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Synlett 2021; 32(11): 1117-1122
DOI: 10.1055/a-1479-4420
letter

An Efficient Strategy for the Synthesis of Naphtho[2,3-b][1,6]naphthyridines Promoted by Acetic Acid

Chunmei Li
a   School of Chemistry and Chemical Engineering, Zhejiang Key Laboratory of Alternative Technologies for Fine Chemicals Process, Shaoxing University, Shaoxing, Zhejiang Province 312000, P. R. of China
b   College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310032, P. R. of China
,
Furen Zhang∗
a   School of Chemistry and Chemical Engineering, Zhejiang Key Laboratory of Alternative Technologies for Fine Chemicals Process, Shaoxing University, Shaoxing, Zhejiang Province 312000, P. R. of China
,
Zhenlu Shen  ∗
b   College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310032, P. R. of China
› InstitutsangabenWe are grateful for financial support from the National Natural Science Foundation of China (21776260) and the Key Research and Development Project of Zhejiang Province (2021C01079) for this research work.
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Abstract

A three-component domino reaction for the synthesis of naphtho[2,3-b][1,6]naphthyridine derivatives has been established. Such strategy exhibited excellent substrate scope including various enaminones and aldehydes that afforded a series of multifunctionalized naphtho[2,3-b][1,6]naphthyridine derivatives with 70–86% yields. The advantages of bond-forming efficiency, accessibility of starting materials, and water as sole byproducts provide invaluable access to biological 1,6-naphthyridines.

Key words

aminopyridinone - 2-hydroxynaphthalene-1,4-dione - naphtho[2,3-b][1,6]naphthyridines - acetic acid - synthesis

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1479-4420.
  • Supporting Information


Publikationsverlauf

Eingereicht: 05. März 2021

Angenommen nach Revision: 10. April 2021

Accepted Manuscript online:
10. April 2021

Artikel online veröffentlicht:
22. April 2021

© 2021. Thieme. All rights reserved

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  • 14 General Procedure for the Synthesis of 5,12-Dihydronaphtho[2,3-b][1,6]naphthyridine-1,6,11(2H)-triones 4a–vA mixture of aminopyridinone 1 (0.5 mmol), aldehyde 2 (0.5 mmol), 2-hydroxynaphthalene-1,4-dione 3 (0.5 mmol), and HOAc (3.0 mL) was stirred and heated at 100 °C for about 4 h. After completion of the reaction as indicated by TLC, the reaction mixture was diluted with cold water (10 mL). The crude products were filtered by Büchner funnel and further purified by recrystallization from hot 95% ethanol to afford the desired pure products 4 as red to red brown solid.3-Methyl-2,5-diphenyl-12-(p-tolyl)-5,12-dihydronaphtho[2,3-b][1,6]naphthyridine-1,6,11(2H)-trione (4a)Red brown solid; mp 290–292 °C. 1H NMR (400 MHz, CDCl3, TMS): δ = 8.03 (d, J = 8.0, 1.2 Hz, 1 H, ArH), 7.82 (d, J = 7.6, 0.8 Hz, 1 H, ArH), 7.63–7.66 (m, 5 H, ArH), 7.42–7.49 (m, 4 H, ArH), 7.51–7.53 (m, 3 H, ArH), 7.19 (d, J = 7.2 Hz, 1 H, ArH), 7.12 (d, J = 8.0 Hz, 2 H, ArH), 7.04–7.08 (m, 1 H, ArH), 5.77 (s, 1 H, CH), 5.58 (s, 1 H, CH), 2.30 (s, 3 H, CH3), 1.82 (s, 3 H, CH3). 13C NMR (100 MHz, CDCl3, TMS): δ = 187.8, 182.1, 165.0, 161.6, 153.6, 145.5, 139.7, 138.1, 135.3, 134.2, 133.9, 133.1, 132.6, 131.2, 129.7, 129.6, 129.5, 129.1, 128.9, 128.3, 127.8, 126.6, 126.4, 124.6, 123.1, 99.5, 35.5, 21.6, 21.0. HRMS (ESI): m/z calcd for C36H27N2O3 [M + H]+: 535.2022; found: 535.2021
  • 15 General Procedure for the Synthesis of 12-Aryl-2,3,4,12-tetrahydro-1H-benzo[b]xanthene-1,6,11-triones 6Similarly, the mixture of 3-(arylamino)cyclohex-2-en-1-one 1 (0.5 mmol), aldehyde 2 (0.5 mmol), 2-hydroxynaphthalene-1,4-dione (3, 0.5 mmol), and HOAc (3.0 mL) was stirred and heated at 100 °C for about 4 h. After completion of the reaction as indicated by TLC, the reaction mixture was diluted with cold water (10 mL). The crude products were filtered by Büchner funnel and further purified by recrystallization from hot 95% ethanol to afford the desired pure products 6 as red to red-brown solid. 3,3-Dimethyl-12-phenyl-2,3,4,12-tetrahydro-1H-benzo[b]xanthene-1,6,11-trione (6a)Red solid; mp 232–234 °C. 1H NMR (400 MHz, CDCl3, TMS): δ = 8.14 (t, J = 5.6 Hz, 1 H, ArH), 8.00–8.02 (m, 1 H, ArH), 7.71–7.73 (m, 2 H, ArH), 7.41 (d, J = 7.6 Hz, 2 H, ArH), 7.28 (t, J = 7.6 Hz, 2 H, ArH), 7.18 (t, J = 7.2 Hz, 1 H, ArH), 5.16 (s, 1 H, CH), 2.65–2.78 (m, 2 H, CH2), 2.25–2.35 (m, 2 H, CH2), 1.17 (s, 3 H, CH3), 1.08 (s, 3 H, CH3). 13C NMR (100 MHz, CDCl3, TMS): δ = 196.2, 182.9, 178.0, 162.8, 149.0, 142.5, 134.5, 133.7, 131.6, 130.6, 128.7, 128.5, 127.2, 126.6, 126.5, 125.3, 114.3, 50.7, 40.7, 32.8, 32.4, 29.1, 27.4. HRMS (ESI): m/z calcd for C25H21O4 [M + H]+: 385.1440; found: 385.1449