Synthesis of 3,4-dialkyl-5-(1-oxo-ethyl)-3h-thiazole-2-thiones derivatives and their pesticidal activity

Article abstract of DOI:10.1002/jhet.1596

By interaction of N-methyl(ethyl)-dithiocarbamate sodium salt with 3-chloro-pentane-2,4-dion the 1-(3-alkyl-4-methyl-2-thioxo-2,3-dihydro-thiazol- 5-yl)-ethanones 1, 2 and corresponding oximes 7, 8 were synthesized. On the basis of the mentioned compounds

Full text of DOI:10.1002/jhet.1596

Month 2013
Synthesis of 3,4-Dialkyl-5-(1-oxo-ethyl)-3H-thiazole-2-thiones Derivatives
and Their Pesticidal Activity
a
b
a
a
a
Karine A. Eliazyan, Aram M. Knyazyan, Vergush A. Pivazyan, Emma A. Ghazaryan, Siranush V. Harutyunyan,
a,b
and Aleksandr P. Yengoyan *
a
Laboratory of Pesticides Synthesis, State Agrarian University of Armenia, Yerevan, Armenia
b
Armenian–Russian (Slavonic) State University, Yerevan, Armenia
*
E-mail: ayengoyan@mail.ru
Received September 21, 2011
DOI 10.1002/jhet.1596
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
H C
H3C
C O
H C
H3C
H C C N
3
3
3
H C
3
C N
H3C
H3C
C N
HN R1
OH
OR2
N
S
N
S
N
S
N
S
R
R
R
R
S
S
S
S
3
-6
1,2
7,8
9-12
By interaction of N-methyl(ethyl)-dithiocarbamate sodium salt with 3-chloro-pentane-2,4-dion the 1-(3-alkyl-4-
methyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanones 1,2 and corresponding oximes 7,8 were synthesized. On the
basis of the mentioned compounds hydrazono (3,4), ureayl and thioureayl (5,6) derivatives, substituted oximes
(9,10) and azinyl oximes (11,12) were obtained. The structures of synthesized compounds were confirmed by
proton nuclear magnetic resonance spectroscopy and elemental analysis. The pesticidal activities of synthesized
compounds were studied. Some of the synthesized compounds simultaneously have shown growth stimulant
and fungicidal activity.
J. Heterocyclic Chem., 00, 00 (2013).
INTRODUCTION
chloro-acetic acid methyl ester, phenyl isocyanate and
various azinyl-trimethylammonium chlorides, corresponding
O-substituted derivatives (9–12) were obtained.
The chemical means of plants protection, which molecules
contain thiazole (thiazoline or thiazolidine) ring, are widely
used in agriculture. Among them, there are known herbicides
1
In H NMR spectra of oximes (7,8) and some of their
derivatives (9,10a), two groups of absorptions corresponding
to E-isomers and Z-isomers appeared. The E/Z-isomers ratio
depended on steric factor. In unsubstituted oximes (7,8),
these isomers were in molar ratio of 1:1. When the hydrogen
atom was replaced by methyl group (9,10a), the amount of
E-isomer was increased (Z/E = 1:7). In cases of more steric
(
mefenacet, thiazopir, metabenzthiazuron, fenthiaprop, bena-
zolin, benzthiazuron), fungicides (ethaboxam, thiabendazole,
fluthianil, thiadifluor, thifluzamide, metsulfovax, isotianil,
octhilinone), insecticides (clothianidin, thiamethoxam, tazim-
carb, thiacloprid, imidaclothiz, thiapronil), acaricides (fluben-
zimine, hexythiazox) and others. At the same time, the search
for new pesticides is continuing among the new series of
thiazole derivatives [1–9], in particular hydrazones, oximes
and their ethers with fungicidal [10,11], herbicidal [12,13]
and insecticidal [14] activities. The purpose of the present
research was the synthesis of thiazole derivatives on the basis
of 1-(3-alkyl-4-methyl-2-thioxo-2,3-dihydro-thiazol-5-
yl)-ethanones and study of their pesticidal activity.
1
bulky substituents (9,10b,c and 11,12) in H NMR spectra,
only signals of E-isomers were observed. Probably, the small
amounts of Z-isomers were lost at purification.
BIOLOGICAL ACTIVITY
In preliminary biological tests, the fungicidal and growth
regulatory properties of synthesized compounds were investi-
gated for their aqueous emulsions. As test objects, the mono-
cotyledonous (wheat) and dicotyledonous (French bean)
culture plants were taken.
RESULTS AND DISCUSSION
The basic 1-(3-alkyl-4-methyl-2-thioxo-2,3-dihydro-thiazol-
The growth regulatory action of emulsions in concentra-
tions of 25 mg/L and 50 mg/L was investigated on the
swelling, germination, growth and survivability of seeds and
seedlings of mentioned plants. The activities of these
compounds were compared with that of heteroauxin. All
investigated substances in varying degrees have shown a
growth stimulant activity (Table 1). Some of them surpassed
heteroauxin on 10–30%.
5
-yl)-ethanones 1,2 were synthesized by interaction of
N-alkyl-dithiocarbamate sodium salt with 3-chloro-pentane-
,4-dion (Scheme 1). The latter with substituted hidrazines,
ureas and thioureas were formed corresponding hydrazones
3,4), ureayl-imino and thioureayl-imino derivatives (5,6).
