Unexpected result for the acylation of arylhydrazonoethanethioamides

Article abstract of DOI:10.1016/j.tet.2013.06.071

The acylation of arylhydrazonoethanethioamides containing primary amino group did not yield acylthioamides as expected. Surprisingly, the cyclic 5-acylimino-2,5-dihydro-1,2,3-thiadiazoles were obtained. The formation of thiadiazoles in this reaction was explained by the higher ability of arylhydrazono-N-acylthioacetamide intermediates to be oxidized comparing to their precursors. The presence of pseudobicyclic aromatic structure in the reaction product was a main factor favoring the formation of 1,2,3-thiadiazole ring.

Full text of DOI:10.1016/j.tet.2013.06.071

Tetrahedron 69 (2013) 7423e7429
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Unexpected result for the acylation of
arylhydrazonoethanethioamides
,
Anastasiya I. Bolgova a, Kseniya I. Lugovik a, Julia O. Subbotina a b, Pavel A. Slepukhin b,
,
Vasiliy A. Bakulev a, Nataliya P. Belskaya a
*
a Urals Federal University, Mira Str. 19, Ekaterinburg 620002, Russia
b I. Ya. Postovsky Institute of Organic Synthesis of the Ural Branch of Russian Academy of Sciences, S. Kovalevskaya Str. 20, Ekaterinburg 620219, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
The acylation of arylhydrazonoethanethioamides containing primary amino group did not yield
acylthioamides as expected. Surprisingly, the cyclic 5-acylimino-2,5-dihydro-1,2,3-thiadiazoles were
obtained. The formation of thiadiazoles in this reaction was explained by the higher ability of arylhy-
drazono-N-acylthioacetamide intermediates to be oxidized comparing to their precursors. The presence
of pseudobicyclic aromatic structure in the reaction product was a main factor favoring the formation of
1,2,3-thiadiazole ring.
Received 21 December 2012
Received in revised form 30 May 2013
Accepted 17 June 2013
Available online 26 June 2013
Keywords:
Arylhydrazonoethanethioamide
Acylation
Ó 2013 Elsevier Ltd. All rights reserved.
1,2,3-Thiadiazole
Oxidation
Thiapentalene
1. Introduction
Arylhydrazonoethanethioamides are often used as precursors to
various heterocyclic compounds.1 Their
-system is highly conju-
p
gated and enriched by lone pairs of electrons and/or mobile pro-
tons. As a result, very simple modifications, such as acylation or
alkylation, quite often lead to unusual cascade-like transformations
and unexpected products.1b,c
We focused our study on acylation of arylhydrazonoethane-
thioamides 1, functionalized with a primary amine group, assuming
that the presence of several nucleophilic centers in thioamides 1
might lead to the formation of linear and cyclic products. Either
N-acylhydrazones 4 or N-acylthioamides 5, and products of their
intramolecular cyclization, 1,2,4-triazinthiones 6 (Scheme 1) were
expected. This is a new approach to the synthesis of 5-thioxo-2,5-
dihydro-1,2,4-triazines 6 and hasn’t been reported previously.
Further modifications of active functional groups in compounds 6
could also open a new route for the synthesis of bioactive 1,2,4-
triazines.2 The convenience of compounds 1 as models to study
the reactivity of functionalized arylhydrazones with multiple nu-
cleophilic centers is also important.1a
Scheme 1. Expected directions of the acylation of hydrazonoethanthioamides 1.
2. Results and discussion
The acylation of hydrazonoethanethioamides 1aee with anhy-
dride 2 or acyl chloride 3 was performed in pyridine (Scheme 2).
Surprisingly for us the 5-acylimino-2,5-dihydro-1,2,3-thiadiazoles
7aej were formed instead of desired compounds 4e6.
Elemental analysis and all spectral data supported the formation
of products 7aej. Mass-spectrometry data exhibited a molecular
ion peak of 5-acylimino-2,5-dihydro-1,2,3-thiadiazoles, which
differed by two units from the molecular ion peak of assumed
* Corresponding author. E-mail address: n.p.belskaya@ustu.ru (N.P. Belskaya).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.06.071

7424
A.I. Bolgova et al. / Tetrahedron 69 (2013) 7423e7429
Scheme 2. Synthesis of (2-aryl-1,2,3-thiadiazol-5(2H)-ylidene)acetamides 7.
structure for acyl derivatives 4 or 5. 1H NMR spectra of compounds
7aej displayed signals for proton-bearing groups for acyl moiety
(R2). Furthermore, there were no signals corresponding to the
protons of NH-groups in 1H NMR spectra.
2-aryl-2,5-dihydro-1,2,3-thiadiazoliminium bromides 8a,b as it
was published earlier.5
13C and 1H NMR spectra, mass spectra, and melting points for
(1,2,3-thiadiazol-5(2H)-ylidene)acetamides 7a,g synthesized by
two different methods were identical (Scheme 4).
