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Rapid synthesis of 1,6-naphthyridines by grindstone chemistry

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Abstract

Many methods to prepare heterocyclic compounds involve toxic solvents and reagents. There is therefore a need to design cleaner synthetic procedures. 1,6-Naphthyridine derivatives are used in many applications such as cancer chemotherapy, antibacterials, antivirals and antiproliferatives. Here, we report the solvent-free and catalyst-free synthesis of 1,6-naphthyridine derivatives. Synthesis is done by grinding of 2 mmol of ketones, 2 mmol of malononitrile and 1 mmol of amines in a mortar at room temperature for 5–7 min. 1,2-Dihydro[1,6]-naphthyridine derivatives were obtained in 90–97 % yields.

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Abbreviations

DMSO:

Dimethyl sulfoxide

1H-NMR:

Proton nuclear magnetic resonance spectroscopy

13C-NMR:

Carbon nuclear magnetic resonance spectroscopy

TLC:

Thin layer chromatography

IR:

Infrared spectroscopy

References

  • Abd Elnabi H, Abdel Hameed AM, Mekeimer RA, Awad RR, Sadek KU (2013) Garlic clove catalyzed Biginelli reaction in water at ambient temperature. Green Sustain Chem 3:141–145

    Article  CAS  Google Scholar 

  • Austin NE, Hadley MS, Harling JD, Harrington FP, Macdonald GJ, Mitchell DE, Riley GJ, Stean TO, Stemp G, Stratton SC, Thompson M, Upton N (2003) The design of 8,8-dimethyl[1,6]naphthyridines as potential anticonvulsant agents. Bioorg Med Chem Lett 13:1627–1629

    Article  CAS  Google Scholar 

  • Bedard J, May S, Heureux L, Stamminger T, Copsey A, Drach J, Huffman J, Chan L, Jin H, Rando RF (2000) Antiviral properties of a series of 1,6-naphthyridine and 7,8-dihydroisoquinoline derivatives exhibiting potent activity against human cytomegalovirus. Antimicrob Agents Chemother 44:929–934

    Article  CAS  Google Scholar 

  • Bhat SI, Trivedi DR (2013) Fast and efficient synthesis of N-substituted β-aminobutyric acids by grinding at room temperature. Environ Chem Lett 11:91–97

    Article  CAS  Google Scholar 

  • Bose AK, Pednekar S, Granguly SN, Chakraborthy G, Manhas SM (2004) A simplified green chemistry approach to the Biginelli reaction using ‘Grindstone Chemistry’. Tetrahedron Lett 45:8351–8353

    Article  CAS  Google Scholar 

  • Chandra A, Singh B, Upadhyaay S, Singh RM (2008) Copper-free Sonogashira coupling of 2-chloroquinolines with phenyl acetylene and quick annulation to benzo[b][1,6]naphthyridine derivatives in aqueous ammonia. Tetrahedron 64:11680–11685

    Article  CAS  Google Scholar 

  • Colandrea VJ, Naylor EM (2000) Synthesis and regioselective alkylation of 1,6- and 1,7-naphthyridines. Tetrahedron Lett 41:8053–8057

    Article  CAS  Google Scholar 

  • Cywin CL, Zhao BP, Mcneil DW, Hrapchack M, Prokopowicz AS, Goldberg DR, Morwick TM, Gao A, Jakes S, Kashem M, Magolda RL, Soll MR, Player MR, Bobko MA, Rinker J, DesJarlais RL, Winters MP (2003) Discovery and sar of novel and naphthyridines as potent inhibitors of spleen tyrosine kinase (SYK). Bioorg Med Chem Lett 13:1415–1418

    Article  CAS  Google Scholar 

  • Hunt JA, Kallashi F, Ruzek RD, Sinclair PJ, Ita I, Mccornick SX, Pivnichny JV, Hop CECA, Kumer S, Wang Z, O’Keefe SJ, O’Neill EA, Porter G, Thompson JE, Woods A, Zaller DM, Doherty JB (2003) p38 Inhibitors: piperidine- and 4-aminopiperidine-substituted naphthyridinones, quinolinones, and dihydroquinazolinones. Bioorg Med Chem Lett 13:467–470

    Article  CAS  Google Scholar 

  • Kumavat PP, Jangale AD, Patil DR, Dalal KS, Meshram JS, Dalal DS (2013) Green synthesis of symmetrical N, N′-disubstituted thiourea derivatives in water using solar energy. Environ Chem Lett 11:177–182

    Article  CAS  Google Scholar 

  • Lemport PS, Bodrin GV, Belyakov AI, Petrovskii PV, Vologzhanina AV, Nifant’ev EE (2009) Friedländer reaction in the synthesis of 2-(phosphoryl)alkyl-substituted 1,6-naphthyridines. Mendeleev Commun 19:303–305

    Article  CAS  Google Scholar 

  • Li TK, Houghton PJ, Desai SD, Daroui P, Liu AE, Hars S, Ruchelman AL, La Voie EJ, Liu LF (2003) Characterization of ARC-111 as a novel topoisomerase I-targeting anticancer drug. Cancer Res 63:8400–8407

    CAS  Google Scholar 

  • Mekeimer RA, Abdel Hameed AM, Sadek KU (2008) Solar thermochemical reactions: four-component synthesis of polyhydroquinoline derivatives induced by solar thermal energy. Green Chem 10:592–593

