Efficient microwave-assisted synthesis of quinolines and dihydroquinolines under solvent-free conditions

Article abstract of DOI:10.1016/S0040-4020(02)01587-9

A convenient and efficient procedure for the synthesis of quinolines and dihydroquinolines has been developed by a simple one-pot reaction of anilines with alkyl vinyl ketones on the surface of silica gel impregnated with indium(III) chloride under microwave irradiation without any solvent.

Full text of DOI:10.1016/S0040-4020(02)01587-9

Tetrahedron 59 (2003) 813–819
Efficient microwave-assisted synthesis of quinolines and
dihydroquinolines under solvent-free conditions
*
Brindaban C. Ranu, Alakananda Hajra, Suvendu S. Dey and Umasish Jana
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta 700 032, India
Received 24 September 2002; revised 11 November 2002; accepted 6 December 2002
Abstract—A convenient and efficient procedure for the synthesis of quinolines and dihydroquinolines has been developed by a simple one-
pot reaction of anilines with alkyl vinyl ketones on the surface of silica gel impregnated with indium(III) chloride under microwave
irradiation without any solvent. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
mixture was then irradiated by microwave in a domestic
microwave oven for a few minutes as required to complete
the reaction. The reaction mixture was then eluted with
ethyl acetate and the extract was washed with brine, dried
and evaporated to leave the crude product which was
purified by column chromatography over silica gel.
The synthesis of the quinoline ring has been the subject of
continued interest as several derivatives of this heterocyclic
unit have been found to possess useful biological activities
such as bactericidal,1 antimalarial,2 antiinflammatory3 etc.
The classical method for quinoline synthesis involves
Skraup’s procedure.4 However, it requires a large amount
of sulfuric acid at temperatures above 1508C and the
reaction is often violent. A number of other methods5 have
been reported for the synthesis of quinolines involving a
variety of metal catalysts and Lewis acids. However, many
of these procedures are not fully satisfactory with regard to
operational simplicity, cost of the reagent and isolated yield.
Thus, the drive is continues to find a better and improved
methodology. In a recent communication6 we have demon-
strated a very simple procedure for the synthesis of 4-
alkylquinolines by a one-pot reaction of anilines and alkyl
vinyl ketones on the surface of silica gel impregnated with
indium(III) chloride under microwave irradiation without
any-solvent and we report here further manipulation of this
methodology for the synthesis of dihydroquinolines
together with the experimental details of our earlier results
(Scheme 1).
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 high yields. When an unsubstituted or an a/b-mono-
substituted alkyl vinyl ketone is used, quinolines are
obtained and the results are summarized in Table 1.
However, use of a b-disubstituted alkyl vinyl ketone such
as mesityl oxide leads to the construction of a dihydroquino-
line ring. This is quite expected as the presence of two
methyl groups at the carbon adjacent to –NH (Scheme 1)
prevents aromatisation to the quinoline ring. The results are
presented in Table 2.
As evident from the results in Table 1 this procedure offers
2. Results and discussion
The experimental procedure is very simple. A mixture of
aniline and alkyl vinyl ketone was added to silica gel
impregnated with indium(III) chloride (30 mol%) and the
whole mass was stirred for 5 min for uniform mixing. The
Keywords: quinoline; 1,2-dihydroquinoline; indium trichloride; microwave
activation.
*
Corresponding author. Tel.: þ91-33-4734971; fax: þ91-33-4732805;
Scheme 1.
e-mail: ocbcr@iacs.res.in
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01587-9

814
B. C. Ranu et al. / Tetrahedron 59 (2003) 813–819
Table 1. Synthesis of quinolines
Entry
1
Aniline
Alkyl vinyl ketone
Time (min)
5
Product
Yield (%)a
85
2
3
10
10
81
84
4
5
10
12
85
80
6
7
10
10
83
81
8
5
87
9
12
7
80
80
10
11
12
10
83
82
7
13
14
15
9
7
81
83
55
12
a
1
Yields refer to those of pure isolated products fully characterized by spectral (IR, H and 13C NMR) and analytical data.

B. C. Ranu et al. / Tetrahedron 59 (2003) 813–819
815
Table 2. Synthesis of dihydroquinolines
Entry
1
Aniline
Alkyl vinyl ketone
Time (min)
20
Product
Yield (%)a
80
2
3
4
5
6
7
8
20
25
30
25
30
25
20
75
71
58
77
63
73
75
9
30
25
20
67
58
78
10
11
12
20
45
a
1
Yields refer to those of pure isolated products fully characterized by spectral (IR, H and 13C NMR) and analytical data.

