Reaction of 1,5-diaryl-3-hydroxy-4-methylsulfonyl-3-pyrrolin-2-ones with urea, hydrazine, ethylenediamine, and o-phenylenediamine

Article abstract of DOI:10.1007/s10593-007-0214-7

With urea 1,5-diaryl-3-hydroxy-4-methylsulfonyl-3-pyrrolin-2-ones form the 3-amino derivatives of pyrrolones. In reactions with hydrazine hydrate and ethylenediamine the corresponding salts are formed. With ethylenediamine at 180-185°C the double salt of 3-hydroxy-4-methylsulfonyl-1,5-diphenyl-3- pyrrolin-2-one forms N,N′-di(4-methylsulfonyl-1,5-diphenyl-3-pyrrolin-2- on-3-yl)-ethylenediamine. The reaction with o-phenylenediamine gives 2,3-diaryl-4-methylsulfonylpyrrolo-[2,3-b]quinoxalines.

Full text of DOI:10.1007/s10593-007-0214-7

Chemistry of Heterocyclic Compounds, Vol. 43, No. 11, 2007
REACTION OF 1,5-DIARYL-
3-HYDROXY-4-METHYLSULFONYL-
3-PYRROLIN-2-ONES WITH UREA,
HYDRAZINE, ETHYLENEDIAMINE,
AND o-PHENYLENEDIAMINE
V. L. Gein, A. V. Kataeva, and L. F. Gein
With urea 1,5-diaryl-3-hydroxy-4-methylsulfonyl-3-pyrrolin-2-ones form the 3-amino derivatives of
pyrrolones. In reactions with hydrazine hydrate and ethylenediamine the corresponding salts are
formed. With ethylenediamine at 180-185°C the double salt of 3-hydroxy-4-methylsulfonyl-1,5-diphenyl-
3-pyrrolin-2-one forms N,N′-di(4-methylsulfonyl-1,5-diphenyl-3-pyrrolin-2-on-3-yl)-ethylenediamine.
The reaction with o-phenylenediamine gives 2,3-diaryl-4-methylsulfonylpyrrolo-[2,3-b]quinoxalines.
Keywords: 3-amino-1,5-diaryl-4-methylsulfonyl-3-pyrrolin-2-ones, 2,3-diaryl-4-methylsulfonylpyrrolo-
[2,3-b]quinoxalines, binucleophilic reagents.
Earlier it was established that the reaction of ethyl ester of methylsulfonylpyruvic acid or its sodium salt
with a mixture of aromatic aldehyde and arylamine leads to the formation of 1,5-diaryl-3-hydroxy-4-
methylsulfonyl-3-pyrrolin-2-ones [1], fusion of which with o-phenylenediamine gives 2,3-diaryl-4-
methylsulfonylpyrrolo-[2,3-b]quinoxalines [2].
While continuing research into the properties of 1,5-diaryl-3-hydroxy-4-methylsulfonyl-3-pyrrolin-
2-ones in relation to binucleophilic reagents we studied their reaction with urea, hydrazine hydrate,
ethylenediamine, and o-phenylenediamine.
It was established that the reaction of 1,5-diaryl-3-hydroxy-4-methylsulfonyl-3-pyrrolin-2-ones with
urea at 170-180°C leads to the formation of 3-amino-1,5-diaryl-4-methylsulfonyl-3-pyrrolin-2-ones 1a-f.
The obtained compounds 1a-f (Table 1) are pinkish crystalline substances insoluble in water and soluble
in DMSO and DMF.
The formation of compounds 1a-f is probably explained by the fact that the urea decomposes to
ammonia under the reaction conditions and acts as an aminating reagent [3].
In addition to the absorption bands of the sulfonyl and lactam groups, the IR spectra of compounds 1a-f
(Table 2) contain absorption bands for the stretching vibrations of the amino group at 3252-3490 cm−1.
1
In the H NMR spectra of compounds 1a-f (Table 3) there is a signal for the two protons of the amino
group at 6.51-6.60 ppm and a characteristic signal for the methine proton at position 5 of the heterocycle at 5.85-
6.09 ppm.
__________________________________________________________________________________________
Perm State Pharmaceutical Academy, Perm 614990, Russia; e-mail: perm@pfa.ru, e-mail:
gein@permonline.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, 1631-1636, November,
2007. Original article submitted October 9, 2006.
0009-3122/07/4311-1385©2007 Springer Science+Business Media, Inc.
1385

