Synthesis and transformations of new 1,2,3,4,5,6,7,8,9,10- decahydroacridine-1,8-dione derivatives

Article abstract of DOI:10.1134/S1070428008080198

Reactions of cyclohexane-1,3-diones with amines and aldehydes led to the formation of 1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-diones containing alkylaryl, aryl, and hydroxy substituents in position 10. Transformations of 10-hydroxy-1,2,3,4,5,6,7,8,9,10

Full text of DOI:10.1134/S1070428008080198

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 8, pp. 1215–1224. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © A.N. Pyrko, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 8, pp. 1227–1236.
Synthesis and Transformations of New 1,2,3,4,5,6,7,8,9,10-Deca-
hydroacridine-1,8-dione Derivatives
A. N. Pyrko
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus,
ul. Akademika Kuprevicha 5/2, Minsk, 220141 Belarus
e-mail: pyrko@yandex.ru
Received March 26, 2007
Abstract—Reactions of cyclohexane-1,3-diones with amines and aldehydes led to the formation of
1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-diones containing alkylaryl, aryl, and hydroxy substituents
in position 10. Transformations of 10-hydroxy-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-diones under oxida-
tion with nitrous acid, reduction with zinc powder, as well as on heating in aprotic solvents and acetic,
phosphoric, and polyphosphoric acids, were studied. NMR spectra of 1,2,3,4,5,6,7,8,9,10-decahydroacridine-
1,8-diones having different substituents in positions 9 and 10 were analyzed.
DOI: 10.1134/S1070428008080198
Decahydroacridinediones contain a 1,4-dihydropyr-
idine ring as structural fragment and are available via
various versions of Hantzsch synthesis [1–4]. These
compounds exhibit a broad spectrum of biological
activity [5, 6]. With the goal of obtaining new 10-hy-
droxydecahydroacridinedione derivatives Iа–Ii, in the
present work hydroxylamine was used as one of the
components for building up 1,4-dihydropyridine ring
according to the above methods. Excess hydroxyl-
amine hydrochloride reacted with 2,2′-phenylmethyl-
enebis(3-hydroxy-5,5-dimethylcyclohex-2-en-1-one)
(II) in anhydrous pyridine, as well as with the corre-
sponding anhydride [7], to give octahydroacridinedi-
one dioxime IIIc (Scheme 1). The use in this reaction
of an equivalent amount of hydroxylamine resulted in
the formation of 10-hydroxydecahydroacridinedione
Ic. The most efficient procedure for the preparation of
10-hydroxydecahydroacridinediones Iа–Ii proved to
be three-component condensation of cyclohexane-1,3-
dione (IVа) or dimedone (IVb) with 1.2 equiv of hy-
droxylamine and 1.1 equiv of appropriate aldehyde in
anhydrous pyridine. Initially, diketones IVа and IVb
were heated with hydroxylamine in pyridine to obtain
the corresponding enamino ketone, aldehyde was then
added to the reaction mixture, and the mixture was
heated further. Decahydroacridinedione Ig was also
prepared by reaction of tetrahydroxanthene V with
hydroxylamine. Heating of compound Id with excess
hydroxylamine in pyridine gave dioxime IIId.
On the basis of published data [8, 9] it was ex-
pected that compounds Iа–Ii could easily lose water
molecule to be converted into the corresponding octa-
hydroacridinediones. However, they turned out to be
stable (except for compound Ie) on heating for 3 h in
acetic acid or propan-2-ol. When compounds Ia and Id
were heated in aprotic solvents, oxygen elimination
occurred with formation of decahydroacridinediones
VIа and VId. Presumably, the reaction involved inter-
mediate formation of N-oxide A [8, 9]. The reduction
of N-hydroxyhydroacridine Ic with zinc powder re-
sulted in the formation of the corresponding deoxy
derivative VIc. The oxidation of If with nitrous acid
according to the procedure reported in [1] gave octa-
hydroacridinedione N-oxide VII and a minor amount
of octahydroacridinedione VIII. Octahydroacridinedi-
one N-oxide IX was obtained by heating compounds Ic
and If in phosphoric or polyphosphoric acid as de-
scribed in [10] or compound If in acetic acid [11]. In
addition, compound IX was obtained from decahydro-
xanthene X (which is available from dimedone and
triethyl orthoformate [12]) and hydroxylamine on heat-
ing in acetic acid. The reaction of X with excess
hydroxylamine gave dioxime IIIj. The reduction of
N-oxide IX with zinc powder afforded octahydroacri-
dinedione XI which was identical to a sample prepared
previously [10]. The structure of the obtained com-
pounds was determined on the basis of their UV, IR,
and NMR spectra and elemental analyses. N-Hydroxy-
1215

PYRKO
1216
Scheme 1.
C6H4OH-p
NOH
R
NOH
O
O
O
HO
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
N
N
O
OH O
II
IIIc, IIId, IIIj
VII
Me
Me
HO
O
O
R
N
O
O
O
NH2OH·HCl, RCHO
R'
R'
R'
R'
R'
Me
Me
O
O
R'
OH
IVa, IVb
Ia–Ii
V
Me
Me
O
O
O
R
O
O
O
OH
O
Me
Me
Me
Me
Me
Me
Me
N
NH
Me
O
O
IX
A
Me
Me
Me
O
Me
X
C6H4OH-p
O
O
O
O
O
R
O
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
N
N
H
N
VIII
XI
VIa, VIc, VId
R = Me (а), i-Bu (b), Ph (c, i), 4-MeOC6H4 (d), 4-Me2NC6H4 (e), 4-HOC6H4 (f), 2-HOC6H4 (g), 2-MeOC6H4 (h), H (j);
Ii, IVa, R′ = H; Iа–Ih, IVb, R′ = Mе.
decahydroacridinediones Iа–Ii displayed in the UV
spectra two absorption bands at λ 251–255 and 270–
271 nm, which are typical of enamino ketone moiety
[13]; in addition, a long-wave absorption band was
observed at λ 384–406 nm, which is characteristic of
3,5-diacyl-1,4-dihydropyridine system. Addition of al-
kali induces red shift of the absorption maxima. The
long-wave maximum shifts to λ 483–509 nm, and the
solution turns purple; therefore, these compounds can
be used as acid–base indicators. The magnitude of the
red shift reaches 99–113 nm; the corresponding shift
for unsubstituted derivatives VIc, VId, and XIIg
amounts to 78–83 nm (see table), while the intensity of
the initial band remains high at the same alkali concen-
tration (10–2 M), indicating high concentration of the
initial form of compounds VI. This means that the
acidity of I is higher than the acidity of VI. No shift of
the absorption maxima was observed in the UV spectra
of N-alkyl- and N-aryldecahydroacridinediones XII
(see below) upon addition of alkali. A conclusion can
be drawn that the observed changes in the electronic
absorption spectra result from formation of anions
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 8 2008

SYNTHESIS AND TRANSFORMATIONS OF NEW 1,2,3,4,5,6,7,8,9,10-DECAHYDRO-...
1217
UV spectra of compounds Iа–Ii, VIc, VId, and XIIg in neutral and alkaline media
UV spectrum, nm (logε)
Compound no.
