Central European Journal of Chemistry

, Volume 3, Issue 2, pp 311–325 | Cite as

2-[3-(Trifluoromethyl)phenyl]furo[3,2-b]pyrroles: synthesis and reactions

  • Peter Gajdoš
  • Soňa Pavlíková
  • Filip Bureš
  • Alžbeta Krutošíková


The synthesis and reactions of methyl 2-[3-(trifluoromethyl)phenyl]-4H-furo[3,2-b]pyrrole-5-carboxylate (1a) are described. Upon reaction with methyl iodide, benzyl chloride, or acetic anhydride, this compound gave N-substituted products 1b-d. By hydrolysis of compounds 1a-c, the corresponding acids 2a-c were formed, or by reaction with hydrazine-hydrate, the corresponding carbohydrazides 3a-c were formed. By heating 2-[3-(trifluoromethyl)phenly]-4H-furo[3,2-b]pyrrole-5-carboxylic acid (2a) in acetic anhydride, 4-acetyl-2-[3-(trifluoromethyl)phenyl]furo[3,2-b]pyrrole (4) was formed. By hydrolysis of 4, 2-[3-(trifluoromethyl)phenyl]-4H-furo[3,2-b]pyrrole (5a) was formed, and reactions with methyl iodide or benzyl chloride gave N-substituted products 5b-c. The reaction of 4 with dimethyl butynedioate gave substituted benzo[b]furan 6. Compound 3a reacted with triethyl orthoesters giving 7a-c, which afforded with phosphorus (V) sulphide the corresponding thiones 8a-c. The thiones 8a-c reacted with hydrazine hydrate to form hydrazine derivatives 9a-c. The reaction of triethyl orthoformiate with compounds 9a-c led to furo[2′,3′: 4,5]pyrrolo[1,2-d][1,2,4]triazolo[3,4-f][1,2,4]triazines 10a-c. Hydrazones 11a-c were formed from 3a-c and 5-[3-(trifluoromethyl)phenyl]furan-2-carboxaldehyde. The effect of microwave irradiation on some condensation reactions was compared with “classical” conditions. The results showed that microwave irradiation shortens the reaction time while affording comparable yields.