2
(
The interaction of ketones 1,2 with hydroxylamine hydrochlo-
ride in alkaline solution lead to 1-(3-alkyl-4-methyl-2-thioxo-
2
,3-dihydro-thiazol-5-yl)-ethanone oximes (7,8) formation.
The fungicidal activity of emulsions in concentrations of
1000; 100 and 10 mg/L was investigated against the fungi
When obtained oximes were reacted with dimethyl sulfate,
©
2013 HeteroCorporation

K. A. Eliazyan, A. M. Knyazyan, V. A. Pivazyan, E. A. Ghazaryan, S. V. Harutyunyan,
and A. P. Yengoyan
Vol 000
Scheme 1. Synthesis of 1-(3-4-dialkyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanones and their derivatives.
Tilletia tritici, Fusarium moniliforme, Fusarium oxysporum,
Helminthosporium sativum, Alternaria solani and Macro-
sporium solani. The most of preparations at concentrations
substances were checked by using the TLC method on UV-254
plates (Silufol, Czech Republic) with the acetone-hexane mixture
(
2:1) as eluent. Melting points are uncorrected.
General procedure: Synthesis of compounds 1,2.
To a
(
1000 and 100 mg/L) suppressed T. tritici fungi pathogen
solution of methyl(ethyl)-dithiocarbamate sodium salt (0.01 mol)
ꢀ
growth (Table 1). At the lowest concentration (10 mg/L),
the inhibitory action, some of them, was in the range of
in 10 mL of water, at 0 C 0.01 mol of 3-chloro-pentane-2,
4
-dion was added dropwise with continuous stirring. The reaction
ꢀ
6
0–90%. The action of preparations on the other fungi was
mixture was allowed to stand at 20 C for 24h, then extracted with
insignificant.
benzene and dried over waterless CaCl . Benzene extract was
2
boiled at reflux for 3 h, benzene was distillated and the residue
was processed with hexane and filtered off. Compounds 1,2 were
recrystallized from hexane/benzene (2:1).
CONCLUSION
1
-(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanone
In conclusion, the preliminary screening data indicate
that some of the synthesized compounds (9c, 11c,e,f,g
and 12e) have simultaneously high growth stimulant and
fungicidal activities. In our opinion, this combination of
properties will be useful for pre-sowing seed treatment of
grain crops. In addition, the use of preparations with dual
action reduces the number of treatments that will have sig-
nificant economic effect. The aforementioned substances
are selected for field trials.
(
1
1).
The compound was obtained as yellowish crystals; mp
ꢀ
1
18–119 C, yield: 1.5 g (80%). H NMR: d 2.22 (s, 3H, 4-CH
3
);
2.30 (s, 3H, C(O)CH ); 3.65 (s, 3H, 3-CH ). Anal. Calcd for
C
4
3
3
7
H
9
2
NOS : C, 44.89; H, 4.84; N, 7.48; S, 34.24. Found: C,
4.69; H, 4.75; N, 7.20; S, 34.02.
1
-(3-Ethyl-4-methyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanone
(2).
The compound was obtained as yellowish crystals; mp
ꢀ
1
1
3
4
22–124 C, yield: 1.33 g (66%). H NMR: d 1.32 (t, J=7.0,
H, 3-CH
.30 (q, J=7.0, 2H, 3-CH CH ).
2 3 3 3
CH ); 2.24 (s, 3H, 4-CH ); 2.31 (s, 3H, C(O)CH );
2
3
General procedure: Synthesis of compounds 3,4. To a
suspension of N-substituted hydrazine (0.002 mol) in 5 mL of
water, 0.35 mL of 20% HCl was added with continuous stirring.
EXPERIMENTAL
To an obtained solution, 0.002 mol of ketone 1 (or 2) was
ꢀ
1
The H NMR spectra were recorded by Mercury-300MHz spec-
trometer (Varian, Palo Alto, CA, USA), in the mixture of solvents
DMSO-d + CCl (1:3), using tetramethylsilane as internal standard.
The reaction course control and individuality of the obtained
added, and reaction mixture was allowed to stand at 20 C for
24 h. The sediment of hydrazone was filtered off, washed with
water and dried in the air. Compounds 3,4 were purified by
boiling in benzene.
6
4
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Synthesis of 3,4-Dialkyl-5-(1-oxo-ethyl)-3H-thiazole-2-thiones Derivatives and
Their Pesticidal Activity
Table 1
The growth stimulant and fungicidal activity of compounds 5–12.
Growth stimulant activity
Fungicidal activity
Growth stimulant activity
Fungicidal activity
Tilletia
Tilletia
tritici
pathogen
tritici
pathogen
growth
growth
Concen-tration
(mg/L)
Activity
(%)
Concen-tration suppression
Concen-tration
(mg/L)
Activity
(%)
Concen-tration suppression
No.
(mg/L)
(%)
No.
