The synthesis of 3-aryl-3-trifluoromethyl-2,3-dihydro-1h-pyrrolizin-1-ones

Authors

  • S. V. Melnykov "Інститут органічної хімії НАН України", Ukraine
  • V. M. Tkachuk "Інститут органічної хімії НАН України", Ukraine
  • A. M. Grozav "Інститут органічної хімії НАН України", Ukraine
  • I. Gillaizeau "Інститут органічної та аналітичної хімії, Університет Орлеана", France
  • V. A. Sukach "Інститут органічної хімії НАН України"; "Інститут органічної та аналітичної хімії Університет Орлеана", Ukraine

DOI:

https://doi.org/10.24959/ophcj.19.961

Keywords:

3-amino-3-aryl-4, 4, 4-trifluorobutanoic acid esters, 2, 5-dimethoxytetrahydrofuran, 3-aryl-3-trifluoromethyl-2, 3-dihydro-1H-pyrrolizin-1-ones, boron tribromide, cyclocondensation

Abstract

Aim. To develop the efficient method for the synthesis of 3-aryl-3-trifluoromethyl-2,3-dihydro-1H-pyrrolizin-1-ones as promising scaffolds in design of bioactive compounds.

Results and discussion. It has been shown that condensation of 3-amino-3-aryl-4,4,4-trifluorobutanoic acid methyl esters with 2,5-dimethoxytetrahydrofuran is a convenient synthetic approach to 4,4,4-trifluoro-3-aryl-3-(1H-pyrrol-1-yl)methylbutanoic acid methyl esters converted to 3-aryl-3-trifluoromethyl-2,3-dihydro-1H-pyrrolizin-1-ones by the intramolecular Friedel-Crafts reaction.

Experimental part. By the interaction of 3-amino-3-aryl-4,4,4-trifluorobutanoic acid methyl esters with 2,5-dimethoxytetrahydrofuranin acetic acid at 70 оC 4,4,4-trifluoro-3-aryl-3-(1H-pyrrol-1-yl)methylbutanoic acid methyl esters were obtained and subsequently cyclized into 3-aryl-3-trifluoromethyl-2,3-dihydro-1H-pyrrolizin-1-ones upon treatment with boron tribromide in dichloromethane at room temperature. The structures of the compounds synthesized were confirmed by LCMS, IR and NMR (1H, 13C, 19F) spectroscopic methods.

Conclusions. An efficient two step protocol for the synthesis of 3-aryl-3-trifluoromethyl-2,3-dihydro-1H-pyrrolizin-1-ones has been developed. It includes transformation of 3-amino-3-aryl-4,4,4-trifluorobutanoic acid methyl esters into the corresponding 3-(1H-pyrrol-1-yl) derivatives and their further intramolecular cyclization.

Downloads

Download data is not yet available.

