Synthesis of novel 2-arylsulfonylimino-3,4-dimethyl-5-(5-S-substituted [1,3,4]oxadiazol-2-yl)-2,3-dihydrothiazole derivatives and their plant growth stimulant activity

Article abstract of DOI:10.1515/hc-2013-0055

2-Arylsulfonylimino-3,4-dimethyl-2,3-dihydrothiazole-5-carboxylic acid hydrazides 2 were obtained from corresponding 2-arylsulfonylimino-4-methyl-2,3- dihydrothiazole-5-carboxylic acid ethyl esters 1 in a twostep synthesis. Heterocyclization of the hydrazide moiety yielded 2-arylsulfonylimino-3,4- dimethyl-5-(5-thioxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl)-2,3-dihydro-thiazoles 3. Treatment of compounds 3 with various alkyl halides gave corresponding S-substituted derivatives 4-6 . The plant growth stimulant activities of synthesized compounds were compared with those of similar [1,2,4]triazol- and [1,3,4,]thiadiazol-2-yl-thiazoles.

Full text of DOI:10.1515/hc-2013-0055

ꢁꢁꢁꢂ
DOI 10.1515/hc-2013-0055ꢀ ꢀHeterocycl. Commun. 2013; 19(4): 275–280
Karine A. Eliazyan, Ruzanna S. Hakobyan, Vergush A. Pivazyan, Emma A. Ghazaryan,
Siranush V. Harutyunyan and Aleksandr P. Yengoyan*
Synthesis of novel 2-arylsulfonylimino-3,4-
dimethyl-5-(5-S-substituted [1,3,4]oxadiazol-
2-yl)-2,3-dihydrothiazole derivatives and their
plant growth stimulant activity
Abstract: 2-Arylsulfonylimino-3,4-dimethyl-2,3-dihydro- octhilinone, thiabendazole, thiadifluor, thifluzamide,),
thiazole-5-carboxylic acid hydrazides 2 were obtained insecticides (clothianidin, imidaclothiz, tazimcarb, thia-
from corresponding 2-arylsulfonylimino-4-methyl-2,3-di- cloprid, thiamethoxam, thiapronil), acaricides (flubenzi-
hydrothiazole-5-carboxylic acid ethyl esters 1 in a two- mine, hexythiazox), and bactericides (amicarthiazol). The
step synthesis. Heterocyclization of the hydrazide moiety arsenal of pesticides based on [1,3,4]oxadiazole is more
yielded
2-arylsulfonylimino-3,4-dimethyl-5-(5-thioxo- limited and includes oxadiazolone herbicides (dimefuron,
4,5-dihydro-[1,3,4]oxadiazol-2-yl)-2,3-dihydro-thiazoles 3. oxadiargyl, oxadiazon) and insecticide (metoxadiazone)
Treatment of compounds 3 with various alkyl halides gave (http://www.alanwood.net/pesticides/class_pesticides.
corresponding S-substituted derivatives 4–6. The plant html). However, the search for new biologically active
growth stimulant activities of synthesized compounds compounds continues among the new, previously unex-
were compared with those of similar [1,2,4]triazol- and plored series of thiazole [1–9] and [1,3,4]oxadiazole deriva-
[1,3,4,]thiadiazol-2-yl-thiazoles.
tives [10–21].
The aim of the present investigation was to develop
Keywords: 2-arylsulfonylimino-3,4-dimethyl-2,3-dihydro- facile and efficient methods for the synthesis of non-
thiazole-5-carboxylic acid hydrazides; heterocyclization; condensed 2-arylsulfonylimino-substituted biheterocyclic
[1,3,4]oxadiazol-2-yl-thiazoles; plant growth stimulant systems with combination of [1,3,4]oxadiazole and thia-
activity.
zole rings and to study their physiological activity.
