Cascade synthesis of thieno[2,3-b]pyridines by using intramolecular cyclization reactions of 3-cyano-2-(organylmethylthio)pyridines

Article abstract of DOI:10.5935/0103-5053.20150309

2-Amino-4-aryl-6-mercaptopyridine-3,5-dicarbonitriles as starting materials have been prepared by reducing of 2-amino-4-aryl-6-(phenylthio)pyridine-3,5-dicarbonitrile derivatives which were synthesized on stepwise one-pot three component reaction of malon

Full text of DOI:10.5935/0103-5053.20150309

http://dx.doi.org/10.5935/0103-5053.20150309
J. Braz. Chem. Soc., Vol. 27, No. 4, 663-669, 2016.
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Article
Cascade Synthesis of Thieno[2,3-b]pyridines by Using Intramolecular Cyclization
Reactions of 3-Cyano-2-(organylmethylthio)pyridines
Fatemeh Alinaghizadeh,a Mahboobeh Zahedifar,b Mohammad Seifia and Hassan Sheibani*,a
aDepartment of Chemistry, Shahid Bahonar University of Kerman, 76169 Kerman, Iran
bDepartment of Chemistry, Faculty of Science, University of Jiroft, 364 Jiroft, Iran
2-Amino-4-aryl-6-mercaptopyridine-3,5-dicarbonitriles as starting materials have been
prepared by reducing of 2-amino-4-aryl-6-(phenylthio)pyridine-3,5-dicarbonitrile derivatives
which were synthesized on stepwise one-pot three component reaction of malononitrile, aldehydes
and thiophenol in the presence of base catalysts such as triethylamine, high surface area (HSA)
MgO or nanocrystalline magnesium oxide. Alkylation of 2-amino-4-aryl-6-mercaptopyridine-
3,5-dicarbonitriles with α-halogen compounds in presence of sodium alkoxide as base catalyst
followed with cyclization afforded the thieno[2,3-b]pyridine derivatives in excellent yields and
in a short reaction time.
Keywords: MgO (HSA-MgO), thieno[2,3-b]pyridine, three component reaction, 2-amino-4-
aryl-6-mercaptopyridine-3,5-dicarbonitriles, intramolecular cyclization reactions
Introduction
inhibiting agents.9 These potential therapeutic applications
made these compounds as a privileged scaffold. Therefore,
the synthesis of highly substituted thieno[2,3-b]pyridine
has attracted much attention and a number of procedures
have been developed to prepare these compounds using a
variety of protocols.10-12 Thieno[2,3-b]pyridine derivatives
have been previously prepared in a multistep procedure from
either a thiophene or a pyridine ring and further ring closure
leading to the other heterocyclic fused system. Unfortunately,
many of these methods suffer from limitations such as long
reaction times, low to moderate yields and co-occurrence
of several side products.13-16 Therefore, reinvestigation of
the classical conditions seemed warranted for developing
conditions for suitable library synthesis. In view of all these
benefits and as a continuation of our interest in the field of
heterocyclic compounds,17-20 we undertook the synthesis
of new thieno[2,3-b]pyridine derivatives by the reaction of
2-amino-4-aryl-6-mercaptopyridine-3,5-dicarbonitriles with
halogen compounds in the presence of sodium alkoxide at
room temperature.
In organic chemistry, derivatives of pyridine fused to
thiophene systems are one important class of heterocyclic
compounds and they attract considerable interest because
of their great practical usefulness, primarily due to
their various biological activities.1 The synthesis of
thienopyridines has been the subject of several reviews
which demonstrate the high importance of this class
of compounds.2 Six isomeric thienopyridine structures
characterized by different annelation modes are known:
thieno[2,3-b]pyridine, thieno[3,2-b]pyridine, thieno[2,3-c]
pyridine, thieno[3,2-c]pyridine, thieno[3,4-b]pyridine and
thieno[3,4-c]pyridine. The first four thienopyridines were
studied in detail in the literature.3 Data on the “isostructural”
isomers thieno[3,4-b]pyridine and thieno[3,4-c]pyridine
are scarce and disembodied and they are beyond the
scope. Our main focus is on synthesis of some new
thieno[2,3-b]pyridine derivatives. These compounds have
been investigated in relation with their biological and
pharmacological activities. Some of them have proved
to possess antibacterial,4,5 antiviral,6 antihypertensive7
and antimicrobial8 activities. So the certain thieno[2,3-b]
pyridine derivatives were prepared as anti-inflammatory
agents, particularly for treating arthritis and bone resorption
Experimental
General procedures
Melting points were measured on a Electrothermal
Engineering LTD apparatus and are uncorrected. Infrared
*e-mail: hsheibani@mail.uk.ac.ir

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Cascade Synthesis of Thieno[2,3-b]pyridines
