Condensation of 2-naphthylamine or N-benzyl-2-naphthylamines with formaldehyde and methyl 2,2-dimethyl-4,6-dioxocyclohexane-3-carboxylate

Article abstract of DOI:10.1134/S1070428012110085

Condensation of 2-naphthylamine with formaldehyde and methyl 2,2-dimethyl-4,6-dioxocyclohexanecarboxylate afforded depending on the reaction conditions methyl 9,9-dimethyl-11-oxo-8,9,10,12-tetrahydro-7H-benzo[a]acridine- 10-carboxylate or 4-alkoxymethyl-1

Full text of DOI:10.1134/S1070428012110085

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 11, pp. 1456−1463. © Pleiades Publishing, Ltd., 2012.
Original English Text © N.G. Kozlov, A.P. Kadutskii, A.V. Baranovskii, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 11, pp. 1472−1479.
Condensation of 2-Naphthylamine
or N-Benzyl-2-Naphthylamines with Formaldehyde
and Methyl 2,2-Dimethyl-4,6-dioxocyclohexane-3-carboxylate
N. G. Kozlova, A. P. Kadutskiia, and A. V. Baranovskiib
aInstitute of Physical Organic Chemistry of the National Academy of Sciences of Belarus’, Minsk, 220072 Belarus’
e-mail: loc@ifoch.bas-net.by
bInstitute of Bioorganic Chemistry of the National Academy of Sciences of Belarus’, Minsk, Belarus
Received December 12, 2011
Abstract—Condensation of 2-naphthylamine with formaldehyde and methyl 2,2-dimethyl-4,6-dioxocyclohexane-
carboxylate afforded depending on the reaction conditions methyl 9,9-dimethyl-11-oxo-8,9,10,12-tetrahydro-
7H-benzo[a]acridine-10-carboxylate or 4-alkoxymethyl-1,4-dihydro-2',6'-dioxo-4',4'-dimethyl-2'H,3H,6'H-
spirobenzo[f]quinoline-2,1'-cyclohexyl-3'-carboxylate. The condensation of N-benzyl-2-naphthylamines with
formaldehyde and methyl 2,2-dimethyl-4,6-dioxocyclohexanecarboxylate provided with the quantitative yield
the corresponding methyl 4-benzyl-1,4-dihydro-2',6'-dioxo-4',4'-dimethyl-2'H,3H,6'H-spirobenzo[f]quinoline-
2,1'-cyclohexyl-3'- carboxylates.
DOI: 10.1134/S1070428012110085
Cyclic β-diketones owing to their high reactivity are
widely used in the synthesis of fused nitrogen hetero-
cycles [1–4]. In the present study aiming at the preparation
of new biologically active derivatives of 8,9,10,12-tetra-
hydro-7H-benzo[a]acridin-11-one and of spiroderivatives
of tetrahydrobenzo[f]quinoline we explored the reaction
of 2-naphthylamine (I) with formaldehyde and methyl
2,2-dimethyl-4,6-dioxocyclohexane-3-carboxylate (II).
carboxylate (II) in an aliphatic alcohol at the room tem-
perature in the absence of a catalyst afforded in high yields
(84–98%) N-alkoxymethylated spirocyclic derivatives of
benzo[f]quinoline, methyl 4-alkoxymethyl-1,4-dihydro-
2',6'-dioxo-4',4'-dimethyl-2'H,3H,6'H-spirobenzo[f]
quinoline-2,1'-cyclohexyl-3'-carboxylates IVa–IVc in
high yields (84–98%) (Scheme 1).
The mechanism of the formation of compounds III,
IVa–IVc may be represented as follows: In the first step
formaldehyde reacts with 2-naphthylamine (I) giving a
Schiff base V (Scheme 2). Then methyl 2,2-dimethyl-
4,6-dioxocyclohexane-3-carboxylate (II) adds to the
polarized double bond C=N of compound V to form
β-aminoketone A. Aminoketone A suffers a reversible
elimination of amine I generating an α,β-unsaturated
ketone B where the double bond is activated due to the
conjugation with two carbonyl groups. Compound B
may also form directly from formaldehyde and methyl
2,2-dimethyl-4,6-dioxocyclohexanecarboxylate along
the Knoevenagel reaction. Further the α,β-unsaturated
ketone B reacts irreversibly with the aromatic frame-
work of 2-naphthylamine (I) giving aminoketone C. At
The reaction resulted in partially hydrogenated ben-
zoquinoline derivatives containing an ester fragment.
Depending on the synthesis conditions and the ratio of
the initial reagents, it was possible to prepare selectively
two types of compounds distinguished by the character
of the fusion and the mechanism of the benzoquinoline
skeleton formation.
The reaction of equimolar amounts of the starting
materials in a boiling aliphatic alcohol furnished ethyl
9,9-dimethyl-11-oxo-8,9,10,12-tetrahydro-7H-benzo[a]
acridine-10-carboxylate (III) in 75% yield. The reaction
of 2-naphthylamine (I) with a large excess of formalde-
hyde and methyl 2,2-dimethyl-4,6-dioxocyclohexane-3-
1456

CONDENSATION OF 2-NAPHTHYLAMINE
1457
Scheme 1.
