β-oxoacids esters in the synthesis of benzo[f]quinoline derivatives

Article abstract of DOI:10.1134/S1070428007050119

Condensation of ethyl acetoacetate and ethyl 3-oxo-3-(2-furyl-, 2-quinolyl-, 3-pyridyl)propanoates with azomethines of 2-naphthylamine series led to the formation of ethyl (3-arylbenzo[f]quinol-1-yl)acetates and of esters of the corresponding 3-aryl-1-heteryl-2-benzo[f]quinolylcarboxylic acids. The intermediate reaction products were isolated: ethyl 5-(2-naphthylamino)-3-oxo-5- phenylpentanoate, 2-[(aryl)(2-naphthylamino)methyl]-3-heteryl-3-oxopropanoates, dihydro and tetrahydro derivatives of benzoquinolylacetic and benzoquinolinecarboxylic acids. Nauka/Interperiodica 2007.

Full text of DOI:10.1134/S1070428007050119

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 5, pp. 706−718. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © K.N. Gusak, N.G. Kozlov, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 5, pp. 711−723.
β-Oxoacids Esters in the Synthesis of Benzo[f]quinoline
Derivatives
K. N. Gusak and N. G. Kozlov
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, Minsk, 220072 Belarus
e-mail: loc@ifoch.bas-net.by
Received March 20, 2006
Abstract—Condensation of ethyl acetoacetate and ethyl 3-oxo-3-(2-furyl-, 2-quinolyl-, 3-pyridyl)propanoates
with azomethines of 2-naphthylamine series led to the formation of ethyl (3-arylbenzo[f]quinol-1-yl)acetates and
of esters of the corresponding 3-aryl-1-heteryl-2-benzo[f]quinolylcarboxylic acids. The intermediate reaction
products were isolated: ethyl 5-(2-naphthylamino)-3-oxo-5-phenylpentanoate, 2-[(aryl)(2-naphthylamino)methyl]-
3-heteryl-3-oxopropanoates, dihydro and tetrahydro derivatives of benzoquinolylacetic and benzoquinoline-
carboxylic acids.
DOI: 10.1134/S1070428007050119
Reactions of ethyl acetoacetate and of other β-oxo-
acids and β-dicarboxylic acids esters with primary
aromatic amines known under the names of Conrad–
Limpach and Knorr reactions are extensily applied to
the synthesis of fused nitrogen-containing heterocycles
with oxygen-including moieties [1–4].
azomethines obtained Ia–Ie with ethyl acetoacetate (II)
and ethyl 3-oxo-3-(2-furyl-, 2-quinolyl-, 3-pyridyl)-
propanoates (III–V).
The condensation of azomethines Ia–Ie with ethyl
acetoacetate (II) was carried out by boiling the reagents
mixture in aliphatic alcohol (EtOH, i-PrOH) in the
presence of catalytic quantities of concn. HCl that activat-
ed both the molecules of azomethine and the β-dicarbonyl
compound [1]. The process resulted in a selective forma-
tion in 30–56% yield of ethyl (3-arylbenzo[f]quinol-1-
yl)acetates VIa–VIe.
Aiming at the synthesis of previously unknown
heterocyclic compounds belonging to azaphenanthrene
series we investigated a condensation of 2-naphthylamine
with ethyl β-oxocarboxylates adding the third
component, aromatic aldehyde. The opportunity of
substituents variation in the benzene ring of the aldehyde
molecule as well as the use of β-ketoesters of various
structures is promising for the synthesis of substituted
carboxy derivatives of benzo[f]quinoline possessing high
potential of biological action [5–7]. Note that
introduction of aldehyde into the condensation with
amine and oxoester reduced the selectivity and hampered
the isolation of individual target products. Alongside the
amine reaction with β-ketoester involving the carbonyl
or alkoxycarbonyl groups of the ketoester occurs the
amine reaction with aldehyde and the aldehyde
condensation with the oxoester with participation of the
CH-acidic function of the latter. As a result various side,
intermediate, and final reaction products form
simultaneously. The selectivity of the process was
improved by preliminary condensation of 2-naphthyl-
amine with arylaldehydes followed by reaction of
Ester II in reactions with Schiff’s bases with
a polarized C=N bond like in reaction with benzaldehyde
behaves as a CH-acid; therewith both methyl and
methylene groups of ketoester II possess CH-acid
qualities.Although the methylene group protons are more
labile, the first reaction stage, the addition of ester II to
the C=N bond in azomethine, involves the sterically less
hindered methyl resulting in formation of intermediate
products, aminoketoesters of 5-arylpentanoic acids.
Subsequently an intramolecular cyclocondensation of
aminoketoesters occurs at the α-position of the naphthal-
ene ring leading to 3,4-dihydrobenzo[f]quinolylacetic
acid esters that undergo dehydrogenation or aromatiz-
ation into benzo[f]quinolylacetic acid esters VIa–VIe.
The first stage of this process pathway was confirmed
by formation of ethyl 5-(2-naphthylamino)-3-oxo-5-
phenylpentanoate (VIIa) at boiling benzylidene-2-
706

β-OXOACIDS ESTERS IN THE SYNTHESIS OF BENZO[f]QUINOLINE DERIVATIVES
707
O
O
R
N
VIа_VIe
R
R
O
R
O
O
O
II
O
O
O
N
VIа
NH
NH
Iа_Ie
VIIа
IXа
O
R
VIe
NH
VIIIe
R = H (a), Br (b), F (c), NO2 (d), MeO (e).
naphthylamine (Ia) with ester II in ethanol without
catalyst (concn. HCl). The second intermediate, ethyl
[3-(p-methoxyphenyl)-3,4-dihydrobenzo[f]quinol-1-yl]-
acetate (VIIIe) we succeeded to obtain from p-methoxy-
phenylmethylene-2-naphthylamine (Ie) by adding HCl
to ethanol solution of azomethine Ie and ester II heated
to 70°C.
benzo[f]quinolylacetates VIa–VIe. Schiff’s bases Ib–Id
with electron-withdrawing substituents (Hlg, NO2) that
increase the polarization of the azomethine bond provide
higher yields of the reaction products VIb–VId compar-
ed with those obtained from benzylidene- and p-
methoxyphenylmethylene-2-naphthylamines Ia and Id.
In reactions of azomethines with heteryl-substituted
ketoesters the reaction direction and products yield
depend both on the substituent in the benzene ring of the
azomethine and on the heteryl moiety at the carbonyl
group of the ketoester.
Aminoester VIIa and dihydro derivative VIIIe at
boiling in ethanol in the presence of concn. HCl were
converted into the corresponding ethyl benzo[f]quinolyl-
acetates VIa and VIe.
The cyclization of aminoketoester VIIa alongside the
cyclic compound VIa led to the formation of benzyl-2-
naphthylamine (IXa) whose appearance was caused
likely by partial decomposition of compound VIIa to
initial ketoester II and azomethine, and the latter was
reduced by hydrogen liberated in dehydrocyclization of
amine VIIa. The cyclization of ester VIIa in the presence
of an oxidant (nitrobenzene) prevented the formation of
amine IXa, but the yield of benzo[f]quinoline VIa did
not considerably grow.
The boiling of azomethines Ia–Id with furoylacetate
III in the presence of HCl and nitrobenzene gave rise to
ethyl 3-aryl-1-(2-furyl)-benzo[f]quinoline-2-carboxylates
Xa–Xd. Like in the case of ethyl acetoacetate (II) the
yield of benzo[f]quinolines Xb–Xd (38–57%) obtained
from halo- and nitro-substituted azomethines Ib–Id was
higher than that (29%) of the product prepared from ester
III and benzylidene-2-naphthylamine (Ia). No benzo[f]-
quinolinecarboxylate formed from azomethine Ie.
