Oxidative cyclization of N-alkyl-2-arylhydrazonothioacetamides

Article abstract of DOI:10.1007/s11172-011-0140-9

Oxidative cyclization of N-alkyl-2-arylhydrazono-2-cyanothioacetamides by the action of N-chlorosuccinimide, bromine, or iodine affords 4-cyano-5-imino-1,2,3-thiadiazoles.

Full text of DOI:10.1007/s11172-011-0140-9

Russian Chemical Bulletin, International Edition, Vol. 60, No. 5, pp. 896—900, May, 2011
896
Oxidative cyclization of Nꢀalkylꢀ2ꢀarylhydrazonothioacetamides*
N. P. Belskaya, A. I. Bolgova, M. L. Kondrat´eva, O. S. El´tsov, and V. A. Bakulev
Ural Federal University named after the First President of Russia B. N. Eltsyn,
19 ul. Mira, 620002 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 5483. Eꢀmail: belska@mail.ustu.ru
Oxidative cyclization of Nꢀalkylꢀ2ꢀarylhydrazonoꢀ2ꢀcyanothioacetamides by the action of
Nꢀchlorosuccinimide, bromine, or iodine affords 4ꢀcyanoꢀ5ꢀiminoꢀ1,2,3ꢀthiadiazoles.
Key words: hydrazones, thioacetamides, oxidation, 1,2,3ꢀthiadiazoles, heterocyclization.
Scheme 1
1,2,3ꢀThiadiazoles have a broad spectrum of biologiꢀ
cal effect,1—9 in particular, antimicrobial,1,2 fungicidal,3,4
and insecticidal5 activity.
Systematic studies of oxidative cyclization of 2ꢀarylꢀ
hydrazononthioacetamides made it possible to develop
a new preparative method for the synthesis of 5ꢀiminoꢀ
2,5ꢀdihydroꢀ1,2,3ꢀthiadiazoles10,11 and 2Hꢀ1,2,3ꢀthiadiꢀ
azoloindoles.12 In order to refine the area of application of
this method, we studied the oxidative cyclization of arylꢀ
hydrazonothioacetamides containing the alkyl substituent
in the thioamide group.
Arylhydrazonothioacetamides 1a—i were transformed
at room temperature by the addition to their solutions of
crystalline Nꢀchlorosuccinimide, a solution of bromine in
acetic acid, or a iodine solution in ethanol. As a result, we
obtained 2Hꢀ1,2,3ꢀthiadiazoliminium salts 2a—m as chloꢀ
rides, bromides, and iodides in good yields (Scheme 1).
We have earlier10 shown that for the oxidative dehydrogeꢀ
nation of arylhydrazonothioacetamides containing the priꢀ
mary thioamide group the enhancement of the electronꢀ
withdrawing properties of the substituent in the aromatic
ring decreases the yield of the final product or even changꢀ
es the direction of cyclization forming intermolecular
oxidation products, viz., 1,2,4ꢀthiadiazoles. Such a drasꢀ
tic substrate dependence was not observed in the series of
Nꢀalkylꢀsubstituted arylhydrazonothioacetamides 1a—i.
However, for arylhydrazonothioacetamides 1a—c bearing
the electronꢀdonating methoxy group in the aromatic ring,
the reaction is ceased with a yield of 90—97% using
a twofold reagent excess and storing for 1—2 h, whereas
an increase in the amount of the oxidant and the elongaꢀ
tion of the reaction duration to 15 h are necessary for
a similar transformation of 4ꢀnitrophenylhydrazones 1h,i.
This fact can be explained by the electronic effect of
the substituent in the aromatic ring, which for compounds
1h,i decreases the nucleophilicity of both the nitrogen atom
A: NCS, EtOAc; B: Br2, AcOH; C: I , EtOH
2
Comꢀ
pound
1a
1b
1c
1d
1e
1f
R1
R2
Hal
4ꢀMeOC6H4
4ꢀMeOC6H4
4ꢀMeOC6H4
Ph
Me
Bn
—
—
—
—
—
—
—
—
—
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
I
cycloꢀC6H11
Me
Bn
Ph
Ph
cycloꢀC6H11
1g
1h
1i
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
4ꢀCF3C6H4
4ꢀNO2C6H4
4ꢀNO2C6H4
4ꢀMeOC6H4
4ꢀMeOC6H4
Ph
Me
Bn
cycloꢀC6H11
Me
Bn
Me
Bn
Ph
Ph
cycloꢀC6H11
4ꢀCF3C6H4
4ꢀMeOC6H4
4ꢀMeOC6H4
4ꢀCF3C6H4
4ꢀNO2C6H4
4ꢀNO2C6H4
4ꢀMeOC6H4
4ꢀNO2C6H4
Me
Me
cycloꢀC6H11
Me
Bn
cycloꢀC6H11
Bn
2m
Bn
I
of the hydrazone group and the sulfur atom, preventing
both the formation of adduct А (see Scheme 1) and its
cyclization to final product 2j,k,m.
