Reaction 5-(Arylmethylidene)-2,4,6-pyrimidine-2,4,6(1H,3H,5H)-triones with Arenecarbaldehyde Phenylhydrazones in the Presence of Sodium N-Chlorobenzenesulfonamide

Article abstract of DOI:10.1134/S1070428019020222

The reactions of 5-(arylmethylidene)-2,4,6-pyrimidine-2,4,6(1H,3H,5H)-triones with arenecarbaldehyde phenylhydrazones in the presence of sodium N-chlorobenzenesulfonamide give 2,3,7,9-tetraasaspiro-[4.5]dec-1-ene-6,8,10-triones in yields of 30–45%.

Full text of DOI:10.1134/S1070428019020222

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2019, Vol. 55, No. 2, pp. 269–272. © Pleiades Publishing, Ltd., 2019.
Russian Text © A.G. Tyrkov, E.A. Yurtaeva, O.B. Rsaeva, 2019, published in Zhurnal Organicheskoi Khimii, 2019, Vol. 55, No. 2, pp. 307–310.
SHORT
COMMUNICATIONS
Reaction 5-(Arylmethylidene)-2,4,6-pyrimidine-2,4,6(1H,3H,5H)-
triones with Arenecarbaldehyde Phenylhydrazones in the
Presence of Sodium N-Chlorobenzenesulfonamide
A. G. Tyrkova,*, E. A. Yurtaevab,**, and O. B. Rsaevaa
a Astrakhan State University, pl. Shaumyana 1, Astrakhan, 414000 Russia
*e-mail: tyrkov@rambler.ru
b Institute for Leprosy Research, Ministry of Health of the Russian Federation,
per. N. Ostrovskogo 3, Astrakhan, 414057 Russia
**e-mail: huitre_88@mail.ru
Received August 31, 2018; revised September 12, 2018; accepted September 12, 2018
Abstract—The reactions of 5-(arylmethylidene)-2,4,6-pyrimidine-2,4,6(1H,3H,5H)-triones with arenecar-
baldehyde phenylhydrazones in the presence of sodium N-chlorobenzenesulfonamide give 2,3,7,9-tetraasaspiro-
[4.5]dec-1-ene-6,8,10-triones in yields of 30–45%.
Keywords: 5-(arylmethylidene)-2,4,6-pyrimidine-2,4,6(1H,3H,5H)-triones, arenecarbaldehyde phenylhydrazones,
sodium N-chlorobenzenesulfonamide, 1,3-dipolar cycloaddition, 2,3,7,9-tetraazaspiro[4.5]dec-1-ene-6,8,10-triones
DOI: 10.1134/S1070428019020222
The information on chemical transformations of
diphenylnitrile imines is scarce. It is only known that
the reactions of 1,3-diphenylnitrile imines with 1-nitro-
2-phenylethene and 2-morpholino-1-nitroethene form
substituted 1,3-diphenylpyrazoles [1], and the
reactions of 1,3-diphenylnitrile imines with 2-aryl-1,1-
dicyanoethenes or trinitroacetonitrile leads to 1,5-di-
hydro-4H-pyrazole-4,4-dicarbonitriles or 5-dinitrome-
thyl-1,3-diphenyl-1,2,4-triazoles, respectively [2, 3].
presence of sodium N-chlorobenzenesulfonamide
under heating in a dry ethanol medium to give
previously unknown 2,3,7,9-tetraazaspiro[4.5]dec-1-
ene-6,8,10-triones 3a–3f in yields of 30–45%. We also
isolated from the reaction medium 1,3,4,6-tetraaryl-
1,2,4,5-tetraazahexa-2,5-dienes 4a and 4b formed by
spontaneous dimerization of nitrile imines 2a and 2b.
