One-step synthesis of pyridine and 4H-pyran derivatives from bisarylidenecyclohexanone and malononitrile under microwave irradiation

Article abstract of DOI:10.1081/SCC-120015564

The 3-cyano-2-methoxylpyridine and 2-amino-3-cyano-4H-pyran derivatives were synthesized by one-step reaction of 2,6-bisarylidenecyclohexanone with malononitrile in sodium hydroxide/methanol or piperidine/ethanol under microwave irradiation with good yiel

Full text of DOI:10.1081/SCC-120015564

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One-Step Synthesis of Pyridine and 4 H -Pyran
Derivatives from Bisarylidenecyclohexanone and
Malononitrile Under Microwave Irradiation
Jian-Feng Zhou a b
a Department of Chemistry, Huaiyin Normal College, Huaiyin, P.R., China
b Department of Chemistry, Huaiyin Normal College, Huaiyin, P.R., China
Version of record first published: 29 Jun 2011
To cite this article: Jian-Feng Zhou (2003): One-Step Synthesis of Pyridine and 4 H -Pyran Derivatives from
Bisarylidenecyclohexanone and Malononitrile Under Microwave Irradiation, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 33:1, 99-103
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 1, pp. 99–103, 2003
One-Step Synthesis of Pyridine and 4H-Pyran
Derivatives from Bisarylidenecyclohexanone and
Malononitrile Under Microwave Irradiation
Jian-FengZhou*
Department ofChemistry, Huaiyin Normal College,
Huaiyin, P.R. China
ABSTRACT
The 3-cyano-2-methoxylpyridine and 2-amino-3-cyano-4H-pyran
derivatives were synthesized by one-step reaction of2,6-bisarylidene-
cyclohexanone with malononitrile in sodium hydroxide/methanol or
piperidine/ethanol under microwave irradiation with good yields.
The pyridine derivatives have shown important biological activities
as pharmaceuticals and potential agrochemicals such as herbicides.[1]
Some other pyridines possess fluorescent properties and have been
used in the liquid-crystal industry. 2-Amino-3-cyano-4H-pyrans possess
photochemical activity.[2] Polyfunctionalized 4H-pyrans are a common
[3]
structural unit in a number ofnatural products,
4H-pyrans ring can
*Correspondence: Jian-Feng Zhou, Department ofChemistry, Husiyin Normal
College, Huaiyin, P.R. China. E-mail: jfchow@sohu.com.
99
DOI: 10.1081/SCC-120015564
Copyright & 2003 by Marcel Dekker, Inc.
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100
Zhou
be transformed to pyridine systems related to pharmacologically
[4–6]
important calcium antagonists ofthe DHP type.
Since the reaction ofmalononitrile and a,b-unsaturated ketones in
presence ofammonium acetate to give pyridines was first reported by
Sakurai and Midorikawa,[7] the use ofmalononitrile and a,b-unsaturated
ketones for the synthesis of pyridine and pyran derivatives has attracted
much attention.[8–11] However, the most ofreaction times were long by
classical methods.
Recently, the wide applicability ofmicrowave irradiation in chemical
reaction enhancement is due to high reaction rate with formation of
cleaner products and the operation simplicity.[12,13] Continuing our inter-
est in the development ofefficient and simple procedures for the synthesis
ofheterocyclic compounds, we have recently reported that a facile synthe-
[14]
sis of4-arylpolyhydroquinolines under microwave irradiation.
In this
communication, we would like to report a facile synthesis of 3-cyano-
2-methoxylpyridine and 2-amino-3-cyano-4H-pyran derivatives by one-
step reaction of2,6-bisarylidenecyclohexanone with malononitrile in
sodium hydroxide/methanol or piperidine/ethanol under microwave
irradiation. The reactions were generally finished in 5–10 min with
70–92% yields and easy work-up.
The synthesis route is shown in Sch. 1.
The results obtained are shown in Table 1.
All oftitle compounds were established by their melting points, IR,
1H NMR and elemental analysis. The formation of compounds 4 was
assumed to proceed vis formation of an Michecal adduct intermediate
followed by cyclization according to Sch. 2.
Scheme 1.

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Pyridine and 4H-Pyran Derivatives
101
Table 1. Comparisons between classic heating and microwave irradiation syn-
thesis of 3a–c and 4a–c.
Classic heating
MWI
Entry
Ar
Time (h) Yield (%) (lit.) Time (min) Yield (%)a
3a
3b
3c
4a
4b
4c
C6H5
3
3
3
4
4
4
80 (10)
70 (10)
85 (10)
60a
5
8
10
5
9
5
92
91
88
70
71
71
4-ClC6H4
4-CH3OC6H4
C6H5
4-ClC6H4
3-O2NC6H4
67a
70a
aYields ofthe isolated products.
Scheme 2.
EXPERIMENTAL
Melting points were determined in open capillaries and uncorrected.
IR spectra were recorded on a Nicolet FT-IR 5DX instrument. 1H NMR
was measured on a Bruker 300 MHz spectrometer in CDCl3 with TMS as
internal standard. Elemental analyzer were determined using
Perkin–Elmer 240C elemental analyzer. The reactions were carried out
with a modified commercial microwave oven (Sanle WP650D 650 W)
under atmospheric pressure.

