Synthesis, S-alkylation, and fungicidal activity of 4-(benzylideneamino)thioglycolurils

Article abstract of DOI:10.1007/s11172-018-2180-x

A series of 1,3-disubstituted 4-benzylideneamino-5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-ones (thioglycolurils) was synthesized via the reaction of 5,7-disubstituted 3-thioxoperhydroimidazo[4,5-e]-1,2,4-triazin-6-ones with hydroxy-, alkoxy-, and fluorocontaining benzaldehyde derivatives. An alkylation of the obtained thioglycolurils with methyl iodide or 4-bromobenzyl bromide provided the corresponding 6-benzylideneamino-5-alkylsulfanyl-3,3a,6,6a-tetrahydroimidazo[4,5-d]imidazol-2(1H)-ones. The fungicidal activity of some synthesized compounds against pathogens causing diseases of agricultural crops was studied.

Full text of DOI:10.1007/s11172-018-2180-x

Russian Chemical Bulletin, International Edition, Vol. 67, No. 6, pp. 1059—1064, June, 2018
1059
Synthesis, S-alkylation, and fungicidal activity
of 4-(benzylideneamino)thioglycolurils
G. A. Gazieva,a T. V. Nechaeva,b N. N. Kostikova,a N. V. Sigay,a S. A. Serkov,a and S. V. Popkovc
aN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. E-mail: gaz@ioc.ac.ru
bThe State Scientific-Research Institute of Chemical Reagents and High Purity Chemical Substances,
National Research Center "Kurchatov Institute",
3 ul. Bogorodskiy Val, 107076 Moscow, Russian Federation
cD. I. Mendeleev University of Chemical Technology of Russia,
9 Miusskaya pl., 125047 Moscow, Russian Federation
A series of 1,3-disubstituted 4-benzylideneamino-5-thioxohexahydroimidazo[4,5-d]imid-
azol-2(1H)-ones (thioglycolurils) was synthesized via the reaction of 5,7-disubstituted
3-thioxoperhydroimidazo[4,5-e]-1,2,4-triazin-6-ones with hydroxy-, alkoxy-, and fluoro-
containing benzaldehyde derivatives. An alkylation of the obtained thioglycolurils with methyl
iodide or 4-bromobenzyl bromide provided the corresponding 6-benzylideneamino-5-alkylsul-
fanyl-3,3a,6,6a-tetrahydroimidazo[4,5-d]imidazol-2(1H)-ones. The fungicidal activity of some
synthesized compounds against pathogens causing diseases of agricultural crops was studied.
Key words: 3-thioxoperhydroimidazo[4,5-e]-1,2,4-triazin-6-ones, ring contraction,
5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-ones, thioglycolurils, S-alkylation,
Triadimefon, fungicidal activity.
Imidazolidine-2-thione derivatives attract an attention
of researchers due to their various biological activity and
contraction caused by aldehydes revealed that all the
studied compounds, including compound 1i, possess the
ability to form complexes with transition metal salts.1—16
.
E-configuration of the C=N bond.7,8,17—19
Thiohydantoins (2-thioxoimidazolidin-4-ones) exhibit
antiproliferative,1—3 fungicidal, and antibacterial activi-
ties3,4 and inhibit the mutant isocitrate dehydrogenase,
which is stimulating carcinogenesis.5 Thioglycolurils
(5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-ones)
cause the sedative,6 fungicidal and cytotoxic effects.7,8
Alkylsulfanyl derivatives of thiohydantoins and thiogly-
colurils inhibit the mycelial growth of phytopathogenic
fungi, while 4-methyl-2-methylsulfanyl-4-phenyl-1-phe-
nylamino-1H-imidazol-5(4H)-one so-called Fenamidon
is used as a fungicidal agent for the agricultural crop pro-
tection.8—10
This work was aimed at the synthesis of 4-(benzylide-
neamino)thioglycolurils and their S-alkyl derivatives and
at the investigation of the fungicidal activity of the prepared
compounds. Thioglycolurils 1a—l were synthesized ac-
cording to our method developed previously17 via a tandem
reaction including the hydrazone formation and triazine
ring contraction of imidazotriazines 2a—c with hydroxy-,
alkoxy- and fluoro-substituted benzaldehydes 3a—j
(Scheme 1).
S-Alkyl derivatives 4 were obtained by the alkylation
of thioglycolurils 1 with methyl iodide or 4-bromobenzyl
bromide in the presence of potassium carbonate (Scheme 2).
The reaction with methyl iodide was carried out in
methanol under heating at 60 °C, while that with 4-bro-
mobenzyl bromide was performed in dimethylsulfoxide at
room temperature. However, the alkylation of thiogly-
coluril 1c with 4-bromobenzyl bromide provided also both
O- and S-alkylation product 4j (the yield of 23% based on
4-bromobenzyl bromide) in addition to desired S-alkyl
derivative 4i (52% yield).
The IR spectra of alkylsulfanyl derivatives 4 did not
contain an absorption band of the NH group in the region
of 3160—3243 cm–1 as compared to the spectra of thio-
glycolurils 1. In the 1H NMR spectra of compounds 4, the
singlet signals from the proton in the NH group (δ =
= 9.85—10.26) disappeared, while the signals arise as the
singlets from protons in the SMe at δ = 2.42—2.45 and
SCH2 at δ = 4.26—4.29 groups, and as the two doublets
of aromatic protons in the 4-bromobenzyl moiety at δ =
= 7.40—7.52. The 13C NMR spectra did not contain a
signal from the C=S group in the region of δ = 178.4—179.7
and contained the signals from the N=C—S, SMe, or
The previous X-ray diffraction studies of single crystals
of thioglycolurils prepared via the reaction of triazine ring
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1059—1064, June, 2018.
1066-5285/18/6706-1059 © 2018 Springer Science+Business Media, Inc.

1060 Russ. Chem. Bull., Int. Ed., Vol. 67, No. 6, June, 2018
Gazieva et al.