OH
MeSO2
Ar1
MeSO2
Ar1
NH2
O
CO(NH2)2
O
N
N
Ar2
Ar2
1a–f
H2N(CH2)2NH2
H2N–NH2
.
OH H2N NH2
MeSO2
Ph
.
MeSO2
H2NCH2
OH
O
Ph
O
N
N
Ar2
Ar 2
2
2a,b
3a,b
H2N
H
MeSO2
Ph
Ar2
MeSO2
Ph
N
CH2
N
H2N
O
N
N
Ph
4
N
2
5a–d
1a,b,d,f Ar1 = Ph, c Ar1 = 4-MeOC6H4, e Ar1 = 4-BrC6H4; 1a,c, 2a,3a Ar2 = Ph; 1b, 5b Ar2 = 4-ClС6H4;
1d Ar2 = 4-FС6H4; 1e Ar2 = 4-BrС6H4; 1f, 2b,3b, 5a Ar2 = 4-HOС6H4; 5c Ar2 = 4-Н2NSO2С6Н4; 5d Ar2 = СН2Ph
Thus, the spectral data indicate that compounds 1a-f exist in the enamine form.
The basicity of the amino group in compounds 1a-f is quite strongly reduced as a result, probably, of
conjugation of the electron pair of the nitrogen atom with the double bond and the strong electron-withdrawing
effect of the sulfonyl substituent at position 4 of the heterocycle. This is demonstrated by the fact that it was not
possible to obtain the corresponding Schiff base during investigation of the reaction of 3-amino-
4-methylsulfonyl-1,5-diphenyl-3-pyrrolin-2-one 1a with benzaldehyde.
Good yields of the salts of 1-aryl-3-hydroxy-4-methylsulfonyl-5-phenyl-3-pyrrolin-2-ones with
hydrazine 2a,b are formed in the reaction of 3-hydroxy-4-methylsulfonyl-1,5-diphenyl-3-pyrrolin-2-one and
3-hydroxy-1-(4-hydroxyphenyl)-4-methylsulfonyl-5-phenyl-3-pyrrolin-2-one with 50% hydrazine hydrate in
dioxane. The formation of the salts is evidently explained by the acidic characteristics of the enolic hydroxyl at
position 3 of the heterocycle.
The obtained compounds 2a,b (Table 1) are colorless crystalline substances soluble in DMSO and DMF.
In the IR spectra of compounds 2a,b (Table 2) there are bands for the stretching vibrations of the OH
group at 3019-3160 cm−1 and the NH2 groups at 3305-3547 cm−1.
1
The signals of the amino group are not seen in the H NMR spectra of compounds 2a,b (Table 3), but
unlike the initial compounds [1] an upfield shift of all the signals is observed. The absence of signals for the
amino groups is probably explained by their broadening on account of exchange processes.
Compounds 2a,b give a cherry-red color with an alcohol solution of FeCl3, which together with the
spectral data indicates that they exist in the enolic form.
1386

TABLE 1. The Characteristics of the Synthesized Compounds
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
mp, °С*
Yield,%
C
H
N
1a
1b
1c
1d
1e
1f
С17H16N2O3S
62.17
62.29
56.27
56.11
60.32
60.39
58.94
58.80
41.99
41.80
59.29
59.09
56.30
56.50
54.30
54.10
60.34
60.15
57.70
57.95
66.59
66.49
63.91
63.66
57.60
57.73
69.79
69.71
4.91
4.85
4.17
4.29
5.06
5.19
4.37
4.19
2.90
2.75
4.68
4.79
5.48
5.30
5.21
5.07
5.21
5.33
5.01
5.10
4.01
4.13
3.62
3.72
3.60
3.79
4.81
4.63
8.53
8.65
7.72
7.70
7.82
7.69
8.09
8.01
5.76
5.67
8.14
8.25
11.85
11.63
11.01
11.13
7.58
7.79
7.68
7.46
10.29
10.11
9.50
9.68
11.93
11.71
10.03
10.16
157-158
157-159
179-180
174-175
240-241
260-261
115-117
163-164
198-200
134-141
294-295
232-233
>300
48
54
50
40
31
33
85
81
65
74
52
53
42
50
С17H15ClN2O3S
С18H18N2O4S
С17H15FN2O3S
С17H14Br2N2O3S
С17H16N2O4S
С17H19N3O4S
С17H19N3O5S
С36H38N4O8S2
С36H38N4O10S2
С23H17N3O3S
С23H16ClN3O2S
С23H18N4O4S2
С24H19N3O3S
2a
2b
3a
3b
5a
5b
5c
5d
196-198
_______
*Solvent: ethanol (compounds 1a-f, 2a,b, and 3a,b), toluene (compounds 5a-d).
TABLE 2. The IR Spectra of Compounds 1a-f, 2a,b, and 5a-d
Com-
pound
ν, cm-1
NH2
SO2
C=C
1666
CON
1720
Others bonds
1a
1132, 1370
3328, 3362,
3424, 3490
1b
1c
1140, 1370
1130, 1378
1664
1664
1696
1704
3342, 3442
3338, 3298,
3252, 3190
3348, 3452
3454, 3336
1d
1e
1f
1132, 1376
1136, 1376
1128, 1378
1664
1664
1664
1716
1716
1694
3328, 3434,
3116 (OH)
2a
2b
1152, 1347
1149, 1347
1616
1629
1680 (С=О), 3019 (ОН),
3334, 3547 (NH2NH2)
1686 (С=О), 3160 (ОН),
3305 (NH2NH2)
5a
5b
5c
1130, 1340
1146, 1317
1139, 1316
1640
1548
1640
3324 (ОН), 1595 (C=N)
1539 (C=N)
1589 (C=N),
3061; 3262, 3361; 3409 (SO2)
5d
1139, 1307
1607
1529 (C=N)
1387

