Cyanothioacetamide in heterocyclic chemistry: Synthesis of piperidine-3-carbonitrile, pyrazolopyridine, thiinopyridine-3-carbonitrile derivatives, and their theoretical calculations

Article abstract of DOI:10.1080/10426500214893

Cyanothioacetamide (1) reacted with acrylonitrile (2) to afford the corresponding 6-oxo-2-sulfanylpiperidine-3-carbonitrile (6), which oxidized to give compounds 7 and 8 under different conditions. Moreover, compound 6 was used as a starting material to synthesize 12a-c, 16a-d, 26a-c, 27a-c, and 30a-c via reactions with aromatic aldehydes 9a-c, diazonium chlorides 13a-d, and 3-arylpropennitrile derivatives 18a-i respectively. Considering the data of IR, ¹H NMR, mass spectra, elemental analyses, and theoretical calculations, all the structures of the newly synthesized heterocyclic compounds were elucidated.

Full text of DOI:10.1080/10426500214893

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Cyanothioacetamide in Heterocyclic Chemistry:
Synthesis of Piperidine-3-carbonitrile,
Pyrazolopyridine, Thiinopyridine-3-carbonitrile
Derivatives, and Their Theoretical Calculations
Fawzy A. Attaby a , Hussein M. Mostafa a , Ahmed H. H. Elghandour a & Yasser M. Ibrahem a
a Cairo University , Giza, Egypt
Published online: 27 Oct 2010.
To cite this article: Fawzy A. Attaby , Hussein M. Mostafa , Ahmed H. H. Elghandour & Yasser M. Ibrahem (2002)
Cyanothioacetamide in Heterocyclic Chemistry: Synthesis of Piperidine-3-carbonitrile, Pyrazolopyridine, Thiinopyridine-3-
carbonitrile Derivatives, and Their Theoretical Calculations, Phosphorus, Sulfur, and Silicon and the Related Elements, 177:12,
2753-2772, DOI: 10.1080/10426500214893
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Phosphorus, Sulfur and Silicon, 2002, Vol. 177:2753–2772
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Copyright 2002 Taylor & Francis
1042-6507/02 $12.00 + .00
DOI: 10.1080/10426500290146758
CYANOTHIOACETAMIDE IN HETEROCYCLIC
CHEMISTRY: SYNTHESIS OF PIPERIDINE-
3-CARBONITRILE, PYRAZOLOPYRIDINE,
THIINOPYRIDINE-3-CARBONITRILE DERIVATIVES,
AND THEIR THEORETICAL CALCULATIONS
Fawzy A. Attaby, Hussein M. Mostafa,
Ahmed H. H. Elghandour, and Yasser M. Ibrahem
Cairo University, Giza, Egypt
(Received January 1, 2002; accepted April 12, 2002)
Cyanothioacetamide (1) reacted with acrylonitrile (2) to afford the
corresponding 6-oxo-2-sulfanylpiperidine-3-carbonitrile (6), which ox-
idized to give compounds 7 and 8 under different conditions. More-
over, compound 6 was used as a starting material to synthesize 12a–c,
16a–d, 26a–c, 27a–c, and 30a–c via reactions with aromatic aldehydes
9a–c, diazonium chlorides 13a–d, and 3-arylpropennitrile derivatives
18a–i respectively. Considering the data of IR, 1H NMR, mass spectra,
elemental analyses, and theoretical calculations, all the structures of
the newly synthesized heterocyclic compounds were elucidated.
Keywords: 5,6-Dihydrothiino[2,3-b]pyridine-3-carbonitrile; 6-oxo-2-
sulfanyl-piperidine-3-carbo-nitrile; acrylonitrile; cyanothioacetamide;
pyrazolo[4,3-c]pyridin-6-one
INTRODUCTION
17
Although several publications1
have appeared concerning the reac-
tions and synthetic potential of cyanothioacetamide (1) no approach
concerning its reaction with acrylonitrile (2) has been published. This
induced our interest to carry out this reaction to isolate pyridine
derivative and, in turn, use it as a good synthon to prepare several
heterocyclic compounds with promising biological activities. In addi-
19
tion, the reported biological activities of each of pyridines18
and
22
pyrazolopyridines20
stimulated our interest for the synthesis of
several new derivatives of these ring systems which are required for
the chemical transformations and medicinal chemistry program.
Address correspondence to F. A. Attaby, Department of Chemistry, Faculty of Science,
Cairo University, Giza, Egypt. E-mail: Fawzy@chem-sci.eun.eg or fattaby@hotmail.com
2753

