Condensation of fluorosubstituted benzaldehydes with amines and cyclic 1,3-diketones

Article abstract of DOI:10.1134/S107042800611011X

Condensation of fluorosubstituted benzaldehydes with 2-naphthyl or 6-quinolylamine and cyclic β-diketones (,3-cyclohexanedione, dimedone, and 1,3-indandione) provided new fluoroderivatives of benzo[a]-acridine, 4,7-phenanthroline, and benzo[f]indeno[1,2-b

Full text of DOI:10.1134/S107042800611011X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2006, Vol. 42, No. 11, pp. 1668−1674.  Pleiades Publishing, Inc. 2006.
Original Russian Text  N.G. Kozlov, K.N. Gusak, 2006, published in Zhurnal Organicheskoi Khimii, 2006, Vol. 42, No. 11, pp. 1680−1686.
Condensation of Fluorosubstituted Benzaldehydes
with Amines and Cyclic 1,3-Diketones
N. G. Kozlov and K. N. Gusak
Institite of Physical Organic Chemistry, National Academy of Sciences of Belarus, Minsk, 220072Belarus
e-mail: loc@ifoch.bas-net.by
Received October 31, 2005
Abstract—Condensation of fluorosubstituted benzaldehydes with 2-naphthyl or 6-quinolylamine and cyclic
β-diketones (,3-cyclohexanedione, dimedone, and 1,3-indandione) provided new fluoroderivatives of benzo[a]-
acridine, 4,7-phenanthroline, and benzo[f]indeno[1,2-b]quinoline. Forming in the course of the reaction
fluorophenylmethylene-2-naphthyl-(or 6-quinolyl)amines, arylbis(cyclohexane-1,3-dion-2-yl)methanes, and
2-(fluorophenylmethylene)-1,3-indandiones were isolated.
DOI: 10.1134/S107042800611011X
the alcoholic medium suffers a hydramine cleavage into
amine and 2-(arylmethylene)cyclohexane-1,3-dione B
which having a double bond activated by conjugation with
two neighboring carbonyl groups reacts with the aromatic
ring of the amine II or III at the carbon atom possessing
the largest electron density and located in the α-position
to the amino group to give aminodiketone C. The
dehydrocyclization of intermediate C results in a selective
formation of 12-[2-(4-)fluorophenyl- or 4-(2-fluoro-
benzyloxy)phenyl]-8,9,10,12-tetrahydro-7H-benzo[a]-
acridin-11-one IXa–IXc, 12-[2-(4-)fluorophenyl- or 4-(2-
fluorobenzyloxy)phenyl]-8,9,10,12-tetrahydro-7H-benzo-
[b][4,7]phenanthrolin-11-one Xa–Xc, and their 9-dimethyl
derivatives XIa–XIc and XIIa–XIIc in 68–84% yield.
Three-component condensation of aldehydes with
aromatic (heteroaromatic) amines and CH-acids of
various classes got recently impact as an efficient
synthetic procedure for fused nitrogen-containing hetero-
cycles [1–4]. Especially worthy of attention are reactions
of fluorosubstituted benzaldehydes with arylamines and
cyclic β-diketones as a pathway to preparation of aza-
heterocycles containing in the molecule a partially hy-
drogenated quinoline fragment, oxo group, and a fluorine
atom thus belonging to analogs of antibiotics from the
fluoroquinolone series, pesticides, compounds with
antitumor, bactericidal, and antienzyme action [5–9].
In this study we investigated for the first time a three-
component condensation of 2- and 4-fluorobenzaldehydes
(Ia and Ib), 4-(2-fluorobenzyloxy)benzaldehyde (Ic) with
2-naphthyl- and 6-quinolylamine (II and III), and β-di-
ketones [1,3-cyclohexanedione (IV), dimedone (V), and
1,3-indandione (VI)].
The conversion of aminodiketone A into aminodione
C analogously to the data of [10] can be interpreted as
a rearrangement of intermediate A by the type of Hof-
mann–Martius rearrangement (migration of N-alkyl
substituents in alkylanilines into the aromatic ring [11]).
The condensation of aldehydes Ia–Ic, amines II and
III, and diketones IV and V was performed by heating
an equimolar mixture of reagents in butanol without
catalyst. The process of building up a structure of a fused
heterocycle involved a cascade of transformations and
could take several routes. Firstly, aldehyde Ia–Ic can
initially condense with arylamine II or III giving
azomethine VIIa–VIIc or VIIIa–VIIIc that further takes
up dione IV or V yielding aminodiketone A. The latter in
We synthesized azomethines VIIa–VIIc and VIIIa–
VIIIc, where compounds VIIc and VIIIc had not been
described before, by condensation of aldehydes Ia–Ic
with amines II and III at boiling in ethanol without
catalyst. On reacting azomethines VIIa–VIIc and VIIIa–
VIIIc with diketones IV and V under the above described
conditions of three-component condensation cleanly
formed benzoacridones and 4,7-phenanthrolinones IXa–
IXc− XIIa–XIIc.
