α-Thioureidoalkylation of functionally substituted ureas: II.* Synthesis of thio analogs of N-hydroxyalkyl-1,5-diphenylglycolurils

Article abstract of DOI:10.1134/S1070428011100216

Reactions of N-(hydroxyalkyl)ureas with 4,5-dihydroxy-4,5- diphenylimidazolidine-2-thiones gave previously unknown 4,6-dialkyl-1- hydroxyalkyl-3a,6a-diphenyl-5-thioxooctahydroimidazo[4,5-d]imidazol-2- ones which may be regarded as thio analogs of N-(hydro

Full text of DOI:10.1134/S1070428011100216

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 10, pp. 1572–1575. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © G.A. Gazieva, V.V. Baranov, A.N. Kravchenko, N.N. Makhova, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47,
No. 10, pp. 1543–1546.
α-Thioureidoalkylation of Functionally Substituted Ureas:
II.* Synthesis of Thio Analogs
of N-Hydroxyalkyl-1,5-diphenylglycolurils
G. A. Gazieva, V. V. Baranov, A. N. Kravchenko, and N. N. Makhova
Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Leninskii pr. 47, Moscow, 119991 Russia
e-mail: gaz@ioc.ac.ru
Received May 5, 2010
Abstract—Reactions of N-(hydroxyalkyl)ureas with 4,5-dihydroxy-4,5-diphenylimidazolidine-2-thiones gave
previously unknown 4,6-dialkyl-1-hydroxyalkyl-3a,6a-diphenyl-5-thioxooctahydroimidazo[4,5-d]imidazol-2-
ones which may be regarded as thio analogs of N-(hydroxyalkyl)glycolurils.
DOI: 10.1134/S1070428011100216
Replacement of oxygen atom in biologically active
compounds by sulfur is known to enhance or change
the kind of activity. For example, dithiopiracetam is
much more effective than piracetam as nootropic and
antihypoxic drug [2]. Substituted thiohydantoins
(2-thioxoimidazolidin-4-ones) are stronger inhibitors
of fatty acid amide hydrolase than the corresponding
oxygen derivatives [3].
Over several years we were interested in the chem-
istry of glycolurils (octahydroimidazo[4,5-d]imidaz-
ole-2.5-diones) [4–9] which constitute a new class of
neurotropic compounds [10–12]. Furthermore, it is
known that diphenylglycolurils containing alkyl sub-
stituents on the nitrogen atoms affect hepatic cyto-
chrome P-450-dependent monooxygenase system [13].
1,3-dialkyl-4,5-dihydroxy-4,5-diphenylimidazolidine-
2-thiones Ia and Ib as a method of synthesis of 1-hy-
droxyalkyl-3a,6a-diphenyl-5-thioxooctahydroimidazo-
[4,5-d]imidazol-2-ones III (thio analogs of N-hydroxy-
alkyldiphenylglycolurils). The reactions were carried
out in boiling methanol in the presence of hydrochloric
acid (reaction time 1–3 h; Scheme 1). The dependence
of the yield of compounds III on the reaction time and
amount of HCl was studied using the reaction of
imidazolidinethione Ia with N-(2-hydroxyethyl)urea as
model (see table).
It is seen that the yield of thioglycoluril IIIa
considerably increases as the amount of HCl rises from
0.2 to 0.5 mol per mole of Ia; further raising of the
amount of HCl to 1 mol almost does not affect the yield
of IIIa. Increase of the reaction time from 1 to 2–3 h
improves the yield of IIIa almost twofold. Taking into
account these results, compounds IIIa–IIIg were syn-
thesized using 1 mol of hydrogen chloride per mole of
We recently initiated a series of studies aimed at
synthesizing glycoluril thio analogs [1, 14]. In the
present communication we report on the reaction of
N-(hydroxyalkyl)ureas IIa–IIe (ureido alcohols) with
Scheme 1.
