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2000
Volume 30, Issue 5
  • ISSN: 1385-2728
  • E-ISSN: 1875-5348

Abstract

A simple and practical method has been developed for the synthesis of -aryl/heteroarylphthalimides, bisphthalimides, 1,8-naphthalimides, and related derivatives. This method involves the reaction of various primary amines with different anhydrides, such as phthalic anhydride and 1,8-naphthalic anhydride, in the presence of a catalytic amount of mandelic acid in aqueous ethanol under reflux conditions. The use of less toxic solvents, excellent yields, shorter reaction times, elimination of column chromatographic purifications, and low-cost and naturally occurring catalysts are some of the major advantages of this developed protocol.

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2026-03-03

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References

  1. AliI. WaniW.A. SaleemK. HaqueA. Thalidomide: A banned drug resurged into future anticancer drug.Curr. Drug Ther.201271323
     [Google Scholar]
  2. PriceD.K. AndoY. KrugerE.A. WeissM. FiggW.D. 5′-OH-thalidomide, a metabolite of thalidomide, inhibits angiogenesis.Ther. Drug Monit.2002241104110 11805730
     [Google Scholar]
  3. ScottL.J. Pomalidomide: A review of its use in patients with recurrent multiple myeloma.Drugs201474554956210.1007/s40265‑014‑0196‑6 24590685
     [Google Scholar]
  4. KumarS. RajeN. HideshimaT. IshitsukaK. RoccaroA. ShiraishiN. HamasakiM. YasuiH. MunshiN.C. RichardsonP. FiggW.D. AndersonK.C. Antimyeloma activity of two novel N-substituted and tetraflourinated thalidomide analogs.Leukemia20051971253126110.1038/sj.leu.2403776 15858615
     [Google Scholar]
  5. MarriottJ.B. WestbyM. CooksonS. GuckianM. GoodbournS. MullerG. ShireM.G. StirlingD. DalgleishA.G. CC-3052: A water-soluble analog of thalidomide and potent inhibitor of activation-induced TNF-α production.J. Immunol.199816184236424310.4049/jimmunol.161.8.4236 9780198
     [Google Scholar]
  6. JelaliH. MansourL. DeniauE. SauthierM. HamdiN. An efficient synthesis of phthalimides and their biological activities.Polycycl. Aromat. Compd.20224241806181310.1080/10406638.2020.1809468
     [Google Scholar]
  7. AssisS.P.O. AraújoT.G. SenaV.L.M. CatanhoM.T.J.A. RamosM.N. SrivastavaR.M. LimaV.L.M. Synthesis, hypolipidemic, and anti-inflammatory activities of arylphthalimides.Med. Chem. Res.201423270871610.1007/s00044‑013‑0673‑6
     [Google Scholar]
  8. PerveenS. OrfaliR. L -proline-catalyzed synthesis of phthalimide derivatives and evaluation of their antioxidant, anti-inflammatory, and lipoxygenase inhibition activities.J. Chem.201820181610.1155/2018/5198325
     [Google Scholar]
  9. BarbarossaA. CatalanoA. CeramellaJ. CarocciA. IacopettaD. RosanoC. FranchiniC. SinicropiM.S. Simple thalidomide analogs in melanoma: Synthesis and biological activity.Appl. Sci. (Basel)20211113582310.3390/app11135823
     [Google Scholar]
  10. Abdel-AzizA.A.M. El-AzabA.S. AttiaS.M. Al-ObaidA.M. Al-OmarM.A. El-SubbaghH.I. Synthesis and biological evaluation of some novel cyclic-imides as hypoglycaemic, anti-hyperlipidemic agents.Eur. J. Med. Chem.20114694324432910.1016/j.ejmech.2011.07.002 21783284
     [Google Scholar]
  11. HomsiA. KasidehA. Synthesis of some N-phthalimide amino acids derivatives and evaluation their biological activity.Int. J. Chemtech Res.20158418171825
     [Google Scholar]