816
B. C. Ranu et al. / Tetrahedron 59 (2003) 813–819
a silica gel surface provides an efficient one-pot synthesis of
substituted quinolines and 1,2-dihydroquinolines from
readily available anilines and alkyl vinyl ketones under
solvent-free conditions. The notable advantages of this
procedure are: (a) operational simplicity; (b) fast and clean
reaction; (c) high yield; (d) general applicability accom-
modating a variety of substitutions on both rings. We
believe that this procedure will provide a better and more
practical alternative to the existing methodologies for the
synthesis of quinolines.
4. Experimental
4.1. General
Scheme 2.
good scope of putting different alkyl groups in the quinoline
ring by use of substituted alkyl vinyl ketones (entries 13–
15). In general, the yields of quinolines are not affected by
the nature of substituents on the anilines and the vinyl
ketones. Interestingly, in the case of m-substituted anilines,
only one regioisomeric quinoline corresponding to p-
cyclization is obtained (entries 3,7,8).
Melting points were determined on a glass disk with an
1
electrical bath and are uncorrected. H NMR (300 MHz)
and 13C NMR (75 MHz) spectra were run in CDCl3
solutions. IR spectra were taken as neat for liquid
compounds and as KBr plates for solids. Elemental analyses
were done by a Perkin–Elmer autoanalyzer. Column
chromatography was performed on silica gel (60–120
mesh, SRL, India). Anilines and alkyl vinyl ketones were
distilled before use. Indium(III) chloride (Aldrich) was used
as such. THF was distilled over potassium-benzophenone
before use.
The access to dihydroquinolines is not very easy as
reduction of the quinoline ring by conventional reducing
agents leads to 1,2,3,4-tetrahydroquinolines.7 However, this
procedure provides an efficient synthesis of a series of 2,2,4-
trimethyl-1,2-dihydroquinolines with varied substituents
such as Cl, Br, OMe, COOMe, Ts on the aromatic ring
(Table 2). The biological activities of quinoline derivatives
are greatly influenced by the nature of substituents on the
aromatic ring.1–3 A fused dihydroquinoline is also obtained
by proper choice of alkyl vinyl ketone (entry 12, Table 2).
4.1.1. General procedure for the synthesis of quinolines:
representative procedure for 4,6-dimethylquinoline
(entry 4, Table 1). A mixture of 4-methyl aniline
(214 mg, 2 mmol) and methyl vinyl ketone (175 mg,
2.5 mmol) was added to silica gel impregnated with
indium(III) chloride (132 mg, 0.6 mmol), prepared by
adding a solution of InCl3 in minimum amount of THF to
silica gel (HF254, E-Merck, activated by heating for 3 h at
1508C under reduced pressure) followed by complete
evaporation of solvent under vacuum. The whole mixture
was stirred for 5 min for uniform mixing and was then
irradiated by microwave in a domestic microwave oven
(BPL, India) at 600 W (50% of total power) for 10 min
(5þ5 min with an intermission of 10 min in between) as
required to complete the reaction (TLC). The reaction
mixture was then eluted with ethyl acetate (20 mL) and the
extract was washed with brine, dried over Na2SO4 and
evaporated to leave the crude product which was purified by
column chromatography over silica gel (hexane–ether 95:5)
to furnish pure product, 4,6-dimethylquinoline as a yellow
oil (270 mg, 85%); IR 3006, 1620, 1500 cm21; 1H NMR d
8.71 (d, J¼4.1 Hz, 1H), 8.01 (d, J¼8.5 Hz, 1H), 7.75 (s,
1H), 7.54 (d, J¼8.5 Hz, 1H), 7.10 (d, J¼4.1 Hz, 1H), 2.68
(s, 3H), 2.56 (s, 3H); 13C NMR d 148.7, 145.7, 144.1, 136.2,
131.4, 129.0, 128.5, 122.7, 121.8, 21.8, 18.6. Anal. calcd for
C11H11N: C, 84.04; H, 7.05; N, 8.91. Found: C, 83.91; H,
7.01; N, 8.79.
