Novel route to quinolines via recyclization of furans

Full text of DOI:10.1007/s10593-011-0707-2

Chemistry of Heterocyclic Compounds, Vol. 46, No. 12, March, 2011 (Russian Original Vol. 46, No. 12, December, 2010)
NOVEL ROUTE TO QUINOLINES
VIA RECYCLIZATION OF FURANS
1
1
1
2
A. V. Butin *, F. A. Tsiunchik , O. N. Kostyukova , and I. V. Trushkov
Keywords: furans, quinolines, Bischler-Napieralski reaction.
The Bischler-Napieralski reaction is a powerful tool for the construction of nitrogen-containing
heterocyclic compounds through the formation of a new C–C bond as the result of the reaction of an
electrophilic carbon atom with an aromatic or heterocyclic nucleus. It is generally used in the synthesis of
3
,4-dihydroisoquinolines from phenylethylamine amides or -carbolines from tryptamine amides [1, 2] but it
can also be used for the annelation of a pyridine ring to other heterocyclic compounds [3-6]. In addition,
variation of the linkage joining the aromatic fragment and the amide function permits the synthesis of a wide
range of nitrogen-containing heterocycles. Thus, under the indicated conditions, 2-acylaminodiphenylmethanes
give dibenzoazepines [7] and their thienyl analogs yield thienoazepines [8].
O
Ph
NH
Ph
MeO
MeO
NH2
N
MeO
MeO
PhCOCl
MeO
MeO
Me
NaHCO3
Me
Me
O
O
O
3
2
1
POCl3
H
Ph
O
MeO
MeO
N
OP(O)Cl2
MeO
MeO
N
Ph
Me
+
H
O
4
Me
_
*
______
To whom correspondence should be addressed, e-mail: alexander_butin@mail.ru.
1
Research Institute of Heterocyclic Compounds Chemistry, Kuban State Technological University, Krasnodar
3
50072, Russia.
2
M. V. Lomonosov State University, Chemistry Faculty, Moscow 119992, Russia.
_
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1900-1903, December, 2010.
Original article submitted October 7, 2010.
009-3122/11/4612-1539©2011 Springer Science+Business Media, Inc.
0
1539

