Mild and Efficient Synthesis of Polysubstituted Phthalimides and Piperidines Catalyzed by DABCO

  • Farideh Paymozd
  • Malek-Taher MaghsoodlouEmail author
  • Reza Heydari
  • Afshin Yazdani-Elah-Abadi
  • Mehrnoush Kangani
  • Claudia Graiff
Research Paper
Part of the following topical collections:
  1. Chemistry


Polysubstituted phthalimide derivatives have been isolated in excellent yield from the addition reaction between acetoacetanilide and dialkyl acetylenedicarboxylates by using DABCO as an efficient basic catalyst in EtOH at room temperature. This procedure led to the formation of new phthalimide derivative in the presence of di-tert-butylacetylendicarboxylate as acetylenic ester. The methodology has also been applied successfully for the synthesis of novel piperidine substitutes via the simple reaction between acetoacetanilide and alkyl propiolates. These reactions have some advantages such as not only the process is eco-friendly but also the yields are good and the work-up is simple.


Polysubstituted phthalimides Piperidine substitutes Acetoacetanilide Acetylenic esters DABCO 



We gratefully acknowledge financial support from the Research Council of the University of Sistan and Baluchestan


  1. Barhoumi-Slimi TM, Ourévitch M (2018) β-chloro-α, β-unsaturated carbonyls as convenient precursors of highly substituted benzenes. J Iran Chem Soc 15(3):629–636CrossRefGoogle Scholar
  2. Buncel E, Dust JM, Terrier F (1995) Rationalizing the regioselectivity in polynitroarene anionic. sigma.-adduct formation. Relevance to nucleophilic aromatic substitution. Chem Rev 95(7):2261–2280CrossRefGoogle Scholar
  3. Carballo RM, Ramirez MA, Rodríguez ML, Martin VS, Padrón JI (2006) Iron (III)-promoted aza-Prins-cyclization: direct synthesis of six-membered azacycles. Org Lett 8(17):3837–3840CrossRefGoogle Scholar
  4. Daly JW, Spande TF, Garraffo HM (2005) Alkaloids from amphibian skin: a tabulation of over eight-hundred compounds. J Nat Prod 68(10):1556–1575CrossRefGoogle Scholar
  5. Dastoorani P, Maghsoodlou MT, Khalilzadeh MA, Sarina E (2016) Synthesis of new dibenzofuran derivatives via Diels–Alder reaction of euparin with activated acetylenicesters. Tetrahedron Lett 57(3):314–316CrossRefGoogle Scholar
  6. Davis FA, Chao B, Rao A (2001) Intramolecular Mannich reaction in the asymmetric synthesis of polysubstituted piperidines: concise synthesis of the dendrobate alkaloid (+)-241D and its C-4 epimer. Org Lett 3(20):3169–3171CrossRefGoogle Scholar
  7. Fustero S, Jiménez D, Moscardó J, Catalán S, del Pozo C (2007) Enantioselectiveorganocatalytic intramolecular aza-Michael reaction: a concise synthesis of (+)-sedamine, (+)-allosedamine, and (+)-coniine. Org Lett 9(25):5283–5286CrossRefGoogle Scholar
  8. Hassan J, Sevignon M, Gozzi C, Schulz E, Lemaire M (2002) Aryl − aryl bond formation one century after the discovery of the Ullmann reaction. Chem Rev 102(5):1359–1470CrossRefGoogle Scholar
  9. Ho B, Crider AM, Stables JP (2001) Synthesis and structure–activity relationships of potential anticonvulsants based on 2-piperidinecarboxylic acid and related pharmacophores. Eur J Med Chem 36(3):265–286CrossRefGoogle Scholar
  10. Jazinizadeh T, Maghsoodlou MT, Heydari R, Yazdani-Elah-Abadi A (2017) Na2EDTA: an efficient, green and reusable catalyst for the synthesis of biologically important spirooxindoles, spiroacenaphthylenes and spiro-2-amino-4H-pyrans under solvent-free conditions. J Iran Chem Soc 14(10):2117–2125CrossRefGoogle Scholar
  11. Lebold TP, Leduc AB, Kerr MA (2009) Zn (II)-catalyzed synthesis of piperidines from propargyl amines and cyclopropanes. Org Lett 11(16):3770–3772CrossRefGoogle Scholar
  12. Mali AS, Potnis CS, Chaturbhuj GU (2018) Aluminized polyborate: a novel catalyst for the multicomponent solvent-free synthesis of alkyl 1, 2, 6-trisubstituted-4-[(hetero) arylamino]-1, 2, 5, 6-tetrahydropyridine-3-carboxylates. J Iran Chem Soc 15(6):1399–1409CrossRefGoogle Scholar
  13. Misra M, Pandey SK, Pandey VP, Pandey J, Tripathi R, Tripathi RP (2009) Organocatalyzed highly atom economic one pot synthesis of tetrahydropyridines as antimalarials. Bioorg Med Chem 17(2):625–633CrossRefGoogle Scholar
