Reaction of enamines and azaenamines containing a thioamide group with dimethyl acetylenedicarboxylate

Article abstract of DOI:10.1007/s10593-014-1543-y

The reaction between enamines and azaenamines containing a thioamide group and dimethyl acetylenedicarboxylate was studied under various conditions. It was shown that exchanging one of the carbon atoms in the structure of the investigated compounds for a nitrogen atom significantly affected the reactivity. Functionalized thiopyrans and thiazolidinones were obtained during this investigation.

Full text of DOI:10.1007/s10593-014-1543-y

Chemistry of Heterocyclic Compounds, Vol. 50, No. 6, September, 2014 (Russian Original Vol. 50, No. 6, June, 2014)
REACTION OF ENAMINES AND AZAENAMINES
CONTAINING A THIOAMIDE GROUP WITH
DIMETHYL ACETYLENEDICARBOXYLATE
1
1
1
1
2
*
N. P. Belskaya , K. I. Lugovik , A. D. Ivina , V. A. Bakulev , and Z. J. Fan
The reaction between enamines and azaenamines containing a thioamide group and dimethyl
acetylenedicarboxylate was studied under various conditions. It was shown that exchanging one of the
carbon atoms in the structure of the investigated compounds for a nitrogen atom significantly affected
the reactivity. Functionalized thiopyrans and thiazolidinones were obtained during this investigation.
Keywords: azaenamines, dimethyl acetylenedicarboxylate, enamines, thiazolidinones, thiopyrans,
cycloaddition, cyclocondensation.
The reactions of thioamide derivatives with activated acetylenes and olefins have long attracted the
attention of synthetic chemists [1-22]. Particularly noteworthy are the transformations of compounds with
several nucleophilic centers in the molecule (thioureas, thiosemicarbazides and their derivatives,
thioacetamides) and those with conjugated multiple bonds (thioacrylamides), as well as heterocycles containing
such functional groups. The formation of various heterocyclic systems may occur during these reactions as a
result of cycloaddition [3-5], cyclocondensation [1, 2, 6-22], and addition [18, 19, 22]. Heterocyclic compounds
obtained in thioamide reactions with dimethyl acetylenedicarboxylate (DMAD) (thiazolidinones,
dihydrothiazines, thiophenes, pyrroles, pyridines, and thiopyrans) can be applicated in materials science and as
biologically active compounds [15, 23-26].
The aim of this work was to study the reaction of enamines and azaenamines containing a thioamide
group with DMAD, including the determination of features of this transformation, depending on the reaction
conditions and the structure of compounds involved. Besides the thioamide group, the molecules of hydrazones
and enamines contain another nucleophilic center – the amine nitrogen atom of hydrazone or enamine group, as
well as a linear spacer linking the aromatic ring with the thiocarbamoyl fragment, which may not only transmit
electronic effects between the opposite units of the molecule, but independently participate in the cycloaddition
reaction as parts of 1-aza-4-thio-1,3-butadiene or 1-thio-1,3-butadiene systems. Thus, comparison of the
_______
*To whom correspondence should be addressed, e-mail: n.p.belskaya@urfu.ru.
1Ural Federal University named after the First President of Russia B. N. Yeltsin, 19 Mir St., Yekaterinburg
620002, Russia.
2State Key Laboratory of Elemento-organic Chemistry, Nankai University, 94 Weijin Rd., Tianjin 300071, P. R.
China; е-mail: fanzj@nankai.edu.cn.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 962-975, June, 2014. Original
article submitted April 28, 2014.
888
0009-3122/14/5006-0888©2014 Springer Science+Business Media New York

reactivity of the compounds containing the same functional groups and a different nature of the atom in the
linear chain, allows to evaluate not only the effect of substituents on their reactivity but heterodiene structural
fragment too. It should be noted that the comparison of enamines and hydrazones is frequently used in the
literature, where hydrazones are formally considered as aza derivatives of enamines (azaenamines) [27, 28].
This is because the structure of the hydrazones can be obtained by the isoelectronic replacing of enamine
α-carbon atom on the nitrogen atom.
Only a single example of a reaction between 3-(morpholin-4-yl)- and 3-(piperidin-1-yl)-3-oxo-
2-(p-tolylhydrazonо)thiopropionamides with DMAD has been described in the literature [17]. As a result of this
reaction with the participation of thioamide nucleophilic centers, thiazolidinones were obtained as
cyclocondensation products, while the analogous aminopropenethioamides did not undergo such a
transformation at all.
All the starting arylhydrazonоthioacetamides 3a-h were obtained by our previously described method
by the interaction of aromatic diazonium salts 1a-d with the 2-cyanoethanethioamides 2a-c [29].
S
CN
AcONa, H2O
0–5°C
H
N
ArN2+ Cl–
+
NC
NHR1
NHR1
Ar
N
1a–d
2a–c
S
3a–h
1 a Ar = 4-MeOC6H4, b Ar = Ph, c Ar = 4-ClC6H4, d Ar = 4-O2NC6H4; 2 a R1 = Me, b R1 = Bn, c R1 = cyclohexyl;
3 a–c R1 = Me, d,e R1 = Bn, f–h R1 = cyclohexyl; a,d,f Ar = 4-MeOC6H4, b,g Ar = Ph, c,h Ar = 4-ClC6H4; e Ar = 4-O2NC6H4
Various schemes for the synthesis of arylaminopropenethioamides 9a-g were used, depending on the
substituent R1 in the thioamide fragment. The arylamino group was introduced by substituting the
dimethylamino moiety of cyanoacrylamides 5a-c or cyanopropenethioamide 8 by reactions with the
corresponding anilines 6a-d [30-33]. The arylaminopropenethioamides 9a-g were obtained in 54-94% yields.
(R1 = Bn, cyclo-C6H11)
ArNH2
6a,b
HCl, EtOH
room temp.
CN
CN
Me2NCH(OMe)2
toluene, 80°C
H
N
Me2N
NHR1
NHR1
Ar
O
O
5a–c
Lawesson's
(R1 = Me) reagent
toluene, 
7a–d
O
Lawesson's
reagent
NC
toluene, 
NHR1
4a–c
ArNH2
6a,c,d
HCl, EtOH
60°C
CN
CN
H
N
Me2N
NHMe
NHR1
Ar
S
S
8
9a–g
6 a Ar = 4-MeOC6H4, b Ar = Ph, c Ar = 4-ClC6H4, d Ar = 4-O2NC6H4; 7 a–b R1 = Bn, c–d R1 = cyclohexyl,
a,c Ar = 4-MeOC6H4, b,d Ar = Ph;9 a–c R1 = Me, d,e R1 = Bn, f,g R1 = cyclohexyl; a,d,f Ar = 4-MeOC6H4,
b Ar = 4-ClC6H4, c Ar = 4-O2NC6H4, e,g Ar = Ph
1
The structure of thioamides 9a-g was proved by IR, Н NMR spectroscopy, mass spectrometry, and
elemental analysis.
1
The Н NMR spectra of thioamides 9а-g exhibited two sets of signals from proton-containing groups
(for compounds 9a-c,e) or three sets (for compounds 9d,f,g), due to the formation of two or three isomers with
different substituent positions around the С=С bond, as well as the relative configuration of С=S and C=C
double bonds. The NH proton signal of one of the isomers was shifted significantly downfield (by 3 ppm), that
may be associated with the formation of hydrogen bonds. Appropriate azaenamines 3a-h exist predominantly in
the form of a single isomer [29].
889