EtOH
10–2 M KOH in EtOH
251 (4.09), 271 (3.70), 392 (3.75)
253 (4.32), 270 (3.87), 385 (3.92)
251 (4.15), 392 (3.78)
271 (4.25), 307 (3.69), 504 (3.94)
272 (4.39), 305 (3.79), 492 (4.05)
276 (4.23), 501 (3.89)
Ia
Ib
Ic
Id
226 (4.06), 251 (4.13), 270 (3.94), 392 (3.88)
251 (4.47), 390 (3.85)
225 (4.17), 270 (4.1), 301 (3.91), 502 (4.00)
258 (4.35), 302 (3.92), 502 (3.93)
Ie
If
226 (3.98), 250 (4.04), 270 (3.83), 391 (3.74)
255 (4.18), 395 (3.79)
245 (4.27), 271 (4.26), 300 (3.85), 502 (3.92)
274 (4.25), 504 (3.88)
Ig
Ih
254 (4.13), 406 (3.75)
273 (4.17), 302 (3.82), 516 (3.84)
269 (4.16), 483 (3.82)
Ii
251 (4.11), 384 (3.71)
VIc
VId
XIIg
250 (4.16), 375 (3.88)
250 (4.22), 376 (3.83), 459 (3.61)
225 (4.19), 250 (4.16), 375 (3.85), 458 (3.35)
265 (4.24), 377 (3.52), 455 (4.03)
227 (4.14), 249 (4.20), 375 (3.96)
250 (4.23), 377 (3.94)
XIII and XIV in alkaline solution; the presence of
a negative charge in the donor part of the molecule
(nitrogen atom) increases the energy of the highest
occupied molecular orbital (HOMO), which is respon-
sible for the red shift of the charge-transfer band [14].
In the IR spectra of decahydroacridinediones Iа–Ii,
absorption bands in the region 1620–1670 cm–1 corre-
spond to the enamino ketone fragments. The carbonyl
absorption band in the IR spectra of octahydroacridine-
diones is located at 1700–1725 cm–1; such a frequency
is fairly high for a carbonyl group conjugated with
aromatic ring. Presumably, interaction between two
identical carbonyl functions (resonance effect) leads to
band splitting [15].
The presence of a 3,5-diacyl-1,4-dihydropyridine
fragment in molecules Iа–Ii is responsible for lumines-
cence of these compounds. Like their N-phenyl-substi-
tuted analogs [16], luminescence of Iа–Ii is observed
under UV irradiation. For example, irradiation of a so-
lution of Id in alcohol (λmax 373 nm) gives rise to
luminescence with its maximum at λfl 464 nm. Irradia-
tion of the same compound in a 10–2 N solution of
sodium hydroxide (λmax 502 nm) induces fluorescence
at λfl 696 nm.
The NMR spectra of decahydroacridinediones Iа–Ii
correspond to structures with a symmetry plane pass-
ing through the С9 and N10 atoms. On the other hand,
the NMR spectra of octahydroacridine derivatives
indicate that their molecules have one more symmetry
plane passing through all 14 atoms of the acridine
skeleton and orthogonal to the first symmetry plane;
therefore, their structure is characterized by the
second-order symmetry axis, and it corresponds to the
С2v point group symmetry [17]. In the 1H NMR spectra
of Iа and Ic–Ih, four methyl groups in positions 3 and
6 appear as two singlets, while in the spectra of III and
VII–IX, protons in the methyl groups give only one
singlet. At least one signal from two equivalent meth-
ylene groups (С2H2/C8H2 and С4H2/C5H2) in com-
pounds Iа–Ih appears as an АВ quartet. Compounds
III and VII–IX display two singlets from the methyl-
ene protons. Obviously, nonequivalence of geminal
O
R3
O
O
R3
O
O
R3
O
Me
Me
R1
R1
R1
R1
R1
R1
Me
Me
Me
Me
N
R2
N
O
N
XIIa–XIIi
XIIIa–XIIIi
XIVa, XIVc, XIVd
XII, R1 = H (c), Me (а, b, d–i); R2 = PhCH2 (а, c, d), 3,4-(MeO)2C6H3CH2CH2 (b), HOCH2CH2 (e), Ph (f), H (g), PhCH2CH2 (h, i);
R3 = H (a), 3,4-(MeO)2C6H3 (b, h), i-Pr (c, d), 2-HOC6H4 (e–g, i); XIII, XIV, R1 = H (i), Mе (а–h); R3 = Me (а), i-Bu (b), Ph (c, i),
4-MeOC6H4 (d), 4-Me2NC6H4 (e), 4-HOC6H4 (f), 2-HOC6H4 (g), 2-MeOC6H4 (h).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 8 2008

PYRKO
1218
protons and methyl groups in decahydroacridinediones
Iа–Ii originates from the effect of different substituents
in position 9. Inversion of the rings does not give two
equivalent structures, and the plane of the acridine
skeleton does not become a symmetry plane.
EXPERIMENTAL
The UV spectra were recorded on a Specord M-400
spectrophotometer. The fluorescence spectra were
measured on a Solar instrument. The IR spectra were
obtained in KBr on a UR-20 spectrometer. The 1Н and
13С NMR spectra of compounds XIIb–XIId were
recorded on a Bruker Avance 500 spectrometer at 500
and 125 MHz, respectively, and the other compounds
were examined on a Bruker AC-200 spectrometer at
200 and 50 MHz, respectively; tetramethylsilane was
used as internal reference. The progress of reactions
and the purity of products were monitored by TLC on
Silufol UV-254 plates using EtOAc–hexane (1:1) as
eluent; spots were visualized under UV radiation or by
treatment with iodine vapor, followed by calcination at
250–350°С. The melting points were determined on
a Boetius hot stage.
Analysis of published data shows that our spectral
data are not always consistent with the data reported
by other authors for the same structures. In particular,
Shchekotikhin and Nikolaeva [7] reported the 1Н NMR
spectrum of octahydroacridinedione IIIc, which con-
tained two singlets from four methyl groups in posi-
tions 3 and 6; compound IIIc isolated in the present
work showed only one singlet in the same spectral
region. In the spectra of decahydroacridinedione
derivatives XII having an ortho-substituted phenyl
ring, more than two signals from methyl groups (3 to
4) were observed [4]. The compounds having no sub-
stituent on C9 and an ortho-substituted phenyl group
on the nitrogen atom revealed nonequivalence of the
С2H2/C8H2 and С4H2/C5H2 methylene groups [18] and
geminal methyl groups on C3 and C6 [2, 6]. This may
be due to the presence of different rotamers arising
from restricted rotation of the aromatic substituent
10-Hydroxy-3,3,6,6-tetramethyl-9-phenyl-1,2,-
3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (Ic).
а. A mixture of 1.10 g (3 mmol) of tetraketone II and
0.21 g (3 mmol) of hydroxylamine hydrochloride in
20 ml of pyridine was heated for 2 h under reflux. The
mixture was cooled to room temperature, diluted with
150 ml of water, and left to stand for 24 h. The precip-
itate was filtered off, washed with water (150 ml),
dried in air, and recrystallized from ethanol. Yield
0.68 g (62%), mp 254–256ºС. IR spectrum, ν, cm–1:
1150, 1235, 1380, 1620–1660 (С=С, С=О), 3250
1
about the С–N bond [4]. The Н NMR spectrum of
10-benzyl-substituted decahydroacridinedione XIIа
reported in [2] contained two singlets from the four
methyl groups, though only one singlet should be ex-
pected on the basis of the above considerations, taking
into account the lack of substituent in position 9.
1
(ОН). Н NMR spectrum (CD3CO2D), δ, ppm: 0.94 s
(6Н, Mе), 1.10 s (6Н, Mе), 2.21 and 2.33 (2Н each,
СН2, АВ system, JАВ = 17 Hz), 2.56 and 2.84 (2Н each,
СН2, АВ system, JАВ = 17 Hz), 5.14 s (1Н, 9-Н), 7.00–
We synthesized compound XIIа and a series of its
N-aralkyl-substituted analogs XIIb–XIIi with a view
to examine their NMR spectra. The syntheses were
performed by three-component condensation of dime-
done or cyclohexane-1,3-dione, appropriate 3-amino-
cyclohex-2-en-1-one, and aldehyde in acetic acid.