A similar reaction has not been reported for 2-(2-acylaminobenzyl)furans although it is known that 2-[2-
(
aminocarbamoyl)phenylthio]furans give furo[2,3-b][1,5]benzothiazepines when treated with phosphorus oxy-
chloride in the presence of P O [9]. In that connection, the aim of this work was to study the possibility of
2
5
preparing the furo[3,2-c]benzazepine 1 under Bischler-Napieralski conditions from the 2-(2-acylamino-
benzyl)furan 2.
When compound 2 (prepared by acylation of the available benzylfuran 3 with benzoyl chloride [10])
was refluxed in benzene in the presence of excess phosphorus oxychloride the quinoline 4 was obtained instead
of the expected furoazepine 1. Evidently, its formation results from electrophilic attack of the formed iminium
ion not at the -position of the furan ring but at the -carbon atom of the furan. There then occurs an
electrophilic opening of the furan ring to form the aromatic quinoline system.
1
13
IR spectra were taken on a Shimadzu IR Prestige-21 instrument for KBr tablets. H and C NMR
spectra were recorded on a Bruker DPX-300 spectrometer (300 and 75 MHz respectively) using DMSO-d (for
6
compound 2) or CDCl (compound 4). The standards used were the residual protons of the deuterated solvent
3
1
13
1
13
CDCl (7.25 ppm for H and 77.0 ppm for C) or DMSO-d (2.50 ppm for H and 39.5 ppm for C). Mass
3
6
spectra were obtained on a Kratos MS-30 spectrometer by EI with ionizing energy 70 eV and ionization
chamber temperature 200ºC.
N-{2-[(5-Methyl-2-furyl)methyl]-4,5-dimethoxyphenyl}benzamide (2). A solution of benzoyl
chloride (2.1 g, 15 mmol) in benzene (25 ml) was added dropwise with stirring to a solution of compound 3
(
2.47 g, 10 mmol) in benzene (30 ml), stirred at room temperature for 1 h (TLC monitoring), and then poured
into water (100 ml). The mixture obtained was neutralized with NaHCO and left for 2 h. The benzene layer was
3
separated and the aqueous extracted with ethyl acetate (230 ml). The combined organic fractions were dried
over Na SO and filtered. The solvent was removed in vacuo and the residue was dissolved in a mixture of
2
4
methylene chloride and petroleum ether (1:8). The obtained solution was passed through a layer of silica gel and
the solvent was evaporated. Recrystallization from a mixture of methylene chloride and petroleum ether (1:5)
-
1
gave compound 2 (2.53 g, 72%) as a white powder with mp 110ºC. IR spectrum,  cm : 3260, 1644, 1612,
1
1
516, 1468, 1308, 1284, 1260, 1220, 1092, 712. H NMR spectrum, , ppm (J, Hz): 2.25 (3H, s, CH ); 3.87 (6H,
3
s, OCH ); 3.90 (2H, s, CH ); 5.89 (1H, d, J = 3.3, H furan); 5.94 (1H, d, J = 3.3, H furan); 6.75 (1H, s, Ph); 7.44-
3
2
1
3
7
3
1
7
3
.58 (3H, m, Ph); 7.61 (1H, s, Ph); 7.85-7.87 (2H, m, Ph); 8.38 (1H, s, NH). C NMR spectrum, , ppm: 13.5,
1.2, 55.9, 56.0, 106.4, 106.9, 108.1, 112.9, 122.0, 127.0 (2C), 128.6 (2C), 128.9, 131.7, 134.7, 146.3, 147.8,
+
51.3, 151.5, 165.5. Mass spectrum, m/z (I , %): 351 [M] (78), 247 (24), 246 (76), 106 (12), 105 (95), 95 (13),
rel
7 (100), 59 (48), 43 (55). Found, %: C 71.61; H 6.11; N 3.81. C H NO . Calculated, %: C 71.78; H 6.02; N
2
1
21
4
.99.
(
3E)-4-(6,7-Dimethoxy-2-phenylquinolin-3-yl)but-3-en-2-one (4). POCl (25 ml) was added to a
3
solution of compound 2 (0.53 g, 1.5 mmol) in benzene (10 ml) and refluxed for 1.5 h (TLC monitoring). The
reaction mixture was then poured onto crushed ice (500 g), neutralized with aqueous NaOH solution (3.5 M, 350
ml), and extracted with methylene chloride (3150 ml). The combined organic extracts were dried over
anhydrous Na SO , filtered, and the solvent was removed in vacuo. The reaction product was separated by
2
4
column chromatography on 50-160 m silica gel using methylene chloride and petroleum ether (1:3) as eluent.
Recrystallization from a mixture of methylene chloride and petroleum ether (1:4) gave quinoline 4 (0.31 g, 61%)
-
1
as a light-yellow powder with mp 200-201ºC. IR spectrum, , cm : 1664, 1616, 1588, 1496, 1432, 1392, 1260,
1
1
228, 1212, 1132, 1008, 704. H NMR spectrum, , ppm (J, Hz): 2.28 (3H, s, CH ); 4.03 (3H, s, OCH ); 4.04
3
3
(
3H, s, OCH ); 6.73 (1H, d, J = 16.2 =CH); 7.10 (1H, s, H Ar); 7.46-7.54 (4H, m, H Ar); 7.58-7.62 (2H, m, H
3
1
3
Ar); 7.66 (1H, d, J = 16.2, =CH); 8.30. (1H, s, H Py). C NMR spectrum, , ppm: 26.9, 56.0, 56.2, 104.8, 107.9,
22.5, 124.8, 128.3 (3C), 128.6, 129.7 (2C), 132.8, 139.3, 142.0, 145.6, 150.2, 153.7, 157.1, 198.2. Mass
1
+
spectrum, m/z (I , %): 333 [M] (27), 290 (100), 275 (31), 274 (38), 246 (30), 217 (26), 101 (29), 59 (55), 43
rel
(
57). Found, %: C 75.37; H 5.60; N 4.19. C H NO . Calculated, %: C 75.66; H 5.74; N 4.20
21 19 3
1
540

This work was carried out within the Federal Target Program "Russian Science and Science Teaching
Innovation" for the years 2009-2013 (application 1.3.1, State Contract P2347).
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