TABLE 1. UV Spectra of Arylhydrazonоthioacetamides 3a-c and
Arylaminopropenethioamides 9a-c in Ethyl Alcohol
CN
H
N
NHR1
X
Ar
Ar
S
Compound
X
N
R1
λmax, nm
log ε
4-MeOC6H4
Ph
Me
399
256
228
378
256
231
378
247
229
360
292
252
227
354
291
251
224
382
319
233
4.33
3.99
4.15
4.02
3.93
4.06
4.38
4.03
4.13
4.32
4.20
4.22
4.17
4.37
4.24
4.22
4.16
4.50
4.09
4.21
3a
N
N
Me
Me
Me
3b
3c
9a
4-ClC6H4
4-MeOC6H4
CH
CH
CH
4-ClC6H4
Me
Me
9b
9c
4-O2NC6H4
There are three (for compounds 3a-c and 9c) or four (compounds 9a,b) absorption bands in the UV
spectra of propenethioamides 9a-с and hydrazonоthioamides 3a-с. (Table 1) It should be noted the light
hypsochromic shift (10-20 nm) for absorption band of enaminothioamides 9a-c in comparison with UV
absorption spectra of hydrazonothioamides 3a-c.
The study of reaction between arylhydrazonоthioamides 3a-h and DMAD in methanol, chloroform,
benzene, and toluene at room temperature and by heating in the presence or absence of triethylamine showed
that it did not occur in the absence of base in any of the solvents used. The interaction of thioamides 3a-h with
DMAD in methanol in the presence of triethylamine occurs over 0.2-1 h and leads to the formation of new
compounds, which were assigned the structure of thiazolidinones 10a-h based on the spectral data, as well as
elemental analysis.
The mass spectra of compounds 10a-h contain a peak of molecular ion, m/z value of which indicates
that the interaction of the two reagents leads to products of condensation with the elimination of one molecule
of methanol. There are one or two intense absorption bands at the 1700-1720 cm-1, corresponding to the valence
vibrations of the C=O carbonyl groups in the IR spectrum of compounds 10a-h, along with bands at 2860-2940
and 2210-2220 cm-1 corresponding to the stretching vibrations of C–H and C≡N bonds.
It should be noted that a key factor for establishing the structures of cyclization products 10 or 11, formed
by the interaction of DMAD with thioamides, according to literature data [1, 18, 20, 21] was the coupling
constant ratio in the 13С NMR spectra for the interaction of =СН–СО2Ме proton (compounds 10) or Н-5 proton
(compounds 11) with the carbonyl carbon atoms of the heterocycle and ester groups. For the products with
3
2
exocyclic double bond (compounds 10), the typical value of JС-4–СН = 5.2-5.8 Hz, while JСОО–СН ≈ 0-1 Hz. In
the case of 1,3-thiazine ring formation (compounds 11), the 3JCОО–Н-5 constant should be higher than 2JC-4–Н-5
.
13
The C NMR spectra of compounds 10 exhibited the carbonyl С-4 signal at 163.5-166.1 ppm. For the
thiazolidinones 10a,f, the coupling constant of the С-4 carbon atom with the =СН–СО2Ме proton was found to be
5.4-5.8 Hz. This provided evidence for the formation of thiazolidinones 10, and not the 1,3-thiazinones 11 in the
studied reaction.
890

CN R1
NH
(from 3a–h):
Et3N, MeOH
room temp., 0.2–1 h
CO2Me
CO2Me
N
CN
..
H
N
Ar
X
NHR1
+
S
CO2Me
CO2Me
Ar
X
(from 9a–d):
Et3N, CHCl3
room temp., 1–4 h
S
3a–h,
9a–g
A
А. CHCl3, room temp., 1–3 h
or
(from 9a–g)
B. benzene, 50°C, 1–4 h
Ar
N
HO OMe
N
Ar
R1
HN
S
MeO2C
X
MeO2C
CN
NHR1
S
NC
N
S
CO2Me
CN
HO
N
X
MeO2C
R1
OMe
D
B
C
Ar
–ArNH2
–MeOH
X
–MeOH
Ar
N
O
S
MeO2C
MeO2C
CN
R1
MeO2C
N
S
S
NR1
CN
NC
N
CO2Me
12a–c
N
O
R1
X
10a–l
Ar
11a–l
10, 11 a–c,i–k R1 = Me, d,e,l R1 = Bn, f–h R1 = cyclohexyl; a,d,f,i,l Ar = 4-MOC6H4,
b,g Ar = Ph, c,h,j Ar = 4-ClC6H4, e,k Ar = 4-O2NC6H4; 10, 11 a–h X = N, i–l X = CH;
12 a R1 = Me, b R1 = Bn, c R1 = cyclohexyl
The reaction of propenethioamides 9a-g with DMAD was investigated under various conditions.
Stirring a mixture of the starting compounds in chloroform at room temperature for 1-3 h produced the
functionalized thiopyrans 12a-c in 62–75% yields. Compounds 12a,b were obtained also by heating the reaction
mixture in benzene at 50°С for 3-4 h, but the yields were lower in that case (51-56%).
1
The Н NMR spectrum of the thiopyran 12b contained two СО2СН3 singlets at 3.83 and 3.88 ppm, a
CH2 singlet at 4.45 ppm, phenyl ring proton signals at 7.27-7.41 ppm, as well as a singlet due to one Н-4 proton
at 7.84 ppm. The mass spectra contained a molecular ion peak corresponding to the molecular mass of the
thiopyrans 12а-с, but its intensity was low (7-8%), similarly to the intensity of fragment peaks containing
thiopyran ring. This heterocycle is apparently unstable under the electron impact ionization conditions.
The formation of thiopyrans 12a-c may be explained by [4+2] cycloaddition mechanism involving the
intermediate D. The subsequent elimination of arylamine molecule results in the final product of this
transformation. It should be noted that examples of thioamide C=S bond participation in [4+2] cycloaddition
reactions are known in the literature [34]. The thioamide group is a part of 1-thia-1,3-butadiene fragment of
thioacrylamides [3-5, 35-36], which react with various dienophiles in hetero-Diels–Alder reactions. This
requires a preliminary stage of thioamide fragment acylation or the presence of an electron-withdrawing cyano
group at the α-position relative to the thioamide group [3, 4, 36]. Thus, 3-aryl(hetaryl)-2-cyanoacrylthioamides
interact with DMAD and other dienophiles with the formation of 4Н-thiopyrancarbonitriles [3, 4]. The study of
891

propenethioamide reaction with DMAD is of interest to elucidate the mechanism of the transformation, defining
its scope and limitation and for the synthesis of new sulfur-containing heterocyclic systems
In order to activate the nucleophilic centers of propenethioamides during this transformation, we
performed the reactions of compounds 9a-d with DMAD in chloroform in the presence of triethylamine as a
base. The products were isolated and identified by spectroscopy and elemental analysis as thiazolidinones 10i-l.
The mass spectra of compounds 10i-l contained an intense molecular ion peak (Irel 51-67%) with a mass
corresponding to the condensation products of the starting compounds, after the elimination of a methanol molecule.
The IR spectrum shows absorption bands corresponding to the stretching vibrations of the C=O and
C≡N bonds at 1722-1735 and 2203-2208 cm-1, respectively. The 1Н NMR spectra of thiazolidinones 10i-l,
unlike those of thiopyrans 12a-c, contained a =СНСО2Ме proton singlet at 6.85-7.02 ppm and one CO2Me group
singlet at 3.84-3.88 ppm.
There are several double bonds in the structure of compounds 10a-l and therefore several pairs of
1
geometric isomers can be formed. The H NMR and 13C spectra of these compounds (except of compounds
1
10d,i) show the doubling of most signals. The isomer ratio according to H NMR spectra can be estimated as
10:1 for compounds 10a-с,e-h,j,k and 4:1 for compound 10l. The existence of thiazolidinones 10 as two
isomers in DMSO-d6 (presumably E and Z, relative to the bond С(6)=С(5)) may be explained by their increased
stability due to intramolecular interactions. It should be noted that compounds 10a-l may form not only =С(6)–
Н···O=C(4) hydrogen bond, but also a non-covalent interaction between the thiazolidine ring sulfur atom and
the N(10) nitrogen atom by overlap of the nitrogen lone electron pair n(N) and the sulfur atom antibonding
orbital σ*(S) [17, 37-42]. The available data indicate that Z-isomer predominates. However, complete
understanding of the spatial structure of the obtained compounds 10a-l requires additional research.
Ar
Ar
N10
N
.
.
.
.
.
9
.
H
X
MeO2C
H
X
.
.
6
S
S
8
5
4
2
MeO2C
CN
CN
.
.
N
N
.
.
O
R1
E-isomer
O
R1
Z-isomer
10a–l
The formation of non-covalent interactions, both intramolecular and intermolecular, has a substantial
impact on the physical, chemical, and biological properties of heterocyclic compounds, may determine the
course of reactions, and also has a crucial role in materials chemistry [37-42]. Therefore, the further structural
study of compounds 10a-l with experimental (X-ray structural analysis and spectroscopic methods), as well as
theoretical (quantum chemistry) methods is very important.
The analysis of UV spectral data for thiazolidinones 10a-l indicated that the change of aromatic
substituent type had the opposite effect on the change of absorption maximum position, compared to the spectra
of the starting hydrazonоthioamides 3a-h and arylaminopropenethioamides 9a-d. If thioamide group serves as a
donor center in the starting compounds 3a-h, it is obvious that the introduction of electron-donating substituents
in the aromatic ring leads to hypsochromic shift of the long-wavelength maximum in the UV spectra (Table 1).
The introduction of electron-donating substituents in the aromatic ring of compounds 10a-l containing a
thiazolidine ring conjugated with an electron acceptor substituent (ethoxycarbonyl group) resulted in
bathochromic shift of the long wave maximum in UV spectra of these compounds by 14-36 nm. For the
thiazolidinones 10a-h containing an azaenamine fragment, this shift was more pronounced than for the
enamines 10i-l.
The investigation of DMAD reaction with azaenamines and enamines – 2-arylhydrazonо-2-cyano-
thioacetamides and 3-(arylamino)-2-cyanoprop-2-enethioamides – showed that the slight structural differences
between these compounds had a marked effect on their reactivity. While the first type of compounds
892