O
O
10
O
8
12
Δ
NH
III
O
O
20oC
AlkOH
O
+ CH2O +
O
N
O
O
N
O
O
OR
IVа_IVc
R
I, VIа_VId
II
6'
O
4'
1
Δ
O
3'
N
R
3 O
O
VIIа_VIId
R = H (I), CH3 (IVa), C2H5 (IVb), C3H7 (IV c), C6H4--4''-OCH3 (VIa, VIIa), C6H4-3'',4''-(OCH2O) (VIb, VIIb), C6H4--
3'',4''-(OCH3)2 (VIc,VIIc), C6H4-4''-CH(CH3)2 (VId, VIId).
Scheme 2.
O
CH2O
II
O
II
_I
O
O
N
NH
O
O
O
O
V
B
I
A
O
O
O
O
CH2O
CH2O, ROH
IVа_IVc
O
III
_H2O
O
NH2
N
H
O
O
C
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 11 2012

KOZLOV et al.
1458
high temperature the free amino group of aminoketone
C attacks intramolecularly the ketone carbonyl group
resulting in the fast cyclization to methyl 9,9-dimethyl-11-
oxo-8,9,10,12-tetrahydro-7H-benzo[a]acridine-10-car-
boxylate (III). The reaction proceeded regioselectively.
The formation of 10-methoxycarbonyl-substituted isomer
III occurs as a result of the cyclization of aminodiketone
intermediate C at the more sterically accessible (non-
shielded by the ester substituent) carbonyl group.
The chemical shift value of the proton attached to the atom
C10 (3.15 ppm) is characteristic and shows that the proton
is in the α-position with respect to a carbonyl group. The
proton of the NH group appears as a broadened singlet
at 9.15 ppm.
In the 1H NMR spectra of spiro derivatives IVa–IVc
the characteristic signals of the corresponding aliphatic
residues of the substituent are observed, and the set of
the signals with the overall integral intensity of 6H cor-
responding to the aromatic protons appears in the region
7.4−8.0 ppm. Two diastereotopic methyl groups of the
dimedone fragment give rise to two singlets with the
integral intensity of 3H each in the region 0.9–1.3 ppm.
The protons at the atom C5’ appear as two doublets at
2.35 ppm (C5’H-trans) and 3.75 ppm (C5’H-cis) with the
coupling constant of 14 Hz in conformity with the gemi-
nal interaction of the protons. The proton of the atom C3’
gives rise to a singlet at 4.75 ppm. The protons attached
to the atom C1 appear as a pair of doublets at 3.27 and
3.19 ppm with the coupling constant of 16 Hz, and the
protons at the atom C3, at 3.50 and 3.95 ppm with the
coupling constant of 12 Hz. The enantiotopic protons of
the NCH2O fragment suffer a deshielding effect of the
neighboring nitrogen and oxygen and therefore appear as
two doublets in a lower field, at ~4.80 ppm.
At the room temperature this reaction proceeds slower,
and in the presence of excess formaldehyde the free amino
group of aminoketone C reacts prevailingly with the
sterically more accessible aldehyde carbonyl to form a
complex Schiff base that may also form in the reaction of
α,β-unsaturated ketone B with the aromatic framework
of Schiff base V. This intermediate compound under-
goes further a cyclization into a spirocyclic system IV
owing to the intramolecular attack of the nucleophilic
carbon of the dicarbonyl fragment on the carbon atom
of the polarized C=N bond. Compounds IVa–IVc form
as a result of the Mannich type reaction between the
spirocyclic amine and formaldehyde and the alcohol
used as the solvent.
The structure of the compounds synthesized was
confirmed by IR and NMR spectra. The IR spectrum of
methyl 9,9-dimethyl-11-oxo-8,9,10,12-tetrahydro-7H-
benzo[a]acridine-10-carboxylate (III) contains a strong
absorption band of the carbonyl group at 1730 cm–1 and
two strong absorption bands at 1570 and 1520 cm –1
corresponding to the stretching vibrations of the double
bond directly conjugated with the nitrogen atom. The
absorption band at 1270 cm –1 belongs to the stretching
vibrations of the C–O–C bond in esters. The spectrum
also contains the characteristic absorption band of the
stretching vibrations of the NH group at 3440 cm–1. In the
IR spectra of alkoxymethylated spiroderivatives IVa–IVc
the three nonequivalent carbonyl groups appear as strong
bands at 1750, 1730, and 1700 cm –1.
Thus, the three-component condensation of 2-naph-
thylamine with formaldehyde and methyl 2,2-dimethyl-
4,6-dioxocyclohexanecarboxylate occurs as a series of
sequential transformations of the initial compounds, and
the main part of the conversions proceeds as the Man-
nich reaction type. Commonly the secondary amines are
regarded as more suitable components in the Mannich
reaction since the dialkylation is the main process with
primary amines due to the greater nucleophility of the
monoalkylation product as compared with the starting
primary amine [5]. Nevertheless the 2-naphthylamine
in our case did not form any dialkylation products most
likely due to the steric hindrance to its formation.
In this connection we decided to bring into the con-
densation with formaldehyde and methyl 2,2-dimethyl-
4,6-dioxocyclohexanecarboxylate secondary amines,
N-benzyl-2-naphthylamines VIa–VId aiming at obtain-
ing further methyl 4-benzyl-1,4-dihydro-2',6'-dioxo-
4',4'-dimethyl-2'H,3H,6'H-spirobenzo[f]quinoline-2,1'-
cyclohexyl-3'-carboxylates.