In the molecules of heteryl-substituted oxoesters III–
V a single center with labile hydrogen atom is present:
the methylene group. The addition of furoylacetate III
The substituents in the aldehyde part of the azo-
methine molecule somewhat affect the yield of target
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GUSAK, KOZLOV
708
O
O
N
R
O
R
O
O
O
O
III
N
Xа_Xd
Iа_Ie
O
O
O
R
O
Ie
NH
XIа_XIe
R
O
O
R
Xа_Xd
O
NH
N
HN
IXа_XIc
XIIb, XIIc
to the C=N bond of azomethine Ia–Ie involving the
methylene group at boiling the alcoholic solution of
reagents without catalyst and oxidant occurred with
formation in high yields (78–94%) of ethyl 3-aryl-3-(2-
naphthylamino)-2-(2-furoyl)propanoates XIa–XIe. At
boiling in ethanol in the presence of HCl and nitro-
benzene aminoesters XIa–XId underwent cyclization
into the corresponding benzoquinolinecarboxylates Xa–
Xd. Methoxy-substituted aminoester XIe suffered a
cleavage of a C–C bond to give the initial ketoester III
and azomethine Ie easily isolable from the reaction
mixture.
azomethines Ia–Ic in the reaction mixture due to the
higher decomposition rate of aminoketoesters XIa–XIc.
This assumption is supported by the considerably higher
yield of amines IXa–IXc (15–20%) in the cyclization of
esters XIa–XIc compared to the yield of compound IXa
(5%) isolated in the cyclization of ester VIIa.
The cyclization products of aminoketoesters XIb and
XIc besides benzo[f]quinolines Xb and Xc and amines
IXb and IXc contained ketoesters naphthylimino deriva-
tives XIIb and XIIc. Azomethines Ib and Ic formed at
the cleavage of aminoesters XIb and XIc under the condi-
tions of the cyclization alongside the reduction are likely
to suffer hydrolysis into the corresponding aldehydes and
2-naphthylamine; the latter reacts with the carbonyl of
esters XIb and XIc giving compounds XIIb and XIIc.
Compared to compound VIIa aminoesters XIa–XIe
are more prone to cleavage under the cyclization condi-
tions. In contrast to the cyclization of compound VIIa
secondary amines IXa–IXc formed during cyclization
of aminoesters XIa–XIc alongside benzoquinolinecarb-
oxylates Xa–Xc also in the presence of nitrobenzene
apparently because of the higher concentration of
Ethyl 3-(2-quinolyl)-3-oxopropanoate (IV) did not
react with azomethines Ia–Ie without catalyst. In all
likelihood the most important here is the steric factor of
the bulky quinolyl substituent. Beside the –I-effect of
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β-OXOACIDS ESTERS IN THE SYNTHESIS OF BENZO[f]QUINOLINE DERIVATIVES
709
the nitrogen in the quinoline ring of the oxoester IV
molecule is less than the–I-effect of the oxygen in the
molecule of furyl-substituted ester III, and therefore in
molecule IV the lability of the hydrogen of methylene
group decreases, therefore its activation for addition to
the C=N bond of azomethine requires the protonation of
carbonyl groups in the molecule of ketoester IV.
1,2,3,4-tetrahydrobenzo[f]quinoline-2-carboxylates
XIVb–XIVd. By now a similar compound has been
isolated only in the condensation of azomethine Ia with
cyclohexanone [8].
At prolonged heating of a solution of Ia–Ic and IV in
ethanol or dimethylformamide in the presence of HCl
we obtained ethyl 3-aryl-1-(2-quinolyl)-3,4-dihydro-
benzo[f]quinoline-2-carboxylates XVa–XVc resulting
from dehydration of intermediate hydroxyesters XIVb
and XIVc and their hypothetic analog XIVa.
In the presence of HCl ester IV reacted with azo-
methines Ia–Ic and Ie under mild conditions (reagents
were maintained at room temperature in ethanol solution
for 10–20 min) and led to the formation of ethyl 3-aryl-
3-(2-naphthylamino)-2-(quinoline-2-carbonyl)propano-
ates XIIIa–XIIIc and XIIIe.
In reaction carried out in rigid conditions (heating at
100°C in a sealed ampule reagents Ia and IV in DMF
solution in the presence of HCl) a dihydration product of
dihydro derivative XVa was obtained: ethyl 1-(2-quinol-
yl)-3-phenylbenzo[f]quinoline-2-carboxylate (XVIa).
The heating of mixtures of azomethines Ib–Id with
ester IV or of aminoketoesters XIIIb, XIIIc, and XIIIe
at 80°C or at their prolonged storage (for several days)
at room temperature in ethanol or benzene solution in
the presence of a catalyst (HCl, BF3 etherate) resulted in
the formation of ethyl 3-aryl-1-hydroxy-1-(2-quinolyl)-
Under the conditions of the synthesis of tetrahydro-
and dihydrobenzoquinoline derivatives XIVb–XIVd and
XVa–XVc alongside the target products XIVb–XIVd
and XVa–XVc side products were formed [ethyl 3-aryl-
O
O
R
R
N
O
N
O
O
O
N
XVIIb, XVIId, XVIIe
IV
O
O
O
R
Iа_Ie
N
NH
XIIIа_XIIIc, XIIIe
O
O
R
O
O
R
O
O
R
N
N
N
+ XVIIb
XVIIb, XVIId
HO
NH
N
NH
XVа_XVc
R = H (a), Br (b), F (c), NO2 (d), MeO (e).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 5 2007
XVIа
XIVb_XIVd

GUSAK, KOZLOV
710
O
O
O
O
N
N
N
O
NH
XX
XVIII
N
O
O
V
O
N
XXI
N
N
XIX
Iа
O
O
N
H
N
XXI
2-(2-quinoline-2-carbonyl)acrylates XVIIb, XVIId, and
XVIIe], and methoxy-substituted azomethine Ie yielded
under these conditions a single reaction product ester
XVIIe. Taking into consideration the results of previous
studies [9, 10] we believe that the formation of unsaturat-
ed ketoesters XVIIa–XVIIe can occur on the one hand
by aldol condensation of ketoester IV with the aldehyde
liberated by the hydrolysis of the initial azomethine and
on the other hand by hydramine cleavage of intermediate
aminoketoesters XIIIa–XIIIc and XIIIe. Evidently the
cleavage and cyclization of intermediates XIII are
governed by the nature of substituent R. At R = H, NO2,
Br, and F the cyclization dominates over the cleavage of
esters XIII, and prevailing reaction products are benzo-
quinolinecarboxylic acids derivatives. On the contrary,
the electron-donor methoxy group shifts the reaction
towards the cleavage of aminoketoester XIIIe, and the
corresponding cyclization products do not form.
at any stage and to obtain all theoretically presumable
reaction products.
Ethyl 3-(3-pyridyl)-3-oxopropanoate (V) unlike
quinolyl-substituted ester IV added to the C=N bond of
azomethine Ia without catalyst. At heating reagents Ia
and V in ethanol to 40–50°C ethyl 3-(2-naphthylamino)-
2-nicotinoyl-3-phenylpropanoate (XVIII) was obtained
in quantitative yield.
At heating the same reagents in ethanol in the presence
of concn. HCl in a sealed ampule at 100°C the only
product obtained was 1-(3-pyridyl)-3-phenylbenzo[f]-
quinoline (XIX). We presume that under given conditions
hydrolysis and decarboxylation of ester group occurs in
ethyl 3-(3-pyridyl)-3-β-oxopropanoate (V) giving 3-acet-
ylpyridine that further undergoes condensation with
azomethine Ia yielding benzo[f]quinoline XIX.
Aminoketoester XVIII is less prone to decarboxyla-
tion than ester V. The heating of compound XVIII in the
presence of HCl under severe conditions brings about
its cyclization into ethyl 1-(3-pyridyl)-3-phenylbenzo[f]-
quinolinecarboxylate (XX).
Comparing the behavior of arylmethylene-2-naphthyl-
amines Ia–Ie in reactions with compound IV and
acetoacetate II or furoylacetate III we showed that the
presence of a bulky quinoline substituent in the molecule
of oxoester IV led to the deceleration of cyclization,
dehydration, and dehydrogenation of the intermediate
compounds. It is therefore possible to stop the process
From the reaction mixture obtained from azomethine
Ia and ester V in toluene solution in the presence of
a basic catalyst (piperidine) an individual product was
isolated, 3-(3-pyridyl)-3-oxopropanoic acid N-(2-
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β-OXOACIDS ESTERS IN THE SYNTHESIS OF BENZO[f]QUINOLINE DERIVATIVES
711
naphthyl)amide (XXI). Amide XXI might form by
reaction of ester V with 2-naphthylamine liberated by
hydrolysis of azomethine Ia catalysed by the base. We
also obtained amide XXI attempting to perform the
cyclization of aminoketoester XVIII in the presence of
piperidine. In all likelihood in the same way as with
amino derivatives of furoylacetates XIa–XIe a C–C bond
in the molecule of aminoketoester XVIII suffered
cleavage generating benzylidene-2-naphthylamine (Ia)
and pyridyloxopropanoate V. The hydrolysis of azo-
methine Ia and the reaction of the liberated 2-naphthyl-
amine with ketoester V along the above described path-
way led to the formation of amide XXI.
