Reactions of 5-aryl-4-(hetaren-2-ylcarbonyl)-3-hydroxy-1-(1,3-thiazol-2-yl)-2,5-dihydro-1H-pyrrol-2-ones with hydrazine, phenylhydrazine, and hydroxylamine

Article abstract of DOI:10.1134/S1070428015010194

Three-component condensation of methyl 4-(furan-2-yl)- and 4-(thiophen-2-yl)-2,4-dioxobutanoates with aromatic aldehydes and 1,3-thiazol-2-amine afforded 5-aryl-4-(hetaren-2-ylcarbonyl)-3-hydroxy-1-(1,3-thiazol-2-yl)-2,5-dihydro-1H-pyrrol-2-ones. Reaction

Full text of DOI:10.1134/S1070428015010194

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 1, pp. 110–115. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © V.L. Gein, M.A. Mar’yasov, 2015, published in Zhurnal Organicheskoi Khimii, 2015, Vol. 51, No. 1, pp. 112–117.
Reactions of 5-Aryl-4-(hetaren-2-ylcarbonyl)-
3-hydroxy-1-(1,3-thiazol-2-yl)-2,5-dihydro-1H-pyrrol-2-ones
with Hydrazine, Phenylhydrazine, and Hydroxylamine
V. L. Gein and M. A. Mar’yasov
Perm State Pharmaceutical Academy, ul. Polevaya 2, Perm, 614990 Russia
e-mail: geinvl48@mail.ru
Received February 7, 2014
Abstract—Three-component condensation of methyl 4-(furan-2-yl)- and 4-(thiophen-2-yl)-2,4-dioxobutano-
ates with aromatic aldehydes and 1,3-thiazol-2-amine afforded 5-aryl-4-(hetaren-2-ylcarbonyl)-3-hydroxy-1-
(1,3-thiazol-2-yl)-2,5-dihydro-1H-pyrrol-2-ones. Reactions of the latter with hydrazine and phenylhydrazine
gave pyrrolo[3,4-c]pyrazol-6-ones and 3-phenylhydrazones, while the corresponding oximes were obtained in
reactions with hydroxylamine.
DOI: 10.1134/S1070428015010194
In continuation of our studies in the field of syn-
thesis and chemical behavior of 1,4,5-trisubstituted
pyrrolidine-2,3-diones [1], we set ourselves the task of
obtaining 3-hydroxy-2,5-dihydro-1H-pyrrol-2-ones
containing a 1,3-thiazol-2-yl substituent on the nitro-
gen atom and a 2-thenoyl or 2-furoyl substituent on C4.
These compounds attracted interest from the viewpoint
of their subsequent transformation into fused hetero-
cyclic systems via reactions with hydrazine, phenylhy-
drazine, and hydroxylamine.
time in acetic acid we synthesized 5-aryl-1-(1,3-thia-
zol-2-yl)-4-(thiophen-2-ylcarbonyl)pyrrolidine-2,3-di-
ones 1–4 and 4-(furan-2-ylcarbonyl)-1-(1,3-thiazol-2-
yl)pyrrolidine-2,3-diones 5–8, respectively (Scheme 1).
Compounds 1–8 are light yellow to yellow–brown
high-melting crystalline substances which are insol-
uble in water and soluble dioxane and glacial acetic
acid, as well as in ethanol on heating. High melting
points of the isolated compounds may be related to
their ability to form intermolecular hydrogen bonds in
crystal to give dimers [5].
By three-component condensation [2–4] of equi-
molar amounts of methyl 4-(furan-2-yl)- and 4-(thio-
phen-2-yl)-2,4-dioxobutanoates with aromatic alde-
hydes and 1,3-thiazol-2-amine on heating for a short
The IR spectra of 1–8 contained absorption bands
in the regions 1680–1690 (C=O, lactam), 1590–1620
(C=O, ketone), and 3200–3240 cm–1 (3-OH). Com-
Scheme 1.
O
O
OMe
X
O
S
O
S
+
RCHO +
R
NH
X
OMe
NH2
N
S
O
O
N
O
HO
R
O
N
O
O
O
–MeOH
N
N
S
R
X
X
N
1–8
1–4, X = S; 5–8, X = O; 1, 5, R = Ph; 2, 6, R = 2-ClC6H4; 3, 7, 4-(i-Pr)C6H4; 4, 8, R = 3-HOC6H4.