1
The H NMR spectrum of methyl 9,9-dimethyl-11-
oxo-8,9,10,12-tetrahydro-7H-benzo[a]acridine-10-car-
boxylate (III) contains a group of signals with an overall
integral of 6H in the region 7.20−7.80 ppm belonging to
the aromatic protons. The protons of the atom C12 are
enantiotopic and give a single singlet signal with the
integral intensity of 2H at 3.85 ppm. The protons at the
atom C8 appear as two doublets at 2.29 (C8H-trans) and
2.66 ppm (C8H-cis) with the coupling constant of 14 Hz
in conformity with the geminal interaction of the protons.
In order to prepare the initial secondary amines we
investigated the reduction of (E)-N-arylidene-2-naphthyl-
amines synthesized along the standard procedure by short
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 11 2012

CONDENSATION OF 2-NAPHTHYLAMINE
1459
heating 2-naphthylamine (I) with substituted benzalde-
hydes in ethanol solution.At boiling the azomethines with
sodium triacetoxyborohydride Na[BH(OAc)3] in benzene
for 0.5–1 h the substituted N-benzyl-2-naphthylamines
VIa–VId were obtained in quantitative yields. These
products were brought into the three-component con-
densation with formaldehyde and methyl 2,2-dimethyl-
4,6-dioxocyclohexane-3-carboxylate (II) which resulted
in the quantitative preparation of the corresponding
methyl 4-benzyl-1,4-dihydro-2',6'-dioxo-4',4'-dimethyl-
2'H,3H,6'H-spirobenzo[f]qinoline-2,1'-cyclohexyl-3'-
carboxylates VIIa–VIId.
compound VIIa exists in the conformation close to the
conformation shown in Fig. 1. This conclusion is based
on the following observations: The proton attached C3'
has intensive cross-peaks with both protons at C3 and
with one of the proton at C5' (2.77 ppm, axial), a cross
peak of low intensity with the proton linked to C2'' of
the methoxybenzyl substituent; it interacts with both
groups attached to C4', therewith the cross-peak with the
protons of the equatorial methyl group (1.20 ppm) is far
more intensive. Most likely only at the axial position of
H3' directed to the side of the protons at C3 this signals
pattern is possible. Alongside the NOESY spectrum
an additional proof follows from the COSY spectrum
where the W-interaction was observed with the axial
methyl group at 1.13 ppm and the equatorial proton H5'
at 2.51 ppm.
The formation of spirocyclic derivatives VIIa–VIId
proceeds obviously because of the intramolecular Man-
nich condensation of intermediate C analogously to the
above described. The thermodynamic and steric feasibil-
ity of this cyclocondensation is governed by the resulting
formation of six-membered tetrahydropyridine ring.
The 1H NMR spectra of esters VIIa–VIId contain a
double set of proton signals corresponding to the presence
in the reaction products of two stereoisomers, (2R,3'R)
and (2S,3'R), in the ratio 3 : 1.
The analysis of the NOESY spectrum with respect
to H5' protons also confirms the assumed structure. The
equatorial proton H5' (2.51 ppm) interacts with both
methyl groups and the axial proton (2.77 ppm) has
cross-peak only with the equatorial methyl group. It has
besides cross-peaks of low intensity with both H3 that
also confirms its axial position as well as the presence
of the W-constant with the protons of the axial methyl
group in the COSY spectrum. Yet it should be noted that
the detection of the coupling of the proton at C3' with the
axial methyl group in the NOESY spectrum and with the
equatorial proton C5' in the COSY spectrum indicates
a certain conformational flexibility of the cycle which
In order to establish the relative stereochemistry of
substituents in isomers of esters VIIa–VIId compound
VIIa was subjected to the study using 2D NMR spec-
troscopy. As a result of the analysis of the 2D spectra
COSY, HSQC, HMBC, and NOESY the structure of the
compound VIIa was proved, the reciprocal position of the
substituents was established, and complete assignment of
the signals in the 13C NMR spectra was obtained.
The assignment of the quaternary carbon atoms was
based on the analysis of the HMBC spectrum, which
contained the following cross-peaks: C2 with H1, H3, H5';
C4a with H6, H5, H1 and CH2 of the benzyl group; C6a
with H10, H5, H6; C10a with H10, H6, H7, H9; C10b with
H5, H10; C2' with H3'; C4' with H3', H5', and the protons
of the methyl groups; C6' with H5'.
H
H
O
H
H
H
H
H H
H
O
H
H
H
O
O
H
H
H
H
The assignment in the methoxybenzyl substituent was
based on the interaction of C4'' with the protons of the
methoxy group H3'' and H2'', whereas C1'' gave a cross-
peak only with H3'.
H
H
H
O
H
H
H
N
H
H
H
H
H
H
H
The analysis of the NOESYspectrum made it possible
both to confirm the attribution of the proton signals
from the dihydrobenzoquinoline ring and to establish
the relative stereochemistry of the cyclohexanedione
spiroring and its substituents. Proceeding from the
spectral data we were able to conclude that in solution
H
H
Fig. 1. Main couplings in the NOESY spectrum of the major
isomer (2R,3'R) of compound VIIa.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 11 2012

KOZLOV et al.
1460
evidently allows the proton at C3' to be present in the
equatorial position.
spectrum are in conformity with the above conclusions:
The cross-peak of the axial proton H5' with the protons
of the axial methyl group is observed and W-constant
between the protons linked to C1 and C3 located on the
same side of the plane; the protons with the signals at
3.42 and 3.77 ppm are located below the plane and the
protons at 3.54 and 3.75 ppm are over the plane of the
dihydrobenzoquinoline framework.