1668

CONDENSATION OF FLUOROSUBSTITUTED BENZALDEHYDES
R'
1669
R'
R'
O
O
R
NH2
R
R'
X
II, III
O
IV, V
O
N
R
O
_
NH
Iа Ic
X
_
_
VIIа VIIc, VIIIа VIIIc
O
VIIc
IV, V
X
A
O
VI
O
R
R'
O
XVb, XVc
O
R
R'
R'
II
O
O
B
II, III
R
R'
O
R
O
X
NH2
NH
C
R'
O
XVIb, XVIc
R'
R'
O
R
R
R'
O
O
R
O
NH
O
N
X
R'
R'
_
_
_
IXа IXc XIIа XIIc
XVIIb, XVIIc
_
_
_
XIIIа XIIIc XIVа XIIc
I, VII–XVII: R = 2-F (a), 4-F (b), 4-OCH2(2-FC6H4) (c); R' = H (IV, IXa–IXc, Xa–Xc, XIIIa–XIIIc), Me (V, XIa–XIc, XIIa–XIIc,
XIVa–XIVc); X = CH (II,VIIa–VIIc, IXa–IXc, XIa–XIc), N (III, VIIIa–VIIIc, Xa–Xc, XIIa–XIIc).
In a three-component reagents mixture (aldehyde +
amine + diketone) 2-(arylmethylene)cyclohexane-1,3-
dione B could form directly from aldehyde Ia–Ic and
dione IV or V and react further with amine II or III
along the above described mechanism. At attempt to
obtain enediones B by heating an equimolar mixture of
aldehyde Ia–Ic with diketones IV or V aiming at involving
them further into reaction with amines II or III we isolated
bisdicarbonyl derivatives XIIIa–XIIIc and XIVa–XIVc
whose formation was consistent with the data of [1]. At
boiling with amines II or III in butanol solution bisdiketones
XIIIa–XIIIc and XIVa–XIVc were converted into aza-
and diazaphenanthrenes IXa–IXc−XIIa–XIIc. Appar-
ently the bisadduct eliminated a molecule of dione IV or
V separating 2-arylidenedione B that further reacted with
amine II or III through a stage of formation of amino-
diketone C to give finally fused reaction product IXa–
IXc−XIIa–XIIc. Thus the second probable route of the
three-component condensation may be initial reaction
between aldehyde Ia–Ic with diketone IV or V and
involvement of arylmethylenedione B in the next stage
of amine II or III addition in situ.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

KOZLOV, GUSAK
1670
In the course of the condensation of aldehydes Ia and
280 for indenoquinolines XVIb and XVIc, XVIIb and
XVIIc). In the spectra of compounds IXa–IXc−XIIa–
XIIc a relatively strong peak (21–28%) is also present
of ion with m/z 192 for acridones IXa–IXc and XIa–
XIc, and 193 for phenanthrolinones Xa–Xc and XIIa–
XIIc corresponding to elimination from ion [M – R]+ of
a fragment CH2CH2CO for compounds IXa–IXc and
Xa–Xc, and Me2CCH2CO for dimedone derivatives XIa–
XIc and XIIa–XIIc.
Ib with amine II and indane-1,3-dione (VI) in butanol
without catalyst we established that before the target
products of the benzoindenoquinoline series started to form
in the reaction mixture analogs of hypothetical inter-
mediate B were present, 2-[4-fluoro-phenyl- or 4-(2-
fluorobenzyloxy)phenyl]methyleneindane-1,3-diones XVb
and XVc. These compounds were obtained in individual
state by boiling equimolar amounts of aldehyde Ia and Ib
and dione VI in ethanol, and in reaction with amine II
under the conditions of the three-component condensation
they led to the formation of 13-[4-fluorophenyl- or 4-(2-
fluorobenzyloxy)phenyl]-7,13-dihydro-12H-benzo[f]-
indeno[1,2-b]quinoline-12-ones (XVIb and XVIc). The
synthesis of indenoquinolines XVIb and XVIc evidently
involves the stages of arylmethylenedione XVb and XVc
addition to amine II at the electron-rich α-position of the
naphthalene skeleton and of cyclization of the intermedi-
ate aminodiketone analogous to intermediate C. Dihydro
compounds XVIb and XVIc on boiling in nitrobenzene
undergo dehydrogenation into 13-[4-fluorophenyl- or
4-(2-fluoro-benzyloxy)phenyl]-12H-benzo[f]indeno[1,2-
b]-quinoline-12-ones (XVIIb and XVIIc).
The UV absorption spectra of compounds IXa–IXc−
XIIa–XIIc, XVIb and XVIc possess pronounced vibronic
structure. The molecules of partially hydrogenated benzo-
acridones IXa–IXc and XIa–XIc and benzophenanthro-
linones Xa–Xc and XIIa–XIIc contain three independent
chromophore fragments: fluorophenyl substituent,
carbonyl group, and naphthalene or quinoline fragment.