TABLE 2. The Electronic Absorption Spectra of Thiadiazolinones 10a-f,h-l
in Ethyl Alcohol
λmax, nm
log ε
Compound
X
N
Ar
R1
4-MeOC6H4
Me
431
334
259
395
322
254
398
327
251
430
336
259
416
329
257
431
336
260
415
330
260
407
329
256
416
334
221
396
303
238
397
321
421
334
4.33
4.14
3.97
4.25
4.21
4.14
4.37
4.22
4.14
4.39
4.27
4.09
4.30
4.10
3.91
4.39
4.32
4.09
4.35
4.30
4.12
4.38
4.28
6.70
4.00
4.10
4.14
4.19
4.12
4.19
4.36
4.24
4.03
4.21
10a
N
N
Ph
Me
Me
10b
10c
10d
10e
10f
10g
10h
10i
4-ClC6H4
4-MeOC6H4
4-O2NC6H4
4-MeOC6H4
Ph
N
Bn
N
Bn
N
Cyclohexyl
Cyclohexyl
Cyclohexyl
Me
N
N
4-ClC6H4
4-MeOC6H4
4-ClC6H4
CH
CH
Me
10j
CH
CH
4-O2NC6H4
4-MeOC6H4
Me
Bn
10k
10l
(azaenamines) formed only five-membered thiazolidinones, the respective enamines, depending on reaction
conditions, could interact with DMAD eiher by cycloaddition mechanism with the formation of a thiopyran
ring, or by cyclocondensation mechanism, giving thiazolidinones. Thus, the combination of С=С–С=S bonds of
the studied enamines is capable of [4+2] cycloaddition. The change from NH–С=С enamine fragment to the
NH–N=C azaenamine directs the reaction towards the cyclocondensation mechanism. Both the enamine and
azaenamine fragments facilitate the cyclization in the presence of a base, due to the migration of the acidic NH
proton and the formation of intermediate 4-hydroxy-4-methoxythiazolidinone.
It should be noted that the structure of these thiazolidinones includes an extended conjugated system,
therefore the nature of substituents in the aromatic ring affects the position of long-wavelength absorption
maxima in the electronic spectra, where a push-pull conjugated system can be identified when the aromatic ring
contains electron-donating substituents.
EXPERIMENTAL
IR spectra were recorded on a Bruker Alpha FT-IR spectrometer (ZnSe ATR accessory). UV spectra
1
were recorded on a Perkin Elmer Lambda 35 spectrometer. Н and 13С NMR spectra were acquired on a
893

Bruker DRX-400 spectrometer (400 and 100 MHz, respectively) in CDCl3 (13С NMR spectra of compounds
10a,c-f,h) and in DMSO-d6 (the rest of the spectra), internal standard was TMS. 13С NMR spectra of
compounds 10a,f were acquired in BB and Gate modes. The mass spectra (EI, 70 eV) were recorded on a
Shimadzu GCMS-QP2010 Ultra spectrometer with direct sample introduction into the ion source. Elemental
analysis was performed on a Perkin Elmer Analyzer 2400 Series II СHNS/O analyzer. Melting points were
determined on a Stuart SMP3 apparatus. The reaction progress and the individuality of the obtained compounds
were checked by TLC on Sorbfil UV-254 plates with 1:1 EtOAc–hexane, 30:1 CHCl3–acetone, and 5:4:1
CHCl3–hexane–acetone systems.
Arylhydrazonоthioacetamides 3a-h [29], N-alkyl-2-cyanoacetamides 4a-c [30], 2-cyano-3-(dimethyl-
amino)prop-2-eneamides 5a-c [31], 3-(arylamino)-2-cyanoprop-2-eneamides 7a-d [32], and 2-cyano-3-(di-
methylamino)-N-methylprop-2-enethioamide (8) [32] were obtained by published procedures.
3-(Arylamino)-2-cyano-N-methylprop-2-enethioamides 9a-с were obtained by reacting 2-cyano-
3-(dimethylamino)-N-methylprop-2-enethioamide (8) with arylamines by heating in EtOH at 60°С in the
presence of HCl.
N-Benzyl- and N-cyclohexyl-3-(arylamino)-2-cyanoprop-2-enethioamides 9d-g were obtained by
refluxing the respective amides 7a-d in toluene with Lawesson's reagent [33].
2-Cyano-3-(4-methoxyphenylamino)-N-methylprop-2-enethioamide (9a). Yield 0.556 g (55%), yellow
powder, mp 174-176°С. IR spectrum, ν, cm-1: 3297, 3058 (N–H), 3000, 2955, 2909, 2834 (C–H), 2195 (C≡N).
1H NMR spectrum, δ, ppm (J, Hz) (2:3 mixture of isomers): 3.10 (1.2Н, s) and 3.11 (1.8Н, s, NHCH3); 3.78
(1.2Н, s) and 3.79 (1.8Н, s, OCH3); 6.89-6.98 (2Н, m, H Ar); 7.25-7.33 (2H, m, H Ar); 8.19 (0.6Н, d, J = 13.4)
and 8.81 (0.4Н, d, J = 13.4, NHСН=); 8.88-8.94 (1Н, m, NHМе); 10.38 (0.4Н, d, J = 13.4) and 13.57 (0.6Н, d,
J = 13.4, NHCH=). 13C NMR spectrum, δ, ppm: 32.1*/33.4; 55.8*/55.9; 81.0*/85.6; 115.2*/115.4 (2С);
117.1*/119.5; 119.3*/119.8 (2С); 132.2*/133.9; 150.6/151.8*; 157.0*/157.3; 188.0/190.2*. Found, %: C 58.33;
H 5.12; N 16.80; S 12.63. C12H13N3OS. Calculated, %: C 58.28; H 5.30; N 16.99; S 12.96.
3-(4-Chlorophenylamino)-2-cyano-N-methylprop-2-enethioamide (9b). Yield 0.905 g (72%), light-
yellow powder, mp 212-214°С. IR spectrum, ν, cm-1: 3329, 3281 (N–H), 3035, 2963 (C–H), 2202 (C≡N). 1H NMR
spectrum, δ, ppm (J, Hz) (2:3 mixture of isomers): 3.06 (1.2Н, d, J = 4.4) and 3.12 (1.8Н, d, J = 4.4, NHCH3);
7.32-7.40 (4H, m, H Ar); 8.35 (0.6Н, d, J = 4.4) and 8.80 (0.4Н, d, J = 14.0, NHСН=); 9.05-9.09 (1Н, m,
NHMe); 10.49 (0.4Н, d, J = 14.0) and 13.60 (0.6Н, d, J = 14.0, NHСН=). 13C NMR spectrum, δ, ppm:
32.3/33.5*; 82.6/87.7*; 116.7*/119.1; 119.5/119.7* (2С); 128.7*/129.3; 129.8*/130.0 (2С); 137.9/139.7*;
150.3/150.4*; 187.8/187.9*. Found, %: C 52.52; H 4.18; N 16.38; S 12.91. C11H10ClN3O. Calculated, %: C 52.48;
H 4.00; N 16.69; S 12.74.
2-Cyano-N-methyl-3-(4-nitrophenylamino)prop-2-enethioamide (9c). Yield 1.205 g (92%), yellow
powder, mp 273-275°С. IR spectrum, ν, cm-1: 3297, 3234, 3197, 3070 (N–H), 2840 (C–H), 2203 (C≡N).
1H NMR spectrum, δ, ppm (J, Hz) (1:4 mixture of isomers): 3.08 (0.6Н, d, J = 4.5) and 3.14 (2.4Н, d, J = 4.5,
NHСН3); 7.53-7.60 (2Н, m, HAr); 8.20-8.22 (2Н, m, HAr); 8.55 (0.2Н, d, J = 12.4) and 8.83 (0.8Н, d, J = 12.4,
NHСН=); 9.32-9.34 (0.2Н, m) and 9.34-9.36 (0.8Н, m, NHMe); 10.76 (0.8Н, d, J = 12.2) and 13.69 (0.2Н, d,
J = 12.2, NHCH=). 13C NMR spectrum, δ, ppm (signals of the main isomer): 33.6; 90.9; 116.2; 117.7; 125.9;
143.2; 146.6; 148.4; 189.4. Found, %: C 50.21; H 4.09; N 21.42; S 12.11. C11H10N4O2S. Calculated, %:
C 50.37; H 3.84; N 21.36; S 12.22.
N-Benzyl-2-cyano-3-(4-methoxyphenylamino)prop-2-enethioamide (9d). Yield 0.911 g (94%), beige
crystals, mp 158-159°С. IR spectrum, ν, cm-1: 3272 (N–H), 2191 (C≡N). 1H NMR spectrum, δ, ppm (J, Hz) (1:2:3
mixture of three isomers): 3.75 (1.50Н, s), 3.76 (0.99Н, s) and 3.77 (0.51Н, s, ОCH3); 4.35 (0.66Н, d, J = 6.2), 4.84
(0.34Н, d, J = 6.2) and 4.93 (1.00Н, d, J = 6.2, HNСН2); 6.81-6.95 (2Н, m, H Ar); 7.38-7.45 (7Н, m,
_______
*Here and further in the Experimental the 13С NMR signals of major isomers in the isomeric mixtures are
marked with an asterix.
894