* Dedicated to Academician V. N. Charushin on the occasion of
his 60th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 876—880, May, 2011.
1066ꢀ5285/11/6005ꢀ896 © 2011 Springer Science+Business Media, Inc.

5ꢀIminoꢀ1,2,3ꢀthiadiazoles
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
897
Scheme 2
Elemental analysis data showed that compounds 2a—m
the ejection of nitrogen and sulfur and formation of
alkynes.1 On heating in pyridine or in the presence of
a base unsubstituted 5ꢀiminoꢀ2Hꢀ1,2,3ꢀthiadiazoles 3 are
easily transformed into 1,2,4ꢀthiadiazoles 4 (Scheme 3).10
are monochlorides, monobromides, and monoiodides. In
1
the H NMR spectra of synthesized compounds 2а—m
(DMSOꢀd6), the signals of protons of the aromatic
ring and alkyl substituent exhibit the downfield shift by
0.10—0.50 ppm compared to the signals of arylhydrazonoꢀ
thioacetamdes 1a—i. The signals of protons of the Me and
Scheme 3
1
CH groups of the iminium substituent in the H NMR
spectra of compounds 2f—h in CDCl3 are presented as a
doublet and the signals of the NH proton represent a quarꢀ
tet (2f,g) and a doublet (2h).
1
It should be mentioned that the H NMR spectra of
thiadiazoles 2 (DMSOꢀd6) are characterized by the presꢀ
ence of a double set of signals of protonꢀcontaining groups.
This indicates that in DMSOꢀd6 solutions these comꢀ
pounds exist as Zꢀ and Eꢀisomers relative to the exocyclic
bond C(5)=N.
C: TEA, Py, NaOH
R
1 = Ar, R2 = CN, CONHAlk
Salts of 5ꢀalkyliminosubstituted derivatives of 2,5ꢀdiꢀ
The mass spectra of salts 2 contain the peak of the
molecular ion (Φ1) and the peaks of stable fragments
formed upon the destruction of the thiadiazole cycle
(Φ3—Φ7) (Scheme 2). In this case, the mass spectrum
exhibits no peak of the fragmentation ion (Φ8), which is
related to sulfur elimination from the 1,2,3ꢀthiadiazole
cycle and is detected in considerable amounts in the mass
spectra of thiadiazolimines (R2 = H)10 (Scheme 2).
It is known that 1,2,3ꢀthiadiazole derivatives easily
undergo rearrangements and in the presence of strong bases
or on heating they are susceptible to ring destruction with
hydroꢀ1,2,3ꢀthiadiazoles 2 in solution in the presence of
a base only lose a hydrohalide molecule and are transꢀ
formed into 5ꢀalkyliminoꢀ2ꢀarylꢀ2,5ꢀdihydroꢀ1,2,3ꢀthiaꢀ
diazoles 5a—d as mixtures of two isomers (Scheme 4).
1
It should be mentioned that the H NMR spectra of
2,5ꢀdihydroꢀ1,2,3ꢀthiadiazoles 5a—d contains no signal
from the proton of the imino group characteristic of the
corresponding hydrohalides 2a—c,h. The signals of proꢀ
tons of the groups NMe, NCH2, and NCH of thiadiazoles 5
are presented as upfield singlets compared to analogous
signals in the starting salts 2. The IR spectra of comꢀ

898
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
Belskaya et al.