*
The latter contribute the most into the system of π,π -
electronic transitions. Therefore the bands in the range
214–290 nm in the spectra of acridones IXa–IXc and
XIa–XIc may be assigned to the system of 2-naphthyl-
amine (II) [UV spectrum, λmax, nm (log ε): 204 (4.06),
246 (4.35), 280 (3.63)], and in the spectra of phenanthro-
linones Xa–Xc and XIIa–XIIc, to the system of 6-quinolyl-
amine (III) [UV spectrum, λmax, nm (log ε): 206 (4.08),
247 (4.35), 279 (3.59)]. The considerable red shift,
increased intensity of the bands, and stronger vibronic
structure observed for acridones in the mentioned spectral
range were apparently due to the superposition of the
absorption bands of the fluorophenyl substituent. The
absorption bands in the longwave spectral region (330–
340, 371–382 nm) are due according to [1] to the presence
of carbonyl group. In the spectra of compounds XVIb
and XVIc a significant shift is observed of the longwave
absorption maximum (476–480 nm) into the visible spectral
range caused evidently by the presence of a fused
indenone ring in the structure of azaphenanthrene. In the
UV spectra of dehydration products XVIIb and XVIIc
appeared a very strong band at 295–314 nm and a less
strong band with a vibronic structure at 223–255 nm.
The presence of these bands (β- and p-bands according
to Clar) makes the spectrum of compounds XVIIb and
XVIIc resembling the spectra of 1,3-diarylbenzo[f]quino-
lines [12]. The increase in the intensity of the mentioned
band observed in the spectra of compounds XVIIb and
XVIIc is apparently caused by the conjugation of the
benzo[f]quinoline core with the indenone system. The
longwave band in the spectra of indenoquinolines XVIIb
and XVIIc at 384–386 nm corresponds to the α-band in
the spectra of benzoquinolines [12], but suffered a red
shift as compared to the latter.
In the IR spectra of compounds IXa–IXc−XIIa–
XIIc, XVIb and XVIc characteristic absorption bands
are present of stretching and bending vibrations of the
NH group from the dihydropyridine ring at 3330–
3260 and 1635–1630 cm–1. The stretching vibrations of
the carbonyl conjugated with the eneamine fragment are
observed at 1655–1605 cm–1. The bands of the stretching
vibrations of the cycloaliphatic CH bonds appear at 2955–
2870 cm–1, of CH bonds in the aromatic rings, at 3060–
3030 cm–1. In the spectra of the oxidation products XVIIb
and XVIIc the band of stretching vibrations of the
carbonyl group is present at 1665 cm–1, and the bands of
NH group vibrations are lacking. The spectra of com-
pounds IXc–XIIc, XVIc, and XVIIc contain an absorp-
tion band in the region 1240–1230 cm–1 corresponding to
the stretching vibrations of C–O–C bonds in the benzoxy-
phenyl substituent.
In mass spectra of azaphenanthrenes the peaks of
molecular ions [M]+ appear, Irel 29–44% for compounds
IXa–IXc−XIIa–XIIc, XVIb and XVIc, and 100% for
indenoquinolines XVIIb and XVIIc, ion peaks [M –
C6H4R]+, Irel 100% for hydrogenated derivatives IXa–
IXc−XIIa–XIIc, XVIb and XVIc and 38% for oxidation
products XVIIb and XVIIc (m/z 248 for compounds IXa–
IXc, 249 for phenanthrolines Xa–Xc, 276 and 277 for
dimethyl derivatives XIa–XIc and XIIa–XIIc, 282 and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

CONDENSATION OF FLUOROSUBSTITUTED BENZALDEHYDES
1671
1H NMR spectra of compounds IXa–IXc−XIIa–
XIIc with respect to the position and multiplicity of signals
from aromatic and cycloaliphatic protons, and protons
of NH group are identical to the previously published
spectra of acridones and 4,7-phenanthrolinones [1, 2, 4].
In the 1H NMR spectra of of indeno derivatives XVIb
and XVIc, XVIIb and XVIIc the signals of aromatic
protons appear in the region 6.81–8.22 ppm. The signals
in the spectra of dihydro compounds XVIb and XVIc at
9.70–9.84 and 5.72–5.84 ppm corresponding respectively
to the protons of NH group and H13 of dihydropyridine
ring are absent in the spectra of oxidation products XVIIb
and XVIIc evidencing the aromatization of the
azaphenanthrene ring.
4-(2-Fluorobenzyloxy)phenylmethylene-6-
quinolylamine (VIIIc). Yield 79%, mp 97–98°C. UV
spectrum, λmax, nm (log ε): 207 (4.49), 235 (4.43), 266
1
(4.40), 328 (4.10). H NMR spectrum, δ, ppm: 5.10 s
(2H, OCH2), 7.04 d, 7.66 d, 7.38 m (8Harom), 7.30 d.d
(1H, H3), 7.46 s (1H, H5), 7.68 d.d (1H, H4), 8.12 d (2H,
H7,8), 8.56 s (1H, CH=N), 8.83 d.d (1H, H2). Found, %:
N 7.59. C23H17FN2O. Caculated, %: N 7.87.
12-Aryl-8,9,10,12-tetrahydro-7H-benzo[a]-
acridin-11-ones IXa–IXc and 12-aryl-8,9,10,12-
tetrahydro-7H-benzo[b][4,7]phenanthrolin-11-ones
Xa–Xc. a. A mixture of 5 mmol of aldehyde Ia–Ic,
5 mmol of 2-naphthylamine (II) for compounds IXa–IXc
or 6-quinolylamine for phenanthrolines Xa–Xc, 5 mmol
of cyclohexane-1,3-dione (IV), and 20 ml of butanol was
boiled for 3–4 h. The separated precipitate was filtered
off and recrystallized from a mixture ethanol–benzene,
2:1.