Presumably, this process involves Michael addition of
aniline to the vinyl ketone8 followed by subsequent
cyclization and aromatization under the catalysis of InCl3/
SiO2, as delineated in Scheme 2. The intermediate tertiary
hydroxy compounds 2 formed by Michael addition followed
by cyclization have been isolated in a couple of reactions
and are properly characterized. These intermediates were
subsequently dehydrated and aromatized to the quinolines
by further microwave heating on SiO2/InCl3. This type of
oxidative aromatization in the presence of Lewis acid and
air is not unprecedented.9
In general, the reactions are fast, clean and high yielding
excepting a few reactions (entry 15 in Table 1 and entries
10, 12 in Table 2) where a considerable amount of
unidentified tarry materials are obtained. However, the
reaction does not proceed with acrolein or other vinyl
aldehydes yielding instead the corresponding imine. The
reaction in the presence of indium(III) chloride alone is
sluggish and the reaction on the silica gel surface without
indium(III) chloride leads to imine formation only.
Conventional heating in place of microwave irradiation
induces considerable polymerization of vinyl ketones
reducing the yields of quinolines drastically.
This procedure is followed for the synthesis of all the
quinolines listed in Table 1. However, in reactions with
aniline (entry 1) and 2-methylaniline (entry 2) the
intermediate tertiary hydroxy compounds 2 have been
isolated as colorless oils. These compounds have been
3. Conclusion
1
easily characterised by IR and H NMR:
The present procedure catalyzed by indium(III) chloride on

B. C. Ranu et al. / Tetrahedron 59 (2003) 813–819
817
4.1.2. 1,2,3,4-Tetrahydro-4-hydroxy-4-methylquinoline
(entry 1). IR 3600–3300 cm21 1H NMR d 7.30–6.80
C, 76.28; H, 6.40; N, 8.09. Found: C, 76.21; H, 6.27; N,
7.99.
;
(m, 4H), 3.20 (m, 2H), 1.80 (broad, 2H), 1.70 (t, J¼6.0 Hz,
2H), 1.30 (s, 3H).
4.1.9. 7-Hydroxy-4-methylquinoline (entry 7, Table 1).
1
Yellow oil (81%); IR 3388, 1601, 1502 cm21; H NMR d
4.1.3. 1,2,3,4-Tetrahydro-4,8-dimethyl-4-hydroxyquino-
1
8.78 (d, J¼6.0 Hz, 1H), 8.14 (d, J¼1.2 Hz, 1H), 7.94 (d,
J¼9.0 Hz, 1H), 7.54 (d, J¼9.0 Hz, 1H), 7.27 (m, 2H), 2.72
(s, 3H); 13C NMR d 155.8, 150.2, 142.5, 140.2, 132.5,
127.8, 122.4, 121.9, 110.2, 17.8. Anal. calcd for C10H9NO:
C, 75.45; H, 5.70; N, 8.80. Found: C, 75.32; H, 5.65; N,
8.65.
line (entry 2). IR 3600–3300 cm21; H NMR d 7.40–7.0
(m, 3H), 3.20 (m, 2H), 2.20 (s, 3H), 1.70 (t, J¼6.0 Hz, 2H),
1.41 (broad, 2H), 1.32 (s, 3H).
These hydroxy compounds are then heated by microwave
irradiation for the second time being absorbed on the surface
of silica gel in presence of InCl3 under the same
experimental conditions as described above for 2 min to
furnish the corresponding quinolines.
4.1.10. 7-Chloro-4-methylquinoline (entry 8, Table 1).
1
Yellow oil (87%); IR 3004, 1624, 1596 cm21; H NMR d
8.77 (d, J¼4.2 Hz, 1H), 8.14 (d, J¼1.8 Hz, 1H), 7.94 (d,
J¼9.0 Hz, 1H), 7.53 (dd, J¼9.0, 1.8 Hz, 1H), 7.25 (d,
J¼4.2 Hz, 1H), 2.71 (s, 3H); 13C NMR d 150.5, 147.5,
145.3, 135.3, 129.3, 128.1, 127.4, 125.2, 122.0, 18.6. Anal.
calcd for C10H8NCl: C, 67.62; H, 4.54; N, 7.89. Found: C,
67.51; H, 4.51; N, 7.81.
For the synthesis of dihydroquinolines also (Table 2) the
same procedure is followed with microwave heating at
120 W (10% of total power) for 20–30 min. (10þ10 min
with an interval of 10 min in between). The products are
1
identified by their IR, H and 13C NMR spectral data and
elemental analysis. These data are presented below in order
of their entries in Tables 1 and 2.
4.1.11. 6-Chloro-4-methylquinoline (entry 9, Table 1).