Scheme 4
A: TEA, EtOH, 20 °C; B: Py, Δ
5: R1 = 4ꢀMeOC6H4, R2 = Me (a), Bn (b), cycloꢀC6H11 (c); R1 = Ph, R2 = Me (d)
1
for H and 100.00 MHz for 13C) in DMSOꢀd6 or CDCl3 soluꢀ
tions using Me4Si as an internal standard. IR spectra were meaꢀ
sured on a Bruker Alpha FTIR spectrometer (Frustrated Total
Internal Reflection, ZnSe). Mass spectra were recorded on
a Varian MAT 311A spectrometer (accelerating voltage 3 kV,
ionization potential 70 eV, direct sample inlet). The reaction
course and individual character of the synthesized substances
were monitored by TLC on Sorbfil UVꢀ254 plates in ethyl aceꢀ
tate—hexane (1 : 1); chloroform—acetone (30 : 1); and chloroꢀ
form—hexane—acetone (5 : 4 : 1) systems. Solvents were puriꢀ
fied according to a standard procedure.
pounds 5 exhibit the shift of the absorption band correꢀ
sponding to stretching vibrations of the cyano group by
29—38 cm–1 to the region of lower frequencies compared
with the IR spectra of chlorides, bromides, and iodides of
5ꢀalkyliminoꢀ1,2,3ꢀthiadiazoles 2.
A new compound (TLC) is formed upon storing salt 2c
in an ethanol solution in the presence of KOH for 2 h at
room temperature. According to the data of spectroscopy
and elemental analysis, this compound turned out to be
ethyl 1,2,3ꢀthiadiazoleꢀ4ꢀcarbimidate 6 (Scheme 5).
Arylhydrazonothioacetamides were synthesized by the methꢀ
od described earlier.13
Scheme 5
Oxidative cyclization of Nꢀalkylꢀ2ꢀarylhydrazonothioacetꢀ
amides 1 (general procedures). Method A. NꢀChlorosuccinimide
(0.25 g, 6 mmol) was added to a solution of arylhydrazonothioꢀ
acetamide 1a,b,d—g (2 mmol) in ethyl acetate (100 mL), and
the mixture was stirred at ~20 °C for 1—15 h (TLC). The precipꢀ
itate was filtered off and washed with ethyl acetate.
Method B. A solution of Br2 (0.1 mL, 6 mmol) in acetic acid
(5 mL) was added to a solution of arylhydrazonothioacetamide
1a,c,g—i (2 mmol) in acetic acid (100 mL) heated to 40 °C. The
reaction mixture was stirred for 5 h at ~20 °C. The precipitate
was filtered off and recrystallized from ethanol.
The 1H NMR spectrum of ethyl carbimidate 6 contains
one set of protonꢀcontaining groups. It can be assumed
that this is the Z,cisꢀisomer, because this structure can be
stabilized due to the formation of an intramolecular hyꢀ
drogen bond between the hydrogen atom of the imino
group and the nitrogen atom of the 5ꢀmethylimino group.
As a result of the study of oxidation of Nꢀalkylꢀ2ꢀarylꢀ
hydrazonoꢀ2ꢀcyanothioacetamides 1, we synthesized new
Nꢀalkyl derivatives of 2ꢀarylꢀ5ꢀiminoꢀ2,5ꢀdihydroꢀ1,2,3ꢀ
thiadiazoles 2 as their hydrohalides and free bases 5. It
should be mentioned that the reaction occurs rather sucꢀ
cessfully regardless of the substituent in the aromatic ring
or at the nitrogen atom of the thioamide group. In the case of
substrates with the alkyl substituent in the 5ꢀimino group, the
corresponding 2,5ꢀdihydroꢀ1,2,3ꢀthiadiazoles are so stable
that even in the presence of strong bases (for example,
KOH) the transformation involves only side substituents,
whereas the heterocyclic fragment remains unchanged.
Method C. A solution of I2 (8 mmol) in EtOH (5 mL) was
added to a solution of arylhydrazonothioacetamide 1b,h (2 mmol)
in EtOH (100 mL). The reaction mixture was stirred for 5 h at
~20 °C. The precipitate was filtered off and washed with EtOH.
Nꢀ[4ꢀCyanoꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ1,2,3ꢀthiadiazolꢀ5ꢀylꢀ
idene]ꢀNꢀmethylammonium chloride (2а). Method A, the yield
was 0.462 g (82%), m.p. 167—168 °C. IR, ν/cm–1: 2231 (C≡N);
2845, 2935 (C—H); 3144 (NH). 1H NMR (DMSOꢀd6), δ: 3.15,
3.59 (both s, 3 H, NMе); 3.86, 3.92 (both s, 3 H, ОMе); 7.09,
7.69, 7.17, 7.72 (two systems AA´XX´, 4 H, Ar, J = 8.8 Hz);
10.88 (br.s, 1 H, =NH). A mixture of Zꢀ and Eꢀisomers in the
ratio 1 : 1. 13C NMR (DMSOꢀd6), δ: 33.1, 47.8, 55.4, 55.5, 112.6,
112,8, 114.8, 115.1, 118.2, 118.4, 119.1, 121.5, 133.6, 135.1,
157.5, 159.6, 160.60, 168.63. MS, m/z (Irel (%)): 246 [M – HCl]+
(43). Found (%): C, 46.52; H, 4.08; Cl, 12.84; N, 20.03; S, 11.19.