XIe, and XIIIe, also to the methoxyphenyl substituent;
also the bands are present of the stretching vibrations of
aliphatic C–H bonds in the region 2920–2890 cm–1 and
of C–H bonds in aromatic and heteroaromatic rings at
3060–3030 cm–1. The vibrations of the fragment C–O–
C in the furan ring in the spectra of compounds Xa–Xd
and XIa–XIe appear as a strong band at 1255–1230 cm–1.
In the spectra of nitro derivatives VId, Xd, XId, and
XIVd characteristic absorption bands of the NO2 group
are observed at 1530 and 1355 cm–1.
In the mass spectra of aminoketoesters VIIa, XIa–
XIe, XIIIa–XIIIc, XIIIe, and XVIII the molecular ion
peak is of low intensity (12–25%). The most abundant
(100%) are fragment ions corresponding to the initial
compounds Ia–Ie and II–V and those arising from to
the rupture of C–C bond and recombination of fragment
ions with simultaneous disproportionation of hydrogen
ions. In the spectra of esters XIa–XIe, XIIIa–XIIIc,
XIIIe, and XVIII intensive peaks are present (Irel 65–
75%) of ions [M – C10H7NH2]+.
The composition and structure of compounds syn-
thesized were confirmed by elemental analysis, IR, UV,
NMR and mass spectra.
In IR spectra of aminoketoesters VIIa, XIa–XIe,
XIIIa–XIIIc, XIIIe, and XVIII the characteristic
absorption band of the stretching vibrations of NH group
appeared at 3400–3375 cm–1 and the absorption band
ν
CO of ester group vibrations was observed at 1740–1730
In the mass spectra of hydroxyesters XIVb–XIVd the
molecular ion peaks are the most abundant, and the other
rather strong peaks (45–60%) are those of [M – 18]+
corresponding to water molecule elimination from the
molecular ion thus confirming the presence of a hydroxy
group in compounds XIVb–XIVd.
cm–1. Carbonyl group in the spectrum of ester VIIa gave
rise to a band at 1715 cm–1, in the spectra of compounds
XIa–XIe, XIIIa–XIIIc, XIIIe, and XVIII this band is
displaced to the region 1680–1660 cm–1 apparently due
to the conjugation with the adjacent heterocyclic ring.
In the IR spectra of cyclic hydroxyesters XIVb–XIVd
a strong broad absorption band was observed in the region
3600–3380 cm–1. In the spectrum of the same compounds
taken in CCl4 solution this absorption appeared as two
bands at 3410 (νNH) and 3605 (νOH) cm–1. The stretching
vibrations νCO of the ester group were present at
1720 cm–1. In the spectra of compounds XIVb–XIVd
lacks the absorption band of the keto group stretching
vibrations characteristic of aminoketoesters VIIa, XIa–
XIe, XIIIa–XIIIc, XIIIe, and XVIII indicating the
fulfilled cyclization.
The mass spectra of dihydro derivatives VIIIe and
XVa–XVc alongside the most abundant molecular ion
peaks contain also fragment ions peaks: [M – COOEt]+
(Irel 35–40%), [M – C6H4R]+ (Irel 48–55%), and the
spectra of quinolyl-substituted compounds XIVb–XIVd
contain also peaks of ions [M – C9H6N–CH=CH–
COOEt]+ (Irel 42–47%).
Mass spectra of final aromatic products VIa–VIe,
Xa–Xd, XVIa, and XX reveal the stability of these
compounds against the electron impact: The spectra
contain the strongest peak of molecular ion and peaks of
low intensity (8–12%) corresponding to [M – COOEt]+
and [M – C6H4R]+.
The IR spectra of dihydro derivatives VIIIe and XVa–
XVc contain a medium band at 3400–3365 (νNH) and
a strong band of ester group (νCO) at 1700–1690 cm–1.
In the IR spectra of final cyclization products VIa–VIe,
Xa–Xd, XVIa, and XX the characteristic band of NH
group stretching vibrations is absent but the band νCO of
the ester group is retained. In the IR spectrum of all
mentioned esters VIa–VIe, VIIa, VIIIe, Xa–Xd, XIa–
XIe, XIIIa–XIIIc, XIIIe, XIVb–XIVd, XVa–XVc,
XVIa, XVIII, and XX a strong band is observed in the
region 1230–1180 cm–1 belonging to the fragment C–
O–C of the ester group, and for compounds VIe, VIIIe,
UV spectra of aminoketoesters VIIa, XIa–XIe,
XIIIa–XIIIc, XIIIe, and XVIII containing the
naphthalene skeleton as the main chromophore fragment
resemble the spectrum of 2-naphthylamine [UV
spectrum, λmax, nm (logε): 246 (4.38), 280 (3.66), 338
(3.25)].As compared to the latter spectrum, in the spectra
of esters VIIa, XIa–XIe, XIIIa–XIIIc, XIIIe, and XVIII
the intensity of all bands was greater evidently because
of the presence in the molecule of additional benzyl
chromophore, and in propanoates XIa–XIe, XIIIa–
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GUSAK, KOZLOV
712
XIIIc, XIIIe, and XVIII the spectrum is also affected
by the introduction of the heterocyclic ring..
at the C4 atom, as a multiplet at 4.58 ppm. Methine proton
at the C2 atom in the spectra of propanoates XIa–XIe,
XIIIa–XIIIc, XIIIe, and XVIII gives rise to a signal in
the region 5.28–5.49 ppm. In the NMR spectra of
hydroxyesters XIVb–XIVd proton signal from the OH
group is observed at 8.40–8.48 ppm. In the spectra of
dihydro derivatives VIIIe and XVa–XVc this signal
disappeares as well as the signal of the methine proton
H2 indicating the dehydration of the hydroxyesters. The
signal of methine proton H3 in the spectra of esters VIIIe
and XVa–XVc is shifted downfield compared to its
position in the spectra of compounds XIVb–XIVd
(δ 4.65–4.70 ppm) and appears at 5.98–6.18 ppm like in
the spectra of fused azaphenanthrenes with the partially
hydrogenated pyridine ring [12]. The amino group proton
in the spectra of dihydro derivatives VIIIe and XVa–
XVc is observed at 4.72–4.98 ppm. In the spectra of
oxidized benzo[f]quinolines VIa–VIe, Xa–Xd, XVIa,
and XX the proton signals of NH and H3 disappear, and
remain proton signals from the CO2Et group at 1.06–
1.22 and 4.05–4.22 ppm and from the aromatic protons
in the region 6.71–8.60 ppm. In the spectra of esters VIa–
VIe a singlet of methylene protons of the fragment
CH2CO is also observed at 4.44–4.66 ppm proving the
fact that the condensation of azomethines Ia–Ie with
ethyl acetoacetate (II) occurs at the methyl group of the
latter. Methoxy-substituted aminoketoesters XIe and
XIIIe and benzo[f]quinolines VIIIe and VIe contain in
the spectra a singlet from the methoxy group protons at
3.70–3.80 ppm.
In the UV spectra of hydroxyesters XIVb–XIVd the
increased intensity of the short-wave absorption band
was observed as compared with the spectra of the
noncyclic precursors XIIIa–XIIIc and XIIIe. Besides
due to the transformation of the carbonyl into a hydroxy
group the former does not affect the quinoline framework,
and in the spectra of hydroxyesters XIVb–XIVd the
absorption band characteristic of quinoline structure is
easily isolated (316–317 nm) since it plays the role of an
independent chromophore [11]. The long-wave band in
the spectra of compounds XIVb–XIVd is less strong and
suffers a red shift with respect to its position in the spectra
of aminoketoesters XIII.
The long-wave band in the UV spectra of dihydro
derivatives VIIIe and XVa–XVc suffered a considerable
red shift evidently because of the formation of a new
double bond in the closed cyclic system. This bond in
the molecule of dihydroquinolylacetate VIIIe is in
conjugation only with the naphthalene core and therefore
produces in the spectra a large red shift of the long-wave
band (λ 412 nm) compared with the spectra of dihydro-
benzoquinolinecarboxylates XVa–XVc (λ 368–384 nm)
where the conjugation system involves also the quinoline
moiety and the ester group.