Scheme 1
Scheme 2
Starting
Compounds
2a, 3a
2a, 3b
2a, 3c
2a, 3d
2a, 3e
2a, 3f
2b, 3a
2b, 3g
2b, 3h
2b, 3i
R1
R2
R3
Product
Yield
(%)
47
48
60
47
44
49
45
69
65
34
59
44
n
Me
Me
Me
Me
Me
Me
Et
Et
Et
Et
Et
Me
Me
Me
Me
Me
2-F
3-MeO
2-HO-3-MeO
2-HO-5-Me
4-HO-3-MeO
1a
1b
1c
1d
1e
1f
1g
1h
1i
X = I, Br
Me 4-BnO-3-MeO
Et
Et
Et
Et
Et
Ph
2-F
4-F
4-MeO
Product R1
R2
R3
Yield
(%)
95
81
79
86
76
75
n
4a
4b
4c
4d
4e
4f
Me
Me
Me
Et
Et
Et
Me
Me
Me
2-F
3-MeO
2-HO-3-MeO
2-F
4-MeO
4-EtO-3-MeO
2-F
Me
Me
Me
Me
Me
Me
4-F3C
4-EtO-3-MeO
4-HO-3-MeO
1j
1k
1l
2b, 3j
2c, 3e
Me
SCH2 groups at δ = 165.3—166.8, 12.9—13.0, and 33.1,
respectively.
4g
4h
4i
4-BrC6H4CH2 91
4-BrC6H4CH2 84
4-BrC6H4CH2 52
4-BrC6H4CH2 23
3-MeO
2-HO-3-MeO
Since the (phenylallylidenamino)thioglycolurils and
their S-alkyl derivatives obtained earlier by us demonstrated
the fungicidal effect on the causative agents of rhizocto-
niose and fusariose, Rhizoctonia solani, Fusarium oxyspo-
rum, and Fusarium moniliforme;8 some of synthesized
compounds 1 and 4 were tested for the fungicidal activity
in vitro according to the known method20,21 in comparison
with Triadimefon as the standard against the six species
of phytopathogenic fungi belonging to the different taxo-
nomic classes: Venturia inaequalis (V.i.) is the causative
agent of apple scab, Rhizoctonia solani (R.s.) is the causative
agent of rhizoctoniose, Fusarium oxysporum (F.o.) and
Fusarium moniliforme (F.m.) are the causative agents of
fusariose, Bipolaris sorokiniana (B.s.) is the causative agent
of root rot, and Sclerotinia sclerotiorum (S.s.) is the caus-
ative agent of white rot. However, the tested compounds
demonstrated a little or no activity against Venturia inae-
qualis, Fusarium oxysporum, Bipolaris sorokiniana, and
Sclerotinia sclerotiorum. Their most noticeable effect was
4j
Me 2-(4-BrC6H4CH2O)-3-MeO
on the mycelial growth of Rhizoctonia solani (R.s.) and
Fusarium moniliforme (F.m.), but the activity of all the
investigated thioglycolurils did not exceed that of the
Triadimefon reference (Table 1). The close to Triadimefon
level of suppression of mycelial growth of Rhizoctonia
solani was demonstrated by methylsulfanyl derivative 4e.
Therefore, (benzylideneamino)thioglycolurils were
synthesized via the tandem reaction including the hydra-
zone formation and triazine ring contraction of imidazo-
triazines with the substituted benzaldehydes. The alkyla-
tion of these thioglycolurils with methyl iodide or 4-bro-
mobenzyl bromide provided their S-alkyl derivatives in the
yields of 75—95%. The obtained compounds demonstrated
the significantly weaker fungicidal activity in comparison
with the (phenylallylidenamino)thioglycolurils and their
S-alkyl derivatives previously studied by us.

S-Alkylation of thioglycolurils
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 6, June, 2018
1061
(E)-4-[(3-Methoxybenzylidene)amino]-1,3-dimethyl-5-
thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one (1b). The
yield was 48%, white crystals, m.p. 203—205 °C (dec.). The
spectral characteristics corresponded to that reported earlier.7
(E)-4-[(2-Hydroxy-3-methoxybenzylidene)amino]-1,3-di-
methyl-5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one
(1c). The yield was 60%, white crystals, m.p. 221—223 °C (dec.).
The spectral characteristics corresponded to that reported ear-
lier.17
(E)-4-[(2-Hydroxy-5-methylbenzylidene)amino]-1,3-dimeth-
yl-5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one (1d).
The yield was 47%, white powder, m.p. 241—243 °C (dec.). IR
(KBr), ν/cm–1: 3407 (OH), 3173 (NH), 1720, 1678 (C=O), 1613
(C=N), 1526, 1492, 1415, 1269, 1201, 1044. 1H NMR, δ: 2.24
(s, 3 H, Me); 2.77 (s, 3 H, NMe); 2.92 (s, 3 H, NMe); 5.48 (d,
1 H, CH, J = 8.2 Hz); 6.15 (d, 1 H, CH, J = 8.2 Hz); 6.83 (d,
1 H, ArH, J = 8.3 Hz); 7.13 (d, 1 H, ArH, J = 8.3 Hz); 7.36 (s,
1 H, ArH); 8.74 (s, 1 H, N=CH); 10.26 (s, 1 H, NH); 10.89 (s,
1 H, OH). 13C NMR, δ: 20.0 (Me); 28.3 (NMe); 30.9 (NMe);
68.9 (CH); 72.2 (CH); 116.6; 118.0; 128.0; 130.1; 132.5; 147.7
(N=CH); 155.2; 157.6 (C=O); 179.7 (C=S). MS (ESI), m/z:
[M + Na]+; found: 342.1000; calculated for C14H17N5O2S:
342.0995.
Table 1. The fungicidal activity of synthesized
compounds in vitro (c = 30 mg L–1
)
Compound
Mycelial growth inhibition (%)
R.s.
F.m.
1a
1c
1e
1f
1g
1i
1j
1k
10
38
16
31
18
19
23
30
47
19
52
20
11
23
22
24
40
17
19
16
15
61
4e
4g
Triadimefon*
*Triadimefon is 3,3-dimethyl-1-(1,2,4-triazol-1-
yl)-1-(4-chlorophenoxy)butan-2-one.
Experimental
(E)-4-[(4-Hydroxy-3-methoxybenzylidene)amino]-1,3-di-
methyl-5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one
(1e). The yield was 44%, white powder, m.p. 132—134 °C (dec.).