EXPERIMENTAL
IR spectra were recorded on a Fourier spectrometer
Nicolet Protege-460 from KBr pellets. Mass spectra
were measured on FINNIGAN MAT INCOS 50
instrument at the ionizing electrons energy 70 eV and on
a chromato-mass spectrometer Hewlett-Packard HP
5890/5972 in an electron impact ionization mode with an
energy 70 eV; column HP-5MS [30 m × 0.25 mm, station-
ary phase film 0.25µm thick (5% PLMe Silicone)];
vaporizer temperature 250°C. UV spectra of compounds
in ethanol (c 10–4 mol l−1) were taken on a spectro-
photometer Specord UV-Vis. NMR spectra were
registered on spectrometers Bruker AC-500 (500 MHz)
and Tesla BS-567 (100 MHz) in DMSO-d6 and CDCl3,
internal reference TMS. Melting points were measured
on a Koeffler heating block.
b. A solution of 5 mmol of azomethine VIIa–VIIc or
VIIIa–VIIIc, 5 mmol of diketone IV in 20 ml of butanol
was boiled for 3 h. Reaction products IXa–IXc and Xa–
Xc were isolated as described above.
12-(2-Fluorophenyl)-8,9,10,12-tetrahydro-7H-
benzo[a]acridin-11-one (IXa). Yield 72% (a), 75% (α),
mp 306–307°C. UV spectrum, λmax, nm (log ε): 215
(4.50), 232 (4.61), 277 (4.20), 290 (4.28), 337 (3.98), 372
1
(3.96). H NMR spectrum, δ, ppm: 1.89 m (2H, CH2),
2.20 m (2H, CH2), 2.63 m (2H, CH2), 5.82 s (1H, H12),
6.81–8.00 m (10Harom), 9.75 s (1H, NH). Found, %:
N 3.79. C23H18FNO. Caculated, %: N 4.08.
12-(4-Fluorophenyl)-8,9,10,12-tetrahydro-7H-
benzo[a]acridin-11-one (IXb). Yield 70% (a), 76% (α),
mp 301–302°C. UV spectrum, λmax, nm (log ε): 216
(4.52), 231 (4.63), 279 (4.21), 291 (4.30), 338 (3.96), 373
2- or 4-Fluorophenylmethylene-2-naphthyl(6-
quinolyl)amines VIIa, VIIb and VIIIa, VIIIb were
prepared by method [13], 2-(4-fluorophenylmethyl-
ene)indane-1,3-dione (XVb) was obtained and
identified by procedure [14].
1
(3.95). H NMR spectrum, δ, ppm: 1.86 m (2H, CH2),
2.22 m (2H, CH2), 2.64 m (2H, CH2), 5.85 s (1H, H12),
6.83–7.98 m (10Harom), 9.76 s (1H, NH). Found, %:
N 3.84. C23H18FNO. Caculated, %: N 4.08.
4-(2-Fluorobenzyloxy)phenylmethylene-2-
naphthyl-(6-quinolyl)amine (VIIc and VIIIc). Asolu-
tion of 5 mmol of aldehyde Ic, 5 mmol of 2-naphthylamine
(II) for azomethine VIIc or 6-quinolylamine (III) for
compound VIIIc in 20 ml of ethanol was boiled for
15 min. The precipitate separated on cooling was filtered
off and recrystallized from ethanol.
2-[4-(2-Fluorobenzyloxy)phenyl]-8,9,10,12-
tetrahydro-7H-benzo[a]acridin-11-one (IXc). Yield
68% (a), 66% (α), mp 268–269°C. UV spectrum, λmax
,
nm (log ε): 216 (4.50), 230 (4.61), 280 (4.18), 292 (4.29),
1
337 (3.98), 375 (3.96). H NMR spectrum, δ, ppm:
1.93 m (2H, CH2), 2.27 m (2H, CH2), 2.63 m (2H, CH2),
4.98 s (2H, OCH2), 5.80 s (1H, H12), 6.76–7.52 m, 7.70–
8.00 m (14Harom), 9.63 C (1H, NH). Found, %: N 2.96.
C30H24FNO2. Caculated, %: N 3.12.
4-(2-Fluorobenzyloxy)phenylmethylene-2-
naphthylamine (VIIc). Yield 82%, mp 100–101°C. UV
spectrum, λmax, nm (log ε): 205 (4.43), 236 (4.42), 265
1
(4.39), 330 (4.06). H NMR spectrum, δ, ppm: 5.07 s
(2H, OCH2), 7.02–8.03 m (15Harom), 8.54 s (1H, CH=N).
Found, %: N 3.76. C24H18FNO. Caculated, %: N 3.94.