110

REACTIONS OF 5-ARYL-4-(HETAREN-2-YLCARBONYL)-3-HYDROXY-...
111
1
The reactions of 2 and 3 with phenylhydrazine gave
the corresponding 3-hydrazones 9 and 10, whereas
pyrrolo[3,4-c]pyrazole derivatives 11–23 were ob-
tained by reactions of 1 and 4–8 with hydrazine
hydrate and phenylhydrazine on heating in glacial
acetic acid (Scheme 2). Compounds 9 and 10 are
yellow crystalline substances soluble in DMF, DMSO,
glacial acetic acid, dioxane, and alcohols and insoluble
in water. The IR spectra of 9 and 10 contained absorp-
tion bands due to stretching vibrations of the lactam
(1670–1710 cm–1) and ketone carbonyl groups (1590–
1650 cm–1) and NH group (3240–3260 cm–1). In the
1H NMR spectra of these compounds we observed
signals from the NH proton (δ 11.82–11.84 ppm) and
two CH protons (δ 4.70–4.80 and 6.07–6.37 ppm),
which indicated their hydrazone structure. This struc-
ture is likely to be stabilized by intramolecular
hydrogen bond.
pounds 1–8 showed in the H NMR spectra
(DMSO-d6) signals from protons in the benzene rings
(δ 6.79–7.56 ppm), doublets from protons in the thia-
zole ring (δ 7.44–8.51 ppm), signals from protons in
the furan (thiophene) ring, and a singlet from the 5-H
proton at δ 6.02–6.40 ppm. No signal from the enolic
hydroxy proton was observed, presumably due to its
strong broadening as a result of exchange processes,
which is typical of structurally related compounds [5].
The mass spectra of 1–8 displayed the molecular and
fragment ion peaks which were consistent with the
assumed structure, in particular m/z 111 [C4H3SCO]+
and 127 [C4NSNHCO]+ for 1–4 and m/z 95
[C4H3OCO]+ and 127 [C4NSNHCO]+ for 5–8. All
compounds 1–8 showed a positive test (cherry color)
for enolic hydroxy group on treatment with an alco-
holic solution of iron(III) chloride. Thus, compounds
1–8 exist mainly as 5-aryl-4-(hetaren-2-ylcarbonyl)-3-
hydroxy-1-(1,3-thiazol-2-yl)-2,5-dihydro-1H-pyrrol-2-
one tautomers.
Ph
H
N
N
R'
H
We previously found that 4-aroyl-, 4-acetyl-, and
4-hetaroyl-3-hydroxy-2,5-dihydro-1H-pyrrol-2-ones
having various substituents on the nitrogen atom
(alkyl, hetaryl, or amino acid residue or hydrogen
atom) react with hydrazine hydrate and arylhydrazines
to produce 3,4,5-trisubstituted pyrrolo[3,4-c]pyrazol-
6-ones [1, 6].
H
Ar
O
N
R
Compounds 11–23 were isolated as light orange to
light brown crystalline substances soluble in DMF,
DMSO, glacial acetic acid, and dioxane, poorly soluble
in other organic solvents, and insoluble in water. They
displayed in the IR spectra absorption bands belonging
to stretching vibrations of the lactam carbonyl (1700–
1710 cm–1) and NH groups (3260–3280 cm–1). Signals
due to aromatic protons, including doublets from
protons in the thiazole ring (δ 7.68–8.17 ppm) and
a singlet from the 4-H proton (δ 6.47–6.94 ppm) were
observed in the 1H NMR spectra of 11–23. Compounds
Scheme 2.
NHPh
N
O
O
PhNHNH2
N
2, 3
S
S
1
N
11–17 characteristically showed in the H NMR
spectra a signal at δ 14.34–14.43 ppm (N2H).
R
Treatment of compounds 1–3 with hydroxylamine
led to the formation of the corresponding oximes 24–
26 (Scheme 3) which were isolated as colorless or light
yellow crystalline substances soluble in DMF, DMSO,
glacial acetic acid, dioxane, and ethanol, as well as
in propan-2-ol on heating, and insoluble in water.