References

  1. Smith, L. W., Culvenor, C. C. J. (1981). Plant sources of hepatotoxic pyrrolizidine alkaloids. Journal of Natural Products, 44 (2), 129–152. https://doi.org/10.1021/np50014a001
  2. Belal, A., El–Gendy Bel–D. (2014). Pyrrolizines : promising scaffolds for anticancer drugs. Bioorganic and Medicinal Chemistry, 22 (1), 46–53. https://doi.org/10.1016/j.bmc.2013.11.040
  3. Jarosinski, M. A., Reddy, P. S., Anderson, W. K. (1993). Synthesis, chemical reactivity, and antitumor evaluation of congeners of carmethizole hydrochloride, an experimental acylated vinylogous carbinolamine tumor inhibitor. Journal of Medicinal Chemistry, 36 (23), 3618–3627. https://doi.org/10.1021/jm00075a017
  4. Atwell, G. J., Fan, J.–Y., Tan, K. & Denny, W. (1998). DNA–directed alkylating agents. 7. Synthesis, DNA interaction, and antitumor activity of bis(hydroxymethyl)– and bis(carbamate)–substituted pyrrolizines and imidazoles. Journal of Medicinal Chemistry, 41, 4744–4754. https://doi.org/10.1021/jm9803119
  5. Liedtke, A. J., Keck, P. R. W. E. F., Lehmann, F, Koeberle, A., Werz, O., Laufer, S. A. (2009). Arylpyrrolizines as inhibitors of microsomal prostaglandin E2 synthase–1 (mPGES–1) or as dual inhibitors of mPGES–1 and 5–lipoxygenase (5-LOX). Journal of Medicinal Chemistry, 52 (15), 4968–4972. https://doi.org/10.1021/jm900481c
  6. Laufer, S. A., Augustin, J., Dannhardt, G, Kiefer, W. (1994). (6,7–Diaryldihydropyrrolizin–5–yl)acetic acids, a novel class of potent dual inhibitors of both cyclooxygenase and 5-lipoxygenase. Journal of Medicinal Chemistry, 37 (12), 1894–1897. https://doi.org/10.1021/jm00038a021
  7. Abbas, S. E., Awadallah, F. M., Ibrahim, Gouda, A. M. (2010). Novel substituted and fused pyrrolizine derivatives : synthesis, anti–inflammatory and ulcerogenecity studies. European Journal of Medicinal Chemistry, 45 (2), 482–491. https://doi.org/10.1016/j.ejmech.2009.10.031
  8. Barsoum, F. F. (2011). Synthesis and molecular modeling studies of anti–inflammatory active 1H–pyrrolizine–5–carboxamides. Archiv der Pharmazie, 344 (1), 56–65. https://doi.org/10.1002/ardp.201000166
  9. Yu, H., Wang, F., Zhang, S. F. (2003). Synthesis of 5–aryl–1,2–dihydro–1–pyrrolizinones. Chinese Chemical Letters, 14 (6), 565–568.
  10. Ritthiwigrom, T., Nash, R. J. & Pyne, S. G. (2010). Synthesis of polyhydroxylated pyrrolizidine and indolizidine compounds and their glycosidase inhibitory activities. Tetrahedron, 66 (48), 9340–9347. https://doi.org/10.1016/j.tet.2010.10.008
  11. Rault, S., Lancelot, J. C., Bouyazza, L., Robba, M., Quermonne, M. A., Nammathao, B., Louchahi-Raoul, J. & Marcy, R. (1991). Synthesis and preliminary study of psychotropic effect of alkylamino and iminopyrrolo[1,2–a]indoles. European Journal of Medicinal Chemistry, 26, 939–946. https://doi.org/10.1016/0223-5234(91)90136-b
  12. Buechter, D. D., Thurston, D. E. (1987). Studies on the pyrrolizidine antitumor agent, clazamycin: interconversion of clazamycins A and B. Journal of Natural Products, 50 (3), 360–367. https://doi.org/10.1021/np50051a004
  13. Wang, J., Sánchez-Roselló, M., Aceña, J. L., del Pozo, C., Sorochinsky, A. E., Fustero, S., … Liu, H. (2013). Fluorine in Pharmaceutical Industry : Fluorine–Containing Drugs Introduced to the Market in the Last Decade (2001–2011). Chemical Reviews, 114 (4), 2432–2506. https://doi.org/10.1021/cr4002879
  14. Schierlinger, C., Burger, K. (1992). Peptide modification by introduction of α-trifluoromethyl α–amino acids via 4–trifluoromethyl–1,3–oxazolidin–2,5–diones. Tetrahedron Letters, 33 (2), 193–194. https://doi.org/10.1016/0040-4039(92)88047-9
  15. Iyer, R. P., Yu, D., Ho, N.–H., Tan, W., & Agrawal, S. (1995). A novel nucleoside phosphoramidite synthon derived from 1R, 2S–ephedrine. Tetrahedron: Asymmetry, 6 (5), 1051–1054. https://doi.org/10.1016/0957-4166(95)00122-6
  16. Chandra Sheker Reddy, A., Shanthan Rao, P.,Venkataratnam, R. (1997). Fluoro organics : facile syntheses of novel 2– or 4–trifluoromethyl–1H–arylo–1,5–diazepines, oxazepines, thiazepines, 2–(1,1,1–trifluoroacetonyl)imidazoles, oxazoles and thiazoles. Tetrahedron, 53 (16), 5847–5854. https://doi.org/10.1016/s0040-4020(97)00244-5
  17. Kawase, M., Niwa, M., Nozaki, M. & Motonashi, N. (1998). Synthesis of 2–trifluoromethyl–2,3,4,5–tetrahydro–1H–3–benzazepine derivatives. Heterocycles, 48 (3), 555–560. https://doi.org/10.3987/com-97-8090
  18. Kalantari, M., Reza Islami, M., Hassani, Z. & Saidi, K. (2006). Synthesis of dimethyl 1–(trifluoromethyl)–3–pyrrolizine–2,3–dicarboxylate using phosphorus compounds. Arkivoc, X, 55–62. https://doi.org/10.3998/ark.5550190.0007.a07
  19. Semenov, V. V, Zolotareva, N. V, Dolgonosova, A. Y. (2009). Oligomerization in the reaction of acetylacetone with organic diisocyanates. Russian Journal of Organic Chemistry, 45 (6), 936–938. https://doi.org/10.1134/s1070428009060232