12-(2-Fluorophenyl)-8,9,10,12-tetrahydro-7H-
benzo[b][4,7]phenanthrolin-11-one (Xa). Yield 82%
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

KOZLOV, GUSAK
1672
339 (3.89), 373 (3.85). 1H NMR spectrum, δ, ppm: 0.90 s
(3H, Me), 1.10 s (3H, Me), 2.21 m (2H, CH2), 2.54 m
(2H, CH2), 5.85s (1H, H12), 6.83–7.96 m (10Harom), 9.79 s
(1H, NH). Found, %: N 3.58. C25H22FNO. Caculated,
%: N 3.77.
(a), 80% (α), mp 301–302°C. UV spectrum, λmax, nm
(log ε): 216 (4.60), 241 (4.26), 293 (4.04), 332 (4.01),
378 (3.90). 1H NMR spectrum, δ, ppm: 1.88 m (2H, CH2),
2.20 m (2H, CH2), 2.62 m (2H, CH2), 5.80 s (1H, H12),
7.28 m (4Harom), 7.38 d.d (1H, H2), 7.50 d, 7.85 d (2H,
H5,6), 8.38 d (1H, H1), 8.66 d (1H, H3), 9.85 s (1H, NH).
Found, %: N 7.95. C22H17FN2O. Calculated, %: N 8.14.
9,9-Dimethyl-12-[4-(2-fluorobenzyloxy)phenyl]-
8,9,10,12-tetrahydro-7H-benzo[a]acridin-11-one
(XIc). Yield 74% (a), 69% (b), mp 271–272°C. UV
spectrum, λmax, nm (log ε): 215 (4.50), 234 (4.60), 275
(4.19), 291 (4.41), 340 (3.90), 375 (3.94). 1H NMR spec-
trum, δ, ppm: 0.88 s (3H, Me), 1.10 s (3H, Me), 2.13 d
(2H, CH2), 2.52 d (2H, CH2), 4.99 s (2H, OCH2), 5.76 s
(1H, H12), 6.78 d, 7.07–7.56 m, 7.70-8.03 m (14Harom),
9.68 s (1H, NH). Found, %: N 2.81. C32H28FNO2.
Caculated, %: N 2.94.
12-(4-Fluorophenyl)-8,9,10,12-tetrahydro-7H-
benzo[b][4,7]phenanthrolin-11-one (Xb). Yield 79%
(a), 76% (α), mp 312–313°C. UV spectrum, λmax, nm
(log ε): 215 (4.62), 242 (4.33), 297 (4.17), 335 (4.05),
378 (3.92). 1H NMR spectrum, δ, ppm: 1.87 m (2H, CH2),
2.21 m (2H, CH2), 2.59 m (2H, CH2), 5.82 s (1H, H12),
6.90 t, 7.18 d.d (4Harom), 7.35 d.d (1H, H2), 7.52 d, 7.86 d
(2H, H5,6), 8.30 d (1H, H1), 8.60 d (1H, H3), 9.82 s (1H,
NH). Found, %: N 8.01. C22H17FN2O. Caculated, %:
N 8.14.
9,9-Dimethyl-12-(2-fluorophenyl)-8,9,10,12-
tetrahydro-7H-benzo[b][4,7]phenanthrolin-11-one
(XIIa). Yield 71% (a), 66% (b), mp 299–300°C. UV
spectrum, λmax, nm (log ε): 215 (4.49), 239 (4.26), 290
(4.31), 337 (4.00), 380 (3.89). 1H NMR spectrum, δ, ppm:
0.89 s (3H, Me), 1.10 s (3H, Me), 2.08 d.d (2H, CH2),
2.48 m (2H, CH2), 5.77 s (1H, H12), 6.99 m, 7.19–7.28 m
(4Harom), 7.30 d.d (1H, H2), 7.49 d, 7.80 d (2H, H5,6),
8.29 d (1H, H1), 8.62 d (1H, H3), 9.51 s (1H, NH). Found,
%: N 7.43. C24H21FN2O. Caculated, %: N 7.53.
12-[(4-(2-Fluorobenzyloxy)phenyl]-8,9,10,12-
tetrahydro-7H-benzo[b][4,7]phenanthrolin-11-one
(Xc). Yield 69% (a), 72% (α), mp 293–294°C. UV spec-
trum, λmax, nm (log ε): 218 (4.61), 249 (4.33), 296 (4.21),
330 (4.09), 382 (4.00). 1H NMR spectrum, δ, ppm: 1.89 m
(2H, CH2), 2.24 m (2H, CH2), 2.60 m (2H, CH2), 5.00 s
(2H, OCH2), 5.90 s (1H, H12), 6.79 m, 7.10 d, 7.48 m
(8Harom), 7.31 d.d (1H, H2), 7.51 d, 7.89 d (2H, H5,6),
8.31 d (1H, H1), 8.60 d (1H, H3), 9.80 C (1H, NH).
Found, %: N 6.13. C29H23FN2O2. Caculated, %: N 6.22.
9,9-Dimethyl-12-(4-fluorophenyl)-8,9,10,12-
tetrahydro-7H-benzo[b][4,7]phenanthrolin-11-one
(XIIb). Yield 78% (a), 75% (b), mp 308–309°C. UV
spectrum, λmax, nm (log ε): 214 (4.50), 242 (4.61), 254
(4.22), 289 (4.30), 338(3.97), 376 (3.84). 1H NMR spec-
trum, δ, ppm: 0.88 s (3H, Me), 1.03 s (3H, Me), 2.10 d.d
(2H, CH2), 2.43 m (2H, CH2), 5.80 s (1H, H12), 6.91 t,
7.18 m (4Harom), 7.34 d.d (1H, H2), 7.51 d, 7.88 d (2H,
H5,6), 8.32 d (1H, H1), 8.64 d (1H, H3), 9.80 s (1H, NH).