Absorption bands typical of lactam carbonyl (1700–
1710 cm–1), ketone carbonyl (1610–1660 cm–1), and
OH group (3260–3280 cm–1) were present in the IR
9, 10
R'
N
N
O
R'NHNH2
N
S
1, 4–8
X
N
1
R
spectra of 24–26. In the H NMR spectra of 24–26,
11–23
aromatic protons resonated in the region δ 6.79–
7.54 ppm, signals from protons in the thiazole ring
appeared as doublets at δ 7.68–8.17 ppm, and the OH
proton gave a singlet at δ 8.73–8.85 ppm; also, two
11–14, 18, 19, X = S; 15–17, 20–23, X = O; 11, 18, 20,
R = H; 9, 12, 15, 21, R = 2-Cl; 14, 17, 19, 23, R = 3-HO;
10, 13, 16, 22, R = 4-i-Pr; 11–17, R′ = H; 18–23, R′ = Ph.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 1 2015

GEIN, MAR’YASOV
Compounds 2–8 were synthesized in a similar way.
112
Scheme 3.
OH
5-(2-Chlorophenyl)-3-hydroxy-1-(1,3-thiazol-2-
yl)-4-(thiophen-2-ylcarbonyl)-2,5-dihydro-1H-pyr-
rol-2-one (2). Yield 1.17 g (58%), yellow crystals,
mp 228–230°C (from glacial AcOH). IR spectrum, ν,
cm–1: 3200 (OH), 1680 (C2=O), 1590 (4-C=O).
1H NMR spectrum, δ, ppm: 6.30 s (1H, 5-H), 6.60–
7.40 m (7H, Harom), 7.98 d and 8.10 d (1H each, 4′-H,
5′-H, J = 4.85 Hz). Found, %: C 53.56; H 2.97; N 7.15;
S 15.74. C18H11ClN2O3S2. Calculated, %: C 53.66;
H 2.75; N 6.95; S 15.92.
N
O
N
O
NH2OH
N
1–3
S
S
R
24–26
24, R = H; 25, R = 2-Cl; 26, R = 4-i-Pr.
3-Hydroxy-5-(4-isopropylphenyl)-1-(1,3-thiazol-
2-yl)-4-(thiophen-2-ylcarbonyl)-2,5-dihydro-1H-
pyrrol-2-one (3). Yield 1.17 g (57%), light yellow
crystals, mp 236–238°C (from glacial AcOH). IR spec-
trum, ν, cm-1: 3220 (OH), 1690 (C2=O), 1620 (4-C=O).
1H NMR spectrum, δ, ppm: 1.09–1.11 d [6H,
CH(CH3)2], 2.74–2.80 m [1H, CH(CH3)2], 6.15 s
(1H, 5-H), 7.10–7.44 m (7H, Harom), 7.98 d and 8.09 d
(1H each, 4′-H, 5′-H, J = 4.85 Hz), 11.40–13.00 s (1H,
OH). Found, %: C 61.92; H 4.67; N 6.31; S 15.74.
C21H18N2O3S2. Calculated, %: C 61.44; H 4.42;
N 6.82; S 15.62.
symmetrical doublets belonging to 4-H and 5-H were
observed at δ 4.86–5.09 and 6.14–6.54 ppm with
a coupling constant J of 10 Hz. These findings
indicated predominantly oxime structure of 24–26,
which is likely to be stabilized by intramolecular
hydrogen bond.
N
R'
O
H
O
Ar
N
R
3-Hydroxy-5-(3-hydroxyphenyl)-1-(1,3-thiazol-
2-yl)-4-(thiophen-2-ylcarbonyl)-2,5-dihydro-1H-
pyrrol-2-one (4). Yield 0.92 g (48%), light brown
crystals, mp 220–222°C (from glacial AcOH). 1H NMR
spectrum, δ, ppm: 6.12 s (1H, 5-H), 6.54–7.44 m
(7H, Harom), 7.99 d and 8.02 d (1H each, 4′-H, 5′-H, J =
4.85 Hz), 9.30 s (1H, OH), 11.60–12.90 s (1H, OH).
Found, %: C 55.77; H 3.57; N 7.11; S 16.93.
C18H12N2O4S2. Calculated, %: C 56.24; H 3.15;
N 7.29; S 16.68.