C11H11ClN4OS. Calculated (%): C, 46.73; H, 3.92; Cl, 12.54;
N, 19.81; S, 11.34.
NꢀBenzylꢀNꢀ[4ꢀcyanoꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ1,2,3ꢀthiadiꢀ
azolꢀ5ꢀylidene]ammonium chloride (2b). Method A, the yield was
0.523 g (73%), m.p. 162—163 °C. IR, ν/cm–1: 2229 (C≡N); 2836,
2920, 3000 (C—H); 3150, 3440 (NH). 1H NMR (DMSOꢀd6), δ:
3.75, 3.86 (both s, 3 H, ОMе); 4.50, 6.02 (both s, 2 H, CH2);
6.85—7.12 (m, 4 H, Ar); 7.20—7.40 (m, 4 H, Ar); 7.53—7.69
(m, 1 H, Ar); 11.33 (br.s, 1 H, =NH). A mixture of Zꢀ and Eꢀisomers
Experimental
1
H and 13C NMR spectra were recorded on Bruker WMꢀ250
and Bruker AVANCE II 400 instruments (250.13 and 400.00 MHz

5ꢀIminoꢀ1,2,3ꢀthiadiazoles
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
899
in the ratio 1 : 1. 13C NMR (DMSOꢀd6), δ: 49.9, 56.0, 56.2,
56.3, 112.9, 113.7, 115.4, 115.9, 120.6, 121.3, 123.1, 126.0,
127.1, 127.9, 128.2, 128.8, 129.1, 129.2, 129.4, 129.6, 132.8,
135.6, 160.4, 161.2, 166.5, 168.4. MS, m/z (Irel (%)): 322
[M – HCl]+ (17). Found (%): C, 56.72; H, 4.01; N, 15.89;
S, 8.65. C17H15ClN4OS. Calculated (%): C, 56.90; H, 4.21;
N, 15.61; S, 8.94.
H, 4.50; Br, 20.61; N, 14.41. C16H19BrN4OS. Calculated (%):
C, 48.61; H, 4.84; Br, 20.21; N, 14.17.
Nꢀ[4ꢀCyanoꢀ2ꢀ(4ꢀtrifluoromethylphenyl)ꢀ1,2,3ꢀthiadiazolꢀ5ꢀ
ylidene]ꢀNꢀmethylammonium bromide (2i). Method B, the yield
was 0.518 g (71%), m.p. 208—209 °C. 1H NMR (DMSOꢀd6), δ:
3.76, 4.37 (both s, 3 H, NMe); 7.62, 7.65 (both s, 4 H, Ar); 10.9
(br.s, 1 H, =NH). A mixture of Zꢀ and Eꢀisomers in the ratio
1 : 1. MS, m/z (Irel (%)): 284 [M – HBr]+ (85). Found (%):
C, 36.45; H, 2.48; Br, 22.03; N, 15.10. C11H8BrF3N4S. Calcuꢀ
lated (%): C, 36.18; H, 2.21; Br, 21.88; N, 15.30.
NꢀBenzylꢀNꢀ[4ꢀcyanoꢀ2ꢀ(4ꢀnitrophenyl)ꢀ1,2,3ꢀthiadiazolꢀ5ꢀ
ylidene]ammonium bromide (2j). Method B, the yield was 0.443 g
(53%), m.p. 180—181 °C. IR, ν/cm–1: 2235 (C≡N), 3440 (NH).
1H NMR (DMSOꢀd6), δ: 4.55, 5.3 (both s, 2 H, CH2); 7.35—7.47
(m, 5 H, Ph); 7.75—8.10 (m, 4 H, Ar); 11.1 (br.s, 1 H, =NH).
A mixture of Zꢀ and Eꢀisomers in the ratio 1 : 3. MS, m/z (Irel (%)):
337 [M – HBr]+ (16). Found (%): C, 46.22; H, 3.01; Br, 19.51;
N, 16.15. C16H12BrN5О2S. Calculated (%): C, 45.93; H, 2.87;
Br, 19.14; N, 16.75.