2-[3-(trifluoromethyl)phenyl]furo[3,2-b]pyrroles hydrazides hydrazones cycloaddition condensation phase transfer catalysis microwave irradiation 1H and13C NMR spectra 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    A. Krutošíková: “Bicyclic 5-5 Systems: Two Heteroatoms 1:1”, In: C.A. Ramsden (Ed.): Comprehensive Heterocyclic Chemistry II, Vol. 7, Pergamon, Oxford, 1996, p. 1–47.Google Scholar
  2. [2]
    A. Krutošíková, M. Dandárová and J. Alföldi: “Substituted Vinyl Azides in the Synthesis of Condensed Nitrogen Heterocycles”, Chem. Papers, Vol. 48, (1994), pp. 268–273.Google Scholar
  3. [3]
    A. Krutošíková and M. Dandárová: “Substituted Vinyl Azides in the Synthesis of Furo[3,2-b:4,5-b′]dipyrroles and Pyrrolo[2′,3′:4,5]furo[3,2-c]pyridines”, Heterocycles, Vol. 48, (1994), pp. 1695–1700.Google Scholar
  4. [4]
    A. Krutošíková and M. Dandárová: “Reactions of Methyl 2-Formylfuro[3,2-b]pyrrole-5-carboxylates”, Chem Papers, Vol. 50, (1996), pp. 72–76.Google Scholar
  5. [5]
    A. Krutošíková, C.A. Ramsden, M. Dandárová and A. Lyčka: “Synthesis and Reactions of Furo[2,3-b]pyrroles”, Molecules, Vol. 2, (1997), pp. 69–79.CrossRefGoogle Scholar
  6. [6]
    R. Sleziak and A. Krutošíková: “Cycloaddition Reactions of Furo[3,2-b]pyrroles”, Collect. Czech. Chem. Commun., Vol. 64, (1999), pp. 321–328.CrossRefGoogle Scholar
  7. [7]
    R. Sleziak, S. Balá ziová and A. Krutošíková: “Reactions of Furo[3,2-b]pyrrole and Furo[2,3-b]pyrrole-type Aldehydes”, Collect. Czech. Chem. Commun., Vol. 64, (1999), pp. 1135–1146.CrossRefGoogle Scholar
  8. [8]
    R. Sleziak, A. Krutošíková, M.K. Cyranski and T.M. Krygovski: “Furo[3,2-b]pyrrole Derivatives. Syntheses and Reactions in the Furan and Pyrrole Ring”, Polish. J. Chem., Vol. 74, (2000), pp. 207–217.Google Scholar
  9. [9]
    A. Krutošíková, M. Dandárová, J. Alföldi and J. Kováč: “Addition and Cycloaddition of Furo[3,2-b]pyrroles and Their Benzo[b]analogues: An NMR Study of Structure of Products”, Collect. Czech. Chem. Commun., Vol. 53, (1988), pp. 1770–1778.CrossRefGoogle Scholar
  10. [10]
    A. Krutošíková: “Synthesis and Reactions of Condensed Furan Derivatives”, Collect. Czech. Chem. Commun., Vol. 55, (1990), pp. 597–621.CrossRefGoogle Scholar
  11. [11]
    S. Soth, M. Farnier and C. Paulmier: “Recherches en série hétérocyclique. XXIX. Sur des voies d'accés à des thiéno. Sélénolo, furo et pyrrolepyrroles”, Can. J. Chem., Vol. 56, (1978), pp. 1429–1434.CrossRefGoogle Scholar
  12. [12]
    H. Behringer and E. Meinestsberger: “Űber die Reaktionen von Cyclopropen(thi)onen mit 1,2-Dithiol-Verbindungen: Thieno[3,2-b]thiophene, Thieno[3,2-b]furane, 4H-Furo[3,2-b]pyrrole und 1,2-Dithiol-3-(thi)one sowie andere Schwefelheterocyclen”, Liebigs Ann. Chem., Vol. 2, (1982), pp. 315–341.Google Scholar
  13. [13]
    M. Welch and R.S. Phillips: “Enzymatic Syntheses of 6-(4H-Selenolo[3,2-b]pyrrolyl)-L-alanine, 6-(4H-Selenolo[2,3-b]pyrrolyl)-L-alanine, and 6-(4H-Furo[3,2-b]pyrrolyl)-L-alanine”, Bioorg. Med. Chem. Lett., Vol. 9, (1999), pp. 637–640.CrossRefGoogle Scholar
  14. [14]
    M. Welch and R.S. Phillips: “Improved syntheses of [3,2-b]- and [2,3-b]-fused selenolo-and thienopyrroles and of furo[3,2-b]pyrrole”, Heterocycl. Commun., Vol. 5, (1999), pp. 305–310.Google Scholar
  15. [15]
    K.L. Milkiewicz, D.J. Parks and T.B. Lu: “Synthesis of a novel series of tetrasubstituted furo[2,3-b]pyrroles”, Tetrahedron Lett., Vol. 44, (2003), pp. 4257–4260.CrossRefGoogle Scholar