(mg/L)
(%)
Hetero-auxin
50
100
100
11b
50
25
121
110
1000
100
100
40
8
2
5
10
5
5
6
6
7
9
9
a
b
a
b
50
100
100
1000
100
100
60
5
100
60
10
11c
11d
11e
11f
50
25
121
90
1000
100
10
1000
100
10
100
100
80
100
100
10
100
100
60
100
100
40
100
100
90
100
60
2
5
10
50
80
80
1000
100
50
25
57
48
2
5
10
50
10
0
50
25
110
86
100
100
2
5
10
50
60
20
50
25
108
131
1000
100
2
5
10
50
88
87
1000
100
100
100
40
11g
11h
50
25
80
82
1000
100
10
1000
100
2
5
10
a
50
110
81
50
25
78
84
2
5
10
25
b
5
2
0
5
37
115
1000
100
100
100
10
100
100
80
12b
12c
12e
12f
50
25
90
90
1000
100
10
1000
100
10
100
90
6
100
100
40
100
100
70
10
9
1
1
c
50
2
80
100
1000
100
50
25
49
74
5
10
0c
1a
50
2
100
90
50
25
123
81
1000
100
5
10
50
90
65
50
25
126
44
1000
100
100
70
2
5
10
5
1
3
,4-Dimethyl-5-[1-(benzene-sulfonyl-hydrazono)-ethyl]-3H-
decomposition), yield: 0.8g (83%). H NMR: d 2.27 (s, 3H, 4-
CH ); 2.48 (s, 3H, N═C–CH ); 2.55 (s, 3H, 4′-CH ); 3.71 (s,
3H, 3-CH ); 7.30–7.80 (m, 4H, C H ); 10.92 (s, 1H, NH); 12.75
thiazole-2-thione (3a).ꢀ The compound was obtained as yellow
crystals; mp 222–224 C (with decomposition), yield: 0.6 g (88%).
H NMR: d 2.11 (3H, s, 4-CH ); 2.45 (s, 3H, N═C–CH ); 3.61 (s,
3
3
3
3
6 5
1
(b.s, 1H, NH). Anal. Calcd for C H N O S : C, 44.89; H, 3.98;
3
3
18 19 5 3 4
3
H, 3-CH
Calcd for C13
Found: C, 45.61; H, 4.49; N, 12.03; S, 28.39.
,4-Dimethyl-5-[1-(p-tolyl-sulfonyl-hydrazono)-ethyl]-3H-thiazole-
3
); 7.40–7.85 (m, 4H, C
6
H
5
); 10.45 (s, 1H, NH). Anal.
N, 14.54; S, 26.63. Found: C, 44.97; H, 4.00; N, 14.72; S, 26.51.
3,4-Dimethyl-5-[1-(2-p-tolyl-sulfonamido-4-methyl-thiazol-5-
yl-carbonyl-hydrazono)-ethyl]-3H-thiazole-2-thione (3d)ꢀ. The
compound was obtained as yellow crystals; mp 260–261 C (with
15 3 2 3
H N O S : C, 45.73; H, 4.43; N, 12.31; S, 28.17.
3
1
2
2
2
-thione (3b). The compound was obtained as yellow crystals; mp
16–218 C (with decomposition), yield: 0.6 g (84.5%). H NMR: d
.11 (3H, s, 4-CH
decomposition), yield: 0.8 g (81%). H NMR: d 2.25 (s, 3H, 4-
ꢀ
1
CH
3H, 4′-CH
C H ); 10.88 (s, 1H, NH); 12.89 (b.s, 1H, NH). Anal. Calcd for
3
); 2.41 (s, 3H, CH
3
-tolyl); 2.50 (s, 3H, N═C–CH
3
); 2.57 (s,
3 3
); 2.34 (s, 3H, CH -tolyl); 2.44 (s, 3H, N═C–
3
); 3.73 (s, 3H, 3-CH
3
); 7.28 and 7.65 (d,d, 4H,
CH ); 3.60 (s, 3H, 3-CH ); 7.33 and 7.76 (d,d, 4H, C H ); 10.47 (s,
3
3
6
4
6 4
1
H, NH). Anal. Calcd for C H N O S : C, 47.30; H, 4.82; N,
C H N O S : C, 46.04; H, 4.27; N, 14.13; S, 25.88. Found:
19 21 5 3 4
14
17
3
2
3
1
1.82; S, 27.06. Found: C, 47.18; H, 4.70; N, 11.58; S, 27.24.
,4-Dimethyl-5-[1-(2-benzene-sulfonamido-4-methyl-thiazol-5-
yl-carbonyl-hydrazono)-ethyl]-3H-thiazole-2-thione (3c).ꢀ The
compound was obtained as yellow crystals; mp 236–238 C (with
C, 46.21; H, 4.20; N, 14.33; S, 25.63.
3
3-Ethyl-4-methyl-5-[1-(benzene-sulfonyl-hydrazono)-ethyl]-
3H-thiazole-2-thione (4a).
yellow crystals; mp 180–182 C (toluene), yield: 0.53 g (75%).
ꢀThe compound was obtained as
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

K. A. Eliazyan, A. M. Knyazyan, V. A. Pivazyan, E. A. Ghazaryan, S. V. Harutyunyan,
and A. P. Yengoyan
Vol 000
1
H NMR: d 1.32 (t, J=7.1, 3H, 3-CH CH ); 2.13 (s, 3H, 4-CH );
continuous stirring and then 0.01 mol of ketone 1 (or 2). The
2
3
3
2
.43 (s, 3H, N═C–CH ); 4.28 (q, J=7.1, 2H, 3-CH CH ); 7.40–
reaction mixture was homogenized with 10 mL of ethanol and
3
2
3
ꢀ
7
.82 (m, 4H, C
: C, 47.30; H, 4.82; N, 11.82; S, 27.06. Found: C,
7.12; H, 4.73; N, 11.64; S, 26.81.