H Ar); 8.12 (0.33Н, d, J = 14.3), 8.24 (0.17Н, d, J = 14.3) and 8.82 (0.50Н, d, J = 14.3, NHСН=); 7.97-8.01
(0.33Н, m), 9.25-9.27 (0.17Н, m) and 9.30-9.34 (0.50Н, m, NHCH2); 10.45 (0.50Н, d, J = 14.6), 11.58 (0.33Н,
d, J = 14.6) and 13.57 (0.17Н, d, J = 14.6, NHCH=). Mass spectrum, m/z (Irel, %): 323 [M]+ (12). Found, %:
C 66.61; H 5.27; N 13.07; S 10.03. C18H17N3OS. Calculated, %: C 66.85; H 5.30; N 12.99; S 9.91.
N-Benzyl-2-cyano-3-phenylaminoprop-2-enethioamide (9e). Yield 0.659 g (75%), orange crystals,
mp 178-179°С. IR spectrum, ν, cm-1: 3335, 3274 (N–H), 3026, 2916 (C–H), 2203 (C≡N). 1H NMR spectrum, δ,
ppm (J, Hz) (1:1 mixture of isomers): 4.85 (1Н, d, J = 6.0) and 4.94 (1Н, d, J = 6.0, NHСН2); 6.91-7.43 (10H,
m, H Ph); 8.39 (0.5Н, d, J = 14.0) and 8.89 (0.5Н, d, J = 14.0, NHСН=); 9.41-9.51 (1Н, m, NНCH2); 10.53
(0.5Н, d, J = 14.0) and 12.50 (0.5Н, d, J = 14.0, NНCH=). Mass spectrum, m/z (Irel, %): 293 [M]+ (13). Found,
%: C 69.44; H 5.29; N 14.12; S 11.13. C17H15N3S. Calculated, %: C 69.60; H 5.15; N 14.32; S 10.93.
2-Cyano-N-cyclohexyl-3-(4-methoxyphenylamino)prop-2-enethioamide (9f). Yield 0.293 g (55%), sand
colored powder, mp 115-118°С. IR spectrum, ν, cm-1: 3274, 3131, 3069 (N–H), 2993, 2934, 2850, 2831 (C–H),
1
2193 (C≡N). H NMR spectrum, δ, ppm (J, Hz) (1:2:7 mixture of three isomers): 1.19-1.95 (10Н, m, (CH2)5);
3.78 (3Н, s, ОCH3); 4.34-4.40 (1Н, m, NHCH(CH2)5); 6.83-6.92 (2Н, m, H Ar); 7.21-7.30 (2H, m, H Ar); 8.37
(0.3Н, d, J = 7.8) and 8.62 (0.7Н, d, J = 7.8, NНCH(CH2)5); 8.12 (0.1Н, d, J = 12.0), 8.23 (0.2Н, d, J = 12.0)
and 8.68 (0.7Н, d, J = 12.0, NHСН=); 10.36 (0.7Н, d, J = 12.2), 11.61 (0.1Н, d, J = 12.2) and 13.52 (0.2Н, d,
J = 12.2, NНCH=). Found, %: C 65.01; H 6.53; N 13.14; S 10.38. C17H21N3ОS. Calculated, %: C 64.73; H 6.71;
N 13.32; S 10.16.
2-Cyano-N-cyclohexyl-3-(4-phenylamino)prop-2-enethioamide (9g). Yield 0.291 g (54%), sand colored
crystals, mp 129-131°С. IR spectrum, ν, cm-1: 3270, 3142, 3072 (N–H), 2989, 2931, 2835 (C–H), 2194 (C≡N).
1H NMR spectrum, δ, ppm (J, Hz) (1:3:4 mixture of three isomers): 1.17-1.96 (10Н, m, (CH2)5); 4.33-4.37 (1Н,
m, NHCH(CH2)5); 6.83-7.05 (5Н, m, H Ph); 7.96 (0.37Н, d, J = 7.7), 8.12 (0.13Н, d, J = 7.7) and 8.64 (0.50Н,
d, J = 7.7, NНCH(CH2)5); 8.17 (0.13Н, d, J = 12.0), 8.37 (0.37Н, d, J = 12.0) and 8.69 (0.50Н, d, J = 12.0,
NHСН=); 10.42 (0.50Н, d, J = 12.4), 11.51 (0.13Н, d, J = 12.4) and 13.27 (0.37Н, d, J = 12.4, NНCH=).
Found, %: C 67.52; H 6.62; N 15.01; S 11.54. C16H19N3S. Calculated, %: C 67.33; H 6.71; N 14.72; S 11.23.
Reaction of Arylhydrazonоthioamides 3a-h with DMAD (General Method). A solution of
arylhydrazonоthioacetamide 3a-h (0.250 g, 1.0 mmol), Et3N (0.15 ml, 1.1 mmol), and DMAD (0.14 ml, 1.1 mmol)
in MeOH (15 ml) was vigorously stirred at room temperature for 0.2-1 h. After the reaction was complete, the
precipitate of compounds 10a-h was filtered off and recrystallized from acetone.
Methyl {2-[(4-Methoxyphenylazo)cyanomethylidene]-3-methyl-4-oxothiazolidin-5-ylidene}-acetate
(10a). Yield 0.233 g (65%), red-orange powder, mp 176-177°C. IR spectrum, ν, cm-1: 3075, 2960, 2860
(C–H), 2230 (C≡N), 1730 (C=O). 1H NMR spectrum, δ, ppm (J, Hz) (10:1 mixture of isomers): 3.73 (3Н, s, NCH3);
3.83 (0.27Н, s) and 3.85 (2.73Н, s, ОCH3); 3.88 (3Н, s, OCH3); 6.84 (0.09Н, s) and 6.95 (0.91Н, s, =СНСО2Ме);
7.06 (2H, AA'XX', J = 8.8) and 7.73 (2H, AA'XX', J = 8.8, H Ar). 13C NMR spectrum, δ, ppm (J, Hz) (signals of
1
1
1
the main isomer): 32.3 (q, JC–H = 143.5, NСН3); 52.8 (q, JC–H = 147.9, OСН3); 55.6 (q, JC–H = 144.4,
1
1
OСН3); 108.3 (=ССN); 111.5 (CN); 114.4 (d, JC–H = 161.2, C-3,5 Ar); 117.1 (d, JC–2H = 173.5,
1
2
=CHCO2Me); 125.2 (d, JC–H = 162.8, C-2,6 Ar); 139.1 (d, JC-5–CHCOOMe = 1.4, C-5); 146.3 (tt, JCi–Ho = 2.2,
3JCi–Hm = 8.4, C-1 Ar); 159.2 (q, JC-2–NCH3 = 3.0, C-2); 162.3-162.7 (m, C-4 Ar); 164.7 (dq, JCO–CHСО2Ме = 5.4,
3JCO–NCH3 = 2.8, 4-CO); 166.5 (q, 3JCO–CH3 = 4.7, CO2Ме). Mass spectrum, m/z (Irel, %): 358 [M]+ (14). Found, %:
C 53.56; H 3.86; N 15.48. C16H14N4O4S. Calculated, %: C 53.62; H 3.94; N 15.63.
2
3
Methyl {3-Methyl-4-oxo-2-[(phenylazo)cyanomethylidene]thiazolidin-5-ylidene}acetate (10b).
Yield 0.217 g (66%), dark-yellow powder, mp 194-195°C. IR spectrum, ν, cm-1: 2940, 2860 (C–H), 2220
1
(C≡N), 1740, 1700 (C=O). H NMR spectrum, δ, ppm (J, Hz) (10:1 mixture of isomers): 3.74 (3Н, s, NCH3);
3.85 (2.73Н, s) and 3.87 (0.27Н, s, ОCH3); 6.86 (0.91Н, s) and 6.98 (0.09Н, s, =СНСО2Ме); 7.47-7.57 (3H, m,
13
H Ph); 7.74 (2H, d, J = 7.5, H Ph). C NMR spectrum, δ, ppm (signals of the main isomer): 32.6; 53.1; 107.8;
111.6; 117.4; 122.6 (2С); 130.1 (2С); 131.7; 139.0; 152.2; 163.5; 165.0; 166.3. Found, %: C 54.73; H 3.79;
N 17.25. C15H12N4O3S. Calculated, %: C 54.87; H 3.68; N 17.06.
895