It can be suggested that 1,3-diphenylnitrile imines
А are generated intermediately in the course of ther-
molysis of arenecarbaldehyde phenylhydrazones 2a
and 2b in the presence of chloramine B [4], and the
intermediate products undergo 1,3-dipolar cycloaddi-
tion to dipolarophiles 1а–1с and thus stabilize into
substituted 2,3,7,9-tetraazaspiro[4.5]dec-1-ene-6,8,10-
triones 3a–3f (Scheme 1). It should be noted that
evidence for the generation of nitrile imines from aromatic
and aliphatic carbaldehyde phenylhydrazones under the
action of sodium N-chloro-p-toluenesulfonamide,
followed by the addition of nitrile imines to
acrylonitrile, phenylethene, and ethyl acrylate to form
pyrazolines was obtained by Rai Lokanatha and
Hassner [5]. The advantage chloramine B offers over
lead tetraacetate in generation of nitrile imines consists
in the absence of the possibility of diacylhydrazide
It should be noted that the heterocyclization of
diphenylnitrile imines, generated in situ by the action
of sodium N-chlorobenzenesulfonamide (chloramine B)
on arenecarbaldehyde phenylhydrazones, to form 5-
(arylmethylidene)-2,4,6-pyrimidine-2,4,6(1H,3H,5H)-
triones have never been studied.
Proceeding with research in this direction, as well
as aimed at assessing the synthetic potential of reactions
of diphenylnitrile imines with dipolarophiles, we have
studied the reaction of 1,3-diphenylnitrile imines with
a new type of compounds – 5-(arylmethylidene)-2,4,6-
pyrimidine-2,4,6(1H,3H,5H)-triones 1а–1с.
It was found that compounds 1а–1с react with
arenecarbaldehyde phenylhydrazones 2a and 2b in the
269

TYRKOV et al.
270
Scheme 1.
O
H
+
PhSO2NNaCl
HN
Ar
N
N
Ar1
Ph
Ar1
N
+
N
Ph
Δ, EtOH
O
N
H
O
1a_1c
A
2a, 2b
Ar1
Ph
O
N
Ar1
N
N
1a_c
N
Ph
HN
+
N
Ar1
Ph
N
Ar
O
N
O
H
H
3a_3f
4a, 4b
1, Ar = Ph (a), 4-MeOC6H4 (b), 4-Me2NC6H4 (c); 2, Ar1 = Ph (a), 4-MeOC6H4 (b); 3, Ar = Ar1 = Ph (a), Ar = 4-MeOC6H4,
Ar1 = Ph (b); Ar = 4-Me2NC6H4, Ar1 = Ph (c); Ar = Ph, Ar1 = 4-MeOC6H4 (d); Ar = Ar1 = 4-MeOC6H4 (e); Ar = 4-Me2NC6H4,
Ar1 = 4-MeOC6H4 (f); 4, Ar1 = Ph (a), Ar1 = 4-MeOC6H4 (b).
formation [6]. The fairly low yields of compounds 3a–
3f, as well as dimerization of nitrile imines can be
explained by the fact that 2,4,6-pyrimidinetriones 1а–
1с are weaker dipolarophiles than 2-aryl-1,1-dicyano-
ethenes or trinitroacetonitrile. The target products are
stable colorless or colored refractory substances
soluble in ethanol.
Thus, the reaction of 5-(arylmethylidene)-2,4,6-
pyrimidine-2,4,6(1Н,3Н,5Н)-triones 1а–1с with arene-
carbaldehyde phenylhydrazones 2a and 2b in the
presence of sodium N-chloro-p-toluenesulfonamide
allowed one-step synthesis of spiro compounds
combining the pyrimidine and pyrazoline rings in one
molecule. The synthesized compounds may present
interest as potential biologically active compounds, in
particular, xanthine oxidase inhibitors [9].