-Ethyl-4-methyl-5-[1-(p-tolyl-sulfonyl-hydrazono)-ethyl]-3H-
thiazole-2-thione (4b). The compound was obtained as
yellow crystals; mp 190–192 C (toluene), yield: 0.0.60 g
6 5
H ); 10.37 (s, 1H, NH). Anal. Calcd for
allowed to stand at 20 C for 24 h. The mixture was heated at
ꢀ
C
4
14
H
17
N
3
O
2
S
3
$32#50–60 C for 3h, cooled, processed with 15 mL of water and
filtered off. Compounds 7,8 were purified by boiling in heptane.
1-(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-
3
ethanone oxime (7). ꢀ The compound was obtained as white
ꢀ
1
crystals; mp 208–210 C, yield: 1.62 g (80%). H NMR: d 2.12
1
(
81%). H NMR: d 1.33 (t, J = 7.1, 3H, 3-CH
2
CH
3
); 2.10 (s,
and 2.15 (s,s, 3H, 4-CH
3
, 1:1); 2.28 and 2.46 (s,s, 3H, N═C–
3
4
1
H, 4-CH ); 2.35 (s, 3H, CH -tolyl); 2.46 (s, 3H, N═C–CH );
CH , 1:1); 3.64 (s, 3H, 3-CH ); 11.15 and 11.29 (s,s, 1H, N-
OH, 1:1). Anal. Calcd for C H N OS : C, 41.56; H, 4.98; N,
7 10 2 2
13.85; S, 31.70. Found: C, 41.65; H, 4.88; N, 13.66; S, 31.58.
3
3
3
3
3
.30 (q, J = 7.1, 2H, 3-CH CH ); 7.30 and 7.75 (d,d, 4H, C H );
2
3
6
4
0.52 (s, 1H, NH). Anal. Calcd for C15
H
19
N
3
O
2
S
3
: C, 48.75;
H, 5.18; N, 11.37; S, 26.03. Found: C, 48.89; H, 5.28; N,
1.16; S, 26.20.
-Ethyl-4-methyl-5-[1-(2-p-tolyl-sulfonamido-4-methyl-thiazol-5-
yl-carbonyl-hydrazono)-ethyl]-3H-thiazole-2-thione (4d). Tꢀhe
compound was obtained as yellow crystals; mp 244–246 C
1-(3-Ethyl-4-methyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanone
1
oxime (8ꢀ).
The compound was obtained as white crystals; mp
1
3
170–172 C, yield: 1.6 g (74%). H NMR: d 1.28 (t, J=7.0, 3H, 3-
CH CH ); 2.14 and 2.17 (s,s, 3H, 4-CH , 1:1); 2.28 and 2.45 (s,s,
2
3
3
3H, N═C–CH
11.18 (s,s, 1H, N-OH, 1:1). Anal. Calcd for C
3
, 1:1); 4.35 (q, J=7.0, 3H, 3-CH
2
CH
8
H
3
); 11.05 and
OS : C,
1
(toluene), yield: 0.75 g (74%). H NMR: d 1.33 (t, J=7.1, 3H,
12
N
2
2
3
2
2
-CH
2
CH
3
); 2.23 (s, 3H, 4-CH
3
); 2.40 (s, 3H, CH
3
-tolyl);
44.42; H, 5.59; N, 12.95; S, 29.65. Found: C, 44.22; H, 5.41; N,
12.72; S, 29.51.
.53 (s, 3H, N═C–CH ); 2.56 (s, 3H, 4′-CH ); 4.28 (q, J = 7.1,
H, 3-CH CH ); 7.30 and 7.68 (d,d, 4H, C H ); 10.75 (s, 1H,
3
3
General procedure: Synthesis of compounds 9a,10a. To a
2
3
6 4
ꢀ
NH); 12.75 (b.s, 1H, NH). Anal. Calcd for C20
4
N, 13.45; S, 25.28.
H
23
N
5
O
3
S
4
: C,
solution of KOH (0.01 mol) in 7 mL of water, at 0–5 C 0.01 mol
of oxime 7 (or 8) was added by portions with continuous stirring,
then 0.01 mol of dimethyl sulfate. The mixture was stirred at
7.13; H, 4.55; N, 13.74; S, 25.16. Found: C, 47.02; H, 4.41;
ꢀ
ꢀ
General procedure: Synthesis of compounds 5,6.
A
20 C for 3–4 h and allowed to stand at 20 C for 24 h. The
residue was filtered off, washed with water and dried in the air.
1-(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-
suspension of semicarbazide (or thiosemicarbazide) hydrochloride
0.005 mol) and ketone 1 (or 2) (0.005mol) in 10 mL of water
(
was boiled with reflux for 4–5 h. The mixture was cooled and
filtered off, and the residue was washed with water and dried in
the air. Compounds 5,6 were purified by boiling in benzene.
ethanone O-methyl-oxime (9a). The compound was obtained
as white crystals; mp 102–104 C (toluene), yield: 1.77 g (82%). H
ꢀ
1
NMR: d 2.12 and 2.13 (s,s, 3H, 4-CH
3H, N═C–CH , 1:7); 3.65 (s, 3H, 3-CH
OCH , 1:7). Anal. Calcd for C OS
2
, 1:7); 2.25 and 2.47 (s,s,
); 3.85 and 3.91 (s,s, 3H,
: C, 44.42; H, 5.59; N,
3
3,4-Dimethyl-5-[1-(urea-1-yl-imino)-ethyl]-3H-thiazole-2-thione
3
3
(
2
5a).ꢀ The compound was obtained as white crystals; mp 285–
3
H N
8 12 2
1
87 C, yield: 0.8 g (66%). H NMR: d 2.16 (s, 3H, 4-CH
3
); 2.44
); 9.52
12.95; S, 29.65. Found: C, 44.59; H, 5.68; N, 12.75; S, 29.31.