2754

2755

2756
F. A. Attaby et al.
RESULTS AND DISCUSSION
It has been found that cyanothioacetamide (1) reacted with acrylonitrile
(2) in an aqueous solution of potassium hydroxide (10%) to afford the
corresponding 6-oxo-2-thioxopiperidine-3-carbonitrile (5), which was
present in equilibrium with the more stable structure 6-oxo-2-sulfanyl-
3,4,5-trihydropyridine-3-carbonitrile (6). Formation of 6 was assumed
to proceed via the addition of a proton from 1 on the olefinic double bond
of 2 to give the nonisolable intermediate 3, which, in turn, hydrolyzed
to give 4 that underwent ammonia elimination (ammonia removal de-
tected by its odor in addition to the formation of the white clouds with
*
glass rod moistened with hydrochloric acid) to afford 5 6. Consider-
)
1
ing both IR and H NMR data and the solubility in alkali, the struc-
ture 5 is eliminated. The IR spectrum of the reaction product showed
1
the bands of SH, CN, and CO groups, and its H NMR spectrum re-
vealed signals of H-3, H-4, H-5 pyridine and SH or piperidine protons
(cf. Tables I, II, and Experimental Part). Moreover, the mass spectrum
of 6 gave m/z = 154 that corresponding to the exact molecular weight of
a molecular formula C6H6N2SO of the assigned structure (cf. Chart 1).
CHART 1
Theoretical Consideration
The reaction products in Chart 1 imply the possible tautomeric equi-
librium between 5 and 6. The ground state electronic properties of
these two forms are given in Table III. The 6 is thermodynamically
more stable. In a polar medium, 6 would be more stabilized due to its
greater dipole moment. For structure 6, two active methylene centres

