Cascade heterocyclization of 2-naphthylamine with substituted benzaldehydes and acetophenones

Article abstract of DOI:10.1134/S1070363206110259

Cascade heterocyclization of 2-naphthylamine with substituted benzaldehydes and acetophenones gave 1,3-diarylbenzo[f]quinoline derivatives in which the aldehyde fragment resides on C¹, and acetophenone fragment, on C ³.

Full text of DOI:10.1134/S1070363206110259

ISSN 1070-3632, Russian Journal of General Chemistry, 2006, Vol. 76, No. 11, pp. 1810 1816.
Pleiades Publishing, Inc., 2006.
Original Russian Text N.G. Kozlov, L.I. Basalaeva, 2006, published in Zhurnal Obshchei Khimii, 2006, Vol. 76, No. 11, pp. 1894 1900.
Cascade Heterocyclization of 2-Naphthylamine
with Substituted Benzaldehydes and Acetophenones
N. G. Kozlov and L. I. Basalaeva
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus,
ul. Surganova 13, Minsk, 220072 Belarus
e-mail: loc@ifoch.bas-net.by
Received April 21, 2006
Abstract Cascade heterocyclization of 2-naphthylamine with substituted benzaldehydes and acetophenones
gave 1,3-diarylbenzo[f]quinoline derivatives in which the aldehyde fragment resides on C1, and acetophenone
fragment, on C3.
DOI: 10.1134/S1070363206110259
Benzo[f]quinoline derivatives containing aryl
groups with various substituents are used in medical
practice as antitumor [1] and antimicrobial drugs [2].
Furthermore, they are structural analogs of some
alkaloids [3] and antibiotics [4].
Schiff base A which takes up a proton in the presence
of acid and adopts a planar conformation; as a result,
its electrophilicity increases [6]. Moreover, acid
medium enhances the nucleophilicity of the carbon
atom neighboring to the carbonyl group in aceto-
phenone molecule. Thus favorable conditions are
created for the addition of acetophenone to Schiff base
with formation of a new bond between the C=N
carbon atom and methyl carbon atom of acetophenone.
Unstable arylamino ketone B decomposes into 2-
naphthylamine (I) and , -unsaturated ketone IV.
The -carbon atom in the latter has a considerable
positive charge; therefore, its electrophilicity is
sufficient to form a new bond with the -carbon atom
(with respect to the amino group) in 2-naphthylamine.
Proton addition at the neighboring carbon atom gives
saturated ketone C which undergoes heterocyclization
with selective formation of 1,3-diarylbenzo[f]quino-
lines Va Vt. In the reactions of acetophenones IIIa,
IIIb, and IIId with 2-naphthylamine and 3-p-fluoro-
phenyl-1H-pyrazole-4-carbaldehyde (IIe), the forma-
tion of chalcones IVu IVw is the terminal stage;
presumably, the positive charge on the carbon atom
in unsaturated ketone is reduced due to effect of the
heterocyclic substituent (Scheme 2).
The present communication reports on the syn-
thesis of new benzo[f]quinoline derivatives via cata-
lytic condensation of 2-naphthylamine (I) with sub-
stituted benzaldehydes IIa IIe and acetophenone
(IIIa) or its derivatives IIIb IIIe. Variation of sub-
stituents in benzaldehyde and acetophenone molecules
could give rise to benzo[f]quinolines containing a
broad spectrum of pharmacophoric groups. The reac-
tions were carried out by heating the initial reactants
in butanol for 6 10 h in the presence of concentrated
hydrochloric acid.
We previously showed [5] that Schiff bases derived
from 2-naphthylamine react with acetophenone to give
initially the corresponding amino ketone, -phenyl- -
2-naphthylaminopropiophenone, which then undergoes
intramolecular ring closure to benzo[f]quinoline.
Intermediate amino ketones were isolated only under
mild conditions (heating in ethanol for 15 20 min in
the presence of a small amount of catalyst). Under the
conditions of cascade heterocyclization, no amino
ketones were isolated, but the formation of , -un-
saturated ketones IVu IVw was established; therefore,
we presumed intermediacy of , -enones in the
cascade heterocyclization under study.
, -Unsaturated ketones IVa IVt were synthesized
previously by aldol condensation of acetophenones
with benzaldehydes; their reaction with 2-naphthyl-
amine in boiling gave the same benzo[f]quinoline
derivatives Va Vf as those obtained by three-com-
ponent condensation. Thus there are grounds to be-
lieve that the scheme of synthesis of benzo[f]quino-
lines includes preliminary formation of , -unsatur-
ated ketones and their subsequent reaction with
2-naphthylamine, which is consistent with the data of
[7, 8].
Judging by the structure of the final products,
which were identified as 1-alkoxyphenyl-3-arylbenzo-
[f]quinoline derivatives on the basis of spectral data,
we propose the following reaction scheme (Scheme 1).
2-Naphthylamine reacts with benzaldehyde to give
1810

CASCADE HETEROCYCLIZATION OF 2-NAPHTHYLAMINE
1811
R
Scheme 1.