(s, 3H, N═C–CH ); 3.62 (s, 3H, 3-CH ); 6.26 (b.s, 2H, NH
3
3
2
1-(3-Ethyl-4-methyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanone
(
s, 1H, NH). Anal. Calcd for C H N OS : C, 39.33; H, 4.95; N,
O-methyl-oxime (10a).
The compound was obtained as white
8
12
4
2
ꢀ
1
2
2.93; S, 26.25. Found: C, 39.19; H, 4.81; N, 22.68; S, 26.09.
,4-Dimethyl-5-[1-(thiourea-1-yl-imino)-ethyl]-3H-thiazole-2-
thione (5b). The compound was obtained as white crystals; mp
crystals; mp 82–84 C (toluene), yield: 1.77 g (77%). H NMR: d
1.30 (t, J=7.0, 3H, 3-CH CH ); 2.12 and 2.13 (s,s, 3H, 4-CH
1:7); 2.25 and 2.47 (s,s, 3H, N═C–CH , 1:7); 3.85 and 3.91 (s,s,
3H, OCH , 1:7); 4.31 (q, J=7.0, 3H, 3-CH CH ). Anal. Calcd for
OS : C, 46.93; H, 6.13; N, 12.16; S, 27.84. Found: C,
3
2
3
3
,
3
ꢀ
1
2
4
40–242 C, yield: 1.15 g (88.5%). H NMR: d 2.17 (s, 3H,
-CH ); 2.45 (s, 3H, N═C–CH ); 3.60 (s, 3H, 3-CH ); 5.12
3
2
3
C H
9
N
3
3
3
14
2
2
(
b.s, 2H, NH ); 8.63 (s, 1H, NH). Anal. Calcd for C H N S :
47.14; H, 6.06; N, 12.38; S, 27.56.
2
8 12 4 3
C, 36.90; H, 4.64; N, 21.52; S, 36.94. Found: C, 36.71; H,
.54; N, 21.29; S, 36.73.
-Ethyl-4-methyl-5-[1-(urea-1-yl-imino)-ethyl]-3H-
[1-(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-
4
ethylid-eneaminooxy]-acetic acid methyl ester (9b).
To a
3
suspension of KOH (0ꢀ.56 g, 0.01 mol) in 7 mL of
dimethylformamide at 0–5 C, 2.02 g (0.01 mol) of oxime (7)
was added by portions with continuous stirring. After the salt
formation, 0.9 mL (r=1.23 g/mL, 0.01 mol) of chloro-acetic
thiazole-2-thione (6a).ꢀ The compound was obtained as white
1
crystals; mp 258–260 C, yield: 1.04 g (80%). H NMR: d 1.30
(
t, J = 7.1, 3H, 3-CH
N═C–CH ); 4.30 (q, J = 7.1, 2H, 3-CH
NH ); 9.62 (s, 1H, NH). Anal. Calcd for C H N OS : C,
2
CH
3
); 2.16 (s, 3H, 4-CH
3
); 2.44 (s, 3H,
CH ); 6.28 (b.s, 2H,
3
acid methyl ester was added dropwise, and the mixture
3
2
ꢀ
allowed to stand at 20 C for 24 h. The suspension was
2
9
14
4
2
4
1.84; H, 5.46; N, 21.69; S, 24.82. Found: C, 41.61; H, 5.32;
N, 21.30; S, 24.49.
-Ethyl-4-methyl-5-[1-(thiourea-1-yl-imino)-ethyl]-3H-
steamed; the residue was washed with water and filtered off.
ꢀ
The compound was obtained as white crystals; mp 96–98 C
1
3
(processed with ethanol), yield: 1.97 g (72%). H NMR: d
thiazole-2-thione (6b).ꢀ The compound was obtained as white
2.21 (s, 3H, 4-CH
3-CH ); 3.72 (s, 3H, OCH
Calcd for C10 : C, 43.78; H, 5.14; N, 10.21; S,
3
); 2.46 (s, 3H, N═C–CH
3
); 3.65 (s, 3H,
1
crystals; mp 218–220 C, yield: 1.1 g (80%). H NMR: d 1.29
3
3
); 4.65 (s, 2H, OCH
2
). Anal.
(
t, J = 7.0, 3H, 3-CH CH ); 2.17 (s, 3H, 4-CH ); 2.45 (s, 3H,
14 2 3 2
H N O S
2
3
3
N═C–CH
3
); 4.30 (q, J = 7.0, 3H, 3-CH
2
CH
3
); 5.20 (b.s, 2H,
23.37. Found: C, 43.61; H, 5.05; N, 10.39; S, 23.11.
General procedure: Synthesis of compounds 9c,10c. The
mixture of oxime 7 (or 8) (0.01 mol), and phenyl isocyanate
(0.01 mol) in 10 mL of absolute toluene in the presence of
catalytic amounts of pyridine was boiled for 3 h. After cooling,
the mixture was filtered off, and the residue was recrystallized
from 50% ethanol.
NH
2 9 14 4 3
); 8.59 (s, 1H, NH).). Anal. Calcd for C H N S : C, 39.39;
H, 5.14; N, 20.42; S, 35.05. Found: C, 39.18; H, 5.06; N,
2
0.21; S, 34.79.