Compound XIIi was obtained by reaction of V with
13
7.20 (5Н, Hароm). C NMR spectrum (CD3CO2D), δC,
ppm: 27.01 (Me), 29.96 (Me), 32.79 (C3, C6), 33.62
(C9), 38.52 (C4, C5), 50.05 (C2, C7), 112.44 (C8a, C9a),
127.29 (C4′), 128.77 (Cароm), 129.01 (Cароm), 146.34
(C1′), 155.50 (C4a, C10a), 199.01 (C1, C8). Found, %:
С 75.72; Н 7.34; N 3.80. C23H27NO3. Calculated, %:
C 75.59; H 7.45; N 3.83.
1
2-phenylethanamine [19]. In the Н NMR spectrum of
decahydroacridinedione XIIа only one singlet from
methyl protons was observed. The spectra of com-
pounds XIIb–XIIi indicated that their molecules have
one symmetry plane with no rotamers. The same
b. A mixture of 2.8 g (20 mmol) of 5,5-dimethyl-
cyclohexane-1,3-dione (dimedone) and 0.76 g
(11 mmol) of hydroxylamine hydrochloride in 15 ml of
pyridine was heated for 1 h under reflux, 1.17 g
(11 mmol) of benzaldehyde was added, and the mix-
ture was heated for 2 h more under reflux. It was then
cooled to room temperature, diluted with 150 ml of
water, and left to stand for 24 h. The precipitate was
filtered off, washed with water (150 ml), and dried in
air. Yield 3.32 g (91%).
1
applies for their N-alkyl derivatives [19]. The Н and
13С NMR spectra of XIIc possessing a chiral center
(С9) contained two signals from the methyl groups in
the isopropyl substituent on C9, while the correspond-
ing groups in symmetric analog XIId gave rise to
a single peak. Octahydroxanthene derivatives having
an oxygen atom instead of nitrogen in position 10
displayed similar spectral patterns [19].
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SYNTHESIS AND TRANSFORMATIONS OF NEW 1,2,3,4,5,6,7,8,9,10-DECAHYDRO-...
1219
10-Hydroxy-3,3,6,6,9-pentamethyl-9-phenyl-
1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (Iа)
was synthesized in a similar way from 2.80 g of di-
medone, 0.83 g of hydroxylamine hydrochloride, and
0.48 g of acetaldehyde. Yield 2.58 g (85%), mp 223–
225°С. IR spectrum, ν, cm–1: 1150, 1240, 1380, 1620–
1660 (С=С, С=О), 2900, 3200 (ОН). Н NMR spec-
trum (CD3CO2D), δ, ppm: 0.92 d (3Н, 9-Mе, J =
7 Hz), 1.04 s (6Н, Mе), 1.07 s (6Н, Mе), 2.06 s (4Н,
119.75 (Сarom), 130.51 (Carom), 158.43 (Cp), 161.70
(C4a, C10a), 199.31 (C1, C8). Found, %: С 72.76;
Н 7.29; N 3.43. C24H29NO4. Calculated, %: C 72.88;
H 7.39; N 3.54.
10-Hydroxy-9-(4-dimethylaminophenyl)-3,3,6,6-
tetramethyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-
1,8-dione (Ie) was synthesized in a similar way from
2.80 g of dimedone, 0.83 g of hydroxylamine hydro-
chloride, and 1.64 g of 4-dimethylaminobenzaldehyde.
Yield 3.67 g (90%), mp 165–167°С. IR spectrum, ν,
cm–1: 1150, 1235, 1375, 1620–1660, 3250, 3300.
1Н NMR spectrum (CD3OD), δ, ppm: 0.96 s (6Н, Mе),
1.12 s (6Н, Mе), 2.11 and 2.27 (2Н each, СН2, АВ
system, JАВ = 17 Hz), 2.67 and 2.79 (2Н each, СН2,
АВ system, JАВ = 17 Hz), 3.25 s (6Н, NMе2), 5.16 s
(1Н, 9-Н), 7.54 m (4Н, Harom). Found, %: С 73.37;
Н 7.82; N 6.94. C25H32N2O3. Calculated, %: C 73.49;
H 7.90; N 6.86.
1
СН2), 2.56 and 2.72 (2Н each, СН2, АВ system, JАВ
=
17 Hz), 4.00 q (1Н, 9-Н, J = 7 Hz). 13C NMR spectrum
(CD3CO2D), δC, ppm: 22.72 (9-Mе), 26.86 (Me), 29.86
(Me), 29.96 (C9), 32.83 (C3, C6), 38.46 (C4, C5), 50.15
(C2, C7), 113.36 (C8a, C9a), 156.04 (C4a, C10a), 199.21
(C1, C8). Found, %: С 67.41; Н 8.58; N 4.25.
C18H25NO3 ·H2O. Calculated, %: С 67.26; Н 8.47;
N 4.36.
10-Hydroxy-3,3,6,6-tetramethyl-9-(2-methyl-
propyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-
dione (Ib) was obtained in a similar way from 2.80 g
of dimedone, 0.83 g of hydroxylamine hydrochloride,
and 0.95 g of 3-methylbutanal. Yield 3.00 g (87%),
mp 242–244°С. IR spectrum, ν, cm–1: 1150, 1235,
10-Hydroxy-9-(4-hydroxyphenyl)-3,3,6,6-tetra-
methyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-
dione (If) was synthesized in a similar way from
2.80 g of dimedone, 0.83 g of hydroxylamine hydro-
chloride, and 1.34 g of 4-hydroxybenzaldehyde. Yield
3.51 g (92%), mp 244–246°С. IR spectrum, ν, cm–1:
1230, 1370, 1520, 1550, 1620 (С=С), 1670 (С=О),
1
1385, 1605 (С=С), 1660 (С=О), 3250 (ОН). Н NMR
spectrum (CF3CO2D–CD3OD, 1:1), δ, ppm: 0.90 d
(6Н, Mе, J = 6.5 Hz), 1.16 s (12Н, Mе), 1.20 m (2Н,
1′-H), 1.42 m (2′-Н), 2.34 s (4Н, СН2), 2.62 and
2.80 (2Н each, СН2, АВ system, JАВ = 18 Hz) 4.15 t
(1Н, 9-Н, J = 6.5 Hz). 13C NMR spectrum (CF3CO2D–
CD3OD, 1:1), δC, ppm: 23.63 (2′-Mе), 25.38 (С),
25.81 (С), 27.18 (Me), 30.26 (Me), 33.21 (C3, C6),
39.17 (C4, C5), 47.29 (9-СН2), 51.02 (C2, C7), 113.43
(C8a, C9a), 157.52 (C4a, C10a), 198.90 (C1, C8). Found,
%: С 69.33; Н 9.00; N 3.82. C21H31NO3·H2O. Calcu-
lated, %: C 69.39; H 9.15; N 3.85.
1
3200 (ОН). Н NMR spectrum (DMSO-d6), δ, ppm:
0.90 s (6Н, Mе), 1.04 s (6Н, Mе), 2.01 and 2.19 (2Н
each, СН2, АВ system, JАВ = 17 Hz), 2.55 and 2.66 (2Н
each, СН2, АВ system, JАВ = 18 Hz), 4.90 s (1Н, 9-Н),
6.58 d (2Н, Нarom, J = 8 Hz), 7.02 d (2Н, Нarom, J =
8 Hz), 9.18 br.s (ОН), 10.96 br.s (ОН). 13C NMR spec-
trum (DMSO-d6), δC, ppm: 26.65 (Me), 29.36 (Me),
30.62 (С9), 31.56 (C3, C6), 39.01 (C4, C5), 49.63 (C2,
C7), 110.00 (C8a, C9a), 114.44 (Сarom), 128.06 (Сarom),
136.51 (Ci), 152.09 (Сp), 155.16 (C4a, C10a), 196.00
(C1, C8). Found, %: С 73.68; Н 6.27; N 4.61.