The composition and structure of compounds 3a–3f
1
were established by elemental analysis and IR, Н and
13С NMR spectroscopy and mass spectrometry. The IR
spectra of cycloadducts 3a–3f show no band of the
ethene bond at 1625 cm–1, which is characteristic of
the starting pyrimidine-2,4,6-triones 1а–1с [7]. The 1Н
The IR spectra were measured on an InfraLUM
FТ-02 instrument in the range 4000–400 cm–1 for KBr
pellets. The 1Н and 13С NMR spectra were obtained on
a Bruker Avence II 300 SF spectrometer at 500 and
125 MHz in DMSO-d6, internal reference HMDS. The
mass spectra were obtained on a Finnigan SSQ-7000
instrument with direct probe, ionizing energy 70 eV,
evaporation temperature 500–550°С. Reaction progress
and product purity were monitored by TLC on Silufol
UV-254 plates in 2 : 3 acetone–hexane with develop-
ment in iodine vapor [10]. Elemental analysis was
performed on EuroVector EA-3000 CHNS analyzer.
The decomposition points were determined on an
OptiMelt automated melting point system.
13
and С NMR spectra are consistent with the proposed
structures and similar to the spectra of structurally
related model pyrazolines [8]. Thus, the 1Н NMR spectra
contain, along with the multiplets of aryl protons, a
series of signals of protons at the pyrazoline С4 atom at
7.01–7.05 ppm, which are lacking in the spectra of the
starting compounds. Compared to the spectra of the star-
ting compounds, the 13С NMR spectra display a new
signal at 156.3–158.1 ppm assignable to the of the
pyrazoline С1 atom. The mass spectra of compounds
3a–3f contain, along with weak molecular and [М – 1]+
ion peaks, peaks of ions formed by dissociative ionization
that occurs as retro-1,3-dipolar cycloaddition at the
pyrazoline С1–С5 and N3–C4 bonds. It should be noted
the mass spectra of pyrazolines contain a series of
peaks, which can be assigned several brutto formulas,
and, therefore, are difficult to interpret in details.
5-(Arylmethylidene)-2,4,6-pyrimidine-2,4,6-
(1Н,3Н,5Н)-triones 1a–1c were synthesized by the
procedure in [11], and arenecarbaldehyde phenylhyd-
razones 2а and 2b, by the procedure in [12].
1,3,4-Triaryl-2,3,7,9-tetraazaspiro[4.5]dec-1-ene-
6,8,10-triones (3a–3f) (general procedure).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 2 2019

REACTION 5-(ARYLMETHYLIDENE)-2,4,6-PYRIMIDINE-2,4,6(1H,3H,5H)-TRIONES
271
Compounds 2a and 2b, 6 mmol, and 6.5 mmol of
chloramine B trihydrate were added to a suspension of
5 mmol of compound 1а–1с in 20 mL of dry ethanol.
The reaction mixture was heated under reflux for 6 h,
the precipitate was filtered off, the solvent was
evaporated in a vacuum. The residue was washed with
water (2 × 15 mL), dried in a vacuum, and subjected to
column chromatography on activated Silica gel
100/400 μm using Trappe's eluotropic series of
solvents. Compounds 3a–3f were eluted with ethanol
and compounds 4a and 4b, with diethyl ether.
1-(4-Methoxyphenyl)-3,4-diphenyl-2,3,7,9-
tetraazaspiro[4,5]dec-1-ene-6,8,10-trione (3d). Yield
0.799 g (32%), pale yellow crystals, decomp. point
225–229°С. IR spectrum, ν, cm–1: 3355 (NH), 1770,
1750 (C=O). 1Н NMR spectrum, δ, ppm: 3.81 s
(3Н, СН3О), 7.03 s (1Н, СН), 6.95–7.72 m (14Harom
,
2C6H5, С6Н4), 11.43 br.s (1H, NH), 11.48 br.s (1H,
NH). 13С NMR spectrum, δ, ppm: 51.6 (C5), 55.1 (CH3O),
73.2 (C4), 112.5–160.1 (Сarom), 156.3 (C1), 161.2 (C6),
161.8 (C10), 162.1 (C8). Mass spectrum, m/z (Irel, %):
440 (10) [М]+, 439 (5) [M – 1], 224 (20), 216 (100).
