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Ionic liquid promoted preparation of 4H-thiopyran and pyrimidine nucleoside-thiopyran hybrids through one-pot multi-component reaction of thioamide

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Abstract

One-pot multi-component reactions of aldehydes, cyanothioacetamide and malononitrile promoted by ionic liquid proved to be an efficient way for the synthesis of thiopyran derivatives. Without any added catalyst, both aromatic and aliphatic aldehydes participated in this reaction smoothly. As an application of this method, a pyrimidine nucleoside-thiopyran chimera with potential biological activities was obtained in high yield from 5-formyl-2’-deoxyuridine. In addition, the ionic liquid used can be easily recovered and effectively reused for at least 5 times.

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Abbreviations

ILs:

Ionic liquids

[bmim]BF4 :

1-Butyl-3-methylimidazolium tetrafluoroborate

r. t.:

Room temperature

THF:

Tetrahydrofuran

VOC:

Volatile organic compound

m. p.:

Melting point

References

  1. Jagodziński TS (2003) Thioamides as useful synthons in the synthesis of heterocycles. Chem Rev 103: 197–228. doi:10.1021/cr0200015

    Article  PubMed  CAS  Google Scholar 

  2. Schaumann E (1991) Synthesis of thioamides and thiolactams, comprehensive organic synthesis. In: Trost BM, Fleming I (eds) Pergamon, vol. 6. Oxford, pp 419–434

  3. Hurd RN, Delamater G (1961) The preparation and chemical properties of thionamides. Chem Rev 61: 45–82. doi:10.1021/cr60209a003

    Article  CAS  Google Scholar 

  4. Dyachenko VD, Chernega AN (2006) Aliphatic aldehydes in multicomponent synthesis of 4-alkyl-substituted partially hydrogenated quinolines, fused 4H-pyrans, and 2-amino-4-ethyl-5-methylbenzene-1,3-dicarbonitrile. Russ J Org Chem 42: 567–576. doi:10.1134/S1070428006040142

    Article  CAS  Google Scholar 

  5. Ingall AH (1996) In comprehensive heterocyclic chemistry II. In: Katritzky AR, Rees CW, Scriven EFV (eds) Pergamon, vol. 5. Oxford, 501 pp

  6. Vedejs E, Krafft GA (1982) Cyclic sulfides in organic synthesis. Tetrahedron 38: 2857–2881. doi:10.1016/0040-4020(82)85013-8

    Article  CAS  Google Scholar 

  7. Casy G, Taylor RJK (1989) The synthesis of 2,3-disubstituted cyclopentenones using Ramberg-Bäcklund reaction in conjunction with organocopper chemistry. Tetrahedron 45: 455–466. doi:10.1016/0040-4020(89)80073-0

    Article  CAS  Google Scholar 

  8. Casy G, Taylor RJK (1988) Facile Ramberg-Bäcklund reactions for the synthesis of 2,3-disubstituted cyclopentenones; A short synthetic route to tetrahydrodicranenone B. J Chem Soc Chem Commun 454–455. doi:10.1039/c39880000454

  9. Ward DE, Jheengut V, Beye GE (2006) Thiopyran route to polypropionates: an efficient synthesis of serricornin. J Org Chem 71: 8989–8992. doi:10.1021/jo061747w

    Article  PubMed  CAS  Google Scholar 

  10. McDonald BP, Steele RW, Sutherland JK (1988) Synthetic approaches to thiathromboxanes. Part. 2 Synthesis of structural isomers of thiathromoxane A2. J Chem Soc, Perkin Trans 1: 675–679. doi:10.1039/p19880000675

    Article  Google Scholar 

  11. Casy G, Lane S, Talor JK (1986) The preparation of thiathromboxane analogues and a formal total synthesis of dithiathromboxane A2 based on conjugate addition reactions of thiin-4-ones. J Chem Soc, Perkin Trans 1: 1397–1404. doi:10.1039/p19860001397

    Article  Google Scholar 

  12. McAllister GD, Taylor RJK (2001) The synthesis of polyoxygenated, enantiopure cyclopentene derivatives using Ramberg-Bäcklund rearrangement. Tetrahedron Lett 42: 1197–1200. doi:10.1016/S0040-4039(00)02209-7