C19H19NO3. Calculated, %: C 73.76; H 6.19; N 4.53.
10-Hydroxy-9-(4-methoxyphenyl)-3,3,6,6-tetra-
methyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-di-
one (Id) was synthesized in a similar way from 2.80 g
of dimedone, 0.83 g of hydroxylamine hydrochloride,
and 1.50 g of 4-methoxybenzaldehyde. Yield 3.52 g
(89%), mp 228–230°С. IR spectrum, ν, cm–1: 1150,
1230, 1375, 1615–1660 (С=С, С=О), 3250 (ОН).
1Н NMR spectrum (CF3CO2D–CD3OD, 1:1), δ, ppm:
1.02 s (6Н, Mе), 1.18 s (6Н, Mе), 2.44 and 2.28 (2Н
each, СН2, АВ system, JАВ = 17 Hz), 2.66 and 2.98 (2Н
each, СН2, АВ system, JАВ = 17 Hz), 3.74 s (3Н,
ОMе), 5.14 s (1Н, 9-Н), 6.79 d (2Н, Нarom, J = 8 Hz),
7.22 d (2Н, Нarom, J = 8 Hz). 13C NMR spectrum
(CF3CO2D–CD3OD, 1:1), δC, ppm: 27.49 (Me), 29.72
(Me), 35.58 (C3, C6, C9), 39.19 (C4, C5), 50.13 (C2,
C7), 56.12 (ОMе), 113.71 (C8a, C9a), 115.30 (Сarom),
10-Hydroxy-9-(2-hydroxyphenyl)-3,3,6,6-tetra-
methyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-
dione (Ig). а. Compound Ig was synthesized as de-
scribed above for Ic from 2.80 g of dimedone, 0.83 g
of hydroxylamine hydrochloride, and 1.34 g of salicyl-
aldehyde. Yield 3.47 g (91%), mp 203–205°С. IR
spectrum, ν, cm–1: 1150, 1240, 1380, 1495, 1600,
1
1630–1660 (С=С, С=О), 3260 (ОН). Н NMR spec-
trum (DMSO-d6), δ, ppm: 0.97 s (6Н, Mе), 1.11 s (6Н,
Mе), 2.05 and 2.22 (2Н each, СН2, АВ system, JАВ
17 Hz), 2.45 and 2.70 (2Н each, СН2, АВ system, JАВ
=
=
18 Hz), 5.08 s (1Н, 9-Н), 6.65 m (1Н, Harom), 6.90 m
(2Н, Harom), 7.29 m (1Н, Harom). 13C NMR spectrum
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 8 2008

PYRKO
1220
(DMSO-d6), δC, ppm: 26.91 (Me), 29.46 (Me), 29.94
(C9), 32.64 (C3, C6) 35.98 (C4, C5), 50.35 (C2, C7),
108.34 (C8a, C9a), 109.31 (Сarom), 111.83 (Сarom),
120.39 Сarom), 128.26 (Сarom), 137.07 (Carom), 153.32
(СOH), 154.03 (C4a, 10a), 196.91 (C1, C8). Found, %:
С 72.30; Н 7.05; N 3.77. C23H27NO4. Calculated, %:
C 72.42; H 7.13; N 3.67.
(С1, C8). Found, %: С 72.30; Н 7.05; N 3.77.
C23H27NO4. Calculated, %: C 72.42; H 7.13; N 3.67.
3,3,6,6-Tetramethyl-9-phenyl-1,2,3,4,5,6,7,8-
octahydroacridine-1,8-dione dioxime (IIIc). A mix-
ture of 1.10 g (3 mmol) of tetraketone II and 1.00 g
(14.4 mmol) of hydroxylamine hydrochloride in 20 ml
of pyridine was heated for 3 h under reflux. The mix-
ture was then cooled to room temperature, diluted with
150 ml of water, and left to stand for 24 h. The precip-
itate was filtered off, washed with 150 ml of water,
dried in air, and recrystallized from ethanol. Yield
0.90 g (80%), mp 263–265°С (from ЕtОН); published
data [1, 8]: mp 250°С. IR spectrum, ν, cm–1: 1250,
1375, 1490, 1555, 1620 (С=С), 1650 (С=О), 2875,
b. A mixture of 0.73 g (2 mmol) of compound V
and 0.15 g (2.2 mmol) of hydroxylamine hydro-
chloride in 20 ml of pyridine was heated for 4 h under
reflux. The mixture was then cooled to room tempera-
ture, diluted with 150 ml of water, and left to stand for
24 h. The precipitate was filtered off, washed with
water (150 ml), dried in air, and recrystallized from
ethanol. Yield 0.57 g (75%).
2965 (СН), 3200–3400 (ОН). UV spectrum (ЕtOH),
1
λ
max, nm (logε): 251 (4.06), 310 (3.50). Н NMR spec-
10-Hydroxy-9-(2-methoxyphenyl)-3,3,6,6-tetra-
methyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-
dione (Ih) was synthesized in a similar way from
2.80 g of dimedone, 0.83 g of hydroxylamine hydro-
chloride, and 1.50 g of 2-methoxybenzaldehyde. Yield
3.48 g (88%), mp 247–249°С. IR spectrum, ν, cm–1:
1150, 1230, 1370, 1500, 1610–1670 (С=С, С=О),
trum (CF3CO2D), δ, ppm: 1.25 s (12H, Me), 3.02 s
(4H, 2-H, 7-H), 3.20 s (4H, 4-H, 5-H), 7.20–7.60 m
(5H, Harom). 13С NMR spectrum (CF3CO2D), δC, ppm:
29.76 (Mе); 32.85 (С3, C6); 39.38 (С2, C7); 43.41 (С4,
C5); 130.82, 131.31, 132.12 (Сarom); 129.81, 135.19
(С9, C8а, C9а); 154.57 (С4а, C10а); 157.88 (С1, C8).
Found, %: С 73.22; Н 7.30; N 11.20. C23H27N3O2. Cal-
culated, %: C 73.18; H 7.21; N 11.13.
1
3250, 3450 (ОН). Н NMR spectrum (CF3CO2D–
CD3OD, 1:1), δ, ppm: 0.92 s (6Н, Mе), 1.12 s (6Н,
Mе), 2.08 and 2.26 (2Н each, СН2, АВ system, JАВ
17 Hz), 2.56 and 2.80 (2Н each, СН2, АВ system, JАВ
=
=
3,3,6,6-Tetramethyl-9-(4-methoxyphenyl)-
1,2,3,4,5,6,7,8-octahydroacridine-1,8-dione dioxime
(IIId). A mixture of 0.79 g (2 mmol) of diketone Id
and 0.56 g (8 mmol) of hydroxylamine hydrochloride
in 20 ml of pyridine was heated for 3 h under reflux.
The mixture was cooled to room temperature, diluted
with 150 ml of water, and left to stand for 24 h. The
precipitate was filtered off, washed with 150 ml of
water, dried in air, and recrystallized from ethanol.
Yield 0.66 g (81%), mp 268–270°С (from ЕtОН). IR
spectrum, ν, cm–1: 1250, 1280, 1375, 1390, 1475,
1520, 1555, 1590 (С=С), 1620 (С=О), 2875, 2965
18 Hz), 3.80 s (3Н, ОMе), 5.16 s (1Н, 9-Н), 6.84 m
(2Н, Harom), 7.08 m (1Н, Harom), 7.38 m (1Н, Harom).