Also, several unusual data were found in spectra for compounds 7.
For example, absorption band of C^N bond for the thiadiazoles 7aef
in IR spectra shifted to the region with higher frequency
(2234e2241 cmꢀ1). The signal for C]O bond of acyl group moved to
lower frequency (1583e1610 cmꢀ1). The singlet of carbon atom of
carbonyl group in 13C NMR spectrawas registered in downfield region.
There was only one set of signals in 1H and 13C spectra. Whereas
compounds with double exocyclic C]N bond usually exist in the
form of two stereoisomers (Scheme 3) with two sets of signals
appearing in NMR spectra. For example, the formation of two ste-
reoisomers for alkyl derivatives of 5-imino-1,2,3-thiadiazole was
registered by two sets of signals in 1H and 13C NMR experements.3
X-ray diffraction data for compounds 7d,g,h were in line with
other spectral data described above and established that the mole-
cules exist in their Z-isomeric form constrained by an S/O bond. The
distance between the carbonyl oxygen and thiadiazole sulfur atoms
was substantially shorter than the sum of Van der Waals radii for
those atoms (Figs. 1e3 and Fig. S1eS3 in Supplementary data). The
bonds in the thiadiazole ring (N(2)]N(3), N(3)eC(4), C(4)eC(5),
C(5)eS(1), S(1)eN(2)), and iminoacyl fragment (C(5)eN(6), N(6)e
C(7), C(7)]O(8)) were substantially distorted for 7d,g,h compared to
standard bond lengths (Fig. S1eS3).6 The
p-conjugated heteroatomic
system was planar. The maximal deviation of terminal atoms in side
ꢀ
chains from the least-squared plane was less than 0.07 A. The bond
angles N(2)eS(1)eO(8) in structures 7d,g,h were approximately
linear (Figs. 1e3). It has been shown previously that such an ar-
rangement of atoms governs an overlapping of non-bonding n(O)
orbital located on oxygen and vacant s*(SeN) orbital located on SeN
bond. Intramolecular non-covalent S/O bond was formed in com-
pounds 7d,g,h and resulted in their extra stabilization (Fig. 4).
The nature of the non-covalent S/X (X¼S, N, O) interaction
between the two electron-rich centers within one molecule has
attracted special attention from experimentalists and theoreticians
from different fields.7,8 It was shown that in some cases that the
S/O interaction determined backgrounds of several biological
phenomena or was responsible for enhanced druggability of com-
pounds. For example, the increase of antitumor activity of angio-
tensin II receptor (AT1) antagonists was linked to the presence of
S/O non-covalent bond.8c Thus, designing new molecular struc-
tures with S/O contact seems to be an efficient approach toward
the development of various drugs.
Furthermore, the introduction of an S/O interaction increased
the conformational rigidity of oligothiophenes and enhanced their
photophysical and conductive properties.9 Thus, molecules con-
strained by strong S/O bond can be used as building blocks to
construct supramolecular structures being of interest to material
science.7c,9
Scheme 3. Proposed isomers for (2-aryl-1,2,3-thiadiazol-5(2H)-ylidene)acetamides 7.
The mechanism for the formation of 5-acylimino-2,5-dihydro-
1,2,3-thiadiazoles 7aej is an oxidative cyclization of interim 4
following the initial acylation (Scheme 2).
It should be mentioned that oxidation is one of the most typical
transformations in the chemistry of thioamides,1a,3,4 although, it does
not occur simultaneously without an added oxidant. Oxidation of
arylhydrazonoethanethioamides takes place only in the presence
of bromine, iodine or N-chlorosuccinimide and yields 5-imino-
thiadiazoles.3,4 Last ones are unstable and exists exclusively in salt
forms (chlorides, bromides, and iodides). They undergo diverse
transformations under the heating in pyridine. As a result, acylation of
5-iminothiadiazoles involves their reflux inpyridine with acyl chloride
and frequently is accompanied by the formation of the byproduct.5
5-Acylimino-1,2,3-thiadiazoles 7aej listed in Table 1 have never
been described before to our best knowledge. To prove their
structure, retrospective synthesis was performed as shown on
Scheme 4. Compounds 7a,g were synthesized via acylation of
The strength and nature of n(O)/[s*(SeN)] interaction can be
studied with the help of computational chemistry methods (NBO,
AIM etc.).8a,c,10 The simplest (but rough) criteria to evaluate benefits
of stabilization due to intramolecular S/O interaction would be

A.I. Bolgova et al. / Tetrahedron 69 (2013) 7423e7429
7425
Table 1
(2-Aryl-1,2,3-thiadiazol-5(2H)-ylidene)acetamides 7aej produced via Scheme 2 (conditions A and B)
Entry
Compound
Ar
R1
R2
T (ꢁC)
Method
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
9
10
7a
7b
7c
7d
7e
7f
7g
7h
7i
4-MeOC6H4
Ph
4-ClC6H4
4-CF3C6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
CN
CN
CN
CN
CN
CN
Me
Me
Me
Me
25
25
25
25
60
60
25
25
60
60
A
A
A
A
B
B
A
A
B
B
6
11
48
10
12
15
11
56
45
40
62
54
69
62
94
70
76
85
79
83
4-MeOC6H4
4-ClC6H4
Me
eCH]CHCOOH
4-MeOC6H4
4-ClC6H4
eN(CH2CH2)2
eN(CH2CH2)2
eN(CH2CH2)2
eN(CH2CH2)2
7j
a
Isolated yield of (2-aryl-1,2,3-thiadiazol-5(2H)-ylidene)acetamides 7aej after purification.
