Condensation of fluorine-substituted benzaldehydes with amines and cyclic ketones

Article abstract of DOI:10.1134/S1070428008060080

Condensation of fluorine-containing benzaldehydes with naphthalen-2-amine or quinolin-6-amine and cyclic ketones (cyclopentanone, cyclohexanone, and 4-methylcyclohexanone) gave new fluorine-containing derivatives of cyclopenta[c]benzo[f]quinoline, benzo[a

Full text of DOI:10.1134/S1070428008060080

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 6, pp. 830–835. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © N.G. Kozlov, K.N. Gusak, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 6, pp. 842–847.
Condensation of Fluorine-Substituted Benzaldehydes
with Amines and Cyclic Ketones
N. G. Kozlov and K. N. Gusak
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 October 12, 2007
Abstract—Condensation of fluorine-containing benzaldehydes with naphthalen-2-amine or quinolin-6-amine
and cyclic ketones (cyclopentanone, cyclohexanone, and 4-methylcyclohexanone) gave new fluorine-contain-
ing derivatives of cyclopenta[c]benzo[f]quinoline, benzo[a]phenanthridine, and cyclopenta[a]- and benzo[a]-
[4,7]phenanthroline. Intermediate products, 2-[(fluorophenyl)(2-naphthylamino or quinolin-6-ylamino)methyli-
dene]cyclohexanones, dihydrobenzo[f]quinolines, and dihydro-4,7-phenanthrolines, were isolated.
DOI: 10.1134/S1070428008060080
Three-component condensations of aldehydes with
aromatic (heteroaromatic) amines and various CH
acids are widely used for the synthesis of fused nitro-
gen-containing heterocycles [1–4]. Reactions of
fluorine-containing benzaldehydes with aromatic
amines and cyclic ketones attract specific interest, for
they provide a synthetic route to aza heterocycles
containing a quinoline ring and fluorine atoms. Such
compounds are structurally related to antibiotics of the
fluoroquinolinone series, pesticides, antitumor agents,
bactericides, and enzyme inhibitors [5–9].
of the dihydropyridine ring in fused heterocyclic
system XI or XII (Scheme 1). As a result, compounds
XIII–XVII containing a benzo[f]quinoline or 4,7-phe-
nanthroline fragment are formed as final products.
Kozlov et al. [12] studied the reaction of N-ben-
zylidenenaphthalen-2-amine with cyclohexanone and
isolated all possible intermediate products, the corre-
sponding β-amino ketone IX (R = H), hydroxy deriv-
ative of fused tetrahydrobenzo[f]quinoline A (R = R′ =
H, X = CH, n = 2), and dihydrobenzo[f]quinoline XI
(R = H); the final product was 5-phenyl-1,2,3,4-tetra-
hydrobenzo[a]phenanthridine (XIII, R = H) having
fused cyclohexene and benzo[f]quinoline fragments.
In the present work we were the first to study three-
component condensations of 2-fluoro-, 4-fluoro-, and
4-(2-fluorobenzyloxy)benzaldehydes Ia–Ic with naph-
thalen-2-amine (II) or quinolin-6-amine (III) and
cyclic ketones, cyclopentanone (IV), cyclohexanone
(V), and 4-methylcyclohexanone (VI). The reactions
were carried out in aliphatic alcohol (ethanol or butan-
1-ol) as solvent in the presence of an acid catalyst.
Taking into account the results of our previous studies
[2, 10], we presume that aldehyde I initially reacts
with aromatic amine II or III to give the correspond-
ing Schiff base VII or VIII, and reaction of the latter
with cyclic ketone IV–VI follows the known mechan-
ism [11] involving addition of the activated methylene
carbon atom of ketone IV–VI at the C=N bond of
Schiff base VII or VIII, intramolecular attack by the
carbonyl group in adduct IX or X at position 1 of the
naphthalene ring or position 5 of the quinoline ring,
dehydration of cyclic alcohol A, and dehydrogenation
We performed three-component condensations of
fluorine-containing benzaldehydes Ia–Ic with equi-
molar amounts of amines II and III and ketones IV–
VI under different conditions: the temperature, reac-
tion time, and the amount of catalyst (concentrated
hydrochloric acid) were varied. In order to prelimi-
narily obtain the corresponding Schiff base, aldehyde I
was added to a solution of amine II or III in alcohol,
the mixture was kept for 5–10 min, and cyclic ketone
IV–VI was then added. 4-Fluorobenzaldehyde (Ib)
reacted with amines II and III and cyclohexanone V
under mild conditions (without heating) in the pres-
ence of 1–2 drops of concentrated hydrochloric acid
per 10 mmol of the reagent to give amino ketones IXb
and Xb. Under analogous conditions, the reactions
with benzaldehydes Ia and Ic having a fluorine atom
in the ortho position of the benzene ring or benzyl
830

CONDENSATION OF FLUORINE-SUBSTITUTED BENZALDEHYDES
831
Scheme 1.