1
Yellow oil (80%); IR 3019, 1601, 1503 cm21; H NMR d
8.76 (d, J¼3.2 Hz, 1H), 8.05 (d, J¼8.9 Hz, 1H), 7.97 (d,
J¼2.3 Hz, 1H), 7.64 (dd, J¼8.9, 2.3 Hz, 1H), 7.25 (d,
J¼3.2 Hz, 1H), 2.68 (s, 3H); 13C NMR d 150.6, 146.6,
144.0, 132.6, 131.9, 130.4, 123.3, 122.9, 118.1, 18.7. Anal.
calcd for C10H8NCl: C, 67.62; H, 4.54; N, 7.89. Found: C,
67.54; H, 4.42; N, 7.78.
4.1.4. 4-Methylquinoline (entry 1, Table 1). Pale yellow
1
oil (85%); IR 3053, 1605, 1494 cm21; H NMR d 8.78 (d,
J¼4.4 Hz, 1H), 8.13 (d, J¼8.5 Hz, 1H), 8.02 (d, J¼8.5 Hz,
1H), 7.73 (t, J¼7.0 Hz, 1H), 7.58 (t, J¼7.0 Hz, 1H), 7.24 (d,
J¼4.4 Hz, 1H), 2.72 (s, 3H).
4.1.5. 4,8-Dimethylquinoline (entry 2, Table 1). Yellow
1
4.1.12. 6-Bromo-4-methylquinoline (entry 10, Table 1).
1
oil (81%); IR 3042, 1601, 1502 cm21; H NMR d 8.87 (d,
Yellow oil (80%); IR 3031, 1623, 1509 cm21; H NMR d
J¼4.5 Hz, 1H), 7.89 (d, J¼8.4 Hz, 1H), 7.60 (d, J¼7.1 Hz,
1H), 7.59 (t, J¼7.1 Hz, 1H), 7.27 (d, J¼4.5 Hz, 1H), 2.86 (s,
3H), 2.74 (s, 3H); 13C NMR d 148.3, 144.5, 144.3, 135.5,
130.4, 128.9, 126.7, 122.3, 122.1, 19.5, 19.1. Anal. calcd for
C11H11N: C, 84.04; H, 7.05; N, 8.91. Found: C, 83.81; H,
7.09; N, 8.76.
8.79 (d, J¼4.5 Hz, 1H), 8.15 (d, J¼2.1 Hz, 1H), 8.04 (d,
J¼9.0 Hz, 1H), 7.78 (dd, J¼9.0, 2.1 Hz, 1H), 7.29 (d,
J¼4.5 Hz, 1H), 2.68 (s, 3H); 13C NMR d 149.6, 145.5,
144.5, 132.9, 130.8, 129.4, 126.2, 122.5, 120.7, 18.6. Anal.
calcd for C10H8NBr: C, 54.08; H, 3.63; N, 6.31. Found: C,
53.95; H, 3.59; N, 6.22.
4.1.6. 4,7-Dimethylquinoline (entry 3, Table 1). Yellow
1
4.1.13. 6-Iodo-8,4-dimethylquinoline (entry 11, Table 1).
1
oil (84%); IR 3029, 1616, 1499 cm21; H NMR d 8.74 (d,
Yellow oil (83%), IR 3053, 1608, 1492 cm21; H NMR d
J¼4.5 Hz, 1H), 7.93 (d, J¼8.5 Hz, 1H), 7.89 (s, 1H), 7.42
(d, J¼8.5 Hz, 1H), 7.21 (d, J¼4.5 Hz, 1H), 2.71 (s, 3H),
2.57 (s, 3H); 13C NMR d 149.5, 147.3, 146.0, 140.5, 132.8,
129.4, 124.4, 121.5, 118.5, 21.8, 18.9. Anal. calcd for
C11H11N: C, 84.04; H, 7.05; N, 8.91. Found: C, 84.01; H,
6.93; N, 8.83.
8.78 (d, J¼4.5 Hz, 1H), 8.20 (d, J¼1.5 Hz, 1H), 7.81 (d,
J¼1.5 Hz, 1H), 7.21 (d, J¼4.5 Hz, 1H), 2.71 (s, 3H), 2.63
(s, 3H); 13C NMR d 149.1, 145.7, 143.5, 139.6, 137.7,
130.8, 126.8, 122.2, 92.2, 18.9, 18.0. Anal. calcd for
C11H10NI: C, 46.67; H, 3.56; N, 4.95. Found: C, 46.58; H,
3.51; N, 4.88.
4.1.7. 8-Methoxy-4-methylquinoline (entry 5, Table 1).