Fig. 3. Molecular structure of 7h (X-ray data).
Scheme 4.
Fig. 4. Non-bonded S/O interaction due to n/
thiadiazoles 7.8c
s* orbital overlap effect in 1,2,3,-
the difference in energies for two isomers. Energy differences (DE)
calculated at B3LYP/6-31G* level of theory are collected in Table 2.
We have found that the Z-isomers of compounds 7 with hyper-
valent thiadiazole sulfur atom were more stable than the E-isomers.
Fig. 1. Molecular structure of 7d (X-ray data).
The stabilization effect, quantitatively expressed via DE, decreased
in the row: 7i (R3¼4-MeOC6H4)>7h (R3¼CH]CHCO2H)>7j (R3¼4-
ClC6H4)>7a (R3¼Me).
An additional factor increasing the stability of compounds 7
could be a stronger aromatic delocalization in heterocyclic frag-
ments composing thiapentalene system. Aromaticity can be
quantitatively described in terms of nuclear independent chemical
shift (NICS).11 A number of extensive reviews11b focused on this
topic were published in the last decade. Different variations of NICS
indexes were proposed as a tool to measure aromaticity. NICS in-
dices are the negative of magnetic shielding values computed at
central points of rings and in the vicinity of molecules. Coordinates
of ring centers can be deduced from the positions of atoms com-
posing the ring or can be taken from Bader’s AIM analysis (Atoms in
Molecule).12 Terms of
calculated separately. NICS(0)p index reflecting the term of
s- and p-orbitals in magnetic shielding can be
zz
Fig. 2. Molecular structure of 7g (X-ray data).
p-bonds has shown the best correlation with experimentally

7426
A.I. Bolgova et al. / Tetrahedron 69 (2013) 7423e7429
Table 2
ꢀ
Relative stability of Z-isomer against E-isomer for compounds 7gej (kcal/mol), NICS(0) calculated in the center of cycles A and B (ppm), calculated S/O bond length (A) and
energy of non-covalent interaction S/O (NBO method)
Entry
Compound
D
E, (kcal/mol)
Z-isomer
E-isomer
NICS(0)A iso, (ppm)
NICS(0)B iso, (ppm)
R(S/O), (A)
E[n(O)/
s*(SN)], (kcal/mol)
NICS(0)A iso, (ppm)
ꢀ
1
2
3
4
7g
7h
7i
8.523
12.538
12.742
12.500
ꢀ9.323
ꢀ9.627
ꢀ8.823
ꢀ9.549
ꢀ7.602
ꢀ8.187
ꢀ7.425
ꢀ7.385
2.231
2.233
2.223
2.238
25.97
25.75
26.76
25.21
ꢀ8.174
ꢀ8.209
ꢀ8.486
ꢀ8.700
7j
measured aromaticity.11b NICS(0)iso, calculated in the plane of the
ring and described the influence of both types of orbitals on aro-
maticity, also performed well and had a high correlation coefficient,
R2¼0.946.11a
The degree of electron density expansion from oxygen to sulfur
atom may be quantitatively characterized by the covalence ratio
factor (c) via equation (Eq. 1), as previously introduced by F.
Weinhold and co-workers.8a,d
We have calculated NICS(0)iso indices for compounds 7gej in
geometrical centers of both five-membered atomic rings A and B at
the B3LYP/6-31G* level of theory (Table 2). Calculated values were
close to NICS(0)iso values calculated at the same level of theory for
benzene (ꢀ11.5 ppm) and naphthalene (ꢀ9.9 ppm)11c molecules.
Thus, we concluded that the aromatic system was established in
both cycles, A and B. But, no linear correlation between values of
stabilization energy and NICS(0)iso was found (Table 2). The loss of
S/O interaction led to the decrease in aromaticity of thiadiazole
ring, since NICS(0)iso values calculated for E-isomers were lower
comparing to those of Z-isomers.
