Synthesis and fungicidal activity of novel 1,3-disubstituted 1H-diazirine derivatives

Article abstract of DOI:10.1002/jhet.524

A convenient method for synthesis of novel 1-[pyrimidinyl], 1-[1,3,5-triazin-2-carbonyl], and 1-[thiazol-5-carbonyl] derivatives of 3-thioxo-diaziridine 1, 3, 5, and 7 from corresponding hydrazides, CS2, and KOH is elaborated. The highest reaction yield w

Full text of DOI:10.1002/jhet.524

118
Synthesis and Fungicidal Activity of Novel 1,3-Disubstituted
1H-Diazirine Derivatives
Vol 48
Karine A. Eliazyan, Frunze V. Avetisyan, Tamara L. Jivanshiryan,
Vergush A. Pivazyan, Emma A. Ghazaryan, Lusya V. Shahbazyan,
Siranush V. Harutyunyan, and Aleksandr P. Yengoyan*
Laboratory of Pesticides Synthesis, Armenian State Agrarian University, Yerevan, Armenia
Armenian-Russian (Slavonic) State University, Yerevan, Armenia
*E-mail: ayengoyan@mail.ru
Received February 19, 2010
DOI 10.1002/jhet.524
Published online 9 September 2010 in Wiley Online Library (wileyonlinelibrary.com).
A convenient method for synthesis of novel 1-[pyrimidinyl], 1-[1,3,5-triazin-2-carbonyl], and 1-[thia-
zol-5-carbonyl] derivatives of 3-thioxo-diaziridine 1, 3, 5, and 7 from corresponding hydrazides, CS2,
and KOH is elaborated. The highest reaction yield was observed when these initial reagents were taken
in molar ratio of 1:1.7:2.0, respectively. By alkylation of compounds 1, 3, 5, and 7 that proceeds exclu-
sively at sulfur atom, the 3-sulfanyl derivatives of 1-[pyrimidinyl]-, 1-[1,3,5-triazin-2-carbonyl]-, and 1-
[thiazol-5-carbonyl]-diazirines 2, 4, 6, and 8 were formed. The structures of synthesized compounds
were confirmed by proton and carbon nuclear magnetic resonance (NMR), mass spectra (MS), and ele-
mental analysis. The fungicidal activities of S-substituted derivatives were studied. Data of preliminary
biological tests testify that these compounds can be of interest in search for new fungicides.
J. Heterocyclic Chem., 48, 118 (2011).
INTRODUCTION
From the 60s, various substituted diaziridines and dia-
zirines were synthesized [29–43]. Halogen derivatives
are ideal precursors for spectroscopic studies of carbens
[44–46]; several derivatives were suggested as alkylating
agents [47] and potential reagents for photolabeling of
biological receptor sites [48–57], some of the substituted
diaziridines and diazirines were investigated as anti-
cancer drugs [58,59], potential monoamine oxidase
inhibitors [60,61] and anesthetics [62,63]. At the same
time, to our astonishment, diazirine and diaziridine
derivatives practically are not investigated as chemical
means of plant protection [64].
Diazirines and diaziridines, highly strained, three-
membered heterocyclic rings with two nitrogen atoms,
were first discovered independently by Abendroth and
Henrich [1], Paulsen [2], and Schmitz and Ohme [3]. In
the following years, the series of diazirine and diaziri-
dine derivatives were synthesized and determined by flu-
orescence [4,5], infrared and electronic absorption spec-
troscopy [6–10], and microwave and electron diffraction
methods [11–13]. Chiroptical properties of several deriv-
atives have been also investigated [14–16].
The most common method of diaziridine synthesis is
a combination of a carbonyl compound, an amine, and
an electrophilic aminating agent such as chloroamine,
N-chloro-alkylamine or hydroxylamine-O-sulfonic acid
[17–19]. As an initial compound, aliphatic Schiff bases
[20,21] or O-sulfonated oximes [22] also can be used.
Schmitz [23] and Gupta [24] obtained several diaziridine
derivatives from aminal.
The purposes of the present research were the synthe-
sis of novel 1,3-disubstituted diazirines and further study
their fungicidal activity.
RESULTS AND DISCUSSION
In our early investigations, it has been established
that, under the action of CS2 and triethylamine on 2-
amino-4-hydrazino-6-methyl-pyrimidine, expected potas-
sium salt of 2-(2-amino-6-methyl-pyrimidin-4-yl)-hydra-
zinecarbodithioic acid was formed [65]. At the same
time, our new research has revealed that in more severe
conditions, when the mixture of CS2 and KOH was
Diazirines were obtained mainly by oxidative dehy-
drogenation of diaziridines by different oxidants [25].
Some diazirine derivatives were synthesized by the reac-
tion of oxime tosylates with O-alkoxyamine [26],
difluoramine with azomethines [27], or amidines with
NaOCl (NaOBr) [28].