The aromatization of the benzoquinoline framework
results in the appearance in the UV spectra of the final
cyclization products VIa–VIe, Xa–Xd, XVIa, and XX
of a strong band at 278–290 nm and less strong bands at
230–241, 250–269, and 341–353, 361–374 nm whose
presence makes the spectra of compounds VIa–VIe, Xa–
Xd, XVIa, and XX to resemble the spectra of 1,3-di-
arylbenzo[f]quinolines [1] and permits interpretation of
the existing bands as Clar p-, β- , and α-bands. The
heteryl moiety and the substituent in the phenyl ring of
the benzo[f]quinoline molecule virtually do not affect
the position and intensity of the spectral bands.
Hence every oxoester imparts specific features to the
reaction with azomethines remaining an efficient synthon
for preparation of functionally substituted benzo[f]quino-
lines and of semiproducts of their synthesis which having
in the structure pharmacophore groups and heterocyclic
fragments are promising as bioactive substances of a wide
range of activity.
EXPERIMENTAL
In the 1H NMR spectra of aminoketoesters VIIa, XIa–
XIe, XIIIa–XIIIc, XIIIe, and XVIII proton signals are
observed from ethyl group at 1.08–1.20 and 4.00–
4.14 ppm, multiplets from aromatic protons in the region
6.61–8.24 ppm, signal of the methine proton attached to
the aryl-substituted carbon in the region 4.14–4.90 ppm,
broadened singlet of the amino group proton at 8.60 ppm
for pentanoate VIIa and 5.42–5.60 ppm for propanoates
XIa–XIe, XIIIa–XIIIc, XIIIe, and XVIII. Methylene
protons at the C2 atom in the spectrum of ester VIIa
appear as a multiplet in the region 5.20–5.45 ppm, those
IR spectra were recorded on a Fourier spectrometer
Nicolet Protege-460 from KBr pellets. Mass spectra were
measured on Finnigan MAT INCOS-50 instrument,
ionizing electrons energy 70 ev, and on GC-MS Hewlett-
Packard HP 5890/5972 device in the electron impact
mode at the energy 70 eV; column HP-5MS [30 m ×
0.25 mm, stationary phase film (5% PLMe Silicone)
0.25 μm thick], vaporizer temperature 250°C. UV spectra
of compounds solutions in ethanol (C 10–4 mol/l) were
taken on a spectrophotometer Specord UV-Vis. NMR
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β-OXOACIDS ESTERS IN THE SYNTHESIS OF BENZO[f]QUINOLINE DERIVATIVES
713
spectra were registered on spectrometers BrukerAC-500
(500 MHz) and Tesla BS-567 (100 MHz) from solutions
in DMSO-d6 and chloroform-d; internal reference TMS.
spectrum, λmax, nm (logε): 236 (4.41), 267 (4.59), 279
(4.68), 346 (3.83), 363 (3.85). 1H NMR spectrum, δ, ppm:
1.22 t, 4.14 q (5H, OEt, 2J 14.0, 3J 6.0 Hz), 4.46 s (2H,
CH2), 7.20 m, 8.22 d (4Harom, 3J 8.2 Hz), 7.64 d.d (2H,
..
The melting points were measured on a Koffler
heating block.
3
4
H8,9, J 7.5, J 2.7 Hz), 7.82 s (1H, H2), 7.95–8.10 m
(3H, H5–7), 8.53 d.d (1H, H10, 3J 7.5, 4J 2.7 Hz). Found,
% N 3.75. C23H18FNO2. Calculated, %: N 3.90.
Arylmethylene-2-naphthylamines Ia–Ie were
prepared by procedure [13].
Ethyl {3-(p-nitrophenyl)benzo[f]quinol-1-yl}acetate
Ethyl 3-oxo-3-(2-furyl)propanoate (III) was obtained
by acylating ethyl acetoacetate with 2-furancarbonyl
chloride [14].
(VId). Yield 43%, mp 196–197°C. UV spectrum, λmax
,
nm (logε): 230 (4.21), 269 (4.40), 282 (4.48), 341 (4.00),
1
362 (3.98). H NMR spectrum, δ, ppm: 1.22 t, 4.20 q
Ethyl 3-oxo-3-(2-quinolyl-, 3-pyridyl)propanoates IV
and V were prepared by ester condensation of ethyl
acetates and ethyl esters of quinaldic and nicotinic acids
respectively [15, 16].
(5H, OΕt, 2J 14.1, 3J 6.1 Hz), 4.60 s (2H, CH2), 7.65 d.d
3
4
(2H, H8,9, J 7.9, J 2.6 Hz), 7.94–8.08 m (3H, H5–7),
8.25 s (1H, H2), 8.36 d, 8.54 d (4Harom, 3J 8.1 Hz), 8.58
d.d (1H, H10, J 7.9, J 2.6 Hz). Found, %: C 71.41;
H 4.46; N 7.17. C23H18N2O4. Calculated, %: C 71.50;
H 4.66; N 7.25.
3
4
1-(3-Pyridyl)-3-phenylbenzo[f]quinoline (XIX) was
identified by the melting point, IR, UV, and mass spectra
[1].
Ethyl {3-(p-methoxyphenyl)benzo[f]-quinol-1-
yl}acetate (VIe). Yield 31%, mp 133–134°C. UV
spectrum, λmax, nm (logε): 234 (4.43), 269 (4.57), 285
(4.69), 354 (4.08), 366 (4.08). 1H NMR spectrum, δ, ppm:
1.20 t, 4.21 q (5H, OΕt, 2J 14.0, 3J 6.1 Hz), 3.85 s (3H,
Ethyl (3-arylbenzo[f]quinol-1-yl)-acetates VIa–
VIe. Amixture of 10 mmol of azomethine Ia–Ie, 40 mmol
of ethyl acetoacetate (II), 20 ml of 2-propanol (azo-
methines Ia–Id) or ethanol (azomethine Ie), and 10 drops
of concn. HCl was boiled for 1 h. The reaction mixture
was neutralized with 25% water solution of ammonia at
room temperature, the separated precipitate of the product
was filtered off and recrystallized from a mixture
2-propanol–tolyene, 2:1.
OMe), 4.45 s (2H, CH2), 7.12 d, 8.28 d (4Harom
,
3J 7.7 Hz), 7.62 d.d (2H, H8,9, 3J 7.8, 4J 2.7 Hz), 7.80 s
(1H, H2), 7.94–8.08 m (3H, H5–7), 8.56 d.d (1H, H10,
3J 7.8, 4J 2.7 Hz). Found, %: C 77.61; H 5.72; N 3.52.
C24H21NO3. Calculated, %: C 77.63; H 5.66; N 3.77.
Ethyl (3-phenylbenzo[f]quinol-1-yl)-acetate (VIa).
Yield 30%, mp 133–134°C. UV spectrum, λmax, nm
(logε): 231 (4.42), 278 (4.61), 344 (3.68), 362 (3.72).
1H NMR spectrum, δ, ppm: 1.21 t, 4.22 q (5H, OEt,
2J 14.2, 3J 6.1 Hz), 4.66 s (2H, CH2), 7.55 d, 8.22 m (5H,
Ethyl 5-(2-naphthylamino)-3-oxo-5-phenyl-
pentanoate (VIIa). Asolution of 10 mmol of azomethine
Ia and 40 mmol of ethyl acetoacetate (II) in 30 ml of
ethanol was boiled for 1 h. The precipitate separated on
cooling the reaction mixture was recrystallized from
3
3
4
Ph, J 8.2 Hz), 7.62 d.d (2H, H8,9, J 7.2, J 2.8 Hz),
2-propanol. Yield 65%, mp 90–91°C. UV spectrum, λmax
,
7.88 s (1H, H2), 7.92–8.06 m (3H, H5–7), 8.58 d.d (1H,
nm (logε): 220 (4.60), 272 (4.42), 338 (4.00), 362 (3.72).
3
4
H10, J 7.2, J 2.8 Hz). Found, %: C 80.69; H 5.35;
N 3.97. C23H19NO2. Calculated, %: C 80.94; H 5.57;
N 4.11.