We failed to establish the reciprocal position of the
protons at C1 and C3 with respect to the plane of the
dihydrobenzoquinoline ring due to the overlapping of
their signals in the NOESY spectrum, and the coupling
with the proton at C10 was observed for both protons at-
tached to C1.Analogous pattern is present for the protons
at C3 where both protons have cross-peaks only with the
protons of the methoxybenzyl substituent.
EXPERIMENTAL
We succeeded to analyze the minor component formed
in the reaction. According to the spectral data the con-
figuration should be as shown in Fig. 2. In contrast to the
major isomer the proton H3' in the NOESY spectrum has
cross-peaks of equal intensity with both methyl groups,
in the COSY spectrum the W-constant with one of the
protons H5' at 2.63 ppm is observed, and the coupling
with the protons of the methyl groups is absent indicating
the equatorial position of the proton at C3'. The analysis
of protons at C5' confirms in general the configuration
in the spirocycle of the minor component. For instance,
the equatorial proton H5' (2.63 ppm) interacts with the
methyl groups and with the protons at C1 (3.53 ppm)
and C3 (3.75 ppm), i.e., is situated over the dihydroben-
zoquinoline cycle plane. The axial proton (3.18 ppm) has
cross-peaks only with the equatorial methyl group, with
one of protons at C3 (3.75 ppm), and with the protons of
the methoxybenzyl substituent. The data of the COSY
IR spectra were obtained on a Fourier spectrophotom-
eter Nikolet Protege-460 from pellets with KBr. 1H NMR
spectra were registered on spectrometers Bruker Avance
(500 MHz) or DRX-500 [500.13 (1H), 125.75 MHz (13C)]
in CDCl3 solutions, internal reference TMS. Mass spectra
were measured on a GC-MS spectrometer Hewlett Pack-
ard 5890/5972 in electron impact mode, ionizing electrons
energy 70 eV. Column HP-5MS (30 m × 0.25 mm). The
thickness of the stationary phase (5% PLMe Silicone) was
0.25 μm, vaporizer temperature 250°C. Melting points
were measured on a Koeffler heating block.
Methyl 2,2-dimethyl-4,6-dioxocyclohexane-3-
carboxylate (II) was obtained as described in [6] by the
reaction of mesityl oxide with dimethyl malonate.
Methyl 9,9-dimethyl-11-oxo-8,9,10,12-tetrahydro-
7H-benzo[a]acridine-10-carboxylate (III). To a mixture
of 0.3 g (0.01 mol) of paraformaldehyde and 1.43 g
(0.01 mol) of 2-naphthylamine in 20 ml of ethanol ~20 mg
of NaOH was added , and the mixture was heated on the
water bath till paraformaldehyde completely dissolved
(3–7 min). To the transparent solution obtained 1.12 g
(0.01 mol) of ester II in 10 ml of ethanol was added at
stirring. The mixture was quickly heated till a precipi-
tate started to separate, then cooled, the precipitate was
filtered off, washed with ethanol, and dried. The product
was recrystallized from DMF. Yield 2.5 g (75%), mp
196°C. IR spectrum, ν, cm–1: 3440 (N–H), 3065 (C–Ha-
rom), 2960 (C–H), 1730 (C=O), 1570, 1520, 1400, 1270
H
H
H
H
H
H
H
H
H
O
H
O
H
O
H
H
H
H
O
H
H
H
H
N
H
H
H
H
1
H
(C–O–C), 1050, 830, 750. H NMR spectrum, δ, ppm:
H
1.15 s [6H, C9(CH3)2], 2.29 d (1H, H8-trans, J 14 Hz),
2.66 d (1H, H8-cis, J 14 Hz), 3.15 s (1H, H10), 3.69 s
(3H, C10COOCH3), 3.85 s (2H, H12), 7.10 d (1H, H5,
J 9 Hz), 7.34 t (1H, H2, J 9 Hz), 7.47 t (1H, H3, J 9 Hz),
7.62 d (1H, H6, J 9 Hz), 7.73 d (1H, H4, J 9 Hz), 7.78 d
(1H, H7, J 9 Hz), 9.15 s (1H, NH). Found, %: C 75.25;
H 6.24; N 4.30. C21H21NO3. Calculated, %: C 75.20;
H 6.31; N 4.18.
H
H
H
H
H
O
H
Fig. 2. Main couplings in the NOESY spectrum of the minor
isomer (2S,3'R) of compound VIIa.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 11 2012

CONDENSATION OF 2-NAPHTHYLAMINE
1461
J 12 Hz), 4.85 d (1H, NCH2O, J 12 Hz), 7.25 d (1H, H6,
J 9 Hz), 7.30 t (1H, H9, J 9 Hz), 7.45 t (1H, H8, J 9 Hz),
7.65 d (1H, H5, J 9 Hz), 7.75 d (1H, H7, J 9 Hz), 7.85 d
(1H, H10, J 9 Hz). Found, %: C 70.67; H 6.71; N 3.40.
C25H29NO5. Calculated, %: C 70.90; H 6.90; N 3.31.
Methyl 4-alkoxymethyl-1,4-dihydro-2',6'-dioxo-
4',4'-dimethyl-2'H,3H,6'H-spirobenzo[f]quinoline-
2,1'-cyclohexyl-3'-carboxylates IVa–IVc. A mixture
of 1.43 g (0.01 mol) of 2-naphthylamine and 2.10 g
(0.07 mol) of paraformaldehyde in 15 ml of an appropri-
ate alcohol was stirred at room temperature for 40 min.
