Condensation of pseudothiohydantoin with substituted isatins

Article abstract of DOI:10.1134/S1070363211090246

Pseudothiohydantoin ?⁵-mono(hydroxymethyl) derivatives were obtained by the reaction of unsubstituted pseudothiohydantoin with substituted isatins.

Full text of DOI:10.1134/S1070363211090246

ISSN 1070-3632, Russian Journal of General Chemistry, 2011, Vol. 81, No. 9, pp. 1886–1888. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © Sun Minyan, S.M. Ramsh, V.N. Plotkin, S.Yu. Solov’eva, 2011, published in Zhurnal Obshchei Khimii, 2011, Vol. 81, No. 9,
pp. 1549–1551.
Condensation of Pseudothiohydantoin
with Substituted Isatins
Sun Minyan, S. M. Ramsh, V. N. Plotkin, and S. Yu. Solov’eva
St. Petersburg State Technological Institute, Moskovskii pr. 26, St. Petersburg, 119013 Russia
e-mail: gsramsh@mail.wplus.net
Received February 24, 2011
Abstract—Pseudothiohydantoin С5-mono(hydroxymethyl) derivatives were obtained by the reaction of
unsubstituted pseudothiohydantoin with substituted isatins.
DOI: 10.1134/S1070363211090246
Typically, the reaction of pseudothiohydantoin I or
its derivatives with carbonyl compounds proceeds as a
crotonic condensation in the 5 position of the hetero-
cycle to form the products of 5-ylide nature [1, 2].
the reaction of pseudothiohydantoin I with the
substituted isatins IIa–IIj. The condensation was
carried out by the method described for the reaction of
isatin derivatives with CH-acids [3]. A mixture of
equimolar amounts of pseudothiohydantoin I and the
corresponding isatin IIa–IIj [4] in 1 ml of ethanol with
diethylamine as a catalyst was kept at room tempera-
ture for 1–10 days under stirring. The reaction com-
pletion was monitored by TLC. The resulting solid was
filtered off, washed on the filter 2–3 times with ethanol
and once with diethyl ether, and dried in a vacuum at
70–80°C. Typically, compounds IIIa–IIIj were ob-
tained in a pure form in high yields (Table 1). Their
O
O
H
N
N
R
O
HN
H2N
R
S
S
I
It was interesting to determine whether it is
possible to stop this process at the stage of the
formation of the aldol condensation product and to
obtain a C5-mono(hydroxymethyl)-substituted derivatives
of pseudothiohydantoin. For this purpose we examined
1
structures were established by H NMR spectroscopy
and confirmed by the mass spectrometry and elemental
analysis.
O
N
O
HO
O
R1
NH2
R1
HNEt2
S
O
N
+
O
H2N
N
N
S
R2
R2
I
IIIа−IIIj
IIа−IIj
а, R1 = R2 = H; b, R1 = CН3, R2 = Н; c, R1 = Н, R2 = СН3; d, R1 = Н, R2 = СН2С(О)NH2; e, R1 = Cl, R2 = СН2-1-naphthyl;
f, R1 = Н, R2 = СН2С(=СН2)СН3; g, R1 = OСН3, R2 = Н; h, R1 = СН2СН3, R2 =Н; i, R1 = Н, R2 = СН2СН=СНС6Н5; j, R1 =
Н, R2 = СН2СН2О-(2-СН3ОС6Н4).
1
Indeed, the characteristic feature of the H NMR
spectrum of the compounds IIIa–IIIj is a clear signal
of hydroxy proton of indole fragment at 6.5–7.1 ppm
and a singlet signal of CH-proton of thiazolidine
fragment at 4.8–5.0 ppm (Table 2).
The fact that the dehydration of the aldol condensa-
tion product III does not occur in the reaction can be
attributed to the considerable conjugation in the
dihydropyrrole ring of a hypothetical product of cro-
tonic condensation.
1886