C
V
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January 2011 Synthesis and Fungicidal Activity of Novel 1,3-Disubstituted 1H-Diazirine Derivatives
119
Scheme 1. Alternative courses of cyclization.
signal of a mobile proton is observed in the range of
14.0 ppm that corresponds to the proton of NH group.
The values of molecular ion peaks (Mþ) in mass spectra
of these compounds are also in agreement with the fact
of diaziridine cycle formation.
Compound 1 can exist in thion or thiol tautomeric
forms. However, it has been established that under the
action of alkyl halides at room temperature in water or
at short-term heating in acetone, only 3-S-substitution
took place. In 13C NMR spectra of compound 2, the sig-
1
nal of C¼¼S group is disappeared, and in H NMR spec-
tra the chemical shifts of attached alkyl groups are also
in agreement with S-substitution.
By the described method, the 1-(4-methoxy-6-methyl-
pyrimidin-2-yl)-diaziridine-3-thion (3) and correspond-
ing S-substituted derivatives (4) also were obtained from
(4-methoxy-6-methyl-pyrimidin-2-yl)-hydrazine (Scheme
2).
With the purpose of investigation, the influence of
carbonyl group on reaction course, the similar interac-
tions were carried out with 4,6-bis-dimethylamino-
[1,3,5]triazine-2-carboxylic acid hydrazide and 3,4-di-
methyl-2-thioxo-2,3-dihydro-thiazole-5-carboxylic acid
hydrazide, obtaining (4,6-bis-dimethylamino-[1,3,5]tria-
zine-2-yl)-(3-thioxo-diaziridin-1-yl)-methanone (5), (3,4-
dimethyl-2-thioxo-2,3-dihydro-thiazole-5-yl)-(3-thioxo-
diaziridin-1-yl)-methanone (7), and corresponding S-sub-
stituted derivatives (6 and 8) (Scheme 2). The structures
1
of compounds 4, 6, and 8 were also confirmed by H
and 13C NMR, MS, and elemental analysis.
Biological activity. For preliminary screening tests,
the compounds 2d,l,i,j,o and 8a,d were selected, and a
added in excess to hydrazide spirit boiling solution, the
hydrogen sulphide evolved. The physical constants of
the obtained compound differed from those of the above
mentioned substance.
Scheme 2. Synthesis of S-substituted diazirines.
As a result of hydrogen sulphide elimination, the
1,3,4-thiadiazolidine (i) or three-membered diaziridine
cycle (ii) may be formed (Scheme 1). In experiments,
the amounts of CS2 and KOH were varied; however, in
all cases, the same substance was formed. The amount
of CS2 affects only the yield of a final product. The
maximal reaction yield was observed when hydrazide,
CS2, and KOH were taken in molar ratio of 1:1.7:2.0.
These data indicate that a diaziridine cycle is formed, as
for thiadiazolidine cycle formation, more than double
excess of CS2 is required. Along the experiment, at first,
the potassium salt is formed, which is converted into
diaziridine derivative under the action of a hydrochloric
acid.
The data of spectral methods also verify mainly a dia-
ziridine cycle formation. In 13C NMR spectra of com-
pounds 1a,b, besides the absorptions of alkyl groups and
pyrimidine cycle, only one signal of thion group C¼¼S
1
(d ¼ 164.6 ppm) is observed. In H NMR spectra, the
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

120
K. A. Eliazyan, F. V. Avetisyan, T. L. Jivanshiryan, V. A. Pivazyan, E. A. Ghazaryan,
L. V. Shahbazyan, S. V. Harutyunyan, and A. P. Yengoyan
Vol 48
Table 1
acidified with 36% HCl up to pH 6. In an hour, the sediment
of compounds 1, 3, 5, and 7 was filtered off and dried in the
air. The compounds 1, 3, 5, and 7 were obtained as white, yel-
lowish, or yellow crystals.
1-(2-Amino-6-methyl-pyrimidin-4-yl)-diaziridine-3-thione
(1a). The compound was obtained in 75% yield; mp 333–
335ꢀC; recrystallized from ethanol:water (1:1); 1H NMR: d
2.13 (d, J ¼ 1.0, 3H, 6-CH3); 6.20 (q, J ¼ 1.0, 1H, 5-H); 9.55
(b.s, 2H, 2-NH2); ꢁ14.0 (v.b.s, 1H, NH). MS (m/z): 181 (Mþ).
Anal. Calcd. for C6H7N5S: C, 39.77; H, 3.89; N, 38.65; S,
17.69; Found: C, 39.60; H, 3.77; N, 38.43; S, 17.34.