R
CHO
NH2
N
+
R
X
X
Ia–Ic
II, III
VIIa–VIIc, VIIIa, VIIIb
R'
O
( )n
O
R
R
( )n
( )n
R'
R'
IV–VI
HO
NH
NH
X
X
IXb, Xb
A
R'
( )n
R'
R
R
( )n
[O]
–H2O
NH
N
X
X
XIb, XIIb
XIIIa–XIIIc, XIVa, XIVb, XVa, XVb
XVIa–XVIc, XVIIa, XVIIb
R = 2-F (a), 4-F (b), 4-(2-FC6H4CH2O) (c); IV, V, IX-XIV, XVI, XVII, R′ = H; VI, XV, R′ = Me; II, VII, IX, XI, XIII, XV, XVI,
X = CH; III, VIII, X, XII, XIV, XVII, X = N; IV, XI, XII, XVI, XVII, n = 1; V, VI, IX, X, XIII–XV, n = 2.
substituent stopped at the stage of formation of the cor-
responding Schiff base which failed to take up cyclic
ketone at the C=N bond. In the attempted condensa-
tion of 2-fluorobenzaldehyde (Ia) with naphthalen-
2-amine (II) and cyclohexanone (V) we isolated
N-(2-fluorobenzylidene)quinolin-6-amine (VIIIb). Pre-
sumably, the presence of a fluorine atom in the ortho
position of the benzene ring or bulky 2-fluorobenzyl-
oxy group hampers approach of cyclohexanone mole-
cule to intermediate Schiff base for steric reasons, and
the three-component condensation of aldehydes Ia and
Ic with amines II and III and ketone V requires more
severe conditions. The corresponding cyclization prod-
ucts, 5-aryl-1,2,3,4-tetrahydrobenzo[a]phenanthridines
XIIIa–XIIIc and 8-aryl-9,10,11,12-tetrahydrobenzo-
[a][4,7]phenanthrolines XIVa and XIVb were ob-
tained by heating the reactants for 5–6 h in boiling
ethanol or butan-1-ol in the presence of concentrated
hydrochloric acid (1 ml per 10 mmol of I). Under these
conditions we were unable to isolate intermediate
products. Preliminarily isolated amino ketones IXb
and Xb were converted into the corresponding phenan-
thridine and phenanthroline derivatives XVb and
XVIb by heating in boiling butan-1-ol in the presence
of concentrated hydrochloric acid.
The condensation of benzaldehydes Ib and Ic with
amine II and 4-methylcyclohexanone (VI) to give
5-aryl-3-methyl-1,2,3,4-tetrahydrobenzo[a]phenanthri-
dines XVb and XVc required exceptionally drastic
conditions. By contrast, cyclopentanone IV reacted
with aldehydes Ia–Ic and amines II and III under mild
conditions with direct formation of dihydro derivatives
XI and XII containing a small amount of cyclic prod-
ucts XVI and XVII. Compounds XIb and XIIb were
isolated as individual substances. If difficultly separ-
able mixtures were formed, the reactions were carried
out under more severe conditions (boiling ethanol or
butan-1-ol, concentrated hydrochloric acid) to ensure
complete conversion of intermediate products into
cyclopenta[c]benzo[f]quinolines XVIa–XVIc and
cyclopenta[a][4,7]phenanthrolines XVIIa and XVIIb.