    Article  Google Scholar 

  • Mirjafari A (2014) Direct synthesis of 2,4,5-trisubstituted imidazoles from alcohols and α-hydroxyketones by microwave. Environ Chem Lett 12:177–183

    Article  CAS  Google Scholar 

  • Mogilaiah K, Jagadeeshwar K, Dhanaja K (2013) Ammonium sulphamate catalyzed Friedlander synthesis of 1,8-naphthyridines in the solid state. Int J Chem Tech Res 5:1575–1577

    CAS  Google Scholar 

  • Mukhopadhyay C, Das P, Butcher R (2011) An expeditious and efficient synthesis of highly functionalized [1,6]-naphthyridines under catalyst-free conditions in aqueous medium. J Org Lett 13:4664–4667

    Article  CAS  Google Scholar 

  • Riadi Y, Mamouni R, Routier S, Guillaumet G, Lazar S (2014) Ecofriendly synthesis of 3-cyanopyridine derivatives by multi-component reaction catalyzed by animal bone meal. Environ Chem Lett 12:523–527

    Article  CAS  Google Scholar 

  • Rudys S, Rios-Luci C, Perez-Roth E, Cikotiene I, Pardon JM (2010) Antiproliferative activity of novel benzo[b][1,6]naphthyridines in human solid tumor cell lines. Bioorg Med Chem Lett 20:1504–1506

    Article  CAS  Google Scholar 

  • Sadek KU, Mekeimer RA, Abdel Hameed AM, Elnahas F, Elnagdi MH (2012) Green and highly efficient synthesis of 2-arylbenzothiazoles using glycerol without catalyst at ambient temperature. Molecules 17:6011–6019

    Article  CAS  Google Scholar 

  • Sharifi A, Abaee MS, Mokhtare Z, Mirzaei M (2014) Room temperature synthesis of 2H-1,4-benzoxazine derivatives using a recoverable ionic liquid medium. Environ Chem Lett 12:365–370

    Article  CAS  Google Scholar 

  • Singh SK, Ruchelman AL, Li TK, Lin FL, Lavoie EJ (2003) Nitro and amino substitution in the D-ring of 5-(2-dimethylaminoethyl)- 2,3-methylenedioxy-5H-dibenzo[c, h][1,6]naphthyridin-6-ones: effect on topoisomerase-I targeting activity and cytotoxicity. J Med Chem 46:2254–2257

    Article  CAS  Google Scholar 

  • Suresh T, Kumar RN, Mohan PS (2003) Synthesis and antibacterial activity of 8-methyl benzo[b]naphtho[f][1,6]-naphthyridines. Asian J Chem 15:855–859

    CAS  Google Scholar 

  • Suzuki H, Sakai N, Iwahara R, Fujiwaka T, Satoh M, Kakehi A, Konakahara T (2007) Novel synthesis of 7-fluoro-8-(trifluoromethyl)-1H-1,6-naphthyridin-4-one derivatives: intermolecular cyclization of an N-silyl-1-azaallyl anion with perfluoroalkene and subsequent intramolecular skeletal transformation of the resulting pentasubstituted pyridines. J Org Chem 72:5878–5881

    Article  CAS  Google Scholar 

  • Tanaka K, Toda F (2000) Solvent-free organic synthesis. Chem Rev 100:1025–1074

    Article  CAS  Google Scholar 

  • Toda F (1993) Solid state organic reactions. Synlett 1993:303–312

  • Turner JA (1990) A general approach to the synthesis of 1,6-, 1,7-, and 1,8-naphthyridines. J Org Chem 55:4744–4750

    Article  CAS  Google Scholar 

  • Zhang Q, Shi C, Zhang HR, Wang KK (2000) Synthesis of 6H-Indolo[2,3-b][1,6]naphthyridines and related compounds as the 5-aza analogues of ellipticine alkaloids. J Org Chem 65:7977–7983

    Article  CAS  Google Scholar 

  • Zhou Y, Proco JA, Snyder JK (2007) Synthesis of 5,6,7,8-tetrahydro-1,6-naphthyridines and related heterocycles by cobalt-catalyzed [2 + 2 + 2] cyclizations. Org Lett 9:393–396

    Article  CAS  Google Scholar 

  • Zhuang L, Wai JS, Embrey MW, Fisher TE, Egberston MS, Payne LS, Guare JP Jr, Vacca JP, Hazuda DJ, Felock PJ, Walf AL, Stillmock KA, Witmer MV, Moyer G, Schleif WA, Gabrylski LJ, Leonard YM, Lynch JJ Jr, Michelson SR, Young SD (2003) Design and synthesis of 8-hydroxy-[1,6]naphthyridines as novel inhibitors of HIV-1 integrase in vitro and in infected cells. J Med Chem 46:453–456

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Chemistry Department, Faculty of Science, Minia University, El-Minia, 61519, Egypt

    Afaf M. Abdel Hameed

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  1. Afaf M. Abdel Hameed
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Correspondence to Afaf M. Abdel Hameed.

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Abdel Hameed, A.M. Rapid synthesis of 1,6-naphthyridines by grindstone chemistry. Environ Chem Lett 13, 125–129 (2015). https://doi.org/10.1007/s10311-015-0494-6

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  • DOI: https://doi.org/10.1007/s10311-015-0494-6

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