1H NMR spectrum, δ, ppm: 1.20 t, 3.90–4.14 m (6H,
OΕt, H5, J 14.2, J 6.1 Hz), 4.58 m (2H, H2), 5.20–
5.45 m (2H, H4), 7.48–8.56 m (13Harom), 8.60 br.s (1H,
NH). Found, %: C 76.17; H 6.30; N 3.70. C23H23NO3.
Calculated, %: C 76.45; H 6.37; N 3.88.
2
3
Ethyl {3-(p-bromophenyl)benzo[f]quinol-1-yl}-
acetate (VIb). Yield 56%, mp 143–144°C. UV spectrum,
λ
max, nm (logε): 230 (4.48), 268 (4.58), 282 (4.72), 349
Ethyl {3-(p-methoxyphenyl)-3,4-dihydro-
benzo[f]quinol-1-yl}acetate (VIIIe). To a solution of
10 mmol of azomethine Ie and 40 mmol of ethyl
acetoacetate (II) in 25 ml of ethanol heated to 70°C was
added 5 drops of concn. HCl. The solution was cooled,
neutralized with NH4OH, the precipitate was filtered off
and recrystallized from ethanol. Yield 37%, mp 155–
156°C. UV spectrum, λmax, nm (logε): 245 (4.50), 276
1
(3.86), 366 (3.91). H NMR spectrum, δ, ppm: 1.22 t,
4.12 q (5H, OEt, 2J 14.2, 3J 6.0 Hz), 4.44 s (2H, CH2),
7.62 d.d (2H, H8,9, J 7.3, J 2.9 Hz), 7.64 d, 8.12 m
(4Harom, 3J 8.0 Hz), 7.83 s (1H, H2), 7.93–8.08 m (3H,
H5–7), 8.59 d.d (1H, H10, 3J 7.3, 4J 2.9 Hz). Found, %:
C 65.53; H 4.19; Br 18.81; N 3.34. C23H18BrNO2.
Calculated, %: C 65.72; H 4.28; Br 19.05; N 3.33.
3
4
1
Ethyl {3-(p-fluorophenyl)benzo[f]quinol-1-
yl}acetate (VIc). Yield 40%, mp 109–110°C. UV
(4.39), 412 (3.71). H NMR spectrum, δ, ppm: 1.18 t,
4.08 q (5H, OΕt, 2J 14.0, 3J 6.1 Hz), 3.48 s (2H, CH2),
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GUSAK, KOZLOV
714
3.72 s (3H, OMe), 4.72 m (1H, NH), 6.18 s (1H, H3),
6.88 d, 7.26 d (4Harom, J 7.9 Hz), 7.00–7.75 m (6H,
H2,5–9), .90 d (1H, H10, 3J 7.8, 4J 2.7 Hz). Found, %:
C 76.99; H 6.13; N 3.58. C24H23NO3. Calculated, %:
C 77.21; H 6.17; N 3.75.
145°C. UV spectrum, λmax, nm (logε): 241 (4.36), 260
3
1
(4.49), 284 (4.69), 348 (3.76), 367 (3.72). H NMR
2
spectrum, δ, ppm: 1.08 t, 4.15 q (5H, OEt, J 14.2,
3J 6.0 Hz), 6.80–8.20 m (13Harom). Found, %: C 65.91;
H 3.58; Br 16.74; N 3.01. C26H18BrNO3. Calculated, %:
C 66.10; H 3.81; Br 16.95; N 2.97.
Cyclization of ethyl 5-(2-naphthylamino)-3-oxo-5-
phenylpentanoate (VIIa). A solution of 10 mmol of
compound VIIa and 7 drops of concn. HCl in 40 ml of
ethanol was boiled for 0.5 h. The tarry precipitate of
benzyl-2-naphthylamine hydrochloride (IXa) was
filtered off, boiled with a water solution of NH4OH,
ground with water, and recrystallized from 2-propanol.
Ethyl 3-(p-fluorophenyl)-1-(2-furyl)-benzo[f]-
quinoline-2-carboxylate (Xc). Yield 39%, mp 97–98°C.
UV spectrum, λmax, nm (logε): 240 (4.39), 265 (4.51),
1
286 (4.72), 349 (3.90), 367 (3.78). H NMR spectrum,
δ, ppm: 1.10 t, 4.13 q (5H, OEt, 2J 14.1, 3J 6.1 Hz), 6.73–
8.11 m (13Harom). Found, %: N 3.26. C26H18FNO3.
Calculated, %: N 3.41.
Benzyl-2-naphthylamine (IXa). Yield 5%, mp 65–
66°C. UV spectrum, λmax, nm (logε): 214 (4.62), 253
(4.70), 292 (4.06), 370 (3.82). 1H NMR spectrum, δ, ppm:
4.30 d (2H, CH2, 2J 14.0 Hz), 6.30 br.s (1H, NH), 6.70–
7.72 m (12Harom). Found, %: C 87.24; H 6.40; N 5.73.
C17H15NO. Calculated, %: C 87.55; H 644; N 6.01.
Ethyl 3-(p-nitrophenyl)-1-(2-furyl)-benzo[f]quino-
line-2-carboxylate (Xd). Yield 40%, mp 188–189°C. UV
spectrum, λmax, nm (logε): 247 (4.40), 261 (4.43), 290
(4.69), 348 (3.73), 366 (3.69). 1H NMR spectrum, δ, ppm:
1.06 t, 4.16 q (5H, OEt, 2J 14.0, 3J 6.0 Hz), 7.02–8.74 m
(13Harom). Found, %: C 71.12; H 3.95; N 6.27.
C26H18N2O5. Calculated, %: C 71.23; H 4.11; N 6.39.
The mother liquor after separating the amine
hydrochloride was neutralized with NH4OH and
evaporated by 1/4 of its volume. The separated precipitate
was treated with ethyl ether to obtain benzo[f]-
quinolylacetate VIa. Yield 25%.
Ethyl 3-aryl-3-(2-naphthylamino)-2-(2-furoyl)-
propanoate XIa–XIe. A solution of 10 mmol of
azomethine Ia–Ie and 20 mmol of ester III in 30 ml of
ethanol was boiled for 1 h, cooled, and the precipitate
was filtered off. Compound XIa was recrystallized from
ethanol.
Dehydrogenation of ethyl {3-(p-methoxyphenyl)-
3,4-dihydrobenzo[f]quinol-1-yl}-acetate (VIIIe).
A solution of 5 mmol of dihydro derivative VIIIe and
10 drops of concn. HCl in 20 ml of ethanol was boiled
for 1 h. The separated precipitate was filtered off, treated
with a water solution of NH4OH, and recrystallized from
a mixture 2-propanol–toluene, 2:1. Yield of ester VIe
56%.
Ethyl 3-(2-naphthylamino)-3-phenyl-2-(2-
furoyl)propanoate (XIa). Yield 78%, mp 107–108°C.
UV spectrum, λmax, nm (logε): 231 (4.60), 247 (4.69),
272 (4.43), 320 (4.11). 1H NMR spectrum, δ, ppm: 1.08
t, 4.00 q (5H, OEt, 2J 14.1, 3J 6.1 Hz), 4.81 d (1H, H3,
3J 9.2 Hz), 5.43 br.s (1H, NH), 5.47 d (1H, H2, 3J 9.2 Hz),
6.85–7.82 m (15Harom). Found, %: C 75.35; H 5.48;
N 3.17. C26H23NO4.Calculated, %: C 75.54; H 5.57; N 3.39.
Ethyl 3-aryl-1-(2-furyl)benzo[f]quinoline-2-carb-
oxylate (Xa–Xd). A mixture of 10 mmol of azomethine
Ia–Id, 20 mmol of furoylacetate III, 20 ml of ethanol,
10 drops of concn. HCl, and 12 drops of nitrobenzene
was boiled for 2 h, cooled, neutralized with a water
solution of NH4OH, and the precipitate was filtered off.
Compounds Xa–Xc were recrystallized from 2-propanol,
carboxylate Xd, from nitromethane.