EXPERIMENTAL
The IR spectra were recorded on a Specord M-80
spectrometer from samples dispersed in mineral oil.
The 1H NMR spectra were measured on a Bruker DRX
500 instrument at 500.13 MHz from solutions in
DMSO-d6 using tetramethylsilane as internal refer-
ence. The mass spectra (electron impact, 70 eV) were
obtained on a Finnigan MAT INCOS-50 mass spec-
trometer. The elemental compositions were determined
on a Perkin Elmer 2400 analyzer.
4-(Furan-2-ylcarbonyl)-3-hydroxy-5-phenyl-1-
(1,3-thiazol-2-yl)-2,5-dihydro-1H-pyrrol-2-one (5).
Yield 0.99 g (56%), brown crystals, mp 223–225°C
3-Hydroxy-5-phenyl-1-(1,3-thiazol-2-yl)-4-(thio-
phen-2-ylcarbonyl)-2,5-dihydro-1H-pyrrol-2-one
(1). A mixture of 1.06 g (5 mmol) of methyl 2,4-dioxo-
4-(thiophen-2-yl)butanoate, 0.74 g (0.91 mL,
5.5 mmol) of benzaldehyde, and 0.5 g (5 mmol) of
1,3-thiazol-2-amine in 10 mL of glacial acetic acid was
heated for 5–10 min under reflux. The mixture was
cooled, and the precipitate was filtered off. Yield
1.10 g (60%), light yellow crystals, mp 218–220°C
(from glacial AcOH). IR spectrum, ν, cm–1: 3240
(OH), 1690 (C2=O), 1620 (4-C=O). 1H NMR spectrum,
δ, ppm: 6.12 s (1H, 5-H), 7.10–7.30 m (8H, Harom),
7.87 d and 7.96 d (1H each, 4′-H, 5′-H, J = 4.8 Hz).
Found, %: C 59.01; H 3.14; N 7.51; S 17.32.
C18H12N2O3S2. Calculated, %: C 58.68; H 3.28;
N 7.60; S 17.41.
1
(from glacial AcOH). H NMR spectrum, δ, ppm:
6.15 s (1H, 5-H), 6.60–7.35 m (8H, Harom), 7.50 d and
7.90 d (1H each, 4′-H, 5′-H, J = 2.56 Hz). Found, %:
C 61.74; H 3.63; N 7.31; S 9.51. C18H12N2O4S. Calcu-
lated, %: C 61.36; H 3.43; N 7.95; S 9.10.
5-(2-Chlorophenyl)-4-(furan-2-ylcarbonyl)-3-
hydroxy-1-(1,3-thiazol-2-yl)-2,5-dihydro-1H-pyrrol-
2-one (6). Yield 1.20 g (62%), light brown crystals,
1
mp 223–225°C (from glacial AcOH). H NMR spec-
trum, δ, ppm: 6.32 s (1H, 5-H), 6.62–7.39 m (7H,
H
arom), 7.63 d and 7.98 d (1H each, 4′-H, 5′-H, J =
2.56 Hz), 11.80–12.20 s (1H, OH). Found, %: C 56.17;
H 2.70; N 7.10; S 7.98. C18H11ClN2O4S. Calculated,
%: C 55.89; H 2.87; N 7.24; S 8.29.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 1 2015

REACTIONS OF 5-ARYL-4-(HETAREN-2-YLCARBONYL)-3-HYDROXY-...
113
4-(Furan-2-ylcarbonyl)-3-hydroxy-5-(4-iso-
propylphenyl)-1-(1,3-thiazol-2-yl)-2,5-dihydro-1H-
pyrrol-2-one (7). Yield 1.09 g (55%), brown crystals,
mp 226–228°C (from glacial AcOH). 1H NMR spec-
trum, δ, ppm: 1.09–1.11 d [6H, CH(CH3)2], 2.74–
2.80 m [1H, CH(CH3)2], 6.20 s (1H, 5-H), 6.71–
7.45 m (7H, Harom), 7.61 d and 7.99 d (1H each, 4′-H,
5′-H, J = 2.56 Hz), 11.40–12.90 s (1H, OH). Found, %:
C 64.34; H 4.73; N 6.79; S 8.31. C21H18N2O4S. Calcu-
lated, %: C 63.95; H 4.60; N 7.10; S 8.13.
glacial acetic acid was heated for 2 h under reflux. The
mixture was cooled and the precipitate was filtered off.