IR (KBr), ν/cm–1: 3436 (OH), 3160 (NH), 1703 (C=O), 1639,
1599 (C=C, C=N), 1510, 1457, 1426, 1269, 1251, 1223, 1042,
1032. 1H NMR, δ: 2.76 (s, 3 H, NMe); 2.84 (s, 3 H, NMe); 3.82
(s, 3 H, OMe); 5.38 (d, 1 H, CH, J = 8.2 Hz); 5.89 (d, 1 H, CH,
J = 8.2 Hz); 6.87 (d, 1 H, ArH, J = 8.3 Hz); 7.20 (d, 1 H, ArH,
J = 8.3 Hz); 7.35 (s, 1 H, ArH); 8.97 (s, 1 H, N=CH); 9.71 (s,
1 H, OH); 9.87 (s, 1 H, NH). 13C NMR, δ: 28.1 (NMe); 29.8
(NMe); 55.5 (OMe); 67.9 (CH); 75.7 (CH); 110.0; 115.5; 122.3;
125.0; 147.9; 149.6; 154.9 (N=CH); 157.5 (C=O); 178.7 (C=S).
MS (ESI), m/z: [M + Na]+; found: 358.0941; calculated for
C14H17N5O3S: 358.0944.
(E)-4-[(4-Benzyloxy-3-methoxybenzylidene)amino]-1,3-di-
methyl-5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one (1f).
The yield was 49%, white powder, m.p. 212—214 °C (dec.). IR
(KBr), ν/cm–1: 3165 (NH), 1708 (C=O), 1599, 1575 (C=C,
C=N), 1509, 1458, 1401, 1267, 1225, 1198, 1141. 1H NMR,
δ: 2.75 (s, 3 H, NMe); 2.84 (s, 3 H, NMe); 3.81 (s, 3 H, OMe);
5.15 (s, 2 H, OCH2); 5.38 (d, 1 H, CH, J = 8.3 Hz); 5.91 (d,
1 H, CH, J = 8.2 Hz); 7.14 (d, 1 H, ArH, J = 8.4 Hz); 7.28 (d,
1 H, ArH, J = 8.4 Hz); 7.32—7.47 (m, 6 H, ArH); 9.03 (s, 1 H,
N=CH); 9.91 (s, 1 H, NH). 13C NMR, δ: 28.2 (NMe); 30.0
(NMe); 55.5 (OMe); 69.0 (OCH2); 69.9 (CH); 75.5 (CH); 109.3;
113.2; 121.9; 126.7; 127.9 (2 C); 128.0; 128.4 (2 C); 136.7; 149.3;
150.2; 153.6 (N=CH); 157.6 (C=O); 178.8 (C=S). MS (ESI),
m/z: [M + Na]+; found: 448.1411; calculated for C21H23N5O3S:
448.1414.
The NMR spectra were recorded on a Bruker AM-300 spec-
trometer (1H, 300.13 MHz; 13C, 75.5 MHz; and 19F, 282 MHz)
in DMSO-d6, the chemical shifts are reported as δ values relative
to Me4Si or CFCl3 used as the internal standards. High-resolution
mass spectra (HRMS) were recorded on a Bruker micrOTOF II
instrument using electrospray ionization (ESI). The measure-
ments were performed in a positive ion mode (the interface
capillary voltage of 4500 V). The mass range interval was from
m/z 50 to 3000 Da using an external or internal calibration
(Electrospray Calibrant Solution, Fluka). A syringe injection
was used for solutions in MeCN or MeOH; the flow rate was
3 μL min–1; N2 was used as the nebulizer gas (4 L min–1); the
interface temperature was set at 180 °C. The melting points of
compounds were determined on a Boetius microblock.
Synthesis of 1,3-disubstituted 4-benzylideneamino-5-
thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-ones 1a—l (gen-
eral procedure). Aldehyde 3a—j (2.1 mmol) and HCl (conc.,
2 drops) were added to a suspension of imidazotriazine 2a—c
(2 mmol) in MeOH (30 mL). The resulting mixture was refluxed
under stirring for 1.5 h, cooled, and kept at room temperature
for 4—48 h. The formed precipitate was isolated by filtration,
wased with methanol, and dried in air.
(E)-4-[(2-Fluorobenzylidene)amino]-1,3-dimethyl-5-
thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one (1a). The
yield was 47%; white crystals, m.p. 189—191 °C (dec.). IR (KBr),
ν/cm–1: 3179 (NH), 1698 (C=O), 1610 (C=N), 1519, 1493, 1419,
1233, 1046. 1H NMR, δ: 2.76 (s, 3 H, NMe); 2.88 (s, 3 H, NMe);
5.41 (d, 1 H, CH, J = 8.3 Hz); 6.01 (d, 1 H, CH, J = 8.3 Hz);
7.29—7.35 (m, 2 H, 3,5-ArH); 7.49—7.56 (m, 1 H, 4-ArH); 7.93
(t, 1 H, 6-ArH, J = 7.5 Hz); 9.45 (s, 1 H, N=CH); 10.13 (s, 1 H,
NH). 13C NMR, δ: 28.1 (NMe); 30.2 (NMe); 68.0 (CH); 75.3
(E)-1,3-Diethyl-4-[(2-f luorobenzylidene)amino]-5-
thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one (1g). The
yield was 45%, white crystals, m.p. 234—236 °C (dec.). IR (KBr),
ν/cm–1: 3199 (NH), 1687 (C=O), 1606 (C=N), 1509, 1482, 1451,
1276, 1252, 1238, 1206. 1H NMR, δ: 1.04—1.10 (m, 6 H, Me);
3.09—3.43 (m, 4 H, NCH2); 5.52 (d, 1 H, CH, J = 8.3 Hz); 6.04
(d, 1 H, CH, J = 8.3 Hz); 7.30—7.35 (m, 2 H, 3,5-ArH);
7.50—7.57 (m, 1 H, 4-ArH); 7.91 (t, 1 H, 6-ArH, J = 7.4 Hz);
9.60 (s, 1 H, N=CH); 10.10 (s, 1 H, NH). 13C NMR, δ: 12.9
2
2
(CH); 116.1 (d, JC,F = 20.7 Hz); 121.5 (d, JC,F = 10.1 Hz);
125.0 (d, JC,F = 3.3 Hz); 126.4 (d, JC,F = 2.5 Hz); 132.5 (d,
JC,F = 8.7 Hz); 143.1 (d, JC,F = 4.9 Hz); 157.5 (C=O); 160.9 (d,
1JC,F = 251.0 Hz); 178.7 (C=S). 19F NMR, δ: –120.94. MS (ESI),
m/z: [M + Na]+; found: 330.0784; calculated for C13H14FN5OS:
330.0795.