To the obtained mixture a solution of 1.98 g (0.01 mol)
of ester II in the same alcohol was slowly (in 30 min)
added. The mixture was stirred for 1 h more and was left
overnight. The separated precipitate was filtered off. The
mother liquor was kept in the open flask till the most part
of the solvent evaporated. The second crop of the reac-
tion product was filtered off. The sample for analysis was
recrystallized from the corresponding alcohol.
Methyl 4-isopropoxymethyl-1,4-dihydro-2',6'-
dioxo-4',4'-dimethyl-2'H,3H,6'H-spirobenzo[f]-
quinoline-2,1'-cyclohexyl-3'-carboxylate (IVc). Yield
84%, mp 163°C. IR spectrum, ν, cm–1: 3414 (N–H),
3060 (C–Harom), 2968, 2926, 2878 (C–H), 1753, 1727
(C=O), 1698 (COOCH3), 1622, 1601, 1514, 1432, 1271
1
(C–O–C), 1169, 1128, 1050, 1008, 958, 738. H NMR
spectrum, δ, ppm: 0.90 C (3H, C4'CH3), 1.10 d [6H,
OCH(CH3)2, J 6 Hz], 1.20 C (3H, C4'CH3), 2.35 d (1H,
H5’-trans, J 14 Hz), 3.20 d (1H, H1, J 16 Hz), 3.30 d
(1H, H1, J 16 Hz), 3.50 d (1H, H3, J 12 Hz), 3.65 C (3H,
C3’COOCH3), 3.70 q [1H, OCH(CH3)2, J 6 Hz], 3.75 d
(1H, H5’-cis, J 14 Hz), 3.95 d (1H, H3, J 12 Hz), 4.75 C
(1H, H3’), 4.80 d (1H, NCH2O, J 12 Hz), 4.85 d (1H,
NCH2O, J 12 Hz), 7.20 d (1H, H6, J 9 Hz), 7.30 t (1H, H9,
J 9 Hz), 7.45 t (1H, H8, J 9 Hz), 7.60 d (1H, H5, J 9 Hz),
7.75 d (1H, H7, J 9 Hz), 7.85 d (1H, H10, J 9 Hz). Found,
%: C 70.51; H 7.33; N 3.35. C26H31NO5. Calculated, %:
C 71.37; H 7.14; N 3.20.
Methyl 4-methoxymethyl-1,4-dihydro-2',6'-dioxo-
4',4'-dimethyl-2'H,3H,6'H-spirobenzo[f]quinoline-
2,1'-cyclohexyl-3'-carboxylate (IVa). Yield 93%,
mp 160°C. IR spectrum, ν, cm –1: 3411 (N–H), 3050
(C–Harom), 2970, 2925, 2875 (C–H), 1751, 1729 (C=O),
1708 (COOCH3), 1612, 1600, 1512, 1435, 1270 (C–O–
C), 1164, 1123, 1054, 1015, 968, 730. 1H NMR spectrum,
δ, ppm: 1.00 s (3H, C4'CH3), 1.25 s (3H, C4'CH3), 2.45 d
(1H, H5’-trans, J 14 Hz), 3.19 d (1H, H1, J 16 Hz), 3.25 d
(1H, H1, J 16 Hz), 3.30 s (3H, OCH3), 3.55 d (1H, H3,
J 12 Hz), 3.60 s (3H, C3’COOCH3), 3.65 d (1H, H5’-cis,
J 14 Hz), 3.70 d (1H, H3, J 12 Hz), 4.55 s (1H, H3’), 4.75 d
(1H, NCH2O, J 12 Hz), 4.85 d (1H, NCH2O, J 12 Hz),
7.25 d (1H, H6, J 9 Hz), 7.30 t (1H, H9, J 9 Hz), 7.45 t
(1H, H8, J 9 Hz), 7.65 d (1H, H5, J 9 Hz), 7.75 d (1H, H7,
J 9 Hz), 7.85 d (1H, H10, J 9 Hz).
N-Benzyl-2-naphthylamines VI were earlier ob-
tained in our laboratory as side products in the synthesis
of benzoquinoline bases [7]. The preparative synthesis
of secondary amines VI was carried out by the reduction
of appropriate Schiff bases with sodium borohydride. A
solution of 5 mmol of azomethine, 10 mmol of NaBH4, 30
mmol of glacial acetic acid in 50 ml of anhydrous benzene
was refluxed for 0.5–1 h. The hot solution was filtered
through a folded paper filter, cooled,and left standing
for 10–15 h at 23–25°C. The separated precipitate was
washed with a little benzene and dried in air. Compounds
VI were purified by recrystallization from benzene. Fur-
ther the compound number, yield % are reported, mp °C:
VIa, 53, 124–126; VIb, 42, 136–138; VIc, 49, 118–120;
VId, 57, 141–143.
Mass spectrum, m/z (Irel, %): 409 (37), 378 (31), 349
(10), 321 (11), 265 (19), 194 (25), 180 (38), 168 (35),
152 (20), 141 (25), 115 (15), 83 (70), 45 (100). Found,
%: C 70.52; H 6.43; N 3.60. C24H27NO5. Calculated, %:
C 70.40; H 6.65; N 3.42.