Yield 0.88 g (75%), light yellow crystals, mp >280°C
(from glacial AcOH). IR spectrum, ν, cm–1: 3200
1
(NH), 1690 (C=O). H NMR spectrum, δ, ppm: 6.62 s
(1H, 5-H), 6.97–7.59 m (10H, Harom), 14.37 s (1H,
NH). Found, %: C 58.96; H 3.44; N 15.73; S 17.25.
C18H12N4OS2. Calculated, %: C 59.32; H 3.32;
N 15.37; S 17.60.
Compounds 12–17 were synthesized in a similar
way.
4-(Furan-2-ylcarbonyl)-3-hydroxy-5-(3-hydroxy-
phenyl)-1-(1,3-thiazol-2-yl)-2,5-dihydro-1H-pyrrol-
2-one (8). Yield 0.62 g (34%), brown crystals,
mp 224–226°C (from glacial AcOH). H NMR spec-
trum, δ, ppm: 6.15 s (1H, 5-H), 6.54–7.44 m (7H,
4-(2-Chlorophenyl)-5-(1,3-thiazol-2-yl)-3-(thio-
phen-2-yl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(2H)-
one (12). Yield 0.92 g (73%), light orange crystals,
mp >280°C (from glacial AcOH). IR spectrum, ν,
1
cm–1: 3240 (NH), 1720 (C=O). H NMR spectrum, δ,
1
H
arom), 7.54 d and 8.00 d (1H each, 4′-H, 5′-H, J =
2.56 Hz), 9.34 s (1H, OH), 11.50–12.70 s (1H, OH).
Found, %: C 58.27; H 3.49; N 7.31; S 8.92.
C18H12N2O5S. Calculated, %: C 58.69; H 3.28;
N 7.60; S 8.70.
ppm: 6.94 s (1H, 5-H), 6.94–7.62 m (9H, Harom),
14.40 s (1H, NH). Found, %: C 54.63; H 3.01;
N 14.58; S 16.59. C18H11ClN4OS2. Calculated, %:
C 54.20; H 2.78; N 14.05; S 16.08.
5-(2-Chlorophenyl)-3-(2-phenylhydrazinyli-
dene)-1-(1,3-thiazol-2-yl)-4-(thiophen-2-ylcarbonyl)-
pyrrolidin-2-one (9). A mixture of 1.21 g (3 mmol) of
compound 2 and 0.5 mL (5 mmol) of phenylhydrazine
in 10 mL of glacial acetic acid was heated for 3 h
under reflux. The mixture was cooled, and the precip-
itate was filtered off. Yield 0.69 g (47%), light yellow
crystals, mp 201–203°C (from glacial AcOH). IR
spectrum, ν, cm–1: 3240 (NH), 1670 (C2=O), 1590
(4-C=O). 1H NMR spectrum, δ, ppm: 4.80 d (1H, 4-H,
J = 5.02 Hz), 6.37 d (1H, 5-H, J = 5.02 Hz), 6.85–
8.24 m (14H, Harom), 11.82 s (1H, NH). Found, %:
C 58.27; H 3.65; N 11.58; S 13.49. C24H17ClN4O2S2.
Calculated, %: C 58.47; H 3.48; N 11.36; S 13.01.
4-(4-Isopropylphenyl)-5-(1,3-thiazol-2-yl)-
3-(thiophen-2-yl)-4,5-dihydropyrrolo[3,4-c]pyrazol-
6(2H)-one (13). Yield 0.85 g (70%), yellow–orange
crystals, mp >280°C (from glacial AcOH). IR spec-
1
trum, ν, cm–1: 1650 (C=O), 3150 (NH). H NMR
spectrum, δ, ppm: 1.11–1.13 d [6H, CH(CH3)2], 2.78–
2.84 m [1H, CH(CH3)2], 6.59 s (1H, 5-H), 6.59–
7.61 m (9H, Harom), 14.36 s (1H, NH). Found, %:
C 61.73; H 4.61; N 13.49; S 16.02. C21H18N4OS2. Cal-
culated, %: C 62.05; H 4.46; N 13.78; S 15.77.