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102
Zhou
2,6-bisArylidenecyclohexanones were prepared according to litera-
ture procedure.[15]
General Procedure for 3-Cyano-2-methoxylpyridine and
2-Amino-3-cyano-4H-pyran Derivatives
Into an Erlenmeyer flask (25 mL) equipped with reflux condenser
were introduced the bisarylidnecyclohexanone 1 (1 mmol), malononitrile
2 (1 mmol), sodium hydroxide (0.05 g) and dry methanol (3 mL) or
piperidine (0.05 mL) and dry ethanol (3 mL). After irradiation with
microwaves for 5–10 min (monitored by TLC), the reaction mixture
was cooled. The precipitate was collected by suction filtration and
washed with cold ethanol. The crude product was recrystallized from
ethanol to give a pure sample.
3a: M.p. 212–214ꢀC (210ꢀC).[10] 3b: M.p. 206–208ꢀC (221–223ꢀC).[10]
3c: M.p. 221–223ꢀC (225ꢀC).[10] 4a: M.p. 228–230ꢀC. H NMR (CD3Cl)
1
ꢀ : 1.60–1.69 (m, 2H, CH2), 1.90–2.04 (m, 2H, CH2), 2.56–2.79 (m, 2H,
CH2), 3.99 (s, 1H, H-4), 4.54 (br, 2H, NH2), 7.25–7.63 (m, 11H, 2 Â C6H5
and ylidene CH). IR (KBr, cmÀ1): 3410, 3310, 3020, 2850, 2200, 1670,
1620, 1600, 1410, 1125. Anal. Calcd. for C23H20N2O (%): C, 81.18;
H, 5.88; N, 8.24. Found: C, 80.77; H, 5.85; N, 8.18. 4b: M.p.
217–219ꢀC. H NMR (CD3Cl) ꢀ : 1.62–1.69 (m, 2H, CH2), 1.83–2.06 (m,
1
2H, CH2), 2.52–2.72 (m, 2H, CH2), 3.97 (s, 1H, H-4), 4.89 (s, 2H, NH2),
7.18–7.63 (m, 9H, 2 Â C6H4 and ylidene CH). IR (KBr, cmÀ1): 3450, 3300,
2800, 2210, 1690, 1585, 1490, 1405, 1180, 1090. Anal. Calcd. for
C23H18Cl2N2O (%): C, 67.48; H, 4.40; N, 6.84. Found: C, 67.10; H,
4.36; N, 6.80. 4c: M.p. 238–240ꢀC. H NMR (CD3Cl) ꢀ : 1.61–1.70 (m,
1
2H, CH2), 1.88–2.10 (m, 2H, CH2), 2.55–2.76 (m, 2H, CH2), 4.02 (s,
1H, H-4), 4.76 (br, s, 2H, NH2), 7.52–8.08 (m, 11H, 2 Â C7H6 and ylidene
CH). IR (KBr, cmÀ1); 3440, 3320, 3090, 2820, 2200, 1680, 1610, 1520,
1420, 1350, 1130. Anal. Calcd. for C23H18N4O5 (%): C, 64.19; H, 4.19; N,
13.02. Found: C, 63.86; H, 4.16; N, 12.94.
REFERENCES
1. Temple, C.; Rener, G.A., Jr.; Raud, W.R.; Noker, P.E. J. Med.
Chem. 1992, 35, 3686.
2. Ocallaghan, C.N.; Mcmurry, T.B.H. J. Chem. Res. (S) 1999, 457.

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Pyridine and 4H-Pyran Derivatives
103
3. Martin, L.N.; Quinteiro, M.; Seoane, C.; Soto, J.L. Liebigs. Ann.
Chem. 1990, 101.
4. Martin, N.; Martin, G.; Secoane, A.C.; Marco, J.L.; Albert, A.;
Cano, F.H. Liebigs. Ann. Chem. 1993, 801.
5. Marco, J.L.; Martin, N.; Grau, A.M.; Seoane, C.; Albert, A.; Cano,
F.H. Tetrahedron 1994, 50, 3509.
6. Albert, D.A.; Cano, F.H.; Martin, N.; Ramos, A.; Rodriguez, M.;
Segura, J.L.; Seoane, C. J. Chem. Soc. Perkin Trans. (I) 1997, 3401.
7. Sakurai, A.; Midorikawa, N. Bull. Chem. Soc. Japn. 1968, 41, 430.
8. Al-Arab, M.M. J. Heterocyclic Chem. 1989, 26, 1665.
9. Al-Arab, M.M.; Atfeh, F.S.; Mayoof, S.M. J. Heterocyclic Chem.
1998, 35, 1473.
10. Elgemeie, G.H.; Abdelaal, F.A.; Abou, K. J. Chem. Res. (S)
1991, 128.
11. Tyndall, T.; Nakib, A.; Meegan, M.J. Tetrahedron Lett. 1988,
29, 2703.
12. Caddick, S. Tetrahedron 1995, 51, 10403.
13. Galema, S.A. Chem. Soc. Rev. 1997, 26, 233.
14. Tu, S.J.; Zhou, J.F.; Deng, X.; Cai, P.J.; Wang, H.; Feng, J.C. Chin.
J. Org. Chem. 2001, 21, 313.
15. Zhou, J.F.; Xu, J.M.; Wei, H.; Zhang, L.L. Chin. J. Org. Chem.
2001, 21, 322.
Received in Japan August 7, 2001

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