Nꢀ[4ꢀCyanoꢀ2ꢀ(4ꢀnitrophenyl)ꢀ1,2,3ꢀthiadiazolꢀ5ꢀylidene]ꢀ
Nꢀcyclohexylammonium bromide (2k). Method B, the yield was
0.435 g (53%), m.p. 198—199 °C. IR, ν/cm–1: 2237 (C≡N); 2854,
2940 (C—H); 3400 (NH). 1H NMR (DMSOꢀd6), δ: 1.21—1.88
(m, 10 H, 5 CH2); 4.41 (m, 1 H, CH); 7.26, 8.05, 8.36, 8.42
(AA´ВВ´ system, 4 H, Ar, J = 8.9 Hz); 11.99 (br.s, 1 H, =NH).
A mixture of Zꢀ and Eꢀisomers in the ratio 1 : 1. MS, m/z
(Irel (%)): 329 [M – HBr]+ (70). Found (%): C, 43.76; H, 3.65;
Br, 19.85; N, 16.81. C15H16BrN5O2S. Calculated (%): C, 43.90;
H, 3.90; Br, 19.51; N, 17.07.
NꢀBenzylꢀNꢀ[4ꢀcyanoꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ1,2,3ꢀthiadiꢀ
azolꢀ5ꢀylidene]ammonium iodide (2l). Method C, the yield was
0.756 g (84%), m.p. 203—204 °C. IR, ν/cm–1: 2226 (C≡N); 3440
(NH). 1H NMR (DMSOꢀd6), δ: 3.86, 3.92 (both s, 3 H, ОMe);
5.2, 6.5 (both s, 2 H, CH2); 7.01, 7.09, 7.24, 7.22 (two AA´XX´
systems, 4 H, Ar, J = 9.0 Hz); 7.25—7.65 (m, 5 H, Ph); 10.85
(br.s, 1 H, =NH). A mixture of Zꢀ and Eꢀisomers in the ratio
1 : 1. MS, m/z (Irel (%)): 322 [M – HI]+ (18). Found (%):
C, 45.10; H, 3.01; I, 28.53; N, 12.18. C17H15IN4OS. Calculatꢀ
ed (%): C, 45.33; H, 3.33; I, 28.22; N, 12.45.
NꢀBenzylꢀNꢀ[4ꢀcyanoꢀ2ꢀ(4ꢀnitrophenyl)ꢀ1,2,3ꢀthiadiazolꢀ5ꢀ
ylidene]ammonium iodide (2m). Method C, the yield was 0.512 g
(55%), m.p. 176—177 °C. IR, ν/cm–1: 2234 (C≡N); 3440 (NH).
1H NMR (DMSOꢀd6), δ: 4.56 (s, 2 H, CH2); 7.35—7.47 (m, 5 H,
Ph); 7.74, 8.41 (AA´ВВ´ system, 4 H, Ar, J = 8.0 Hz); 10.90
(br.s, 1 H, =NH). MS, m/z (Irel (%)): 337 [M – HI]+ (14).
Found (%): C, 41.56; H, 2.35; I, 27.05; N, 15.31. C16H12IN5O2S.
Calculated (%): C, 41.30; H, 2.60; I, 27.28; N, 15.05.
Bases 5a—d (general procedures). Method A. Triethylamine
(0.139 mL, 1 mmol) was added to a solution of thiadiazolium
salts 2a,b,g,h in EtOH (20 mL). The reaction mixture was stirred
for 1 h at ~20 °C, and the precipitate was filtered off.
Method B. Iminium chloride 2a (1 mmol) in pyridine (4 mL)
was refluxed for 10 min, and then the reaction mixture was poured
into ice with water. The precipitate was filtered off.
Method C. Potassium hydroxide (0.26 g, 4 mmol) was added
to a solution of iminium chloride 2c (2 mmol) in EtOH (20 mL),
the mixture was stirred for 2 h at ~20 °C, then ice was added, and
the precipitate was filtered off.
Nꢀ(4ꢀCyanoꢀ2ꢀphenylꢀ1,2,3ꢀthiadiazolꢀ5ꢀylidene)ꢀNꢀmethylꢀ
ammonium chloride (2c). Method A, the yield was 0.403 g (80%),
m.p. 241—242 °C. IR, ν/cm–1: 2230 (C≡N); 2850, 2920, 2960,
1
3000 (C—H); 3360 (NH). H NMR (DMSOꢀd6), δ: 3.57, 4.31
(both s, 3 H, Mе); 7.34—7.38 (m, 1 H, Ph); 7.54—7.65 (m, 3 H,
Ph); 7.78—7.84 (m, 1 H, Ph); 10.99 (br.s, 1 H, =NH). A mixture
of Zꢀ and Eꢀisomers in the ratio 1 : 1. MS, m/z (Irel (%)): 216
[M – HCl]+ (56). Found (%): C, 47.75; H, 3.32; Cl, 13.85;
N, 22.46; S, 12.92. C10H9ClN4S. Calculated (%): C, 47.53;
H, 3.59; Cl, 14.03; N, 22.17; S, 12.69.