*Corresponding author: Aleksandr P. Yengoyan, Armenian
National Agrarian University, Teryan, 74, Yerevan 0009, Armenia;
and Armenian-Russian (Slavonic) State University, H. Emin, 123,
Yerevan 0051, Armenia, e-mail: ayengoyan@mail.ru
Results and discussion
Karine A. Eliazyan, Ruzanna S. Hakobyan, Vergush A. Pivazyan,
Emma A. Ghazaryan and Siranush V. Harutyunyan: Armenian
National Agrarian University, Teryan, 74, Yerevan 0009, Armenia
Synthesis
The treatment of 2-arylsulfonylimino-4-methyl-2,3-di-
hydrothiazole-5-carboxylic acid ethyl esters with dime-
thyl sulfate gave the corresponding N-methylated
derivatives 1a–c (Scheme 1). In principle, alkylation
can proceed on both exocyclic and endocyclic nitro-
gen atoms of the substrate. The structure determination
Introduction
Derivatives of N,S,O-containing five-membered heterocy- could not be based on analysis of 13C NMR spectra due
cles, in particular thiazole and [1,3,4]oxadiazole, exhibit to lack of model compounds. Therefore, X-ray diffrac-
a broad spectrum of biological activity. In agriculture, tion analysis of methyl derivative 1a was carried out,
the thiazole derivatives are widely used for chemical which showed that methylation occurs exclusively at
means of plant protection and growth regulation. They the endocyclic nitrogen atom (Figure 1). The reaction of
are known as herbicides (benazolin, benzthiazuron, fen- compounds 1a–c with hydrazine hydrate yielded cor-
thiaprop mefenacet, metabenzthiazuron, thiazopir), fun- responding hydrazides 2a–c. By their heterocyclization
gicides (ethaboxam, fluthianil, isotianil, metsulfovax, with carbon disulfide and potassium hydroxide in ethanol
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276ꢀ ꢀK.A. Eliazyan et al.: Synthesis of [1,3,4]oxadiazolylthiazole derivatives with plant growth stimulant activity
Me
N
Me
HN
O
O
OEt
OEt
OEt
DMS
O
S
O
S
O
S
O
S
R1
NH
R1
N
Me
O
Me
N
O
Me
O
S
Me
O
S
N
NHNH2
N2H4
CS2, KOH
EtOH
S
S
R1
N
R1
N
1a-c
2a-c
O
O
Me
N
NH
N
Me
N
N
SR2
S
Me
O
S
R2Hal
O
Me
O
S
O
N
N
S
S
R1
N
R1
3a-c
O
O
1a, 4a, 5a, 6a: R1 = H
1b, 4b, 5b, 6b: R1 = Cl
1c, 4c, 5c, 6c: R1 = Me
4a-c: R2 = Me
5a-c: R2 = CH2COOMe
6a-c: R2 = CH2CN
Scheme 1ꢀ
2-arylsulfonylimino-3,4-dimethyl-5-(5-thioxo-4,5-dihy- was studied. The seeds were incubated for 24 h in an
dro-[1,3,4]oxadiazol-2-yl)-2,3-dihydro-thiazoles 3a–c appropriate medium in the dark at 25°C. Then, the seeds
were obtained. These compounds have thione structure were transplanted into soil and watered daily.
because their 13C NMR spectra contain the signal for the
In the second experimental setup, the bean seeds
C=S moiety at 176 ppm. Treatment of 3a–c with dimethyl were placed in the soil in small vessels. When the length
sulfate, chloroacetic acid methyl ester or chloroacetoni- of the stems reached 15–20 cm, the plants were dug out,
trile yielded the S-substituted derivative 4a–c, 5a–c, or the root parts were washed with water and cut off. A series
6a–c, respectively. Alkylation of these compounds occurs of 8–10 cut plants were immersed in the prepared aqueous
at the sulfur atom because 13C NMR spectra display new solutions of IAA or 3–6 at concentrations of 25 mg/L and
signals for a C=N bond of [1,3,4]oxadiazole and the C=S 50 mg/L. After 24 h, they were washed and dipped into the
signals are not observed.
vessels with water. Water in the vessels was changed every
day. For every compound, the two experimental schemes
were repeated three times. The experiments were con-
ducted for 20–25 days. The number of plant roots of each
series, and their length and weight in the moist and dry
Biological activity
The object of study was the seeds and seedlings of dicoty-
ledonous common bean (Phaseolus vulgaris L.) collected
in September 2012 from the Syunik region of Armenia. At
preliminary screening, the possible herbicidal, fungicidal,
and growth regulatory activities of novel compounds 3–6
were studied. All preparations did not show noticeable
herbicidal or antifungal properties, but they showed a
growth stimulant effect. Subsequently, more detailed
studies of the activity of compounds 3–6 on the germina-
tion, growth, and survivability of seeds and seedlings of
common bean were performed.