ðRX þ RY Þ ꢀ dXY
c
¼
ꢂ 1
(1)
ðRX þ RY Þ ꢀ ðrX þ rY Þ
where Rx and Ry stand for van der Waals radii and rx j ry for covalent
radii of the interacting atoms; dxy is experimentally determined
(or calculated) contact.
The expansion factors (c) were calculated to be relatively high
for compounds 7d,g,h:
ð1:50 þ 1:85Þ ꢀ 2:108
c7d
c7g
c7h
¼
¼
¼
¼ 0:74
¼ 0:68
¼ 0:74
(2)
(3)
(4)
ð1:50 þ 1:85Þ ꢀ ð0:66 þ 1:02Þ
To evaluate the strength of the n(O)/[s*(SeN)] interaction we
have applied a second order perturbation theory analysis of Fock
matrix on natural bond orbitals (NBO) basis.13 This method is used
to calculate the energy of interaction between certain donor and
acceptor in terms of bond orbitals. NBO analysis was performed at
B3LYP/6-31G* level. The correlation between the stabilization
ð1:50 þ 1:85Þ ꢀ 2:225
ð1:50 þ 1:85Þ ꢀ ð0:66 þ 1:02Þ
energy
DE and the energy of interaction between donor/acceptor
orbitals, E[n(O)/
s*(SN)] was ambiguous also (Table 2).
ð1:50 þ 1:85Þ ꢀ 2:113
To determine the participation of sulfur and oxygen atoms in the
bicyclic aromatic system we calculated Wiberg bond indexes and
the electron population of atoms S and O by applying NBO method
(Table 3). Symbathic decrease in occupancy of lone pair of oxygen
ð1:50 þ 1:85Þ ꢀ ð0:66 þ 1:02Þ
Summarizing the results of this computational study we suggest
that the cooperative interplay of all reviewed factors could con-
tribute to increased stability of (1,2,3-thiadiazol-5(2H)-ylidene)
acetamides 7, but the formation of an S/O dative bond was the
most important.
atom and increase of occupancy of vacant s*(SN) orbital, and non-
zero values of Wiberg bond indexes advocate the existence of da-
tive S/O bond. AIM analysis has also confirmed the formation of
S/O bond and a new ring: bond critical points of (3,ꢀ1) type and
ring critical point of (3,þ1) type were found for all listed com-
pounds. The amount of electron density located in bond critical
points is shown in Table 3. Thus, the formation of an aromatic-like
3. Conclusion
A
new simple atom-economical method to obtain 5-
6al
4-thiapentalene framework was confirmed.
acyliminothiadiazoles is described. Acylation of arylhydrazonoe-
thanethioamides did not stop at the formation of acyl derivatives as
it was expected; instead, acylated hydrazonoethanethioamides
were oxidized by atmospheric oxygen yielding 5-acylimino-2,5-
dihydro-1,2,3-thiadiazoles. The main factor controlling the di-
rection of this reaction was the formation of an aromatic bicyclic
system in final products.
Combined analysis of spectral and crystallographic data con-
firmed the existence of three-centered four electrons NeSeO
bond. Computational methods applied to the problem have de-
termined factors, responsible for enhanced stability of thiadia-
zoles 7. The most important was the formation of dative S/O
Table 3
Wiberg bond indexes n(S/O), occupancy of n(O) and s*(SN) orbitals, obtained by
NBO calculations, and the electron density
r in (3,-1) S/O bond critical point
obtained by AIM calculations for 1-oxa-6a
l
4-thia-3,5,6-triazapentalene 7gej
Entry
Compound
n(S/O)
Occupancy
(SN)
s
*
Occupancy
n(O)
r(BCP), (a.u).
1
2
3
4
7g
7h
7i
0.2437
0.1617
0.2443
0.2372
0.1909
0.1885
0.1949
0.1900
1.7709
1.7730
1.7679
1.7730
5.810$10ꢀ2
5.842$10ꢀ2
5.916$10ꢀ2
5.734$10ꢀ2
7j

A.I. Bolgova et al. / Tetrahedron 69 (2013) 7423e7429
7427
contact. In turn, the formation of additional ring increased aro-
4.2. General procedures for the synthesis of 5-acylimino-2,5-
matic stability of thiadiazoles 7. The aromaticity of compounds 7
was close to the one of benzene/naphthalene molecules based on
calculated NICS(0)iso values. The shift of electron density from
oxygen to sulfur was evaluated by NBO method. The covalent
character for the S/O bond was relatively high: Weinhold’s
covalency ratio factors were 0.67e0.74. All descriptors advocate
that obtained compounds 7 can be classified as new examples
dihydro-1,2,3-thiadiazoles 7 and 1,2,3-thiadiazol-5(2H)-imi-
nium bromide 8
Procedure A. To a solution of arylhydrazonoethanethioamide 1
(1 mmol) in 10 mL anhydrous pyridine was added anhydride 2
(2 mmol) with intensive stirring. The resulting mixture was stirred
at room temperature until starting hydrazone completely con-
sumed (TLC). The solution was poured into a mixture of water with
ice. The formed precipitate was filtered off, washed with water, and
dried.