13C NMR spectrum (CF3CO2D–CD3OD, 1:1), δC, ppm:
26.63 (Me), 29.82 (Me), 30.26 (C9), 33.25 (С3, C6),
38.91 (C4, C5), 50.00 (C2, C7), 55.72 (ОMе), 111.37
(C8a, C9a), 111.91 (Сarom), 112.00 (Сarom), 120.93 (Сarom),
128.86 (Carom), 133.67 (Carom), 156.13 (COMe), 160.15
(C4a, C10a), 199.10 (C1, C8). Found, %: С 72.75;
Н 7.47; N 3.62. C24H29NO4. Calculated, %: C 72.88;
H 7.39; N 3.54.
(СН), 3200–3300 (ОН). UV spectrum (ЕtOH), λmax
,
10-Hydroxy-9-phenyl-1,2,3,4,5,6,7,8,9,10-deca-
hydroacridine-1,8-dione (Ii) was synthesized in
a similar way from 2.24 g of cyclohexane-1,3-dione,
0.83 g of hydroxylamine hydrochloride, and 1.17 g of
benzaldehyde. Yield 2.66 g (86%), mp 254–256°С. IR
spectrum, ν, cm–1: 1140, 1185, 1240, 1310, 1370, 1620
nm (logε): 228 (4.34), 257 (4.24), 312 (3.78). 1Н NMR
spectrum (CF3CO2D), δ, ppm: 1.16 s (12H, Me), 2.76 s
(4H, 2-H, 7-H), 3.05 s (4H, 4-H, 5-H), 3.83 s (3Н,
ОMе), 6.92 d (2Н, Нarom, J = 8 Hz), 7.07 d (2Н, Нarom
,
J = 8 Hz). 13С NMR spectrum (CF3CO2D), δC, ppm:
28.65 (Mе), 31.62 (С3, C6), 38.16 (С2, C7), 42.46 (С4,
C5), 55.79 (ОMе), 114.58 (С3′, C5′), 130.34 and 130.63
(С8а, C9а, C1′), 131.73 (С2′, C6′), 151.75 (С9), 154.42
(С4а, C10а), 156.37 (COMe), 161.04 (С1, C8). Found,
%: С 70.67; Н 7.19; N 10.23. C24H29N3O3. Calculated,
%: C 70.73; H 7.17; N 10.31.
1
(С=С), 1635, 1660 (С=О), 3230 (ОН). Н NMR spec-
trum (DMSO-d6), δ, ppm: 1.78 m (2Н), 1.96 m (2Н),
2.43 m (4Н), 2.68 m (2Н), 2.83 d.t (2Н, J1 = 18, 5 Hz),
5.09 s (1Н, 9-Н), 7.07–7.19 (5Н, Harom), 10.81 br.s
(1Н, ОН). 13C NMR spectrum (DMSO-d6), δC, ppm:
22.50 (СН2), 30.41 (С9), 36.62 (СН2), 37.27 (СН2),
110.42 (С8а, C9а), 126.36 (Сarom), 126.52 (Сarom),
127.68 (Сarom), 146.01 (Сi), 154.1 (С4а, C10а), 194.62
3,3,6,6-Tetramethyl-9-phenyl-1,2,3,4,5,6,7,8,9,10-
decahydroacridine-1,8-dione (VIc). Zinc dust,
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SYNTHESIS AND TRANSFORMATIONS OF NEW 1,2,3,4,5,6,7,8,9,10-DECAHYDRO-...
1221
2.10 g, was dispersed in 10 ml of 10% hydrochloric
acid, and the suspension was intermittently shaken for
several minutes. The liquid part was separated by
decanting, and the remaining zinc material was washed
with ethanol (2 × 10 ml). A solution of 122 mg
(0.33 mmol) of compound Ic in 20 ml of ethanol was
added to the wet residue, and the mixture was stirred
for 5 h at room temperature. The precipitate was
filtered off, the filtrate was evaporated under reduced
pressure, and the residue was treated with water
(20 ml) and chloroform (100 ml). The chloroform
extract was dried with magnesium sulfate, and the
solvent was distilled off. Yield 95 mg (81%), mp 290–
292°С; published data [1]: mp 290–292°С.
spectrum, ν, cm–1: 1220, 1245, 1270, 1365, 1425,
1470, 1530, 1605, 1620 (С=С), 1725 (С=О), 2880,
2970 (СН), 3200–3300 (ОН). UV spectrum (ЕtOH),
λ
max, nm (logε): 228 (4.30), 245 (4.38), 285 (3.88).
1Н NMR spectrum (DMSO-d6), δ, ppm: 1.05 s (12H,
Me), 2.48 s (4H, 2-H, 7-H), 3.10 s (4H, 4-H, 5-H),
6.66 d (2Н, Нarom, J = 8 Hz), 6.80 d (2Н, Нarom, J =
8 Hz). Found, %: С 72.71; Н 6.52; N 3.76. C23H25NO4.
Calculated, %: C 72.80; H 6.64; N 3.69.
The filtrate was subjected to column chromatog-
raphy on silica gel (100–160 μm) using ethyl acetate–
hexane (2:1) as eluent to isolate 0.04 g (8%) of
N-oxide VII and 0.05 g (11%) of 9-(4-hydroxyphenyl)-
3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydroacridine-
1,8-dione (VIII), mp 267–270°С (from EtOH). IR
spectrum, ν, cm–1: 1230, 1280, 1365, 1485, 1525, 1545,
1605, 1625 (С=С), 1720 (С=О), 2880, 2965 (СН),
3,3,6,6,9-Pentamethyl-1,2,3,4,5,6,7,8,9,10-deca-
hydroacridine-1,8-dione (VIa). A mixture of 100 mg
of compound Ia and 25 ml of dioxane was heated for
5 h under reflux. It was then cooled to room tempera-
ture and left to stand for 24 h, and the precipitate was
filtered off. Yield 81 mg (85%), mp 265–268°C; pub-
lished data [20]: mp 265–267°C.
1
3200–3300 (ОН). Н NMR spectrum (DMSO-d6), δ,
ppm: 1.02 s (12H, Me), 2.46 s (4H, 2-H, 7-H), 3.02 s
(4H, 4-H, 5-H), 6.64 and 6.74 (2Н each, СН2, АВ
system, JАВ = 8 Hz), 9.32 br.s (1Н, ОН). Found, %:
С 75.91; Н 6.82; N 3.76. C23H25NO3. Calculated, %:
C 76.00; H 6.93; N 3.85.
9-(4-Methoxyphenyl)-3,3,6,6-tetramethyl-1,2,-
3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (VId).
a. A mixture of 100 mg of compound Id and 30 ml of
toluene was heated for 2 h under reflux. The solution
was evaporated by half and was left to stand for 24 h at
room temperature, and the precipitate was filtered off.
Yield 85 mg (89%), mp 269–271°С (from toluene);
published data [21]: mp 270–272°С.
3,3,6,6-Tetramethyl-1,2,3,4,5,6,7,8-octahydro-
acridine-1,8-dione 10-oxide (IX). а. A mixture of
1.10 g (3 mmol) of compound Ic and 30 g of poly-
phosphoric acid was stirred for 1.5 h at 115°С. It was
then cooled to room temperature and cautiously diluted
with 200 ml of water. After 15 h, solid impurities were
filtered off, and the filtrate was neutralized with solid
sodium hydroxide to pH 7–8. The precipitate was
filtered off, washed with water, dried in air, and recrys-
tallized from ethanol. Yield 0.71 g (82%), mp 223–
225°С (from EtOH). IR spectrum, cm–1: 1240, 1305,
1470, 1570 (С=С), 1700 (С=О), 2880, 2960 (СН). UV
spectrum (ЕtOH), λmax, nm (logε): 224 (4.25), 249
b. A mixture of 100 mg of compound Id and 15 ml
of diethylene glycol dimethyl ether was heated for
30 min under reflux, the solution was diluted with
50 ml water and was left to stand for 24 h at room
temperature, and the precipitate was filtered off. Yield
82 mg (85%).