In the first set of experiments, the effect of aqueous
solutions of compounds 3–6 and heteroauxin (indole-
3-acetic acid, IAA) in concentrations of 25 and 50 mg/L Figure 1ꢀMolecular structure of compound 1a.
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K.A. Eliazyan et al.: Synthesis of [1,3,4]oxadiazolylthiazole derivatives with plant growth stimulant activityꢀ
ꢀ277
forms were calculated. The results were compared with [24]. The results of preliminary bioassays show that the
similar data of plants placed in IAA solutions, and the obtained new compounds show promise for the develop-
activities of preparations in comparison with IAA (in %) ment as new growth stimulators and fungicides.
were determined (Table 1). The data show that the growth
stimulant properties increase in the following order 4 ≈
6 < 3 < 5.
Experimental
Conclusions
General
1H NMR (300 MHz) and 13C NMR (75 MHz, decoupled and coupled
modes) spectra were recorded on a Varian Mercury 300 spectrometer in
the mixture of DMSO-d6 and CCl4 (1:3) or in pure DMSO-d6. The reaction
progress and purity of the obtained substances were checked by using
TLC on ‘Silufol UV-254’ plates with an acetone/hexane mixture (2:1) as
eluent. Melting points were determined in open capillaries and are un-
corrected. An X-ray diffraction experiment was carried out at room tem-
perature on an Enraf-Nonius automatic diffractometer CAD-4.
This research is the continuation of our previous efforts
on the synthesis of new non-condensed biheterocyclic
systems with 1,2,3-triazole, 1,3,4-thiadiazole, or 1,3,4-oxa-
diazole moieties, additionally substituted with a thiazolyl,
arylsulfonylimino [22], arylsulfonylethylamino [23], or
thioxo [24–26] group. Practically, all derivatives of these
systems manifest growth stimulant activity, in certain
cases equal to the activity of heteroauxin. The triazolyl-
thiazole derivatives also possess fungicidal properties
General procedure for 1а–с
2-Arylsulfonylimino-3-methylthiazol-5-carboxylic acid ethyl ester po-
tassium salts were obtained by treatment of esters (0.01 mol) with
KOH (0.01 mol) at 0°C. These products (0.01 mol) in water (10 mL)
were allowed to react with dimethyl sulfate for 24 h at 20–25°C. The
precipitate was filtered off, washed with water, and dried.
Table 1ꢁGrowth stimulant activity of compounds 3–6.
Compound
IAA
Concentration, mg/L
Activity
50
25
100
100
2-Benzenesulfonylimino-3,4-dimethyl-2,3-dihydrothiazol-5-car-
boxylic acid ethyl ester (1a)ꢀFlesh-colored crystals; mp 125–127°C;
3a
3b
3c
4a
4b
4c
5a
5b
5c
6a
6b
6c
50
25
74.6
75.3
1
yield 3.05 g (90%); H NMR: δ 1.36 (t, 3H, J = 7.0 Hz, OCH2CH3), 2.58
(s, 3H, 4-CH3), 3.47 (s, 3H, 3-NCH3), 4.32 (q, 2H, J = 7.0 Hz, OCH2CH3),
7.45–7.90 (m, 5H, C6H5). Anal. Calcd for C14H16N2O4S2: C, 49.40; H, 4.74;
N, 8.23; S, 18.84. Found: C, 49.26; H, 4.63; N, 7.88; S, 18.48.
50
25
73.8
63.4
50
25
47.2
49.5
Crystal data for 1aꢀC14H14N4O3S3, monoclinic, space group P21/c, a =
50
25
60.5 10.914(2), b = 15.176(3), c = 10.285(2) Å, β = 92.45(3)°, V = 1702.0(6) Å3,
55.5 Z = 4, T = 293(2)K, dx = 1.493 g cm-3, μ(MoKα) = 0.71073 mm-1, 4967
data were collected up to θmax = 30° (Rint = 0.0675, Rσ = 0.1575). Final
40.2
50
25
R-indices for 1802 reflections with I > 2σ(I) and 220 refined param-
41.7
eters are: R1 = 0.0626, wR2 = 0.1150 (R1 = 0.2395, wR2 = 0.1532 for all
50
25
41.1
42.2
4967 data). Crystallographic data for compound 1a have been depo-
sited with the Cambridge Crystallographic Data Centre, deposition
no. CCDC 940247.