Cyanothioacetamide in Heterocyclic Chemistry
TABLE II IR and 1H NMR Spectral Data
2757
1
Comp.
IR (KBr, cm
)
1H NMR ( ppm)
6
2987 (sat CH); 2569 (SH); 2218
(CN); 1692 (CO amidic); 1629
(C N) and 1600 (C C)
2.3 (s, br., 1H, SH); 2.9 (t, 1H, pyridine
H-3); 3.5 (m, 2H, pyridine H-4) and
4.7 (t, 2H, pyridine H-5)
7
2982 (sat. CH); 2221 (CN); 1687
(CO amidic); 1635 (C N) and
1604 (C C)
2.7 (t, 2H, at H-3 of the two pyridine
rings); 3.6 (m, 4H, at H-4 of the two
pyridine rings) 5.2 (t, 4H, at H-5 of
the two pyridine rings)
8
3267–3442 (OH); 3079 (
stretch); 2568 (SH); 2215 (CN);
1624 (C N) and 1600 (C C)
C
H
2.1 (s, br., 1H, SH) and 5.7 (dd, 2H, at
Pyridine H-4, H-5)
12a
3098 (
H); 2559 (SH); 2218 (CN); 1624
(C N) and 1600 (C C)
C
H streth.); 2979 (sat
2.2 (s, br., 1H, SH); 2.8 (s, 1H,
C
pyridine H-3); 4.8 (s, 2H, pyridine
H-5) and 6.9–7.3 (m, 6H, aromatic
and CH protons)
12b
12c
14a
14b
14c
14d
16a
16b
3087 (
C
H streth.); 2985 (sat
2.5 (s, br., 1H, SH); 3.1 (s, 1H,
C
H); 2560 (SH); 2214 (CN); 1636
pyridine H-3); 5.2 (s, 2H, pyridine
H-5) and 7.0–7.9 (m, 5H, aromatic
and CH protons)
1.3 (s, 3H, CH3); 2.4 (s, br., 1H, SH);
2.9 (s, 1H, pyridine H-3); 5.3 (s, 2H,
pyridine H-5) and 7.0–7.9 (m, 5H,
aromatic and CH protons)
2.6 (s, br., 1H, SH); 3.2 (s, 1H, pyridine
H-3); 5.1 (s, 2H, pyridine H-5); 5.9 (s,
br., 1H, NH) and 6.9–7.8 (m, 5H,
aromatic protons)
2.4 (s, br., 1H, SH); 3.1 (s, 1H, pyridine
H-3); 4.9 (s, 2H, pyridine H-5); 5.7
(s, br., 1H, NH) and 7.0–7.9 (m, 4H,
aromatic protons)
1.7 (s, 3H, OCH3); 2.2 (s, br., 1H, SH);
3.3 (s, 1H, pyridine H-3); 5.3 (s, 2H,
pyridine H-5); 5.9 (s, br., 1H, NH) and
7.3–8.2 (m, 5H, aromatic protons)
0.9 (s, 3H, CH3); 2.5 (s, br., 1H, SH);
3.4 (s, 1H, pyridine H-3); 4.7 (s, 2H,
pyridine H-5); 5.6 (s, br., 1H, NH) and
6.9–7.5 (m, 4H, aromatic protons)
2.3 (s, br., 1H, SH); 5.7 (s, br., 2H, NH2);
6.9–8.1 (m, 6H, aromatic and
(C N) and 1602 (C C)
3112 (
C
H streth.); 2989 (sat
C
H); 2552 (SH); 2222 (CN); 1640
(C N) and 1607 (C C)
3187 (NH); 2982 (sat. CH);
2552 (SH); 2220 (CN); 1687 (CO
amidic); 1623 (C N) and 1602
(C C)
3191 (NH); 2987 (sat. CH); 2556
(SH); 2218 (CN); 1690 (CO
amidic); 1631 (C N) and 1600
(C C)
3197 (NH); 2977 (sat. CH); 2560
(SH); 2221 (CN); 1690 (CO
amidic); 1633 (C N) and 1605
(C C)
3196 (NH); 2989 (sat. CH); 2555
(SH); 2220 (CN); 1690 (CO
amidic); 1631 (C N) and 1600
(C C)
3545–3207 (broad, OH and NH2);
3087 (
(CN); 1635 (C N) and 1601
(C C)
3556–3221 (broad, OH and NH2);
3101 (
(CN); 1630 (C N) and 1600
C H); 2556 (SH); 2221
pyridine H-5) and 12.4 (s, br., 1H, OH)
2.0 (s, br., 1H, SH); 5.8 (s, br., 2H,
NH2); 7.0–8.1 (m, 5H, aromatic and
pyridine H-5) and 12.5 (s, br., 1H, OH)
C H); 2562 (SH); 2218
(C C)
(Continued on next page)