4-(3-Hydroxyphenyl)-5-(1,3-thiazol-2-yl)-3-(thio-
phen-2-yl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(2H)-
one (14). Yield 0.75 g (61%), light orange crystals,
1
mp >280°C (from glacial AcOH). H NMR spectrum,
δ, ppm: 6.53 s (1H, 5-H), 6.53–7.63 m (9H, Harom),
9.35 s (1H, OH), 14.35 s (1H, NH). Found, %:
C 56.33; H 3.41; N 14.50; S 17.05. C18H12N4O2S2. Cal-
culated, %: C 56.83; H 3.18; N 14.73; S 16.86.
5-(4-Isopropylphenyl)-3-(2-phenylhydrazinyli-
dene)-1-(1,3-thiazol-2-yl)-4-(thiophen-2-ylcarbonyl)-
pyrrolidin-2-one (10) was synthesized in a similar
way from compound 3. Yield 0.71 g (47%), yellow–
orange crystals, mp 206–208°C (from glacial AcOH).
IR spectrum, ν, cm–1: 1650 (4-C=O), 1710 (C2=O),
4-(2-Chlorophenyl)-3-(furan-2-yl)-5-(1,3-thiazol-
2-yl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(2H)-one
(15). Yield 0.69 g (57%), light brown crystals,
1
3260 (NH). H NMR spectrum, δ, ppm: 1.14–1.21 d
1
[6H, CH(CH3)2], 2.76–2.83 m [1H, CH(CH3)2], 4.70 d
(1H, 4-H, J = 5.02 Hz), 6.07 d (1H, 5-H, J = 5.02 Hz),
6.85–8.13 m (14H, Harom), 11.84 s (1H, NH). Found,
%: C 64.37; H 4.52; N 11.58; S 13.25. C27H24N4O2S2.
Calculated, %: C 64.78; H 4.83; N 11.19; S 12.81.
mp 259–261°C (from glacial AcOH). H NMR spec-
trum, δ, ppm: 6.57 s (1H, 5-H), 6.57–7.72 m (9H,
H
arom), 14.43 s (1H, NH). Found, %: C 56.30; H 3.12;
N 14.38; S 8.51. C18H11ClN4O2S. Calculated, %:
C 56.47; H 2.90; N 14.63; S 8.38.
4-Phenyl-5-(1,3-thiazol-2-yl)-3-(thiophen-2-yl)-
4,5-dihydropyrrolo[3,4-c]pyrazol-6(2H)-one (11).
A mixture of 1.1 g (3 mmol) of compound 1 and
0.2 mL (4.1 mmol) of hydrazine hydrate in 10 mL of
3-(Furan-2-yl)-4-(4-isopropylphenyl)-5-(1,3-thia-
zol-2-yl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(2H)-
one (16). Yield 0.41 g (35%), light gray crystals,
mp 241–243°C (from glacial AcOH). IR spectrum, ν,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 1 2015

GEIN, MAR’YASOV
114
1
cm–1: 3150 (NH), 1650 (C=O). H NMR spectrum, δ,
ppm: 1.11–1.13 d [6H, CH(CH3)2], 2.77–2.83 m [1H,
CH(CH3)2], 6.54 s (1H, 5-H), 6.54–7.77 m (9H, Harom),
14.39 s (1H, NH). Found, %: C 64.82; H 4.75;
N 14.13; S 7.99. C21H18N4O2S. Calculated, %:
C 64.60; H 4.65; N 14.35; S 8.21.
C24H15ClN4O2S. Calculated, %: C 62.81; H 3.29;
N 12.21; S 6.99.
3-(Furan-2-yl)-4-(4-isopropylphenyl)-2-phenyl-5-
(1,3-thiazol-2-yl)-4,5-dihydropyrrolo[3,4-c]pyrazol-
6(2H)-one (22). Yield 0.37 g (26%), light yellow
crystals, mp 237–239°C (from glacial AcOH). 1H NMR
spectrum, δ, ppm: 1.12–1.14 d [6H, CH(CH3)2], 2.76–
2.83 m [1H, CH(CH3)2], 6.66 s (1H, 5-H), 6.54–
8.25 m (14H, Harom). Found, %: C 69.85; H 4.60;
N 12.34; S 7.01. C27H22N4O2S. Calculated, %:
C 69.51; H 4.75; N 12.01; S 6.87.