  20. Sonnet, P., Dallemagne, P., Guillon, J., Enguehard, C., Stiebing, S., Tanguy, J., … Séralini, G.–E. (2000). New aromatase inhibitors. Synthesis and biological activity of aryl–substituted pyrrolizine and indolizine derivatives. Bioorganic & Medicinal Chemistry, 8 (5), 945–955. https://doi.org/10.1016/s0968-0896(00)00024-9
  21. Belloir, P. F., Laurent, A., Mison, P., Lesniak, S., & Bartnik, R. (1986). A New Approach to the Synthesis of Pyrrolizines: A One–pot Procedure from 2H–Pyrroles. Synthesis, 1986 (08), 683–686. https://doi.org/10.1055/s-1986-31750
  22. Pinho e Melo, T. M. V. D., Soares, M. I. L., Paixão, J. A., Beja, A. M., Silva, M. R., Alte da Veiga, L., & Pessoa, J. C. (2002). Synthesis of Chiral Pyrrolo[1,2–c]thiazoles via Intramolecular Dipolar Cycloaddition of Münchnones : An Interesting Rearrangement to Pyrrolo[1,2–c]thiazines. The Journal of Organic Chemistry, 67 (12), 4045–4054. https://doi.org/10.1021/jo010807p
  23. Yavari, I., Adib, M. (2001). Efficient synthesis of 5,6,7–trisubstituted 1H–pyrrolizines. Tetrahedron, 57 (27), 5873–5878. https://doi.org/10.1016/s0040-4020(01)00525-7
  24. Tasgin, D. I., Unaleroglu, C. (2016). Ring annulation versus alkylation of pyrrole with α–phosphoryl–α,β–unsaturated ketones. Tetrahedron, 72 (39), 5934–5942. https://doi.org/10.1016/j.tet.2016.08.045
  25. Campbell, S. E., Comer, M. C., Derbyshire, P. A., Despinoy, X. L. M., McNab, H., Morrison, R., … Thornley, C. (1997). Synthesis of pyrrolizin–3–ones by flash vacuum pyrolysis of pyrrol–2–ylmethylidene Meldrum’s acid derivatives and 3– (pyrrol–2–yl)propenoic esters. Journal of the Chemical Society, Perkin Transactions 1, (15), 2195–2202. https://doi.org/10.1039/a701749i
  26. Unaleroglu, C., Tasgin, D., Aytac, S., & Temelli, B. (2009). An Efficient Synthetic Route for Pyrrolizinone Synthesis through Functionalized C–Alkylpyrroles. Synthesis, 2009 (19), 3243–3250. https://doi.org/10.1055/s-0029-1216951
  27. Tasgin, D. I., Unaleroglu, C. (2013). Michael addition of N–heteroaromatics to vinylphosphonates and synthesis of phosphoryl pyrrolizones by cyclization of Michael adducts. Synthesis, 45 (02), 193–198. https://doi.org/10.1055/s-0032-1317894
  28. Byers, J. H., DeWitt, A., Nasveschuk, C. G., & Swigor, J. E. (2004). Tandem radical–electrophilic annulations to pyrrole. Tetrahedron Letters, 45 (35), 6587–6590. https://doi.org/10.1016/j.tetlet.2004.07.037
  29. Unaleroglu, C., Yazici, A. (2007). Gadolinium triflate catalyzed alkylation of pyrroles : efficient synthesis of 3–oxo–2,3–dihydro–1H–pyrrolizine derivatives. Tetrahedron, 63 (25), 5608–5613. https://doi.org/10.1016/j.tet.2007.04.018
  30. Clauson–Kaas, N., Tyle, Z., Rottenberg, M., Stenhagen, E., & Östling, S. (1952). Preparation of Cis– and Trans 2,5–Dimethoxy–2–(acetamidomethyl)–2,5–dihydrofuran, of Cis– and Trans 2,5–Dimethoxy–2–(acetamidomethyl)–tetrahydrofuran and of 1–Phenyl–2–(acetamidomethyl)–pyrrole. Acta Chemica Scandinavica, 6, 667–670. https://doi.org/10.3891/acta.chem.scand.06-0667
  31. Elming, N., Clauson–Kaas, N., Rottenberg, M., Stenhagen, E., & Östling, S. (1952). The Preparation of Pyrroles from Furans. Acta Chemica Scandinavica, 6, 867–874. https://doi.org/10.3891/acta.chem.scand.06-0867
  32. Kolicheva, M. E., Gerus, I. I., Yagupolskiy, Yu. L. & Kuchar, V. P. (1991). Zhurnal organicheskoy chimii, 27 (1), 117–121.
  33. Jefford, C. W., Sienkiewicz, K., Thornton, S. R. (1995). Short, enantiospecific syntheses of indolizidines 209 B and 209 D, and piclavine a from diethyl–L–Glutamate. Helvetica Chimica Acta, 78 (6), 1511–1524. https://doi.org/10.1002/hlca.19950780610

Downloads

Published

2019-03-13

How to Cite

(1)
Melnykov, S. V.; Tkachuk, V. M.; Grozav, A. M.; Gillaizeau, I.; Sukach, V. A. The Synthesis of 3-Aryl-3-Trifluoromethyl-2,3-Dihydro-1h-Pyrrolizin-1-Ones. J. Org. Pharm. Chem. 2019, 17, 13-19.

Issue

Vol. 17 No. 1(65) (2019)

Section

Original Researches

License

Copyright (c) 2019 National University of Pharmacy

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors publishing their works in the Journal of Organic and Pharmaceutical Chemistry agree with the following terms:

1. Authors retain copyright and grant the journal the right of the first publication of the work under Creative Commons Attribution License allowing everyone to distribute and re-use the published material if proper citation of the original publication is given.

2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal’s published version of the work (e.g., post it to an institutional repository or publish it in a book) providing proper citation of the original publication.

3. Authors are permitted and encouraged to post their work online (e.g. in institutional repositories or on authors’ personal websites) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (see The Effect of Open Access).