Oxidation of 10-hydroxy-9-(4-hydroxyphenyl)-
3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8,9,10-decahydro-
acridine-1,8-dione (If). Compound If, 0.5 g, was
dissolved in a mixture of 10 ml of acetic and 1 ml of
concentrated hydrochloric acid, the solution was
cooled to 0°С, two drops of a saturated aqueous solu-
tion of sodium nitrite was added, and the mixture was
kept at 0°C for 2 h and evaporated under reduced pres-
sure, The residue was treated with 40 ml of water and
200 ml of ethyl acetate. The ethyl acetate solution was
dried over magnesium sulfate and evaporated to a vol-
ume of 7 ml, and the precipitate of 9-(4-hydroxy-
phenyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydro-
acridine-1,8-dione 10-oxide (VII) was filtered off.
Yield 0.35 g (71%), mp 296–298°С (from EtOH). IR
1
(4.56), 296 (3.72). Н NMR spectrum (СD2Сl2), δ,
ppm: 1.13 s (12H, Me), 2.53 s (4H, 2-H, 7-H), 3.14 s
(4H, 4-H, 5-H), 8.30 s (1Н, 9-Н). 13С NMR spectrum
(CD2Cl2), δC, ppm: 28.67 (Mе), 32.07 (С3, C6), 39.00
(С2, C7), 51.27 (С4, C5), 119.13 (С9), 128.36 (С8а, C9а),
10a
156.73 (C4a,
), 195.67 (С1, C8). Found, %: С 71.17;
Н 7.33; N 4.69. C17H21NO3. Calculated, %: C 71.08;
H 7.32; N 3.81.
b. A mixture of 0.68 g (2 mmol) of compound If in
28 g of 85% phosphoric acid was stirred for 1.5 h at
95°С. It was then cooled to room temperature and
diluted with 200 ml of water. After 15 h, solid impu-
rities were filtered off, the filtrate was neutralized with
solid sodium hydroxide to pH 7–8, and the precipitate
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 8 2008

PYRKO
1222
was filtered off, washed with water, dried in air, and
recrystallized from ethanol. Yield 0.52 g (82%).
10-Benzyl-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8,-
9,10-decahydroacridine-1,8-dione (XIIa). A mixture
of 2.80 g (20 mmol) of dimedone, 1.07 g (10 mmol) of
benzylamine, and 0.30 g of paraformaldehyde in 20 ml
of glacial acetic acid was heated for 50 min under
reflux. The solvent was distilled off, and the residue
was recrystallized from ethyl acetate. Yield 1.10 g
(30%), mp 198–200°С; published data [2]: mp 168–
170°С. IR spectrum, ν, cm–1: 1175, 1200, 1255, 1390,
1575, 1600 (С=С), 1635 (С=О), 2870, 2960 (СН). UV
spectrum (MеOH), λmax, nm (logε): 247 (4.12), 278
c. A mixture of 0.41 g (1 mmol) of compound Ie
and 10 ml of acetic acid was heated for 2 h under
reflux, the solution was evaporated, and the residue
was recrystallized from ethanol. Yield 0.22 g (77%).
d. A mixture of 0.82 g (2 mmol) of compound X
[12], 0.15 g (2.2 mmol) of hydroxylamine hydro-
chloride, and 0.18 g (2.2 mmol) of sodium acetate in
20 ml of acetic acid was heated for 1.5 h under reflux.
The solvent was distilled off, the residue was treated
with 100 ml of ethanol, the precipitate of sodium
chloride was filtered off, and the solution was evapo-
rated to a volume of 7 ml. Yield 0.52 g (91%).
1
(3.90), 390 (3.75). Н NMR spectrum (CDCl3), δ,
ppm: 0.98 s (12Н, Mе), 2.26 s (4Н, СН2), 2.30 s
(4Н, СН2), 3.18 s (1Н, 9-Н), 4.80 s (NCH2), 7.05–7.38
(5Н, Harom). Found, %: С 79.36; Н 7.95; N 3.80.
C24H29NO2. Calculated, %: C 79.30; H 8.04; N 3.85.
3,3,6,6-Tetramethyl-1,2,3,4,5,6,7,8-octahydroac-
ridine-1,8-dione dioxime (IIIj). A mixture of 0.41 g
(1 mmol) of compound X [12], 0.35 g (5 mmol) of
hydroxylamine hydrochloride, and 0.41 g (5 mmol) of
sodium acetate in 20 ml of acetic acid was heated for
2 h under reflux. The solvent was distilled off, the
residue was treated with 100 ml of ethanol, the precip-
itate of sodium chloride was filtered off, and the fil-
trate was evaporated to a volume of 5 ml. Yield 0.52 g
(91%), mp 278–280°С (from ЕtOH); published data
[1]: mp 280°С. IR spectrum, ν, cm–1: 1270, 1285, 1595
(С=С), 1640 (С=О), 2875, 2960 (СН), 3200–3300
(ОН). UV spectrum (ЕtOH), λmax, nm (logε): 253
9-(3,4-Dimethoxyphenyl)-10-[2-(3,4-dimethoxy-
phenyl)ethyl]-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8,-
9,10-decahydroacridine-1,8-dione (XIIb). A mixture
of 2.80 g (20 mmol) of dimedone and 1.81 g (10 mmol)
of 2-(3,4-dimethoxyphenyl)ethanamine in 20 ml of
gla-cial acetic acid was heated for 30 min under reflux,
1.66 g (10 mmol) of 3,4-dimethoxybenzaldehyde was
added, and the mixture was heated under reflux for
an additional 1.5 h. The solvent was distilled off, and
the residue was recrystallized from ethyl acetate. Yield
4.07 g (71%), mp 147–149°С (from EtOAc). IR spec-
trum, ν, cm–1: 1145, 1160, 1200, 1235, 1270, 1360,
1380, 1470, 1520, 1575 (С=С), 1635 (С=О), 2875,
2960 (СН). UV spectrum (EtOH), λmax, nm (logε): 231
1
(4.22), 317 (3.63). Н NMR spectrum (CF3CO2D), δ,
ppm: 1.22 s (12H, Me), 2.97 s (4H, 2-H, 7-H), 3.16 s
(4H, 4-H, 5-H), 9.31 (1Н, 9-Н). 13С NMR spectrum
(CF3CO2D), δC, ppm: 28.47 (Mе), 32.13 (С3, C6),
37.66 (С2, C7), 42.66 (С4, C5), 130.12 (С8а, C9а),
137.45 (С9), 153.74 (С4а, C10а), 156.72 (С1, C8).
Found, %: С 67.80; Н 7.59; N 13.86. C17H23N3O2. Cal-
culated, %: C 67.75; H 7.69; N 13.94.
1
(4.36), 253 (4.24), 277 (4.16), 378 (3.82). Н NMR
spectrum (CDCl3), δ, ppm: 0.98 s (6Н, Mе), 1.09 s
(6Н, Mе), 2.23 s (4Н, СН2), 2.41 and 2.48 (2Н each,
СН2 АВ system, JАВ = 17 Hz), 2.83 t (2H, СН2, J =
7 Hz), 3.79 s (3Н, ОMе), 3.80 s (3Н, ОMе), 3.84 s
(3Н, ОMе), 3.86 s (3Н, ОMе), 3.90 t (2Н, СН2, J =
7 Hz), 5.25 s (1Н, 9-Н), 6.63–6.66 m (2Н, Harom),
3,3,6,6-Tetramethyl-1,2,3,4,5,6,7,8-octahydro-
acridine-1,8-dione (XI). Zinc dust, 2.10 g, was dis-
persed in 10 ml of 10% hydrochloric acid, and the sus-
pension was intermittently shaken for several minutes.