R1
R1
Ph
H
Ph
H
N
OH
OH
N
N
H2N
N
MeOH, HCl
R2
+
S
S
O
O
N
N
N
Ph
Ph
IIIa–IIIg
R1
R1
R2
Ia, Ib
IIa–IIe
I, R1 = Me (a), Et (b); II, R2 = HO(CH2)2 (a), HO(CH2)3 (b), MeCH(OH)CH2 (c), 4-HOC6H4(CH2)2 (d), HOCH2CH(Et) (e); III, R1 =
Me, R2 = HO(CH2)2 (a), HO(CH2)3 (b), MeCH(OH)CH2 (c), HOCH2CH(Et) (d); R1 = Et, R2 = HO(CH2)2 (e), 4-HOC6H4(CH2)2 (f),
MeCH(OH)CH2 (g).
* For communication I, see [1].
1572

α-THIOUREIDOALKYLATION OF FUNCTIONALLY SUBSTITUTED UREAS: II.
1573
Yields of thioglycoluril IIIa in the reaction of 4,5-dihydroxy-
1,3-dimethyl-4,5-diphenylimidazolidine-2-thione (Ia) with
N-(2-hydroxyethyl)urea (IIa)
Ia or Ib, the reaction time being 2 h; their yields
ranged from 59 to 90%.
1-(2-Hydroxypropyl)- and 1-(1-hydroxybutan-2-
yl)-4,6-dialkyl-3a,6a-diphenyl-5-thioxooctahydroimid-
azo[4,5-d]imidazol-2-ones IIIc, IIId, and IIIg whose
molecules contain three asymmetric carbon atoms were
formed as two diastereoisomers: (2′R*,3aS*,6aR*)-
and (2′R*,3aR*,6aS*)-4,6-dialkyl-1-(2-hydroxypro-
pyl)-3a,6a-diphenyl-5-thioxooctahydroimidazo[4,5-d]-
imidazol-2-ones IIIc and IIIg and (2′R*,3aS*,6aR*)-
and (2′R*,3aR*,6aS*)-1-(1-hydroxybutan-yl)-4,6-di-
methyl-3a,6a-diphenyl-5-thioxooctahydroimidazo-
[4,5-d]imidazol-2-one (IIId).
Time, h
HCl, mol
Yield, %
1
1
1
2
3
2
3
0.2
0.5
1.0
0.5
0.5
1.0
1.0
18
32
34
65
67
68
64
The NMR spectra of compounds IIIc and IIIg con-
tained double sets of signals from protons and carbon
atoms at a ratio of 1:1. By repeated recrystallizations
from methanol we isolated one diastereoisomer of IIIc
and IIIg. In the reaction of thione Ia with urea IIe, one
diastereoisomer of IIId (A) with a small impurity of
the other diastereoisomer separated first from the reac-
tion mixture, and then the second diastereoisomer (B)
containing some impurity of the first one separated.
Pure diastereoisomers of IIId were isolated in approxi-
mately equal amounts (31 and 28%) by recrystalliza-
tion of the crude products from methanol.
tetramethylsilane as internal reference. 1,3-Dialkyl-
4,5-dihydroxy-4,5-diphenylimidazolidine-2-thiones Ia
and Ib were synthesized by condensation of N,N′-di-
methyl- and N,N′-diethylureas with 1,2-diphenylethane-
1,2-dione according to the procedures reported in
[15, 16]. Alcohols IIa–IIe were prepared by reaction
of 2-aminoethanol, 3-aminopropan-1-ol, 1-aminopro-
pan-2-ol, 2-aminobutan-1-ol, and 4-(2-aminoethyl)-
phenol, respectively, with potassium cyanate [17].