Methyl {2-[(4-Chlorophenylazo)cyanomethylidene]-3-methyl-4-oxothiazolidin-5-ylidene}acetate
(10c). Yield 0.348 g (96%), orange powder, mp 199-200°C. IR spectrum, ν, cm-1: 3070, 2940, 2860 (C–H),
1
2235 (C≡N), 1740, 1720 (C=O). H NMR spectrum, δ, ppm (J, Hz) (10:1 mixture of isomers): 3.75 (2.73Н, s)
and 3.83 (0.27Н, s, NCH3); 3.86 (2.73Н, s) and 3.88 (0.27Н, s, ОCH3); 6.89 (0.91Н, s) and 7.00 (0.09Н, s,
=СНCO2Me); 7.51 (0.18Н, AA'XX', J = 8.8) and 7.56 (1.82Н, AA'XX', J = 8.8), 7.55 (0.18Н, AA'XX', J = 8.8)
13
and 7.75 (1.82Н, AA'XX', J = 8.8, H Ar). C NMR spectrum, δ, ppm (signals of the main isomer): 32.3; 52.8;
108.4; 111.0; 117.9; 124.3 (2С); 129.6 (2С); 137.6; 138.5; 150.3; 161.6; 164.6; 166.3. Mass spectrum, m/z (Irel,
%): 362 [M]+ (15). Found, %: C 49.57; H 3.11; N 15.32. C15H11ClN4O3S. Calculated, %: C 49.66; H 3.06;
N 15.44.
Methyl {3-Benzyl-2-[(4-methoxyphenylazo)cyanomethylidene]-4-oxothiazolidin-5-ylidene}acetate
(10d). Yield 0.300 g (69%), scarlet powder, mp 240-242°С. IR spectrum, ν, cm-1: 3000, 2940, 2860, 2840
(C–H), 2180 (C≡N), 1650 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 3.88 (6Н, s, 2ОCH3); 5.52 (2Н, s, NCH2);
6.94 (1Н, s, =CHCO2Me); 7.06 (2H, AA'XX', J = 8.8) and 7.73 (2H, AA'XX', J = 8.8, H Ar); 7.26-7.33 (3Н, m,
H Ph); 7.34-7.39 (2Н, m, H Ph). 13C NMR spectrum, δ, ppm (signals of the main isomer): 47.9; 52.6; 55.6;
108.6; 111.2; 114.5; 117.3; 125.2; 127.2; 128.3; 129.0; 133.8; 139.1; 146.4; 158.4; 162.7; 165.2; 166.5. Mass
spectrum, m/z (Irel, %): 434 [M]+ (7). Found, %: C 60.64; H 4.03; N 13.02; S 7.51. C22H18N4O4S. Calculated, %:
C 60.82; H 4.18; N 12.90; S 7.38.
Methyl
{3-Benzyl-2-[(4-nitrophenylazo)cyanomethylidene]-4-oxothiazolidin-5-ylidene}acetate
(10e). Yield 0.325 g (72%), orange powder, mp 250-252°С. 1H NMR spectrum, δ, ppm (J, Hz) (10:1 mixture of
isomers): 3.87 (2.73Н, s) and 3.89 (0.27Н, s, ОCH3); 5.40 (1.82Н, s) and 5.52 (0.18Н, s, NCH2); 7.07 (0.91Н, s)
and 7.19 (0.09Н, s, =CHCO2Me); 7.25-7.42 (5Н, m, H Ph); 7.87 (2H, AA'XX', J = 8.8) and 8.42 (2H, AA'XX',
J = 8.8, H Ar). 13C NMR spectrum, δ, ppm: 48.7*/51.5; 53.4*53.6; 110.8*/112.0; 119.0*/120.3; 123.6*/123.7
(2С); 125.1/125.7* (2С); 126.2/126.9* (2С); 127.8*/128.3; 129.1/129.3* (2С); 134.6*/135.3; 138.0/138.2*;
148.5/148.8*; 155.3*/155.5; 165.3*/165.4; 165.9*/166.0; 166.3*/166.5. Found, %: C 55.76; H 3.60; N 15.24; S
7.47. C21H15N5O5S. Calculated, %: C 56.12; H 3.36; N 15.58; S 7.13.
Methyl
{3-Cyclohexyl-2-[(4-methoxyphenylazo)cyanomethylidene]-4-oxothiazolidin-5-ylidene}-
acetate (10f). Yield 0.264 g (62%), orange powder, mp 178-179°C. IR spectrum, ν, cm-1: 3080, 2940, 2860 (C–H),
1
2220 (C≡N), 1740 (C=O). H NMR spectrum, δ, ppm (J, Hz) (10:1 mixture of isomers): 1.18-1.51 (3Н, m),
1.66-1.77 (1Н, m), 1.85-1.99 (4Н, m) and 2.27-2.46 (2Н, m, (СН2)5); 3.84 (0.27Н, s) and 3.86 (2.73Н, s,
ОCH3); 3.88 (3Н, s, OCH3); 4.75-4.92 (1Н, m, NСН(СН2)5); 6.75 (0.09Н, s) and 6.88 (0.91Н, s, =СНCO2Me);
7.06 (2H, AA'XX', J = 8.8) and 7.72 (2H, AA'XX', J = 8.8, H Ar). 13C NMR spectrum, δ, ppm (J, Hz) (signals
of the main isomer): 24.8 (CH2); 25.5 (2CH2); 29.1 (2CH2); 52.6 (OCH3); 55.6 (OCH3); 60.5 (CH(СН2)5); 107.6
(=ССN); 111.1 (CN); 114.4 (C-3,5 Ar); 116.0 (=СНCO2Me); 125.1 (C-2,6 Ar); 140.4 (C-5); 146.4 (C-1 Ar);
3
3
160.3 (C-2); 162.5 (C-4 Ar); 164.9 (dd, JCO–CHСО2Ме = 5.8, JCO–NCH = 2.8, 4-CO); 166.7 (CO2Ме). Mass
spectrum, m/z (Irel, %): 426 [M]+ (18). Found, %: C 59.23; H 5.07; N 13.29. C21H22N4O4S. Calculated, %:
C 59.14; H 5.20; N 13.14.
Methyl {3-Cyclohexyl-4-oxo-2-[(phenylazo)cyanomethylidene]thiazolidin-5-ylidene}acetate (10g).
Yield 0.305 g (77%), orange powder, mp 192-193°C. IR spectrum, ν, cm-1: 2940, 2860 (C–H), 2220 (C≡N),
1
1740, 1720 (C=O). H NMR spectrum, δ, ppm (J, Hz) (10:1 mixture of isomers): 1.21-1.49 (4Н, m), 1.68-1.78
(1Н, m), 1.89-1.97 (4Н, m) and 2.35-2.50 (1Н, m, (СН2)5); 3.85 (2.73Н, s) and 3.87 (0.27Н, s, ОСН3);
4.79-4.92 (1Н, m, NСН(СН2)5); 6.79 (0.91Н, s) and 6.92 (0.09Н, s, =СНСО2Ме); 7.49-7.59 (3H, m, H Ph);
7.74 (2H, d, J = 7.5, H Ph). 13C NMR spectrum, δ, ppm (signals of the main isomer): 24.8; 25.5; 29.1; 52.6;
60.5; 107.6; 111.1; 114.4; 116.0; 125.1; 140.4; 146.4; 160.3; 162.5; 164.9; 166.7. Mass spectrum, m/z (Irel, %):
396 [M]+ (24). Found, %: C 60.49; H 5.17; N 13.96. C20H20N4O3S. Calculated, %: C 60.59; H 5.08; N 14.13.
Methyl {2-[(4-Chlorophenylazo)cyanomethylidene]-3-cyclohexyl-4-oxothiazolidin-5-ylidene}acetate
(10h). Yield 0.292 g (68%), orange powder, mp 215-216°C. IR spectrum, ν, cm-1: 3060, 2940, 2860 (C–H),
1
2220 (C≡N), 1720, 1700 (C=O). H NMR spectrum, δ, ppm (J, Hz) (10:1 mixture of isomers): 1.22-1.37 (2Н,
896