Ethyl 3-(p-bromophenyl)-3-(2-naphthylamino)-2-
(2-furoyl)propanoate (XIb). Yield 87%, mp 103–
104°C. UV spectrum, λmax, nm (logε): 230 (4.58), 249
(4.66), 270 (4.41), 319 (4.13). 1H NMR spectrum, δ, ppm:
1.10 t, 4.12 q (5H, OEt, 2J 14.2, 3J 6.2 Hz), 4.89 d (1H, H3,
3J 9.0 Hz), 5.40 br.s (1H, NH), 5.45 d (1H, H2, 3J 9.0 Hz),
6.90–8.01 m (14Harom). Found, %: C 63.33; H 4.41;
Br 15.96; N 2.77. C26H22BrNO4. Calculated, %: C 63.41;
H 4.47; Br 16.26; N 2.85.
Ethyl 3-phenyl-1-(2-furyl)benzo[f]-quinoline-2-
carboxylate (Xa). Yield 29%, mp 111–112°C. UV
spectrum, λmax, nm (logε): 239 (4.40), 267 (4.50), 284
(4.74), 348 (3.82), 365 (3.80). 1H NMR spectrum, δ, ppm:
1.07 t, 4.08 q (5H, OEt, 2J 14.0, 3J 6.1 Hz), 6.71–8.18 m
(14Harom). Found, %: C 79.15; H 4.62; N 3.44.
C26H19NO3. Calculated, %: C 79.39; H 4.85; N 3.56.
Ethyl 3-(2-naphthylamino)-3-(p-fluorophenyl)-2-
(2-furoyl)propanoate (XIc). Yield 84%, mp 93–94°C.
UV spectrum, λmax, nm (logε): 234 (4.56), 248 (4.70),
273 (4.45), 322 (4.19). 1H NMR spectrum, δ, ppm: 1.11 t,
Ethyl 3-(p-bromophenyl)-1-(2-furyl)-benzo[f]-
quinoline-2-carboxylate (Xb). Yield 57%, mp 144–
3
4.03 q (5H, OEt, 2J 14.0, J 6.0 Hz), 4.90 d (1H, H3,
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β-OXOACIDS ESTERS IN THE SYNTHESIS OF BENZO[f]QUINOLINE DERIVATIVES
715
3
3J 9.1 Hz), 5.40 d (1H, H2, J 9.1 Hz), 5.44 br.s (1H,
NH), 6.84–8.00 m (14Harom). Found, %: N 3.09.
C26H22FNO4. Calculated, %: N 3.25.
Ethyl 2-[(p-bromophenyl)(2-naphthylamino)-
methyl]-3-(2-naphthylimino)-3-(2-furyl)propanoate
(XIIb). Yield 6%, mp 227–228°C. UV spectrum, λmax
,
nm (logε): 227 (4.60), 249 (4.70), 278 (4.49), 316 (4.18).
Ethyl 3-(2-naphthylamino)-3-(p-nitrophenyl)-2-(2-
furoyl)propanoate (XId). Yield 93%, mp 92–93°C. UV
spectrum, λmax, nm (logε): 230 (4.59), 246 (4.63), 269
1H NMR spectrum, δ, ppm: 1.14 t, 4.10 q (5H, OEt,
3
3
2J 14.0, J 6.0 Hz), 4.83 d (1H, H3, J 8.9 Hz), 5.23 d
(1H, H2, J 8.9 Hz), 5.60 br.s (1H, NH), 6.81–8.02 m
3
1
(4.40), 320 (4.09). H NMR spectrum, δ, ppm: 1.10 t,
4.04 q (5H, OEt, 2J 14.1, 3J 6.0 Hz), 4.90 d (1H, H3,
(21Harom). Found, %: C 69.91; H 4.58; Br 12.66; N 4.37.
C36H29BrN2O3. Calculated, %: C 70.02; H 4.70; Br 12.97;
N 4.54.
3
3J 8.9 Hz), 5.42 d (1H, H2, J 8.9 Hz), 5.46 br.s (1H,
NH), 7.13–8.24 m (14Harom). Found, %: C 67.89; H 4.67;
N 5.92. C26H22N2O6. Calculated, %: C 68.12; H 4.80;
N 6.11.
Ethyl 2-[(p-fluorophenyl)(2-naphthylamino)-
methyl]-3-(2-naphthylimino)-3-(2-furyl)-propanoate
(XIIc). Yield 7%, mp 270–271°C. UV spectrum, λmax
,
Ethyl 3-(p-methoxyphenyl)-3-(2-naphthylamino)-
2-(2-furoyl)propanoate (XIe). Yield 78%, mp 94–95°C.
UV spectrum, λmax, nm (logε): 233 (4.61), 247 (4.68),
273 (4.48), 314 (4.06). 1H NMR spectrum, δ, ppm: 1.09 t,
4.03 q (5H, OEt, 2J 14.2, 3J 6.1 Hz), 3.70 s (3H, OMe),
nm (logε): 226 (4.62), 246 (4.71), 275 (4.45), 318 (4.22).
1H NMR spectrum, δ, ppm: 1.11 t, 4.02 q (5H, OEt,
3
3
2J 14.1, J 6.2 Hz), 4.81 d (1H, H3, J 9.1 Hz), 5.29 d
(1H, H2, J 9.1 Hz), 5.60 br.s (1H, NH), 6.78–8.00 m
3
3
4.88 d (1H, H3, J 8.8 Hz), 5.43 br.s (1H, NH), 5.49 d
(21Harom). Found, %: N 4.92. C36H29FN2O3. Calculated,
%: N 5.04.
(1H, H2, 3J 8.8 Hz), 6.63–7.94 m (14Harom). Found, %:
C 72.92; H 5.41; N 3.04. C27H25NO5. Calculated, %: C 73.14;
H 5.64; N 3.16.
From the cooled mother liquors in 2-propanol benzo-
[f]carboxylates Xa–Xc were isolated in respective yields
28, 30, and 25%. Benzo[f]quinolinecarboxylate Xd was
isolated by neutralization of the reaction mixture with
a water solution of NH4OH and recrystallization of the
separated precipitate from nitromethane. Yield 26%. In
the case of aminoketoester Ie the treatment of the reaction
mixture with NH4OH and evaporation of the mixture
by 1/3 of volume a precipitate was obtained of azo-
methine Ie.
Cyclization of ethyl 3-aryl-3-(2-naphthylamino)-
2-(2-furoyl)propanoates XIa–XIe. A solution of
10 mmol of aminoester XIa–XIe, 10 drops of concn.
HCl, and 12 drops of nitrobenzene in 30 ml of ethanol
was boiled for 2 h. The tarry precipitate formed from
compound XIa–XIc was filtered off, boiled with a water
solution of NH4OH, then ground with water. We obtained
compounds IXa–IXc. Yield of benzylnaphthylamine IXa
18%, its characteristics are given above.
Ethyl 3-aryl-3-(2-naphthylamino)-2-(quinoline-2-
carbonyl)propanoates XIIIa–XIIIc and XIIIe.
A solution of 10 mmol of azomethine Ia–Ic and Ie,
10 mmol of ester IV, 3 drops of concn. HCl in 20 ml of
ethanol was stirred for 10–20 min at 20°C. The precipitate
formed was treated with aqueous NH4OH and
recrystallized from ethanol.
p-Bromobenzyl-2-naphthylamine (IXb). Yield
15%, mp 110–111°C. UV spectrum, λmax, nm (logε):
215 (4.65), 257 (4.72), 291 (4.03), 372 (3.90). 1H NMR
spectrum, δ, ppm: 4.28 d (2H, CH2, 2J 14.1 Hz), 6.31 br.s
(1H, NH), 7.00–7.82 m (11Harom). Found, %: C 65.23;
H 4.31; Br 25.28; N 4.11. C17H14BrN. Calculated, %:
C 65.38; H 4.49; Br 25.64; N 4.49.
Ethyl 3-(2-naphthylamino)-3-phenyl-2-(quinoline-
2-carbonyl)propanoate (XIIIa). Yield 79%, mp 115–
116°C. UV spectrum, λmax, nm (logε): 213 (4.63), 224
(4.65), 248 (4.69), 270(4.48), 320 (4.30). 1H NMR spec-
trum, δ, ppm: 1.20 t, 4.00 q (5H, OEt, 2J 14.0, 3J 6.1 Hz),
p-Fluorobenzyl-2-naphthylamine (IXc). Yield 20%,
mp 86–87°C. UV spectrum, λmax, nm (logε): 214 (4.60),
1
251 (4.69), 290 (4.00), 368 (3.80). H NMR spectrum,
2
δ, ppm: 4.32 d (2H, CH2, J 14.0 Hz), 6.25 br.s (1H,
3
4.88 d (1H, H3, J 9.0 Hz), 5.46 br.s (1H, NH), 5.49 d
NH), 6.92–7.74 m (11Harom). Found, %: N 5.36.