1-(2-Amino-5-butyl-6-methyl-pyrimidin-4-yl)-diaziridine-3-thione
(1b). The compound was obtained in 85% yield; mp 240–
242ꢀC; recrystallized from ethanol:water (1:1); 1H NMR: d
0.99 (m, 3H, CH3-Bu); 1.30–1.38 (m, 4H, CH2CH2); 2.09 (s,
3H, 6-CH3); 2.55 (b.t, 2H, Pyr-CH2); 6.61 (b.s, 2H, 2-NH2);
ꢁ14.0 (v.w.s, 1H, NH); 13C NMR: d 13.62; 18.60; 22.08;
24.10; 30.63; 112.18; 152.85; 153.81; 164.43. MS (m/z): 237
(Mþ). Anal. Calcd. for C10H15N5S: C, 50.61; H, 6.37; N,
29.51; S, 13.51; Found: C, 50.48; H, 6.24; N, 29.24; S, 13.85.
1-(4-methoxy-6-methyl-pyrimidin-2-yl)-diaziridine-3-thione
(3). The compound was obtained in 70% yield; mp 337–
339ꢀC; recrystallized from ethanol:water (1:1); 1H NMR: d
3.10 (d, J ¼ 1.0, 3H, 6-CH3); 3.97 (s, 3H, OCH3); 6.08 (q, J
¼ 1.0, 1H, 5-H); 13.88 (b.s, 1H, NH). MS (m/z): 196 (Mþ).
Anal. Calcd. for C7H8N4OS: C, 42.85; H, 4.11; N, 28.55; S,
16.34; Found: C, 42.68; H, 3.91; N, 28.38; S, 15.97.
(4,6-Bis-dimethylamino-[1,3,5]triazin-2-yl)-(3-thioxo-diaziri-
din-1-yl)-methanone (5). The compound was obtained in 74%
yield; mp 227–229ꢀC; recrystallized from ethanol:water (1:1);
1H NMR: d 3.18 and 3.24 [s,s, 6H,6H, N(CH3)4]; 14.28 (b.s,
1H, NH). MS (m/z): 267 (Mþ). Anal. Calcd. for C9H13N7OS:
C, 40.44; H, 4,.90; N, 36.68; S, 11.99; Found: C, 40.21; H,
4,.72; N, 36.48; S, 11.63.
The fungicidal activity of compounds 2 and 8.
Water solution
concentration (%)
Pathogen
growth (%)
Preparation
Control
Dividend
Pure water
0.1
0.01
0.001
0.1
0.01
0.001
0.1
100
0
0
0
2d
2l
0
50
100
0
0.01
0.001
0.1
20
100
0
2i
0.01
0.001
0.1
0.01
0.001
0.1
0
0
2j
0
40
100
0
2o
8a
8d
0.01
0.001
0.1
0
70
0
0.01
0.001
0.1
0.01
0.001
0
40
0
60
100
fungicidal activity of their water solutions in concentra-
tions of 0.1, 0.01, and 0.001% against the fungal disease
of grain-crops Tilletia tritici was investigated. The activ-
ity of compounds was compared with that of the divi-
dend—a systemic seed treatment fungicide that is
widely used in agriculture. All investigated substances
in a various degree suppressed the growth of fungal
pathogen (Table 1), testifying the necessity of deeper
research of the fungicidal activity among the diazirine
derivatives. One substance (2i) with highest activity was
selected for field trials.
(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-(3-thioxo-
diaziridin-1-yl)-methanone (7). The compound was obtained
in 76% yield; mp 223–224ꢀC; recrystallized from methanol;
1H NMR: d 2.67 (s, 3H, 4-CH3); 3.69 (s, 3H, 3-CH3); 14.40
(v.b.s, 1H, NH); 13C NMR: d 14.47; 34.20; 101.96; 143.84;
153.58; 176.35; 186.36. MS (m/z): 245 (Mþ). Anal. Calcd. for
C7H7N3OS3: C, 34.27; H, 2.88; N, 17.13; S, 39.21; Found: C,
33.97; H, 2.68; N, 16.85; S, 38.54.
Synthesis of compounds 2, 4, 6, and 8.
General procedure. To a solution of 0.05 mol KOH and
0.05 mol of compound 1, 3, 5, or 7 in 10 mL of water, 0.05
mol of alkyl halide was added with continuous stirring at
20ꢀC, and the mixture was allowed to stand overnight. The
residue was filtered off, washed with water and dried in the
air. Aryloxyethyl derivatives were obtained at heating in ace-
tone at 50 to 55ꢀC for 3 to 4 h. The compounds 2, 4, 6, and 8
were obtained as white, yellowish or yellow crystals.
EXPERIMENTAL
The 1H NMR and 13C NMR spectra were determined by
Varian Mercury-300 MHz spectrometer, in the mixture of sol-
vents DMSO-d6 and CCl4 (1:3), mass spectra were recorded
on MX-1321A MS system. The reaction course control and
individuality of the obtained substances were checked by using
the TLC method on ‘‘Silufol UV-254’’ plates and acetone:hex-
ane mixture (2:1) as eluent. Melting points are uncorrected.
Initial hydrazides were prepared as described in [66,67].
Synthesis of compounds 1, 3, 5, and 7.