1062 Russ. Chem. Bull., Int. Ed., Vol. 67, No. 6, June, 2018
Gazieva et al.
(Me); 13.3 (Me); 35.9 (NCH2); 37.2 (NCH2); 66.2 (CH); 74.5
(d, 1 H, CH, J = 8.5 Hz); 6.87 (d, 1 H, ArH, J = 8.2 Hz); 7.12
(t, 1 H, Ph, J = 7.3 Hz); 7.22 (d, 1 H, ArH, J = 8.2 Hz); 7.34—
7.39 (m, 3 H, ArH, Ph); 7.59 (d, 2 H, Ph, J = 8.1 Hz); 9.09
(s, 1 H, N=CH); 9.68 (s, 1 H, OH); 10.05 (s, 1 H, NH).
13C NMR, δ: 29.8 (NMe); 55.6 (OMe); 66.4 (CH); 75.5 (CH);
110.0; 115.6; 199.4 (2 C, Ph), 122.5; 123.5 (Ph); 124.9; 128.8
(2 C, Ph); 137.8 (Ph); 148.0; 149.8; 155.1 (C=O); 156.6 (N=CH);
179.2 (C=S). MS (ESI), m/z: [M + Na]+; found: 420.1096;
calculated for C19H19N5O3S: 420.1101.
Synthesis of methylsulfanyl derivatives 4a—f (general proce-
dure). Methyl iodide (0.125 mL, 2 mmol) was added to a stirred
suspension of thioglycoluril 1 (1 mmol) and potassium carbonate
(0.138 g, 1 mmol) in MeOH (30 mL). The resulting mixture was
stirred at 60 °C for 2 h and then concentrated in vacuo. The
residue was resuspended with water; the formed precipitate was
isolated by filtration, wased with water, and dried in air.
(CH); 116.2 (d, 2JC,F = 20.7 Hz); 121.4 (d, 2JC,F = 9.9 Hz); 125.1
(d, JC,F = 3.2 Hz); 126.3 (d, JC,F = 2.2 Hz); 132.7 (d, JC,F
=
= 8.6 Hz); 144.5 (d, JC,F = 4.5 Hz); 156.8 (C=O); 160.9 (d,
1JC,F = 251.2 Hz); 178.4 (C=S). 19F NMR, δ: –120.90. MS (ESI),
m/z: [M + Na]+; found: 358.1096; calculated for C15H18FN5OS:
358.1108.
(E)-1,3-Diethyl-4-[(4-f luorobenzylidene)amino]-5-
thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one (1h). The
yield was 69%, white crystals, m.p. 208—210 °C (dec.). IR (KBr),
ν/cm–1: 3199 (NH), 1680 (C=O), 1601 (C=N), 1509, 1477, 1450,
1267, 1251, 1227, 1191. 1H NMR, δ: 1.01—1.10 (m, 6 H, Me);
3.11—3.40 (m, 4 H, NCH2); 5.51 (d, 1 H, CH, J = 8.4 Hz); 5.97
(d, 1 H, CH, J = 8.4 Hz); 7.33 (t, 2 H, ArH, J = 8.7 Hz); 7.82
(dd, 2 H, ArH, J = 8.3 Hz, J = 5.8 Hz); 9.25 (s, 1 H, N=CH);
9.97 (s, 1 H, NH). 13C NMR, δ: 12.9 (Me); 13.4 (Me); 35.9
(NCH2); 37.1 (NCH2); 66.2 (CH); 74.7 (CH); 116.0 (d, 2 C,
(E)-6-[(2-Fluorobenzylidene)amino]-1,3-dimethyl-5-methyl-
sulfanyl-3,3a,6,6a-tetrahydroimidazo[4,5-d]imidazol-2(1H)-one
(4a). The yield was 91%, white powder, m.p. 208—210 °C.
IR (KBr), ν/cm–1: 1718, 1563, 1488, 1404, 1282, 1215, 1039.
1H NMR, δ: 2.44 (s, 3 H, SMe); 2.83 (s, 3 H, NMe); 2.92 (s,
3 H, NMe); 5.59 (d, 1 H, CH, J = 7.8 Hz); 6.03 (d, 1 H, CH,
J = 7.9 Hz); 7.26—7.32 (m, 2 H, 3,5-ArH); 7.41—7.47 (m, 1 H,
4-ArH); 7.79 (t, 1 H, 6-ArH, J = 7.7 Hz); 8.16 (s, 1 H, N=CH).
13C NMR, δ: 13.0 (SMe); 28.4 (NMe); 30.8 (NMe); 72.3 (CH);
2JC,F = 22.0 Hz); 129.6 (d, 2 C, 3JC,F = 8.8 Hz); 130.3 (d, 4JC,F
=
= 3.0 Hz); 152.8 (C=N); 156.8 (C=O); 163.6 (d, 1JC,F = 248.9 Hz);
178.7 (C=S). 19F NMR, δ: –110.22. MS (ESI), m/z: [M + Na]+;
found: 358.1110; calculated for C15H18FN5OS: 358.1108.
(E)-1,3-Diethyl-4-[(4-methoxybenzylidene)amino]-5-
thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one (1i). The yield
was 65%, white crystals, m.p. 208—210 °C (dec.). The spectral
characteristics corresponded to that reported earlier.6,7
2
2
(E)-1,3-Diethyl-4-{[4-(trifluoromethyl)benzylidene]amino}-
5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one (1j). The
yield was 34%, white crystals, m.p. 212—213 °C (dec.). IR (KBr),
ν/cm–1: 3243 (NH), 1686, 1677 (C=O), 1618 (weak, C=N), 1501,
1480, 1324, 1254, 1235, 1166, 1127, 1066. 1H NMR, δ: 1.01—1.11
(m, 6 H, Me); 3.10—3.45 (m, 4 H, NCH2); 5.54 (d, 1 H, CH,
J = 8.4 Hz); 6.05 (d, 1 H, CH, J = 8.3 Hz); 7.85 (d, 2 H, ArH,
J = 8.0 Hz); 7.97 (d, 2 H, ArH, J = 8.0 Hz); 9.36 (s, 1 H, N=CH);
10.13 (s, 1 H, NH). 13C NMR, δ: 13.0 (Me); 13.5 (Me); 36.0
(NCH2); 37.4 (NCH2); 66.4 (CH); 74.3 (CH); 124.1 (q, CF3,
79.9 (CH); 116.0 (d, JC,F = 20.6 Hz); 122.0 (d, JC,F =
= 10.2 Hz); 124.9 (d, JC,F = 3.2 Hz); 126.0 (d, JC,F = 2.6 Hz);
130.8 (d, JC,F = 4.3 Hz); 131.3 (d, JC,F = 8.4 Hz); 157.7 (C=O);
1
160.3 (d, JC,F = 250.1 Hz); 166.6 (N=C—S). 19F NMR,
δ: –121.63. MS (ESI), m/z: [M + Na]+; found: 344.0952; cal-
culated for C14H16FN5OS: 344.0952.
