-dihydroquinoline (2b, Table 4). colorless oil (65%); IR 3365 cm-1; 1HNMR δ
1.25 (s, 6H), 1.98 (d, J = 1.0 Hz, 3H), 2.25 (s, 3H), 5.30 (d, J = 1.0 Hz, 1H), 6.35 (d, J = 7.8 Hz, 1H), 6.76

HETEROCYCLES, Vol. 68, No. 3, 2006
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(dd, J = 2.3, 7.8 Hz, 1H), 6.88 (s, 1H); 13CNMR (CDCl3): δ 19.1, 21.0, 31.4 (2C), 52.1, 96.3, 113.2, 124.5,
126.8, 129.8, 129.2, 129.3, 141.6. Anal. Calcd for C13H17N: C, 83.37; H. 9.15; N, 7.48. Found: C, 83.22;
H, 8.97; N, 7.34.
2,2,4-Trimethyl-5,6,7-trimethoxydihydroquinoline (2c, Table 4). Yellow crystal (80%),
(recrystallization solvent EtOAc-hexane). mp 93-950C; IR 3385, 1600 cm-1; 1HNMR δ 1.22 (s, 6H), 2.12
(s, 3H), 3.42-3.64 (br s, 1H), 3.72 (s, 3H), 3.76 (s, 3H), 3.85 (s, 3H), 5.12 (s, 1H), 5.78 (s, 1H). 13CNMR
(CDCl3): δ 22.1, 29.7 (2C), 50.9, 55.7, 60.9, 61.0, 93.7, 108.6, 127.9, 128.6, 134.6, 141.0, 153.2. EIMS:
m/z (%) 263 (M+, 5), 249(100), 218(45), 190(28), 147(23), 118 (15). Anal. Calcd for C15H21NO3: C,
68.41; H. 8.04; N, 5.32. Found: C, 68.29; H, 7.92; N, 5.26.
8-Carbomethoxy-2,2,4-trimethyl-1,2-dihydroquinoline (2d, Table 4). colorless oil (68%); IR 3327,
1680 cm-1; 1HNMR δ 1.21 (s, 6H), 1.95 (s, 3H), 3.42-3.64 (br s, 1H), 3.81 (s, 3H), 5.30 (s, 1H), 6.43 (t, J
7.3 Hz, 1H), 7.15 (d, J = 7.3 Hz, 1H), 7.62 (d, J = 8.2 Hz, 1H), 7.90 (bs, 1H). 13CNMR (CDCl3): δ 19.6,
33.0 (2C), 51.6, 52.1, 96.4, 114.5, 122.5, 128.0, 128.2, 129.0, 131.0, 147.8, 169.5. Anal. Calcd for
C14H17NO2: C, 72.70; H. 7.41; N, 6.06. Found: C, 72.58; H, 7.35; N, 6.03.
6-Bromo-2,2,4-trimethyl-1,2-dihydroquinoline (2e, Table 4). Pale yellow crystal (72%);
(recrystallization solvent EtOAc-hexane). mp 76-780C; IR 3370, 755 cm-1; 1HNMR δ 1.23 (s, 6H), 2.25 (s,
3H), 3.45-3.48 (br s, 1H), 5.29 (s, 1H), 6.29 (d, J = 8.3 Hz, 1H), 7.05 (dd, J = 2.3, 8.3 Hz, 1H), 7.10 (d, J
= 2.2 Hz, 1H), 13CNMR (CDCl3): δ 19.0, 31.0 (2C), 52.2, 109.0, 114.5, 122.5, 126.7, 128.2, 129.0, 131.0,
142.8. Anal. Calcd for C12H14NBr: C, 57.16; H. 5.60; N, 5.55. Found: C, 57.06; H, 5.51; N, 5.49.
6-tert-Butyl-2,2,4-trimethyl-1,2-dihydroquinoline (2f, Table 4). Pale yellow oil (67%); IR 3350, 750
cm-1; 1HNMR δ 1.23 (s, 6H), 1.27 (s, 9H), 2.01(s, 3H), 5.25 (s, 1H), 6.34 (d, J = 8.3 Hz, 1H), 6.96 (dd, J =
2.3, 8.3 Hz, 1H), 7.02 (s, 1H); EIMS: m/z (%) 229 (M+, 5), 214(100), 198(27), 86(13). Anal. Calcd for
C16H23N: C, 83.78; H. 10.11; N, 6.11. Found: C, 83.55; H, 9.85; N, 6.06.
2,2,4-Trimethyl-1,2-dihydro[7,8]benzoquinoline (2g, Table 4). Colourless oil (75%); IR 3417, cm-1;
1HNMR δ 1.25 (s, 6H), 2.25 (s, 3H), 5.31 (s, 1H), 7.26 (d, J = 8.5 Hz, 1H), 7.42-7.46 (m, 3H), 7.77-7.80
(m, 2H). 13CNMR (CDCl3): δ 19.5, 31.4(2C), 52.3, 116.0, 116.5, 120.5, 122.5, 123.0, 125.2, 125.7, 126.7,
129.0, 123.0, 134.2, 138.8. Anal. Calcd for C16H17N: C, 86.05; H. 7.67; N, 6.27. Found: C, 85.85; H, 7.52;
N, 6.23.

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2-(p-Chlorophenyl)-4-phenylquinoline (3a): yellow crystal (65%). (recrystallization solvent EtOAc-
hexane). mp 106-1080C; .1HNMR δ 7.38-7.61 (m, 8H), 7.66-7.78 (m, 2H), 7.84-7.92 (m, 1H), 8.12-8.204
(m, 3H); 13CNMR (CDCl3): δ 118.1, 125.0, 125.2, 126.5, 127.77 (8C), 134.8, 137.2, 137.3, 148.6, 150.0,
154.7, 196.0. EIMS: m/z (%) 315 (M+, 100), 202(15), 154(11), 139 (85), 111 (33), 43 (9). Anal. Calcd for
C22H17N: C, 89.46; H. 5.80; N, 4.74. Found: C, 89.27; H, 5.69; N, 4.71.
2-(p-Methylphenyl)-4-phenylquinoline (3b): yellow crystal (78%). (recrystallization solvent EtOAc-
hexane). mp 74-760C; 1HNMR δ 2.41 (s, 3H), 7.21-7.65 (m, 9H), 7.67-7.92 (m, 4H), 8.06-8.25 (m, 4H);
13CNMR (CDCl3): δ 22.5, 118.5, 126.2, 127.1, 127.7 (8C), 135.3, 137.2, 138.9, 140.2, 143.7, 149.8,
158.2, 170.0, 198.5. EIMS: m/z (%) 295 (M+, 100), 202(7). Anal. Calcd for C21H14NCl: C, 80.10; H. 4.45;
N, 4.44. Found: C, 79.46; H, 4.50; N, 4.39.
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