General procedure: Synthesis of compounds 7,8.
solution of NaOH (0.014 mol) in 5 mL of water, at 0 C 0.014mol
of hydroxylamine hydrochloride was added by portions with
To a
ꢀ
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Synthesis of 3,4-Dialkyl-5-(1-oxo-ethyl)-3H-thiazole-2-thiones Derivatives and
Their Pesticidal Activity
3,4-Dimethyl-5-[1-(N-phenyl-formamide-1-yl-oxime)-ethyl]-3H-
1-(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanone
thiazole-2-thione (9c). The compound was obtained as yellow
O-(4-amino-6-diisobutyl-amino-1-yl-[1,3,5]triazin-2-yl)-oxime
ꢀ
ꢀ
crystals; mp 188–189 C (with decomposition), yield: 2.4 g
(11e). The compound was obtained as white crystals; mp 176–178 C
1
1
(
75%). H NMR: d 2.34 (s, 3H, 4-CH
3
); 2.60 (s, 3H, N═C–
(hexane/benzene, 1:1), yield: 2.11 g (50%). H NMR: d 1.02
CH
3
); 3.69 (s, 3H, 3-CH
3
); 6.90–7.55 (m, 5H, C ); 9.48
6
H
5
[m, 12H, (CH
3 4 2
) -isobut.]; 2.09 [m, 2H, (CH) -isobut.]; 2.30
(
s, 1H, NH). Anal. Calcd for C H N O S : C, 52.32; H,
(s, 3H, 4-CH ); 2.62 (s, 3H, N═C–CH ); 3.42 [m, 4H,
14
15
3
2
2
3
3
4
1
.70; N, 13.07; S, 19.95. Found: C, 52.12; H, 4.57; N, 13.21; S,
9.69.
(NCH ) ]; 3.70 (s, 3H, 3-CH ); 6.12 (s, 2H, NH ). Anal.
2 2 3 2
Calcd for C18H N OS : C, 51.04; H, 6.90; N, 23.15; S,
29 7 2
3-Ethyl-4-methyl-5-[1-(N-phenyl-formamide-1-yl-oxime)-ethyl]-
15.14. Found: C, 51.18; H, 6.74; N, 22.85; S, 14.87.
3
H-thiazole-2-thione (10c). The compound was obtained as
1-(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanone
ꢀ
white crystals; mp 130–132 C (with decomposition), yield:
2
O-(2-amino-6-methyl-pyrimidin-4-yl)-oxime (11f). The
ꢀ
1
.5 g (75%). H NMR: d 1.28 (t, J = 7.0, 3H, 3-CH
2
CH
3
); 2.35
compound was obtained as yellow crystals; mp 203–204 C
1
(
s, 3H, 4-CH ); 2.62 (s, 3H, N═C–CH ); 4.31 (q, J = 7.0, 3H,
(processed with ethanol), yield: 2.3 g (74%). H NMR: d
3
3
3
-CH CH ); 6.92–7.56 (m, 5H, C H ); 9.39 (s, 1H, NH). Anal.
2.26 (s, 3H, CH -pyrim.); 2.40 (s, 3H, 4-CH ); 2.58 (s, 3H,
2
3
6
5
3
3
Calcd for C15
Found: C, 53.62; H, 5.03; N, 12.31; S, 18.81.
H
17
N
3
O
2
S
2
: C, 53.71; H, 5.11; N, 12.53; S, 19.12.
N═C–CH ); 3.69 (s, 3H, 3-CH ); 6.06 (s, 2H, NH ); 6.32
(s, 1H, CH-pyrim.). Anal. Calcd for C H N OS : C,
12 15 5 2
3 3 2
General procedure: Synthesis of compounds 11,12. To a
suspension of KOH (0.01 mol) in 10 mL of dioxane, 0.01 mol of
oxime 7 (or 8) was added with continuous stirring. When salt
formation was completed, 0.01 mol of corresponding azinyl-
trimethylammonium chloride was added by portions. The
reaction mixture was stirred at 20 C, then at 50–60 C for 3 h
for trimethylamine moving off. The suspension was steamed,
processed with water, and the sediment of compounds 11,12
was filtered off.
46.58; H, 4.89; N, 22.63; S, 20.73. Found: C, 46.70; H,
4.99; N, 22.47; S, 20.51.
1-(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanone
O-(4-methoxy-6-methyl-pyrimidin-2-yl)-oxime (11g). The compound
ꢀ
was obtained as white crystals; mp 170–172 C (processed with
ꢀ
ꢀ
1
ethanol), yield: 1.94 g (60%). H NMR: d 2.37 (s, 3H, CH
3
-pyrim.);
); 3.69 (s, 3H, 3-CH );
); 6.35 (s, 1H, CH-pyrim.). Anal. Calcd for
C H N O S : C, 48.13; H, 4.97; N, 17.27; S, 19.77. Found:
2.38 (s, 3H, 4-CH
3
); 2.66 (s, 3H, N═C–CH
3
3
3.95 (s, 3H, OCH
3
1
3 16 4 2 2
1
-(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanone
C, 48.01; H, 4.85; N, 17.00; S, 19.51.