Methyl 4-ethoxymethyl-1,4-dihydro-2',6'-dioxo-
4',4'-dimethyl-2'H,3H,6'H-spirobenzo[f]quinoline-
2,1'-cyclohexyl-3'-carboxylate (IVb). Yield 98%, mp
138°C. IR spectrum, ν, cm –1: 3420 (N–H), 3063 (C–Ha-
rom), 2975, 2930, 2870 (C–H), 1755, 1720 (C=O), 1691
(COOCH3), 1629, 1608, 1512, 1436, 1270 (C–O–C),
Methyl 4-benzyl-1,4-dihydro-2',6'-dioxo-4',4'-
dimethyl-2'H,3H,6'H-spirobenzo[f]quinoline-2,1'-
cyclohexyl-3'-carboxylates VIIa–VIId. A mixture of
1 mmol of an appropriate amine VIa–VId and 0.12 g
(4 mmol) of paraformaldehyde in 25 ml of ethanol was
boiled till both components completely dissolved (5 min).
To the obtained solution 0.2 g (1 mmol) of ester II was
added, the mixture was refluxed for extra 5 min, cooled,
the separated precipitate was filtered off and washed with
1
1159, 1130, 1020, 1010, 957, 741. H NMR spectrum,
δ, ppm: 1.15 s (3H, C4'CH3), 1.25 s (3H, C4'CH3), 1.30 t
(3H, OCH2CH3, J 7 Hz), 2.45 d (1H, H5’-trans, J 14 Hz),
3.20 d (1H, H1, J 16 Hz), 3.25 d (1H, H1, J 16 Hz), 3.50 q
(2H, OCH2CH3, J 7 Hz), 3.55 d (1H, H3, J 12 Hz), 3.60 s
(3H, C3’COOCH3), 3.65 d (1H, H5’-cis, J 14 Hz), 3.70 d
(1H, H3, J 12 Hz), 4.55 s (1H, H3’), 4.80 d (1H, NCH2O,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 11 2012

KOZLOV et al.
1462
2',6'-dioxo-4',4'-dimethyl-2'H,3H,6'H-spirobenzo[f]-
quinoline-2,1'-cyclohexyl-3'-carboxylate (VIIb).
Yield 0.41 g (82%), mp 187°C. IR spectrum, ν, cm–1:
3440 (N–H), 3013 (C–Harom), 2950, 2935, 2875, 2835
(C–H), 1750, 1730 (C=O), 11705 (COOCH3), 1625,
1590, 1514, 1132, 1348,1221 (C–O–C), 1149, 1026,
ethanol (2 × 5 ml). The mother liquors were kept in air till
the most part of the solvent evaporated, and the second
crop of the reaction product was filtered off.
Methyl 4-(4-methoxybenzyl)-1,4-dihydro-2',6'-
dioxo-4',4'-dimethyl-2'H,3H,6'H-spirobenzo[f]quino-
line-2,1'-cyclohexyl-3'-carboxylate (VIIa). Yield 0.4 g
(83%), mp 168°C. IR spectrum, ν, cm–1: 3420 (N–H),
3060, 3000 (C–Harom), 2957, 2935, 2825 (C–H), 1747,
1726 (C=O), 1698 (COOCH3), 1619, 1597, 1510, 1434,
1
812, 740. H NMR spectrum, δ, ppm, main isomer:
0.95 s (3H, C4'CH3 ), 1.15 s (3H, C4'CH3 ), 2.45 d (1H,
H5’e, J 15 Hz), 2.60 d (1H, H5’a, J 15 Hz), 3.25 d (1H,
H3, J 12 Hz), 3.42 d (1H, H1, J 16 Hz), 3.55 d (1H,
H1, J 16 Hz), 3.65 d (1H, H3, J 12 Hz), 3.70 s (3H,
C3’COOCH3), 4.05 s (1H, H3’), 4.50 s (2H, NCH2O),
6.05 s (2H, OCH2O), 6.75 d (1Harom, H5, J 9 Hz), 6.80 s
(1Harom), 6.85 d (1Harom, J 9 Hz), 6.90 d (1Harom, J 9 Hz),
7.25 m (1H, H8), 7.45 m (1H, H9), 7.55 d (1H, H6, J 9 Hz),
7.70 d (1H, H7, J 9 Hz), 7.80 d (1H, H10, J 9 Hz); minor
a
e
1
1357,1241 (C–O–C), 1176, 1032, 800, 741. H NMR
spectrum, δ, ppm, main isomer: 1.13 s (3H, C4'CH3 ),
a
1.20 s (3H, C4'CH3 ), 2.51 d (1H, H5’e, J 14.8 Hz), 2.77 d
e
(1H, H5’a, J 14.8 Hz), 3.44 d (1H, H3, J 11.7 Hz), 3.46 d
(1H, H1, J 16 Hz), 3.56 d (1H, H1, J 16 Hz), 3.59 d (1H,
H3, J 11.7 Hz), 3.78 s (3H, C3’COOCH3), 3.82 s (3H,
OCH3), 3.94 s (1H, H3’), 4.54 s (2H, NCH2O), 6.91 d
(2Harom, J 8.7 Hz), 7.07 d (1H, H5, J 8.6 Hz), 7.23 d
(2Harom, J 8.7 Hz), 7.29 m (1H, H8), 7.49 m (1H, H9),
7.57 d (1H, H6, J 9 Hz), 7.72 d (1H, H7, J 8.2 Hz), 7.92 d
isomer: 0.93 s (3H, C4'CH3 ), 1.10 s (3H, C4'CH3 ), 2.50 d
(1H, H5’e, J 15 Hz), 3.20 d (1H, H5’a, J 15 Hz), 3.40 d
(1H, H1, J 15 Hz), 3.50 d (1H, H1, J 15 Hz), 3.67 C (3H,
C3’COOCH3), 3.70 C (1H, H3’), 3.75 d (1H, H3), 3.77 d
(1H, H3), 4.60 d (2H, NCH2O, J 16 Hz), 6.06 s (2H,
OCH2O), 6.80 s (1Harom, J 9 Hz), 6.90 d (1H, H5, J 9 Hz),
7.20 d (2Harom, J 9 Hz), 7.25 m (1H, H8), 7.46 m (1H, H9),
7.54 d (1H, H6, J 9 Hz), 7.70 d (1H, H7, J 9 Hz), 7.90 d
(1H, H10, J 9 Hz). Found, %: C 72.32; H 5.68; N 2.65.