m), 1.43-1.53 (1Н, m), 1.69-1.78 (1Н, m), 1.88-1.99 (4Н, m) and 2.41-2.55 (2Н, m, (СН2)5); 3.86 (0.27Н, s) and
3.88 (2.73Н, s, ОCH3); 4.92-5.01 (1Н, m, NСН(СН2)5); 6.92 (0.91Н, s) and 7.00 (0.09Н, s, =СНCO2Me); 7.45
13
(2H, AA'XX', J = 8.8) and 7.78 (2H, AA'XX', J = 8.8, H Ar). C NMR spectrum, δ, ppm (signals of the main
isomer): 24.7; 25.5; 29.1; 52.6; 60.7; 107.7; 110.7; 116.7; 124.2 (2С); 129.5 (2С); 137.3; 139.8; 150.4; 162.7;
164.9; 166.5. Mass spectrum, m/z (Irel, %): 430 [M]+ (8). Found, %: C 55.69; H 4.34; N 12.79. C20H19ClN4O3S.
Calculated, %: C 55.75; H 4.44; N 13.00.
Reaction of 3-Arylamino-2-cyanoprop-2-enethioamides 9a-d with DMAD in the presence of Et3N.
A solution of thioamide 9a-d (0.7 mmol), Et3N (0.21 ml, 1.5 mmol), and DMAD (0.18 ml, 1.5 mmol) in CHCl3
(5 ml) was stirred at room temperature for 1-4 h, until the reaction was complete. Hexane was added, the
crystalline precipitate of compounds 10i-l was filtered off, washed with hexane, and dried.
Methyl {2-[1-Cyano-2-(4-methoxyphenyl)iminoethylidene]-3-methyl-4-oxothiazolidin-5-ylidene}-
acetate (10i). Yield 0.175 g (70%), yellow crystals, mp 170-172°С. IR spectrum, ν, cm-1: 3056, 2954, 2884,
1
2837 (C–H), 2207 (C≡N), 1714 (C=O). H NMR spectrum, δ, ppm (J, Hz): 3.75 (3Н, s, NCH3); 3.82 (3Н, s,
OCH3); 3.86 (3Н, s, OCH3); 6.85 (1Н, s, =СНCO2Me); 6.98 (2H, AA'XX', J = 8.8) and 7.28 (2H, AA'XX',
J = 8.8, H Ar); 8.34 (1Н, s, СН=N). 13C NMR spectrum, δ, ppm: 32.9; 53.2; 55.8; 86.4; 115.0; 116.8; 117.6;
123.0; 140.4; 142.5; 151.6; 157.4; 159.0; 164.9; 166.4. Found, %: C 56.93; H 4.32; N 11.62; S 9.08. Mass
spectrum, m/z (Irel, %): 357 [M]+ (61). C17H15N3O4S. Calculated, %: C 57.13; H 4.23; N 11.76; S 8.97.
Methyl
{2-[2-(4-Chlorophenyl)imino-1-cyanoethylidene]-3-methyl-4-oxothiazolidin-5-ylidene}-
acetate (10j). Yield 0.187 g (74%), brown crystals, mp 198-200°С. IR spectrum, ν, cm-1: 3054, 2995, 2951,
2902 (C–H), 2203 (C≡N), 1722 (C=O). 1H NMR spectrum, δ, ppm (J, Hz) (9:1 mixture of isomers): 3.73 (0.3Н,
s) and 3.75 (2.7Н, s, NCH3); 3.86 (2.7Н, s) and 3.88 (0.3Н, s, OCH3); 6.88 (0.9Н, s) and 6.92 (0.1Н, s,
=СНCO2Me); 7.28-7.30 (2H, m, H Ar); 7.31-7.41 (2H, m, H Ar); 8.16 (0.1Н, s) and 8.39 (0.9Н, s, СН=N).
13C NMR spectrum, δ, ppm: 32.3*/34.2; 52.5*/52.6; 85.9*; 115.3/115.8*; 117.1/117.4*; 122.5*/122.9 (2С);
128.9/129.0* (2С); 130.6/130.8*; 138.6*/139.2; 148.0*/149.1; 152.7/154.3*; 157.4/158.4*; 164.2*/166.1;
166.5*/166.8. Mass spectrum, m/z (Irel, %): 361 [M]+ (67). Found, %: C 53.14; H 3.61; N 11.51; S 8.43.
C16H12ClN3O3S. Calculated, %: C 53.12; H 3.34; N 11.61; S 8.86.
Methyl {2-[1-Cyano-2-(4-nitrophenyl)iminoethylidene]-3-methyl-4-oxothiazolidin-5-ylidene}acetate
(10k). Yield 0.180 g (69%), yellow-orange powder, mp 209-211°С. IR spectrum, ν, cm-1: 3048, 2959 (C–H),
2208 (C≡N), 1735 (C=O). 1H NMR spectrum, δ, ppm (J, Hz) (9:1 mixture of isomers): 3.73 (0.3Н, s) and 3.75
(2.7Н, s, NCH3); 3.85 (2.7Н, s) and 3.88 (0.3Н, s, OCH3); 6.92 (0.9Н, s) and 6.96 (0.1Н, s, =СНСО2Ме); 7.46
(2H, d, J = 8.9, H Ar); 8.21-8.28 (2H, m, H Ar); 8.48 (0.9Н, s) and 8.81 (0.1Н, s, СН=N). 13C NMR spectrum,
δ, ppm: 33.1*/35.0; 53.2*/53.4; 86.2*; 115.8/116.3*; 118.4/118.6*; 122.5*/122.7; 125.3/125.4*; 139.0/139.5*;
145.8*; 155.8*; 156.0/157.7*; 160.9*; 166.0*; 166.2*. Mass spectrum, m/z (Irel, %): 372 [M]+ (51). Found, %:
C 51.32; H 3.19; N 14.82; S 8.47. C16H12N4O5S. Calculated, %: C 51.61; H 3.25; N 15.05; S 8.61.
Methyl {3-Benzyl-2-[1-cyano-2-(4-methoxyphenyl)iminoethylidene]-4-oxothiazolidin-5-ylidene}-
1
acetate (10l). Yield 0.203 g (67%), dark-red crystals, mp 170-171°С. H NMR spectrum, δ, ppm (J, Hz) (4:1
mixture of isomers): 3.75 (0.6Н, s) and 3.78 (2.4Н, s, OCH3); 3.84 (2.4Н, s) and 3.87 (0.6Н, s, OCH3); 5.47
(0.4Н, s) and 5.54 (1.6Н, s, NСН2); 6.95 (0.8Н, s) and 7.02 (0.2Н, s, =СНCO2Me); 6.72 (0.4Н, d, J = 8.7) and
6.99 (1.6Н, d, J = 8.7, H Ar); 6.83 (0.4Н, d, J = 8.8) and 7.25 (1.6Н, d, J = 8.8, H Ar); 7.30-7.33 (3Н, m, H Ph);
7.37-7.39 (0.4Н, m) and 7.40-7.45 (1.2Н, m, H Ph); 8.18 (0.2Н, s) and 8.37 (0.8Н, s, СН=N). 13C NMR spectrum,
δ, ppm: 48.0*; 53.2*/53.4; 55.8*/55.9; 86.8*/89.8; 114.8/115.1* (2С); 116.2*; 117.5/118.3*; 122.9/123.0* (2С);
126.0/126.5* (2С); 128.0*/128.3; 129.2*/129.6 (2С); 134.6/135.3*; 139.5/139.9*; 142.2/142.6*; 149.8/151.7*;
156.4*; 159.0*/159.1; 165.3*; 166.3*/166.4. Mass spectrum, m/z (Irel, %): 433 [M]+ (55). Found, %: C 63.61;
H 4.39; N 9.53; S 7.68. C23H19N3O4S. Calculated, %: C 63.73; H 4.42; N 9.69; S 7.40.
Reaction of Arylamino-2-cyanoprop-2-enethioamides 9a-g with DMAD without the Addition of
Et3N. А. A solution of thioamide 9a-g (0.7 mmol) and DMAD (0.18 ml, 1.5 mmol) in CHCl3 (5 ml) was stirred
at room temperature for 1-3 h, until the reaction was complete. Hexane (10 ml) was added, the obtained
precipitate of thiopyran 12а-с was filtered off, washed with hexane, and dried.
897