O-(4,6-bis-dimethyl-amino-[1,3,5]triazin-2-yl)-oxime (11a). The
1-(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanone
ꢀ
compound was obtained as white crystals; mp 213–215 C
O-(4-methyl-6-pirrolidin-1-yl-pyrimidin-2-yl)-oxime (11h). The
ꢀ
1
(
(
(
processed with ether), yield: 2.4 g (66%). H NMR: d 2.34
s, 3H, 4-CH ); 2.67 (s, 3H, N═C–CH ); 3.14 [s, 12H, N
compound was obtained as white crystals; mp 176–178 C
1
(processed with ethanol), yield: 2.8 g (77%). H NMR: d 2.01
3
3
CH
3
)
4
]; 3.68 (s, 3H, 3-CH
3
). Anal. Calcd for C14
H
21
N
7
OS
2
:
(b.m, 4H, CH
(s, 3H, 4-CH
(CH -pyrrol.]; 3.69 (s, 3H, 3-CH
Anal. Calcd for C H N OS : C, 52.87; H, 5.82; N, 19.27; S,
2
CH
); 2.66 (s, 3H, N═C–CH
); 5.94 (s, 1H, CH-pyrim.).
2
-pyrrol.); 2.26 (s, 3H, CH
3
-pyrim.); 2.34
C, 45.76; H, 5.76; N, 26.68; S, 17.45. Found: C, 45.49; H,
.61; N, 26.42; S, 17.21.
-(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanone O-
3
3
); 3.45 [b.m, 4H, N
5
)
2 2
3
1
16
21
5
2
(
(
1
(
3
4-dimethyl-amino-6-pyrrolidin-1-yl-[1,3,5]triazin-2-yl)-oxime
17.64. Found: C, 52.87; H, 5.82; N, 19.27; S, 17.64.
1-(3-Ethyl-4-methyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanone
O-(4-dimethyl-amino-6-pyrrolidin-1-yl-[1,3,5]triazin-2-yl)-oxime
11b). The compound was obtained as white crystals; mp
ꢀ
1
95–196 C (toluene), yield: 2.95 g (75%). H NMR: d 1.90
ꢀ
b.m., 4H, CH
2
CH
2
-pyrrol.); 2.33 (s, 3H, 4-CH
3
); 2.67 (s,
(12b). The compound was obtained as white crystals; mp 150–152 C
1
H, N═C–CH ); 3.13 [s, 6H, N(CH ) ]; 3.53 [b.m, 4H, N
(processed with ethanol), yield: 3.3 g (82%). H NMR: d 1.35
3
3 2
(
CH ) -pyrrol.]; 3.68 (s, 3H, 3-CH3). Anal. Calcd for
(t, J = 7.0, 3H, 3-CH CH ); 1.97 (b.m., 4H, CH CH -pyrrol.);
2
2
2
3
2
2
C
16
H
23
N
7
OS
2
: C, 48.83; H, 5.89; N, 24.91; S, 16.30.
2.34 (s, 3H, 4-CH
(CH ]; 3.55 [b.m, 4H, N(CH
3-CH CH ). Anal. Calcd for C17
N, 24.06; S, 15.74. Found: C, 50.22; H, 6.27; N, 24.31; S, 15.98.
1-(3-Ethyl-4-methyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanone
O-(4-ethyl-amino-6-pyrrolidin-1-yl-[1,3,5]triazin-2-yl)-oxime
3-ethyl-4-methyl-5-[1-(4-ethylamino-6-pyrrolidin-1-yl-[1,3,5]
3
); 2.66 (s, 3H, N═C–CH
-pyrrol.]; 4.33 (q, J = 7.0,
OS : C, 50.10; H, 6.18;
3
); 3.13 [s, 6H, N
Found: C, 48.98; H, 5.97; N, 24.71; S, 16.12.
-(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanone
O-(4-ethyl-amino-6-pyrrolidin-1-yl-[1,3,5]triazin-2-yl)-oxime
3
)
2
2 2
)
1
2
3
H
25
N
7
2
ꢀ
(11c). The compound was obtained as white crystals; mp 170–172 C
1
(
(
processed with ether), yield: 3.14 g (80%). H NMR: d 1.16
t, J
1
= 7.1, 3H, CH
3 2 2 2
CH N); 1.94 (b.m., 4H, CH CH -pyrrol.);
2
.32 (s, 3H, 4-CH ); 2.62 (s, 3H, N═C–CH ); 3.34 (m, J = 7.1,
triazin-2-yl-oxime)-ethyl]-3H-thiazole-2-thione (12c). The
3
3
1
ꢀ
J = 5.2, 2H, NCH CH ); 3.52 [b.m, 4H, N(CH ) -pyrrol.]; 3.69
compound was obtained as white crystals; mp 188–189 C
2
2
3
2 2
1
(
s, 3H, 3-CH ); 6.73 and 6.90 (t,t, J = 5.2, 1H, NH). Anal. Calcd
(processed with ethanol), yield: 2.9 g (71%). H NMR: d 1.16
3
2
23 7 2
for C16H N OS : C, 48.83; H, 5.89; N, 24.91; S, 16.30. Found:
(t, J
1
= 7.1, 3H, CH
3
CH
2
NH); 1.34 (t, J = 7.0, 3H, 3-CH
2 3
CH );
C, 48.70; H, 5.71; N, 24.61; S, 16.08.
-(3,4-Dimethyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanone
O-(4-ethyl-amino-6-piperidin-1-yl-[1,3,5]triazin-2-yl)-oxime
1.95 (b.m., 4H, CH
2
CH
2
-pyrrol.); 2.32 (s, 3H, 4-CH ); 2.65
3
1
(s, 3H, N═C–CH3); 3.34 (m, J1 = 7.1, J2 = 5.1, 2H,
HNCH CH ); 3.51 (b.m, 4H, N(CH ) -pyrrol.); 4.31 (m,
2
3
2 2
ꢀ
(
11d). The compound was obtained as white crystals; mp 158–160 C
J = 7.0, 2H, 3-CH
2
CH
3
2
); 6.73 and 6.88 (t,t, J = 5.1, 1H, NH).