50
25
93.0
85.1
2-(4-Chlorobenzenesulfonylimino)-3,4-dimethyl-2,3-dihydro-
50
25
73.8
62.1
thiazole-5-carboxylic acid ethyl ester (1b)ꢀFlesh-colored crystals;
1
mp 156–158°C; yield 3.08 g (82%); H NMR: δ 1.35 (t, 3H, J = 7.0 Hz,
50
25
81.7
59.6
OCH2CH3), 2.59 (s, 3H, 4-CH3), 3.48 (s, 3H, 3-NCH3), 4.31 (q, 2H, J = 7.0
Hz, OCH2CH3), 7.47–7.87 (m, 4H, C6H4). Anal. Calcd for C14H15СlN2O4S2:
C, 44.86; H, 4.03; N, 7.47; S, 17.11. Found: C, 44.72; H, 3.91; N, 7.08; S,
16.77.
50
25
62.3
79.9
50
25
60.1
73.5
2-(4-Methylbenzenesulfonylimino)-3,4-dimethyl-2,3-dihydro-
thiazole-5-carboxylic acid ethyl ester (1c)ꢀFlesh-colored crys-
tals; mp 184–186°C; yield: 3.18 g (90%); 1H NMR: δ 1.35 (t, 3H, J = 7.0
Hz, OCH2CH3), 2.42 (s, 3H, CH3C6H4), 2.61 (s, 3H, 4-CH3), 3.48 (s, 3H,
50
25
42.6
60.5
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278ꢀ ꢀK.A. Eliazyan et al.: Synthesis of [1,3,4]oxadiazolylthiazole derivatives with plant growth stimulant activity
1
NCH3), 4.30 (q, 2H, J = 7.0 Hz, OCH2CH3), 7.26–7.75 (m, 4H, C6H4); 13C tals; mp 236–238°C (with decomp.); yield 2.87 g (78%); H NMR: δ
NMR (coupled): δ 12.9 (4-CH3); 14.0 (OCH2CH3), 20.8 (CH3C6H4), 32.7 2.60 (s, 3H, 4-CH3), 3.55 (s, 3H, 3-NCH3), 7.50–7.90 (m, 5H, C6H5), 14.50
3
(3-NCH3), 61.2 (OCH2CH3), 106.0 (C-5; J = 4.2 Hz), 125.9; 129.4, 138.7; (brs, 1H, NH); 13C NMR (coupled): δ 13.2 (4-CH3), 32.8 (3-NCH3), 99.0
146.6, (Ar); 142.8 (C-4; 2J = 6.6 Hz), 160.4 (С=О, 3J = 3.2 Hz), 165.2 (С-2, (q, 3J = 4.8 Hz, C-5), 125.8, 128.4, 131.8, 140.3 (Ph), 141.5 (q, 2J = 6.6 Hz,
3J = 3.2 Hz). Anal. Calcd for C15H18N2O4S2: C, 50.83; H, 5.12; N, 7.90; S, C-4), 154.5 (C-2′), 164.6 (q, 3J = 3.1 Hz, C-2), 176.4 (C=S). Anal. Calcd for
18.09. Found: C, 50.60; H, 5.06; N, 7.69; S, 17.88.
C13H12N4O3S3: C, 42.38; H, 3.28; N, 15.21; S, 26.11. Found: C, 42.21; H,
3.16; N, 15.00; S, 25.92.
2-(4-Chlorobenzenesulfonylimino)-3,4-dimethyl-5-(5-thi-
oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl)-2,3-dihydrothiazole
(3b)ꢀYellow crystals; mp 242–244°C (with decomp.); yield 3.30 g
(82%); 1H NMR: δ 2.61 (s, 3H, 4-CH3), 3.53 (s, 3H, 3-NCH3), 7.60–7.92 (m,
4H, C6H4), 14.55 (brs, 1H, NH); 13C NMR (coupled): δ 13.12 (4-CH3), 32.8
General procedure for 2а–c
The suspension of 2-arylsulfonylimino-3,4-dimethylthiazol-5-car-
boxylic acid ethyl ester 1 (0.01 mol) in 15 mL of hydrazine hydrate
(48%) was stirred at 20°С for 2 days. The precipitate was filtered off,
washed with water, and dried. Compounds 2 were purified by boil-
ing in hexane.