of 6a
atom.
l
4-thiapentalene systems with central hypervalent sulfur
Procedure B. To a solution of arylhydrazonoethanethioamide 1
(1 mmol) in 10 mL anhydrous pyridine was added acyl chloride 3
(2 mmol) with intensive stirring. The resulting mixture was stirred
at 60 ꢁC until the hydrazone was completely consumed. The solu-
tion was cooled to room temperature and poured into a mixture of
water with ice. The solid was filtered off, washed with water, and
dried.
Procedure C. A solution of bromine (0.4 mL, 8 mmol) in 5 mL of
acetic acid was added with stirring to a solution of arylhy-
drazonoethanethioamide 1 (2 mmol) in 100 mL of acetic acid at
40 ꢁC. The mixture was allowed to cool to room temperature and
stirred for 5 h. The precipitate was filtered off and recrystallized
from ethanol.
4. Experimental section
4.1. General information and materials
Melting points were determined with a Stuart SMP3 apparatus.
1H NMR and 13C NMR spectra were recorded on a Bruker Avance II
(400 MHz for 1H and 100.6 MHz for 13C) spectrometer using DMSO-
d6 and CDCl3 as solvents. Chemical shifts (d) are reported in parts
per million (ppm) relative to TMS in 1H and 13C spectra. Coupling
constants (J) values are given in Hertz. Mass spectra were per-
formed on a Varian MAT 311A mass spectrometer using the elec-
tron impact ionization technique (40e200 ꢁC, 70 eV). The IR data
were recorded on a Bruker Alpha (NPVO, ZnSe) IR-Fur spectrome-
ter. Elemental analyses were carried out using a CHNS/O analyzer
PerkineElmer 2400 Series II instrument. Single crystal X-ray dif-
fraction analyses were performed on an Xcalibur S CCD area-
Procedure D. To the mixture of 2-aryl-2,5-dihydro-[1,2,3]-thia-
diazoliminium bromide 8 (1 mmol) in 4 mL pyridine was added
acetic anhydride (0.5 mL, 5 mmol). The reaction mixture was
refluxed for 2 h (TLC) and then was poured into water with ice. The
precipitate was filtered off, washed with water, and dried.
detector diffractometer (Mo Ka irradiation,
u-scanning with
step 1ꢁ, 295(2) K). Absorption correction not performed. Solution
and refinement of structures were accomplished with SHELXTL
program package.14
4.2.1. N-[4-Cyano-2-(4-methoxyphenyl)-1,2,3-thiadiazol-5(2H)-yli-
dene]acetamide (7a). Procedure A gave the title compound 7a
(170 mg, 62%) and procedure D gave the title compounds 7a
(214 mg, yield 78%) as a yellow solid, mp 108e109 ꢁC; [Found: C,
52.8; H, 3.5; N, 20.3; S, 11.9. C12H10N4O2S requires C, 52.54; H, 3.67;
ꢀ
For 7d crystal system is orthorhombic, a¼8.6795(8) A,
ꢀ
ꢀ
b¼7.7947(5) A, c¼40.653(5) A, space group Pbca, Volume
3
ꢀ
2750.3(4) A , Z¼8,
m
¼0.273 mmꢀ1
. Reflections collected/in-
dependent/with [I>2
s
(I)] 7139/2686/1209, Rint¼0.0509, com-
N, 20.43; S, 11.69%]; nmax 2238 (C^N), 1604 (C]O) cmꢀ1
; dH
pleteness to
q
¼25.00ꢁ 96.5%. S¼1.005, final R indices: R1¼0.0534,
(400 MHz, DMSO-d6) 2.56 (3H, s, COMe), 3.87 (3H, s, OMe), 7.09 and
7.77 (4H, AA0XX0, J 8.8 Hz, ArH); dC (100.6 MHz, DMSO-d6) 182.2,
167.5, 160.0, 133.4, 122.0, 117.9, 115.2, 112.2, 55.7, 23.3; m/z, 274 (Mþ,
100%).
wR2¼0.0607 [I>2
s(I)], R1¼0.1448, wR2¼0.0693 (all data). Largest
ꢀꢀ3
ꢁ
diff. peak and hole: 0.246 and 0.190 eA
.
ꢀ
For 7g crystal system is triclinic, a¼8.2623(8) A,
ꢀ
ꢀ
b¼8.4228(16) A, c¼12.2293(16) A,
a
¼81.076(13)ꢁ,
b
¼88.581(10)ꢁ,
3
¼80.413(12)ꢁ, space group Pꢀ1, Volume 829.0(2) A , Z¼2,
4.2.2. N-(4-Cyano-2-phenyl-1,2,3-thiadiazol-5(2H)-ylidene)acet-
amide (7b). Procedure A gave the title compound 7b (132 mg, 54%)
as a yellow solid, mp 110e111 ꢁC; [Found: C, 54.3; H, 3.4; N, 23.1; S,
13.3. C11H8N4OS requires C, 54.09; H, 3.30; N, 22.94; S, 13.13%]; nmax
ꢀ
g
m
¼0.218 mmꢀ1. Reflections collected/independent/with [I>2
s(I)]
6191/3987/1505, Rint¼0.0480, completeness to
q
¼28.28ꢁ 97.1%.
S¼1.011, final
R
indices: R1¼0.0508, wR2¼0.1032 [I>2
s(I)],
R1¼0.1721, wR2¼0.1152 (all data). Largest diff. peak and hole: 0.283
2234 (C^N), 1591 (C]O) cmꢀ1
; dH (400 MHz, DMSO-d6) 7.86e7.90
ꢀꢀ3
ꢁ
and ꢀ0.206 eA
.
(2H, m, ArH), 7.69e7.56 (2H, m, ArH), 7.54e7.48 (1H, m, ArH), 2.58
(3H, s, COMe); dC (100.6 MHz, DMSO-d6) 182.0, 168.9, 140.5, 130.7,
129.9, 120.8, 119.4, 112.5, 23.8; MS (EI) m/z 244 (Mþ, 100%).
ꢀ
ꢀ
For 7h crystal system is triclinic, a¼8.289(2) A, b¼8.6627(12) A,
ꢀ
c¼13.0570(14) A,
a
¼94.191(12)ꢁ,
b
¼93.649(16)ꢁ,
g
¼99.640(16)ꢁ,
3
ꢀ
space group Pꢀ1, Volume 919.1(3) A , Z¼2,
m
¼0.216 mmꢀ1
.
Reflections collected/independent/with [I>2
s
(I)] 9038/5775/
4.2.3. N-(2-(4-Chlorophenyl)-4-cyano-1,2,3-thiadiazol-5(2H)-yli-
dene)acetamide (7c). Procedure A gave the title compound 7c
(192 mg, 69%) as a yellow solid, mp 124e125 ꢁC; [Found: C 47.7; H
2.3; N 20.3; S 11.6. C11H7ClN4OS requires C 47.40; H 2.53; N 20.10; S
2453, Rint¼0.0315, completeness to
q
¼26.00ꢁ 98.5%. S¼1.001,
final R indices: R1¼0.0487, wR2¼0.0806 [I>2 (I)], R1¼0.1296,
s
wR2¼0.0888 (all data). Largest diff. peak and hole: 0.461
ꢀꢀ3
ꢁ
and ꢀ0.419 eA
.
11.50%]; nmax 2236 (C^N), 1595 (C]O) cmꢀ1
; dH (400 MHz, DMSO-
CCDC 902766, 902767, and 912581 contains the supplementary
crystallographic data for this paper. These data can be obtained free
of charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
d6) 7.59 and 7.89 (4H, AA0XX0, J 8.0 Hz, ArH), 2.57 (3H, s, COMe); dC
(100.6 MHz, DMSO-d6) 183.0, 168.4, 139.3, 134.2, 130.6, 122.4, 119.6,
112.4, 23.4; MS (EI) m/z 278 (Mþ, 100%).
Chromatography purification compounds 7aej were done using
silica gel (0.035e0.070, 60 A). The reactions were monitored on
silica gel plates (Sorbfil UVe254) and visualization was effected by
short wavelength UV light (254 nm). Solvents were dried and dis-
tilled according to the common procedure.
4.2.4. N-[4-Cyano-2-[4-(trifluoromethyl)phenyl]-1,2,3-thiadiazol-
5(2H)-ylidene]acetamide (7d). Procedure A gave the title compound
7d (193 mg, 62%) as a yellow solid, mp 116e117 ꢁC; [Found: C, 46.3;
H, 2.4; N, 18.2; S, 10.4. C12H7F3N4OS requires C, 46.16; H, 2.26; N,
ꢀ
17.94; S,10.27%]; nmax 2240 (C^N),1591 (C]O) cmꢀ1
; dH (400 MHz,
Arylhydrazonoethanethioamides
1
were prepared by the
DMSO-d6) 7.89 and 8.12 (4H, AA0XX0, J 8.8 Hz, ArH), 2.61 (3H, s,
COMe); dC (100.6 MHz, DMSO-d6) 182.9, 168.0, 142.8, 128.8 (q, J
procedure reported in our previous articles.4

7428
A.I. Bolgova et al. / Tetrahedron 69 (2013) 7423e7429
32 Hz), 127.4, 123.3 (q, J 270 Hz), 120.6, 119.9, 111.7, 23.3; MS (EI) m/z
174.4, 164.8, 160.0, 159.6, 142.2, 138.2, 134.3, 132.5, 131.2, 129.3,
312 (Mþ, 100%).
122.3, 115.8, 56.2, 47.9, 46.4, 26.0, 24.3; MS (EI) m/z 442 (Mþ, 5%).
4.2.5. N-(4-Cyano-2-(4-methoxyphenyl)-1,2,3-thiadiazol-5(2H)-yli-
dene)-4-methoxybenzamide (7e). Procedure B gave the title com-
pound 7e (259 mg, 94%) as a yellow solid, mp 206e207 ꢁC; [Found:
C, 51.4; H 2.3; N 15.2; S 8.7. C16H8Cl2N4O2S requires C, 51.21; H, 2.15;
N, 14.93; S, 8.55%]; nmax 2240 (C^N), 1590 (C]O); dH (400 MHz,
DMSO-d6) 8.45 and 7.26 (4H, AA0XX0, J 8.8 Hz, ArH), 7.96 and 7.21
(4H, AA0XX0, J 9.2 Hz, ArH), 4.05 (3H, s, OMe), 4.02 (3H, s, OMe); dC
(100.6 MHz, DMSO-d6) 181.8, 164.0, 160.5, 160.2, 141.9, 135.0, 132.1,
127.8, 122.7, 115.9, 114.9, 113.2, 56.2, 56.1; MS (EI) m/z 366 (Mþ, 2%).
4.2.11. 4-Cyano-2-(4-methoxyphenyl)-1,2,3-thiadiazol-5(2H)-imi-
nium bromide (8a). Procedure C gave the title compound 8a
(459 mg, 74%). as a yellow solid, mp 134e135 ꢁC. [Found: C 38.2; H
2.9; N 17.5; S 10.2. C10H9BrN4OS requires C 38.35; H 2.90; N 17.89; S
10.24]; dH (400 MHz, CDCl3) 10.55 (2H, br s, NH2), 7.67 and 7.06 (4H,
AA0XX0, J 8.9 Hz, ArH), 3.91 (3H, s, OMe). (100.6 MHz, CDCl3) 170.7,
161.9, 132.6, 122.4, 115.7, 109.7, 100.1, 56.0.
4.2.12. 2-(4-Methoxyphenyl)-4-(pyrrolidine-1-carbonyl)-1,2,3-
thiadiazol-5(2H)-iminium bromide (8b). Procedure C gave the title
compound 8a (483 mg, 63%) as a yellow solid, mp 232e233 ꢁC.
[Found: C 43.8; H 4.6; N 14.7; S 7.5. C14H17BrN4O2S requires C 43.64;
H 4.45; N 14.54; S 8.32]; dH (400 MHz, DMSO-d6) 10.46 (1H, s, NH),
10.01 (1H, s, NH), 7.65 and 7.07 (4H, AA0XX0, J 9.0 Hz, ArH),
3.98e3.95 (2H, m, CH2), 3.65e3.63 (2H, m, CH2), 2.05e2.02 (2H, m,
CH2), 1.90e1.95 (2H, m, CH2); dC (100.6 MHz, DMSO-d6) 171.5, 160.3,
159.4, 133.3, 132.9, 122.3, 115.8, 56.2, 49.3, 47.6, 26.5, 27.6.
4.2.6. N-(2-(4-Methoxyphenyl)-4-cyano-1,2,3-thiadiazol-5(2H)-yli-
dene) 4-chlorobenzamide (7f). Procedure B gave the title compound
7f (353 mg, 70%) as a yellow solid, mp 204e205 ꢁC; [Found: C, 55.3;
H, 3.3; N, 15.3; S, 8.8. C17H11ClN4O2S requires C, 55.06; H, 2.99; N,
15.11; S, 8.65]; nmax 2237 (C^N), 1584 (C]O) cmꢀ1
; dH (400 MHz,
DMSO-d6), 8.33 and 7.58 (4H, AA0XX0, J 8.8 Hz, ArH), 7.83 and 7.12
(4H, AA0XX0, J 9.2 Hz, ArH), 3.88 (3H, s, OMe); dC (100.6 MHz, DMSO-
d6) 174.5, 168.3, 160.2, 138.4, 133.3, 130.9, 130.6, 129.0, 122.1, 119.1,
115.2, 111.8, 55.6; MS (EI) m/z 370 (Mþ, 24%).