B. A solution of thioamide 9a-e (0.7 mmol) and DMAD (0.18 ml, 1.5 mmol) in benzene (10 ml) was
heated for 3-4 h at 50°C, until the reaction was complete. The solvent was evaporated under vacuum, the residue
was treated with hexane, the obtained crystals of thiopyran 12а,b were filtered off, washed with hexane, and dried.
Dimethyl 3-Cyano-2-methylimino-2Н-thiopyran-5,6-dicarboxylate (12a). Yield 0.140 g (75%,
method А), 0.095 g (51%, method B), yellow crystals, mp 125-127°С. IR spectrum, ν, cm-1: 3059, 2957, 2923,
2851 (C–H), 2230 (C≡N), 1739, 1719 (C=O). 1H NMR spectrum, δ, ppm (J, Hz) (9:1 mixture of isomers): 3.17
(2.7Н, s) and 4.00 (0.3Н, s, NCH3); 3.79 (2.7Н, s) and 3.82 (0.3Н, s, OCH3); 3.83 (0.3Н, s) and 3.86 (2.7Н, s,
OCH3); 7.83 (0.9Н, s) and 8.44 (0.1Н, s, Н-4). 13C NMR spectrum, δ, ppm (signals of the main isomer): 40.7;
53.8; 54.7; 112.5; 115.4; 123.2; 140.8; 144.0; 147.1; 162.8; 163.3. UV spectrum (EtOH), λmax, nm (log ε): 397
(3.54), 329 (3.89), 230 (4.24). Mass spectrum, m/z (Irel, %): 266 [M]+ (8). Found, %: C 49.74; H 3.87; N 10.43;
S 11.97. C11H10N2O4S. Calculated, %: C 49.62; H 3.79; N 10.52; S 12.04.
Dimethyl 2-Benzylimino-3-cyano-2Н-thiopyran-5,6-dicarboxylate (12b). Yield 0.168 g (70%,
method А), 0.134 g (56%, method B), yellow crystals, mp 170-171°С. IR spectrum, ν, cm-1: 2988, 2958, 2901
(C–H), 2227 (C≡N), 1734, 1723 (C=O). UV spectrum (EtOH), λmax, nm (log ε): 398 (3.48), 342 (3.26), 236
1
(4.33). H NMR spectrum, δ, ppm (J, Hz): 3.83 (3Н, s, OCH3); 3.88 (3Н, s, OCH3); 4.45 (2Н, s, NСН2);
13
7.27-7.28 (1H, m, H Ph); 7.34-7.41 (4H, m, H Ph); 7.84 (1Н, s, Н-4). C NMR spectrum, δ, ppm: 53.4; 54.1;
57.0; 113.4; 114.6; 121.3; 127.3; 127.6 (2С); 128.6 (2С); 137.3; 139.6; 145.4; 146.4; 162.5; 162.8. Mass
spectrum, m/z (Irel, %): 342 [M]+ (7). Found, %: C 60.04; H 4.35; N 8.08; S 9.60. C17H14N2O4S. Calculated, %:
C 59.64; H 4.12; N 8.18; S 9.37.
Dimethyl 3-Cyano-2-cyclohexylimino-2Н-thiopyran-5,6-dicarboxylate (12c). Yield 0.145 g (62%,
method А), yellow crystals, mp 163-165°С. IR spectrum, ν, cm-1: 2957, 2927, 2854 (C–H), 2230 (C≡N), 1737,
1721 (C=O). UV spectrum (EtOH), λmax, nm (log ε): 395 (3.39), 237 (4.25). 1H NMR spectrum, δ, ppm (J, Hz):
1.36-1.50 (5Н, m) and 1.67-1.81 (5Н, m, (СН2)5); 3.29 (1Н, br. s, СН(СН2)5); 3.83 (3Н, s, OCH3); 3.88 (3Н, s,
OCH3); 7.73 (1Н, s, Н-4). 13C NMR spectrum, δ, ppm: 24.2; 25.5; 31.5; 53.7; 54.6; 62.1; 112.5; 115.5; 122.5;
141.3; 142.7; 144.7; 162.8; 163.1. Mass spectrum, m/z (Irel, %): 334 [M]+ (8). Found, %: C 57.51; H 5.13;
N 8.17; S 9.72. C16H18N2O4S. Calculated, %: C 57.47; H 5.43; N 8.38; S 9.59.
V. A. Bakulev would like to express his gratitude to the Russian Foundation for Basic Research (grant
14-03-01033), Z. J. Fan – to the N. N. S. Foundation of China (21372132) and International Science &
Technology Cooperation Program of China (2014DFR41030) for the received financial support.
REFERENCES
1.
2.
3.
N. A. Danilkina, L. E. Mikhailov, and B. A. Ivin, Zh. Org. Khim., 42, 807 (2006). [Russ. J. Org. Chem.,
42, 783 (2006).]
V. N. Britsun and M. O. Lozinskii, Khim. Geterotsikl. Soedin., 43, 1283 (2007). [Chem. Heterocycl.
Compd., 43, 1083 (2007).]
T. G. Deryabina, M. A. Demina, N. P. Belskaya, and V. A. Bakulev, Izv. Akad. Nauk, Ser. Khim., 2784
(2005). [Russ. Chem. Bull., 54, 2880 (2005).]
4.
5.
J. Bloxham and C. P. Dell, J. Chem. Soc., Perkin Trans. 1, 989 (1994).
G. T. Manh, H. Bakkali, L. Maingot, M. Pipelier, U. Joshi, J. P. Pradere, S. Sabelle, R. Tuloup, and
D. Dubreuil, Tetrahedron Lett., 45, 5913 (2004).
6.
7.
A. Marwaha, V. Sudan, and M. P. Mahajan, Heterocycles, 76, 1087 (2008).
A. A. Hassan, Y. R. Ibrahim, A. A. Aly, E. M. El-Sheref, and T. Yamato, J. Heterocycl. Chem., 50, 473
(2013).
K. L. Obydennov, E. L. Klimareva, M. F. Kosterina, P. A. Slepukhin, and Yu. Yu. Morzherin, Tetrahedron
Lett., 54, 4876 (2013).
8.
898