2758
F. A. Attaby et al.
TABLE II IR and 1H NMR Spectral Data (Continued)
1
Comp.
IR (KBr, cm
)
1H NMR ( ppm)
16c
3551–3218 (broad, OH and NH2);
3080 ( H); 2981 (sat. CH);
2552 (SH); 2214 (CN); 1628 (C N)
1.5 (s, 3H, OCH3); 2.2 (s, br., 1H, SH);
5.5 (s, br., 2H, NH2); 6.9–8.3 (m, 5H,
aromatic and pyridine H-5) and 12.3
(s, br., 1H, OH)
C
and 1602 (C C)
16d
3582–3224 (broad, OH and NH2);
1.0 (s, 3H, CH3); 2.3 (s, br., 1H, SH);
5.3 (s, br., 2H, NH2); 6.8–7.2 (m, 5H,
aromatic and pyridine H-5) and 12.7
(s, br., 1H, OH)
3076 (
C H); 2551 (SH); 2222
(CN); 1630 (C N) and 1600
(C C)
26a
26b
26c
3432, 3253 (NH2); 2976 (sat CH);
2217 (CN); 1687 (CO amidic);
1633 (C N) and 1604 (C C)
3421, 3249 (NH2); 2978 (sat CH);
2218 (CN); 1691 (CO amidic);
1630 (C N) and 1600 (C C)
3441, 3258 (NH2); 2982 (sat CH);
2222 (CN); 1695 (CO amidic);
1623 (C N) and 1601 (C C)
2.7 (t, 2H, at pyridine H-4); 4.8 (t, 2H,
at pyridine H-3); 5.6 (s, br., 2H, NH2)
and 6.9–7.7 (m, 5H, aromatic protons)
3.1 (t, 2H, at pyridine H-4); 4.5 (t, 2H,
at pyridine H-3); 5.8 (s, br., 2H, NH2)
and 7.0–7.8 (m, 4H, aromatic protons)
1.5 (s, 3H, OCH3); 3.3 (t, 2H, at
pyridine H-4); 4.8 (t, 2H, at pyridine
H-3); 5.3 (s, br., 2H, NH2) and
7.0–7.9 (m, 4H, aromatic protons)
1.0 (t, 3H, CH3CH2); 2.8 (t, 2H, at
pyridine H-4); 4.2 (q, 2H, CH3CH2);
5.0 (t, 2H, at pyridine H-3); 5.7
(s, br., 2H, NH2) and 6.8–7.8 (m, 5H,
aromatic protons)
1.2 (t, 3H, CH3CH2); 3.1 (t, 2H, at
pyridine H-4); 4.3 (q, 2H, CH3CH2);
4.9 (t, 2H, at pyridine H-3); 5.8
(s, br., 2H, NH2) and 6.9–7.6 (m, 4H,
aromatic protons)
0.9 (t, 3H, CH3CH2); 1.6 (s, 3H, OCH3);
3.3 (t, 2H, at pyridine H-4); 4.1
(q, 2H, CH3CH2); 5.2 (t, 2H, at
pyridine H-3); 5.9 (s, br., 2H, NH2)
and 7.1–8.2 (m, 4H, aromatic
protons)
28a
28b
28c
3452, 3224 (NH2); 2987 (sat CH);
2218 (CN); 1721 (CO ester); 1690
(CO amidic); 1630 (C N) and
1602 (C C)
3434, 3218 (NH2); 2980 (sat CH);
2214 (CN); 1719 (CO ester); 1684
(CO amidic); 1635 (C N) and
1605 (C C)
3441, 3223 (NH2); 2987 (sat CH);
2217 (CN); 1723 (CO ester); 1693
(CO amidic); 1632 (C N) and
1601 (C C)
are available for consideration, viz., atoms 4 and 5. The net charge on
the two atoms is 0.067e and 0.033e respectively. These charge densities
would thus favor C4 over C5. The electrostatic potential map (EPM) for
6 is given in Figure 1. This map supports our conclusion that C4 is the
most favorable center of consideration.
Compound 6 was oxidized by refluxing in ethanol containing a cat-
alytic amount of triethylamine for 3 h to give a reaction product
corresponding to dehydrogenation. The IR spectrum of this reaction
product showed bands corresponding to the CN and CO groups, and
1
its H NMR spectrum revealed the signals of only pyridine protons.

2759

2760
F. A. Attaby et al.
Moreover, its mass spectrum gave m/z = 306 which corresponding to the
exact molecular weight of a molecular formula C12H10N4S2O2. Consid-
ering the above data, in addition to the elemental analyses, this reaction
product could be formulated as the corresponding disulphide derivative
7. Compound 6 was aromatized by stirring in cold ethanol containing a
FIGURE 1 Prospective drawing of compounds drawn at its AM1 geometry.
(Continued)

Cyanothioacetamide in Heterocyclic Chemistry
2761
FIGURE 1 (Continued)
catalytic amount of triethylamine to give the corresponding 6-hydroxy-
2-sulfanylpyridine-3-carbonitrile (8). The structure of 8 was elucidated
1
by considering the data of IR and H NMR spectra in addition to its
mass spectrum which gave m/z = 152 and which corresponded to the
molecular weight of a molecular formula C6H4N2SO of the assigned
structure (cf. Chart 2).