NꢀBenzylꢀNꢀ(4ꢀcyanoꢀ2ꢀphenylꢀ1,2,3ꢀthiadiazolꢀ5ꢀylidene)ꢀ
ammonium chloride (2d). Method A, the yield was 0.485 g (74%),
m.p. 179—180 °C. IR, ν/cm–1: 2238 (C≡N); 2855, 2920, 2963,
1
3010 (C—H); 3460 (NH). H NMR (DMSOꢀd6), δ: 3.91, 4.42
(both s, 2 H, CH2); 7.37—7.35 (m, 1 H, Ph); 7.40 (d, 2 H, Ph,
J = 7.6 Hz); 7.46 (t, 2 H, Ph, J = 7.6 Hz); 7.53 (d, 2 H, Ph,
J = 7.7 Hz); 7.65—7.63 (m, 1 H, Ph); 7.81 (d, 2 H, Ph, J = 7.6 Hz);
11.47 (br.s, 1 H, =NH). MS, m/z (Irel (%)): 282 [M – HCl]+ (7).
Found (%): C, 52.92; H, 3.74; Cl, 9.58; N, 15.11. C16H13ClN4S.
Calculated (%): C, 52.67; H, 3.57; Cl, 9.74; N, 15.36.
Nꢀ(4ꢀCyanoꢀ2ꢀphenylꢀ1,2,3ꢀthiadiazolꢀ5ꢀylidene)ꢀNꢀcycloꢀ
hexylammonium chloride (2e). Method A. The yield was 0.531 g
(83%), m.p. 170—171 °C. IR, ν/cm–1: 2228 (C≡N); 2929 (C—H);
3440 (NH). 1H NMR (DMSOꢀd6), δ: 1.35—2.12 (m, 10 H,
5 CH2); 3.95, 4.57 (both m, 1 H, CH); 7.46—7.78 (m, 5 H, Ph);
10.99, 11.37 (both s, 1 H, =NH). A mixture of Zꢀ and Eꢀisomers
in the ratio (1 : 1). MS, m/z (Irel (%)): 284 [M – HCl]+ (34).
Found (%): C, 42.58; H, 4.39; Cl, 8.62; N, 13.52. C15H17ClN4S.
Calculated (%): C, 42.81; H, 4.04; Cl, 8.44; N, 13.32.
Nꢀ[4ꢀCyanoꢀ2ꢀ(4ꢀtrifluoromethylphenyl)ꢀ1,2,3ꢀthiadiazolꢀ5ꢀ
ylidene]ꢀNꢀmethylammonium chloride (2f). Method A, the yield
was 0.416 g (65%), m.p. 193—194 °C. 1H NMR (CDCl3), δ: 3.67
(d, 3 H, Mе, J = 5.5 Hz); 7.98—7.80 (m, 4 H, Ar); 11.26 (br.q,
1 H, =NH, J = 5.5 Hz). MS, m/z (Irel (%)): 284 [M – HCl]+ (5).
Found (%): C, 41.31; H, 2.34; Cl, 11.34; N, 17.25. C11H8ClF3N4S.
Calculated (%): C, 41.19; H, 2.50; Cl, 11.08; N, 17.47.
Nꢀ[4ꢀCyanoꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ1,2,3ꢀthiadiazolꢀ5ꢀylꢀ
idene]ꢀNꢀmethylammonium bromide (2g). Method B, the yield
was 0.403 g (62%), m.p. 208—209 °C. IR, ν/cm–1: 2228 (C≡N);
2929 (C—H), 3445 (NH). 1H NMR (CDCl3), δ: 3.65 (d, 3 H,
Mе, J = 5.6 Hz); 3.91 (s, 3 H, ОMе); 7.04, 7.64 (AA´XX´ sysꢀ
tem, 4 H, Ar, J = 9.2 Hz); 10.52 (br.q, 1 H, =NH, J = 5.6 Hz).
MS, m/z (Irel (%)): 246 [M – HBr]+ (16). Found (%): C, 40.61;
H, 3.22; Br, 24.20; N, 17.45. C11H11BrN4ОS. Calculated (%):
C, 40.38; H, 3.39; Br, 24.42; N, 17.12.
Nꢀ[4ꢀCyanoꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ1,2,3ꢀthiadiazolꢀ5ꢀ
ylidene]ꢀNꢀcyclohexylammonium bromide (2h). Method B, the
yield was 0.670 g (85%), m.p. 160—161 °C. IR, ν/cm–1: 2231
1
(C≡N); 2854, 2928 (C—H); 3445 (NH). H NMR (CDCl3), δ:
1.55—2.16 (m, 10 H, 5 CH2); 3.91 (s, 3 H, ОMe); 4.53 (m, 1 H,
CH); 7.05, 7.65 (AA´ВВ´ system, 4 H, Ar, J = 8.6 Hz); 10.56
(br.d, 1 H, =NH, J = 7.0 Hz). 13C NMR (CDCl3), δ: 23.0, 24.4,
31.9, 55.4, 55.9, 112.2, 113.7, 115.5, 122.8, 132.3, 160.8, 166.3.
MS, m/z (Irel (%)): 314 [M – HBr]+ (18). Found (%): C, 48.86;
2ꢀ(4ꢀMethoxyphenyl)ꢀ5ꢀmethyliminoꢀ2,5ꢀdihydroꢀ1,2,3ꢀthiaꢀ
diazoleꢀ4ꢀcarbonyl (5а). Methods A and B, the yield was 0.354 g
(72 and 73%), m.p. 203—204 °C. IR, ν/cm–1: 2200 (C≡N); 2840,

900
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
Belskaya et al.
2930, 2960 (C—H). 1H NMR (DMSOꢀd6), δ: 3.17, 4.13 (both s,
3 H, Me); 3.81, 3.84 (both s, 3 H, ОMe); 6.96—7.02 (m, 2 H,
Ar); 7.40 (d, 1 H, Ar, J = 9.1 Hz); 7.73 (d, 1 H, Ar, J = 9.0 Hz).
A mixture of Zꢀ and Eꢀisomers in the ratio 1 : 1. 13C NMR
(DMSOꢀd6), δ: 37.5, 40.1, 55.4, 55.5, 110.2, 110.3, 113.3, 114.8,
115.1, 118.6, 119.1, 121.5, 133.6, 135.1, 156.2, 157.5, 159.4,
159.6. MS, m/z (Irel (%)): 246 [M]+ (66). Found (%): C, 53.82;
H, 4.27; N, 22.54; S, 13.28. C11H10N4OS. Calculated (%):
C, 53.64; H, 4.09; N, 22.75; S, 13.02.
H, 5.23; N, 21.15; S, 12.38. C12H14N4OS. Calculated (%):
C, 54.96; H, 5.34; N, 21.37; S, 12.21.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 10ꢀ03ꢀ
96084_r_uralꢀa).
References
5ꢀBenzyliminoꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ2,5ꢀdihydroꢀ1,2,3ꢀthiaꢀ
diazoleꢀ4ꢀcarbonitrile (5b). Method A, the yield was 0.470 g
(75%), m.p. 162—163 °C. IR, ν/cm–1: 2200 (C≡N); 2840, 2920,
3040, 3060 (C—H). 1H NMR (DMSOꢀd6), δ: 3.79, 3.85 (both s,
3 H, ОMe); 4.50, 6.03 (both s, 2 H, CH2); 6.86—7.10 (m, 4 H,
Ar); 7.20—7.38 (m, 4 H, Ph); 7.76 (d, 1 H, Ph, J = 7.7 Hz).
A mixture of Zꢀ and Eꢀisomers in the ratio 1 : 3. MS, m/z
(Irel (%)): 322 [M]+ (29). Found (%): C, 63.59; H, 4.61; N, 17.57;
S, 9.61. C17H14N4OS. Calculated (%): C, 63.34; H, 4.38;
N, 17.38; S, 9.95.
1. V. A. Bakulev, W. Dehaen, The Chemistry of 1,2,3ꢀThiadiꢀ
azoles, Eds E. C. Taylor, P. Wipf, John Wiley and Sons,
Chichester, 2004, 62, 241 pp.
2. T. Balasankar, M. Gopalakrishnan, S. Nagarajan, Eur. J.
Med. Chem., 2005, 40, 728.
3. F. Gozzo, J. Agric. Food Chem., 2003, 51, 4487.
4. Z. Fan, Z. Shi, H. Zhang, X. Liu, L. Bao, L. Ma, X. Zuo,
Q. Zheng, N. Mi, J. Agric. Food Chem., 2009, 57, 4279.
5. G. Nombela, S. Pascual, M. Aviles, E. Guillard, M. Muniz,
J. Econ. Entom., 2005, 98, 2266.
5ꢀCyclohexyliminoꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ2,5ꢀdihydroꢀ1,2,3ꢀ
thiadiazoleꢀ4ꢀcarbonitrile (5c). Method A, the yield was 0.340 g
(54%), m.p. 74—75 °C. 1H NMR (DMSOꢀd6), δ: 1.20—1.36
(m, 3 H, CH2); 1.44—1.55 (m, 2 H, CH2); 1.60—1.66 (m, 1 H,
CH2); 1.78—1.87 (m, 4 H, CH2); 2.39—2.45 (m, 1 H, CH); 3.81
(s, 3 H, ОMe); 7.70, 7.37 (AA´XX´ system, 4 H, Ar, J = 8.8 Hz).
MS, m/z (Irel (%)): 314 [M]+ (42). Found (%): C, 60.90; H, 5.54;
N, 17.60. C16H18N4OS. Calculated (%): C, 61.12; H, 5.77;
N, 17.82.
5ꢀMethyliminoꢀ2ꢀphenylꢀ2,5ꢀdihydroꢀ1,2,3ꢀthiadiazoleꢀ4ꢀ
carbonitrile (5d). Method A, the yield was 0.260 g (60%), m.p.
241—242 °C. IR, ν/cm–1: 2200 (C≡N); 2850, 2920, 2960, 3000
(C—H). 1H NMR (DMSOꢀd6), δ: 3.25, 4.25 (both s, 3 H, Me);
7.29—7.34 (m, 1 H, Ph); 7.42—7.60 (m, 3 H, Ph); 7.77 (d, 1 H,
Ph, J = 7.3 Hz). A mixture of Zꢀ and Eꢀisomers in the ratio 1 : 3.
MS, m/z (Irel (%)): 216 [M]+ (54). Found (%): C, 55.35; H, 3.53;
N, 26.14; S, 15.07. C10H8N4S. Calculated (%): C, 55.54; H, 3.73;
N, 25.91; S, 14.83.
6. M. Orober, J. Siegrist, H. Buchenauer, Eur. J. Plant Path.,
2004, 108, 345.
7. R. C. Plymale, G. W. Felton, K. Hoover, J. Chem. Ecol.,
2007, 33, 1570.
8. F. Pasquer, E. Isidor, J. Zarn, B. Keller, Plant Mol. Biol.,
2005, 57, 693.
9. Z. Li, Z. Wu, F. Luo, J. Agric. Food Chem., 2005, 53, 3872.
10. M. L. Vasil´eva, M. V. Mukhacheva, N. P. Belskaya, V. A.
Bakulev, R. Dzh. Anderson, P. V. Graundvoter, Zh. Org.
Khim., 2004, 818 [Russ. J. Org. Chem. (Engl. Transl.), 2004,
40, No. 6].
11. K. Gewald, U. Hain, J. Prakt. Chem./Chem.ꢀZtg., 1975,
317, 329.
12. M. L. Kondratieva, A. V. Pepeleva, N. P. Belskaia, A. V.
Koksharov, P. V. Graundwater, K. Robeyns, L. Van Meerꢀ
velt, W. Dehaen, J.ꢀZ. Fan, V. A. Bakulev, Tetrahedron,
2007, 63, 3042.
13. T. G. Deryabina, N. P. Belskaya, M. I. Kodess, V. A. Bakuꢀ
lev, Khim. Geterotsikl. Soedin., 2007, 794 [Chem. Heterocycl.
Compd. (Engl. Transl.), 2007, 43, 18].
Ethyl 5ꢀmethyliminoꢀ2ꢀphenylꢀ2,5ꢀdihydroꢀ1,2,3ꢀthiadiazꢀ
oleꢀ4ꢀcarbimidate (6). Method C, the yield was 0.49 g (93%),
m.p. 92—93 °C. 1H NMR (DMSOꢀd6), δ: 1.33 (t, 3 H, OCH2CH3,
J = 7.2 Hz); 3.20 (s, 3 H, Me); 4.30 (q, 2 H, OCH2CH3, J = 7.2 Hz);
7.21—7.17 (m, 1 H, Ph); 7.44—7.30 (m, 4 H, Ph); 9.56 (s, 1 H,
NH). MS, m/z (Irel (%)): 262 [M]+ (45). Found (%): C, 55.15;
Received February 14, 2011;
in revised form April 25, 2011