1
4.1.14. 4-Methyl-7,8-benzoquinoline (entry 12, Table 1).
1
Yellow oil (80%); IR 3084, 1616, 1519 cm21; H NMR d
Yellow oil (82%); IR 3039, 1601, 1504 cm21; H NMR d
8.75 (d, J¼4.5 Hz, 1H), 8.01 (d, J¼6.0 Hz, 1H), 7.46 (t,
J¼6.0 Hz, 1H), 7.24–7.19 (m, 2H), 3.89 (s, 3H), 2.69 (s,
3H); 13C NMR d 155.4, 148.2, 140.4, 135.7, 128.3, 125.6,
122.5, 118.3, 109.1, 54.1, 18.1. Anal. calcd for C11H11NO:
C, 76.28; H, 6.40; N, 8.09. Found: C, 76.12; H, 6.31; N,
8.01.
9.31 (d, J¼8.1 Hz, 1H), 8.85 (d, J¼4.5 Hz, 1H), 7.90–7.65
(m, 5H), 7.34 (d, J¼4.5 Hz, 1H), 2.76 (s, 3H); 13C NMR d
148.0, 147.1, 144.0, 133.2, 128.1, 127.5, 126.9, 126.7,
125.7, 125.1, 123.9, 122.8, 121.7, 19.7. Anal. calcd for
C14H11N: C, 87.01; H, 5.74; N, 7.25. Found: C, 86.94; H,
5.69; N, 7.21.
4.1.8. 6-Methoxy-4-methylquinoline (entry 6, Table 1).
1
4.1.15. 4-(4-Methoxyphenyl)-2-methylquinoline (entry
13, Table 1). Yellow oil (81%); IR 3053, 1593,
Yellow oil (83%); IR 3021, 1617, 1496 cm21; H NMR d
1
8.63 (d, J¼4.4 Hz, 1H), 8.02 (d, J¼9.2 Hz, 1H), 7.38 (d,
J¼9.2 Hz, 1H), 7.21–7.18 (m, 2H), 3.95 (s, 3H), 2.66 (s,
3H); 13C NMR d 156.0, 145.8, 142.0, 141.1, 127.6, 127.5,
120.4, 119.8, 110.2, 53.8, 17.2. Anal. calcd for C11H11NO:
1448 cm21; H NMR d 8.03 (d, J¼8.7 Hz, 1H), 7.92 (d,
J¼11.4 Hz, 2H), 7.69 (d, J¼8.7 Hz, 1H), 7.44 (d, J¼8.7 Hz,
1H), 7.29 (m, 1H), 7.03 (m, 1H), 6.90 (d, J¼11.4 Hz, 2H),
3.85 (s, 3H), 2.75 (s, 3H); 13C NMR d 136.3, 130.6 (2C),

818
B. C. Ranu et al. / Tetrahedron 59 (2003) 813–819
130.4, 129.2, 128.6, 127.3, 127.0, 125.8, 124.7, 114.7, 114.2
(2C), 113.5, 113.0, 55.3, 24.0. Anal. calcd for C17H15NO: C,
81.90; H, 6.06; N, 5.62. Found: C, 81.75; H, 6.01; N, 5.54.
(entry 5, Table 2). Yellowish oil (77%); IR 3384,
1
1606 cm21; H NMR d 6.73 (d, J¼7.7 Hz, 1H), 6.64 (d,
J¼8.0 Hz, 1H), 6.51 (dd, J¼7.7, 8.0 Hz, 1H), 5.27 (s, 1H),
3.78 (s, 3H), 1.98 (s, 3H), 1.26 (s, 6H); 13C NMR d 145.8,
133.4, 128.9, 128.5, 116.6, 115.9, 109.9, 96.6, 55.9, 31.6
(2C), 19.3. Anal. calcd for C13H17NO: C, 76.81; H, 8.43; N,
6.89. Found: C, 76.66; H, 8.24; N, 6.68.
4.1.16. 7-Chloro-4-(4-methoxyphenyl)-2-methylquino-
line (entry 14, Table 1). Yellow oil (83%); IR 3044,
1623, 1501 cm21; 1H NMR d 8.14 (d, J¼1.9 Hz, 1H), 7.94
(d, J¼11.2 Hz, 2H), 7.51 (d, J¼9.0 Hz, 1H), 7.25–6.92 (m,
4H), 3.82 (s, 3H), 2.77 (s, 3H); 13C NMR d 148.9, 146.8,
144.2, 133.5, 131.1 (2C), 129.2, 128.6, 127.5, 127.1, 124.8,
115.4 (2C), 114.0, 113.7, 55.3, 26.2. Anal. calcd for
C17H14NOCl: C, 71.96; H, 4.97; N, 4.94. Found: C, 71.81;
H, 4.91; N, 4.88.