(E)-6-[(3-Methoxybenzylidene)amino]-1,3-dimethyl-5-meth-
ylsulfanyl-3,3a,6,6a-tetrahydroimidazo[4,5-d]imidazol-2(1H)-one
(4b). The yield was 81%, white powder, m.p. 160—162 °C.
IR (KBr), ν/cm–1: 1715, 1603 (weak), 1562, 1489, 1450, 1426,
1398, 1285, 1272, 1210, 1186, 1156, 1048, 1033. 1H NMR, δ: 2.43
(s, 3 H, SMe); 2.83 (s, 3 H, NMe); 2.91 (s, 3 H, NMe); 3.79
(s, 3 H, OMe); 5.59 (d, 1 H, CH, J = 7.7 Hz); 5.92 (d, 1 H, CH,
J = 7.8 Hz); 6.96 (d, 1 H, ArH, J = 7.6 Hz); 7.24—7.28 (m, 2 H,
ArH); 7.35 (t, 1 H, ArH, J = 7.7 Hz); 8.06 (s, 1 H, N=CH).
13C NMR, δ: 12.9 (SMe); 28.3 (NMe); 30.5 (NMe); 55.1 (OMe);
72.2 (CH); 80.0 (CH); 111.4; 115.2; 119.0; 129.9; 135.9; 137.9
(N=CH); 157.6 (C=O); 159.5; 166.8 (N=C—S). MS (ESI), m/z:
[M + H]+; found: 334.1320; calculated for C15H19N5O2S:
334.1332.
(E)-6-[(2-Hydroxy-3-methoxybenzylidene)amino]-1,3-di-
methyl-5-methylsulfanyl-3,3a,6,6a-tetrahydroimidazo[4,5-d]-
imidazol-2(1H)-one (4c). The yield was 79%, white powder, m.p.
187—189 °C. IR (KBr), ν/cm–1: 3301, 1704, 1606, 1579, 1566,
1480, 1444, 1403, 1267, 1213, 1193, 1066, 1036. 1H NMR, δ: 2.45
(s, 3 H, SMe); 2.82 (s, 3 H, NMe); 2.91 (s, 3 H, NMe); 3.81
(s, 3 H, OMe); 5.58 (d, 1 H, CH, J = 7.7 Hz); 5.96 (d, 1 H, CH,
J = 7.8 Hz); 6.84 (t, 1 H, ArH, J = 7.8 Hz); 6.99 (d, 1 H, ArH,
J = 7.8 Hz); 7.20 (d, 1 H, ArH, J = 7.8 Hz); 8.29 (s, 1 H, N=CH);
9.61 (s, 1 H, OH). 13C NMR, δ: 13.0 (SMe); 28.4 (NMe); 30.9
(NMe); 55.9 (OMe); 72.7 (CH); 80.1 (CH); 113.0; 118.6; 119.3;
120.2; 137.0 (N=CH); 145.8; 148.0; 157.8 (C=O); 166.6
(N=C—S). MS (ESI), m/z: [M + H]+; found: 350.1276; calcu-
lated for C15H19N5O3S: 350.1281.
3
1JC,F = 272.4 Hz); 125.9 (q, 2 C, JC,F = 3.8 Hz); 128.0 (2 C);
2
130.3 (q, JC,F = 31.8 Hz); 137.9; 149.9 (C=N); 157.0 (C=O);
178.8 (C=S). 19F NMR, δ: –62.05. MS (ESI), m/z: [M + Na]+;
found: 408.1061; calculated for C16H18F3N5OS: 408.1076.
(E)-4-[(4-Ethoxy-3-methoxybenzylidene)amino]-1,3-diethyl-
5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one (1k). The
yield was 59%, white powder, m.p. 197—199 °C (dec.). IR (KBr),
ν/cm–1: 3224 (NH), 1699, 1685 (C=O), 1602, 1571 (C=C, C=N),
1503, 1476, 1454, 1334, 1257, 1197, 1136, 1034. 1H NMR,
δ: 1.03—1.10 (m, 6 H, Me); 1.35 (t, 3 H, Me, J = 7.0 Hz);
3.11—3.41 (m, 4 H, NCH2); 3.80 (s, 3 H, OMe); 4.07 (q, 2 H,
OCH2, J = 7.0 Hz); 5.48 (d, 1 H, CH, J = 8.5 Hz); 5.93 (d, 1 H,
CH, J = 8.4 Hz); 7.04 (d, 1 H, ArH, J = 8.2 Hz); 7.26 (d, 1 H,
ArH, J = 8.2 Hz); 7.36 (s, 1 H, ArH); 9.17 (s, 1 H, N=CH); 9.85
(s, 1 H, NH). 13C NMR, δ: 12.9 (Me); 13.4 (Me); 14.6 (Me);
35.9 (NCH2); 37.1 (NCH2); 55.4 (OMe); 63.8 (OCH2); 66.1
(CH); 75.1 (CH); 109.0; 112.4; 122.2; 126.1; 149.1; 150.6; 155.6
(N=CH); 156.9 (C=O); 178.5 (C=S). MS (ESI), m/z: [M + Na]+;
found: 414.1566; calculated for C18H25N5O3S: 414.1570.
(E)-4-[(4-Hydroxy-3-methoxybenzylidene)amino]-3-methyl-
1-phenyl-5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one
(1l). The yield was 44%, white powder, m.p. 224—226 °C (dec.).