4,6-Dialkyl-2-[hydroxyalkyl, 2-(4-hydroxyphe-
nyl)ethyl]-3a,6a-diphenyl-5-thioxooctahydroimid-
azo[4,5-d]imidazol-2-ones IIIa–IIIg (general proce-
dure). A mixture of 0.005 mol of compound Ia or Ib,
0.005 mol of urea IIa–IIe, 15 ml of methanol, and
0.42 ml (0.005 mol) of concentrated hydrochloric acid
was heated for 2 h under reflux. After cooling, the
precipitate was filtered off and recrystallized from
EXPERIMENTAL
The NMR spectra were recorded on Bruker AM-
250 (1H, 250 MHz) and Bruker AM-300 spectrometers
(13C, 75.5 MHz) from solutions in DMSO-d6 using
R
R
Me
Me
Ph
Ph
Ph
Ph
H
N
H
N
H
N
H
N
N
N
N
N
(S)
(R)
(S)
(R)
O
S
S
O
O
S
S
O
(R)
(S)
(R)
(S)
N
N
N
N
N
N
N
N
(R)
(S)
Ph
H
Ph
Ph
Ph
7
R
R
Me
Me
8
H
H
H
HO
OH
(R)
(S)
Et
Et
HO
OH
Me
Me
IIIc, IIIg
(3aS*,6aR*,8R*)-Racemate
IIId
(3aS*,6aR*,7R*)-Racemate
R
R
Me
Me
Ph
Ph
Ph
Ph
H
H
N
H
N
H
N
N
N
N
N
N
(S)
(R)
(S)
(R)
O
S
S
O
O
S
S
O
(R)
(S)
(R)
(S)
N
N
N
N
N
N
N
N
(S)
(R)
Ph
Ph
Ph
Ph
7
R
R
Me
Me
8
H
H
H
H
HO
OH
(S)
(R)
Et
Et
HO
OH
Me
Me
IIIc, IIIg
(3aS*,6aR*,8S*)-Racemate
IIId
(3aS*,6aR*,7S*)-Racemate
R = Me (c), Et (g).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 10 2011

GAZIEVA et al.
1574
2.94 s and 3.09 s (3H each, NMe), 3.38–3.47 m (1H,
NCH2), 3.97–4.08 m (1H, OCH), 4.77 d (1H, OH, J =
2.8 Hz), 6.77 br.s (4H, Harom), 7.12 br.s (6H, Harom),
8.87 s (1H, NH).
methanol. Individual stereoisomers of IIIc, IIId, and
IIIg (as racemates) were isolated by repeated crystal-
lization from methanol.
2-(2-Hydroxyethyl)-4,6-dimethyl-3a,6a-diphenyl-
(2′R*,3aS*,6aR*)- and (2′R*,3aR*,6aS*)-1-(1-
Hydroxybutan-2-yl)-4,6-dimethyl-3a,6a-diphenyl-
5-thioxooctahydroimidazo[4,5-d]imidazol-2-one
(IIId). Yield of diastereoisomer mixture 1.21 g (59%).
5-thioxooctahydroimidazo[4,5-d]imidazol-2-one
(IIIa). Yield 1.3 g (68%), mp 245–247°C. H NMR
spectrum, δ, ppm: 2.75–2.84 m (1H, NCH2), 2.92 s and
3.11 s (3H each, NMe), 3.42–3.64 m (3H, NCH2,
OCH2), 4.78 t (1H, OH, J = 5.1 Hz), 6.78 br.s (4H,
1
Diastereoisomer A. Yield 0.63 g (31%), mp 282–
284°C. 1H NMR spectrum, δ, ppm: 0.84 t (3H, Me, J =
7.4 Hz), 1.89–2.04 m and 2.14–2.28 m (1H each,
CH2), 2.75–2.83 m (1H, CH), 2.89 s and 3.18 s (3H
each, NMe), 2.56–3.61 m and 2.69–3.75 m (1H each,
OCH2), 4.76 t (1H, OH, J = 5.1 Hz), 6.87–6.96 m
(4H, Harom), 7.08–7.18 m (6H, Harom), 8.59 s (1H, NH).