Found, %: C 68.02; H 4.41; N 12.51. C25H20N4O4.
Calculated, %: C 68.18; H 4.55; N 12.73. M 440.45.
1,3,4-Triphenyl-2,3,7,9-tetraazaspiro[4,5]dec-1-
ene-6,8,10-trione (3а). Yield 0.626 g (30%), colorless
crystals, decomp. point 250–253°С. IR spectrum, ν,
cm–1: 3355 (NH), 1770, 1750 (C=O). 1Н NMR spectrum,
1,4-[4-(Dimethylamino)phenyl]-3-phenyl-2,3,7,9-
tetraazaspiro[4,5]dec-1-ene-6,8,10-trione (3е). Yield
0.987 g (42%), pale yellow crystals, decomp. point
305–309°С. IR spectrum, ν, cm–1: 3355 (NH), 1770,
δ, ppm: 7.05 s (1Н, СН), 7.26–7.72 m (15Ha1ro3m
,
3C6H5), 11.43 br.s (1H, NH), 11.48 br.s (1H, NH). С
NMR spectrum, δ, ppm: 52.6 (C5), 72.5 (C4), 113.8–
147.2 (Сarom), 151.9 (C6), 157.8 (C1), 161.3 (C10),
162.2 (C8). Mass spectrum, m/z (Irel, %): 410 (8) [М]+,
409 (5) [M – 1], 216 (100), 194 (22.5). Found, %: С
70.09; H 4.27; N 13.51. C24H18N4O3. Calculated, %: C
70.24; H 4.39; N 13.66. M 410.43.
1
1750 (C=O). Н NMR spectrum, δ, ppm: 3.80 s (3Н,
СН3О), 3.81 s (3Н, СН3О), 7.05 s (1Н, СН), 6.90–7.75
m (13Harom, 2C6H4, С6Н5), 11.42 br.s (1H, NH), 11.46
br.s (1H, NH). 13С NMR spectrum, δ, ppm: 52.8 (C5),
55.2 (СН3О), 55.4 (СН3О), 72.5 (C4), 112.1–160.3
(Сarom), 158.1 (C1), 161.6 (C6), 161.8 (C10), 162.5 (С8).
Mass spectrum, m/z (Irel, %): 470 (8) [М]+, 469 (5)
[M – 1], 246 (100), 224 (18). Found, %: C 66.23; H
4.55; N 11.76. C26H22N4O5. Calculated, %: C 66.38; H
4.68; N 11.92. M 470.48.
4-(4-Methoxyphenyl)-1,3-diphenyl-2,3,7,9-
tetraazaspiro[4,5]dec-1-ene-6,8,10-trione (3b). Yield
0.77 g (35%), light yellow crystals, decomp. point 282–
286°С. IR spectrum, ν, cm–1: 3355 (NH), 1770, 1750
(C=O). 1Н NMR spectrum, δ, ppm: 3.80 s (3Н, СН3О),
6.90–7.75 m (14Harom, 2C6H5, С6Н4), 7.04 s (1Н, СН),
11.41 br s (1H, NH), 11.49 br.s (1H, NH). 13С NMR
spectrum, δ, ppm: 52.6 (C5), 55.2 (CH3O), 72.5 (C4),
112.4–159.7 (Сarom), 157.9 (C1), 161.3 (C6), 161.7
(С10), 162.5 (C8). Mass spectrum, m/z (Irel, %): 440 (9)
[М]+, 439 (6.5) [M – 1], 246 (100), 194 (20). Found,
%: С 68.05; H 4.45; N 12.57. С25H20N4O4. Calculated,
%: C 68.18; H 4.55; N 12.73. M 440.45.