2762
F. A. Attaby et al.
FIGURE 1 (Continued)
An investigation of the CH2-activity in 6 was examined through
its reaction with aromatic aldehydes 9a–c. It was found that 6 reacted
with benzaldehyde (9a) in ethanol containing a catalytic amount of
triethylamine under reflux for 5 h to afford a condensation product
1
12a. The elemental analyses, IR, and H NMR data were the basis on
which the structure of 12a was established and the structures 10a and
11a were eliminated (cf. Tables I and II). Similarly, 6 reacted with both
p-chlorobenzaldehyde and p-methoxybenzaldehyde 9b,c to afford the
corresponding condensation products 12b,c respectively.
Theoretical Consideration
Condensation reactions on 6 may yield the ArCH derivative either 10
or 12 depending on the condensation site. The ground state electronic
structural properties of 10–12 are presented in Table III. Careful in-
spection of these data reveals that condensation at C4 or C5 are equally
probable and perhaps allows simultaneous attack on the two centres
(cf. Figure 1). Figure 2 plots free energy relationships of Et, 1Hf, , and
1Egap against the ( p) Hammet constant for substituents a–c of 12.
Work was extended to shed more light on the CH2-activity in 6
through its coupling reaction with aryl diazonium chlorides. Thus,
it was found that a cold solution of 6 in ethanol containing sodium

Cyanothioacetamide in Heterocyclic Chemistry
2763
CHART 2
acetate was stirred with a cold solution of diazotized aromatic amines
13a–d for 3 h to afford the corresponding hydrazo derivatives 14a–d
respectively. The IR spectra of 14a–d showed bands for NH, SH, CN,
1
and CO groups and the H NMR spectra revealed signals of pyridine
H-3, H-5, NH, SH, and aromatic protons (cf. Tables I and II). More-
over, the mass spectra of 14a,c as typical examples, gave m/z = 258 and
288 which corresponds to the exact molecular weights of the molecular
formulas C12H10N4SO and C13H12N4SO2 of the assigned structures (cf.
Chart 3). The structures of 14a–d were further confirmed through their
cyclization in ethanol containing catalytic amounts of triethylamine
under reflux for 3–5 h to give 3-amino-2-(phenyl-, 4-chlorophenyl, 4-
methoxyphenyl and 4-methylphenyl)-4-sulfan-yl-7-hydro-pyrazolo[4,3-
c]pyridin-6-one 15a–d respectively. The IR spectra of these products
showed no bands for the CN group and, instead, the newly formed
NH2 group was detected in each case. The absence of C O band
and the presence of newly formed OH group were detected. This
proves the presence of 16a–d rather than 15a–d (c.f. Tables I, II and
Chart 3).

2764
F. A. Attaby et al.
CHART 3
Theoretical Consideration
The reaction of 6 with ArN2Cl may yield 14 or 17 depending on
the rate of condensation. The 14 is thermodynamically and ener-
getically more stable than 17 and 14 is stabilized by its cycliza-
tion to 15, which is further stabilized by its tautomeric equilib-
rium with 16. The ground state properties of the formed compounds
are given in Table III. The effect of substituents is best visualized
via analysis of the free-energy relationships (cf. Figure 1). Figure 3
presents such relationships for compounds a–d for the most stable
compound 16.

