4416
L. M. Sanchez et al. / Tetrahedron Letters 52 (2011) 4412–4416
19. Plaskon, A. S.; Ryabukhin, S. V.; Volochnyuk, D. M.; Gavrilenko, K. S.; Shivanyuk,
A. N.; Tolmachev, A. A. J. Org. Chem. 2008, 73, 6010–6013.
of 1:1:1, respectively. The solvent-free reactions were completed
within 15–30 min at 80 °C. In all cases, only products with struc-
ture 3 were obtained with excellent yields (60–99%) and selectiv-
ity, and also free of secondary products (Table 1, entries 7–13).23
Recycling of the catalyst (Table 1, entry 7b)23 was checked in
two consecutive batches after the first one; the catalysts showed
almost constant activity, 99%, 98% and 98%, respectively. On the
other hand, the experiments performed using acetonitrile as reac-
tion solvent showed a decrease of the reaction yields (Table 1, en-
try 7c, 89%).23 All the 6-substituted-3-formylchromones studied
showed no stereoelectronic effects on the reaction yields.
In summary, we have described the synthesis of polysubstituted
pyridines from commercial starting materials and under green
reaction conditions.29 This procedure makes the current method
feasible and an attractive protocol for the generation of novel het-
erocycles. The use of HPA catalysts provides very good yields, also
leading to an easy separation and recovery of the catalysts for fur-
ther use. We continue to study the procedure to synthesize Han-
tzsch products from 3-formylchromones as aldehydes. We expect
to report the results of these investigations in due course.
20. Ibrahim, M. A.; Ali, T. E.; Alnamer, Y. A.; Gabr, Y. A. ARKIVOC 2010, i, 98–135.
21. Sosnovskikh, V. Ya.; Usachev, B. I. Mendeleev Commun. 2000, 240.
22. Sosnovskikh, V. Ya.; Usachev, B. I. Russ. Chem. Bull. 2001, 50, 1426–1429.
23. General Procedures. All the yields were calculated from crystallized products.
All the products were identified by comparison of analytical data, melting
point (mp), thin layer chromatography (TLC) and nuclear magnetic resonance
(NMR) data with those reported. The starting materials are commercial
products. 2-Acethyl-3(-chromonyl)-acylic acid methyl ester 4 was prepared
using a literature procedure25, and 3-amino-2-butenoic acid methyl ester 5 by
warming a 1:5 mixture of methyl acetoacetate and ammonium acetate at 80 °C
for 120 min. Melting points of the compounds were determined in open
capillary tubes and are uncorrected. 13C NMR and 1H NMR spectra were
recorded at room temperature on Bruker AC 400 using tetramethylsilane (TMS)
as internal standard.
Catalyst Preparation. The Dawson acid (H6P2W18O62Á24H2O) was prepared by
the Drechsel method from an
a
/b K6P2W18O62Á10H2O isomer mixture.26 This
Dawson-type salt was prepared according to the technique reported by Lyon
et al.27,28 General Procedures for the preparation of substituted pyridines. The
solid catalyst (1 mmol %) was added to
a mixture of 3-formylchromones
(1 mmol), alkyl or aryl acetylacetates (1 mmol) and ammonium acetate
(1 mmol). The mixture was stirred at 80 °C for the indicated time (Table 1).
The progress of the reaction was monitored by TLC. After completion of the
reaction, hot toluene was added (2 Â 2.5 mL) and the catalyst was filtered. The
extracts were combined; their solvents were evaporated and then
concentrated in vacuum. All the solid crude products were recrystallized.
24. Shen, L.; Cao, S.; Wu, J.; Zhang, J.; Li, H.; Liu, N.; Qian, X. Green Chem. 2009, 11,
1414–1420.
Acknowledgements
25. Haas, G.; Stanton, J. L.; Von Sprecher, A.; Wenk, P. J. Heterocycl. Chem. 1981, 18,
607–612.
26. Baronetti, G.; Briand, L.; Sedran, U.; Thomas, H. Appl. Catal. A:Gen 1998, 172(2),
265–272.
27. Lyon, D. K.; Miller, W. K.; Novet, T.; Domaille, P. J.; Evitt, E.; Johnson, D. C.;
Finke, R. G. J. Am. Chem. Soc. 1991, 113(19), 7209–7221.
28. Recycling of catalyst. After reaction, the catalyst was washed with toluene
(2 Â 2 mL), dried under vacuum, and reused in the next catalytic cycle.