Me
NH2
O
O
R
R
+
N
I
IIa IId
IIIa IIIe
A
R
R
O
H2N
O
R
R
O
NH
R
R
C
IVa IVt
B
R
R
R
R
5
2
3
6
4
2
4
2
5
3
1
3
6
0
1
N
N
9
8
5
6
7
Va Vt
D
II, R = 4-EtO (a), 4-PrO (b), 3-Br-4-HO-5-EtO (c), 2-FC6H4CH2O (d); III, R = H (a), 4-Cl (b), 4-Br (c), 4-HO (d), 2-HO
(e); IV, V, R = 4-EtO, R = H (a), 4-Cl (b), 4-Br (c), 4-HO (d), 2-HO (e); R = 4-PrO, R = H (f), 4-Cl (g), 4-Br (h), 4-HO
(i), 2-HO (j), R = 3-Br-4-HO-5-EtO, R = H (k), 4-Cl (l), 4-Br (m), 4-HO (n), 2-HO (o), R = 2-FC6H4CH2O, R = H (p),
4-Cl (q), 4-Br (r), 4-HO (s), 2-HO (t).
Scheme 2.
F
F
O
R
+ IIIa, IIIb, IIId
I +
O
N
N
N
H
N
H
IIe
IVu IVw
IV, R = H (u), 4-Cl (v), 4-HO (w).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 11 2006

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KOZLOV, BASALAEVA
As shown in [9, 10], reactions of , -unsaturated
EXPERIMENTAL
ketones with amines could give rise to structures like
D which correspond to a different cyclocondensation
pathway. Compounds Va Vt and D are regioisomers,
and they are very difficult to distinguish. In the present
study we applied two-dimensional COSY, HSQC, and
HMBC techniques to assign proton signals, signals
from carbon atoms attached to protons, and signals
from quaternary carbon atoms, respectively; in addi-
tion, the NOESY spectrum of compound Vo was
recorded. As a result, we were able to unambiguously
determine the product structure and assign all proton
signals in their NMR spectra.
The IR spectra were recorded on a Nicolet Protege-
460 spectrometer with Fourier transform. The H and
1
13C NMR spectra were measured on Tesla BS-567A
(100 MHz) and Bruker AC-500 spectrometers
(500 MHz) from 2 5% solutions in DMSO-d6; the
chemical shifts were determined relative to tetrame-
thylsilane as internal reference. The mass spectra
(electron impact, 70 eV) were obtained on a Hewlett
Packard 5890/5972 GC/MS instrument (HP-5MS
column; samples were injected as solutions in
methylene chloride).
The chemical shifts of the key protons 2-H, 2 -H,
, -Unsaturated ketones IVa IVt were synthesized
by aldol condensation of acetophenones IIIa IIIe
with benzaldehydes IIa IId according to the standard
procedure [13]. Their physical constants coincided
with those reported in [8, 14, 15].
5-H, 6 -H , 6 -H, and 10-H in molecule Vo are equal
to
7.94, 8.12, 8.02, 7.89, 7.33, and 7.98 ppm.
1-[(3-Bromo-5-ethoxy-4-hydroxyphenyl)-3-(2-hyd-
roxyphenyl)benzo[f]quinoline (Vo) was selected tak-
ing into account that one phenyl group in its molecule
has no protons in the meta positions, in contrast to
the acetophenone fragment. According to our previous
data [11], protons in the meta positions of the benzene
ring attached to C1 should give cross-peaks with the
10-H protons in the two-dimensional NOESY spec-
trum due to spatial interaction. The absence of such
peaks in the NOESY spectrum of Vo indicates that
the 3,4,5-trisubstituted benzene ring is attached to C1.
The 13C NMR spectrum of Vo (see Experimental)
confirms the assumed structure.
1-Aryl-3-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-
prop-2-en-1-ones IVu IVw (general procedure). A
mixture of 0.01 mol of 3-(4-fluorophenyl)-1H-pyra-
zole-4-carbaldehyde (IIe), 0.01 mol of 2-naphthyl-
amine, 0.01 mol of acetophenone IIIa IIId, and
5 8 drops of hydrochloric acid in 60 ml of butanol
was heated for 4 5 h on a water bath. The precipitate
was filtered off and recrystallized from ethanol.
3-[3-(4-Fluorophenyl)-1H-pyrazol-4-yl]-1-phe-
nylprop-2-en-1-one (IVu). Yield 54%, colorless crys-
The HMBC spectrum contained correlation peaks
between the 10-H and 5-H protons and carbon nucleus
talline substance, mp 256 257 C. IR spectrum,
,
1
cm : 3060, 2920, 1650, 1527, 1519, 1400, 1433,
1382, 1305, 1271, 1109, 1033, 920, 835, 759, 704.
1H NMR spectrum, , ppm: 7.75 8.00 m and 8.10
8.35 m (9H, Harom), 9.30 9.50 m (3H, CH=CH,
=CHN), 10.70 s (1H, NH). Mass spectrum, m/z (Irel,
%): 279 (100) [M]+, 184 (40), 186 (37), 95 (50).