C30H29NO6. Calculated, %: C 72.13; H 5.85; N 2.80.
a
e
(1H, H10, J 8.5 Hz); minor isomer: 1.12 s (3H, C4'CH3 ),
a
1.14 s (3H, C4'CH3 ), 2.64 d (1H, H5’e, J 15 Hz), 3.19 d
e
(1H, H5’a, J 15 Hz), 3.42 d (1H, H1, J 15 Hz), 3.55 d
(1H, H1, J 15 Hz), 3.67 s (3H, C3’COOCH3), 3.75 s
(1H, H3’), 3.74 d (1H, H3), 3.78 d (1H, H3), 3.80 s (3H,
OCH3), 4.60 d (2H, NCH2O, J 16 Hz), 6.88 d (2Harom
,
,
J 8.6 Hz), 6.99 d (1H, H5, J 9.1 Hz), 7.20 d (2Harom
Methyl 4-(3,4-dimethoxybenzyl)-1,4-dihydro-
2',6'-dioxo-4',4'-dimethyl-2'H,3H,6'H-spirobenzo[f]-
quinoline-2,1'-cyclohexyl-3'-carboxylate (VIIc). Yield
0.38 g (75%), mp 164°C. IR spectrum, ν, cm–1: 3443,
3407 (N–H), 3003 (C–Harom), 2954, 2934, 2872, 2835
(C–H), 1749, 1725 (C=O), 1698 (COOCH3), 1621, 1594,
1514, 1134, 1342, 1227 (C–O–C), 1142, 1022, 808, 745.
1H NMR spectrum, δ, ppm, main isomer: 1.00 s (3H,
C4'CH3 ), 1.20 s (3H, C4'CH3 ), 2.51 d (1H, H5’e, J 15 Hz),
2.70 d (1H, H5’a, J 15 Hz), 3.25 d (1H, H3, J 12 Hz),
3.44 d (1H, H1, J 16 Hz), 3.50 d (1H, H1, J 16 Hz), 3.79 d
(1H, H3, J 12 Hz), 3.71 s (3H, C3’COOCH3), 3.72 s (3H,
OCH3), 3.78 s (3H, OCH3), 4.00 s (1H, H3’), 4.60 s (2H,
NCH2O), 6.75 d (1Harom, H5, J 9 Hz), 6.80 s (1Harom),
6.85 d (1Harom, J 9 Hz), 6.90 d (1Harom, J 9 Hz), 7.25 m
(1H, H8), 7.45 m (1H, H9), 7.55 d (1H, H6, J 9 Hz), 7.70 d
(1H, H7, J 9 Hz), 7.90 d (1H, H10, J 9 Hz); minor iso-
J 8.6 Hz), 7.24 m (1H, H8), 7.46 m (1H, H9), 7.54 d (1H,
H6, J 9.1 Hz), 7.70 d (1H, H7, J 8.8 Hz), 7.80 d (1H, H10,
J 8.6 Hz). 13C NMR spectrum, δ, ppm, main isomer:
22.61 (C4'CH3 ), 25.05 (C1H), 28.30 (C4'CH3 ), 34.13
(C4'), 52.26 (COOCH3), 53.21 (C5’), 55.48 (COCH3),
55.74 (NCH2C6H4OCH3), 55.78 (C3), 63.13 (C3’), 64.87
(C2), 113.59 (C6a), 114.35 (2Carom), 115.54 (C5), 122.08
(C10), 122.74 (C8), 126.65 (C9), 127.30 (C6), 128.11
(C10b), 128.44 (C7), 128.51 (2Carom), 130.14 (CCH2N),
132.89 (C10a), 141.49 (C4a), 159.15 (COCH3), 168.33
(COOCH3), 201.24 (C2’), 204.39 (C6’); minor isomer:
a
e
a
e
25.04 (C4'CH3 ), 28.81 (C4'CH3 ), 29.62 (C1H), 33.48
(C4'), 49.68 (C5’), 52.46 (COOCH3), 53.21 (C3), 64.97
(C3’), 55.44 (COCH3), 55.97 (NCH2C6H4OCH3), 62.89
(C2), 110.57 (C6a), 114.21 (2Carom), 115.46 (C5), 121.13
(C10), 122.00 (C8), 126.65 (C9), 127.67 (C6), 127.36
(C10b), 128.66 (C7), 127.83 (2Carom), 130.14 (CCH2N),
132.69 (C10a), 142.03 (C4a), 158.81 (COCH3), 169.02
(COOCH3), 202.51 (C2’), 205.73 (C6’). Found, %:
C 74.50; H 6.31; N 3.05. C30H31NO5. Calculated, %:
C 74.21; H 6.43; N 2.88.