  16. [16]
    E.S.H. El Ashry, N. Rashed, M. Taha and E. Ramadan: “Condensed 1,2,4-Triazines: I. Fused to Heterocycles with Three-, Four-, and Five-Membered Rings”, Adv. Heterocycl. Chem., Vol. 59, (1994), pp. 39–177.CrossRefGoogle Scholar
  17. [17]
    E.S.H. El Ashry, N. Rashed, A. Mousaad and E. Ramadan: “Condensed 1,2,4-Triazines: II. Fused to Heterocycles with Six-, and Seven-Membered Rings and Fused to Two Heterocyclic Rings”, Adv. Heterocycl. Chem., Vol. 61, (1994), pp. 207–326.Google Scholar
  18. [18]
    A. Krutošíková, J. Kováč, M. Dandárová and M. Bobál'ová: “Synthesis and Reactions of Substituted Benzofuro[3,2-b]pyrrole Derivatives”, Collect. Czech. Chem. Commun., Vol. 47, (1982), pp. 3288–3296.Google Scholar
  19. [19]
    A. Krutošíková, J. Kováč and E. Král'ovičová: “The Synthesis and Reactions of Arylfurocondensed Derivatives”, Collect. Czech. Chem. Commun., Vol. 48, (1983), pp. 1878–1884.Google Scholar
  20. [20]
    A. Krutošíková, J. Kováč and M. Dandárová: “Synthesis and Reactions of Furocondensed Derivatives”, Collect. Czech. Chem. Commun., Vol. 49, (1984), pp. 65–70.Google Scholar
  21. [21]
    A. Koreňová, A. Krutošíková, M. Dandárová and J. Kováč: “Synthesis and Reactions of Furocondensed Systems Containing Indole Skeleton”, Collect. Czech. Chem. Commun., Vol. 49, (1984), pp. 1529–1535.Google Scholar
  22. [22]
    A. Krutošíková, J. Kováč and P. Banák: “Furan derivatives CXXVI. Synthesis and reactions of 3,4-dichlorophenyl-substituted furocondensed derivatives”, Chem. zvesti, Vol. 38, (1984), pp. 707–713.Google Scholar
  23. [23]
    A. Krutošíková, S. Mastik, M. Dandárová and A. Lyčka: “Synthesis and Reactions of 8-Hydrazinofuro[2′,3′:4,5]pyrrolo[1,2-d][1,2,4]triazines”, Collect. Czech. Chem. Commun., Vol. 62, (1997), pp. 1612–1622.CrossRefGoogle Scholar
  24. [24]
    D. Zbojek, R. Gašparová, M. Lácová, K. Král'ová, A. Gatial, B. Horváth and A. Krutošíková: “Reactions of substituted furo[3,2-b]pyrrole-5-carboxhydrazides and their biological activity”, Arkivoc, submitted for publication.Google Scholar
  25. [25]
    D. Villemin, B. Martin and N. Bar: “Application of Microwave in Organic Synthesis. Dry Synthesis of 2-Arylmethylene-3(2)-napthofuranones”, Molecules, Vol. 3, (1998), pp. 88–93.Google Scholar
  26. [26]
    M. Lacová, R. Gašparová, S. Loos, T. Liptay and N. Prónayová: “Effect of Microwave Irradiation on the Condensation of 6-Substituted 3-Formylchromones with Some Fivemembered Heterocyclic Compounds”, Molecules, Vol. 8, (2000), pp. 167–178.Google Scholar
  27. [27]
    D. Azarifar and H. Ghasemnejad: “Microwave-Assisted Synthesis of Some 3,5-Arylated 2-Pyrazolines”, Molecules, Vol. 8, (2003), pp. 642–648.Google Scholar
  28. [28]
    P. Gajdoš, J. Miklovič and A. Krutošíková: “Reactions of 5-[3-(Trifluoromethyl)phenyl]furan-2-carbaldehyde”, Khim. Geterotsikl. Soed., submitted for paper.Google Scholar

Copyright information

© Central European Science Journals 2005

Authors and Affiliations

  • Peter Gajdoš
    • 1
  • Soňa Pavlíková
    • 1
  • Filip Bureš
    • 2
  • Alžbeta Krutošíková
    • 1
  1. 1.Department of Chemistry of Faculty of Natural SciencesUniversity of St. Cyril and Methodius in TrnavaTrnavaSlovak Republic
  2. 2.Department of Organic Chemistry of Faculty of Chemical TechnologyUniversity of PardubicePardubiceCzech Republic

Personalised recommendations