Found, %: N 7.38. C24H20FN2O. Caculated, %: N 7.53.
12-Aryl-9,9-dimethyl-8,9,10,12-tetrahydro-7H-
benzo[a]acridin-11-ones XIa–XIc and 12-aryl-9,9-
dimethyl-8,9,10,12-tetrahydro-7H-benzo[b][4,7]-
phenanthrolin-11-ones XIIa–XIc were obtained from
aldehydes Ia–Ic, amines II or III, and dimedone (V)
(method a) or from ketone V and azomethine VIIa–VIIc
or VIIIa-VIIIc (method b) in the same way as com-
pounds IXa–IXc and Xa–Xc. Reaction products were
recrystallized from a mixture ethanol–benzene, 4:1.
9,9-Dimethyl-12-[4-(2-fluorobenzyloxy)phenyl]-
8 , 9 , 1 0 , 1 2 - t e t r a h y d r o - 7 H - b e n z o [ b ] [ 4 , 7 ] -
phenanthrolin-11-one (XIIc). Yield 72% (a), 65% (b),
mp 269–270°C. UV spectrum, λmax, nm (log ε): 215
(4.51), 241 (4.60), 252 (4.19), 288 (4.29), 339 (3.99), 373
9,9-Dimethyl-(2-fluorophenyl)-8,9,10,12-
tetrahydro-7H-benzo[a]acridin-11-oneOν (XIa).
Yield 71% (a), 67% (b), mp 288–289°C. UV spectrum,
λ
max, nm (log ε): 217 (4.49), 233 (4.60), 278 (4.19), 291
(4.29), 338 (3.90), 371 (3.93). 1H NMR spectrum, δ, ppm:
0.90 C (3H, Me), 1.11 s (3H, Mε), 2.19 m (2H, CH2),
2.57 m (2H, CH2), 5.83 s (1H, H12), 6.85 m, 7.12–7.96 m,
8.02 m (10Harom), 9.71 s (1H, NH). Found, %: N 3.49.
C25H22FNO. Caculated, %: N 3.77.
1
(3.97). H NMR spectrum, δ, ppm: 0.89 s (3H, Me),
1.06 s (3H, Me), 2.12 d.d (2H, CH2), 2.50 m (2H, CH2),
5.02 s (2H, OCH2), 5.87 s (1H, H12), 6.80 d, 7.14 d,
7.47 m (8Harom), 7.32 d.d (1H, H2), 7.52 d, 7.84 d (2H,
H5,6), 8.32 d (1H, H1), 8.59 d (1H, H3), 9.79 s (1H, NH).
Found, %: N 5.61. C31H27FN2O2. Caculated, %: N 5.86.
9,9-Dimethyl-(4-fluorophenyl)-8,9,10,12-
tetrahydro-7H-benzo[a]acridin-11-one (XIb). Yield
78 % (a), 80% (b), mp 313–314°C. UV spectrum, λmax
,
Arylbis(cyclohexane-1,3-dion-2-yl)methanes
XIIIa–XIIIc and XIVa–XIVc. A solution of 5 mmol of
nm (lgε): 216 (4.52), 231 (4.58), 277 (4.20), 293 (4.32),
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CONDENSATION OF FLUOROSUBSTITUTED BENZALDEHYDES
1673
an appropriate aldehyde Ia–Ic, 10 mmol of cyclohexane-
1,3-dione (IV) for compounds XIIIa–XIIIc or dimedone
(V) for dimethyl derivatives XIVa–XIVc in 20 ml of
ethanol was boiled for 20–30 min. Reaction products
XIIIa, XIIIb and XIVa, XIVb were recrystal-lized from
ethanol, compounds XIIIc and XIVc, from methanol.
Mε), 2.36–2.48 m, (8H, CH2), 5.10 s (2H, OCH2), 5.50 s
(1H, CH), 6.85–7.60 m (8Harom), 11.90 br.s (2H, OH).
Found, %: F 3.59. C30H33FO5. Caculated, %: F 3.86.
Condensation of arylbis(cyclohexane-1,3-dion-2-
yl)methanes XIIIa–XIIIc and XIVa–XIVc with
2-naphthyl- and 6-quinolylamines (II and III).
A solution of 5 mmol of tetraketone XIIIa–XIIIc and
XIVa–XIVc, 5 mmol of amine II or III in 20 ml of ethanol
was boiled for 3 h The separated precipitate was filtered
off, compounds IXa–IXc and Xa–Xc were recrystallized
from a mixture ethanol–benzene, 2:1, compounds XIa–
XIc and XIIa–XIIc, from a mixture ethanol–benzene,
4:1. Yield of azaphenanthrenes IXa–IXc − XIIa–XIIc
was 62–76%.