The same conditions promoted dehydrogenation of the
isolated compounds XIb and XIIb to benzo[f]quino-
line XVIb and 4,7-phenanthroline XVIIb, respec-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008

KOZLOV, GUSAK
832
tively. Shorter reaction time (3 h) and higher yields
(66–72%) of cyclopentane derivatives XVIa–XVIc,
XVIIa, and XVIIb as compared to benzophenanthri-
dines XIIIa–XIIIc, XVb, and XVc and benzophenan-
throlines XIVa and XIVb (yield 48–62%) indicate
higher reactivity of cyclopentanone (IV) as compared
to ketones of the cyclohexane series V and VI.
and medium-intensity [M – H – F]+ ion peak was
present (Irel = 21–24%).
The electronic absorption spectra of amino ketones
IXb and Xb in the UV region were analogous to those
of naphthalen-2-amine and quinolin-6-amine [UV
spectrum, λmax, nm (logε): 246–247 (4.35–4.37), 279–
280 (3.64–3.65), 337–338 (3.25–3.27)]; they consisted
of three bands in the regions λ 253–256, 292–299, and
360–363 nm, corresponding to π–π* transitions in the
aromatic system. Bathochromic shift of all absorption
maxima and simultaneous increase in their intensity in
the spectra of amino ketones IXb and Xb are likely to
be related to the presence of a fluorophenyl chromo-
phore and cycloalkanone fragment. Dihydro deriva-
The amine nature also affects the yield of the
products: the yields of 4,7-phenanthroline derivatives
XIVa, XIVb, XVIIa, and XVIIb were lower (48–
55%) than those of phenanthridine derivatives XIIIa–
XIIIc and XVIa–XVIc (56–72%). Obviously, nucleo-
philicity of the amino group in III is reduced due to
the presence of electron-withdrawing nitrogen atom in
the para position; therefore, the reactivity of III in the
condensation with aldehydes is lower than that of
amine II and polarization of the C=N bond in the
intermediate Schiff base is weaker.
tives XIb and XIIb showed in the UV spectra [λmax
,
nm (logε): 258–260 (4.46–4.49), 284–285 (3.99–4.00),
381–384 (3.8–43.87)] a considerable red shift of the
long-wave absorption band, obviously as a result of
formation of a new double bond in the closed cyclic
system. Aromatization of the azaphenanthrene nucleus
leads to appearance in the UV spectra of cyclization
products XIII–XVII of a very strong absorption band
at λ 278–293 nm and less intense bands at λ 230–241,
250–269 and 341–353, 361–374 nm; as a result, the
UV spectra of XIII–XVII resemble those of 1,3-diaryl-
benzo[f]quinolines and 4,7-phenanthrolines [11, 13].
Therefore, the observed absorption bands may be inter-
preted as p-, β-, and α-bands according to Clar. The R
and R′ substituents almost do not affect the spectral
pattern.
The condensations of cyclic ketones with prelimi-
narily prepared and purified (by recrystallization from
aliphatic alcohol) Schiff bases VIIa–VIIc and VIIIa–
VIIIc gave the same products as those obtained from
mixtures of their precursors, aldehydes Ia–Ic and
amines II and III.
Amino ketones IXb and Xb characteristically
showed in the IR spectra absorption bands due to
stretching vibrations of the carbonyl and amino groups
at 1700–1690 and 3400–3380 cm–1, respectively. The
IR spectra of compounds XIb and XIIb lacked car-
bonyl absorption band but retained the NH stretching
vibration band at 3400–3385 cm–1. Neither carbonyl
nor NH absorption was observed in the spectra of
cyclization products XIII–XVII. Both compounds
XIII–XVII and their precursors IX–XII displayed
absorption bands belonging to stretching vibrations of
aliphatic and aromatic C–H bonds in the regions 2920–
2890 and 3060–3030 cm–1, respectively. A strong ab-
sorption band in the region 1235–1230 cm–1, corre-
sponding to stretching vibrations of the C–O–C frag-
ment (benzyloxyphenyl group), was present in the IR
spectra of XIIIc, XVc, and XVIc.
1
In the H NMR spectra of amino ketones IXb and
Xb, methylene protons in the cyclohexane ring reso-
nated as multiplets in the region δ 1.73–2.40 ppm, and
the 2-H signal appeared as a multiplet at δ 2.80 ppm.