IR (KBr), ν/cm–1: 3539 (OH), 3200 (NH), 1718, 1692 (C=O),
1597 (C=C, C=N), 1498, 1461, 1450, 1429, 1403, 1377, 1269,
1249, 1227, 1198, 1175, 1118, 1030. 1H NMR, δ: 2.94 (s, 3 H,
NMe); 3.83 (s, 3 H, OMe); 6.01 (d, 1 H, CH, J = 8.4 Hz); 6.15
(E)-1,3-Diethyl-6-[(2-fluorobenzylidene)amino]-5-methyl-
sulfanyl-3,3a,6,6a-tetrahydroimidazo[4,5-d]imidazol-2(1H)-one

S-Alkylation of thioglycolurils
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 6, June, 2018
1063
(4d). The yield was 86%, white powder, m.p. 149—151 °C.
IR (KBr), ν/cm–1: 1686, 1581, 1566, 1469, 1453, 1399, 1234,
1200, 1187, 1065. 1H NMR, δ: 1.04 (t, 3 H, Me, J = 7.0 Hz); 1.13
(t, 3 H, Me, J = 7.1 Hz); 2.44 (s, 3 H, SMe); 3.12—3.55 (m, 4 H,
NCH2); 5.70 (d, 1 H, CH, J = 7.8 Hz); 6.10 (d, 1 H, CH, J =
= 7.9 Hz); 7.27—7.33 (m, 2 H, 3,5-ArH); 7.42—7.49 (m, 1 H,
4-ArH); 7.79 (t, 1 H, 6-ArH, J = 7.5 Hz); 8.04 (s, 1 H, N=CH).
13C NMR, δ: 13.0 (SMe); 13.3 (Me); 13.7 (Me); 36.2 (NCH2);
37.7 (NCH2); 70.5 (CH); 78.5 (CH); 116.0 (d, 2JC,F = 20.6 Hz);
1 H, N=CH). 13C NMR, δ: 28.3 (NMe); 30.8 (NMe); 33.1
(SCH2); 72.2 (CH); 80.0 (CH); 116.0 (d, 2JC,F = 20.6 Hz); 120.4;
121.8 (d, 2JC,F = 10.0 Hz); 124.9; 126.0; 130.9 (d, JC,F = 4.5 Hz);
131.2 (2 C); 131.3 (d, JC,F = 8.2 Hz); 131.4 (2 C); 137.2 (N=CH);
157.6 (C=O); 160.3 (d, 1JC,F = 249.7 Hz); 165.4 (N=C—S). 19
F
NMR, δ: –121.58. MS (ESI), m/z: [M + H]+; found: 476.0536;
calculated for C20H19BrFN5OS: 476.0550.
(E)-5-[(4-Bromobenzyl)sulfanyl]-6-[(3-methoxybenzylidene)-
amino]-1,3-dimethyl-3,3a,6,6a-tetrahydroimidazo[4,5-d]imid-
azol-2(1H)-one (4h). The yield was 84%, white powder, m.p.
178—180 °C. IR (KBr), ν/cm–1: 1715, 1607 (weak), 1568, 1487,
2
121.8 (d, JC,F = 10.0 Hz); 124.9 (d, JC,F = 2.9 Hz); 125.8
(d, JC,F = 2.4 Hz); 130.2 (d, JC,F = 4.6 Hz); 131.3 (d, JC,F
=
1
1
= 8.3 Hz); 156.9 (C=O); 160.4 (d, JC,F = 249.5 Hz); 166.1
(N=C—S). 19F NMR, δ: –122.47. MS (ESI), m/z: [M + Na]+;
found: 372.1262; calculated for C16H20FN5OS: 372.1265.
(E)-1,3-Diethyl-6-[(4-methoxybenzylidene)amino]-5-meth-
ylsulfanyl-3,3a,6,6a-tetrahydroimidazo[4,5-d]imidazol-2(1H)-one
(4e). The yield was 76%, white powder, m.p. 109—111 °C.
IR (KBr), ν/cm–1: 1704, 1605, 1576, 1510, 1467, 1398, 1301, 1249,
1230, 1196, 1187, 1166, 1028. 1H NMR, δ: 1.00 (t, 3 H, Me,
J = 6.8 Hz); 1.14 (t, 3 H, Me, J = 7.0 Hz); 2.42 (s, 3 H, SMe);
3.18—3.51 (m, 4 H, NCH2); 3.80 (s, 3 H, OMe); 5.68 (d, 1 H,
CH, J = 7.8 Hz); 5.96 (d, 1 H, CH, J = 7.9 Hz); 7.01 (d, 2 H,
ArH, J = 8.4 Hz); 7.61 (d, 2 H, ArH, J = 8.4 Hz); 7.91 (s, 1 H,
N=CH). 13C NMR, δ: 12.9 (SMe); 13.3 (Me); 13.9 (Me); 36.2
(NCH2); 37.6 (NCH2); 55.3 (OMe); 70.8 (CH); 78.5 (CH); 114.4
(2 C); 127.0; 128.0 (2 C); 137.9 (N=CH); 157.0 (C=O); 160.4;
166.5 (N=C—S). MS (ESI), m/z: [M + H]+; found: 362.1642;
calculated for C17H23N5O2S: 362.1645.
1410, 1264, 1201, 1188, 1044. H NMR, δ: 2.84 (s, 3 H, NMe);
2.90 (s, 3 H, NMe); 3.77 (s, 3 H, OMe); 4.27 (s, 2 H, SCH2);
5.63 (d, 1 H, CH, J = 7.5 Hz); 5.92 (d, 1 H, CH, J = 7.5 Hz);
6.95 (d, 1 H, ArH, J = 7.4 Hz); 7.21—7.26 (m, 2 H, ArH); 7.34
(t, 1 H, ArH, J = 7.6 Hz); 7.41 (d, 2 H, ArH, J = 7.7 Hz); 7.51
(d, 2 H, ArH, J = 7.7 Hz); 8.06 (s, 1 H, N=CH). 13C NMR,
δ: 28.3 (NMe); 30.5 (NMe); 33.1 (SCH2); 55.1 (OMe); 72.1
(CH); 80.0 (CH); 111.6; 115.2; 118.9; 120.3; 129.9; 131.2 (2 C);
131.4 (2 C); 135.8; 137.3; 138.1 (N=CH); 157.5 (C=O); 159.5;
165.6 (N=C—S). MS (ESI), m/z: [M + H]+; found: 488.0744;
calculated for C21H22BrN5O2S: 488.0750.