13C NMR spectrum, δC, ppm: 12.8 (Me), 25.5 (CH2),
30.8 and 33.8 (NMe), 57.6 (CH), 63.2 (OCH2), 87.2
and 91.0 (C3a, C6a); 127.1, 128.0, 128.1, 128.2, 128.4,
128.6, 128.7, 133.1, 134.0 (Carom); 158.7 (C2), 183.0
(C5). Found, %: C 64.42; H 6.43; N 13.59; S 7.67.
C22H26N4O2S. Calculated, %: C 64.36; H 6.38;
N 13.65; S 7.81.
H
arom), 7.08–7.13 m (6H, Harom), 8.81 s (1H, NH).
13C NMR spectrum, δ, ppm: 30.7 and 32.6 (NMe),
44.8 (NCH2), 59.1 (OCH2), 86.7 and 90.9 (C3a, C6a);
127.1, 127.8, 128.1, 128.3, 128.8, 132.3, 133.7 (Carom);
158.9 (C2), 183.0 (C5). Found, %: C 62.77; H 5.89;
N 14.57; S 8.28. C20H22N4O2S. Calculated, %:
C 62.81; H 5.80; N 14.65; S 8.38.
2-(3-Hydroxypropyl)-4,6-dimethyl-3a,6a-di-
phenyl-5-thioxooctahydroimidazo[4,5-d]imidazol-
2-one (IIIb). Yield 1.23 g (62%), mp 272–274°C.
1H NMR spectrum, δ, ppm: 1.48–1.60 m (1H, CH2),
1.80–1.92 m (1H, CH2), 2.77–2.87 m (1H, NCH2),
2.93 s and 3.08 s (3H each, NMe), 3.34–3.50 m (3H,
NCH2, OCH2), 4.43 t (1H, OH, J = 5.3 Hz), 6.78 br.s
(4H, Harom), 7.10–7.14 m (6H, Harom), 8.71 s (1H, NH).
13C NMR spectrum, δC, ppm: 30.6 (CH2), 32.5 and
32.6 (NMe), 40.3 (NCH2), 58.3 (OCH2), 86.7 and 90.6
(C3a, C6a); 127.0, 128.1, 128.3, 128.7, 128.8, 129.2,
132.4, 133.6 (Carom), 158.7 (C2), 182.9 (C5). Found, %:
C 63.67; H 6.02; N 14.20; S 7.95. C21H24N4O2S. Cal-
culated, %: C 63.61; H 6.10; N 14.13; S 8.09.
Diastereoisomer B. Yield 0.58 g (28%), mp 212–
214°C. 1H NMR spectrum, δ, ppm: 0.86 t (3H, Me, J =
7.4 Hz), 1.43–1.59 m and 1.89–2.04 m (1H each,
CH2), 2.87–2.92 m (1H, CH), 2.92 s and 3.11 s (3H
each, NMe), 3.85–4.00 m (2H, OCH2), 4.96 t (1H, OH,
J = 4.5 Hz), 6.87–6.96 m (4H, Harom), 7.08–7.18 m
(6H, Harom), 8.68 s (1H, NH). 13C NMR spectrum, δC,
ppm: 10.8 (Me), 23.2 (CH2), 30.6 and 34.0 (NMe),
57.3 (CH), 62.2 (OCH2), 87.8 and 90.7 (C3a, C6a);
127.2, 128.0, 128.1, 128.2, 128.4, 128.7, 128.8, 130.5,
132.9, 133.6 (Carom); 159.1 (C2), 183.0 (C5). Found, %:
C 64.39; H 6.44; N 13.56; S 7.72. C22H26N4O2S. Cal-
culated, %: C 64.36; H 6.38; N 13.65; S 7.81.