C17H14FN. Calculated, %: N 5.58.
(1H, H2, 3J 9.0 Hz), 6.69–8.20 m (18Harom). Found, %:
C 78.21; H 5.19; N 5.83. C31H26N2O3. Calculated, %:
C 78.48; H 5.49; N 5.91.
The mother liquor obtained after separating amines
IXa–IXc was evaporated to dryness, the solid residue
was treated with a water solution of NH4OH, with water,
and then was dissolved in 2-propanol. The insoluble
residue of compounds XIIb and XIIc was filtered off
and recrystallized from nitromethane.
Ethyl 3-(p-bromophenyl)-3-(2-naphthylamino)-2-
(quinoline-2-carbonyl)propanoate (XIIIb). Yield 64%,
mp 121–122°C. UV spectrum, λmax, nm (logε): 215
(4.62), 226 (4.64), 249 (4.66), 273 (4.46), 280 m (4.28),
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GUSAK, KOZLOV
716
1
330 (4.21). H NMR spectrum, δ, ppm: 1.18 t, 4.01 q
(5H, OEt, 2J 14.2, 3J 6.1 Hz), 4.73 d (1H, H3, 3J 9.3 Hz),
λ
max, nm (logε): 208(4.75), 235 (4.83), 256 (4.68), 246
1
(4.67), 284 (4.10), 317 (3.80), 349 (3.60). H NMR
5.32 d (1H, H2, J 9.3 Hz), 5.48 br.s (1H, NH), 6.82–
3
2
spectrum, δ, ppm: 1.08 t, 4.07 q (5H, OEt, J 14.1,
3J 6.00 Hz), 4.65 d (1H, H3, 3J 9.2 Hz), 5.27 d (1H, H2,
3J 9.2 Hz), 5.66 br.s (1H, NH), 6.78–8.14 m (16Harom),
8.40 C (1H, OH). Found, %: N 5.46. C31H25FN2O3.
Calculated, %: N 5.69.
8.19 m (17Harom). Found, %: C 67.20; H 4.35; Br 14.10;
N 4.83. C31H25BrN2O3. Calculated, %: C 67.27; H 4.52;
Br 14.47; N 5.06.
Ethyl 3-(2-naphthylamino)-3-(p-fluorophenyl)-2-
(quinoline-2-carbonyl)propanoate (XIIIc). Yield 58%,
mp 117–118°C. UV spectrum, λmax, nm (logε): 214
(4.61), 228 (4.63), 256 (4.68), 286 (4.48), 326 (4.00).
1H NMR spectrum, δ, ppm: 1.15 t, 4.00 q (5H, OEt,
2J 14.1, 3J 6.01 Hz), 4.63 d (1H, H3, 3J 9.1 Hz), 5.28 d
(1H, H2, J 9.1 Hz), 5.51 br.s (1H, NH), 6.73–8.16 m
(17Harom). Found, %: N 5.51. C31H25FN2O3. Calculated,
%: N 5.69.
Ethyl 1-hydroxy-3-(p-nitrophenyl)-1-(2-quinolyl)-
1,2,3,4-tetrahydrobenzo[f]quinoline-2-carboxylate
(XIVd). Yield 36%, mp 249–250°C. UV spectrum, λmax
,
nm (logε): 207(4.77), 235 (4.81), 246 (4.70), 281 (4.30),
1
317 (3.91), 347 (3.60). H NMR spectrum, δ, ppm:
3
1.09 t, 4.03 q (5H, OEt, 2J 14.2, 3J 6.2 Hz), 4.69 d (1H,
H3, 3J 8.9 Hz), 5.14 d (1H, H2, 3J 8.9 Hz), 5.62 br.s (1H,
NH), 7.12–8.44 m (16Harom), 8.48 C (1H, OH). Found,
%: C 71.49; H 4.76; N 7.88. C31H25N3O5. Calculated,
%: C 71.68; H 4.82; N 8.09.
Ethyl 3-(p-methoxyphenyl)-3-(2-naphthylamino)-
2-(quinoline-2-carbonyl)propanoate (XIIIe). Yield
68%, mp 103–104°C. UV spectrum, λmax, nm (logε): 214
(4.65), 229 (4.69), 238 (4.65), 286 (4.50), 326 (4.32).
1H NMR spectrum, δ, ppm: 1.11 t, 4.08 q (5H, OEt,
2J 14.2, 3J 6.0 Hz), 3.70 s (3H, OMe), 4.65 d (1H, H3,
Ethyl 3-aryl-1-(2-quinolyl)-3,4-dihydrobenzo[f]-
quinoline-2-carboxylates XVa–XVc. A solution of
equimolar mixture (5 mmol each) of azomethine Ia–Ic
and ester IV containing 5 drops of concn. HCl in 5 ml of
DMF for benzylidene-2-naphthylamine (Ia) or in 20 ml
of ethanol for compounds Ib and Ic was heated for 2.5 h
at 80–100°C. The solution was evaporated to 1/2 of
volume. The tarry precipitate was treated with NH4OH,
hexane, and recrystallized from 2-propanol (ester XVa)
or ethanol (esters XVb and XVc).
3J 8.9 Hz), 5.28 d (1H, H2, J 8.9 Hz), 5.60 br.s (1H,
3
NH), 6.61–8.12 m (17Harom). Found, %: C 75.93; H 5.37;
N 5.44. C32H28N2O4. Calculated, %: C 76.19; H 5.56;
N 5.56.
Ethyl 3-aryl-1-hydroxy-1-(2-quinolyl)-1,2,3,4-
tetrahydrobenzo[f]quinoline-2-carboxylates XIVb–
XIVd. An equimolar mixture (5 mmol each) of Schiff’s
base Ib–Id and ester IV or 2.5 mmol of aminoketoester
XIIIb–XIIId in 20 ml of benzene containing 5 drops of
BF3 etherate for azomethines Ib and Ic or in 20 ml of
ethanol containing 3 drops of concn. HCl for compound
Id was heated at 80°C for 20 min or maintained for 72 h
at 20°C. Reaction products XIVb–XIVd were isolated
as described for compounds XIIIb–XIIId.
Ethyl 3-phenyl-1-(2-quinolyl)-3,4-dihydrobenzo-
[f]quinoline-2-carboxylate (XVa). Yield 63%, mp 119–
120°C. UV spectrum, λmax, nm (logε): 206 (4.64), 239
(4.59), 265 (4.41), 317(3.92), 368 (3.15). 1H NMR spec-
trum, δ, ppm: 1.14 t, 4.09 q (5H, OEt, 2J 14.1, 3J 6.1 Hz),
4.98 br.s (1H, NH), 5.98 s (1H, H3), 6.74–8.09 m
(17Harom). Found, %: C 81.36; H 5.19; N 5.94.
C31H24N2O2. Calculated, %: C 81.58; H 5.26; N 6.14.
Ethyl 3-(p-bromophenyl)-1-hydroxy-1-(2-
quinolyl)-1,2,3,4-tetrahydrobenzo[f]quinoline-2-
carboxylate (XIVb). Yield 29%, mp 218–219°C. UV
spectrum, λmax, nm (logε): 208 (4.76), 236 (4.80), 249
Ethyl 3-(p-bromophenyl)-1-(2-quinolyl)-3,4-
dihydrobenzo[f]quinoline-2-carboxylate (XVb). Yield
52%, mp 207–208°C. UV spectrum, λmax, nm (logε):
207 (4.63), 238 (4.58), 270 (4.43), 316 (3.90), 384
(3.60). 1H NMR spectrum, δ, ppm: 1.10 t, 4.03 q (5H,
OEt, 2J 14.2, 3J 6.1 Hz), 4.43 br.s (1H, NH), 6.00 s (1H,
H3), 6.96–8.12 m (16Harom). Found, %: C 69.21; H 4.11;
Br 14.59; N 5.08. C31H23BrN2O2. Calculated, %: C 69.53;
H 4.30; Br 14.95; N 5.23.
