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Synlett 2015; 26(16): 2306-2312
DOI: 10.1055/s-0034-1378823
DOI: 10.1055/s-0034-1378823
letter
One-Pot, Three-Component Synthesis of 1,8-Naphthyridine Derivatives from Heterocyclic Ketene Aminals, Malononitrile Dimer, and Aryl Aldehydes
Weitere Informationen
Publikationsverlauf
Received: 19. Mai 2015
Accepted after revision: 24. Juni 2015
Publikationsdatum:
10. August 2015 (online)
![](https://www.thieme-connect.de/media/synlett/201516/lookinside/thumbnails/st-2015-w0380-l_10-1055_s-0034-1378823-1.jpg)
Abstract
An efficient and versatile method was developed for the access of multisubstituted 1,8-naphthyridine derivatives through a one-pot, three-component protocol from heterocyclic ketene animals, malononitrile dimer, and aryl aldehydes in high yields. The 1,8-naphthyridines were formed via Knoevenagel condensation, aza–ene reaction, imine–enamine tautomerization, and intramolecular cyclization.
Key words
one-pot - multicomponent reactions - heterocyclic ketene aminals - 1,8-naphthyridine - co-catalystsSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0034-1378823.
- Supporting Information
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References and Notes
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- 17 Typical Procedure for the Synthesis of 4 Heterocyclic ketene aminals (1 mmol), aryl aldehydes (1.2 mmol), malononitrile dimer (1.5 mmol), AcOH (1 mmol), piperidine (1 mmol), and EtOH (10 mL) were stirred at refluxing for 1 h. After completion of the reaction (confirmed by TLC), the reaction mixture was filtered to afford the crude product, which was further washed with 95% EtOH to give pure product 4. The structures of the products were well characterized by NMR and HRMS studies. The characterization data of representative compounds 4a and 4u are given below. Compound 4a: light yellow solid; mp 300.9–302.0 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 9.33 (s, 1 H), 7.37 (d, J = 7.6 Hz, 2 H), 7.25 (d, J = 7.6 Hz, 2 H), 6.41 (s, 2 H), 6.24 (s, 2 H), 5.40 (s, 1 H), 4.08 (t, 2 H), 3.89–3.73 (m, 2 H) ppm. 13C NMR (100 MHz, DMSO-d 6): δ = 159.8, 154.2, 152.4, 149.1, 142.5, 130.9, 129.7, 127.6, 116.6, 106.6, 92.6, 69.9, 44.4, 43.3, 36.6 ppm. ESI-HRMS: m/z calcd for C17H14 35ClN7O2 [M – H]–: 382.0898; found: 382.0811; calcd for C17H14 37ClN7O2 [M – H]–: 384.0898; found: 384.0771 Compound 4u: light yellow solid; mp 281.4–282.0 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 11.49 (s, 1 H), 8.07 (d, J = 8.4 Hz, 2 H), 7.61 (d, J = 8.4 Hz, 2 H), 6.50 (d, 4 H), 5.66 (s, 1 H), 4.08 (m, 2 H), 3.51 (m, 2 H), 2.04 (m, 2 H) ppm. 13C NMR (100 MHz, DMSO-d 6): δ = 159.2, 154.8, 151.0, 150.6, 149.2, 146.1,128.9, 123.0, 116.3, 107.8, 91.9, 70.5 41.3, 38.7, 35.8, 19.5 ppm. ESI-HRMS: m/z calcd for C18H16N8O4 [M – H]–: 407.1295; found: 407.1216.