Found, %: F 6.79; N 10.25. C17H12FN2O. Calculated,
%: F 6.81; N 10.40.
resonating at
145.5 ppm; therefore, the latter was
C
identified as C1. The presence of 2 -H/C1 and 6 -H/C1
correlation peaks unambiguously indicates that the
benzene ring with Br, OH, and OEt groups is located
at C1, whereas correlation between 2 -H and C3
suggests localization of the ortho-hydroxyphenyl
substituent on C3 ( 146.5) ppm. These data confirm
the structure of the Cfinal products as 1-alkoxyphenyl-
3-arylbenzo[f]quinolines.
1-(4-Chlorophenyl)-3-[3-(4-fluorophenyl)-1H-
pyrazol-4-yl]prop-2-en-1-one (IVv). Yield 58%, co-
lorless crystalline substance, mp 273 274 C. IR spec-
The structure of 1,3-diarylbenzo[f]quinolines Va
Vt was also supported by the IR and GC MS data. In
the IR spectra of Va Vt, stretching vibrations of
1
trum, , cm : 3030, 3010, 2970, 1640, 1542, 1437,
1385, 1298, 1264, 1100, 910, 850, 754, 700. 1H NMR
spectrum, , ppm: 7.70 8.00 m and 8.10 8.30 m (8H,
Harom), 9.35 9.50 m (3H, CH=CH, =CHN), 10.75 s
(1H, NH). Mass spectrum, m/z (Irel, %): 314 (20) [M +
1]+, 313 (100) [M]+, 218 (33), 217 (28). Found, %:
Cl 11.19; F 6.04; N 8.93. C17H11ClFN2O. Calculated,
%: Cl 11.18; F 6.07; N 8.95.
1
aromatic C H bonds appear at 3060 3030 cm . Ab-
1
sorption bands at 725 715 and 860 859 cm , which
are insensitive to substituent effects, correspond to
out-of-plane bending vibrations of two neighboring
C H bonds [12]. The mass spectra of 1,3-diarylbenzo-
[f]quinolines Va Vt characteristically contain a small
number of fragment ion peaks. The most abundant ion
(Irel 100%) is [C6H4]+, the molecular ion peaks have a
relative intensity of 70 80%, and medium-intensity
peaks (48 64%) belonging to [M C2H5]+ (Va Ve)
3-[3-(4-Fluorophenyl)-1H-pyrazol-4-yl]-1-(4-
hydroxyphenyl)prop-2-en-1-one (IVw). Yield 42%,
colorless crystalline substance, mp 298 300 C. IR
1
and [M
C3H7]++ (Vf Vj) are present.
spectrum, , cm : 3530, 3100, 2965, 2800, 1570,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 11 2006

CASCADE HETEROCYCLIZATION OF 2-NAPHTHYLAMINE
1813
1
1
1430, 1367, 1250, 1090, 830. H NMR spectrum, ,
ppm: 7.65 7.90 m and 8.00 8.40 m (8H, Harom, 1H,
OH), 9.27 9.42 m (3H, CH=CH, =CHN), 10.70 s
(1H, NH). Mass spectrum, m/z (Irel, %): 295 (100)
[M]+, 200 (37), 203 (18), 95 (42). Found, %: F 6.46;
N 9.47. C17H12FN2O2. Calculated, %: F 6.44; N 9.49.
1038, 930, 751, 702, 664, 569. H NMR spectrum, ,
ppm: 1.37 t (3H, OCH2Me), 4.00 q (2H, OCH2Me),
7.00 7.18 m (3H, Harom), 7.40 7.50 m (6H, Harom),
7.90 8.15 m (4H, Harom), 8.24 d (1H, Harom, J =
7.9 Hz), 8.40 d (1H, Harom, J = 8.0 Hz). Mass spec-
trum, m/z (Irel, %): 455 (10) [M + 1]+, 454 (100) [M]+,
427 (11) [M C2H5]+, 425 (42), 397 (12). Found, %:
C 71.32; H 4.43; Br 17.60; N 3.10. C27N20BrNO.
Calculated, %: C 71.36; H 4.40; Br 17.62; N 3.08.
1,3-Diarylbenzo[f]quinolines Va Vt (general
procedure). A mixture of 0.01 of substituted benzal-
dehyde IIa IIe, 0.01 mol of 2-naphthylamine (I),
0.01 mol of acetophenone IIIa IIIe, and 5 8 drops of
hydrochloric acid in 60 ml of butanol was heated for
6 10 h on a water bath. The resulting tarry material
was treated with diethyl ether under stirring. After
24 h or more, a solid precipitated from the ether solu-
tion and was filtered off, washed with warm (30
40 C) 25% aqueous ammonia, and repeatedly recrys-
tallized from butanol, benzene, or toluene until a
purity of no less than 95% was attained. If no solid
precipitated upon treatment of the tarry material with
ether, it was treated with ammonia (see above), stirred
for 3 h, and the precipitate was filtered off recrystal-
lized. Compounds Vp Vs were isolated in such a way.