1
(processed with ether), yield: 3.3 g (81%). H NMR: d 1.18
(t, J = 7.1, 3H, CH CH N); 1.89 [b.m., 6H, (CH -piper.]; 2.32
(s, 3H, 4-CH ); 2.65 (s,s, 3H, N═C–CH ); 3.36 (m, J = 7.1,
Anal. Calcd for C17H N OS : C, 50.10; H, 6.18; N, 24.06; S,
15.74. Found: C, 49.95; H, 6.06; N, 24.24; S, 15.92.
1-(3-Ethyl-4-methyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-ethanone
O-(4-amino-6-diisobutyl-amino-1-yl-[1,3,5]triazin-2-yl)-oxime
25 7 2
1
3
2
)
2 3
3
3
1
J = 5.2, 2H, NCH CH ); 3.52 [b.m, 4H, N(CH ) -piper.]; 3.69
2
2
3
2 2
(
s, 3H, 3-CH
3
); 6.70 and 6.85 (t, J
OS
Found: C, 50.21; H, 6.03; N, 23.79; S, 15.61.
2
= 5.2, 1H, NH). Anal. Calcd
2
: C, 50.10; H, 6.18; N, 24.06; S, 15.74.
(12e).
165–166 C (benzene), yield: 2.97 g (68%). H NMR: d 1.04
[m, 12H, (CH -isobut.]; 1.34 (t, J = 7.0, 3H, 3-CH CH );
The compound was obtained as white crystals; mp
ꢀ
1
for C17
H
25
N
7
3
)
4
2
3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

K. A. Eliazyan, A. M. Knyazyan, V. A. Pivazyan, E. A. Ghazaryan, S. V. Harutyunyan,
and A. P. Yengoyan
Vol 000
2
.10 [m, 2H, (CH) -isobut.]; 2.28 (s, 3H, 4-CH ); 2.66 (s, 3H,
[3] Sanemitsu, Y.; Kawamura, S.; Satoh, J.; Katayama, T.;
Hashimoto, S. J Pestic Sci 2006, 31(3), 305
2
3
N═C–CH ); 3.42 [m, 4H, (NCH ) -isobut.]; 4.30 (q, J = 7.0,
3
3
2 2
[
[
4] Sanemitsu, Y.; Kawamura, S. J Pestic Sci 2008, 33(2), 175
5] Mori, M.; Takagi, M.; Noritake, C.; Kagabu, S. J Pestic Sci
-CH
2
CH
3
); 6.05 (s, 2H, NH
2
31 7 2
). Anal. Calcd for C19H N OS :
C, 52.15; H, 7.14; N, 22.40; S, 14.65. Found: C, 52.01; H,
.08; N, 22.22; S, 14.36.
-(3-Ethyl-4-methyl-2-thioxo-2,3-dihydro-thiazol-5-yl)-
2008, 33(4), 357
7
[6] Dovlatyan, V. V.; Eliazyan, K. A.; Pivazyan, V. A.; Yengoyan,
1
A. P. Chem Heterocycl Comp 2003, 39(9), 1238
ethanone O-(2-amino-6-methyl-pyrimidin-4-yl)-oxime (12f). The
[7] Dovlatyan, V. V.; Jivanshiryan, T. L.; Avetisyan, F.; Yengoyan,
A. P. Chem Heterocycl Comp 2004, 40(1), 84
ꢀ
compound was obtained as yellow crystals; mp 174–176 C
1
[
8] Dovlatyan, V. V.; Eliazyan, K. A.; Pivazyan, V. A.; Yengoyan,
A. P. Chem Heterocycl Comp 2006, 42(3), 383
9] Ghazaryan, E. A.; Shahbazyan, L. V.; Eliazyan, K. A.; Yengo-
yan, A. P. Vestnik RAU (ser. phys-math., estestv.nauki) 2009, №2, 120
Russian), (Bulletin of Russian-Armenian University, ser. phys-math.
(
benzene), yield: 2.0g (61%). H NMR: d 1.32 (t, J = 7.0, 3H,
3
-CH CH ); 2.28 (s, 3H, 4-CH ); 2.42 (s, 3H, CH -pyrim.); 2.60
2 3 3 3
[
(
s, 3H, N═C–CH ); 4.30 (q, J =7.0, 3-CH CH ); 6.15 (s, 2H,
3 2 3
2 17 5 2
NH ); 6.35 (s, 1H, CH-pyrim.). Anal. Calcd for C13H N OS : C,
(
4
2
8.27; H, 5.30; N, 21.65; S, 19.83. Found: C, 48.11; H, 5.25; N,
1.39; S, 19.60.
and natural sciences)
[10] Massolini, G.; Kitsos, M.; Gandini, C.; Caccialanza, G. Pestic
Sci 1989, 26(2), 209
[11] Aspinall, I. H.; Worthington, P. A. Pestic Sci 1999,
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[12] Koo, S. J.; Ahn, S.-C.; Lim, J. S.; Chae, S. H.; Kim, J. S.; Lee,
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1] Dayan, F. E.; Vincent, A. C.; Romagni, J. G.; Allen, S. N.;
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K.; Greenhow, D.T. Pest Manag Sci 2000, 56(2), 127
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Duke, S. O.; Duke, M. V.; Bowling, J. J.; Zjawiony, J. K. J Agric Food
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet