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

letter

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

Authors

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

Abstract

All articles of this category

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

Full Text

References

References and Notes

1a Clark RD, Repke DP, Klipatrick AT, MacKinnon AC, Clauge RU, Spedding M. J. Med. Chem. 1989; 32: 2034
1b Clark RD, Repke DP, Berger J, Nelson JT, Kilpatrick AT, Brown CM, MacKinnon AC, Clauge RU, Spedding M. J. Med. Chem. 1991; 34: 705

2a Gross H, Goeger DE, Hills P, Mooberry SL, Ballantine DL, Murray TF, Valeriote FA, Gerwick WH. J. Nat. Prod. 2006; 69: 640
2b Zhang A, Ding C, Cheng C, Yao Q. J. Comb. Chem. 2007; 9: 916
2c Turner JA. J. Org. Chem. 1990; 55: 4744
2d Baldwin JJ, Mender K, Panticello GS. J. Org. Chem. 1978; 43: 4878
2e Jiang B, Fan W, Sun M.-Y, Ye Q, Wang S.-L, Tu S.-J, Li G. J. Org. Chem. 2014; 79: 5258

3a Egbertson MS. Curr. Top. Med. Chem. 2007; 7: 1251
3b Frasson I, Spanò V, S. Martino D, Nadai M, Doria F, Parrino B, Carbone A, Cascioferro SM, Diana P, Cirrincione G, Freccero M, Barraja P, Richter SN, Montalbano A. Eur. J. Med. Chem. 2019; 162: 176
3c Wang M.-S, Zhuo L.-S, Yang F.-P, Wang W.-J, Huang W, Yang G.-F. Eur. J. Med. Chem. 2020; 185: 111803
3d Chen D.-M, Liu J.-Y, Wei M, Wang B.-W, Chu R.-H, Chen D.-S. Heterocycl. Commun. 2019; 25: 15
3e Wortmann L, Lindenthal B, Muhn P, Walter A, Nubbemeyer R, Heldmann D, Sobek L, Morandi F, Schrey AK, Moosmayer D, Günther J, Kuhnke J, Koppitz M, Luecking U, Roehn U, Schäfer M, Nowak-Reppel K, Kuehne R, Weinmann H, Langer G. J. Med. Chem. 2019; 62: 10321
3f Wang P, Huang J, Kurtán T, Mándi A, Jia H, Cheng W, Lin W. Org. Lett. 2020; 22: 8215
3g Dong W, Yuan Y, Gao X, Hu B, Xie X, Zhang Z. ChemCatChem 2018; 10: 2878

4a Tsuruoka R, Yoshikawa N, Konishi T, Yamano M. J. Org. Chem. 2020; 85: 10797
4b Mohammadi H, Reza Shaterian H. Monatsh. Chem. 2019; 150: 327
4c Utkina NK, Denisenko VA. Nat. Prod. Commun. 2016; 11: 1259
4d Vennila KN, Selvakumar B, Satish V, Sunny D, Madhuri S, Elango KP. Med. Chem. Res. 2021; 30: 133

5 Litvinov VP. Adv. Heterocycl. Chem. 2006; 91: 189
6 Fiorito J, Vendome J, Saeed F, Staniszewski A, Zhang H, Yan S, Deng S.-X, Arancio O, Landry DW. J. Med. Chem. 2017; 60: 8858

7a Muthukrishnan I, Vachan BS, Karuppasamy M, Eniyaval A, Uma MaheswariC, Nagarajan S, Menéndez JC, Sridharan V. Org. Biomol. Chem. 2019; 17: 6872
7b Khakwani S, Aslam S, Shahi MN, Mussadiq S, Bernaedino AM. R, Khan MA. Asian J. Chem. 2017; 29: 27
7c Bernardino AM. R, Castro HC, Frugulhetti IC. P. P, Loureiro NI. V, Azevedo AR, Pinheiro LC. S, Souza TM. L, Giongo V, Passamani F, Magalhães UO, Albuquerque MG, Cabral LM, Rodrigues CR. Bioorg. Med. Chem. 2008; 16: 313

8a Prabha K, Rajendra PrasadK. J. MedChemComm 2013; 4: 340
8b Vichai V, Kirtikara K. Nat. Protoc. 2006; 1: 1112

9 Arslan BS, Güzel E, Kaya T, Durmaz V, Keskin M, Avc D, Nebioğlu M, Şişman İ. Dyes Pigm. 2019; 164: 188

10a Wang Q, Zhu J. Domino Reactions . Tietze LF. Wiley-VCH; Weinheim: 2014. 57
10b Pellissier H. Chem. Rev. 2013; 113: 442
10c Clavier H, Pellissier H. Adv. Synth. Catal. 2012; 354: 3347
10d Jiang B, Rajale T, Wever W, Tu S.-J, Li G. Chem. Asian J. 2010; 5: 2318
10e Tietze LF, Modi A. Med. Res. Rev. 2000; 20: 304
10f Enders D, Grondal C, Huttl MR. M. Angew. Chem. Int. Ed. 2007; 46: 1570

11a Zhu JP, Bienayme H. Multicomponent Reactions . Wiley-VCH; Weinheim: 2004
11b Anastas PT, Warner JC. Green Chemistry Theory and Practice . Oxford University Press; New York: 1998
11c Indumathi S, Menendez JC, Perumal S. Curr. Org. Chem. 2013; 17: 2038
11d Ma G.-H, Tu X.-J, Ning Y, Jiang B, Tu S.-J. ACS Comb. Sci. 2014; 16: 281

12a Li CM, Zhang FR, Qi CZ. Green Chem. 2019; 21: 3109
12b Zhang FR, Li CM, Qi CZ. Org. Chem. Front. 2020; 7: 2456

13a Li CM, Qi CZ, Zhang FR. Synlett 2020; 31: 1313
13b Li CM, Fan WM, Qi CZ, Zhang FR. Tetrahedron Lett. 2020; 61: 152144

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

16a Dabiri M, Noroozi TissehZ, Bazgir A. J. Heterocycl. Chem. 2010; 47: 1062
16b Maleki B, Akbarzadeh E, Babaee S. Dyes Pigm. 2015; 123: 222
16c Khurana JM, Lumb A, Chaudhary A, Nand B. Synth. Commun. 2013; 43: 2147

Supplementary Material

Supporting Information (PDF) (opens in new window)