General Procedure. To a mixture of 0.02 mol azinyl-, azi-
nylcarbonyl, or 1-[thiazol-5-carbonyl] hydrazide, 10 mL etha-
nol and 0.034 mol CS2, a solution of 0.04 mol KOH in 10 mL
ethanol at boiling was added dropwise with continuous stir-
ring, and then the mixture was boiled for 7 to 8 h. After evap-
oration of ethanol, the residue was dissolved in water and
1-(2-Amino-6-methyl-pyrimidin-4-yl)-3-methylsulfanyl-1H-
diazirine (2a). The compound was obtained in 70% yield; mp
1
186–187ꢀC; recrystallized from dioxane:water (1:2); H NMR:
d 2.28 (d, J ¼ 1.0, 3H, 6-CH3); 2.65 (s, 3H, SCH3); 6.62 (q, J
¼ 1.0, 1H, 5-H); 7.62 (b.s, 2H, 2-NH2). MS (m/z): 195 (Mþ).
Anal. Calcd. for C7H9N5S: C, 43.06; H, 4.65; N, 35.87; S,
16.42; Found: C, 42.94; H, 4.47; N, 35.67; S, 16.16.
1-(2-Amino-5-butyl-6-methyl-pyrimidin-4-yl)-3-ethylsulfanyl-
1H-diazirine (2b). The compound was obtained in 59% yield;
mp 103–105ꢀC; recrystallized from dioxane:water (1:2);
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January 2011 Synthesis and Fungicidal Activity of Novel 1,3-Disubstituted 1H-Diazirine Derivatives
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1H NMR d (ppm): 0.98 (t, J ¼ 7.4, 3H, CH3-Pr); 1.30 (t, J ¼
1-(2-Amino-5-butyl-6-methyl-pyrimidin-4-yl)-3-phenoxy-eth-
ylsulfanyl-1H-diazirine (2i). The compound was obtained in
75% yield; mp 110–112ꢀC; recrystallized from toluene; 1H
NMR: d 0.97 (t, J ¼ 7.4, 3H, CH3-Bu); 1.43 and 1.58 (m, 4H,
CH2CH2); 2.23 (3H, s, 6-CH3); 2.77 (t, J ¼ 7.4, 2H, Pyr-
CH2); 3.42 (t, J ¼ 7.1, 2H, SCH2); 4.23 (t, J ¼ 7.1, 2H,
OCH2); 6.72–7.23 (m, 5H, C6H5); 7.40 (b.s, 2H, 2-NH2). MS
(m/z): 357 (Mþ). Anal. Calcd. for C18H23N5OS: C, 60.48; H,
6.49; N, 19.59; S, 8.97; Found: C, 60.28; H, 6.25; N, 19.21; S,
8.65.
7.4, 3H, CH3CH2S); 1.42 and 1.58 (m, 4H, CH2CH2); 2.24 (s,
3H, 6-CH3); 2.75 (t, J ¼ 7.4, 2H, 5-CH2-Pr); 3.08 (q, J ¼ 7.4,
2H, CH3CH2S); 7.42 (b.s, 2H, NH2); 13C NMR: d 13.55;
14.19; 19.24; 22.08; 25.17; 30.82; 31.43; 109.09; 136.07;
142.83; 147.67; 153.41. MS (m/z): 265 (Mþ). Anal. Calcd. for
C12H19N5S: C, 54.31; H, 7.22; N, 26.39; S, 12.08; Found: C,
54.48; H, 7.37; N, 26.05; S, 11.84.
1-(2-Amino-5-ethyl-6-methyl-pyrimidin-4-yl)-3-methylsulfanyl-
1H-diazirine (2c). The compound was obtained in 80% yield;
mp 203–205ꢀC; recrystallized from dioxane:water (1:2); 1H
NMR: d 1.20 (t, J ¼ 7.4, 3H, CH3CH2); 2.25 (s, 3H, 6-CH3);
2.67 (s, 3H, SCH3); 2.78 (q, J ¼ 7.4, 2H, CH2CH3); 7.30 (b.s,
2H, 2-NH2). MS (m/z): 223 (Mþ). Anal. Calcd. for C9H13N5S:
C, 48.41; H, 5.87; N, 31.36; S, 14.36; Found: C, 48.27; H,
5.69; N, 31.08; S, 14.61.
1-(2-Amino-5-ethyl-6-methyl-pyrimidin-4-yl)-3-ethylsulfanyl-
1H-diazirine (2d). The compound was obtained in 80% yield;
mp 155–157ꢀC; recrystallized from dioxane:water (1:2); 1H
NMR: d 1.19 (t, J ¼ 7.4, 3H, CH3CH2); 1.24 (t, J ¼ 7.4, 3H,
CH3CH2S); 2.32 (s, 3H, 6-CH3); 2.75 (q, J ¼ 7.4, 2H,
CH3CH2); 3.21 (q, J ¼ 7.4, 2H, CH3CH2S); 6.93 (2H, b.s, 2-
NH2). MS (m/z): 237 (Mþ). Anal. Calcd. for C10H15N5S: C,
50.61; H, 6.37; N, 29.51; S, 13.51; Found: C, 50.49; H, 6.18;
N, 29.20; S, 13.80.