1-(4-Ethoxyphenyl)-3-(4-hydroxyphenyl)benzo-
[f]quinoline (Vd). Yield 53%, colorless crystalline
1
substance, mp 217 218 C. IR spectrum, , cm :
3445, 3327, 2978, 1601, 1572, 1539, 1517, 1477,
1458, 1381, 1359, 1303, 1286, 1234, 1176, 1115,
1039, 925, 831, 803, 759, 701, 668. H NMR spec-
1
trum, , ppm: 1.09 t (3H, OCH2Me), 3.49 q (2H,
OCH2Me), 6.60 6.72 m (2H, Harom), 6.80 6.90 m
(2H, Harom), 7.05 7.15 m (6H, Harom), 7.30 7.50 m
(3H, Harom), 7.90 8.10 m (2H, Harom), 8.20 s (1H,
OH). Mass spectrum, m/z (Irel, %): 392 (48) [M + 1]+,
391 (100) [M]+, 362 (45) [M C2H5]+, 353 (38), 143
(84), 115 (62). Found, %: C 82.84; H 5.39; N 3.60.
C27H21NO2. Calculated, %: C 82.87; H 5.37; N 3.58.
1-(4-Ethoxyphenyl)-3-phenylbenzo[ f]quinoline
(Va). Yield 48%, colorless crystalline substance, mp
152 C. IR spectrum, , cm : 3442, 2973, 1605, 1577,
1541, 1524, 1509, 1473, 1451, 1388, 1357, 1307,
1288, 1236, 1177, 1115, 1039, 923, 835, 805, 757,
704, 661, 594. H NMR spectrum, , ppm: 1.42 t (3H,
OCH2Me), 4.10 q (2H, OCH2Me), 7.00 7.20 m (3H,
Harom), 7.48 7.62 m (7H, Harom), 7.80 8.10 m (4H,
Harom), 8.20 d (1H, Harom, J = 8.0 Hz), 8.30 d
(1H, Harom, J = 7.6 Hz). Mass spectrum, m/z (Irel, %):
376 (40) [M + 1]+, 375 (100) [M]+, 346 (42) [M
C2H5]+. Found, %: C 86.44; H 5.57; N 3.70. C27H21
NO. Calculated, %: C 86.40; H 5.60; N 3.73.
1-(4-Ethoxyphenyl)-3-(2-hydroxyphenyl)benzo-
1
[f]quinoline (Ve). Yield 53%, colorless crystalline
1
substance, mp 210 C. IR spectrum, , cm : 3442,
3321, 2973, 1600, 1572, 1534, 1522, 1471, 1455,
1379, 1352, 1288, 1239, 1176, 1113, 1037, 922, 834,
806, 759, 668. H NMR spectrum, , ppm: 1.06 t
1
1
(3H, OCH2Me), 3.42 q (2H, OCH2Me), 6.68 6.79
m (2H, Harom), 6.84 6.97 m (2H, Harom), 7.10
7.23 m (6H, Harom), 7.32 7.52 m (3H, Harom), 8.00
8.16 m (2H, Harom), 8.27 s (1H, OH). Mass spec-
trum, m/z (Irel, %): 392 (43) [M + 1]+, 391 (100) [M]+,
362 (34) [M C2H5]+, 353 (27), 143 (76), 115 (52).
Found, %: C 82.90; H 5.34; N 3.57. C27H21NO2.
Calculated, %: C 82.87; H 5.37; N 3.58.
3-(4-Chlorophenyl)-1-(4-ethoxyphenyl)benzo[f]-
quinoline (Vb). Yield 68%, yellow crystalline sub-
stance, mp 210 212 C. IR spectrum, , cm : 3440,
2970, 1603, 1574, 1547, 1513, 1509, 1470, 1452,
1386, 1351, 1300, 1232, 1176, 1046, 931, 852, 750,
700, 663, 592. H NMR spectrum, , ppm: 1.40 t (3H,
OCH2Me), 4.07 q (2H, OCH2Me), 7.03 7.15 m (3H,
Harom), 7.45 7.58 m (6H, Harom), 7.90 8.10 m (4H,
Harom), 8.18 d (1H, Harom, J = 7.7 Hz), 8.34 d (1H,
Harom, J = 7.9 Hz). Mass spectrum, m/z (Irel, %): 410
(40) [M + 1]+, 409 (100) [M]+, 382 (13) [M C2H5]+,
380 (38), 352 (12), 346 (14), 315 (12). Found, %: C
79.24; H 4.90; Cl 8.53; N 3.44. C27H20ClNO. Calcu-
lated, %: C 79.22; H 4.89; Cl 8.56; N 3.42.
1
3-Phenyl-1-(4-propoxyphenyl)benzo[f]quinoline
(Vf). Yield 32%, colorless crystalline substance, mp
138 C. IR spectrum, , cm : 3440, 2975, 1627, 1544,
1472, 1436, 1379, 1323, 1300, 1288, 1231, 1172,
1110, 1041, 923, 835, 801, 762, 704, 669. H NMR
spectrum, , ppm: 0.80 t (3H, OCH2CH2Me), 1.50 t
(2H, OCH2CH2Me), 3.50 t (2H, OCH2CH2Me), 7.06
7.18 m (3H, Harom), 7.42 7.60 m (7H, Harom), 7.85
8.12 m (4H, Harom), 8.18 d (1H, Harom, J = 8.0 Hz),
8.27 d (1H, Harom, J = 7.9 Hz). Mass spectrum, m/z
(Irel, %): 390 (16) [M + 1]+, 389 (100) [M]+, 347 (63)
[M C2H5]+, 346 (84), 252 (13). Found, %: C 86.41;
H 6.02; N 3.57. C28H23NO. Calculated, %: C 86.37;
H 5.91; N 3.60.