J. Braz. Chem. Soc.
(IR) spectra were measured on a Mattson 1000 Fourier
transform IR (FTIR) spectrometer. The proton and carbon
nuclear magnetic resonance (NMR) spectra were recorded
with a Bruker DRX-400 AVANCE spectrometer at 400
and 100 MHz, respectively. Mass spectra (MS) were
recorded on a Shimadzu MS-QP2000A mass spectrometer
operating at an electrospray ionization (ESI) potential
of 70 eV. Elemental analyses were performed using a
Heracus CHN-O-Rapid analyzer. 2,2-Dicyanooxiranes
1a-d were prepared according to a literature procedure.19
malononitrile in 2.0 mL of ethanol was added, and the
reaction mixture was refluxed for a further 60 min. The
reaction mixture was then exposed to air overnight. The
yellow crystalline precipitate formed was collected by
suction filtration, washed with n-hexane/ethanol (9:1),
followed by n-hexane.
Methods B and C (high surface area and nanosized MgO
as base catalysts)
To a stirred solution of aldehyde (1 mmol) and
malononitrile (1 mmol) in 10 mL ethanol were added
50 mg MgO (high surface area or nanosized) at ambient
temperature. The resulting mixture was heated to 50 oC,
the thiophenol (1 mmol) was added and the reaction
mixture was refluxed for 45 min. Another 1 mmol of
malononitrile in 2.0 mL of ethanol was added, and the
reaction mixture was refluxed for a further 60 min. The
reaction mixture was then exposed to air overnight. The
mixture was centrifuged to separate the catalyst and the
catalyst was washed with ethyl acetate (3 × 5 mL). The
solvent was evaporated under reduced pressure and the
crude product obtained was purified by recrystallization
from ethanol.
Preparation of high surface area MgO
The catalysts used in this study were obtained by
calcinations of rehydrated Mg(OH)2. The experimental
results showed that an optimal calcination temperature in
the range 400-500 oC gives poorly crystalline, high surface
area (HSA) MgO that can be regenerated by washing, and
then reused. After separation of the product by filtration,
the recovered solvent containing MgO was reused twice
without loss of activity of the catalyst.21,22
Preparation of nanosized MgO
The MgO nanoparticles were synthesized by
precipitation of the magnesium hydroxide gels in aqueous
solution using Mg(NO3)2 as salt and liquid ammonia as the
precipitating agent. Initially, the pH of 200 mL of distilled
water was adjusted to 10.5 by addition of liquid ammonia.
To this solution, 0.1 mol L-1 magnesium nitrate solution
(0.0148 g mL-1) was added dropwise with continuous
stirring. The rate of addition of the salt solution was kept
at 20 mL h-1. During the addition, the pH of the mixture
decreased due to hydrolysis of the salt. The pH was
maintained at 10.5 by controlled addition of liquid ammonia
solution. After completion of the precipitation procedure,
the mixture was stirred at ambient temperature for 12 h,
filtered, repeatedly washed with distilled water, dried at
120 oC, and calcined at 500 oC for 2 h.23
2-Amino-4-phenyl-6-(phenylthio)pyridine-3,5-dicarbonitrile
(4a)
m.p.: 213-215 ºC (lit.23 216-218 ºC); IR (KBr) nmax / cm-1
3470, 3360, 2935, 2222, 1639, 1550; 1H NMR (400 MHz,
DMSO-d6) d 7.32-7.65 (m, 10H, Ar), 7.9 (broad, 2H,
NH2).
2-Amino-4-(4-chlorophenyl)-6-(phenylthio)pyridine-3,5-
dicarbonitrile (4b)
o
m.p.: 220-222 C (lit.24 222-224 ºC); IR (KBr)
n
max / cm-1 3470, 3350, 2945, 2220, 1630, 1552; 1H NMR
(400 MHz, DMSO-d6) d 7.40-7.44 (m, 3H, Ar), 7.49-7.65
(m, 6H, Ar), 7.75 (broad, 2H, NH2).