(E)-5-[(4-Bromobenzyl)sulfanyl]-6-[(2-hydroxy-3-methoxy-
benzylidene)amino]-1,3-dimethyl-3,3a,6,6a-tetrahydro-
imidazo[4,5-d]imidazol-2(1H)-one (4i). The yield was 52%, white
powder, m.p. 174—176 °C. IR (KBr), ν/cm–1: 1706, 1604 (weak),
1571, 1489, 1453, 1405, 1251, 1206, 1195, 1041. 1H NMR, δ: 2.84
(s, 3 H, NMe); 2.90 (s, 3 H, NMe); 3.80 (s, 3 H, OMe); 4.29 (s,
2 H, SCH2); 5.61 (d, 1 H, CH, J = 7.7 Hz); 5.96 (d, 1 H, CH,
J = 7.7 Hz); 6.81 (t, 1 H, ArH, J = 7.9 Hz); 6.97 (d, 1 H, ArH,
J = 7.8 Hz); 7.17 (d, 1 H, ArH, J = 7.8 Hz); 7.41 (d, 2 H, ArH,
J = 8.0 Hz); 7.52 (d, 2 H, ArH, J = 8.0 Hz); 8.28 (s, 1 H, N=CH);
9.54 (s, 1 H, OH). 13C NMR, δ: 28.3 (NMe); 30.9 (NMe); 33.1
(SCH2); 55.9 (OMe); 72.6 (CH); 80.1 (CH); 112.9; 118.3; 119.2;
120.2; 120.4; 131.2 (2 C); 131.4 (2 C); 136.7 (N=CH); 137.2;
145.8; 148.0; 157.6 (C=O); 165.3 (N=C—S). MS (ESI), m/z:
[M + H]+; found: 504.0689; calculated for C21H22BrN5O3S:
504.0699.
(E)-6-({2-[(4-Bromobenzyl)oxy]-3-methoxybenzylidene}-
amino)-5-[(4-bromobenzyl)sulfanyl]-1,3-dimethyl-3,3a,6,6a-
tetrahydroimidazo[4,5-d]imidazol-2(1H)-one (4j). The yield was
23%, white powder, m.p. 166—167 °C. 1H NMR, δ: 2.63 (s,
3 H, NMe); 2.82 (s, 3 H, NMe); 3.86 (s, 3 H, OMe); 4.26 (s,
2 H, SCH2); 4.97 (d, 1 H, OCH2, J = 11.2 Hz); 5.03 (d, 1 H,
OCH2, J = 11.2 Hz); 5.59 (d, 1 H, CH, J = 7.5 Hz); 5.76 (d,
1 H, CH, J = 7.5 Hz); 7.10—7.13 (m, 2 H, ArH); 7.28 (t, 1 H,
ArH, J = 6.8 Hz); 7.40 (d, 4 H, ArH, J = 7.9 Hz); 7.51 (d, 2 H,
ArH, J = 7.9 Hz); 7.59 (d, 2 H, ArH, J = 7.9 Hz); 8.03 (s, 1 H,
N=CH). 13C NMR, δ: 28.3 (NMe); 30.7 (NMe); 33.1 (SCH2);
55.8 (OMe); 72.6 (CH); 73.9 (OCH2); 80.1 (CH); 113.7; 116.5;
120.3; 121.2; 124.5; 127.7; 130.3 (2 C); 131.2 (2 C); 131.27 (2 C);
131.31 (2 C); 133.3 (N=CH); 136.5; 137.2; 145.9; 152.5; 157.5
(C=O); 165.7 (N=C—S).
(E)-6-[(4-Ethoxy-3-methoxybenzylidene)amino]-1,3-diethyl-
5-methylsulfanyl-3,3a,6,6a-tetrahydroimidazo[4,5-d]imidazol-
2(1H)-one (4f). The yield was 75%, white powder, m.p. 138—
140 °C. IR (KBr), ν/cm–1: 1692, 1597, 1569, 1514, 1458, 1417,
1384, 1264, 1245, 1230, 1199, 1176, 1133, 1032. 1H NMR, δ: 0.99
(t, 3 H, Me, J = 7.0 Hz); 1.14 (t, 3 H, Me, J = 7.1 Hz); 1.34 (t,
3 H, Me, J = 6.9 Hz); 2.42 (s, 3 H, SMe); 3.19—3.50 (m, 4 H,
NCH2); 3.80 (s, 3 H, OMe); 4.05 (q, 2 H, OCH2, J = 6.9 Hz);
5.68 (d, 1 H, CH, J = 7.8 Hz); 5.95 (d, 1 H, CH, J = 7.9 Hz);
7.01 (d, 1 H, ArH, J = 8.3 Hz); 7.17 (d, 1 H, ArH, J = 8.3 Hz);
7.27 (s, 1 H, ArH); 7.88 (s, 1 H, N=CH). 13C NMR, δ: 13.0
(SMe); 13.3 (Me); 13.9 (Me); 14.7 (Me); 36.2 (NCH2); 37.6
(NCH2); 55.3 (OMe); 63.8 (OCH2); 70.9 (CH); 78.5 (CH);
108.3; 112.5; 120.7; 127.1; 138.1 (N=CH); 149.1; 149.5; 157.1
(C=O); 166.5 (N=C—S). MS (ESI), m/z: [M + H]+; found:
406.1892; calculated for C19H27N5O3S: 406.1907.
Synthesis of 4-bromobenzylsulfanyl derivatives 4g—j (general
procedure). 4-Bromobenzyl bromide (0.255 mL, 1.02 mmol) was
added to a stirred solution of thioglycoluril 1 (1 mmol) and potas-
sium carbonate (0.152 g, 1.1 mmol) in DMSO (5 mL). The result-
ing mixture was stirred for 5 h, then poured into icy water and
kept in a refrigerator for 16 h. The formed precipitate was iso-
lated by filtration, wased with water, dried in air, and recrystallized
from methanol.
(E)-5-[(4-Bromobenzyl)sulfanyl]-1,3-dimethyl-6-[(2-fluoro-
benzylidene)amino]-3,3a,6,6a-tetrahydroimidazo[4,5-d]imidaz-
ol-2(1H)-one (4g). The yield was 91%, white powder, m.p.