    Article  CAS  Google Scholar 

  13. Barthakur MG, Chetia A, Boruah RC (2006) Microwave-promoted one-pot synthesis of 4H-thiopyrans from α,β-unsaturated ketones via a three-component reaction. Tetrahedron Lett 47: 4925–4927. doi:10.1016/j.tetlet.2006.05.020

    Article  CAS  Google Scholar 

  14. Dyachenko VD (2005) Cyclohexene-4-carbaldehyde in the synthesis of 4-(cyclohex-3-enyl)-substituted 4H-chromenes, 4H-thiopyrans, 1,4,5,6,7,8-hexahydroquinolines, 1,4-dihydropyridines, pyridines, and 6,7-dihydro-5H-[1]pyrindines. Russ J Gen Chem 75: 1537–1544. doi:10.1007/s11176-005-0463-z

    Article  CAS  Google Scholar 

  15. Bi XH, Dong DW, Li Y, Liu Q, Zhang Q (2005) [5C + 1S] Annulation: a facile and efficient synthetic route toward functionalized 2,3-dihydrothiopyran-4-ones. J Org Chem 70: 10886–10889. doi:10.1021/jo052032g

    Article  PubMed  CAS  Google Scholar 

  16. Rosiak A, Mueller RM, Christoffers J (2007) Synthesis of 2,3-dihydrothiapyran-4-ones from 3-oxo-1-pentene-4-ynes. Monatsh Chem 138: 13–26. doi:10.1007/s00706-006-0571-4

    Article  CAS  Google Scholar 

  17. Zhao GL, Vesely J, Rios R, Ibrahem I, Sunden H, Cordova A (2008) Highly diastereo- and enantioselective catalytic domino thia-Michael/Aldol reactions: synthesis of benzthiopyrans with three contiguous stereocenters. Adv Synth Catal 350: 237–242. doi:10.1002/adsc.200700407

    Article  CAS  Google Scholar 

  18. Kobayashi K, Horiuchi M, Miyamoto K, Morikawa O, Konishi H (2006) Synthesis of 4-aryl-2-sulfenyl-2H-1-benzothiopyran derivatives by cyclization of [2-(1-aryl-2-methoxyvinyl)phenylthio][methyl(or phenyl)thio] methyllithiums. Bull Chem Soc Jpn 79: 1977–1979. doi:10.1246/bcsj.79.1977

    Article  CAS  Google Scholar 

  19. Rosiak A, Christoffers J (2006) Synthesis of 3-aryl-substituted tetrahydropyran-4-ones and tetrahydrothiopyran-4-ones. Synlett 1434–1436.

  20. Jagodziński TS, Sośnicki JG, Wesołowska A (2003) Reaction of β-keto thioamides with α,β-unsatured aldehydes. Synthesis of 6-hydroxypiperidine-2-thiones and 6H-thiopyrans. Tetrahedron 59: 4183–4192. doi:10.1016/S0040-4020(03)00576-3

    Article  CAS  Google Scholar 

  21. Saito T, Takekawa K, Takahashi T (1999) The first catalytic, highly enantioselective hetero-Diels-Alder reaction of thiabutadienes. Chem Commun 1001–1002. doi:10.1039/a902076d

  22. Dyachenko VD, Krivokolysko SG, Litvinov VP (1996) Synthesis of 2,6-diamino-3,5-dicyano-4-ethyl-4H-thiopyran and its recyclization to 6-amino-3,5-dicyano-4-ethylpyrimidine-2(1H)-thione. Chem Heterocycl Compd 32: 947–951. doi:10.1007/BF01176972

    Article  Google Scholar 

  23. Fan XS, Wang X, Zhang XY, Li XY, Qu GR (2007) MWI-promoted preparation of 4H-thiopyran derivatives through one-pot multi-component reactions. J Chem Res (s):693–695

  24. Quintela JM, Moreira MJ, Peinador C (2000) A convenient method for the synthesis of thiopyrano[2,3-d:6,5-d′]dipyrimidine derivatives. Heterocycles 52: 333–348

    Article  CAS  Google Scholar 

  25. Sharanin YA, Shestopalov AM, Nesterov VN, Melenchuk SN, Promonenkov VK, Shklover VE, Struchkov YT, Litvinov VP (1989) Cyclization of nitriles .XXXIII. Synthesis and structure of 4-aryl-2,6-diamino-3,5-dicyanothiopyrans and their recyclization to 6-amino-4-aryl-3,5-dicyano-2(1H)-pyridinethiones. Russ J Org Chem 25: 1189–1200

    Google Scholar 

  26. Dyachenko VD, Krivokolysko SG, Sharanin YA, Litvinov VP (1997) New route to 6-amino-4-aryl-3,5-dicyano-pyridine-2(1H)-thiones. Russ J Org Chem 33: 1014–1017

    CAS  Google Scholar 

  27. Earle MJ, Katdare SP, Seddon KR (2004) Paradigm confirmed: the first use of ionic liquids to dramatically influence the outcome of chemical reactions. Org Lett 6: 707–710. doi:10.1021/ol036310e

    Article  PubMed  CAS  Google Scholar 

  28. Fan X, Hu X, Zhang X, Wang J (2004) Ionic liquid promoted Knoevenagel and Michael reactions. Aust J Chem 57: 1067–1071. doi:10.1071/CH04060

    Article  CAS  Google Scholar 

  29. Fan X, Hu X, Zhang X, Wang J (2005) InCl3·4H2O Promoted green preparation of xanthenedione derivatives in ionic liquids. Can J Chem 83: 16–20. doi:10.1139/v04-155

    Article  CAS  Google Scholar 

  30. Fan X, Li Y, Zhang X, Qu G, Wang J (2006) A novel and green version of the Passerini reaction in an ionic liquid ([bmim][BF4]). Can J Chem 84: 794–799. doi:10.1139/V06-070

    Article  CAS  Google Scholar 

  31. Zhang X, Fan X, Niu H, Wang J (2003) An ionic liquid as a recyclable medium for the green preparation of α, α’-bis(substituted benzyli-dene)cycloalkanones catalyzed by FeCl3·6H2O. Green Chem 5: 267–269. doi:10.1039/b212155g

    Article  CAS  Google Scholar 

  32. Fan X, Zhang X, Zhou L, Keith KA, Prichard MN, Kern ER, Torrence PF (2006) Toward orthopoxvirus countermeasures: a novel heteromorphic nucleoside of unusual structure. J Med Chem 49: 4052–4054. doi:10.1021/jm060404n

    Article  PubMed  CAS  Google Scholar 

  33. Fan X, Zhang X, Zhou L, Keith KA, Prichard MN, Kern ER, Torrence PF (2006) 5-(dimethoxymethyl)-2′-deoxyuridine: a novel gem diether nucleoside with anti-orthopoxvirus activity. J Med Chem 49: 3377–3382. doi:10.1021/jm0601710

    Article  PubMed  CAS  Google Scholar 

  34. Fan X, Zhang X, Zhou L, Keith KA, Prichard MN, Kern ER, Torrence PF (2006) Assembling a smallpox biodefense by interrogating 5-substituted pyrimidine nucleoside chemical space. Antiviral Res 71: 201–205. doi:10.1016/j.antiviral.2006.04.015

    Article  PubMed  CAS  Google Scholar 

  35. Fan X, Zhang X, Zhou L, Keith KA, Prichard MN, Kern ER, Torrence PF (2006) A pyrimidine-pyrazolone nucleoside chimera with potent in vitro anti-orthopoxvirus activity. Bioorg Med Chem Lett 16: 3224–3228. doi:10.1016/j.bmcl.2006.03.043

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Henan Key Laboratory for Environmental Pollution Control, School of Chemistry and Environmental Sciences, Henan Normal University, Xinxiang, Henan, 453007, People’s Republic of China

    Xinying Zhang, Xiaoyan Li, Xuesen Fan, Xia Wang, Dongfang Li, Guirong Qu & Jianji Wang

Authors
  1. Xinying Zhang
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  2. Xiaoyan Li
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  3. Xuesen Fan
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  4. Xia Wang
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  5. Dongfang Li
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  6. Guirong Qu
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  7. Jianji Wang
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Correspondence to Xinying Zhang or Xuesen Fan.

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Zhang, X., Li, X., Fan, X. et al. Ionic liquid promoted preparation of 4H-thiopyran and pyrimidine nucleoside-thiopyran hybrids through one-pot multi-component reaction of thioamide. Mol Divers 13, 57–61 (2009). https://doi.org/10.1007/s11030-008-9098-4

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  • DOI: https://doi.org/10.1007/s11030-008-9098-4

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