The proton on the carbon atom linked to the amino
group and phenyl and cyclohexane rings gave a broad-
ened singlet at δ 4.67–4.70 ppm. A broadened singlet
at δ 5.12–5.15 ppm was assigned to the NH proton.
Signals from aromatic protons in the fluorophenyl
substituent and naphthalene or quinoline ring were
located in the region δ 6.50–8.56 ppm. The spectra of
compounds XIb and XIIb lacked signals assignable to
2-H in the cycloalkane fragment and proton in position
1 of the naphthalene ring or position 5 of the quinoline
ring, indicating that the cyclization involved the corre-
sponding carbon atoms. The signal from the CH group
neighboring to the fluorophenyl substituent was dis-
placed downfield relative to its position in the spectra
of IXb and Xb; it was located at δ 5.90–6.08 ppm, as
in the spectra of fused azaphenanthrenes with partially
hydrogenated pyridine ring [1]. The NH proton in the
The molecular ion peaks in the mass spectra of
amino ketones IXb and Xb had a moderate intensity
(Irel = 25–30%), while the base peak (Irel = 100%) was
that of the [M – C6H10O]+ ion. Also, weak (Irel = 6–7%)
[M – F]+ and [M – F – C6H10O]+ ion peaks were
observed. In the mass spectra of compounds XIb and
XIIb and final cyclization products XIII–XVII, the
molecular ion was the most abundant, the [M – H]+ ion
peak had a fairly strong intensity (Irel = 60–65%),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008

CONDENSATION OF FLUORINE-SUBSTITUTED BENZALDEHYDES
833
1H NMR spectra of XIb and XIIb resonated at δ 4.76–
4.91 ppm. The spectra of benzophenanthridines benzo-
[f]quinoline, and 4,7-phenanthroline derivatives XIII–
XVII contained no NH and ArCH signals; signals in
the regions δ 1.29–3.70 and 7.10–9.00 ppm were
assigned to protons in the cycloaliphatic and aromatic
fragments, respectively. Protons of the methyl group in
methyl-substituted benzophenanthridines XVb and
XVc gave a singlet at δ 1.02–1.08 ppm; and methylene
protons in the 2-fluorobenzyloxy substituent in com-
pounds XIIIc, XVc, and XVIc resonated as a singlet at
δ 5.23–5.29 ppm.
ing one drop of concentrated hydrochloric acid was
kept for 24 h at room temperature. The product was
isolated as described above in a.
Compound IXb. Yield 76% (a), 74% (b); mp 145–
1
146°C. H NMR spectrum, δ, ppm: 1.77 m, 1.95 m,
and 2.40 m (8H, CH2); 2.80 m (1H, CH); 4.67 br.s (1H,
CH); 5.12 br.s (1H, NH); 6.6–7.93 m (11H, Harom).
Found, %: N 3.74. C23H22FNO. Calculated, %: N 4.03.
Compound Xb. Yield 57% (a), 59% (b); mp 187–
1
188°C. H NMR spectrum, δ, ppm: 1.73 m, 1.96 m,
and 2.39 m (8H, CH2); 2.80 m (1H, CH); 4.70 br.s (1H,
4
CH); 5.15 br.s (1H, NH); 6.50 d (5′-H, J = 2.6 Hz);
3
7.00 t and 7.39 d (4H, Harom, J = 8.4 Hz); 7.10 d.d
EXPERIMENTAL
3
4
(1H, 4′-H, J = 8.6, J = 2.2 Hz); 7.18 d.d (1H, 3′-H,
4
3J = 8.6, J = 4.2 Hz); 7.74 d and 7.82 d (1H each,
The IR spectra were recorded in KBr on a Nicolet
Protégé-460 spectrometer with Fourier transform. The
mass spectra (electron impact, 70 eV) were obtained
on a Finnigan MAT Incos-50 instrument and on
a Hewlett–Packard HP 5972 mass-selective detector
coupled with an HP 5890 gas chromatograph (HP-5MS
capillary column, 30 m×0.25 mm; stationary phase
5% PhMe Silicone, film thickness 0.25 μm; injector
temperature 250°C). The UV spectra were measured
from solutions in ethanol (c = 10–4 M) on a Specord
UV-Vis spectrophotometer. The NMR spectra were
recorded on Bruker AC-500 (500 MHz) and Tesla BS-
567 spectrometers (100 MHz) using DMSO-d6 or
chloroform-d as solvent and tetramethylsilane as
internal reference. The melting points were determined
using a Kofler microscope.