1-(2-Amino-5-ethyl-6-methyl-pyrimidin-4-yl)-3-(2-p-tolyloxy-
ethylsulfanyl)-1H-diazirine (2j). The compound was obtained
in 82% yield; mp 132–134ꢀC; recrystallized from toluene; 1H
NMR: d 1.20 (t, J ¼ 7.4, 3H, CH3CH2); 2.23 (s, 3H, 6-CH3);
2.25 (s, 3H, CH3-tolyl); 2.80 (q, J ¼ 7.4, 2H, CH3CH2); 3.42
(t, J ¼ 7.1, 2H, SCH2); 4.22 (t, J ¼ 7.0, 2H, OCH2); 6.62 and
6.96 (m,m, 2H,2H, C6H4); 7.38 (b.s, 2H, 2-NH2). MS (m/z):
343 (Mþ). Anal. Calcd. for C17H21N5OS: C, 59.45; H, 6.16;
N, 20.39; S, 9.34; Found: C, 59.23; H, 6.01; N, 20.12; S, 8.97.
1-(2-Amino-5-ethyl-6-methyl-pyrimidin-4-yl)-3-(2-o-tolyloxy-
ethylsulfanyl)-1H-diazirine (2k). The compound was obtained
in 73% yield; mp 163–165ꢀC; recrystallized from toluene; 1H
NMR: d 1.20 (t, J ¼ 7.4, 3H, CH3CH2); 2.23 (s, 3H, 6-CH3);
2.25 (s, 3H, CH3-tolyl); 2.80 (q, J ¼ 7.4, 2H, CH3CH2); 3.42
(t, J ¼ 7.1, 2H, SCH2); 4.22 (t, J ¼ 7.0, 2H, OCH2); 6.62 and
6.96 (m,m, 2H,2H, C6H4); 7.38 (b.s, 2H, 2-NH2). MS (m/z):
343 (Mþ). Anal. Calcd. for C17H21N5OS: C, 59.45; H, 6.16;
N, 20.39; S, 9.34; Found: C, 59.21; H, 6.13; N, 20.25; S, 9.03.
[1-(2-Amino-5-ethyl-6-methyl-pyrimidin-4-yl)-1H-diazirin-3-
ylsulfanyl]-acetonitrile (2l). The compound was obtained in
85% yield; mp 178–180ꢀC; recrystallized from acetone:water
[1-(2-Amino-5-ethyl-6-methyl-pyrimidin-4-yl)-1H-diazirin-3-
ylsulfanyl]-acetic acid methyl ester (2e). The compound was
obtained in 67% yield; mp 177–179ꢀC; recrystallized from hex-
1
ane; H NMR: d 1.20 (t, J ¼ 7.5, 3H, CH3CH2); 2.27 (s, 3H, 6-
CH3); 2.80 (q, J ¼ 7.5, 2H, CH3CH2); 3.63 (s, 3H, OCH3); 3.90
(s, 2H, SCH2); 7.38 (b.s, 2H, 2-NH2). MS (m/z): 281 (Mþ).
Anal. Calcd. for C11H15N5O2S: C, 46.96; H, 5.37; N, 24.89; S,
11.40; Found: C, 46.75; H, 5.22; N, 24.60; S, 11.64.
1
(1:2); H NMR: d 1.23 (t, J ¼ 7.4, 3H, CH3CH2); 2.27 (s, 3H,
6-CH3); 2.80 (q, J ¼ 7.4, 2H, CH3CH2); 4.10 (s, 2H, SCH2);
7.33 (b.s, 2H, 2-NH2). MS (m/z): 248 (Mþ). Anal. Calcd. for
C10H12N6S: C, 48.37; H, 4.87; N, 33.85; S, 12.91; Found: C,
48.19; H, 4.67; N, 33.59; S, 12.65.
[1-(2-Amino-5-ethyl-6-methyl-pyrimidin-4-yl)-1H-diazirin-3-
ylsulfanyl]-acetic acid ethyl ester (2f). The compound was
obtained in 71% yield; mp 201–203ꢀC; recrystallized from
hexane; 1H NMR: d 1.18 (t, J ¼ 7.5, 3H, CH3CH2); 1.22 (t,
J ¼ 7.3, 3H, CH3CH2O); 2.28 (s, 3H, 6-CH3); 2.82 (q, J ¼
7.5, 2H, CH3CH2); 3.85 (s, 2H, SCH2); 4.08 (q, J ¼ 7.3, 2H,
CH3CH2O); 7.38 (b.s, 2H, 2-NH2). MS (m/z): 295 (Mþ). Anal.
Calcd. for C12H17N5O2S: C, 48.80; H, 5.80; N, 23.71; S,
10.83; Found: C, 48.69; H, 5.58; N, 23.46; S, 10.51.