The liquid part was separated by decanting, and the
remaining zinc material was washed with ethanol (2×
10 ml). A solution of 90 mg (0.33 mmol) of N-oxide
IХ in 20 ml of ethanol was added to the wet residue,
and the mixture was stirred for 7 h at room tempera-
ture. The precipitate was filtered off, the filtrate was
evaporated under reduced pressure, and the residue
was treated with 20 ml of water and 100 ml of chloro-
form. The chloroform extract was dried over magne-
sium sulfate and evaporated. Yield 95 mg (81%),
mp 145–147°С (from chloroform–hexane); published
data [10]: mp 144–145°С.
13
6.70–6.78 m (3Н, Harom), 7.00 s (1Н, Harom). C NMR
spectrum (CDCl3), δC, ppm: 27.72, 29.56 (Me); 31.13
(C9); 32.32 (C3, C6); 37.43 (C4, C5); 40.64, 46.28
(СН2); 49.88 (C2, C7); 55.77, 55.83, 55.93, 55.97
(ОMе); 110.71, 111.66, 111.79, 111.89 (Сarom); 115.40
(C8a, C9a); 118.89, 120.75, 129.58, 138.72, 148.30,
148.52, 149.30, 149.74; 162.19 (C4a, C10a); 195.70 (C1,
C8). Found, %: С 73.33; Н 7.49; N 2.51. C35H43NO6.
Calculated, %: C 73.27; H 7.56; N 2.44.
10-Benzyl-9-isopropyl-3,3-dimethyl-1,2,3,4,5,6,-
7,8,9,10-decahydroacridine-1,8-dione (XIIc). A mix-
ture of 687 mg (3 mmol) of 3-benzylamino-5,5-di-
methylcyclohex-2-en-1-one, 336 mg (3 mmol) of
cyclohexane-1,3-dione, and 259 mg (3.6 mmol) of
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SYNTHESIS AND TRANSFORMATIONS OF NEW 1,2,3,4,5,6,7,8,9,10-DECAHYDRO-...
1223
isobutyraldehyde in glacial acetic acid was heated for
1 h under reflux. The solvent was distilled off, and the
residue was recrystallized from ethyl acetate. Yield
690 mg (61%), mp 112–114°С (from EtOAc). IR spec-
trum, ν, cm–1: 1185, 1245, 1350, 1385, 1460, 1570
(С=С), 1645 (С=О), 2875, 2965 (СН). UV spectrum
(EtOH), λmax, nm (logε): 253 (4.24), 270 (4.12), 377
(С=С), 1625 (С=О), 2875, 2960 (СН), 3440 (OH). UV
spectrum (MeOH), λmax, nm (logε): 255 (4.26), 312
1
(4.39), 384 (3.93). Н NMR spectrum (CDCl3), δ,
ppm: 0.99 s (6Н, Mе), 1.07 s (6Н, Mе), 2.25 s (4Н,
2-H, 7-H), 2.40 and 2.72 (2Н, СН2, АВ system, JАВ
=
17 Hz), 3.46 t (2H, СН2, J = 5 Hz), 3.60 t (2Н, СН2,
J = 5 Hz), 5.20 s (1Н, 9-Н), 6.60–7.60 m (4Н, Harom),
9.54 s (ОН). Found, %: С 73.28; Н 7.69; N 3.51.
C25H31NO4. Calculated, %: C 73.32; H 7.63; N 3.42.
1
(3.79). Н NMR spectrum (CDCl3), δ, ppm: 0.74 d
(3Н, Mе, J = 7 Hz), 0.75 d (3Н, Mе, J = 7 Hz) 1.01 s
(3Н, Mе), 1.04 s (3Н, Mе), 1.52 m (1Н, СН), 1.90–
2.72 m (10Н, СН2), 4.19 s (1Н, 9-Н), 4.87 s (2Н,
СН2N), 6.80–7.20 m (5Н, Harom). 13C NMR spectrum
(CDCl3), δC, ppm: 19.46 (Mе); 21.52, 26.94 (СН2);
28.23, 28.99, 30.61 (Mе); 32.73 (C3, C6); 34.81 (C9);
36.89, 40.35, 49.16, 50.48 (CH2); 114.33, 114.68,
125.48 (Сarom); 127.88 (СНarom); 129.29 (CН); 137.32
(Сarom); 151.56, 153.72 (C4a, C10a); 196.50, 196.70 (C1,
C8). Found, %: С 79.60; Н 8.19; N 3.75. C25H31NO2.
Calculated, %: C 79.53; H 8.28; N 3.71.
9-(2-Hydroxyphenyl)-3,3,6,6-tetramethyl-10-
phenyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-
dione (XIIf) was synthesized in a similar way from
2.15 g (10 mmol) of 5,5-dimethyl-3-phenylamino-
cyclohex-2-en-1-one, 1.40 g (10 mmol) of dimedone,
and 1.34 g (11 mmol) of salicylaldehyde. Yield 3.31 g
(75%), mp 272–274°С. IR spectrum, ν, cm–1: 1230,
1372, 1390, 1600, 1625 (С=С), 1655 (С=О), 2875,
2960 (СН), 3160 (OH). UV spectrum (MeOH), λmax
nm (logε): 255 (4.26), 385 (3.93). Н NMR spectrum
(CDCl3), δ, ppm: 0.83 s (6Н, Mе), 0.95 s (6Н, Mе),
,
1
10-Benzyl-9-isopropyl-3,3,6,6-dimethyl-1,2,3,4,-
5,6,7,8,9,10-decahydroacridine-1,8-dione (XIId) was
synthesized in a similar way from 916 mg (4 mmol)
of 3-benzylamino-5,5-dimethylcyclohex-2-en-1-one,
560 mg (4 mmol) of dimedone, and 415 mg
(4.8 mmol) of isobutyraldehyde. Yield 1199 mg (74%),
mp 198–200°С (from EtOAc). IR spectrum, ν, cm–1:
1155, 1185, 1220, 1245, 1375, 1400, 1480, 1575 (С=С),
1645 (С=О), 2875, 2960 (СН). UV spectrum (EtOH),
λmax, nm (logε): 255 (4.40), 270 (4.11), 377 (3.86).
1Н NMR spectrum (CDCl3), δ, ppm: 0.75 d (6Н, Mе,
J = 7 Hz), 0.98 s (6Н, Mе), 1.03 s (6Н, Mе), 1.52 m
(1Н, СН), 2.24 d (2Н, 4-H, 5-H, J = 18 Hz), 2.49 d
(2Н, 4-H, 5-H, J = 18 Hz), 2.20 and 2.30 (2Н each,
2-H, 7-H, АВ system, JАВ = 18 Hz), 4.20 d (1Н, 9-Н,
J = 7 Hz), 4.84 s (2Н, СН2N), 7.16 d (2Н, Нarom, J =
1.90 and 2.18 (2Н each, 2-H, 7-H, АВ system, JАВ
17 Hz), 1.97 and 2.17 (2Н each, 4-H, 5-H, АВ system,
JАВ = 17 Hz), 5.32 s (1Н, 9-Н), 6.76–7.76 m (9Н,
=
Harom), 9.45 s (ОН). Found, %: С 78.88; Н 7.23; N 3.11.
C29H31NO3. Calculated, %: C 78.88; H 7.08; N 3.17.