9.
K. L. Obydennov, M. F. Kosterina, E. L. Klimareva, V. A. Bakulev, and Yu. Yu. Morzherin, Izv. Akad.
Nauk, Ser. Khim., 991 (2011). [Russ. Chem. Bull., 60, 1016 (2011).]
10.
M. F. Kosterina, T. V. Rybalova, Yu. V. Gatilov, and Yu. Yu. Morzherin, Khim. Geterotsikl. Soedin.,
541 (2009). [Chem. Heterocycl. Compd., 45, 422 (2009).]
11.
12.
A. Darehkordi, K. Saidi, and M. R. Islami, ARKIVOC, i, 180 (2007).
M. M. Heravi, N. Nami, H. A. Oskooie, R. Hekmatshoar, and Z. Jaddi, Phosphorus, Sulfur Silicon
Relat. Elem., 181, 87 (2006).
13.
14.
15.
16.
17.
V. A. Bakulev, V. S. Berseneva, N. P. Belskaia, Yu. Yu. Morzherin, A. Zaitsev, W. Dehaen, I. Luyten,
and S. Toppet, Org. Biomol. Chem., 1, 134 (2003).
O. S. Yel'tsov, V. S. Mokrushin, N. P. Belskaya, and N. M. Kozlova, Izv. Akad. Nauk, Ser. Khim., 440
(2003). [Russ. Chem. Bull., 52, 461 (2003).]
A. Ane, G. Prestat, M. Thiam, S. Josse, M. Pipelier, J. P. Pradere, and D. Dubreuil, Nucleosides,
Nucleotides Nucleic Acids, 21, 335 (2002).
V. S. Berseneva, Yu. Yu. Morzherin, W. Dehaen, I. Luyten, and V. A. Bakulev, Tetrahedron, 57, 2179
(2001).
V. S. Berseneva, A. V. Tkachev, Yu. Yu. Morzherin, W. Dehaen, I. Luyten, S. Toppet, and
V. A. Bakulev, J. Chem. Soc., Perkin Trans. 1, 2133 (1998).
18.
19.
20.
21.
22.
23.
24.
G. Giammona, M. Neri, B. Carlisi, A. Palazzo, and C. La Rosa, J. Heterocycl. Chem., 28, 325 (1991).
L. I. Giannola, G. Giammona, S. Palazzo, and L. Lamartina, J. Chem. Soc., Perkin Trans. 1, 2707 (1984).
R. M. Acheson and J. D. Wallis, J. Chem. Soc., Perkin Trans. 1, 415 (1981).
U. Vogeli and W. Philipsborn, Helv. Chim. Acta, 61, 607 (1978).
J. W. Lown and J. C. N. Ma, Can. J. Chem., 45, 939 (1967).
S. Manzhos, H. Segawa, and K. Yamashita, Chem. Phys Lett., 527, 51 (2012).
V. A. Bren, A. D. Dubonosov, V. I. Minkin, A. V. Tsukanov, T. N. Gribanova, E. N. Shepelenko,
Y. V. Revinsky, and V. P. Rybalkin, J. Phys. Org. Chem., 20, 917 (2007).
A. C. Tripathi, S. J. Gupta, G. N. Fatima, P. K. Sonar, A. Verma, and S. K. Saraf, Eur. J. Med. Chem.,
72, 52 (2014).
25.
26.
27.
D. Kaminskyy, A. K. Gzella, and R. Lesyk, Synth. Commun., 44, 231 (2014).
E. S. Darwish, I. A. Abdelhamid, M. A. Nasra, F. M. Abdel-Gallil, and D. H. Fleita, Helv. Chem. Acta,
93, 1204 (2010).
28.
29.
N. Ghavtadze, R. Narayan, B. Wibbeling, and E.-U. Wurthwein, J. Org. Chem., 76, 5185 (2011).
N. P. Belskaya, A. I. Bolgova, M. L. Kondrat'eva, O. S. Yel'tsov, and V. A. Bakulev, Izv. Akad. Nauk,
Ser. Khim., 876 (2011). [Russ. Chem. Bull., 60, 896 (2011).]
30.
31.
32.
A. I. Mikhalev, S. V. Ukhov, and M. E. Konshin, Khim. Geterotsikl. Soedin., 629 (1994). [Chem.
Heterocycl. Compd., 30, 551 (1994).]
Y. Kobayashi, T. Nakatani, R. Tanaka, M. Okada, E. Torii, T. Harayama, and T. Kimachi, Tetrahedron,
67, 3457 (2011).
A. S. Ivanov, N. Z. Tugusheva, L. M. Alekseeva, and V. G. Granik, Izv. Akad. Nauk, Ser. Khim., 837
(2004). [Russ. Chem. Bull., 53, 873 (2004).]
M. P. Cava and M. I. Levinson, Tetrahedron, 41, 5061, (1985).
33.
34.
Y. Vallee, P.-Y. Chavant, S. Pinet, N. Pelloux-Leon, R. Arnaud, and V. Barone, Phosphorus, Sulfur
Silicon Relat. Elem., 120, 245 (1997).
35.
36.
37.
38.
39.
A. S. Bell, C. W. G. Fishwick, and J. E. Reed, Tetrahedron, 54, 3219 (1998).
I. T. Barnish, C. W. G. Fishwick, D. R. Hill, and C. Szantay, Jr., Tetrahedron Lett., 30, 4449 (1989).
M. Iwaoka and N. Isozumi, Molecules, 17, 7266 (2012).
V. I. Minkin and R. M. Minyaev, Chem. Rev., 101, 1247 (2001).
Y. Nagao, T. Honjo, H. Iimori, S. Goto, S. Sano, M. Shiro, K. Yamaguchi, and Y. Sei, Tetrahedron
Lett., 45, 8757 (2004).
899

40.
41.
S. Scheiner, J. Chem. Phys., 134, 164313 (2011).
A. Pena-Hueso, F. Tellez; R. Vieto-Pena, R. O. Esquivel, A. Esparza-Ruiz, I. Ramos-Garcia,
R. Contreras, N. Barba-Behrens, and A. Flores-Parra, J. Mol. Struct., 984, 409 (2010).
A. I. Bolgova, K. I. Lugovik, J. O. Subbotina, P. A. Slepukhin, V. A. Bakulev, and N. P. Belskaya,
Tetrahedron, 69, 7423 (2013).
42.
900