1-(2-Amino-5-ethyl-6-methyl-pyrimidin-4-yl)-3-benzylsulfanyl-
1H-diazirine (2g). The compound was obtained in 80% yield;
mp 168–170ꢀC; recrystallized from dioxane:water (1:2); 1H
NMR d (ppm): 1.20 (3H, t, J ¼ 7.4, CH3CH2); 2.24 (3H, s, 6-
CH3); 2.80 (q, J ¼ 7.4, 2H, CH3CH2); 4.29 (s, 2H, SCH2);
7.18–7.22 (5H, m, C6H5); 7.23 (2H, b.s, 2-NH2); 13C NMR: d
13.28; 18.67; 19.01; 41.98; 110.29; 127.12; 127.97; 128.47;
128.50; 135.46; 136.00; 142.65; 147.46; 153.06. MS (m/z):
299 (Mþ). Anal. Calcd. for C15H17N5S: C, 60.18; H, 5.72; N,
23.39; S, 10.71; Found: C, 60.02; H, 5.58; N, 23.12; S, 10.52.
1-(2-Amino-5-ethyl-6-methyl-pyrimidin-4-yl)-3-phenoxy-eth-
ylsulfanyl-1H-diazirine (2h). The compound was obtained in
69% yield; mp 138–140ꢀC; recrystallized from toluene; 1H
NMR: d 1.21 (t, J ¼ 7.5, 3H, CH3CH2); 2.25 (s, 3H, 6-CH3);
2.80 (q, J ¼ 7.5, 2H, CH3CH2); 3.42 (t, J ¼ 7.1, 2H, SCH2);
4.25 (t, J ¼ 7.1, 2H, OCH2); 6.70–7.23 (m, 5H, C6H5); 7.40
(b.s, 2H, 2-NH2). MS (m/z): 329 (Mþ). Anal. Calcd. for
C16H19N5OS: C, 58.34; H, 5.81; N, 21.26; S, 9.73; Found: C,
58.14; H, 5.65; N, 20.92; S, 9.85.
2-[1-(2-Amino-5-ethyl-6-methyl-pyrimidin-4-yl)-1H-diazirin-3-
ylsulfanyl]-acetamide (2m). The compound was obtained in
87% yield; mp 177–179ꢀC; recrystallized from ethanol:water
1
(1:1); H NMR: d 1.20 (t, J ¼ 7.5, 3H, CH3CH2); 2.27 (s, 3H,
6-CH3); 2.80 (q, J ¼ 7.5, 2H, CH3CH2); 3.75 (s, 2H, SCH2);
6.97 and 7.51 (b.s, 1H,1H, NH2-amid); 7.46 (b.s, 2H, 2-NH2);
13C NMR: d 13.46; 18.72; 19.25; 40.85; 109.98; 136.96;
143.40; 148.00; 153.30; 168.51. MS (m/z): 266 (Mþ). Anal.
Calcd. for C10H14N6OS: C, 45.10; H, 5.30; N, 31.56; S, 12.04;
Found: C, 45.21; H, 5.13; N, 31.30; S, 11.84.
2-[1-(2-Amino-5-butyl-6-methyl-pyrimidin-4-yl)-1H-diazirin-3-
ylsulfanyl]-acetamide (2n). The compound was obtained in
88% yield; mp 203–205ꢀC; recrystallized from ethanol:water
(1:1); 1H NMR: d 0.97 (t, J ¼ 7.4, 3H, CH3-Bu); 1.45 and
1.60 (m, 4H, CH2CH2); 2.24 (s, 3H, 6-CH3); 2.75 (q, J ¼ 7.4,
2H, Pyr-CH2); 3.75 (s, 2H, SCH2); 7.10 and 7.53 (b.s, 1H,1H,
NH2-amid); 7.54 (b.s, 2H, 2-NH2). MS (m/z): 294 (Mþ). Anal.
Calcd. for C12H18N6OS: C, 48.96; H, 6.16; N, 28.55; S, 10.89;
Found: C, 48.75; H, 6.02; N, 28.19; S, 10.76.
3-[1-(2-Amino-5-ethyl-6-methyl-pyrimidin-4-yl)-1H-diazirin-
3-ylsulfanyl]-pentane-2,4-dione (2o). The compound was
obtained in 77% yield; mp 175–177ꢀC; recrystallized from
acetone:water (1:2); 1H NMR: d 1.20 (t, J ¼ 7.5, 3H,
CH3CH2); 2.25 (s, 3H, 6-CH3); 2.50 [s, 6H, (CH3)2 of ketone
and enol]; 2.77 (q, J ¼ 7.5, 2H, CH3CH2); 5.98 (s, CH-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

122
K. A. Eliazyan, F. V. Avetisyan, T. L. Jivanshiryan, V. A. Pivazyan, E. A. Ghazaryan,
L. V. Shahbazyan, S. V. Harutyunyan, and A. P. Yengoyan
Vol 48
ketone-15%); 7.10 (b.s, 2H, 2-NH2); 17.2 (v.b.s, OH-enol-
85%); 13C NMR: d 13.21; 18.75; 18.84; 24.44; 101.13;
110.42; 138.91; 142.49; 146.69; 152.93; 196.92. MS (m/z):
307 (Mþ). Anal. Calcd. for C13H17N5O2S: C, 50.80; H, 5.57;
N, 22.78; S, 10.43; Found: C, 50.69; H, 5.39; N, 22.51; S,
10.78.