3
(3-NCH3), 99.3 (q, J = 4.8 Hz, C-5), 127.6, 128.5, 137.5, 140.1 (Ar), 140.3
(q, 2J = 6.6 Hz, C-4), 154.3 (C-2′), 160.0 (q, 3J = 3.1 Hz, C-2), 176.35 (C=S).
Anal. Calcd for C13H11ClN4O3S3: C, 38.75; H, 2.75; N, 13.91; S, 23.88.
Found: C, 38.62; H, 2.69; N, 13.70; S, 23.61.
2-Benzenesulfonylimino-3,4-dimethyl-2,3-dihydrothiazole-
5-carboxylic acid hydrazideꢀ(2a) White crystals; mp 174–176°C
(with decomp.); yield 2.28 g (70%); 1H NMR: δ 2.45 (s, 3H, 4-CH3), 3.42
(s, 3H, 3-NCH3), 4.50 and 4.84 (brs, 2H, NH2), 7.50–7.87 (m, 5H, C6H5),
8.85 and 9.50 (brs, 1H, NH); 13C NMR: δ 13.0 (4-CH3), 32.7 (3-NCH3),
109.7 (C-5), 125.9, 128.9, 132.3, 140.0 (Ph), 141.7 (C-4), 160.2 (C=O), 164.8
(C-2). Anal. Calcd for C12H14N4O3S2: C, 44.16; H, 4.32; N, 17.17; S, 19.65.
Found: C, 44.02; H, 4.20; N, 16.89; S, 19.44.
2-(4-Methylbenzenesulfonylimino)-3,4-dimethyl-5-(5-thioxo-4,5-
dihydro-[1,3,4]oxadiazol-2-yl)-2,3-dihydrothiazole (3c)ꢀYellow
1
crystals; mp 242–244°C (with decomp.); yield 3.30 g (82%); H NMR:
δ 2.43 (s, 3H, PhCH3), 2.60 (s, 3H, 4-CH3), 3.53 (s, 3H, 3-NCH3) , 7. 2 8 –7.78
(m, 4H, C6H4), 14.50 (brs, 1H, NH); 13C NMR (coupled): δ 13.3 (4-CH3),
20.9 (PhCH3), 33.1 (2-NCH3), 98.6 (q, 3J = 4.8 Hz, C-5), 125.9, 129.4, 138.4,
2
3
141.4 (Ar), 142.7 (q, J = 6.6 Hz, C-4), 154.9 (C-2′), 164.6 (q, J = 3.2 Hz,
C-2), 176.4 (C=S). Anal. Calcd for C14H14N4O3S3: C, 43.96; H, 3.69; N,
14.65; S, 25.15. Found: C, 43.82; H, 3.57; N, 14.31; S, 24.85.
2-(4-Chlorobenzenesulfonylimino)-3,4-dimethyl-2,3-dihydro-
thiazole-5-carboxylic acid hydrazideꢀ(2b) White crystals; mp
191–193°C (with decomp.); yield 3.25 g (90%); 1H NMR: δ 2.50 (s, 3H,
4-CH3), 3.43 (s, 3H, 3-NCH3), 4.50 and 4.80 (brs, 2H, NH2), 7.61–7.92 (m,
4H, C6H4), 8.80 and 9.40 (brs, 1H, NH); 13C NMR: δ 13.0 (4-CH3), 32.7
(3-NCH3), 109.7 (C-5), 127.8, 129.3, 137.3, 140.1 (Ar), 141.7 (C-4), 160.2
(C=O), 164.8 (C-2). Anal. Calcd for C12H13ClN4O3S2: C, 39.94; H, 3.63; N,
15.53; S, 17.77. Found: C, 39.85; H, 3.54; N, 15.30; S, 17.52.
General procedure for 4а–с
To a solution of compound 3 (0.01 mol) and KOH (0.01 mol) in 20 mL
of water at 20°C, 1 mL (0.01 mol) of dimethyl sulfate was added por-
tion-wise. The mixture was stirred at 20°С for 24 h, and the resultant
precipitate of compound 3 was filtered off, washed with water, dried,
and crystallized from benzene.