2-[(2,6-Dioxocyclohexyl)(2-fluorophenyl)-
methyl]cyclohexane-1,3-dione (XIIIa). Yield 76%, mp
200–201°C. UV spectrum, λmax, nm (log ε): 204 (4.63),
251 (4.64), 276 (4.29), 329 (3.85). 1H NMR spectrum, δ,
ppm: 1.99 m, 2.28 m, 2.59 m (12H, CH2), 4.98 s (1H,
CH), 6.82–7.10 m (4Harom), 11.98 br.s (2H, OH). Found,
%: F 5.38. C19H19FO4. Caculated, %: F 5.76.
2-[(2,6-Dioxocyclohexyl)(4-fluorophenyl)-
methyl]-1,3-cyclohexanedione (XIIIb). Yield 70%,
mp 186–187°C. UV spectrum, λmax, nm (log ε): 205
(4.66), 260 (4.67), 279 (4.30), 330 (3.87). 1H NMR spec-
trum, δ, ppm: 1.92 m, 2.29 m, 2.60 m (12H, CH2), 5.10 s
(1H, CH), 6.90 t, 7.12 d (4Harom), 11.93 br.s (2H, OH).
Found, %: F 5.49. C19H19FO4. Caculated, %: F 5.76.
2-[4-(2-Fluorobenzyloxy)phenyl]methylene-
indane-1,3-dione (XVc). A solution of 5 mmol of
aldehyde Ic and 5 mmol of diketone VI in 20 ml of butanol
was boiled for 2 h, the precipitate separated on cooling
was filtered off, washed with ether, and recrystallized
from dioxane. Yield 78%, mp 170–171°C. UV spectrum,
2-{(2,6-Dioxocyclohexyl)[4-(2-fluorobenzyloxy)-
phenyl]methyl}cyclohexane-1,3-dione (XIIIc). Yield
71%, mp 197–198°C. UV spectrum, λmax, nm (log ε):
206 (4.61), 260 (4.64), 280 (4.28), 329 (3.90). 1H NMR
spectrum, δ, ppm: 2.00 m, 2.30 m, 2.58 m (12H, CH2),
4.73 s (1H, CH), 5.04 s (2H, OCH2), 6.78–7.11 m
(8Harom), 11.96 br.s (2H, OH). Found, %: F 4.11.
C26H25FO5. Caculated, %: F 4.36.
λ
max, nm (log ε): 204 (4.23), 248 (4.19), 260 (4.10), 300
1
(3.53), 370 (4.23). H NMR spectrum, δ, ppm: 5.21 s
(2H, OCH2), 7.00–7.52 m, 7.70–8.02 m, 8.52 m (13Harom
C=CH). Found, %: F 5.18. C23H15FO3. Caculated, %:
F 5.31.
,
13-Aryl-7,13-dihydro-12H-benzo[f]indeno[1,2-
b]quinoline-12-ones XVIb and XVIc. A solution of
5 mmol of an appropriate aldehyde Ib or Ic, 5 mmol of
2-naphthylamine (II), 5 mmol of indane-1,3-dione (VI)
(a) or 5 mmol of amine II and 5 mmol of dione XVb or
XVc (b) in 20 ml of butanol was boiled for 6 h. The
precipitate of reaction product was boiled with benzene
and washed with ether.
2-[(4,4-Dimethyl-2,6-dioxocyclohexyl)(2-
fluorophenyl)methyl]-5,5-dimethylcyclohexane-1,3-
dione (XIVa). Yield 68%, mp 153–154°C. UV spectrum,
λ
max, nm (log ε): 207 (4.61), 258 (4.63), 272 (4.20), 331
1
(3.83). H NMR spectrum, δ, ppm: 1.12 s (12H, Me),
2.30–2.51 m (8H, CH2), 5.60 s (1H, CH), 6.90–7.30 m
(4Harom), 11.94 br.s (2H, OH). Found, %: F 4.67.
C23H27FO4. Caculated, %: F 4.92.
13-(4-Fluorophenyl)-7,13-dihydro-12H-benzo-
[f]indeno[1,2-b]quinolin-12-one (XVIb). Yield 84%
(a), 78% (b), mp 313–314°C. UV spectrum, λmax, nm
(log ε): 219 (4.79), 238 (4.76), 274 (4.78), 350 (3.98),
500 (3.57). 1H NMR spectrum, δ, ppm: 5.94 s (1H, H13),
7.20–7.92 m (14Harom), 9.82 s (1H, NH). Found, %:
N 3.56. C26H16FNO. Caculated, %: N 3.71.
2-[(4,4-Dimethyl-2,6-dioxocyclohexyl)(4-fluoro-
phenyl)methyl]-5,5-dimethylcyclohexane-1,3-dione
(XIVb). Yield 76%, mp 167–168°C. UV spectrum, λmax
,
nm (log ε): 206 (4.58), 257 (4.67), 273 (4.19), 329 (3.92).
1H NMR spectrum, δ, ppm: 1.11 s, 1.18 s (12H, Me),
2.34–2.45 m, (8H, CH2), 5.53 s (1H, CH), 6.89 t, 7.28 d
(4Harom), 11.97 br.s (2H, OH). Found, %: F 4.74.