1
(4.63), 288 (4.24), 316 (3.84), 342 (4.63). H NMR
2
spectrum, δ, ppm: 1.07 t, 4.12 q (5H, OEt, J 14.0,
3
3J 6.0 Hz), 4.70 d (1H, H3, J 9.5 Hz), 5.22 br.s (1H,
NH), 5.68 d (1H, H2, 3J 9.5 Hz), 6.98–8.20 m (16Harom),
8.44 C (1H, OH). Found, %: C 67.01; H 4.43; Br 14.24;
N 4.91. C31H25BrN2O3. Calculated, %: C 67.27; H 4.52;
Br 14.47; N 5.06.
Ethyl 3-(p-fluorophenyl)-1-(2-quinolyl)-3,4-
dihydrobenzo[f]quinoline-2-carboxylate (XVc). Yield
34%, mp 131–132°C. UV spectrum, λmax, nm (logε): 208
(4.62), 235 (4.56), 266 (4.40), 315 (3.88), 373 (3.15).
1H NMR spectrum, δ, ppm: 1.07 t, 4.01 q (5H, OEt,
Ethyl 1-hydroxy-3-(p-fluorophenyl)-1-(2-quinol-
yl)-1,2,3,4-tetrahydrobenzo[f]quinoline-2-carboxy-
late (XIVc). Yield 38%, mp 140–141°C. UV spectrum,
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β-OXOACIDS ESTERS IN THE SYNTHESIS OF BENZO[f]QUINOLINE DERIVATIVES
717
3
2J 14.0, J 6.02 Hz), 4.90 br.s (1H, NH), 5.95 C (1H,
H3), 6.82–8.05 m (16Harom). Found, %: N 5.73.
C31H23FN2O2. Calculated, %: N 5.91.
Found, %: C 73.01; H 5.08; N 3.63. C22H19NO4.
Calculated, %: C 73.13; H 5.26; N 3.88.
Ethyl 3-(2-naphthylamino)-2-nicotinoyl-3-
phenylpropanoate (XVIII). A mixture of 10 mmol of
azomethine Ia, 12.5 mmol of ester V, and 30 ml of ethanol
was heated on a water bath at 40–60°C for 30 min. The
precipitate separated on cooling was filtered off and
recrystallized from 2-propanol. Yield 97%, mp 101–
102°C. UV spectrum, λmax, nm (logε): 232 (4.62), 248
(4.70), 271 (4.46), 318 (4.20). 1H NMR spectrum, δ, ppm:
1.12 t, 4.00 q (5H, OEt, 2J 14.0, 3J 6.0 Hz), 4.70 d (1H,
H3, 3J 9.3 Hz), 5.42 d (1H, H2, 3J 9.3 Hz), 5.60 br.s (1H,
NH), 6.73–8.58 m (16Harom). Found, %: C 76.41; H 5.66;
N 6.60. C27H24N2O3. Calculated, %: C 76.19; H 5.52;
N 6.36.
Ethyl 3-phenyl-1-(2-quinolyl)benzo-[f]quinoline-2-
carboxylate (XVIa). An equimolar mixture (5 mmol
each) of azomethine Ia and ester IV in 5 ml of DMF and
1 ml of concn. HCl was heated in a sealed ampule for
3 h at 100°C. The tarry mass obtained was kept in air for
48 h, treated with aqueous NH4OH, ground with
2-propanol, and recrystallized from ethanol. Yield 26%,
mp 187–188°C. UV spectrum, λmax, nm (logε): 209
(4.70), 217 (4.69), 234 (4.69), 279 (4.78), 318 (4.10),
347 (3.66), 361 (3.61). 1H NMR spectrum, δ, ppm: 1.12 t,
2
3
4.05 q (5H, OEt, J 14.0, J 6.1 Hz), 6.77–8.11 m
(17Harom). Found, %: C 81.75; H 4.58; N 6.02.
C31H22N2O2. Calculated, %: C 81.94; H 4.85; N 6.17.
Ethyl 3-phenyl-1-(3-pyridyl)benzo[f]quinoline-2-
carboxylate (XX). A mixture of 5 mmol of aminoester
XVIII, 30 ml of ethanol, 0.5 ml of concn. HCl, and
0.5 ml of nitrobenzene was heated in a sealed ampule
for 12 h at 100°C. The reaction mixture was evaporated
to 1/4 of volume, the tarry residue was treated with
alcoholic NH4OH, with water, dried, and ground with 2-
propanol. The precipitate of reaction product was filtered
off and recrystallized from ethanol. Yield 30%, mp 151–
152°C. UV spectrum, λmax, nm (logε): 234 (4.42), 250
Ethyl 3-aryl-2-(quinoline-2-carbonyl)acrylates
XVIIb, XVIId, and XVIIe were obtained by procedures
described for compounds XIVb–XIVd and XVa–XVc
by evaporating the mother liquors after isolating
precipitates of benzo[f]quinolines XIVb, XIVd, and
XVb for esters XVIIb and XVIId and by evaporating
the reaction mixture by 1/3 of volume for compound
XVIIe. The tarry residues of esters XVIIb and XVIId
and the precipitate of the methoxy derivative XVIIe were
treated with aqueous NH4OH, 2-propanol, and
recrystallized from ethanol (compounds XVIIb and
XVIIe) or nitromethane (nitroester XVIId).
1
(4.40), 282 (4.67), 353(3.77), 374 (3.72). H NMR
spectrum, δ, ppm: 1.19 t, 4.10 q (5H, OEt, 2J 14.1, 3J 6.1
Hz), 6.79–8.60 m (15Harom). Found, %: C 80.43; H 5.11;
N 6.31. C27H20N2O2.Calculated, %: C 80.57; H 5.26; N 6.48.
Ethyl
3-(p-bromophenyl)-2-(quinoline-2-
carbonyl)-acrylate (XVIIb). Yield 11%, mp 149–
150°C. UV spectrum, λmax, nm (logε): 210 (4.43), 253
(4.51), 273 (4.46), 270 (4.39), 329 (4.20). 1H NMR spec-
trum, δ, ppm: 1.15 t, 4.08 q (5H, OEt, 2J 14.1, 3J 6.0 Hz),
6.83–8.22 m (12H, 10Harom, CH=CH). Found, %: C 61.29;
H 3.63; Br 19.11; N 3.26. C21H16BrNO3. Calculated, %:
C 61.46; H 3.90; Br 19.51; N 3.41.
3-Oxo-3-(3-pyridyl)propanoic acid N-(2-
naphthyl)amide (XXI). In 20 ml of toluene containing
5 drops of piperidine was boiled for 3 h 5 mmol of
amineketoester XVIII or a mixture of 10 mmol of
azomethine Ia and 12.5 mmol of ester V. The precipitate
separated on cooling was filtered off and recrystallized
from 2-propanol. Yield 18% from ester XVIII and 36%
from reagents mixture Ia and V, mp 170–171°C. UV
spectrum, λmax, nm (logε): 216(4.76), 245 (4.82), 278
Ethyl 3-(p-nitrophenyl)-2-(quinoline-2-carbonyl)-
acrylate (XVIId). Yield 14%, mp 179–180°C. UV
spectrum, λmax, nm (logε): 213 (4.41), 255 (4.49), 272
1
(4.46), 330 (4.50). H NMR spectrum, δ, ppm: 5.22 s
1
(4.23), 326 (4.16). H NMR spectrum, δ, ppm: 1.19 t,
(2H, CH2), 6.38 br.s. (1H, NH), 7.41–8.51 m (11Harom).
Found, %: C 74.25; H 4.81; N 9.53. C18H14N2O2.
Calculated, %: C 74.46; H 4.87; N 9.65.
4.10 q (5H, OEt, 2J 14.2, 3J 6.1 Hz), 7.22–8.44 m (12H,
10Harom, CH=CH). Found, %: C 66.84; H 4.20; N 7.33.
C21H16N2O5. Calculated, %: C 67.02; H 4.26; N 7.45.
REFERENCES
Ethyl 3-(p-methoxyphenyl)-2-(quinoline-2-
carbonyl)acrylate (XVIIe). Yield 54%, mp 101–102°C.
UV spectrum, λmax, nm (logε): 211 (4.40), 254 (4.50),
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1
238 (4.65), 274 (4.43), 336 (4.21). H NMR spectrum,
2
3
δ, ppm: 1.16 t, 4.04 q (5H, OEt, J 14.1, J 6.0 Hz),
3.70 s (3H, OMe), 6.60–7.98 m (12H, 10Harom, CH=CH).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 5 2007

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