2-(4-Methylbenzenesulfonylimino)-3,4-dimethyl-2,3-dihydro-
thiazole-5-carboxylic acid hydrazide (2c)ꢀWhite crystals; mp
190–192°C (with decomp.); yield 2.70 g (79%); 1H NMR: δ 2.36 (s, 3H,
PhCH3), 2.45 (s, 3H, 4-CH3), 3.41 (s, 3H, 3-NCH3), 4.51 and 4.83 (brs,
2H, NH2), 7.30–7.78 (m, 4H, C6H4), 8.83 and 9.49 (brs, 1H, NH); 13C
NMR (coupled): δ 13.0 (4-CH3), 20.9 (PhCH3), 32.6 (2-NCH3), 109.6 (m,
C-5), 125.9, 129.4, 138.9 (t, 2J =8.3 Hz), 140.0 (m) (Ar), 142.6 (q, 3J = 6.6
2-Benzenesulfonylimino-3,4-dimethyl-5-(5-methylsulfa-
nyl-[1,3,4]oxadiazol-2-yl-)-2,3-dihydro-thiazole (4a)ꢀWhite crys-
tals; mp 180–182°C; yield 2.98 g (78%); 1H NMR: δ 2.62 (s, 3H, 4-CH3),
2.78 (s, 3H, SCH3), 3.57 (s, 3H, 3-NCH3), 7.48–7.90 (m, 5H, C6H5); 13C
NMR: δ 13.1 (4-CH3), 14.1 (SCH3), 32.8 (3-NCH3), 99.3 (C-5), 125.7, 128.2,
131.6, 139.6 (Ph); 141.5 (C-4), 158.9 (C-2′), 163.3 (C-5′), 164.7 (C-2). Anal.
Calcd for C14H14N4O3S3: C, 43.96; H, 3.69; N, 14.65; S, 25.15. Found: C,
43.82; H, 3.60; N, 14.32; S, 24.84.
3
Hz, C-4), 160.3 (brs, C=O), 164.7 (q, J = 3.0 Hz, C-2). Anal. Calcd for
C13H16N4O3S2: C, 45.87; H, 4.74; N, 16.46; S, 18.84. Found: C, 45.69; H,
4.62; N, 16.20; S, 18.61.
2-(4-Chlorobenzenesulfonylimino)-3,4-dimethyl-5-(5-methyl-
General procedure for 3а–с
sulfanyl-[1,3,4]oxadiazol-2-yl-)-2,3-dihydrothiazole (4b)ꢀWhite
1
crystals; mp 158–160°C; yield 3.12 g (75%); H NMR: δ 2.57 (s, 3H,
To a mixture of hydrazide 2 and 1.2 mL (0.02 mol) of carbon disulfide
in 20 mL of ethanol, at boiling, 1.12 g (0.02 mol) of KOH in 10 mL of
ethanol was added dropwise with continuous stirring. Afer 7 h eth-
anol was evaporated, 10 mL of water was added, and the resultant
suspension was acidified with HCl to pH 4. Afer 2–3 h the precipitate
was filtered off, washed with water, and purified by boiling in etha-
nol (50%).
4-CH3), 2.75 (s, 3H, SCH3), 3.50 (s, 3H, 3-NCH3), 7.60–7.92 (m, 4H, C6H4);
13C NMR (coupled): δ 13.3 (4-CH3), 14.3 (SCH3), 33.3 (3-NCH3), 99.3 (q,
2
3J = 4.8 Hz, C-5), 127.8, 129.2, 137.3, 140.2 (Ar), 141.0 (q, J = 6.6 Hz,
C-4), 159.1 (C-2′), 164.0 (C-5′), 165.0 (q, 3J = 3.1 Hz, C-2). Anal. Calcd for
C14H13ClN4O3S3: C, 40.33; H, 3.14; N, 13.44; S, 23.07. Found: C, 40.20; H,
3.05; N, 13.21; S, 22.79.