  14. Mohebat R, Yazdani-Elah-Abadi A, Maghsoodlou MT, Hazeri N (2017) DABCO-catalyzed multi-component domino reactions for green and efficient synthesis of novel 3-oxo-3H-benzo[a]pyrano[2,3-c]phenazine-1-carboxylate and 3-(5-hydroxybenzo[a]phenazin-6-yl) acrylate derivatives in water. Chin Chem Lett 28(5):943–948CrossRefGoogle Scholar
  15. Murty MS, Ram KR, Yadav JS (2008) BiCl3 promoted aza-Prins type cyclization: a rapid and efficient synthesis of 2, 4-disubstituted piperidines. Tetrahedron Lett 49(7):1141–1145CrossRefGoogle Scholar
  16. O’Hagan D (2000) Pyrrole, pyrrolidine, pyridine, piperidine and tropane alkaloids. Nat Prod Rep 17(5):435–446CrossRefGoogle Scholar
  17. Pearson DE, Buehler CA (1972) Friedel–Crafts acylations with little or no catalyst. Synthesis 10:533–542Google Scholar
  18. Petit S, Nallet JP, Guillard M, Dreux J, Chermat R, Poncelet M, Bulach C, Simon P, Fontaine C, Barthelmebs M, Imbs JL (1991) Synthesis and psychotropic activity of 3,4-diarylpiperidines: structure-activity relationship and antihypertensive activity antihypertensive. Eur J Med Chem 26(1):19–32CrossRefGoogle Scholar
  19. Saito S, Yamamoto Y (2000) Recent advances in the transition-metal-catalyzed regioselective approaches to polysubstituted benzene derivatives. Chem Rev 100(8):2901–2916CrossRefGoogle Scholar
  20. Sajadikhah SS, Hazeri N, Maghsoodlou MT, Habibi-Khorassani SM, Beigbabaei A, Willis AC (2013) Al(H2PO4)3 as an efficient and reusable catalyst for the multi-component synthesis of highly functionalized piperidines and dihydro-2-oxypyrroles. J Iran Chem Soc 10(5):863–871CrossRefGoogle Scholar
  21. Sales M, Charette AB (2005) A Diels–Alder approach to the stereoselective synthesis of 2, 3, 5, 6-tetra-and 2, 3, 4, 5, 6-pentasubstituted piperidines. Org Lett 7(26):5773–5776CrossRefGoogle Scholar
  22. Samai S, Ghosh D, Das UK, Atta S, Manna SK, Maiti DK (2016) Water–the best solvent for DMAP-mediated dual cyclization towards metal-free first synthesis of fully substituted phthalimides. Green Chem 18(10):2961–2965CrossRefGoogle Scholar
  23. Sharghi H, Aberi M, Doroodmand MM, Shiri P (2017) Chromium (III)-salen complex nanoparticles on AlPO4: as an efficient heterogeneous and reusable nanocatalyst for mild synthesis of highly functionalized piperidines, 2-arylbenzimidazoles, and 2-arylbenzothiazoles. J Iran Chem Soc 14(7):1557–1573CrossRefGoogle Scholar
  24. Sharghi H, Aboonajmi J, Aberi M, Shiri P (2018) Heterogeneous AlPO4(SO3H) nanosheets: novel catalyst for the multi-component synthesis of quinazolinones and highly functionalized piperidines. J Iran Chem Soc 15(5):1107–1118CrossRefGoogle Scholar
  25. Sheldrick GM (1990) Phase annealing in SHELX-90: direct methods for larger structures. Actacrystallogr A 46(6):467–473CrossRefGoogle Scholar
  26. Smith MB (2001) J. March in advanced organic chemistry. Wiley, New YorkGoogle Scholar
  27. Snieckus V (1990) Directed orthometalation: tertiary amide and O-carbamate directors in synthetic strategies for polysubstituted aromatics. Chem Rev 90(6):879–933CrossRefGoogle Scholar
  28. Takasu K, Shindoh N, Tokuyama H, Ihara M (2006) Catalytic imino Diels–Alder reaction by triflic imide and its application to one-pot synthesis from three components. Tetrahedron 62(51):11900–11907CrossRefGoogle Scholar
  29. Trost BM (1991) The atom economy: a search for synthetic efficiency. Science 254(5037):1471–1477CrossRefGoogle Scholar
  30. Zhou Y, Gregor VE, Ayida BK, Winters GC, Sun Z, Murphy D, Haley G, Bailey D, Froelich JM, Fish S, Webber SE, Hermann T, Wall D (2007) Synthesis and SAR of 3, 5-diamino-piperidine derivatives: novel antibacterial translation inhibitors as aminoglycoside mimetics. Bioorg Med Chem Lett 17(5):1206–1210CrossRefGoogle Scholar

Copyright information

© Shiraz University 2019

Authors and Affiliations

  • Farideh Paymozd
    • 1
  • Malek-Taher Maghsoodlou
    • 1
    Email author
  • Reza Heydari
    • 1
  • Afshin Yazdani-Elah-Abadi
    • 2
    • 3
    • 4
  • Mehrnoush Kangani
    • 1
  • Claudia Graiff
    • 5
  1. 1.Department of ChemistryThe University of Sistan and BaluchestanZahedanIran
  2. 2.Department of ChemistryPayame Noor UniversityTehranIran
  3. 3.Research Center of Environmental ChemistryPayame Noor UniversityArdakan, YazdIran
  4. 4.Department of BiologyScience and Arts UniversityYazdIran
  5. 5.Department of ChemistryUniversità degli Studi di ParmaParmaItaly

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