Cyanothioacetamide in Heterocyclic Chemistry
2765
FIGURE 2 Free energy relationships for ET, 1Hf, energy gab, and as plotted
against the constant of compounds 12a–c.
Hammet
Synthon 6 reacted with 2-(aminothioxomethyl)-3-phenylprop-2-
ennitrile (18a) in ethanol containing a catalytic amount of piperidine
to afford the corresponding 4-amino-7-oxo-2-phenyl-5,6-dihydrothiino-
[2,3-b]pyridine-3-carbonitrile (26a). This reaction product formed via
the addition of the SH group in 7 to the double bond of 18a af-
forded the nonisolable product 19a which underwent elimination of
hydrogen sulphide followed by elimination of hydrocyanic acid to give
1
23a that rearranged to give 26a. The IR and H NMR spectrum of
this reaction product confirmed its structure (cf. Table II). Moreover,
the mass spectrum of reaction product gave m/z = 281 which corre-
sponds to the molecular weight for a molecular formula C15H11N3OS
of the assigned structure (cf. Chart 8). Similarly, other analogues 2-
(amino-thioxomethyl)-3-(4-chlorophenyl and 4-methoxyphenyl)-prop-
2-ennitrile (18b,c) reacted with 6 under the same reaction con-
dition to afford the corresponding 4-amino-7-oxo-2(4-chlorophenyl
and 4-methoxyphenyl)-5,6-dihydrothiino[2,3-b]pyridine-3-carbonitrile
26b,c, respectively via the nonisolable 20b,c and 23b,c. By considering
the data of IR and 1H NMR data and the elemental analyses, structures
24a–c and 25a–c were eliminated (cf. Tables I, II, and Chart 4).

2766
F. A. Attaby et al.
CHART 4
Theoretical Consideration
Chart 4 reveals 26 may be formed from the reaction of 6 with 18 via
three main possible intermediate products, namely 20–22. The inter-
mediate 20 is thermodynamically the most stable as revealed by the
1H values presented in Table III. Furthermore the loss of HCN would
lead to compounds 23–25 of which 23 is thermodynamically much more

Cyanothioacetamide in Heterocyclic Chemistry
2767
FIGURE 3 Free energy relationships for ET, 1Hf, energy gab, and as plotted
against the constant of compounds 16a–d.
Hammet
favorable than 24 and 25. It is interesting to note that the more favor-
able route 6 > 20 > 23 involves the less polar components (cf. Figure 1).
Figures 4 plots the free-energy relationships between the p-Hammet
substituent constants for substituted 26a–c and Et, Egap
, , and 1Hf.
In a surprise reaction, synthon 6 reacted with each of (phenyl-,
4-chloro-phenyl and 4-methoxyphenylmethylene)methane-1,1-dicarbo-
nitrile 18d–f under the same previously mentioned conditions to af-
ford the reaction products which were identical in all aspects with
that given from the reaction of 18a–c with 6. The obtained reaction
products 26a–c were formed via the non-isolable intermediates 19d–f
respectively. It is important to report here that compounds 26a–c ob-
tained by this route were identical in all aspects with that given from
the reaction of 6 with 18a–c. Moreover, compound 6 reacted with each
ethyl-3-(phenyl, 4-chlorophenyl and 4-methoxyphenyl)-2-cyanoprop-
2-enoate 18g–i to give the corresponding ethyl 4-amino-7-oxo-2-
(phenyl-, 4-chlorophenyl and 4-methoxyphenyl)-5,6-dihydrothiino[2,3-
b]pyridine-3-carboxylate (28a–c) via the nonisolable products 19g–i
and 27a–c. The IR, 1H NMR spectra, and the elemental analyses
data were the basis on which the structures 28a–c were confirmed,
and the structures 29a–c were eliminated. Further confirmation of

2768
F. A. Attaby et al.
FIGURE 4 Free energy relationships for ET, 1Hf, energy gab, and as plotted
against the constant of compounds 26a–c.
Hammet
28a–c structures was given from their mass spectra. The m/z = 328,
362 and 358 corresponded to the molecular weights of the molecular
formulae C17H16N2O3S, C17H15ClN2O3S, and C18H18N2O4S of the as-
signed structures 28a–c, respectively (cf. Chart 5).
Theoretical Consideration
The ground state electronic properties for 27–29 are given in Table III
and Figure 1. The 27 is much more stable energetically and thermody-
namically than 29. In the polar reaction medium 27 is further stabi-
lized. Once 27 is formed, it would be stabilized by tautomeric equilib-
rium with 28.
EXPERIMENTAL
All melting points were uncorrected. IR spectra (KBr discs) were
recorded on Brucker Vector 22 and Perkin-Elmer FT-IR type 4
spectrophotometers. 1H NMR spectra were recorded on Varian EM
390 MHz, Gemnai-200 MHz and Brucker WP-80 spectrometers using
TMS as an internal standard and CDCl3, DMSO-d6 and (CD3)2CO as