29. Representative compounds synthesized. Compound entry 1, Product 2. Yield 30%,
mp: 250–252 °C (ethanol) (lit mp: 258 °C30), 13C NMR (100 MHz, CDCl3) d 18.5,
33.6, 51.1, 98.2, 118.7, 124.6, 125.5, 125.6, 126.5, 134.1, 147.2, 154.7, 155.8,
167.8, 176.8.1H NMR (400 MHz, CDCl3) d 2.20 (s, 6H), 3.55 (s, 6H), 4.85 (s, 1H),
7.44 (t, J = 8 Hz, 1H), 7.57 (d, J = 8 Hz, 1H), 7.75 (t, J = 8 Hz, 1H), 7.95 (s, 1H),
8.03 (d, J = 8 Hz, 1H), 8.97 (s, 1H).
We thank CONICET, Agencia Nacional de Promoción Científica y
Tecnológica (Argentina), and Universidad Nacional de La Plata for
financial support. JLJ acknowledges the DAAD (Bonn, Germany)
for the grant provided for the purchase of rotary evaporator equip-
ment. AGS, GPR, GTB, and HJT are members of CONICET.
References and notes
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Compound entry 2, Product 2. Yield 25%, mp: 258–260 °C (ethanol) (lit. mp:
260 °C30), 13C NMR (100 MHz, CDCl3) d 18.6, 20.9, 33.4, 51.0, 98.5, 118.4, 124.2,
124.8, 126.6, 135.0, 135.1, 147.1, 154.1, 154.5, 167.9, 175.7.1H NMR (400 MHz,
CDCl3) d 2.20 (s, 6H), 2.39 (s, 3H), 3.55 (s, 6H), 4.86 (s, 1H), 7.46 (d, J = 8 Hz, 1H),
7.55 (dd, J = 8 and 2 Hz, 1H), 7.79 (d, J = 2 Hz, 1H), 7.89 (s, 1H), 8.95 (s, 1H).
Compound entry 8. Yield 93%, mp: 109–111 °C (hexanes) (lit. no data), 13C
NMR (100 MHz, CDCl3) d 20.7, 24.8, 52.8, 118.5, 118.7, 125.4, 128.5, 131.4,
132.3, 138.4, 139.5, 150.8, 161.1, 163.0, 165.8, 198.0. 1H NMR (400 MHz, CDCl3)
d 2.29 (s, 3H), 3.00 (s, 3H), 3.98 (s, 3H), 7.03 (d, J = 8 Hz, 1H), 7.28–7.30 (m, 1H),
7.40 (dd, J = 8 and 2 Hz, 1H), 8.58 (d, J = 2 Hz, 1H), 8.92 (d, J = 2 Hz, 1H), 11.65
(s, 1H). Anal. Calcd. for C16H15NO4: C, 67.36; H, 5.30; N, 4.91; O, 22.43. Found:
C, 67.40; H, 5.31; N, 4.90.
Compound entry 9. Yield 98%, mp: 87–89 °C (hexanes) (lit. no data), 13C NMR
(100 MHz,CDCl3) d 52.4, 119.4, 120.5, 124.1, 125.7, 130.8, 131.5, 137.1, 139.5,
150.7, 24,8 161.7, 163.6, 165.6. 1H NMR (400 MHz, CDCl3) d 3.01 (s, 3H), 3.98 (s,
3H), 7.10 (d, J = 9 Hz, 1H), 7.48–7.56 (m, 2H), 8.58 (d, J = 2 Hz, 1H),8.93 (d,
J = 2 Hz, 1H), 11.65 (s, 1H). Anal. Calcd. for C15H12ClNO4: C, 58.93; H, 3.96; Cl,
11.60; N, 4.58; O, 20.93. Found: C, 58.90; H, 3.99; N, 4.90.
Compound entry 13. Yield 60%, mp: 88–90 °C (hexanes) (lit no data), 13C NMR
(50 MHz, CDCl3) d 13.89, 62.20, 119.02,119.1, 119.50, 127.4, 128.55, 128.95,
129.72, 131.57, 133.12, 137.47, 138.78, 139.31, 151.02, 161.44, 163.39, 167.53,
198.34. 1H NMR (200 MHz, CDCl3) d 1.09 (t, J = 7 Hz, 3H), 4.20 (q, J = 7 Hz, 2H),
6.94 (dt, J = 8 and 2 Hz, 1H), 7.11(d, J = 8 Hz, 1H), 7.43–7.53 (m, 3H), 7.54–7.67
(m, 4H), 8.41 (d, J = 2 Hz, 1H), 9.04 (d, J = 2 Hz, 1H), 11.81 (s, 1H).
30. Satyanarayana Reddy, M.; Krupadanam, G. L. D.; Srimannarayarta, G. Indian J.
Chem. 1990, 29B, 978–979.
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