3-(Furan-2-yl)-4-(3-hydroxyphenyl)-5-(1,3-thia-
zol-2-yl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(2H)-
one (17). Yield 0.52 g (45%), light orange crystals,
mp 273–275°C (from glacial AcOH). H NMR spec-
trum, δ, ppm: 6.55 s (1H, 5-H), 6.55–7.78 m (9H,
1
H
arom), 9.35 s (1H, OH), 14.40 s (1H, NH). Found, %:
3-(Furan-2-yl)-4-(3-hydroxyphenyl)-2-phenyl-5-
(1,3-thiazol-2-yl)-4,5-dihydropyrrolo[3,4-c]pyrazol-
6(2H)-one (23). Yield 0.33 g (25%), light yellow crys-
tals, mp 266–268°C (from glacial AcOH). H NMR
spectrum, δ, ppm: 6.56 s (1H, 5-H), 6.56–8.25 m (14H,
C 59.51; H 3.48; N 15.11; S 8.60. C18H12N4O3S. Cal-
culated, %: C 59.33; H 3.32; N 15.38; S 8.80.
1
2,4-Diphenyl-5-(1,3-thiazol-2-yl)-3-(thiophen-
2-yl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(2H)-one
(18). A mixture of 1.1 g (3 mmol) of compound 1 and
0.5 mL (5 mmol) of phenylhydrazine in 10 mL of
glacial acetic acid was heated for 3 h under reflux. The
mixture was cooled, and the precipitate was filtered
off. Yield 0.40 g (30%), light yellow crystals, mp 277–
279°C (from glacial AcOH). IR spectrum: ν 1720 cm–1
Harom), 9.38 s (1H, OH). Found, %: C 65.67; H 3.81;
N 12.39; S 6.97. C24H16N4O3S. Calculated, %:
C 65.44; H 3.66; N 12.72; S 7.28.
3-Hydroxyimino-5-phenyl-1-(1,3-thiazol-2-yl)-
4-(thiophen-2-ylcarbonyl)pyrrolidine-2-one (24).
A mixture of 1.1 g (3 mmol) of compound 1 and 0.12 g
(3.6 mmol) of hydroxylamine in 10 mL of ethanol–
glacial acetic acid (1:1) was heated for 3 h under
reflux and was then left to stand for 24 h at room
temperature. The resinous material was ground with
ethanol, and the precipitate was filtered off. Yield
0.24 g (21%), light yellow crystals, mp 217–219°C
(from EtOH). IR spectrum, ν, cm–1: 3260 (OH), 1700
1
(C=O). H NMR spectrum, δ, ppm: 6.75 s (1H, 5-H),
7.01–8.24 m (15H, Harom). Found, %: C 65.75; H 3.91;
N 12.33; S 14.12. C24H16N4OS2. Calculated, %:
C 65.43; H 3.66; N 12.72; S 14.56.
Compounds 19–23 were synthesized in a similar
way.
4-(3-Hydroxyphenyl)-2-phenyl-5-(1,3-thiazol-2-
yl)-3-(thiophen-2-yl)-4,5-dihydropyrrolo[3,4-c]pyr-
azol-6(2H)-one (19). Yield 0.51 g (37%), light yellow
crystals, mp 257–259°C (from glacial AcOH). 1H NMR
spectrum, δ, ppm: 6.47 s (1H, 5-H), 6.58–8.16 m (14H,
1
(C2=O), 1660 (4-C=O). H NMR spectrum, δ, ppm:
4.86–4.89 d (1H, 4-H, J = 10 Hz), 6.20–6.23 d (1H,
5-H, J = 10 Hz), 6.92–8.17 m (10H, Harom), 8.76 s (1H,
OH). Found, %: C 56.65; H 3.53; N 10.57; S 16.61.
C18H13N3O3S2. Calculated, %: C 56.38; H 3.42;
N 10.96; S 16.72.
Harom), 9.36 s (1H, OH). Found, %: C 63.51; H 3.86;
N 12.01; S 13.82. C24H16N4O2S2. Calculated, %:
C 63.14; H 3.53; N 12.27; S 14.05.