e
a
mer: 0.95 s (3H, C4'CH3 ), 1.15 s (3H, C4'CH3 ), 2.50 d
(1H, H5’e, J 15 Hz), 3.20 d (1H, H5’a, J 15 Hz), 3.40 d
(1H, H1, J 15 Hz), 3.50 d (1H, H1, J 15 Hz), 3.65 s (3H,
C3’COOCH3), 3.70 s (1H, H3’), 3.75 d (1H, H3), 3.77 d
(1H, H3), 3.80 s (3H, OCH3), 3.82 s (3H, OCH3), 4.65 d
a
e
Methyl 4-(3,4-methylenedioxybenzyl)-1,4-dihydro-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 11 2012

CONDENSATION OF 2-NAPHTHYLAMINE
1463
(2H, NCH2O, J 16 Hz), 6.80 s (1Harom), 6.90 d (1H,
H5, J 9 Hz), 7.20 d (2Harom, J 9 Hz), 7.25 m (1H, H8),
7.46 m (1H, H9), 7.54 d (1H, H6, J 9 Hz), 7.70 d (1H, H7,
J 9 Hz), 7.95 d (1H, H10, J 9 Hz). Found, %: C 72.44;
H 6.36; N 2.61. C31H33NO6. Calculated, %: C 72.21;
H 6.45; N 2.72.
(1H, H5’a, J 15 Hz), 3.42 d (1H, H1, J 15 Hz), 3.55 d (1H,
H1, J 15 Hz), 3.67 s (3H, C3’COOCH3), 3.80 s (1H, H3’),
3.81 d (1H, H3), 3.95 d (1H, H3), 4.58 d (2H, NCH2O,
J 16 Hz), 6.95 d (1H, H5, J 9 Hz), 7.20 m (4Harom), 7.25 m
(1H, H8), 7.45 m (1H, H9), 7.60 d (1H, H6, J 9 Hz), 7.80 d
(1H, H7, J 9 Hz), 7.95 d (1H, H10, J 9 Hz). Found, %:
C 77.12; H 7.34; N 2.98. C32H35NO5. Calculated, %:
C 77.24; H 7.09; N 2.81.
Methyl 4-(4-isopropylbenzyl)-1,4-dihydro-2',6'-
dioxo-4',4'-dimethyl-2'H,3H,6'H-spirobenzo[f]
quinoline-2,1'-cyclohexyl-3'-carboxylate (VIId).
Yield 0.35 g (97%), mp 187°C. IR spectrum, ν, cm–1:
3420 (N–H), 3050 (C–Harom), 2958, 2924, 2871 (C–H),
1747, 1730 (C=O), 1701 (COOCH3), 1620, 1599, 1514,
REFERENCES
1. Kadutskii, A.P., Kozlov, N.G., and Zhikharko, Yu.D., Zh.
Org. Khim., 2011, vol. 47, p. 419.
2. Kurlovich, A.L., Tarasevich, V.A., and Kozlov, N.G., Zh.
Org. Khim., 2009, vol. 45, p. 1519.
3. Kozlov, N.G. and Tereshko, A.B., Zh. Org. Khim., 2010,
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4. Kozlov, N.G. and Gusak, K.N., Zh. Org. Khim., 2010,
vol. 46, p. 1075.
5. Keri, F. and Sandberg, R., Uglublennyi kurs organicheskoi
khimii (Deep Course of Organic Chemistry), Moscow:
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p. 14.
1
1351, 1230 (C–O–C), 1130, 1014, 738. H NMR spec-
trum, δ, ppm, main isomer: 1.10 s (3H, C4'CH3 ), 1.19 s
a
(3H, C4'CH3 ), 1.25 t [6H, CH(CH3)2, J 7 Hz], 2.40 d
e
(1H, H5’e, J 15 Hz), 2.80 d (1H, H5’a, J 15 Hz), 2.90 m
[1H, CH(CH3)2], 3.40 d (1H, H3, J 12 Hz), 3.45 d (1H,
H1, J 16 Hz), 3.60 d (1H, H1, J 16 Hz), 3.65 d (1H, H3,
J 12 Hz), 3.72 s (3H, C3’COOCH3), 3.90 s (1H, H3’),
4.60 s (2H, NCH2O), 6.90 d (1H, H5, J 9 Hz), 7.00 m (1H,
H8), 7.23 m (4Harom), 7.30 m (1H, H9), 7.50 d (1H, H6,
J 9 Hz), 7.70 d (1H, H7, J 9 Hz), 7.90 d (1H, H10, J 9 Hz);
minor isomer: 1.05 s (3H, C4'CH3 ), 1.15 s (3H, C4'CH3 ),
1.20 t [6H, CH(CH3)2, J 7 Hz], 2.60 d (1H, H5’e, J 15 Hz),
2.90 m [1H, CH(CH3)2], 2.95 m [1H, CH(CH3)2], 3.20 d
a
e
7. Kozlov, N.G., Basalaeva, L.I., Firgang, S.I., and Shash-
kov, A.S., Zh. Org. Khim., 2004, vol. 40, p. 549.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 11 2012