4.1.23. 8-Carbomethoxy-2,2,4-trimethyl-1,2-dihydroqui-
noline (entry 6, Table 2). Colorless oil (63%); IR 3327,
1681 cm21; 1H NMR d 7.90 (broad, 1H), 7.66 (d, J¼8.2 Hz,
1H), 7.10 (d, J¼7.3 Hz, 1H), 6.43 (t, J¼7.3 Hz, 1H), 5.32 (s,
1H), 3.83 (s, 3H), 1.96 (s, 3H), 1.33 (s, 6H); 13C NMR d
169.4, 147.7, 130.9, 128.8, 128.4, 127.9, 122.3, 114.2, 96.6,
52.2, 51.7, 32.8 (2C), 19.4. Anal. calcd for C14H17NO2: C,
72.70; H, 7.41; N, 6.06. Found: C, 72.52; H, 7.29; N, 6.01.
4.1.17. 3-Ethyl-4-methyl-2-propylquinoline (entry 15,
Table 1). Yellow oil (55%); IR 3111, 1625, 1483 cm21
;
1H NMR d 8.04 (d, J¼8.4 Hz, 1H), 7.66 (d, J¼8.4 Hz, 1H),
7.58 (t, J¼7.0 Hz, 1H), 7.38 (t, J¼7.0 Hz, 1H), 2.89 (t,
J¼7.6 Hz, 2H), 2.71 (s, 3H), 2.68 (q, J¼7.2 Hz, 2H), 1.83
(m, 2H), 1.18 (t, J¼7.6 Hz, 3H), 1.04 (t, J¼7.2 Hz, 3H); 13C
NMR d 139.5, 134.1, 130.2, 128.5, 128.3, 127.1, 126.9,
124.7, 122.3, 38.6, 25.1, 22.4, 18.4, 14.6, 14.1. Anal. calcd
for C15H19N: C, 84.46; H, 8.98; N, 6.57. Found: C, 84.30; H,
8.91; N, 6.49.
4.1.24. 7-Chloro-2,2,4-trimethyl-1,2-dihydroquinoline
(entry 7, Table 2). Pale yellow crystal (73%); mp 56–
1
608C; IR 3382, 829 cm21; H NMR d 6.53 (d, J¼8.1 Hz,
1H), 6.54 (dd, J¼1.9, 8.1 Hz, 1H), 6.36 (d, J¼1.9 Hz, 1H),
5.30 (d, J¼1.0 Hz, 1H), 1.94 (d, J¼1.0 Hz, 3H), 1.22 (s,
6H); 13C NMR d 144.7, 134.0, 128.7, 128.2, 125.0, 117.3,
112.8, 96.6, 52.5, 31.7 (2C), 18.9. Anal. calcd for
C12H14NCl: C, 69.39; H, 9.15; N, 7.48. Found: C, 69.18;
H, 9.00; N, 7.29.
4.1.18. 2,2,4-Trimethyl-1,2-dihydroquinoline (entry 1,
1
Table 2). Colorless oil (80%); IR 3365 cm21; H NMR d
7.07 (dd, J¼1.4, 7.6 Hz, 1H), 6.99 (dt, J¼1.4, 7.6 Hz, 1H),
6.64 (dt, J¼1.1, 7.5 Hz, 1H), 6.46 (dt, J¼1.1, 7.5 Hz, 1H),
5.32 (d, J¼1.3 Hz, 1H), 1.99 (d, J¼1.3 Hz, 3H), 1.27 (s,
6H); 13C NMR d 143.5, 128.9, 128.7 (2C), 124.0, 122.0,
117.7, 113.4, 52.2, 31.2 (2C), 18.9. Anal. calcd for
C12H15N: C, 83.19; H, 8.73; N, 8.08. Found: C, 83.01; H,
8.55; N, 8.00.