1
1
1
3-(4-Bromophenyl)-1-(4-ethoxyphenyl)benzo[f]-
quinoline (Vc). Yield 72%, colorless crystalline sub-
stance, mp 216 C. IR spectrum, , cm : 3431, 2968,
1
3-(4-Chlorophenyl)-1-(4-propoxyphenyl)benzo-
[f]quinoline (Vg). Yield 90%, yellow crystalline
1614, 1578, 1509, 1464, 1387, 1308, 1230, 1174,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 11 2006

1814
KOZLOV, BASALAEVA
1
substance, mp 176 C. IR spectrum, , cm : 3444,
2961, 2922, 2545, 1598, 1573, 1516, 1450, 1367,
1320, 1301, 1257, 1197, 1159, 1014, 971, 847, 750,
1]+, 405(100) [M]+, 363 (57) [M C3H7]+, 362 (54),
107 (23), 143 (51), 115 (34), 107 (25). Found, %: C
82.94; H 5.68; N 3.42. C28H23NO2. Calculated, %: C
82.96; H 5.67; N 3.46.
1
738, 588. H NMR spectrum, , ppm: 0.85 t (3H,
OCH2CH2Me), 1.47 t (2H, OCH2CH2Me), 3.46 t (2H,
OCH2CH2Me), 7.06 7.20 m (3H, Harom), 7.42 7.60
m (6H, Harom), 7.80 8.14 m (4H, Harom), 8.20 d (1H,
Harom, J = 7.6 Hz), 8.33 d (1H, Harom, J = 7.6 Hz).
Mass spectrum, m/z (Irel, %): 424 (33) [M + 1]+, 423
(100) [M]+, 380 (65) [M C2H5]+, 291 (63), 149 (84),
107 (85). Found, %: C 79.40; H 5.18; Cl 8.25; N 3.37.
C28H22ClNO. Calculated, %: C 79.43; H 5.20; Cl 8.27;
N 3.30.
1-(3-Bromo-5-ethoxy-4-hydroxyphenyl)-3-phe-
nylbenzo[f]quinoline (Vk). Yield 42%, light brown
1
substance, mp 229 230 C. IR spectrum, , cm :
3452, 3446, 3323, 2971, 1594, 1526, 1478, 1459,
1384, 1363, 1301, 1287, 1232, 1178, 1110, 1043, 938,
1
843, 762, 571. H NMR spectrum, , ppm: 1.40 t (3H,
OCH2Me), 4.25 q (2H, OCH2Me), 7.20 m (1H, Harom),
7.40 7.68 m (7H, Harom), 7.85 8.18 m (6H, Harom),
9.70 s (1H, OH). Mass spectrum, m/z (Irel, %): 470
(100) [M]+, 441 (57), 425 (15), 390 (23). Found, %:
C 68.95; H 4.27; Br 17.02; N 2.96. C27H20NO2Br.
Calculated, %: C 68.93; H 4.25; Br 17.02; N 2.98.
3-(4-Bromophenyl)-1-(4-propoxyphenyl)benzo-
[f]quinoline (Vh). Yield 76%, colorless crystalline
1
substance, mp 183 C. IR spectrum, , cm : 3440,
2960, 2921, 2543, 1592, 1500, 1457, 1362, 1318,
1254, 1191, 1157, 1014, 970, 823, 750, 736, 579. H
1-(3-Bromo-5-ethoxy-4-hydroxyphenyl)-3-(4-
chlorophenyl)benzo[f]quinoline (Vl). Yield 20%,
colorless crystalline substance, mp 230 231 C. IR
1
NMR spectrum, , ppm: 0.87 t (3H, OCH2CH2Me),
1.46 t (2H, OCH2CH2Me), 3.49 t (2H, OCH2CH2Me),
7.06 7.20 m (3H, Harom), 7.46 7.59 m (6H, Harom),
7.94 8.19 m (4H, Harom), 8.24 d (1H, Harom, J =
7.6 Hz), 8.38 d (1H, Harom, J = 7.9 Hz). Mass spec-
trum, m/z (Irel, %): 469 (40) [M + 1]+, 468 (100) [M]+,
425 (59) [M C3H7]+, 345 (30), 108 (27). Found, %:
C 71.81; H 4.69; Br 17.01; N 2.98. C28H22BrNO.
Calculated, %: C 71.79; H 4.70; Br 17.05; N 2.99.
