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Solution-phase reductive cyclization of 2-quinoxalinol analogs: Systematic study of parallel synthesis

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Abstract

1,5-Difluoro-2,4-dinitrobenzene starting material was treated via primary and/or secondary substitution with a variety of amino acids or amines and the aromatic m-dinitro groups were then reductively cyclized provide the 2-quinoxalinol analogs. The conditions for 1,5-dialkylamino-2,4-dinitrobenzene reduction have been systematically studied and optimized in solution. Three effective methods are described for the high-throughout generation of 2-quinoxalinol analogs.

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References

  1. Liu, G., Zhang, L., Zhang, S. D., Yang, H. Z., Li, L., Wu, X. H., Sun G. C., Kou, B. B., Xu, S., Ji, Y. F. and Cheng, G. F., A novel and parallel approach for synthesis of 2-quinoxalinol analogs and their inhibition of TNF-α stimulation by LPS on macrophage in vitro, submitted.

  2. Nicholas A. Meanwell, Herbert R. Roth, Edward C. R. Smith, Donald L. Wedding J. J. Kim Wright, J. Stuart Fleming and Elizabeth Gillespie, 1,3-Dihydro-2H-imidazo[4,5-b]quinolin-2-ones — inhibitors of blood platelet cAMP phosphodiesterase and induced aggregation, J. Med. Chem., 34 (1991) 2906–2916.

    PubMed  Google Scholar 

  3. Kim, J. N., Lee, K. Y., Kim, H. S. and Kim, T. Y., Synthesis of 3-Ethoxycarbonyl-4-hydroxyquinoline N-Oxides from the Baylis-Hillman Adducts of o-Nitrobenzaldehydes, Org. Lett. (Communication), 2 (2000) 343–345.

    PubMed  Google Scholar 

  4. Robert L. Wear and Cliff S. Hamilton, The synthesis of some quinoxaline derivatives, J. Am. Chem. Soc., 72(7) (1950) 2893–2894.

    Google Scholar 

  5. Norman H. Cromwell and Gerald D. Mercer, Amino derivatives of nitrochalcones. II.1 A new synthetic method for 3-aminoquinolines, J. Am. Chem. Soc., 79(23) (1957) 6201–6203.

    Google Scholar 

  6. Fox, B. A. and Threfall, T. L., 2,3-diaminopyridine, Org Synth., Coll., 5 (1973) 346–349.

    Google Scholar 

  7. Ono, A., Terasaki S. and Tsuruoka Y., Selective reduction of dinitrobenzenes, Chem. Ind. (Lond.), (1983) 477–478.

  8. For reviews, see Rylander, P. N., Hydrogenation Methods, Ref. 497, p. 104, Catalytic Hydrogenation over Platinuim Metals, Academic Press, NY, 1967, p. 168.

    Google Scholar 

  9. Moody, C. J. and Pitts, M. R., Indium as a reducing agent: reduction of aromatic nitro groups, Synlett., 9 (1998) 1028.

    Google Scholar 

  10. Banik, B. K., Mukhopadhyay, C., Venkatraman, M. S. and Becker, F. F., A facile reduction of aromatic nitro compounds to aromatic amines by samarium and iodine, Tetrahedron Lett., 39 (1998) 7243–7246.

    Google Scholar 

  11. Fitch, R. W. and Luzzio, F. A., The aluminum amalgam reduction of 2-nitroalkanols promoted by ultrasound, Tetrahedron Lett., 35 (1994) 6013–6016.

    Google Scholar 

  12. Brinkman, H. R., The reduction of nitrobenzenes by triethylsilane using Wilkinson's catalysts, Synth. Commun., 26 (1996) 973–980.

    Google Scholar 

  13. Terpko, M. O. and Heck, R. F., Palladium-catalyzed triethylammonium formate reduction. 3. Selective reduction of dinitroaromatic compounds, J. Org. Chem., 45 (1980) 4992–4993.

    Google Scholar 

  14. Ram, S. and Ehrenkaufer, R. E., A general procedure for mild and rapid reduction of aliphatic and aromatic nitro compounds using ammonium formate as a catalytic hydrogen transfer agent, Tetrahedron Lett., 25 (1984) 3415–3418.

    Google Scholar 

  15. Barrett, A. G. M. and Spilling, C. D., Transfer hydrogenation: a stereospecific method for the conversion of nitro alkanes into amines, Tetrahedron Lett., 29 (1988) 5733–5734.

    Google Scholar 

  16. Entwistle, I. D., Jackson, A. E., Johnstone R. A. W. and Telford, R. P., Reduction of nitro-compound, J. Chem. Soc. Perkin Trans., 1 (1977) 443–444.

    Google Scholar 

  17. Petrini, M., Ballini, R. and Rosini, G., Reduction of aliphatic and aromatic nitro compounds with sodium borohydride in tetrahydrofuran using 10% palladium-on-carbon as catalyst, Synthesis, (1987) 713–714.

  18. Ayyangar, N. R., Lugade, A. G., Nikrad, P. V. and Sharma, V. K., Catalytic reduction of nitroarenes with hydrazine hydrate in suitable solvents, Synthesis, (1981) 640–643.