Cyanothioacetamide in Heterocyclic Chemistry
2769
CHART 5
solvents. Chemical shifts are expressed as ppm units. Mass spectra
were recorded on Hewlett-Packard GC-MS type 2988 using an inlet
type at 70eV. Microanalyses were performed by the Microanalytical
Center of Cairo University. Molecular orbital calculations were per-
formedby considering the Schrodinger equation,23 variational methods,
and Hartree-Fock theory,24 and semiempirical methods,25 Modified ne-
30
glect of the Diatomic Overlap (MNDO)26 and Austin mode 1 (AM1).27
Synthesis of 6-Oxo-2-sulfanyl-3,4,5-trihydropyridine-
3-carbonitrile (6)
A solution of cyanothioacetamide (1) and acrylonitrile (2) (0.01 mmol of
each) in potassium hydroxide (25 mL, 10%) was refluxed for 5 h. The
reaction mixture was then cooled and acidified with hydrochloric acid.

2770
F. A. Attaby et al.
The product formed was collected by filtration, washed with cold water,
and then crystallized from ethanol to give 6 (cf. Tables I and II).
Synthesis of 7
A solution of 2-sulfanylpyridine derivative 6 in ethanol (50 mL) con-
taining a catalytic amount of triethyl amine (0.05 mL) was refluxed for
5 h. The reaction mixture was then cooled, and the product formed was
collected by filtration, washed with cold water, and then crystallized
from ethanol to give 7 (cf. Tables I and II).
Synthesis of 6-Hydroxy-2-sulfanylpyridine-
3-carbonitrile (8)
A solution of 2-sulfanylpyridine derivative 6 in ethanol (50 mL) con-
taining a catalytic amount of triethylamine (0.05 mL) was stirred for
1 h at room temperature. The product formed was collected by filtra-
tion, washed with cold water, and then crystallized from ethanol to give
8 (cf. Tables I and II).
Synthesis of 12a c
A solution of 2-sulfanylpyridine derivative 6 was refluxed for 5 h with
each aromatic aldehyde 9a–c in ethanol (50 mL) containing a catalytic
amount of triethylamine (0.5 mL). The reaction mixture was then
cooled, and the products formed were collected by filtration, washed
with cold water, and then crystallized from proper solvent to give 12a–c
respectively (cf. Tables I and II).
Synthesis of 14a d
To a cold solution of 2-sulfanylpyridine derivative 6 (0.01 mmol) in
ethanol (50 mL) was added 0.01 mmol sodium acetate. The solution
was stirred, and then each of diazonium chlorides 13a–d (0.01 mmol
of each) was added dropwise. Stirring was continued for 2–3 h. The
products formed were collected by filtration and washed with water, fol-
lowed by cold ethanol. The isolated compounds were crystallized from
ethanol to give the products 14a–d, respectively (cf. Tables I and II).
Synthesis of 16a d
A solution of each of hydrazones 14a–d in ethanol (50 mL) containing
a catalytic amount of triethylamine (0.5 mL) was refluxed for 3 h. The

Cyanothioacetamide in Heterocyclic Chemistry
2771
reaction mixture was then cooled, and the products formed were col-
lected by filtration, washed with water, and then crystallized from the
proper solvent to give 16a–d respectively (cf. Tables I and II).
Synthesis of 26a c and 28a c
A solution of 36 with 2-(aminothioxomethyl)-3-(phenyl or subs.
phenyl)prop-2-ennitrile 18a–c or (phenyl-or subs. phenylmethylene)-
methane-1,1-dicarbonitrile 18d–f and 18g–i in ethanol (50 mL) con-
taining the catalytic amounts of triethylamine or piperidine (0.5 mL)
was refluxed for 4–7 h. The reaction mixture was then cooled and acid-
ified with acetic acid and, the products formed were collected by filtra-
tion and crystallized from the proper solvent to afford 26a–c and 28a–c
respectively (cf. Tables I and II).
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