3.49; N, 13.24; S, 30.31; Found: C, 37.70; H, 3.25; N, 13.00;
S, 29.95.
2-[1-(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-carbonyl)-
1H-diazirin-3-ylsulfanyl]-acetamid (8d). The compound was
obtained in 81% yield; mp 192–194ꢀC; purified at boiling
1
from ethanol; H NMR: d 2.70 (s, 3H, 4-CH3); 3.70 (s, 3H, 3-
1-(4-methoxy-6-methyl-pyrimidin-2-yl)-3-ethylsulfanyl-1H-
diazirine (4a). The compound was obtained in 67% yield; mp
CH3); 4.00 (s, 2H, SCH2); 7.12 and 7.58 (b.s, 2H, NH2); 13C
NMR: d 14.51; 34.34; 35.90; 102.30; 143.78; 158.16; 162.79;
167.14; 186.30. MS (m/z): 302 (Mþ). Anal. Calcd. for
C9H10N4O2S3: C, 35.75; H, 3.33; N, 18.53; S, 31.81; Found:
C, 35.53; H, 3.14; N, 18.33; S, 31.94.
1
147–149ꢀC; recrystallized from dioxane:water (1:2); H NMR:
d 1.45 (t, J ¼ 7.2, 3H, CH3CH2); 2.90 (d, J ¼ 1.0, 3H, 6-
CH3); 3.27 (q, J ¼ 7.2, 2H, SCH2); 4.00 (s, 3H, OCH3); 6.30
(q, J ¼ 1.0, 1H, 5-H). MS (m/z): 224 (Mþ). Anal. Calcd. for
C9H12N4OS: C, 48.20; H, 5.39; N, 24.98; S, 14.30; Found: C,
48.02; H, 5.22; N, 24.67; S, 13.91.
[1-(4-methoxy-6-methyl-pyrimidin-2-yl)-1H-diazirine-3-ylsul-
fanyl]-acetonitrile (4b). The compound was obtained in 75%
yield; mp 210–212ꢀC; recrystallized from acetone:water (1:2);
1H NMR: d 2.89 (d, J ¼ 1.0, 3H, 6-CH3); 4.04 (s, 3H, OCH3);
4.25 (s, 2H, SCH2); 6.40 (q, J ¼ 1.0, 1H, 5-H); 13C NMR d:
18.70; 19.92; 53.89; 102.58; 116.47; 137.05; 146.44; 155.09;
164.48. MS (m/z): 235 (Mþ). Anal. Calcd. for C9H9N5OS: C,
45.95; H, 3.86; N, 29.77; S, 13.63; Found: C, 45.82; H, 3.67;
N, 29.51; S, 13.81.
(4,6-Bis-dimethylamino-[1,3,5]triazin-2-yl)-(3-methylsulfanyl-
diazirin-1-yl)-methanone (6a). The compound was obtained in
80% yield; mp 158–160ꢀC; recrystallized from hexane:benzene
(1:1); 1H NMR: d 2.80 (s, 3H, SACH3); 3.15 and 3.23 [s,s,
6H,6H, N(CH3)4]. MS (m/z): 281 (Mþ). Anal. Calcd. for
C10H15N7OS: C, 42.69; H, 5.37; N, 34.85; S, 11.40; Found: C,
42.42; H, 5.26; N, 34.59; S, 11.12.
3-[1-(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-carbonyl)-
1H-diazirin-3-ylsulfanyl]-pentane-2,4-dione (8e). The com-
pound was obtained in 90% yield; mp 174–176ꢀC; recrystal-
lized from hexane:benzene (1:1); 1H NMR: d 2.45 [s, 6H,
(CH3)2 ketone and enol]; 2.69 (s, 3H, 4-CH3); 3.70 (s, 3H, 3-
CH3); 5.76 (s, CH-ketone 20%); 17.35 (b.s, OH-enol 80%);
13C NMR: d 14.43; 23.93; 34.20; 38.66; 102.17; 143.68;
158.77; 161.36; 186.39; 197.08. MS (m/z): 343 (Mþ). Anal.
Calcd. for C12H13N3O3S3: C, 41.97; H, 3.82; N, 12.23; S,
28.01; Found: C, 41.72; H, 3.79; N, 11.92; S, 27.74.