CONDENSATION OF PSEUDOTHIOHYDANTOIN
Table 1. Yields and melting points of compounds IIIа–IIIj
1887
Comp. no.
R1
R2
Yield, %
mp, °С
Formula
H
H
95
90
89
91
86
89
95
80
83
91
139–145
175–182
162–168
188–192
155–160
152–158
154–161
164–172
124–130
123–128
C11H9N3O3S
C12H9N3O3S
C12H9N3O3S
C13H12N4O4S
IIIа
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IIIi
CН3
H
H
CН3
H
СН2С(О)NH2
СН2-1-naphthyl
СН2С(=СН2)СН3
H
Cl
H
C22H16ClN3O3S
C15H15N3O3S
C12H11N3O4S
C13H13N3O3S
C20H17N3O3S
C20H19N3O5S
ОСН3
СН2СН3
H
H
СН2СН=СНС6Н5
СН2СН2О-(2-СН3ОС6Н4)
H
IIIj
Table 2. The 1Н NMR (DMSO-d6) spectral data of compounds IIIа–IIIj (δ, ppm)
Comp.
N2'Н2
САrН, m
C3OH, 1Н, s C5'H, 1Н, s
C5R1
–
N1R2
no.
8.74 s (2Н)
6.67–7.44 m
(4H, С6Н4)
6.65–7.25 m
(3H, С6Н3)
6.55
6.47
6.61
6.78
4.80
4.78
4.83
4.97
10.34 s (1H, H)
10.22 s (1H, H)
3.12 s (3H, СН3)
IIIа
8.79 s (2Н)
2.22 s (3H, СН3)
IIIb
IIIc
IIId
8.78 s (1Н, NНА), 6.94–7.49 m
8.86 s (1H, NНВ) (4H, С6Н4)
–
–
hеm
9.03 s (2Н)
7.32–7.54 m
4.00 d [1H, СНАНВС(О)NH2, J
4.38 d [1H, СНАНВС(О)NH2, J
17.7 Hz],
17.7 Hz],
А В
hеm
А В
(4H, С6Н4)
7.31 s [1H, СН2С(О)NНАНВ], 7.41 s [1H,
СН2С(О)NНАНВ]
hе
8.93 s (2Н)
6.64–8.20 m
(10H, С6Н3,
С10Н7)
7.05
6.69
5.02
4.89
–
–
5.33 d (1H, СНАНВ-1-naphthyl, JА m 16.7 Hz),
IIIe
IIIf
В
hеm
5.37
d
(1H, СНАНВ-1-naphthyl,
J
А В
16.7 Hz)
8.81 s (1Н, NНА), 6.81–7.52 m
8.90 s (1H, NНВ) (4H, С6Н4)
1.78 s [3H, СН2С(=СН2)СН3], 4.15 d [1H,
hеm
СНАНВС(=СН2)СН3, J
16.7 Hz], 4.20 d
А В
hеm
[1H, СНАНВС(=СН2)СН3, J
16.7 Hz],
А В
4.86 s [1H, СН2С(=СНАНВ)СН3], 5.02 s
[1H, СН2С(=СНАНВ)СН3]
8.80 s (2Н)
6.67–7.07 m
6.56
6.48
4.77
4.76
3.66 s (3H, СН3O) 10.16 s (1H, H)
IIIg
IIIh
(3H, С6Н3)
8.74 s (1Н, NНА), 6.67–7.32 m
8.84 s (1H, NНВ) (3H, С6Н3)
1.14 t (3H, СН2СН3, 10.22 s (1H, H)
J 7.9 Hz), 2.52 q
(2H,
СН2СН3,
J 7.9 Hz)
hеm
8.81 s (1Н, NНА), 6.73–7.53 m
8.89 s (1H, NНВ) (9H, С6Н4,
С6Н5)
6.71
6.67
4.91
4.86
–
4.38 d.d (1H, СНАНВСН=СНС6Н5, J
А В
IIIi
IIIj
16.7, Jvic 4.9 Hz), 4.52 d.d (1H, СНАНВСН=
hеm
СНС6Н5, J
16.7, J vic 4.9 Hz), 6.26 d.t
А В
(1Н, J 15.8, J 5.4 Hz), 6.75 d (1Н, J 15.8 Hz)
3.76 s [3H, СН2СН2О-(2-СН3ОС6Н4)], 4.05
m [(2H, СНАНВСН2О-(2-СН3ОС6Н4)], 4.16
t [(2H, СН2СН2О-(2-СН3ОС6Н4, J 5.9 Hz]
8.79 s (1Н, NНА), 6.90–7.52 m
8.87 s (1H, NНВ) (8H, С6Н4,
С6Н4)
–
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 9 2011

1888
SUN MINYAN et al.
EXPERIMENTAL
139–145°C. IR spectrum (KBr), ν, cm-1: 3448 (N1H),
3298 (С5ОН), 3183 (N2'H), 3136 (N2'H), 1719 (C2=O),
1
1
1621 (C4=O), 1503 (C2=N3). Н NMR spectrum, δ,
The H NMR spectra were recorded on a Bruker
AM-400 spectrometer (400 MHz) in DMSO-d6. The
IR spectra were taken on a Shimadzu FTIR-8400S
spectrophotometer from KBr pellets. The elemental
analysis of compound IIIa was carried out on a Leco
CHNS(O) 942 analyzer. The TLC was performed on
Silufol UV-254 plates eluting with chloroform–ethanol
mixture (1:4). The mass spectra (ESI) were recorded
on a Bruker micrOTOF 10 223 mass spectrometer in
methanol–formic acid mixture.
ppm (J, Hz): 10.34 s (1Н, N1H), 8.74 br.s (2Н, N2'H2),
6.67–7.44 m (4Н, CArH), 6.55 br.s (1Н, C3OH), 4.80 s
(1Н, С5Н). Found, %: С 49.93; Н 3.46; N 15.88; S
12.12. C11H9N3O3S. Calculated, %: C 50.18; Н 3.45; N
15.96; S 12.18. Mass spectrum, m/z: 264.0436.
[C11H9N3O3S + H]+ (calculated 264.0437).
Compounds IIIb–IIIj were obtained similarly.
Their characteristics are shown in Tables 1 and 2.
3-(2-Amino-4-oxo-4,5-dihydro-1,3-thiazol-5-yl)-
3-hydroxy-1,3-dihydro-2H-indol-2-one (IIIa). To a
mixture of 0.491 g (4.23 mmol) of pseudothio-
hydantoin I and 0.620 g (4.21 mmol) of isatin IIa in
1 ml of ethanol was added 1 drop of diethylamine
under stirring. After 48 h the TLC analysis of the solid
white precipitate indicated the absence of the starting
compounds. The product was washed on the filter with
ethanol (2×1 ml) and diethyl ether (1×1 ml) and dried
at 70°C in a vacuum (10–15 mm Hg). Yield 95%, mp
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 9 2011