(2′R*,3aS*,6aR*)- and (2′R*,3aR*,6aS*)-1-
(2-Hydroxypropyl)-4,6-dimethyl-3a,6a-diphenyl-5-
thioxooctahydroimidazo[4,5-d]imidazol-2-one (IIIc)
(mixture of diastereoisomers). Yield 1.61 g (81%),
mp 236–238°C. 13C NMR spectrum, δC, ppm: 21.0,
21.8 (Me); 30.5, 30.7, 32.8, 33.2 (NMe); 50.4, 50.6
(NCH2); 65.1, 65.4 (OCH); 86.7, 87.0, 91.1 (C3a, C6a);
126.9, 127.0, 128.0, 128.1, 128.3, 128.7, 128.8, 132.3,
133.6, 133.8 (Carom); 159.0, 159.7 (C2); 182.9, 183.0
(C5). Found, %: C 63.56; H 6.10; N 14.18; S 7.91.
C21H24N4O2S. Calculated, %: C 63.61; H 6.10;
N 14.13; S 8.09.
4,6-Diethyl-1-(2-hydroxyethyl)-3a,6a-diphenyl-
5-thioxooctahydroimidazo[4,5-d]imidazol-2-one
1
(IIIe). Yield 1.85 g (90%), mp 212–215°C. H NMR
spectrum, δ, ppm: 1.14 t and 1.32 t (3H each, Me, J =
6.6 Hz), 2.88–2.96 m (1H, NCH2), 3.03–3.12 m (2H,
NCH2), 3.37–3.56 m (4H, NCH2, OCH2), 3.71–3.79 m
(1H, OCH2), 4.78 t (1H, OH, J = 5.1 Hz), 6.74 m (4H,
13
1
H
arom), 7.15 m (6H, Harom), 8.67 s (1H, NH). C NMR
Diastereoisomer A. H NMR spectrum, δ, ppm:
spectrum, δC, ppm: 13.5, 14.4 (Me); 39.3, 40.4, 44.0
(NCH2); 59.1 (OCH2); 87.2, 91.7 (C3a, C6a); 127.3,
127.8, 128.0, 128.2, 128.9, 129.0, 132.4, 134.0 (Carom);
159.0 (C2); 182.8 (C5). Found, %: C 64.33; H 6.34;
N 13.66; S 7.74. C22H26N4O2S. Calculated, %:
C 64.36; H 6.38; N 13.65; S 7.81.
1.01 d (3H, Me, J = 6.2 Hz), 2.66 d.d (1H, NCH2, J =
14.2, 6.6 Hz), 2.93 s and 3.12 s (3H each, NMe), 3.38–
3.47 m (1H, NCH2), 3.77–3.87 m (1H, OCH), 4.76 d
(1H, OH, J = 3.7 Hz), 6.77 br.s (4H, Harom), 7.12 br.s
(6H, Harom), 8.76 s (1H, NH).
Diastereoisomer B. Yield 0.59 g (30%), mp 246–
1
4,6-Diethyl-1-[2-(4-hydroxyphenyl)ethyl]-3a,6a-
248°C. H NMR spectrum, δ, ppm: 1.01 d (3H, Me,
diphenyl-5-thioxooctahydroimidazo[4,5-d]imidazol-
J = 6.2 Hz), 2.72 d.d (1H, NCH2, J = 14.2, 5.1 Hz),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 10 2011

α-THIOUREIDOALKYLATION OF FUNCTIONALLY SUBSTITUTED UREAS: II.
1575
3. Muccioli, G.G., Fazio, N., Scriba, G.K.E., Poppitz, W.,
Cannata, F., Poupaert, J.H., Wouters, J., and
Lambert, D.M., J. Med. Chem., 2006, vol. 49, p. 417.
4. Kravchenko, A.N., Sigachev, A.S., Maksareva, E.Yu.,
Gazieva, G.A., Trunova, N.S., Lozhkin, B.V., Pivi-
na, T.S., Il’in, M.M., Lysenko, K.A., Nelyubina, Yu.V.,
Davankov, V.A., Lebedev, O.V., Makhova, N.N., and
Tartakovskii, V.A., Izv. Ross. Akad. Nauk, Ser. Khim.,
2005, p. 680.