Compounds 25 and 26 were synthesized in a sim-
ilar way.
3-(Furan-2-yl)-2,4-diphenyl-5-(1,3-thiazol-2-yl)-
4,5-dihydropyrrolo[3,4-c]pyrazol-6(2H)-one (20).
Yield 0.45 g (35%), light yellow crystals, mp 245–
5-(2-Chlorophenyl)-3-hydroxyimino-1-(1,3-thia-
zol-2-yl)-4-(thiophen-2-ylcarbonyl)pyrrolidin-2-one
(25). Yield 0.25 g (20%), white crystals, mp 194–
196°C (from EtOH). IR spectrum, ν, cm–1: 3280 (OH),
1
247°C (from glacial AcOH). H NMR spectrum, δ,
ppm: 6.69 s (1H, 5-H), 6.53–8.26 m (15H, Harom).
Found, %: C 67.49; H 3.57; N 13.39; S 7.91.
C24H16N4O2S. Calculated, %: C 67.91; H 3.80;
N 13.20; S 7.55.
1710 (C2=O), 1610 (4-C=O). H NMR spectrum, δ,
1
ppm: 5.07–5.09 d (1H, 4-H, J = 10 Hz), 6.51–6.54 d
(1H, 5-H, J = 10 Hz), 6.81–7.92 m (9H, Harom), 8.85 s
(1H, OH). Found, %: C 52.01; H 3.12; N 9.85;
S 15.10. C18H12ClN3O3S2. Calculated, %: C 51.74;
H 2.89; N 10.06; S 15.35.
4-(2-Chlorophenyl)-3-(furan-2-yl)-2-phenyl-5-
(1,3-thiazol-2-yl)-4,5-dihydropyrrolo[3,4-c]pyrazol-
6(2H)-one (21). Yield 0.26 g (18.8%), light yellow
crystals, mp 252–254°C (from glacial AcOH). 1H NMR
spectrum, δ, ppm: 6.55 s (1H, 5-H), 6.61–8.25 m (14H,
3-Hydroxyimino-5-(4-isopropylphenyl)-1-
(1,3-thiazol-2-yl)-4-(thiophen-2-ylcarbonyl)pyrrol-
idin-2-one (26). Yield 0.45 g (35%), light yellow
Harom). Found, %: C 63.13; H 3.49; N 12.01; S 6.62.
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1
2. Gein, V.L., Gein, L.F., Porseva, N.Yu., Voronina, E.V.,
Vakhrin, M.I., Potemkin, K.D., Kolla, V.E., Drovoseko-
va, L.P., Milyutin, A.V., Shchuklina, N.S., and Veikh-
man, G.A., Pharm. Chem. J., 1998, vol. 32, no. 9, p. 477.
crystals, mp 195–197°C (from EtOH). H NMR spec-
trum, δ, ppm: 1.10–1.12 d [6H, CH(CH3)2], 2.64–
2.80 m [1H, CH(CH3)2], 4.86–4.88 d (1H, 4-H, J =
10 Hz), 6.14–6.16 d (1H, 5-H, J = 10 Hz), 6.79–8.17 m
(9H, Harom), 8.73 s (1H, OH). Found, %: C 59.51;
H 4.68; N 9.69; S 14.85. C21H19N3O3S2. Calculated, %:
C 59.28; H 4.50; N 9.87; S 15.07.
3. Silina, T.A., Pulina, N.A., Gein, L.F., and Gein, V.L.,
Chem. Heterocycl. Compd., 1998, vol. 34, no. 6, p. 739.
4. Gein, V.L., Yushkov, V.V., Silina, T.A., Gein, L.F.,
Yatsenko, K.V., and Shevtsova, V.G., Pharm. Chem. J.,
2008, vol. 42, no. 5, p. 255.
REFERENCES
5. Andreichikov, Yu.S., Gein, V.L., and Anikina, I.N.,
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1. Mar’yasov, M.A. and Gein, V.L., Tetragidropirrol-2,3-
diony (Tetrahydropyrrole-2,3-diones): Perm: Perm. Gos.
Farm. Akad., 2013, p. 155.
6. Southwick, P.I., Previc, E.P., Casanova, L., and Carl-
son, E.H., J. Org. Chem., 1956, vol. 21, p. 1087.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 1 2015