4-[4-(Dimethylamino)phenyl]-1-(4-methoxy-
phenyl)-3-phenyl-2,3,7,9-tetraazaspiro[4,5]dec-1-
ene-6,8,10-trione (3f). Yield 1.091 g (45%), pale
yellow crystals, decomp. point 290–296°С. IR spectrum,
1
ν, cm–1: 3355 (NH), 1770, 1750 (C=O). Н NMR
spectrum, δ, ppm: 2.40 s (6Н, 2СН3N), 3.80 s (3Н,
СН3О), 7.01 s (1Н, СН), 6.95–7.72 m (13Harom, 2C6H4,
С6Н5), 11.42 br.s (1H, NH), 11.48 br.s (1H, NH). 13С
NMR spectrum, δ, ppm: 40.2 (CH3N), 52.9 (C5), 55.6
(СН3О), 72.1 (C4), 112.6–159.2 (Сarom), 157.6 (C1),
161.3 (C6), 161.6 (C10), 162.7 (C8). Mass spectrum,
m/z (Irel, %): 483 (15) [М]+, 482 (10), [М – 1], 259
(100), 224 (25). Found, %: С 66.95; H 5.03; N 14.33.
С27H25N5O4. Calculated, %: C 67.08; H 5.18; N 14.49.
M 483.52.
4-[4-(Dimethylamino)phenyl]-1,3-diphenyl-
2,3,7,9-tetraazaspiro[4,5]dec-1-ene-6,8,10-trione
(3с). Yield 0.909 g (40%), red crystals, decomp. point
315–318°С. IR spectrum, ν, cm–1: 3355 (NH), 1770,
1
1750 (C=O). Н NMR spectrum, δ, ppm: 2.42 s (6Н,
2СН3N), 7.02 s (1Н, СН), 6.95–7.76 m (14Harom
,
2C6H5, С6Н4), 11.43 br.s (1H, NH), 11.48 br.s (1H,
NH). 13С NMR spectrum, δ, ppm: 40.6 (CH3N), 52.7
(C5), 72.8 (С4), 113.5–149.2 (Сarom), 157.8 (C1), 161.3 (C6),
161.5 (C10), 162.3 (C8). Mass spectrum, m/z (Irel, %):
453 (10) [М]+, 452 (5) [M – 1], 259 (100), 194 (25).
Found, %: С 68.75; H 4.96; N 15.31. С26H23N5O3.
Calculated, %: C 68.87; H 5.08; N 15.45. M 453.49.
1,3,4,6-Tetraphenyl-1,2,4,5-tetraazahexa-2,5-
diene (4a). Yield 1.456 g (62%), colorless crystals, mp
200–201°С [6].
3,6-(4-Methoxyphenyl)-1,4-diphenyl-1,2,4,5-
tetraazahexa-2,5-diene (4b). Yield 1.760 g (65%),
pale pink crystals, mp 212–215°С [6].
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 2 2019

TYRKOV et al.
6. Gladstone, W.A.F., Aylward, J.B., and Norman, R.O.C.,
272
FUNDING
J. Chem. Soc. C, 1969, p. 2587. doi 10.1039/
J39690002587
The work was financially supported by the Ministry
of Education and Science of the Russian Federation
(project no. 4.9288.2017BCh).
7. Tyrkov, A.G., Nosachev, S.B., and Vladimirova, T.S.,
Russ. J. Org. Chem., 2016, vol. 52, p. 762. doi 10.1134/
S1070428016050274
8. Structure Determination of Organic Compounds: Tables
of Spectral Data, Pretsch, E., Bühlmann, P., and
Affolter, C., Eds., Berlin: Springer, 2000, 3rd ed.
Translated under the title Opredelenie stroeniya
organicheskikh soedinenii. Tablitsy spektral’nykh
dannykh, Moscow: Mir, 2006,
CONFLICT OF INTEREST
The authors declare no conflict of interest.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 2 2019