4.1.25. 6-Chloro-2,2,4-trimethyl-1,2-dihydroquinoline
(entry 8, Table 2). Colorless oil (75%); IR 3375, 2243,
1
738 cm21; H NMR d 7.00 (d, J¼2.3 Hz, 1H), 6.93–6.90
(m, 1H), 6.37 (d, J¼7.9 Hz, 1H), 5.30 (s, 1H), 1.95 (s, 3H),
1.26 (s, 6H); 13C NMR d 143.6, 132.9, 129.9, 128.2, 123.8,
118.4, 114.2, 96.2, 51.7, 31.3 (2C), 18.8. Anal. calcd for
C12H14NCl: C, 69.39; H, 9.15; H, 7.48. Found: C, 69.20; H,
8.95; N, 7.31.
4.1.19. 2,2,4,8-Tetramethyl-1,2-dihydroquinoline (entry
2, Table 2). Colorless oil (75%); IR 3408 cm21; 1H NMR d
6.94 (d, J¼7.6 Hz, 1H), 6.89 (d, J¼7.6 Hz, 1H), 6.55–6.50
(m, 1H), 5.27 (s, 1H), 2.06 (s, 3H), 1.98 (s, 3H), 1.28 (s, 6H);
13C NMR d 141.5, 130.2, 129.3, 128.0 (2C), 121.1, 116.7,
96.6, 52.1, 31.9 (2C), 19.3, 17.4. Anal. calcd for C13H17N:
C, 83.37; H, 9.15; N, 7.48. Found: C, 83.18; H, 9.01; N,
7.27.
4.1.26. 6-Bromo-2,2,4-trimethyl-1,2-dihydroquinoline
(entry 9, Table 2). Pale yellow crystal (67%); mp 788C;
IR 3371, 759 cm21; 1H NMR d 7.12 (d, J¼2.2 Hz, 1H), 7.04
(dd, J¼2.2, 8.3 Hz, 1H), 6.30 (d, J¼8.3 Hz, 1H), 5.33 (d,
J¼1.1 Hz, 1H), 1.94 (d, J¼1.1 Hz, 3H), 1.26 (s, 6H); 13C
NMR d 142.6, 131.1, 129.8, 128.1, 126.7, 123.8, 114.7,
109.1, 52.4, 31.4 (2C), 18.9. Anal. calcd for C12H14NBr: C,
57.16; H, 5.60; N, 5.55. Found: C, 57.01; H, 5.48; N, 5.36.
4.1.20. 2,2,4,7-Tetramethyl-1,2-dihydroquinoline (entry
3, Table 2). Colorless oil (71%); IR 3367 cm21; 1H NMR d
6.96 (d, J¼7.7 Hz, 1H), 6.46 (d, J¼7.7 Hz, 1H), 6.28 (s,
1H), 5.26 (d, J¼1.2 Hz, 1H), 2.23 (s, 3H), 1.98 (d,
J¼1.2 Hz, 3H), 1.27 (s, 6H); 13C NMR d 143.6, 128.9,
127.8, 123.9, 119.5, 118.4, 113.9, 110.1, 52.2, 31.4 (2C),
21.7, 18.9. Anal. calcd for C13H17N: C, 83.37; H, 9.15; N,
7.48. Found: C, 83.20; H, 8.98; N, 7.29.
4.1.27. 8-Tosyl-2,2,3-trimethyl-1,2-dihydroquinoline
(entry 10, Table 2). Colorless oil (58%); IR 3406,
1
2256 cm21; H NMR d 7.77 (d, J¼8.4 Hz, 2H), 7.32 (d,
J¼8.4 Hz, 2H), 6.90 (dd, J¼0.7, 7.7 Hz, 1H), 6.69 (dd,
J¼0.7, 7.7 Hz, 1H), 6.41 (t, J¼7.7 Hz, 1H), 5.26 (s, 1H),
4.00 (broad, 1H), 2.44 (s, 3H), 1.93 (s, 3H), 1.26 (s, 6H); 13C
NMR d 145.9, 135.6, 130.2 (2C), 130.1, 129.9, 128.9 (2C),
128.0, 123.8, 122.4, 122.0, 115.6, 107.4, 52.1, 31.6 (2C),
19.1, 14.5. Anal. calcd for C19H21NSO2: C, 69.69; H, 6.46;
N, 4.28. Found: C, 69.48; H, 6.38; N, 4.10.