163—164 °C. IR (KBr), ν/cm–1: 1697, 1584, 1568, 1487, 1459,
1449, 1412, 1398, 1341, 1287, 1242, 1206, 1167, 1040. 1H NMR,
δ: 2.85 (s, 3 H, NMe); 2.91 (s, 3 H, NMe); 4.29 (s, 2 H, SCH2);
5.64 (d, 1 H, CH, J = 7.8 Hz); 6.04 (d, 1 H, CH, J = 7.8 Hz);
7.25—7.30 (m, 2 H, ArH); 7.41—7.46 (m, 3 H, ArH); 7.52 (d,
2 H, ArH, J = 8.3 Hz); 7.76 (t, 1 H, ArH, J = 7.2 Hz); 8.15 (s,
The antifungal activity was evaluated in vitro according to the
known procedure20,21 using six phytopathogenic fungi species:
Venturia inaequalis, Rhizoctonia solani, Fusarium oxysporum,
Fusarium moniliforme, Bipolaris sorokiniana, and Sclerotinia
sclerotiorum. Triadimefon was used as the reference standard.
The effect of the compounds at the concentration of 30 mg L–1
on the radial growth of the mycelium was studied. Aliquots of
the tested compound solutions in acetone (3 mg mL–1) were

1064 Russ. Chem. Bull., Int. Ed., Vol. 67, No. 6, June, 2018
Gazieva et al.
added to the molten sterilized potato-sucrose agar, which was
dispensed under aseptic conditions into Petri dishes. The final
concentrations of the test substances and acetone in these media
were 30 mg L–1 and 1%, respectively. Mycelial pieces of the
fungi were placed on the solid nutrient medium and incubated
at 25 °C for 72 h; then the radial mycelial growth was measured.
Each experiment was repeated 3 times. The percentile value of
mycelial growth inhibition was calculated acording to Abbott's
method.22
11. H. R. Kim, H. J. Lee, Y. J. Choi, Y. J. Park, Y. Woo, S. J.
Kim, M. H. Park, H. W. Lee, P. Chun, H. Y. Chung, H. R.
Moon, Med. Chem. Commun., 2014, 5, 1410.
12. N. I. Vorozhtsov, L. A. Sviridova, O. S. Grigorkevich, D. D.
Korablina, E. K. Beloglazkina, A. G. Majouga, N. V. Zyk,
Russ. Chem. Bull., 2017, 66, 506.
13. R. Mahmood, S. Ahmad, M. Fettouhi, T. Roisnel, M. A.
Gilani, K. Mehmood, G. Murtaza, A. A. Isab, J. Mol. Struct.,
2018, 1156, 235.
14. K. I. Tishchenko, E. K. Beloglazkina, M. A. Proskurnin,
A. G. Mazhuga, M. E. Muratova, D. A. Skvortsov, N. V. Zyk,
Russ. Chem. Bull., 2016, 65, 1254.
References
15. E. K. Beloglazkina, N. I. Vorozhtsov, L. A. Sviridova, O. S.
Grigorkevich, D. D. Korablina, A. A. Moiseeva, N. V. Zyk,
A. G. Majouga, Inorg. Chem. Commun., 2016, 71, 86.
16. L. D. Popov, G. A. Gazieva, A. N. Kravchenko, Yu. N.
Tkachenko, O. I. Askalepova, S. I. Levchenkov, T. B.
Karpova, Yu. P. Tupolova, V. V. Lukov, V. A. Kogan, Russ.
J. Gen. Chem., 2015, 85, 92.
17. G. A. Gazieva, P. A. Poluboyarov, L. D. Popov, N. G.
Kolotyrkina, A. N. Kravchenko, N. N. Makhova, Synthesis,
2012, 44, 3366.
18. G. A. Gazieva, T. B. Karpova, L. D. Popov, Yu. V. Nelyubina,
and A. N. Kravchenko, J. Heterocycl. Chem., 2015, 52, 1390.
19. G. A. Gazieva, T. B. Karpova, T. V. Nechaeva, A. N.
Kravchenko, Russ. Chem. Bull., 2016, 65, 2172.
20. Metodicheskiye rekomendatsii po opredeleniyu fungitsidnoi
aktivnosti novykh soedinenii [Guidelines for Determination of
Fungicidal Activity of New Compounds], NIITEKHIM,
Cherkassy, 1984, 32 p. (in Russian).
1. E. A. Dlin, G. M. Averochkin, A. V. Finko, N. S. Vorobyeva,
E. K. Beloglazkina, N. V. Zyk, Y. A. Ivanenkov, D. A.
Skvortsov, V. E. Koteliansky, A. G. Majouga, Tetrahedron
Lett., 2016, 57, 5501.
2. M. Zuo, X. Xu, Z. Xie, R. Ge, Z. Zhang, Z. Li, J. Bian, Eur.
J. Med. Chem., 2017, 125, 1002.
3. A. I. El-Shenawy, Rus. J. Bioorg. Chem., 2016, 42, 100.
4. J. Thanusu, V. Kanagarajan, M. Gopalakrishnan, Bioorg.
Med. Chem. Lett., 2010, 20, 713.
5. F. Wu, H. Jiang, B. Zheng, M. Kogiso, Y. Yao, C. Zhou,
X.-N. Li, Y. Song, J. Med. Chem., 2015, 58, 6899.
6. G. A. Gazieva, Yu. B. Vikharev, L. V. Anikina, T. B. Karpova,
A. N. Kravchenko, E. A. Permyakov, I. V. Svitanko, Mendeleev
Commun., 2013, 23, 202.
7. G. A. Gazieva, L. V. Anikina, S. A. Pukhov, T. B. Karpova,
Yu. V. Nelyubina, A. N. Kravchenko, Mol. Divers., 2016,
20, 837.
8. G. A. Gazieva, L. V. Anikina, T. V. Nechaeva, S. A. Pukhov,
T. B. Karpova, S. V. Popkov, Yu. V. Nelyubina, N. G.
Kolotyrkina, A. N. Kravchenko, Eur. J. Med. Chem., 2017,
140, 141.
21. S. V. Popkov, A. A. Makarenko, G. I. Nikishin, Russ. Chem.
Bull., 2016, 65, 513.
22. N. M. Golyshin, Fungicidy v selskom khozyaistve [Fungicides
in the agriculture], Kolos, Moscow, 1970, 167 p. (in Russian).
9. L. D. Porter, T. F. Cummings, D. A. Johnson, Plant Dis.,
2006, 90, 964.
10. M. W. Ding, Y. F. Chen, N. Y. Huang, Phosphorus, Sulfur,
Silicon, Relat. Elem., 2004, 179, 2287.
Received March 19, 2018;
accepted April 9, 2018