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

Chunmei Li; Furen Zhang; Zhenlu Shen

doi:10.1055/a-1479-4420

Synlett, Table of Contents

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

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

Chunmei Li

^aSchool 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

^bCollege of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310032, P. R. of China

,

Furen Zhang∗

^aSchool 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 ∗

^bCollege of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310032, P. R. of China

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Abstract

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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

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References

References and Notes

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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

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