4.1.21. 2,2,3,6-Tetramethyl-1,2-dihydroquinoline (entry
4, Table 2). Colorless oil (58%); IR 3367 cm21; 1H NMR d
6.86 (s, 1H), 6.78 (dd, J¼2.3, 7.8 Hz, 1H), 6.34 (d,
J¼7.8 Hz, 1H), 5.29 (d, J¼1.0 Hz, 1H), 2.22 (s, 3H), 1.97
(d, J¼1.0 Hz, 3H), 1.24 (s, 6H); 13C NMR d 141.4, 129.2,
129.1, 129.0, 126.6, 124.6, 113.4, 96.5, 52.1, 31.2 (2C),
21.1, 19.0. Anal. calcd for C13H17N: C, 83.37; H, 9.15; N,
7.48. Found: C, 83.17; H, 8.97; N, 7.29.
4.1.28. 2,2,4-Trimethyl-1,2-dihydro-[7,8]-benzoquino-
line (entry 11, Table 2). Colorless oil (78%); IR
3417 cm21; 1H NMR d 7.82–7.78 (m, 2H), 7.48–7.41 (m,
3H), 7.26 (d, J¼8.5 Hz, 1H), 5.44 (d, J¼0.8 Hz, 1H), 2.20
(d, J¼0.8 Hz, 3H), 1.45 (s, 6H); 13C NMR d 138.6, 134.5,
129.8, 129.2, 126.9, 125.9, 125.1, 123.0, 122.3, 120.3,
116.7, 116.1, 52.5, 31.6 (2C), 19.7. Anal. calcd for
4.1.22. 8-Methoxy-2,2,4-trimethyl-1,2-dihydroquinoline

B. C. Ranu et al. / Tetrahedron 59 (2003) 813–819
819
4. (a) Skraup, H. Chem. Ber. 1880, 13, 2086. (b) Mansake, R. H.
F.; Kulka, M. Org. React. 1953, 7, 59.
C16H17N: C, 86.05; H, 7.67; N, 6.27. Found: C, 85.87; H,
7.46; N, 6.05.
5. (a) Huma, H. Z. S.; Halder, R.; Kalra, S. S.; Das, J.; Iqbal, J.
Tetrahedron Lett. 2002, 43, 6485. (b) Ali, M. M.; Tasneem;
Rajanna, K. C.; Prakash, P. K. S. Synlett 2001, 251. (c) Cho,
C. S.; Kim, B. T.; Kim, T.-J.; Shim, S. C. Chem. Commun.
2001, 2576. (d) Wang, M.-X.; Liu, Y.; Huang, Z.-T.
Tetrahedron Lett. 2001, 42, 2553. (e) Arisawa, M.;
Theeralandanon, C.; Nishida, A.; Nakagawa, M. Tetrahedron
Lett. 2001, 42, 8029. (f) Cho, C. S.; Kim, J. S.; Oh, B. H.; Kim,
T.-J.; Shim, S. C.; Yoon, N. S. Tetrahedron 2000, 56, 7747.
(g) Beller, M.; Thiel, O. R.; Trauthwein, H.; Hartung, C. G.
Chem. Eur. J. 2000, 6, 2513. (h) Matsugi, M.; Tabusa, F.;
Minamikawa, J. Tetrahedron Lett. 2000, 41, 8523. (i) Zhou,
L.; Zhang, Y. J. Chem. Soc., Perkin Trans. 1 1998, 2899.
(j) Larock, R. C.; Kero, M.-Y. Tetrahedron Lett. 1991, 32, 569.
(k) Zhou, L.; Tu, S.; Shi, D.; Dai, G.; Chen, W. Synthesis 1988,
851. (l) Tsuji, Y.; Hu, K.-T.; Watanabe, Y. J. Org. Chem.
1987, 52, 1673.
4.1.29. 2,4-Dimethyl-1,2-dihydrocyclopenta[b]quinoline
(entry 12, Table 2). Colorless oil (45%); IR (neat)
1
3381 cm21; H NMR d 7.09–6.96 (m, 2H), 6.70 (m, 1H),
6.54–6.51 (m, 1H), 1.88 (s, 3H), 1.26–0.83 (m, 9H); 13C
NMR d 142.8, 139.8, 126.9, 124.4, 123.1, 121.0, 118.1,
113.7, 59.5, 41.8, 27.4, 24.5, 21.7, 14.3. Anal. calcd for
C14H17N: C, 84.37; H, 8.60; N, 7.03. Found: C, 84.18; H,
8.39; N, 6.91.
Acknowledgements
We are pleased to acknowledge the financial support from
CSIR, New Delhi [Grant No. 01(1739)/02] for this
investigation. A. H., S. S. D. and U. J. are also thankful to
CSIR for their fellowships.
6. Ranu, B. C.; Hajra, A.; Jana, U. Tetrahedron Lett. 2000, 41,
531.
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