1
spectrum, , cm : 3338, 2985, 1607, 1572, 1529,
1474, 1448, 1381, 1352, 1307, 1238, 1174, 1043, 929,
1
848, 741, 725, 572. H NMR spectrum, , ppm: 1.43
t (3H, OCH2Me), 4.23 q (2H, OCH2Me), 7.25 m (1H,
Harom), 7.36 7.54 m (7H, Harom), 7.63 7.72 m (3H,
Harom), 7.79 d (1H, Harom, J = 7.6 Hz), 8.06 d (1H,
Harom, J = 7.9 Hz), 9.65 s (1H, OH). Mass spectrum,
m/z (Irel, %): 504 (100) [M]+, 475 (53), 463 (20), 459
(17). Found, %: C 65.23; H 3.76; Cl 6.92; Br 15.79;
N 2.75. C27H19ClBrNO2. Calculated, %: C 65.28; H
3.77; Cl 6.94; Br 15.87; N 2.78.
3-(4-Hydroxyphenyl)-1-(4-propoxyphenyl)ben-
zo[f]quinoline (Vi). Yield 94%, yellow crystalline
1
substance, mp 199 200 C. IR spectrum, , cm :
3442, 3104, 2923, 1611, 1587, 1516, 1446, 1363,
1320, 1250, 1190, 1156, 1069, 1012, 975, 881, 848,
830, 758, 736, 518, 480. H NMR spectrum, , ppm:
1-(3-Bromo-5-ethoxy-4-hydroxyphenyl)-3-(4-
bromophenyl)benzo[f]quinoline (Vm). Yield 40%,
light brown substance, mp 235 236 C. IR spectrum, ,
1
1
0.88 t (3H, OCH2CH2Me), 1.49 t (2H, OCH2CH2Me),
3.45 t (2H, OCH2CH2Me), 6.64 6.78 m (2H, Harom),
6.82 6.94 m (2H, Harom), 7.00 7.22 m (6H, Harom),
7.32 7.48 m (3H, Harom), 7.82 8.05 m (2H, Harom),
8.20 s (1H, OH). Mass spectrum, m/z (Irel, %): 406
(14) [M + 1]+, 405 (100) [M]+, 363 (51) [M C3H7]+,
362 (61), 107 (15), 143 (98), 115 (48), 107 (19).
Found, %: C 82.95; H 5.67; N 3.44. C28H23NO2.
Calculated, %: C 82.96; H 5.67; N 3.46.
cm : 3341, 3328, 2963, 1604, 1568, 1514, 1472,
1443, 1376, 1342, 1301, 1235, 1170, 1039, 930, 740,
1
720, 569. H NMR spectrum, , ppm: 1.40 t (3H,
OCH2Me), 4.37 q (2H, OCH2Me), 7.34 m (1H, Harom),
7.39 7.52 m (7H, Harom), 7.60 7.70 m (3H, Harom),
7.82 d (1H, Harom, J = 8.2 Hz), 8.03 d (1H, Harom, J =
8.0 Hz), 9.68 s (1H, OH). Mass spectrum, m/z (Irel,
%): 549 (100) [M]+, 520 (53), 504 (27), 424 (16).
Found, %: C 59.00; H 3.47; Br 29.08; N 2.58. C27H19
Br2NO2. Calculated, %: C 59.02; H 3.16; Br 29.14;
N 2.55.
3-(2-Hydroxyphenyl)-1-(4-propoxyphenyl)ben-
zo[f]quinoline (Vj). Yield 84%, colorless crystalline
1
substance, mp 200 C. IR spectrum, , cm : 3439,
1-(3-Bromo-5-ethoxy-4-hydroxyphenyl)-3-(4-
hydroxyphenyl)benzo[f]quinoline (Vn). Yield 23%,
colorless crystalline substance, mp 257 258 C. IR
3101, 2927, 1611, 1593, 1484, 1375, 1324, 1266,
1190, 1163, 1068, 1017, 970, 874, 832, 750, 732, 522,
1
1
484. H NMR spectrum, , ppm: 0.90 t (3H, OCH2
spectrum, , cm : 3341, 3333, 2970, 2815, 1612,
CH2Me), 1.45 t (2H, OCH2CH2Me), 3.48 t (2H,
OCH2CH2Me), 6.65 6.72 m (2H, Harom), 6.86 6.98 m
(2H, Harom), 7.05 7.19 m (6H, Harom), 7.37 7.53 m
(3H, Harom), 7.82 8.07 m (2H, Harom), 8.26 s (1H,
OH). Mass spectrum, m/z (Irel, %): 406 (22) [M +
1573, 1509, 1467, 1441, 1358, 1311, 1234, 1162,
1031, 928, 713, 563. H NMR spectrum, , ppm: 1.40
t (3H, OCH2Me), 4.25 q (2H, OCH2Me), 7.00 7.60 m
(6H, Harom), 7.70 8.20 m (7H, Harom), 9.45 s (1H,
OH), 9.68 s (1H, OH). Mass spectrum, m/z (Irel, %):
1
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 11 2006

CASCADE HETEROCYCLIZATION OF 2-NAPHTHYLAMINE
1815
486 (100) [M]+, 457 (41), 440 (25), 360 (11). Found,
%: C 66.63; H 4.06; Br 16.50; N 2.88. C27H20BrNO3.