2-Amino-4-(4-methoxyphenyl)-6-(phenylthio)pyridine-3,5-
dicarbonitrile (4c)
Stepwise one-pot general procedure for the preparation of
2-amino-4-aryl-3,5-dicarbonitrile-6-(phenylthio)pyridines in
the presence of base catalysts (4a-d)
m.p.: 236-238 oC (lit.24 238-240 ºC); IR (KBr) nmax / cm-1
3440, 3330, 3220, 2882, 2218, 1641; 1H NMR (400 MHz,
DMSO-d6) d 3.85 (s, 3H, OCH3), 7.05-7.10 (m, 3H, Ar),
7.49-7.71 (m, 6H, Ar), 7.80 (broad, 2H, NH2).
Method A (triethylamine as base catalyst)
To a stirred solution of aldehyde (1 mmol) in ethanol
(10 mL) was added a solution of malononitrile (1 mmol
in 2.0 mL of ethanol) and 3 drops of triethylamine. The
pale yellow solution was then refluxed for 60 min. To this
was then added thiophenol (1 mmol), and the mixture
was refluxed for a further 45 min. Another 1 mmol of
2-Amino-6-(phenylthio)-4-(p-tolyl)pyridine-3,5-dicarbonitrile
(4d)
m.p.: 206-209 oC (lit.24 208-211 ºC); IR (KBr) nmax / cm-1
1
3475, 3345, 3220, 2915, 2215, 1616, 1538; H NMR
(400 MHz, CDCl3) d 2.41 (s, 3H, CH3), 7.37-7.48 (m, 6H,
Ar), 7.55-7.65 (m, 3H, Ar), 7.87 (broad, 2H, NH2).

Vol. 27, No. 4, 2016
Alinaghizadeh et al.
665
General procedure for the preparation of 2-amino-4-aryl-6-
for C21H14N4OS: C, 68.09; H, 3.81; N, 15.12; found: C,
67.78; H, 3.65; N, 14.78.
mercaptopyridine-3,5-dicarbonitriles (5)
The compound 4 (2-amino-4-aryl-3,5-dicarbonitrile-
6-(phenylthio)pyridine) (3 mmol) was dissolved in
N,N-dimethylformamide (DMF) (10 mL) and to this was
added sodium sulfide (0.78 g, 10 mmol) and the mixture
stirred at 80 oC for 2 h. Upon cooling at ambient temperature,
1 mol L-1 HCl (20 mL) was added, resulting in the formation
of a yellow precipitate. The crude product was collected by
filtration. Compounds 5a-d have been reported previously.25
3,6-Diamino-2-benzoyl-4-(4-chlorophenyl)thieno[2,3-b]
pyridine-5-carbonitrile (6b)
o
Yield: 78%; m.p.: 252 C (decompose); IR (KBr)
n
max / cm-1 3485, 3307 and 3161 (2NH2), 2212 (CN), 1647
(C=O), 1589, 1568 (C=C); 1H NMR (400 MHz, DMSO-d6)
d 6.89 (broad, 2NH2), 7.49-7.74 (m, 9H, Ar); 13C NMR
(100 MHz, DMSO-d6) d 90.83, 99.57, 112.32, 115.35
(CN), 126.97, 129.47, 129.51, 129.94, 130.83, 130.87,
132.03, 135.16, 140.94, 151.17, 152.68, 159.12, 166.25,
187.67 (C=O); MS (ESI) 404 [M+] (52), 406 (34), 405 (61),
403 (100), 367 (2), 327 (4), 297 (4), 264 (32), 219 (4),
193 (5), 165 (6), 105 (62), 77 (94.5), 51 (20); anal. calcd.
for C21H13ClN4OS: C, 62.30; H, 3.24; N, 13.84; found: C,
61.98; H, 3.08; N, 13.49.
Preparation of 2-amino-6-(2-oxo-2-phenyl-ethylsulfanyl)-4-
phenyl-pyridine-3,5-dicarbonitrile (I)
A mixture of 2-amino-4-phenyl-6-(phenylthio)pyridine-
3,5-dicarbonitrile 5a (2 mmol), 2-bromoacetophenone
(2 mmol) and Et3N (0.1 mL) in ethanol (20 mL) was
stirred at ambient temperature. After 10 min a pale yellow
solid appeared. It was washed with diethyl ether to afford
intermediate I.Yield: 92%; m.p.: 276-278 oC (decompose);
IR (KBr) nmax / cm-1 3473, 3346 (NH2), 2209 (CN), 1678
(C=O), 1617, 1578 (C=C); 1H NMR (400 MHz, DMSO-d6)
d 5.01 (s, 2H, CH2), 7.90 (broad, NH2), 7.56-8.09 (m, 10H,
Ar); 13C NMR (100 MHz, DMSO-d6) d 40.60, 86.56, 93.84,
115.64, 115.85 (2CN), 128.90, 128.93, 129.21, 129.32,
130.89, 134.20, 134.35, 136.05, 158.84, 159.97, 166.38,
193.24 (C=O).
3,6-Diamino-2-benzoyl-4-(4-methoxyphenyl)thieno[2,3-b]
pyridine-5-carbonitrile (6c)
o
Yield: 84%; m.p.: 242-245 C; IR (KBr) nmax / cm-1
3480, 3302 and 3147 (2NH2), 2212 (CN), 1637 (C=O),
1590, 1573 (C=C); 1H NMR (400 MHz, DMSO-d6) d 3.53
(s, 3H, OCH3), 7.63 (broad, 2NH2), 7.49-7.67 (m, 9H, Ar);
13C NMR (100 MHz, DMSO-d6) d 55.31 (OCH3), 91.12,
99.33, 112.57, 114.77, 115.62 (CN), 124.98, 126.97,
128.45, 129.45, 130.81, 141.01, 151.40, 153.89, 159.30,
160.42, 166.24, 187.53 (C=O); MS (ESI) 400 [M+] (57.5),
401 (16.5), 399 (75), 355 (6), 295 (5), 251 (13), 200
(4), 165 (4), 105 (93), 77 (100), 51 (17); anal. calcd. for
C22H16N4O2S: C, 65.98; H, 4.03; N, 13.99; found: C, 65.67;
H, 3.88; N, 13.61.
General procedure for the preparation of 3,6-diamino-2-
benzoyl-4-aryl-thieno[2,3-b]pyridine-5-carbonitrile (6a-f)
A mixture of 2-amino-4-aryl-6-mercaptopyridine-
3,5-dicarbonitriles 5a-d (2 mmol), 2-bromoacetophenone
(2 mmol) and NaOEt in absolute ethanol (20 mL) was
stirred at ambient temperature for 10 min. After this time
a yellow solid appeared which was collected by filtration.
The crude product was purified by ethanol.
3,6-Diamino-2-benzoyl-4-(4-methylphenyl)thieno[2,3-b]
pyridine-5-carbonitrile (6d)
o
Yield: 82%; m.p.: 308 C (decompose); IR (KBr)
n
max / cm-1 3457, 3356 and 3264 (2NH2), 2213 (CN), 1611
(C=O), 1592, 1557 (C=C); 1H NMR (400 MHz, DMSO-d6)
d 2.46 (s, 3H, CH3), 6.77 (broad, 2NH2), 7.20 (d, 2H,
3JHH 8 Hz, Hortho (4-CH3OC6H4)), 7.49-7.63 (m, 5H, Ar),
3,6-Diamino-2-benzoyl-4-phenylthieno[2,3-b]pyridine-5-
carbonitrile (6a)
7.67 (d, 2H, JHH 8 Hz, Hmeta (4-CH3OC6H4)); 13C NMR
3
o
Yield: 80%; m.p.: 323 C (decompose); IR (KBr)
(100 MHz, DMSO-d6) d 21.02, 90.88, 99.47, 112.44,
115.47 (CN), 126.97, 127.71, 128.45, 129.95, 130.29,
130.83, 139.87, 140.97, 151.22, 154.00, 159.21, 166.18,
187.58 (C=O); MS (ESI) 384 [M+] (63.7), 385 (16.5), 383
(80), 307 (2), 278 (7), 264 (21), 193 (2.4), 179 (2.4), 140
(5.5), 105 (90), 91 (2.4), 77 (100), 51 (18).
n
max / cm-1 3463, 3363 (2NH2), 2216 (CN), 1611 (C=O),
1590, 1557 (C=C); 1H NMR (400 MHz, DMSO-d6) d 6.58,
6.93 (broad, 2NH2), 7.49-7.67 (m, 10H, Ar); 13C NMR
(100 MHz, DMSO-d6) d 90.77, 99.54, 112.38, 115.37
(CN), 128.97, 127.79, 128.47, 129.39, 130.28, 130.88,
133.25, 140.85, 157.12, 153.84, 158.17, 168.17, 187.83
(C=O); MS (ESI) 370 [M+] (35.4), 371 (10), 369 (46.4),
293 (2.4), 264 (14), 221 (5.5), 204 (6.7), 178 (4.7), 140
(8), 105 (78.7), 89 (4), 77 (100), 51 (26.8); anal. calcd.
Preparation of methyl-3,6-diamino-4-(4-chlorophenyl)-5-
cyanothieno[2,3-b]pyridine-2-carboxylate (6e)
A mixture of 2-amino-4-(4-chlorophenyl)-6-

666
Cascade Synthesis of Thieno[2,3-b]pyridines
J. Braz. Chem. Soc.
mercaptopyridine-3,5-dicarbonitrile 5b (2 mmol), methyl
2-bromoacetate (2 mmol) and NaOMe in absolute methanol
(20 mL) was stirred at ambient temperature. After 7 min a
yellow solid appeared. Yield: 80%; m.p.: 285-287 oC; IR
(KBr) nmax / cm-1 3486 and 3367 (2NH2), 2212 (CN), 1668
(C=O), 1618, 1597 (C=C); 1H NMR (400 MHz, DMSO-d6)
d 3.71 (s, 3H, OCH3), 7.52 (broad, 2NH2), 7.56-7.59 (m, 2H,
Ar), 7.68-7.72 (m, 2H,Ar); 13C NMR (100 MHz, DMSO-d6)
d 51.20 (OCH3), 91.93, 98.77, 113.42, 115.15 (CN), 129.27,
129.74, 130.08, 139.54, 150.28, 153.44, 158.14, 165.22,
174.23 (C=O); MS (ESI) 358 [M+] (37.8), 341 (100), 325
(30.7), 297 (23.6), 264 (8.7), 171 (4.8), 163 (6.3), 149 (5.5);
anal. calcd. for C16H11ClN4O2S: C, 53.56; H, 3.09; N, 15.61;
found: C, 53.31; H, 2.85; N, 15.29.
2-amino-4-aryl-6-mercaptopyridine-3,5-dicarbonitriles 5.
The final step was the reaction of the free thiol 5 with
α-halogen compounds in the presence of base catalyst
such as sodium alkoxide at room temperature which led
to preparation of thieno[2,3-b]pyridine derivatives (6a-f)
(Scheme 1). Reaction time for the synthesis of compounds 6
from compounds 5 is very short at room temperature, about
5-10 min.
A few multicomponent reactions (MCRs) are also
reported for synthesis of diverse substituted 2-amino-3,5-
dicarbonitrile-6-thiopyridines, such as three-component
condensations of aldehyde, malononitrile and thiol using
various base catalysts.24,27 When the one-pot procedures
such as using high surface area MgO or nanocrystalline
magnesium oxide were applied to preparation of 2-amino-
3,5-dicarbonitrile-6-thiopyridines as starting materials, the
yields were significantly lower than 60% (Table 1).
For this reason, a simple variation on these one-pot
procedures was employed for the improvement of the
reaction conditions. These reactions were carried out
by a stepwise addition of reagents which were followed
by preparation of products 6 with improvement of the
reaction yields up to 75%. The reported mechanism of
pyridine dicarbonitrile formation involves the attack of
a malononitrile anion upon the aromatic aldehyde which
was activated by MgO followed by elimination of water
to form aryllidenemalononitriles. Subsequent addition of
a second malononitrile anion along with addition of thiol
to nitrile group of malononitrile provides penultimate
intermediate II, which is followed by loss of molecular
hydrogen to furnish the product (Scheme 2).
The reaction of 2-amino-4-aryl-6-(phenylthio)pyridine-
3,5-dicarbonitriles 4 in the presence of potassium hydroxide
in dimethylformamide is a convenient method to obtain
2-amino-4-aryl-6-mercaptopyridine-3,5-dicarbonitrile
derivatives 5. Treatment of these compounds with
α-halogen compounds in the presence of base catalyst
such as sodium alkoxide can undergo the intramolecular
cyclization which formed thieno[2,3-b]pyridines 6 without
preliminary isolation. The 2-amino-6-(2-oxo-2-phenyl-
ethylsulfanyl)-4-phenyl-pyridine-3,5-dicarbonitrile I
has been isolated from reaction solution and then the
compound I was heated under an alkaline condition to
produce compound 6a. A plausible mechanism for the
formation of compounds 6 is shown in Scheme 3.
Preparation of 3,6-diamino-4-(4-methoxyphenyl)-2-(4-
nitrophenyl)thieno[2,3-b]pyridine-5-carbonitrile (6f)
A mixture of 2-amino-4-(4-methoxyphenyl)-6-
mercaptopyridine-3,5-dicarbonitrile 5c (2 mmol),
4-nitrobenzyl chloride (2 mmol) and NaOEt in absolute
ethanol (20 mL) was stirred at ambient temperature. After
10 min a red solid appeared.Yield: 74%; m.p.: 280-282 oC;
IR (KBr) nmax / cm-1 3470, 3426 and 3349 (2NH2), 2203
(CN), 1621, 1591 (C=C); 1H NMR (400 MHz, DMSO-d6)
d 3.87 (s, 3H, OCH3), 7.36 (s, NH2), 7.36-7.74 (m, 6H,
Ar), 8.20 (d, 2H, 3JHH 6 Hz, Hortho (4-NO2C6H4)); 13C NMR
(100 MHz, DMSO-d6) d 54.22 (OCH3), 90.87, 99.42,
111.54, 115.24 (CN), 117.32, 126.97, 128.21, 129.02,
130.47, 135.24, 140.23, 152.42, 153.57, 158.26, 160.85,
167.21; MS (ESI) 417 [M+] (74), 418 (10), 371 (7), 327
(21), 295 (6), 239 (7.5), 178 (18), 165 (14), 105 (56.7),
91 (22), 77 (100), 66 (24), 55 (90); anal. calcd. for
C21H15N5O3S: C, 60.42; H, 3.62; N, 16.78; found: C, 60.47;
H, 3.34; N, 16.41.
Results and Discussion
In our preliminary studies, the 2-amino-4-aryl-
6-(phenylthio)pyridine-3,5-dicarbonitrile derivatives
4a-d have been prepared by an efficient stepwise one-
pot three multicomponent reaction of aldehydes 1a-d,
malononitrile 2, and benzenethiol 3 in the presence
of base catalysts such as triethylamine, HSA-MgO or
nanocrystalline magnesium oxide in moderate to good
yields. Pyridine formation occurred according to a
preparation by Kambe et al.26 to give the phenyl protected
sulfides 4 in the 6-position of the ring. To obtain the free
thiol in the 6-position of the pyridine ring 5, the 2-amino-
4-aryl-6-(phenylthio)pyridine-3,5-dicarbonitriles 4 along
with 3.3 eq of sodium sulfide in DMF were heated at
Conclusions
In summary, we have developed a simple and efficient
method for the synthesis of thieno[2,3-b]pyridines via
reaction of α-halogen compounds with 2-amino-4-aryl-
o
80 C for 2-3 h which resulted in quantitative yields of

Vol. 27, No. 4, 2016
Alinaghizadeh et al.
667
Scheme 1. Synthetic route to the synthesis of compounds 6.
Table 1. Synthesis of compounds 4a-d in the presence of base catalysts
Triethylamine
HAS-MgOa
Yield / %
Nanosized MgO
Compound
Ar
time / h
Yield / %
time / h
time / h
Yield / %
4a
4b
4c
4d
C6H5
5
3
7
7
44
45
50
40
4
3
5
5
65
49
58
54
3
2
5
4
75
65
70
69
4-ClC6H4
4-CH3OC6H4
4-CH3C6H4
aHigh surface area MgO.
Scheme 2. Synthesis of compound 4 in the presence of MgO as catalyst.

668
Cascade Synthesis of Thieno[2,3-b]pyridines
J. Braz. Chem. Soc.
Ar
Ar
Ar
N
N
NC
CN
S
NC
CN
SH
NC
NaOR', R'OH
NaOR'
R'OH
+
X
R
H2N
N
H2N
N
R
H2N
S
R
5
I
Ar
Ar
NH2
NH
NC
NC
R
R
S
S
H2N
N
H2N
N
6
Scheme 3. Putative mechanism for the formation of compounds 6.
6-mercaptopyridine-3,5-dicarbonitriles which were
prepared from 2-amino-4-aryl-6-(phenylthio)pyridine-
3,5-dicarbonitrile derivatives. These compounds as
starting materials have been prepared on stepwise one-pot
three component reaction of malononitrile, aldehydes
and thiophenol by using high surface area MgO or
nanocrystalline magnesium oxide as base catalysts. The
advantage of these procedures reported here are: short
reaction times, high purity of products and easy workup.
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Supplementary Information
11. Dotsenko, V. V.; Krivokolysko, S. G.; Litvinov, V. P.; Chem.
Heterocycl. Compd. 2009, 45, 253.
1
Supplementary data (IR, H NMR, 13C NMR, and
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Submitted: August 27, 2015
Published online: November 13, 2015