C23H27FO4. Caculated, %: F 4.92.
13-[4-(2-Fluorobenzyloxy)phenyl]-7,13-dihydro-
12H-benzo[f]indeno[1,2-b]quinolin-12-one (XVIc).
Yield 64% (a), 60% (b), mp 321–322°C. UV spectrum,
λ
max, nm (log ε): 220 (4.69), 235 (4.68), 275 (4.76), 354
2-{(4,4-Dimethyl-2,6-dioxocyclohexyl)[4-(2-
fluorobenzyloxy)phenyl]methyl}cyclohexane-1,3-
dione (XIVc). Yield 67%, mp 177–178°C. UV spectrum,
1
(3.92), 496 (3.61). H NMR spectrum, δ, ppm: 5.00 s
(2H, OCH2), 5.72 s (1H, H13), 6.81 d, 7.08–7.67 m, 7.80–
7.97 m (18Harom), 9.70 s (1H, NH). Found, %: N 2.69.
C33H22FNO2. Caculated, %: N 2.90.
λ
max, nm (log ε): 207 (4.60), 259 (4.69), 271 (4.23), 330
(3.90). 1H NMR spectrum, δ, ppm: 1.10 s, 1.22 s (12H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

KOZLOV, GUSAK
1674
13-Aryl-12H-benzo[f]indeno[1,2-b]quinolin-12-
kov,A.S., Zh. Org. Khim., 2004, vol. 40, p. 549.
3. Kozlov, N.G., Basalaeva, L.I., and Tychinskaya, L.Yu., Zh.
Org. Khim., 2002, vol. 38, p. 1218.
4. Kozlov, N.G., Pashkovskii, F.S., Gusak, K.N., Koroleva, E.V.,
Tereshko, A.B., and Lokot’, I.P., Zh. Org. Khim., 2004,
vol. 40, p. 549.
ones XVIIb and XVIIc. A solution of 1 mmol of an
appropriate dihydro derivative XVIb or XVIc in 10 ml of
nitrobenzene was boiled for 8 h. The reaction products
were recrystallized from a mixture toluene–nitrobenzene,
2:1.
5. Mashkovskii, M.D., Lekarstvennye sredstva (Drugs),
Khar’kov: Torsing, 1998, vol. 2, p. 320.
6. Kozlov, N.S., Sauts, R.D., Serzhanina, V.A., Gusak, K.N.,
Andreeva, E.I., and Rozhkova, N.G., Izv. Akad. Nauk BSSR,
Ser. Khim., 1988, p. 42.
7. Martinez, R., Cogordan, J.A., Mancera, C., and Diaz, Ma.L.,
Il Farmaco, 2000, vol. 55, p. 631.
8. Husseini, R. and Stretton, R.J., Microbios., 1981, vol. 30,
p. 7.
9. Wang, L.K., Johnson, R.K., and Hecht, S.M., Chem. Res.
Toxicol., 1993, vol. 6, 813.
10. Martinez, R., Cortes, E., and Toscano, R.A., J. Heterocycl.
Chem., 1990, vol. 27, 363.
11. Gauptman, Z., Grefe,Yu., and Remane, Kh., Organicheskaya
khimiya (Organic Chemistry), Moscow: Khimiya, 1979,
p. 487.
12. Kozlov, N.S., 5,6-Benzokhinoliny (5,6-Benzoquinolines),
Minsk: Nauka i Tekhnika, 1970, p. 28.
13-(4-Fluorophenyl)-12H-benzo[f]indeno[1,2-
b]quinolin-12-one (XVIIb). Yield 62%, mp 301–302°C.
UV spectrum, λmax, nm (log ε): 224 (4.65), 255 (4.59),
295 (4.66), 314 (4.62), 386 (3.81). 1H NMR spectrum, δ,
ppm: 7.18–7.98 m (14Harom). Found, %: N 3.49.
C26H14FNO. Caculated, %: N 3.73.
13-[4-(2-Fluorobenzyloxy)phenyl]-12H-benzo-
[f]indeno[1,2-b]quinolin-12-one (XVIIc). Yield 79%,
mp 229–230°C. UV spectrum, λmax, nm (lgε): 223 (4.63),
252 (4.60), 297 (4.64), 313 (4.61), 384 (3.89). 1H NMR
spectrum, δ, ppm: 5.34 s (2H, OCH2), 7.10–8.22 m
(18Harom). Found, %: N 2.74. C33H20FNO2. Caculated,
%: N 2.91.
The study was carried out under a financial support
of Belorussian-Russian Foundation for Fundamental
Research (grant X04P-017).
REFERENCES
13. Gusak, K.N, Tereshko,A.B., and Kozlov, N.G., Zh. Obshch.
Khim., 1999, vol. 70, p. 320.
14. Kozlov, N.S., Pak, V.D., and Nugumanov, Z.Z., Khim.
Geterotsikl. Soedin., 1970, p. 194.
1. Kozlov, N.G., Gusak, K.N., Tereshko,A.B., Firgang, S.I., and
Shashkov,A.S., Zh. Org. Khim., 2004, vol. 40, p. 1228.
2. Kozlov, N.G., Basalaeva, L.I., Firgang, S.I., and Shash-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006