Calculated, %: C 66.66; H 4.11; Br 16.46; N 2.88.
3-(4-Bromophenyl)-1-[4-(2-fluorophenylmeth-
oxy)phenyl]benzo[f]quinoline (Vr). Yield 82%,
colorless crystalline substance, mp 210 212 C. IR
1
spectrum, , cm : 3334, 2967, 2820, 1604, 1581,
1-(3-Bromo-5-ethoxy-4-hydroxyphenyl)-3-(2-
hydroxyphenyl)benzo[f]quinoline (Vo). Yield 16%,
colorless crystalline substance, mp 256 258 C. IR
1510, 1468, 1353, 1236, 1167, 1158, 1024, 930, 564.
1H NMR spectrum, , ppm: 5.40 s (2H, OCH2), 7.10
7.75 m (14H, Harom), 7.85 d (1H, Harom, J = 8.5 Hz),
7.90 8.05 m (2H, Harom), 8.10 8.20 m (2H, Harom).
Mass spectrum, m/z (Irel, %): 535 (9) [M + 1]+, 534
(100) [M]+, 409 (53), 314 (15), 126 (23). Found, %: C
71.91; H 3.96; Br 14.94; N 2.60. C32H21BrFNO.
Calculated, %: C 71.91; H 3.93; Br 14.98; N 2.62.
1
spectrum, , cm : 3339, 2992, 2823, 1618, 1574,
1509, 1468, 1443, 1361, 1321, 1239, 1167, 1026, 924,
1
717, 560. H NMR spectrum, , ppm: 1.35 t (3H,
OCH2Me), 4.20 q (2H, OCH2Me), 7.02 d (1H, 3 -H,
J3 ,4 = 8 Hz), 7.05 d.d (1H, 5 -H, J4 ,5 = 8, J5 ,6
7 Hz), 7.22 t (1H, 8-H, J8,9 = 7 Hz), 7.33 d (1H, 6 -H,
J6 ,5 = 8 Hz), 7.41 d.d (1H, 4 -H, J3 ,4 = 7, J4 ,5
=
=
1-[4-(2-Fluorophenylmethoxy)phenyl]-3-(4-hyd-
roxyphenyl)benzo[f]quinoline (Vs). Yield 51%,
colorless crystalline substance, mp 229 230 C. IR
8 Hz), 7.52 t (1H, 9-H, J9,10 = 8 Hz), 7.81 d (1H, 7-H,
J7,8 = 7 Hz), 7.89 s (1H, 6 -H), 7.94 s (1H, 2-H),
7.98 d (1H, 10-H, J10,9 = 8 Hz), 8.02 d (1H, 5-H,
J5,6 = 9 Hz), 8.09 d (1H, 6-H, J5,6 = 9 Hz), 8.12 s
(1H, 2 -H), 9.30 s (1H, OH), 9.45 s (1H, OH). 13C
NMR spectrum, C, ppm: 145.5 (C1), 121.2 (C2),
146.5 (C3), 148.5 (C4a), 128.7 (C5), 131.2 (C6), 130.0
(C6a), 125.9 (C7), 126.1 (C8), 126.4 (C9), 128.6 (C10),
131.9 (C10a), 130.3 (C10b), 129.5 (C1 ), 123.2 (C2 ),
122.8 (C3 ), 147.7 (C4 ), 124.2 (C5 ), 110.8 (C6 ), 122.8
(C1 ), 153.9 (C2 ), 115.8 (C3 ), 129.7 (C4 ), 119.9
(C5 ), 129.5 (C6 ). Mass spectrum, m/z (Irel, %): 486
(100) [M]+, 457 (43), 440 (29), 360 (17). Found, %: C
66.62; H 4.07; Br 16.47; N 2.87. C27H20BrNO3. Cal-
culated, %: C 66.66; H 4.11; Br 16.46; N 2.88.
1
spectrum, , cm : 3330, 3324, 3010, 2971, 2818,
1599, 1573, 1512, 1463, 1358, 1234, 1179, 1150,
1
1016, 929, 831, 646, 512. H NMR spectrum, , ppm:
5.25 s (2H, OCH2), 7.10 7.60 m (12H, Harom), 7.80
8.10 m (5H, Harom), 8.25 d (1H, Harom, J = 7.6 Hz),
8.38 d (1H, Harom, J = 7.9 Hz), 9.40 s (1H, OH). Mass
spectrum, m/z (Irel, %): 472 (22) [M + 1]+, 471 (100)
[M]+, 346 (65), 251 (18), 234 (15), 233 (21), 232 (11).
Found, %: C 81.55; H 4.63; N 3.00. C32H22FNO2.
Calculated, %: C 81.53; H 4.67; N 2.97.