  19. Ayyangar, N. R., Kalkote, U. R. Lugad, A. G., NiKrad, P. V. and Sharma, V. K., Partial reduction of dinitroarenes to nitroanilines with hydrazine hydrate, Bull. Chem. Soc. Jpn., 56 (1983) 3159–3164.

    Google Scholar 

  20. Romanelli, M. G. and Beckers, E. I., Ethyl p-Dimethylaminophenylacetate, Org Synth, coll., 5 (1973) 552–554.

    Google Scholar 

  21. He, Y., Zhao, H., Pan, X. F. and Wang, S. F., Reduction with metal borohydride-transition metal salt system. I. Redction of aromatic nitro compounds with potassium borohydride-copper (I) chloride, Synth. Commun., 19 (1989) 3047–3050.

    Google Scholar 

  22. Hanaya, K., Muramatus, T., Kudo, H. and Chow, Y. L., Reduction of aromatic nitro-compounds to amines with sodium borohydridecopper(II) acetylacetonate, J. Chem. Soc. Perkin Trans., 1 (1979) 2409–2410.

    Google Scholar 

  23. Gillespie, H. B., Spano, F. and Graff, S., Synthesis of some substituted benzimidazoles, benzotriazoles, and quinoxalines, 25 (1960) 942–944.

    Google Scholar 

  24. For a review of the Zinin reduction, see Porter, H.K., Org. React., 20 (1973) 455.

    Google Scholar 

  25. Hughes, I., Application of polymer-bound phosphonium salts as traceless supports for solid phase synthesis, Tetrahedron Lett., 37 (1996) 7595–7598.

    Google Scholar 

  26. Babler, J. H. and Sarussi, S. J., Non-catalyzed reductions with formate salts: conversion of nitroaromatic compounds to the corresponding primary amines, Synth. Commun., 11 (1981) 925–930.

    Google Scholar 

  27. Baik, W., Han, J. l., Lee, K. C., Lee, N. H., Kim, B. H. and Hahn, J. T., Selective reduction of aromatic nitro compounds to aromatic amines by baker's yeast in basic solution, Tetrahedron Lett., 35 (1994) 3965–3966.

    Google Scholar 

  28. Wei, G. P. and Phillips, G. B., Solid phase synthesis of benzimidazolones, Tetrahedron Lett., 39 (1998) 179–182.

    Google Scholar 

  29. Mayer, J. P., Zhang, J. W., Bjergarde, K., Lenz, D. M. and Gaudino, J. J., Solid phase synthesis of 1,4-benzodiazepine-2,5-diones, Tetrahedron Lett., 37 (1996) 8081–8084.

    Google Scholar 

  30. Meyer, H. V., Dilley, G. J., Durgin, T. L., Powers, T. S., Winssinger, N. A., Zhu, W. and Pavia, M. R., Multiple simultaneous synthesis of phenolic libraries, Molecular Diversity, 1 (1995) 13–20.

    PubMed  Google Scholar 

  31. Xing, W. K. and Ogata, Y., Steric acceleration by ortho substituent of the stannous chloride reduction of nitrobenzenes in aqueous ethanol, J. Org. Chem., 47 (1982) 3577–3581.

    Google Scholar 

  32. Inoue, H., Konda, M., Hashiyama, T., Otsuka, H., Watanabe, A., Gaino, M., Takahashi, H., Date, T., Okamura, K., Takeda, M., Narita, H., Murata, S., Odawara. A., Sasaki, H. and Nagao, T., Synthesis and biological evaluation of alkyl, alkoxy, alkylthio, or Amino-substituted 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones, Chem. Pharm. Bull., 45 (1997) 1008–1026.

    PubMed  Google Scholar 

  33. Bellamy, F. D. and Ou, K. Selective reduction of nitro compounds with stannous chloride in non acidic and non aqueous medium, Tetrahedron Lett., 25 (1984) 839–842.

    Google Scholar 

  34. Liu, G., Fan, Y. M., Calson, J. R. and Lam, K. S., Solution-phase synthesis of 1,5-dialkylamino-2,4-dinitrobenzene library and the identification of novel antibacterial compounds from this library, J. Combi Chem., 2(5) (2000) 467–474.

    Google Scholar 

  35. R. J. Booth and J. C. Hodges, Polymer-support quenching reagents for parallel purification, J. Am. Chem. Soc., 119 (1997) 4882–4886.

    Google Scholar 

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Authors and Affiliations

  1. Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, P. R. China

    Xiang-Hong Wu, Gang Liu, Jing Zhang, Zhan-Guo Wang, Song Xu, Suo-De Zhang, Liang Zhang & Lin Wang

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  1. Xiang-Hong Wu
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  2. Gang Liu
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Correspondence to Gang Liu.

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Wu, XH., Liu, G., Zhang, J. et al. Solution-phase reductive cyclization of 2-quinoxalinol analogs: Systematic study of parallel synthesis. Mol Divers 8, 165–174 (2004). https://doi.org/10.1023/B:MODI.0000025639.89179.60

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