5. Kravchenko, A.N., Lysenko, K.A., Chikunov, I.E.,
Belyakov, P.A., Il’in, M.M., Baranov, V.V., Nelyubi-
na, Yu.V., Davankov, V.A., Pivina, T.S., Makhova, N.N.,
and Antipin, M.Yu., Izv. Ross. Akad. Nauk, Ser. Khim.,
2009, p. 390.
6. Kravchenko, A.N., Sigachev, A.S., Belyakov, P.A.,
Il’in, M.M., Lysenko, K.A., Davankov, V.A., Lebe-
dev, O.V., Makhova, N.N., and Tartakovskii, V.A., Izv.
Ross. Akad. Nauk, Ser. Khim., 2009, p. 1229.
7. Gazieva, G.A., Lozhkin, P.V., Baranov, V.V., Nelyubi-
na, Yu.V., Kravchenko, A.N., and Makhova, N.N., Izv.
Ross. Akad. Nauk, Ser. Khim., 2009, p. 2408.
8. Gazieva, G.A., Lozhkin, P.V., Baranov, V.V., Kravchen-
ko, A.N., and Makhova, N.N., Izv. Ross. Akad. Nauk,
Ser. Khim., 2010, p. 628.
9. Gazieva, G.A., Baranov, V.V., and Kravchenko, A.N.,
Izv. Ross. Akad. Nauk, Ser. Khim., 2010, p. 1267.
10. Mashkovskii, M.D., Lekarstvennye sredstva (Drugs),
2-one (IIIf). Yield 2.06 g (85%), mp 133–135°C.
1H NMR spectrum, δ, ppm: 1.18 t and 1.34 t (3H each,
Me, J = 6.6 Hz), 2.63–2.72 m and 2.77–2.87 m (1H
each, CH2), 2.95–3.12 m (2H, NCH2), 3.36–3.63 m
(3H, NCH2), 3.73–3.83 m (1H, NCH2), 6.64 m (2H,
C6H4), 6.74 m (4H, Harom), 6.97 d (2H, C6H4, J =
8.1 Hz), 7.08–7.16 m (6H, Harom), 8.66 s (1H, NH),
9.20 s (1H, OH). Found, %: C 69.08; H 6.16; N 11.55;
S 6.51. C28H30N4O2S. Calculated, %: C 69.11; H 6.21;
N 11.51; S 6.59.
(2′R*,3aS*,6aR*)- and (2′R*,3aR*,6aS*)-4,6-Di-
ethyl-1-(2-hydroxypropyl)-3a,6a-diphenyl-5-thioxo-
octahydroimidazo[4,5-d]imidazol-2-one (IIIg) (mix-
ture of diastereoisomers). Yield 1.4 g (66%), mp 207–
209°C. Found, %: C 65.11; H 6.67; N 13.18; S 7.42.
C23H28N4O2S. Calculated, %: C 65.07; H 6.65;
N 13.20; S 7.55.
1
Diastereoisomer A. H NMR spectrum, δ, ppm:
1.04 d (3H, Me, J = 6.2 Hz), 1.17 t (3H, Me, J =
6.6 Hz), 1.33 t (3H, Me, J = 6.7 Hz), 2.79–2.85 m (1H,
CH2), 2.95–3.11 m (2H, CH2), 3.31–3.43 s (3H, CH2),
3.58–3.69 m (1H, CH2), 3.82–3.93 m (1H, CH2), 4.05–
4.13 m (1H, CH), 4.70 br.s (1H, OH), 6.63–6.88 m
(4H, Harom), 7.03–7.24 m (6H, Harom), 8.65 s (1H, NH).
13C NMR spectrum, δC, ppm: 13.6, 14.7, 21.5 (Me);
39.5, 40.6, 48.7 (NCH2); 65.8 (CH); 87.0, 92.2 (C3a,
C6a); 128.0, 128.2, 129.0, 132.0, 133.7 (Carom); 158.9
(C2); 182.7 (C5).