We tried to prepare the 3-hydrazones of 1,5-diaryl-3-hydroxy-4-methylsulfonyl-3-pyrrolin-2-ones under
more rigid conditions. The reaction was conducted with 98% hydrazine hydrate by boiling in glacial acetic acid
and gave a mixture of compounds that could not be separated into the individual compounds. This is probably
explained by the presence of the acylated form of the 3-hydrazone in the reaction mixture in addition to
3-aminoimino-3-pyrrolin-2-one, as demonstrated by the peaks of the fragment ions in the mass spectrum of the
mixture.
While studying the reaction of 1,5-diaryl-3-hydroxy-4-methylsulfonyl-3-pyrrolin-2-ones with
ethylenediamine we established that the reaction takes place at room temperature with the reagents in ratios of
1:1 or 2:1 and leads to the formation of a double salt of ethylenediamine and 1,5-diaryl-3-hydroxy-
4-methylsulfonyl-3-pyrrolin-2-ones 3a,b. When the reaction was carried out under more rigid conditions, i.e., by
boiling the reagents in dioxane for 1 h, the yields of the compounds were reduced.
The formation of an adduct of two molecules of the pyrrolone and one molecule of ethylenediamine is
obviously due to the high basicity of the amino groups in ethylenediamine. Compounds 3a,b (Table 1) are
colorless crystalline substances with limited solubility in organic solvents.
The 1H NMR spectra of compounds 3a,b (Table 3) contain a signal for the protons of the (CH2)2 groups
at 2.87-3.38 ppm.
Compounds 3a,b give a cherry-red color with an alcohol solution of FeCl3, indicating together with the
spectral data that they exist in the enolic form.
When compound 3a is kept at 180-185°C until the release of gases has stopped N,N′-di(4-methyl-
sulfonyl-1,5-diphenyl-3-pyrrolin-2-on-3-yl)ethylenediamine (4) is formed. It is a white crystalline substance
soluble in DMSO and DMF and does not give a cherry-red color with an alcohol solution of FeCl3. The
constants and spectral data of this compound are given in the experimental section.
During further study of the reaction of 1,5-diaryl-3-hydroxy-4-methylsulfonyl-3-pyrrolin-2-ones with
o-phenylenediamine we obtained the previously undescribed [2] 2,3-diaryl-4-methylsulfonylpyrrolo-
[2,3-b]quinoxalines 5a-d (Table 1), which are greenish-yellow crystalline compounds readily soluble in DMSO
and DMF.
The IR spectra of compounds 5a-d (Table 2) contain bands for the stretching vibrations of the C=N
(1529-1595 cm−1) and C=C (1584-1640 cm−1) bonds.
1
In the H NMR spectra of compounds 5a-d (Table 3) there are a group of signals for the aromatic
protons in the region of 6.72-8.34 ppm and a singlet for the three protons of the methylsulfonyl group at
3.39-3.52 ppm.
TABLE 3. The 1H NMR Spectra of Compounds 1a-f, 2a,b, 3a,b, and 5a-d
Com-
pound
Chemical shifts, δ, ppm.
Ar–H, m
Н-5, s
МеSO2, s
NH2, s
Other protons
1a
1b
1c
1d
1e
1f
7.05-7.60 (10H)
7.20-7.67 (9H)
6.80-7.57 (9H)
7.04-7.58 (9H)
7.20-7.53 (8H)
6.62-7.34 (9H)
6.58-7.17 (10H)
6.04
6.05
5.95
6.02
6.09
5.85
2.32
2.34
2.35
2.34
2.48
2.30
2.47
6.60
6.57
6.51
6.57
6.53
5.52
3.71 (3H, s, H3CO)
9.21 (1H, s, HO)
2a
5.79,
5.68
2b
3a
3b
5a
5b
5c
5d
6.98-7.57 (9H)
5.79 (10H)
5.61 (9H)
7.15 (13H)
7.61 (13H)
8.34 (13H)
6.72 (14H)
5.79
5.61
2.49
2.41
2.47
3.51
3.52
3.46
3.39
9.20 (1H, s, НО)
3.28 (4H, m, СН2)2)
2.87 (4H, m, СН2)2)
9.58 (1H, s, OН)
5.40 (2H, s, СН2)
1388