(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-(3-benzylsul-
fanyl-diazirin-1-yl)-methanone (8f). The compound was
obtained in 94% yield; mp 132–134ꢀC; recrystallized from
1
hexane:benzene (1:1); H NMR: d 2.68 (s, 3H, 4-CH3); 3.69 (s,
3H, 3-CH3); 4.50 (s, 2H, SCH2); 7.23–7.46 (m, 5H, C6H5); 13C
NMR: d 14.44; 34.17; 36.01; 102.20; 127.32; 128.05; 128.58;
135.36; 143.36; 158.27; 162.19; 186.35. MS (m/z): 335 (Mþ).
Anal Calcd. for C14H13N3OS3: C, 50.12; H, 3.91; N, 12.53; S,
28.67; Found: C, 50.23; H, 3.79; N, 12.23; S 28.36.
(4,6-Bis-dimethylamino-[1,3,5]triazin-2-yl)-(3-benzylsulfanyl-
diazirin-1-yl)-methanone (6b). The compound was obtained in
55% yield; mp 125–127ꢀC; recrystallized from hexane:benzene
(1:1); 1H NMR: d 3.16 and 3.23 [s,s, 6H,6H, N(CH3)4]; 4.56
(s, 2H, SACH2); 7.22–7.50 (m, 5H, C6H5). MS (m/z): 357
(Mþ). Anal. Calcd. for C16H19N7OS: C, 53.76; H, 5.36; N,
27.43; S, 8.97; Found: C, 53.62; H, 5.17; N, 27.13; S, 8.68.
(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-(3-methylsul-
fanyl-diazirin-1-yl)-methanone (8a). The compound was
obtained in 76% yield; mp 154–156ꢀC; recrystallized from tol-
uene; 1H NMR: d 2.70 (s, 3H, 4-CH3); 2.78 (s, 3H, SCH3);
3.71 (s, 3H, 3-CH3); 13C NMR: d 14.08; 14.46; 34.21; 102.29;
143.28; 158.18; 163.36; 186.33. MS (m/z): 259 (Mþ). Anal.
Calcd. for C8H9N3OS3: C, 37.05; H, 3.50; N, 16.20; S, 37.09;
Found: C, 36.85; H, 3.28; N, 15.89; S, 36.78.
(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-[3-(4-chloro-
benzylsulfanyl)-diazirin-1-yl]-methanone (8g). The compound
was obtained in 88% yield; mp 168–169ꢀC; recrystallized
from hexane:benzene (1:1); 1H NMR: d 2.68 (s, 3H, 4-CH3);
3.69 (s, 3H, 3-CH3); 4.49 (s, 2H, SCH2); 7.30 and 7.46 (m,m,
2H,2H, C6H4); 13C NMR: d 14.45; 34.19; 35.17; 102.19;
128.10; 130.28; 132.84; 134.46; 143.43; 158.35; 162.03;
186.36. MS (m/z): 369 and 371 (Mþ). Anal. Calcd. for
C14H12ClN3OS3: C, 45.46; H, 3.27; N, 11.36; S, 26.00; Cl,
9.58; Found: C, 45.27; H, 3.09; N, 11.12; S, 25.78, Cl, 9.28.
(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-{3-[2-(4-bromo-
phenoxy)-ethylsulfanyl]-diazirin-1-yl}-methanone
(8h). The
compound was obtained in 90% yield; mp 158–160ꢀC; recrys-
tallized from hexane:benzene (1:1); 1H NMR: d 2.69 (s, 3H,
4-CH3); 3.65 (t, J ¼ 6.1, 2H, SCH2); 3.70 (s, 3H, 3-CH3);
4.36 (t, J ¼ 6.1, 2H, OCH2); 6.86 and 7.35 (m,m, 2H,2H,
C6H4); 13C NMR: d 14.44; 31.12; 34.19; 65.63; 102.20;
112.44; 116.12; 131.63; 143.40; 156.76; 158.33; 162.38;
186.37. MS (m/z): 443 and 445 (Mþ). Anal. Calcd. for
C15H14BrN3O2S3: C, 40.54; H, 3.18; N, 9.46; S, 21.65. Found:
C, 40.30; H, 2.95; N, 9.68; S, 21.56.
(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-(3-propylsulfanyl-
diazirin-1-yl)- methanone (8b). The compound was obtained in
87% yield; mp 124–126ꢀC; recrystallized from hexane:benzene
1
(1:1); H NMR: d 1.09 (t, J ¼ 7.3, 3H, CH3-Pr); 1.87 (m, 2H,
CH3CH2CH2); 2.71 (s, 3H, 4-CH3); 3.26 (t, J ¼ 7.2, 2H,
SCH2); 3.70 (s, 3H, 3-CH3); 13C NMR: d 12.58; 14.43; 22.09;
33.83; 34.18; 102.33; 143.16; 158.05; 162.71; 186.30. MS (m/
z): 287 (Mþ). Anal. Calcd. for C10H13N3OS3: C, 41.79; H,
4.56; N, 14.62; S, 33.47; Found: C, 41.62; H, 4.34; N, 14.21;
S, 33.62.
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