1-[4-(2-Fluorophenylmethoxy)phenyl]-3-(2-hyd-
roxyphenyl)benzo[f]quinoline (Vt). Yield 47%,
colorless crystalline substance, mp 224 225 C. IR
1-[4-(2-Fluorophenylmethoxy)phenyl]-3-phenyl-
1
spectrum, , cm : 3328, 3318, 3007, 2976, 2823,
benzo[f]quinoline (Vp). Yield 29%, colorless crystal-
1
1592, 1569, 1514, 1462, 1358, 1231, 1179, 1156,
line substance, mp 176 C. IR spectrum, , cm : 3305,
1
1012, 927, 832, 646, 521. H NMR spectrum, , ppm:
2954, 2807, 1594, 1568, 1514, 1462, 1352, 1237,
1
5.19 s (2H, OCH2), 7.00 7.40 m (12H, Harom), 7.64
8.00 m (5H, Harom), 8.28 d (1H, Harom, J = 7.9 Hz),
8.43 d (1H, Harom, J = 8.0 Hz), 9.36 s (1H, OH). Mass
spectrum, m/z (Irel, %): 472 (12) [M + 1]+, 471 (100)
[M]+, 346 (61), 251 (25), 234 (11), 233 (29), 232 (9).
Found, %: C 81.54; H 4.68; N 2.99. C32H22FNO2.
Calculated, %: C 81.53; H 4.67; N 2.97.
1160, 1153, 1035, 936, 918, 725. H NMR spectrum,
, ppm: 5.20 s (2H, OCH2), 7.05 7.25 m (7H, Harom),
7.38 7.50 m (6H, Harom), 7.80 7.94 m (3H, Harom),
8.05 s (1H, Harom), 8.24 s (1H, Harom), 8.37 d (1H,
Harom, J = 7.8 Hz), 8.50 d (1H, Harom, J = 7.8 Hz).
Mass spectrum, m/z (Irel, %): 456 (12) [M + 1]+, 455
(100) [M]+, 356 (36), 330 (28). Found, %: C 84.35; H
4.80; N 3.10. C32H22FNO. Calculated, %: C 84.39; H
4.83; N 3.08.
REFERENCES
3-(4-Chlorophenyl)-1-[4-(2-fluorophenylmeth-
oxy)phenyl]benzo[f]quinoline (Vq). Yield 27%,
colorless crystalline substance, mp 196 198 C. IR
1. Ferlin, M.G., Marzano, C., Chiarelotto, G., Bacci-
chetti, F., and Bordin, F., Eur. J. Med. Chem., 2000,
vol. 35, no. 9, p. 827.
1
spectrum, , cm : 3328, 3306, 2953, 2810, 1597,
2. Dyson, G.M. and May, P., The Chemistry of Synthetic
Drugs, London: Longmans, 1959, 5th ed.
1576, 1508, 1464, 1350, 1232, 1164, 1150, 1031, 934,
1
848. H NMR spectrum, , ppm: 5.20 s (2H, OCH2),
7.10 7.50 m (11H, Harom), 7.70 7.90 m (3H, Harom),
8.00 s (1H, Harom), 8.30 8.40 m (2H, Harom), 8.54 d
(1H, Harom, J = 7.7 Hz). Mass spectrum, m/z (Irel, %):
490 (15) [M + 1]+, 489 (100) [M]+, 364 (44), 269 (13).
Found, %: C 78.59; H 4.31; Cl 7.18; N 2.87. C32H21
ClFNO. Calculated, %: C 78.52; H 4.29; Cl 7.18;
N 2.86.
3. Smidrekal, J., Collect. Czech. Chem. Commun., 1988,
vol. 53, no. 9, p. 3186.
4. Watts, W.J., Lawler, C.P., and Knoerzer, T., Eur. J.
Pharmacol., 1993, vol. 239, no. 2, p. 271.
5. Kozlov, N.S., Kozlov, G.N., and Britan, E.A., Zh.
Obshch. Khim., 1963, vol. 33, no. 9, p. 3089.
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1816
KOZLOV, BASALAEVA
6. Kozlov, N.S., 5,6-Benzokhinoliny (5,6-Benzoquino-
11. Kozlov, N.G., Basalaeva, L.I., Firgang, S.I., and
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Krot, N.A., Khim. Geterotsikl. Soedin., 1985, no. 10,
p. 1398.
13. Obshchii praktikum po organicheskoi khimii (General
Practicum on Organic Chemistry), Kost, A.N., Ed.,
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7. Desenko, S.M., Orlov, V.D., Getmanskii, N.V.,
Shishkin, O.V., Lindeman, S.V., and Struchkov, Yu.T.,
Khim. Geterotsikl. Soedin., 1993, no. 4, p. 41.
8. Desenko, S.M. and Orlov, V.D., Azageterotsikly na
osnove aromaticheskikh nepredel’nykh ketonov (Aza
Heterocycles on the Basis of Aromatic Unsaturated
Ketones), Khar’kov: Folio, 1998.
14. Macovski, E. and Silberg, A., J. Prakt. Chem., 1933,
9. Wermann, K. and Hartmann, M., Synthesis, 1991,
vol. 137, no. 3, p. 131.
no. 3, p. 189.
15. Kozlov, N.S., Pak, V.D., and Simonova, E.V., Izv.
Akad. Navuk BSSR, Ser. Khim. Navuk, 1968, no. 4,
p. 111.
10. Desenko, S.M., Orlov, V.D., and Estrada, Kh., Khim.
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 11 2006