Moscow: Novaya Volna, 2005, 14th ed., vol. 1, p. 86.
11. Lebedev, O.V., Khmel’nitskii, L.I., Epishina, L.V., Su-
vorova, L.I., Zaikonnikova, I.V., Zimakova, I.E., Kir-
shin, S.V., Karpov, A.M., Chudnovskii, V.S., Povstya-
noi, M.V., and Eres’ko, V.A., Tselenapravlennyi poisk
novykh neirotropnykh preparatov (Purposeful Search for
New Neurotropic Agents), Riga: Zinatne, 1983, p. 81.
12. Vikharev, Yu.B., Anikina, L.V., Chikunov, I.E., Siga-
chev, A.S., Kravchenko, A.N., Shklyaev, Yu.V., and
Makhova, N.N., Vopr. Biol. Med. Farm. Khim., 2006,
no. 2, p. 12.
13. Bakibaev, A.A., Akhmedzhanov, R.R., Yagovkin, A.Yu.,
Novozheeva, T.P., Filimonov, V.D., and Saratikov, A.S.,
Khim.-Farm. Zh., 1993, vol. 27, no. 6, p. 29.
14. Gazieva, G.A., Nelyubina, Yu.V., Kravchenko, A.N.,
Sigachev, A.S., Glukhov, I.V., Struchkova, M.I., Lysen-
ko, K.A., and Makhova, N.N., Izv. Ross. Akad. Nauk,
Ser. Khim., 2009, p. 1884.
1
Diastereoisomer B. mp 237–239°C. H NMR spec-
trum, δ, ppm: 1.03 d (3H, Me, J = 6.2 Hz), 1.16 t (3H,
Me, J = 6.6 Hz), 1.33 t (3H, Me, J = 6.7 Hz), 2.79–
2.85 m (1H, CH2), 3.00–3.17 m (2H, CH2), 3.31–3.43 s
(3H, CH2), 3.51–3.58 m (1H, CH2), 3.74–3.81 m (1H,
CH2), 4.05–4.13 m (1H, CH), 4.72 br.s (1H, OH),
6.66–6.90 m (4H, Harom), 7.03–7.24 m (6H, Harom),
8.70 s (1H, NH). 13C NMR spectrum, δC, ppm: 13.6,
14.5, 21.2 (Me); 39.3, 40.9, 50.1 (NCH2); 65.0 (CH);
87.2, 92.4 (C3a, C6a); 128.1, 128.2, 129.0, 132.3, 133.9
(Carom); 159.7 (C2); 182.8 (C5).
This study was performed under financial support
by the Chemistry and Materials Science Department of
the Russian Academy of Sciences (basic research
program “Medicinal and Biomolecular Chemistry”).
15. Broan, C.J., Butler, A.R., Reed, D., and Sadler, I.H.,
J. Chem. Soc., Perkin Trans. 2, 1989, p. 731.
16. Baranov, V.V., Nelyubina, Yu.V., Lysenko, K.A., and
Kravchenko, A.N., Mendeleev Commun., 2009, vol. 19,
p. 211.
17. Kravchenko, A.N., Maksareva, E.Yu., Belyakov, P.A,
Sigachev, A.S., Chegaev, K.Yu., Lysenko, K.A., Lebe-
dev, O.V., and Makhova, N.N., Izv. Ross. Akad. Nauk,
Ser. Khim., 2003, p. 180.
REFERENCES
1. Baranov, V.V., Gazieva, G.A., Nelyubina, Yu.V., Krav-
chenko, A.N., and Makhova, N.N., Russ. J. Org. Chem.,
2011, vol. 47, p. 1564.
2. Granik, V.G., Lekarstva (Medicines), Moscow: Vuzov-
skaya Kniga, 2001, p. 150.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 10 2011