4.3. Computational details
All calculations have been done with a help of G09 2 suit.15
Structures were initially optimized at B3LYP/6-31G* level of the-
ory. All located points had a minima character according to Hessian
calculation. An NBO analysis was performed at the same level of
theory by calling appropriate module, implemented in G09.16 NICS
values were calculated with GIAO approach17 and using 6-31G*
basis set and B3LYP hybrid functional on ring geometric centers.
Obtained B3LYP/6-31G* wave functions were studied by AIM
method with the help of AIMAll software.18
4.2.7. N-(2-(4-Methoxyphenyl)-4-(pyrrolidine-1-carbonyl)-1,2,3-
thiadiazol-5(2H)-ylidene)acetamide (7g). Procedure A gave the title
compound 7g (223 mg, 76%), procedure D gave the title compound
7g (294 mg, 85%) as a yellow solid, mp 122e123 ꢁC. [Found: C, 56.2;
H, 5.2; N, 16.5; S, 9.2. C16H18N4O3S requires C, 55.48; H, 5.24; N,
16.17; S, 9.26]; nmax 2973, 2877 (CH), 1606 (C]O) cmꢀ1
; dH
(400 MHz, DMSO-d6) 7.72 and 7.06 (4H, AA0XX0, J 8.8 Hz, ArH), 3.85
(3H, s, OMe), 3.62 (2H, t, J 6.8 Hz, CH2), 3.48 (2H, t, J 6.8 Hz, CH2),
2.46 (3H, s, Me), 1.94e2.02 (4H, m, CH2); dC (100.6 MHz, DMSO-d6)
181.2, 163.9, 159.8, 159.6, 140.9, 134.2, 122.0, 115.6, 56.0, 47.9, 46.3,
25.9, 24.3, 23.9; MS (EI) m/z 346 (Mþ, 11%).
Acknowledgements
4.2.8. 4-(2-(4-Methoxyphenyl)-4-(pyrrolidine-1-carbonyl)-1,2,3-
thiadiazol-5(2H)-ylideneamino)-4-oxobut-2-enoic acid (7h). Procedure
A gave the title compound 7h (342 mg, 85%) as a yellow solid, mp
207e208 ꢁC. [Found: C, 53.9; H, 4.7; N, 13.8; S, 8.1. C18H18N4O5S re-
quires C, 53.72; H, 4.51; N, 13.92; S, 7.97]; dH (400 MHz, DMSO-d6)
12.56 (1H, s, OH), 7.26 and 7.03 (4H, AA0XX0, J 8.7 Hz, ArH), 6.62 and
6.35 (2H, AX, J 6.2 Hz, 2CH), 3.75 (3H, s, OMe), 3.35e3.48 (4H, m, CH2),
1.59e1.72 (4H, m, CH2); dC (100.6 MHz, DMSO-d6) 173.9, 167.1, 164.4,
160.3,159.8,142.6,137.2,134.5,133.6,122.7,116.1, 56.5, 48.3, 46.8, 26.4,
24.7; MS (EI) m/z 402 (Mþ, 6%).
The authors thank the Russian Foundation for Basic Research for
financial support (grant RFBR # 11-03-00579_a, RFBR # 10-03-
96084-r_ural_a, RFBR # 12-03-31574 mol_a). J.O.S. personally
thanks Prof. Arvi Rauk (University of Calgary, Canada) for assis-
tance. J.O.S. also thanks Compute CanadadCalcul Canada and
Western Canada Research Grid for provided computational
resources.
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.06.071. These data include MOL files
and InChiKeys of the most important compounds described in this
article.
4.2.9. N-(2-(4-Methoxyphenyl)-4-(pyrrolidine-1-carbonyl)-1,2,3-
thiadiazol-5(2H)-ylidene)-4-methoxybenzamide (7i). Procedure
B
gave the title compound 7i (346 mg, 79%) as a yellow solid, mp
180e181 ꢁC. [Found: C, 60.4; H, 5.2; N, 12.6; S, 7.5. C22H22N4O4S
requires C, 60.26; H, 5.06; N,12.78; S, 7.31]; dH (400 MHz, DMSO-d6)
8.23 and 7.05 (4H, AA0XX0, J 8.9 Hz, ArH), 7.75 and 7.02 (4H, AA0XX0, J
9.2 Hz, ArH), 3.88 (3H, s, OMe), 3.86 (3H, s, OMe), 3.68 (2H, t, J
6.7 Hz, CH2), 3.58 (2H, t, J 6.6 Hz, CH2), 1.96e2.05 (4H, m, CH2); dC
(100.6 MHz, DMSO-d6) 174.8, 164.4, 163.5, 159.8, 159.6, 141.5, 134.3,
131.6, 125.9, 122.0, 115.7, 114.7, 56.1, 56.0, 48.0, 46.5, 24.4, 26.1; MS
(EI) m/z 438 (Mþ, 4%).
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