2-Benzenesulfonylimino-3,4-dimethyl-5-(5-thioxo-4,5-dihy- 2-(4-Methylbenzenesulfonylimino)-3,4-dimethyl-5-(5-methylsul-
dro-[1,3,4]oxadiazol-2-yl)-2,3-dihydrothiazole (3a)ꢀYellow crys- fanyl-[1,3,4]oxadiazol-2-yl-)-2,3-dihydrothiazole (4c)ꢀWhite crys-
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K.A. Eliazyan et al.: Synthesis of [1,3,4]oxadiazolylthiazole derivatives with plant growth stimulant activityꢀ
ꢀ279
tals; mp 230–232°C; yield 3.37 g (85%); 1H NMR: δ 2.42 (s, 3H, PhCH3), NMR: δ 2.42 (s, 3H, PhCH3), 2.62 (s, 3H, 4-CH3), 3.55 (s, 3H, 3-NCH3),
2.62 (s, 3H, 4-CH3), 2.78 (s, 3H, SCH3), 3.54 (s, 3H, 3-NCH3), 7.27–7.78 (m, 3.78 (s, 3H, OCH3), 4.18 (s, 2H, SCH2), 7.25–7.78 (m, 4H, C6H4); 13C
4H, C6H4); 13C NMR: δ 13.1 (4-CH3), 14.2 (SCH3), 20.8 (PhCH3), 32.9 (3- NMR: δ 13.1 (4-CH3), 20.8 (PhCH3), 32.8 (3-NCH3), 33.4 (SCH2), 52.2
NCH3), 99.1 (C-5); 125.8, 129.0; 138.6, 140.1 (Ar), 142.3 (C-4), 159.0 (C-2′), (OCH3), 99.1 (C-5), 125.8, 128.8; 138.7, 140.0 (Ar), 142.0 (C-4), 159.2 (C-
163.6 (C-5′), 164.6 (C-2). Anal. Calcd for C15H16N4O3S3: C, 45.44; H, 4.07; 2′), 161.6 (C-5′), 164.6 (C-2), 167.1 (C=O). Anal. Calcd for C17H18N4O5S3:
N, 14.13; S, 24.26. Found: C, 45.22; H, 3.97; N, 13.88; S, 24.01.
C, 44.92; H, 3.99; N, 12.33; S, 21.16. Found: C, 44.79; H, 3.88; N, 12.03;
S, 20.90.
General procedure for 5a–c and 6а–с
2-Benzenesulfonylimino-3,4-dimethyl-5-(5-cyanomethylsulfa-
nyl-[1,3,4]oxadiazol-2-yl)-2,3-dihydro-thiazole (6a)ꢀFlesh-color-
ed crystals; mp 198–200°C; yield 3.38 g (83%); 1H NMR: δ 2.62 (s, 3H,
4-CH3), 3.55 (s, 3H, 3-NCH3), 4.42 (s, 2H, SCH2), 7.48–7.89 (m, 5H, C6H5);
13C NMR: δ 13.2 (4-CH3); 17.7 (SCH2); 32.7 (3-NCH3); 99.9 (C-5); 115.6
(C≡N); 125.7, 128.1, 131.6, 139.6 (Ph); 142.1 (C-4); 159.9 (C-2′); 160.3 (C-
5′); 164.6 (C-2). Anal. Calcd for C15H13N5O3S3: C, 44.21; H, 3.22; N, 17.19;
S, 23.61. Found: C, 44.09; H, 3.13; N, 16.88; S, 23.30.
A potassium salt of 3a–c (0.01 mol) was obtained by treatment of
compound 3a–c (0.01 mol) with KOH (0.01 mol) in 30 mL of acetone
at 10–15°C. A suspension of this salt was treated with chloroacetic
acid methyl ester or chloroacetonitrile (0.011 mol), and the mixture
was heated at 50–60°C for 3 h. Afer filtration the solution was con-
centrated, and the residue was treated with water. The resultant pre-
cipitate was filtered off and dried. Compounds 5a and 6a were crys-
tallized from benzene and others were purified by boiling in hexane.
2-(4-Chlorobenzenesulfonylimino)-3,4-dimethyl-5-(5-cyano-
methylsulfanyl-[1,3,4]oxadiazol-2-yl)-2,3-dihydrothiazole
2-Benzenesulfonylimino-3,4-dimethyl-5-(5-methoxycarbon-
yl-methylsulfanyl-[1,3,4]oxadiazol-2-yl)-2,3-dihydrothiazole
(5a)ꢀWhite crystals; mp 168–169°C; yield 3.87 g (88%); H NMR: δ
2.62 (s, 3H, 4-CH3), 3.53 (s, 3H, 3-NCH3), 3.80 (s, 3H, OCH3), 4.20 (s, 2H,
SCH2), 7.47–7.88 (m, 5H, C6H5); 13C NMR: δ 13.1 (4-CH3); 32.7 (3-NCH3);
33.5 (SCH2); 52.2 (OCH3); 99.2 (C-5); 125.7, 128.2, 131.6, 139.6 (Ph); 142.1
(C-4); 159.2 (C-2′); 162.3 (C-5′); 164.6 (C-2); 167.2 (C=O). Anal. Calcd for
C16H16N4O5S3: C, 43.62; H, 3.66; N, 12.72; S, 21.84. Found: C, 43.50; H,
3.55; N, 12.46; S, 21.56.