9-(2-Hydroxyphenyl)-3,3,6,6-tetramethyl-
1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione
(XIIg) was synthesized in a similar way from 1.39 g
(10 mmol) of 3-amino-5,5-dimethylcyclohex-2-en-1-
one, 1.40 g (10 mmol) of dimedone, and 1.34 g
(11 mmol) of salicylaldehyde. Yield 2.96 g (86%),
mp 307–309°С (from EtOAc). IR spectrum, ν, cm–1:
1230, 1375, 1487, 1600, 1625 (С=С), 1650 (С=О),
2875, 2960 (СН), 3220, 3300 (OH). 1Н NMR spectrum
(CDCl3), δ, ppm: 1.00 s (6Н, Mе), 1.00 s (6Н, Mе),
2.07 m (4Н, 2-H, 7-H), 2.30 m (4Н, 4-H, 5-H), 5.16 s
(1Н, 9-Н), 6.70–7.10 m (3Н, Harom), 7.54 m (1Н, Harom).
Found, %: С 75.63; Н 7.37; N 3.91. C23H27NO3. Cal-
culated, %: C 75.59; H 7.45; N 3.83.
8 Hz), 7.34 t (1Н, Нarom, J = 8 Hz), 7.41 t (2Н, Нarom
,
J = 8 Hz). 13C NMR spectrum (CDCl3), δC, ppm:
19.44, 28.07, 28.87 (Me); 30.61 (СН); 32.40 (C3, C6);
34.75 (C9); 40.21, 49.03, 50.34 (CH2); 113.83 (Сarom);
125.40, 127.77, 129.11 (CНarom); 137.24 (Сarom);
151.90 (C4a, C10a); 196.31 (C1, C8). Found, %: С 79.89;
Н 8.78; N 3.49. C27H35NO2. Calculated, %: C 79.96;
H 8.70; N 3.45.
9-(3,4-Dimethoxyphenyl)-3,3,6,6-tetramethyl-10-
(2-phenylethyl)-1,2,3,4,5,6,7,8,9,10-decahydroacri-
dine-1,8-dione (XIIh) was synthesized in a similar
way from 2.43 g (10 mmol) of 5,5-dimethyl-3-(2-
phenylethylamino)cyclohex-2-en-1-one, 1.40 g
(10 mmol) of dimedone, and 1.81 g (11 mmol) of
3,4-dimethoxybenzaldehyde. Yield 3.94 g (77%),
mp 172–174°С (from EtOAc). IR spectrum, ν, cm–1:
1150, 1170, 1240, 1270, 1375, 1470, 1520, 1575 (С=С),
1640 (С=О), 2870, 2960 (СН). UV spectrum (MеOH),
10-(2-Hydroxyethyl)-9-(2-hydroxyphenyl)-
3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8,9,10-decahydro-
acridine-1,8-dione (XIIe) was synthesized in a similar
way from 1.83 g (10 mmol) of 3-(2-hydroxyethyl-
amino)-5,5-dimethylcyclohex-2-en-1-one, 1.40 g
(10 mmol) of dimedone, and 1.34 g (11 mmol) of
salicylaldehyde. Yield 3.11 g (76%), mp 209–211°С
(from EtOAc). IR spectrum, ν, cm–1: 1245, 1375, 1600
λ
max, nm (logε): 254 (4.30), 273 (4.18), 379 (3.91).
1Н NMR spectrum (CDCl3), δ, ppm: 0.96 s (6Н, Mе),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 8 2008

PYRKO
1224
5. Loev, B., Goodman, M.M., Snader, K.M., Tedechi, R.,
and Macko, E., J. Med. Chem., 1974, vol. 17, p. 956.
6. Shchekotikhin, Yu.M., Nikolaeva, T.G., Shub, G.M., and
Kriven’ko, A.P., Khim.-Farm. Zh., 2001, vol. 35, p. 29.
7. Shchekotikhin, Yu.M. and Nikolaeva, T.G., Khim. Gete-
rotsikl. Soedin., 2006, p. 32.
1.08 s (6Н, Mе), 2.22 s (4Н, 2-H, 7-H), 2.37 and 2.53
(2Н each, 4-H, 5-H, АВ system, JАВ = 17 Hz), 2.86 t
(2H, СН2, J = 7 Hz), 3.79 s and 3.83 s (3Н each,
ОMе), 3.90 t (2Н, NСН2, J = 7 Hz), 5.25 s (1Н, 9-Н),
6.68–7.40 m (8Н, Harom). Found, %: С 77.11; Н 7.58;
N 2.80. C33H39NO4. Calculated, %: C 77.16; H 7.65;
N 2.73.
8. Joule, J.A. and Smith, G.F., Heterocyclic Chemistry,
London: Van Nostrand Reinhold, 1972.
9-(2-Hydroxyphenyl)-3,3,6,6-tetramethyl-10-(2-
phenylethyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-
1,8-dione (XIIi). A mixture of 1.83 g (5 mmol) of
compound V, 1.21 g (10 mmol) of 2-phenylethan-
amine, and 5 mg of p-toluenesulfonic acid in 40 ml of
toluene was heated for 2 h under reflux. The solvent
was distilled off, and the residue was recrystallized
from ethyl acetate. Yield 1.83 g (78%), mp 216–218°С
(from EtOAc). IR spectrum, ν, cm–1: 1243, 1378, 1600,
1630 (С=С), 1652 (С=О), 2875, 2960 (СН), 3250
(ОН). UV spectrum (MеOH), λmax, nm (logε): 254
9. Paquette, L.A., Principles of Modern Heterocyclic
Chemistry, New York: W.A. Benjamin, 1968. Tran-
slated under the title Osnovy sovremennoi khimii getero-
tsiklicheskikh soedinenii, Moscow: Mir, 1971, p. 352.
10. Pyrko, A.N., Russ. J. Org. Chem., 2002, vol. 38,
p. 1817.
11. Dzvinchuk, I.B. and Tolmacheva, N.A., Khim. Getero-
tsikl. Soedin., 2001, p. 554.
12. Hegde, V., Hung, C., Madhukar, P., Cunningham, R.,
Hopfner, T., and Thummel, R.P., J. Am. Chem. Soc.,
1993, vol. 115, p. 872.
13. Freimanis, Ya.F., Khimiya enaminoketonov, enamino-
iminov, enaminotionov (Chemistry of Enamino Ketones,
Enamino Imines, and Enamino Thiones), Riga: Zinatne,
1974, p. 274.
14. Milliaresi, E.E., Ruchkin, V.E., Orlova, T.I., and Efre-
mov, V.V., Dokl. Akad. Nauk SSSR, 1972, vol. 205,
p. 353.
1
(4.28), 272 (4.04), 385 (3.78). Н NMR spectrum
(CDCl3), δ, ppm: 0.94 s (6Н, Mе), 1.08 s (6Н, Mе),
2.24 s (4Н, 2-H, 7-H), 2.46 and 2.54 (2Н each, 4-H,
5-H, АВ system, JАВ = 17 Hz), 2.96 t (2H, СН2, J =
7 Hz), 4.00 t (2Н, NСН2, J = 7 Hz), 5.18 s (1Н, 9-Н),
6.6–7.4 m (9Н, Harom). Found, %: С 79.21; Н 7.60;
N 2.89. C31H35NO3. Calculated, %: C 79.28; H 7.51;
N 2.98.
15. Bellamy, L.J., The Infra-red Spectra of Complex Mole-
cules, London: Methuen, 1958.
16. Gutsulyak, Kh.V., Manzhara, V.S., Mel’nik, M.V., and
Kalin, T.I., Zh. Prikl. Spektrosk., 2005, vol. 72, p. 454.
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