New cascade synthesis of pyrido[2′,3′:4,5]thieno- [2,3-b]pyridine derivatives

Full text of DOI:10.1007/s10593-009-0260-4

Chemistry of Heterocyclic Compounds, Vol. 45, No. 2, 2009
NEW CASCADE SYNTHESIS
OF PYRIDO[2',3':4,5]THIENO-
[2,3-b]PYRIDINE DERIVATIVES
V. V. Dotsenko1**, S. G. Krivokolysko1, and V. P. Litvinov2*
Keywords: acetone, dipyridothiophenes, malononitrile, 1,2,3,4-tetrahydropyridine-2(1H)-thiones,
multicomponent synthesis.
In previous work [1-5], we showed that the triple cyclocondensation of partially hydrogenated
3-cyano-2-pyridinethiolates with acetone and malononitrile leads to the formation of derivatives of
pyrido[2',3':4,5]thieno[2,3-b]pyridine. The mechanism of this unusual reaction involves the oxidation of the
starting thiolates by atmospheric oxygen to give bis(2-pyridyl) disulfides, subsequent nucleophilic cleavage of
the S–S bond by the isopropylidenemalononitrile anion, and cascade heterocyclization [6]. As a rule, the
partially hydrogenated pyridine system remains unchanged during the reaction although, in some cases, the
formation of oxidation products was noted [4, 5]. In a continuation of our investigation, we decided to study the
behavior of readily available 5-acetyl-4-aryl-3-cyano-6-methyl-3,4-dihydropyridine-2(1H)-thiones 1a and 1b
[7-11] under conditions for cyclocondensation with acetone and malononitrile.
NH2
O
Ar
O
Ar
N
N
N
N
B, EtOH, to
Me
Me
+
Me
S
Me
N
H
S
Me
N
N
Me
Me
2a,b
1a,b
O
В = N-methylmorpholine; a Ar = 2-ClC6H4; b Ar = 4-O2NC6H4
We have found that dipyridothiophene derivatives are also formed during this reaction but, in contrast to
other tetrahydropyridine derivatives [1-3], cyclocondensation in this case is accompanied by aromatization of
the tetrahydropyridine ring. The structure of dipyridothiophenes 2a and 2b was supported by the spectroscopic
data. We should also note that these products have a highly pronounced blue-green UV photoluminescence.
_______
* Deceased.
** To whom correspondence should be addressed, e-mail: ksg@lep.lg.ua, Victor_Dotsenko@bigmir.net
1Chimex Laboratory, Vladimir Dal' East-Ukrainian National University, Lugansk 91034, Ukraine.
2 N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913, Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 311-313, February, 2009. Original
article submitted October 14, 2008.
0009-3122/09/4502-0253©2009 Springer Science+Business Media, Inc.
253

1
The H NMR spectra were taken on a Varian Gemini 200 spectrometer at 200 MHz in DMSO-d6 with
TMS as the internal standard. The IR spectra were taken on an IKS-29 spectrometer for vaseline mulls.
Dipyridothiophenes 2a,b. N-Methylmorpholine (1 ml, 9 mmol) was added to a mixture of
corresponding thiolactam 1a,b (8 mmol), malononitrile (0.8 g, 12 mmol), and acetone (5.9 ml, 80 mmol) in
ethanol (30 ml), heated at reflux for 15 h with stirring, and left for 72 h at ~20°C. The crystalline product was
separated and recrystallized from the indicated solvent.
8-Acetyl-2-amino-9-(2-chlorophenyl)-4,7-
dimethylpyrido[2',3':4,5]thieno[2,3-b]pyridine-3-carbonitrile- (2a) was obtained in 36% yield as yellow
crystals; mp 340-342°C (dec., DMF). IR spectrum, ν, cm-1: 1695 (C=O); 2213 (C≡N); 3345, 3450 (NH2).
1H NMR spectrum, δ, ppm: 7.56-7.19 (4H, m, Ar); 5.94 (2H, br. s, NH2); 2.62 and 2.61 (3H each, both s, 4-CH3
and 7-CH3); 2.14 (3H, s, C(O)CH3). Found, %: C 61.60; H 3.74; N 13.87. C21H15ClN4OS. Calculated, %:
C 61.99; H 3.72; N 13.77.
8-Acetyl-2-amino-4,7-dimethyl-9-(4-nitrophenyl)pyrido[2',3':4,5]thieno[2,3-b]pyridine-8-carbo-
nitrile (2b) was obtained in 20% yield; mp 310-313°C (dec., 4:1 AcOH–DMF). IR spectrum, ν, cm-1: 1698
1
3
(C=O); 2218 (C≡N); 3360, 3450 (NH2). H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 8.26 (2H, d, J = 8.6,
H-3, H-5 Ar); 7.48 (2H, d, 3J = 8.6, H-2, H-6 Ar); 6.28 (2H, br. s, NH2); 2.59 and 2.57 (3H each, both s, 4-CH3
and 7-CH3); 2.09 (3H, s, C(O)CH3). Found, %: C 60.04; H 3.63; N 16.83. C21H15N5O3S. Calculated, %: C 60.42;
H 3.62; N 16.76.
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