The mass spectrum of compound 5b contains a molecular ion peak with m/z 433 [M]+ and 99.9%
intensity and also peaks for fragment ions with m/z 354 [M−CH3SO2]+ (30.6%) and 319 [M−Cl]+ (39.39%),
confirming the structure.
EXPERIMENTAL
1
The H NMR spectra were obtained in DMSO-d6 on a Bruker AM-300 spectrometer (300 MHz) with
TMS as internal standard. The IR spectra were recorded in vaseline oil on a Specord-85 spectrometer. The mass
spectra were obtained on a MAT-311A spectrometer (40 eV).
3-Amino-4-methylsulfonyl-1,5-diphenyl-3-pyrrolin-2-one (1a). A mixture of 3-hydroxy-4-methyl-
sulfonyl-1,5-diphenyl-3-pyrrolin-2-one (1.64 g, 5 mmol) and urea (0.60 g, 10 mmol) was kept at 170-180°C for
1 h until the release of gases had stopped. The reaction mixture was treated with ethanol, and the precipitate was
filtered off. Yield 48%; mp 157-158°C (ethanol).
Compounds 1b-f were obtained similarly.
The Salt of 3-Hydroxy-4-methylsulfonyl-1,5-diphenyl-3-pyrrolin-2-one and Hydrazine (2a). A
mixture of 3-hydroxy-4-methylsulfonyl-1,5-diphenyl-3-pyrrolin-2-one (1.64 g, 5 mmol) and 50% hydrazine
hydrate (0.16 g, 5 mmol) was boiled in dioxane (20 ml) for 1 h. The solvent was evaporated. Yield 85%;
mp 115-117°C (ethanol).
Compound 2b was obtained similarly.
The Double Salt of 3-Hydroxy-4-methylsulfonyl-1,5-diphenyl-3-pyrrolin-2-one and Ethylene-
diamine (3a). A solution of 3-hydroxy-4-methylsulfonyl-1,5-diphenyl-3-pyrrolin-2-one (1.64 g, 5 mmol) and
50% ethylenediamine (0.30 g, 5 mmol) in dioxane (10 ml) was kept at room temperature for 1 h. The solvent
was evaporated under vacuum, and the residue was treated with ethanol. Yield 65%; mp 198-200°C (ethanol).
Compound 3b was obtained similarly.
N,N′-Di(4-methylsulfonyl-1,5-diphenyl-3-pyrrolin-2-on-3-yl)ethylenediamine (4). Compound 3a
(2.16 g, 3 mmol) was kept at 180-185°C for 30 min, ethanol (20 ml) was added, and the crystals that separated
1
were filtered off. Yield 50%; mp 151-153°C (ethanol). H NMR spectrum, δ, ppm (J, Hz): 2.85 (6Н, s,
(CH3SO2)2); 5.93 (1Н, s, Н-5); 6.00 (1Н, s, Н-5); 7.00-7.50 (20Н, m, 4С6Н5); 3.90-4.20 (4Н, m, (СН2)2). Found,
%: N 7.96. C36H34N4O6S2. Calculated, %: N 7.84.
2-(4-Hydroxyphenyl)-4-methylsulfonyl-3-phenylpyrrolo[2,3-b]quinoxaline (5a). A mixture of 1-(3-
hydroxy-4-hydroxyphenyl-4-methylsulfonyl-5-phenyl-3-pyrrolin-2-one (1.64 g, 5 mmol) and o-phenylene-
diamine (0.54 g, 5 mmol) was kept at 190-200°C for 30 min, ethanol (20 ml) was added, and the crystals that
separated were filtered off. Yield 52%; mp 294-295°C (toluene).
Compounds 5b-d were obtained similarly.
The work was carried out with financial support from the Russian Fundamental Research Fund (project
No. 04-03-96042).
REFERENCES
1.
2.
3.
Z. G. Aliev, L. O. Atovmyan, V. L. Gein, L. F. Gein, and A. V. Kataeva, Izv. Akad. Nauk., Ser. Khim.,
1343 (2003).
V. L. Gein, L. F. Gein, and A. V. Kataeva, Khim. Geterotsikl. Soedin., 1692 (1999). [Chem. Heterocycl.
Comp., 35, 1487 (1999)].
L. Fieser and M. Fieser, Reagents for Organic Synthesis [Russian translation], Mir, Moscow (1970),
p. 321.
1389