1
(6b)ꢀFlesh-colored crystals; mp 158–160°C; yield 3.97 g (90%); H
NMR: δ 2.62 (s, 3H, 4-CH3), 3.53 (s, 3H, 3-NCH3), 4.40 (s, 2H, SCH2),
7.58–7.90 (m, 4H, C6H4); 13C NMR: δ 13.21 (4-CH3); 17.6 (SCH2); 32.8 (3-
NCH3); 99.9 (C-5); 115.5 (C≡N); 127.8, 129.2, 137.4, 140.3 (Ar); 141.9 (C-4);
159.9 (C-2′); 160.2 (C-5′); 164.6 (C-2). Anal. Calcd for C15H12ClN5O3S3: C,
40.77; H, 2.74; N, 15.85; S, 21.77. Found: C, 40.70; H, 2.69; N, 15.62; S,
21.49.
1
2-(4-Methylbenzenesulfonylimino)-3,4-dimethyl-5-(5-cyano-
methylsulfanyl-[1,3,4]oxadiazol-2-yl)-2,3-dihydrothiazole
(6c)ꢀFlesh-colored crystals; mp 188–190°C; yield 4.0 g (95%); 1H
NMR: δ 2.42 (s, 3H, PhCH3), 2.62 (s, 3H, 4-CH3), 3.53 (s, 3H, 3-NCH3),
4.40 (s, 2H, SCH2), 7.27–7.78 (m, 4H, C6H4); 13C NMR (coupled): δ 13.2
(4-CH3), 17.5 (SCH2), 20.9 (PhCH3), 32.8 (3-NCH3), 100.0 (q, 3J = 4.8 Hz,
C-5), 115.6 (t, 2J = 8.1 Hz, C≡N), 125.8, 128.8; 138.6, 140.5 (Ar), 142.1 (q,
2-(4-Chlorobenzenesulfonylimino)-3,4-dimethyl-5-(5-methox-
ycarbonyl-methylsulfanyl-[1,3,4]oxadiazol-2-yl)-2,3-dihydro-
thiazole (5b)ꢀWhite crystals; mp 190–192°C; yield 3.94 g (83%); H
NMR: δ 2.60 (s, 3H, 4-CH3), 3.50 (s, 3H, 3-NCH3), 3.80 (s, 3H, OCH3),
4.20 (s, 2H, SCH2), 7.60–7.92 (m, 4H, C6H4); 13C NMR: δ 13.1 (4-CH3); 32.9
(3-NCH3); 33.4 (SCH2); 52.3 (OCH3); 99.2 (C-5); 127.8, 129.1, 137.3, 140.3
(Ar); 141.6 (C-4); 159.0 (C-2′); 162.5 (C-5′); 164.6 (C-2); 167.2 (C=O). Anal.
Calcd for C16H15ClN4O5S3: C, 40.46; H, 3.18; N, 11.80; S, 20.25. Found: C,
40.29; H, 3.07; N, 11.52; S, 20.02.
1
3
3
2J = 6.6 Hz, C-4), 159.9 (C-2′), 160.2 (t, J = 6.2 Hz, C-5′), 164.6 (q, J =
3.1 Hz, C-2). Anal. Calcd for C16H15N5O3S3: C, 45.59; H, 3.59; N, 16.61; S,
22.82. Found: C, 45.41; H, 3.48; N, 16.36; S, 22.58.
2-(4-Methylbenzenesulfonylimino)-3,4-dimethyl-5-(5-methox-
ycarbonyl-methylsulfanyl-[1,3,4]oxadiazol-2-yl)-2,3-dihydro-
thiazole (5c)ꢀWhite crystals; mp 194–196°C; yield 4.10 g (90%); 1H
Received April 8, 2013; accepted June 7, 2013; previously published
online July 10, 2013
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