3
3
7′-H, 8′-H, J = 9.1 Hz); 8.56 d.d (1H, 2′-H, J = 4.2,
4J = 2.2 Hz). Found, %: N 7.92. C22H21FN2O. Calculat-
ed, %: N 8.04.
4-(2-Fluorophenyl)-2,3,4,5-tetrahydro-1H-cyclo-
penta[c]benzo[f]quinoline (XIb) and 8-(2-fluoro-
phenyl)-8,9,10,11-tetrahydro-7H-cyclopenta[a][4,7]-
phenanthroline (XIIb) (general procedure). Cyclo-
pentanone (IV), 5 mmol, and concentrated hydro-
chloric acid, 2 drops, were added to a solution of
5 mmol of aldehyde Ib and 5 mmol of amine II or III
(method a) or of 5 mmol of Schiff base VIIb or VIIIb
(method b) in 20 ml of ethanol. The mixture was left to
stand for 6 h at room temperature, and the precipitate
was filtered off, treated with aqueous ammonia,
washed with water, dried, and recrystallized from
ethanol.
N-Benzylidenenaphthalen-2-amines VIIa–VIIc and
N-Benzylidenequinolin-6-amines VIIIa and VIIIb
were synthesized according to the procedure described
in [14].
Compound XIb. Yield 63% (a), 68% (b); mp 161–
1
162°C. H NMR spectrum, δ, ppm: 2.22 m, 3.29 m,
and 3.67 m (6H, CH2); 4.76 br.s (1H, NH); 5.90 s (1H,
CH); 7.28–8.59 m (10H, Harom). Found, %: N 4.41.
C22H18FN. Calculated, %: N 4.44.
2-[(2-Fluorophenyl)(2-naphthylamino)methyl]-
cyclohexan-1-one (IXb) and 2-[(2-fluorophenyl)-
(quinolin-6-ylamino)methyl]cyclohexan-1-one (Xb)
(general procedure). a. A solution of 5 mmol of alde-
hyde Ib and 5 mmol of amine II or III in 20 ml of
ethanol was heated for 10 min at 40–50°C. The mix-
ture was cooled to 20°C, 5 mmol of cyclohexanone V
and one drop of concentrated hydrochloric acid were
added, and the mixture was left to stand for 24 h at
room temperature. The solvent was removed, the
residue was treated with aqueous ammonia, and the
precipitate was filtered off, washed with water, dried,
and recrystallized from ethanol.
Compound XIIb. Yield 58% (a), 53% (b); mp 153–
1
154°C. H NMR spectrum, δ, ppm: 2.24 m, 3.31 m,
and 3.70 m (6H, CH2); 4.91 br.s (1H, NH); 6.08 s
3
(1H, CH); 7.31 t and 7.78 d (4H, Harom, J = 8.5 Hz);
3
4
7.49 d.d (1H, 2-H, J = 7.9, J = 4.2 Hz); 8.16 d (2H,
3
3
5-H, 6-H, J = 8.9 Hz); 8.86 d (1H, 3-H, J = 4.2 Hz);
3
8.91 d (1H, 1-H, J = 7.9 Hz). Found, %: N 8.62.
C21H17FN2. Calculated, %: N 8.86.
5-Aryl-1,2,3,4-tetrahydrobenzo[a]phenanthri-
dines XIIIa–XIIIc (general procedure). A solution of
5 mmol of aldehyde Ia–Ic, 5 mmol of naphthalen-2-
amine (II), and 5 mmol of cyclohexanone (V) (method
a) or a solution of 5 mmol of ketone V and 5 mmol of
b. A solution of 5 mmol of ketone V and 5 mmol of
Schiff base VIIb or VIIIb in 20 ml of ethanol contain-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008

KOZLOV, GUSAK
834
Schiff base VIIa–VIIc (method b) in 20 ml of ethanol
containing 0.5 ml of concentrated hydrochloric acid
was heated for 6 h under reflux. The products were
isolated as described above for XIb and XIIb.
5-Aryl-3-methyl-1,2,3,4-tetrahydrobenzo[a]phen-
anthridines XVb and XVc were synthesized from
the corresponding aldehyde Ib or Ic, naphthalen-2-
amine (II), and 4-methylcyclohexan-1-one (VI)
(method a) or from ketone VI and Schiff base VIIb or
VIIc (method b), following the procedure described
above for the synthesis of compounds XIIIa–XIIIc but
using 10 mmol of ketone VI and double volume of
ethanol (60 ml). After removal of 3/4 of the solvent,
the tarry material was treated with diethyl ether. The
precipitate of XVb or XVc hydrochloride was treated
with aqueous ammonia, washed with water, and re-
crystallized from ethanol–benzene (2:1).
5-(2-Fluorophenyl)-1,2,3,4-tetrahydrobenzo[a]-
phenanthridine (XIIIa). Yield 56% (a), 60% (b);
1
mp 236–237°C. H NMR spectrum, δ, ppm: 1.89 m,
2.88 m, and 3.60 m (8H, CH2); 7.38 m, 7.69 m,
8.10 m, and 8.81 m (10H, Harom). Found, %: N 4.07.
C23H18FN. Calculated, %: N 4.28.
5-(4-Fluorophenyl)-1,2,3,4-tetrahydrobenzo[a]-
phenanthridine (XIIIb). Yield 62% (a), 65% (b);
1
mp 258–259°C. H NMR spectrum, δ, ppm: 1.85 m,
5-(2-Fluorophenyl)-3-methyl-1,2,3,4-tetrahydro-
benzo[a]phenanthridine (XVb). Yield 52% (a), 56%
(b); mp 205–206°C. 1H NMR spectrum, δ, ppm: 1.08 s
(3H, Me); 1.30 m, 1.88 m, 2.52 m, 2.93 m, 3.61 m, and
3.70 m (7H, CH2, CH); 7.47 m, 7.71 m, and 7.98–
8.86 m (10H, Harom). Found, %: N 3.95. C24H20FN.
Calculated, %: N 4.11.
2.90 m, and 3.65 m (8H, CH2); 7.44 m, 7.87 s, 8.11 m,
and 8.84 m (10H, Harom). Found, %: N 4.12. C23H18FN.
Calculated, %: N 4.28.
5-[4-(2-Fluorobenzyloxy)phenyl]-1,2,3,4-tetrahy-
drobenzo[a]phenanthridine (XIIIc). Yield 61% (a),
1
60% (b); mp 213–214°C. H NMR spectrum, δ, ppm:
1.90 m, 2.90 m, and 3.70 m (8H, CH2); 5.29 s (2H,
OCH2); 7.27 m and 8.95 m (14H, Harom). Found, %:
N 3.08. C30H24FNO. Calculated, %: N 3.23.
5-[4-(2-Fluorobenzyloxy)phenyl]-3-methyl-
1,2,3,4-tetrahydrobenzo[a]phenanthridine (XVc).
1
Yield 57% (a), 55% (b); mp 187–188°C. H NMR
8-Aryl-9,10,11,12-tetrahydrobenzo[a][4,7]phen-
anthrolines XIVa and XIVb were synthesized as
described above for compounds XIIIa–XIIIc from the
corresponding aldehyde Ia or Ib, quinolin-6-amine
(III), and cyclohexanone (V) (method a) or from
ketone V and Schiff base VIIIa or VIIIb (method b)
using butan-1-ol as solvent. The solvent was evapo-
rated, and the solid residue was treated with aqueous
ammonia. Compound XIVa was recrystallized from
ethanol–benzene (3:1), and compound XIVb, from
ethanol.
spectrum, δ, ppm: 1.02 s (3H, Me); 1,29 m, 1.91 m,
2.42 m, 2.97 m, 3.57 m, and 3.67 m (7H, CH2, CH);
5.23 s (2H, OCH2); 7.28–7.61 m (8H, Harom); 7.69 d
(2H, 10-H, 11-H, 3J = 8.0 Hz); 7.82 d and 8.01 m (2H,
7-H, 8-H, J = 9.0 Hz); 8.06 d (1H, 9-H, J = 8.0 Hz);
8.83 s (1H, 12-H). Found, %: N 3.04. C31H26FNO. Cal-
culated, %: N 3.13.
3
3
4-Aryl-2,3-dihydro-1H-cyclopenta[c]benzo[f]-
quinolines XVIa–XVIc and 8-aryl-10,11-tetrahy-
dro-9H-cyclopenta[a][4,7]phenanthrolines XVIIa
and XVIIb (general procedure). Cyclopentanone
(IV), 5 mmol, and concentrated hydrochloric acid,
0.5 ml, were added to a solution of 5 mmol of alde-
hyde Ia–Ic and 5 mmol of amine II or III (method a)
or to a solution of 5 mmol of Schiff base VIIa–VIIc,
VIIIa, or VIIIb (method b) in 20 ml of butan-1-ol, and
the mixture was heated for 3 h under reflux. After
cooling, the precipitate was filtered off, treated with
aqueous ammonia, washed with water, dried, and re-
crystallized from ethanol.
8-(2-Fluorophenyl)-9,10,11,12-tetrahydrobenzo-
[a][4,7]phenanthroline (XIVa). Yield 48% (a), 51%
(b); mp 171–172°C. 1H NMR spectrum, δ, ppm: 1.88 m,
2.91 m, and 3.62 m (8H, CH2); 7.31 m and 7.59 m
3
4
(4H, Harom); 7.52 d.d (1H, 2-H, J = 7.9, J = 4.1 Hz);
3
8.23 d (2H, 5-H, 6-H, J = 9.0 Hz); 8.89 d (1H, 3-H,
3J = 4.1 Hz); 9.02 d (1H, 1-H, 3J = 7.9 Hz). Found, %:
N 8.41. C22H17FN2. Calculated, %: N 8.54.
8-(4-Fluorophenyl)-9,10,11,12-tetrahydrobenzo-
[a][4,7]phenanthroline (XIVb). Yield 51% (a), 57%
(b); mp 189–190°C. H NMR spectrum, δ, ppm:
Benzo[f]quinoline XVIb and 4,7-phenanthroline
XVIIb were also synthesized by heating for 3 h under
reflux 2.5 mmol of compound XIb or XIIb, respec-
tively, in 20 ml of butan-1-ol containing 10 drops of
concentrated hydrochloric acid. The products were
isolated as described above; yield 74% (XVIb), 69%
(XVIIb).
1
1.92 m, 2.87 m, and 3.58 m (8H, CH2); 7.30 m and
3
7.54 m (5H, 2-H, C6H4F); 8.20 d (2H, 5-H, 6-H, J =
3
9.2 Hz); 8.97 d (1H, 3-H, J = 4.5 Hz); 9.13 d (1H,
3
1-H, J = 8.7 Hz). Found, %: N 8.29. C22H17FN2. Cal-
culated, %: N 8.54.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008

CONDENSATION OF FLUORINE-SUBSTITUTED BENZALDEHYDES
835
4-(2-Fluorophenyl)-2,3-dihydro-1H-cyclopenta-
[c]benzo[f]quinoline (XIVa). Yield 70% (a), 71% (b);
mp 240–241°C. H NMR spectrum, δ, ppm: 2.24 m,
3.26 m, and 3.69 m (6H, CH2); 7.21–8.09 and 8.73 m
(10H, Harom). Found, %: N 4.23. C22H16FN. Calculated,
%: N 4.47.
IXb or Xb, 10 drops of concentrated hydrochloric
acid, and 20 ml of butan-1-ol was heated for 4 h under
reflux. The precipitate was treated as described above
for the synthesis of XIIIb and XIVb. Yield 68%
(XIIIb), 61% (XIVb).
1
REFERENCES
4-(4-Fluorophenyl)-2,3-dihydro-1H-cyclopenta-
[c]benzo[f]quinoline (XIVb). Yield 72% (a), 74% (b);
mp 240–241°C. H NMR spectrum, δ, ppm: 2.21 m,
3.19 m, and 3.59 m (6H, CH2); 7.14–8.10 m and
8.62 m (10H, Harom). Found, %: N 4.19. C22H16FN.
Calculated, %: N 4.47.
1. Kozlov, N.G., Gusak, K.N., Tereshko, A.B., Fir-
gang, S.I., and Shashkov, A.S., Russ. J. Org. Chem.,
2004, vol. 40, p. 1181.
1
2. Kozlov, N.G. and Gusak, K.N., Russ. J. Org. Chem.,
2007, vol. 43, p. 241.
4-[4-(2-Fluorobenzyloxy)phenyl]-2,3-dihydro-
1H-cyclopenta[c]benzo[f]quinoline (XIVc). Yield
66% (a), 69% (b); mp 265–266°C. 1H NMR spectrum,
δ, ppm: 2.18 m, 3.20 m, and 3.63 m (6H, CH2); 5.23 s
(2H, OCH2); 7.10–8.08 m and 8.55 m (14H, Harom).
Found, %: N 3.26. C29H22FNO. Calculated, %: N 3.34.
3. Kozlov, N.G., Basalaeva, L.I., and Tychinskaya, L.Yu.,
Russ. J. Org. Chem., 2002, vol. 38, p. 1166.
4. Kozlov, N.G., Pashkovskii, F.S., Gusak, K.N., Korole-
va, E.V., Tereshko, A.B., and Lokot’, I.P., Russ. J. Org.
Chem., 2004, vol. 40, p. 555.
5. Mashkovskii, M.D., Lekarstvennye sredstva (Medi-
cines), Khar’kov: Torsing, 1998, vol. 2, p. 320.
8-(2-Fluorophenyl)-10,11-dihydro-9H-cyclo-
penta[a][4,7]phenanthroline (XVIIa). Yield 52% (a),
6. Kozlov, N.S., Sauts, R.D., Serzhanina, V.A., Gu-
sak, K.N., Andreeva, E.I., and Rozhkova, N.G., Izv.
Akad. Nauk BSSR, Ser. Khim. Nauk, 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,
1
59% (b); mp 163–164°C. H NMR spectrum, δ, ppm:
2.29 m, 3.30 t, and 3.70 t (6H, CH2, 3J = 8.0 Hz); 7.46 t
3
and 7.82 d (4H, Harom); 7.58 d.d (1H, 2-H, J = 8.4,
4J = 4.2 Hz); 8.25 d (2H, 5-H, 6-H, 3J = 9.1 Hz); 8.88 d
3
3
(1H, 3-H, J = 8.4 Hz); 9.00 d (1H, 1-H, J = 4.2 Hz).
vol. 30, p. 7.
Found, %: N 8.69. C21H15FN2. Calculated, %: N 8.92.
9. Wang, L.K., Johnson, R.K., and Hecht, S.M., Chem.
Res. Toxicol., 1993, vol. 6, p. 813.
10. Kozlov, N.G., Tereshko, A.B., and Gusak, K.N., Russ. J.
Org. Chem., 2006, vol. 42, p. 266.
8-(4-Fluorophenyl)-10,11-dihydro-9H-cyclo-
penta[a][4,7]phenanthroline (XVIIb). Yield 55% (a),
1
58% (b); mp 189–190°C. H NMR spectrum, δ, ppm:
2.25 m, 3.36 t, and 3.65 t (6H, CH2, 3J = 8.0 Hz); 7.28 t
and 7.79 d (4H, Harom, 3J = 7.9 Hz); 7.50 d.d (1H, 2-H,
11. Kozlov, N.S., 5,6-Benzokhinoliny (5,6-Benzoquino-
lines), Minsk: Nauka i Tekhnika, 1970, p. 28.
12. Kozlov, N.S., Vorob’eva, G.V., and Bychkova, G.S., Izv.
Akad. Nauk BSSR, Ser. Khim. Nauk, 1969, p. 796.
4
3
3J = 8.2, J = 4.1 Hz); 8.19 d (2H, 5-H, 6-H, J =
3
9.0 Hz); 8.89 d (1H, 3-H, J = 8.2 Hz); 8.99 d (1H,
1-H, J = 4.1 Hz). Found, %: N 8.74. C21H15FN2. Cal-
3
13. Kozlov, N.S., Gusak, K.N., Serzhanina, V.A., and
culated, %: N 8.92.
Krot, N.A., Khim. Geterotsikl. Soedin., 1985, p. 1398.
Cyclization of amino ketones IXb and Xb (gen-
eral procedure). A mixture of 2.5 mmol of compound
14. Gusak, K.N., Tereshko, A.B., and Kozlov, N.G., Russ. J.
Gen. Chem., 2000, vol. 70, p. 298.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008