  12. KokS.H.L. GambariR. ChuiC.H. YuenM.C.W. LinE. WongR.S.M. LauF.Y. ChengG.Y.M. LamW.S. ChanS.H. LamK.H. ChengC.H. LaiP.B.S. YuM.W.Y. CheungF. TangJ.C.O. ChanA.S.C. Synthesis and anti-cancer activity of benzothiazole containing phthalimide on human carcinoma cell lines.Bioorg. Med. Chem.20081673626363110.1016/j.bmc.2008.02.005 18295491
     [Google Scholar]
  13. PhatakP.S. BakaleR.D. DhumalS.T. DahiwadeL.K. ChoudhariP.B. Siva KrishnaV. SriramD. HavalK.P. Synthesis, antitubercular evaluation and molecular docking studies of phthalimide bearing 1,2,3-triazoles.Synth. Commun.201949162017202810.1080/00397911.2019.1614630
     [Google Scholar]
  14. HolandaV.N. LimaE.M.A. SilvaW.V. MaiaR.T. MedeirosR.L. GhoshA. LimaV.L.M. FigueiredoR.C.B.Q. Identification of 1,2,3-triazole-phthalimide derivatives as potential drugs against COVID-19: A virtual screening, docking and molecular dynamic study.J. Biomol. Struct. Dyn.202240125462548010.1080/07391102.2020.1871073 33459182
     [Google Scholar]
  15. OthmanI.M.M. Gad-ElkareemM.A.M. El-NaggarM. NossierE.S. AmrA.E.G.E. Novel phthalimide based analogues: Design, synthesis, biological evaluation, and molecular docking studies.J. Enzyme Inhib. Med. Chem.20193411259127010.1080/14756366.2019.1637861 31287341
     [Google Scholar]
  16. StewartS.G. SpagnoloD. PolomskaM.E. SinM. KarimiM. AbrahamL.J. Synthesis and TNF expression inhibitory properties of new thalidomide analogues derived via Heck cross coupling.Bioorg. Med. Chem. Lett.200717215819582410.1016/j.bmcl.2007.08.042 17851074
     [Google Scholar]
  17. ChenD.C. YeH.Q. WuH. A more efficient synthetic process of N-arylphthalimides in ionic liquid [bmim] [BF4].Catal. Commun.20078101527153010.1016/j.catcom.2006.12.024
     [Google Scholar]
  18. DabiriM. SalehiP. BaghbanzadehM. ShakouriM. OtokeshS. EkramiT. DoostiR. Efficient and eco-friendly synthesis of dihydropyrimidinones, bis(indolyl)methanes, and N-alkyl and N-arylimides in ionic liquids.J. Indian Chem. Soc.20074439340110.1007/BF03247224
     [Google Scholar]
  19. ZhouM.Y. LiY.Q. XuX.M. A new simple and efficient synthesis of N-aryl phthalimides in ionic liquid [bmim] [PF6].Synth. Commun.200333213777378010.1081/SCC‑120025187
     [Google Scholar]
  20. LiangJ. LvJ. FanJ. ShangZ. Polyethylene glycol as a nonionic liquid solvent for the synthesis of N-alkyl and N-arylimides.Synth. Commun.200939162822282810.1080/00397910802474966
     [Google Scholar]
  21. LoboH.R. SinghB.S. ShankarlingG.S. Deep eutectic solvents and glycerol: A simple, environmentally benign and efficient catalyst/reaction media for synthesis of N- aryl phthalimide derivatives.Green Chem. Lett. Rev.20125448753310.1080/17518253.2012.669500
     [Google Scholar]
  22. SenaV.L.M. SrivastavaR.M. SilvaR.O. LimaV.L.M. Synthesis and hypolipidemic activity of N-substituted phthalimides. Part V.Farmaco200358121283128810.1016/S0014‑827X(03)00185‑X 14630240
     [Google Scholar]
  23. ShindeS.B. TekaleS.U. KauthaleS.S. DeshmukhS.U. MaratheR.P. NawaleR.B. SonekarV.S. ThoratV.V. PawarR.P. A facile and efficient synthesis of N-aryl imides using trifluoroacetic acid.Int. J. Ind. Chem.201122112116
     [Google Scholar]
  24. LeZ.G. ChenZ.C. HuY. ZhengQ.G. Organic reactions in ionic liquids: Ionic liquid-promoted efficient synthesis of N -alkyl and N -arylphthalimides.J. Heterocycl. Chem.200542473573710.1002/jhet.5570420442
     [Google Scholar]
  25. XieY.T. HouR.S. WangH.M. KangI.J. ChenL.C. An efficient protocol for the synthesis of N-alkyl-and N-arylimides using the lewis acidic ionic liquid choline chloride· 2ZnCl2.J. Chin. Chem. Soc. (Taipei)200956483984210.1002/jccs.200900124
     [Google Scholar]
  26. MogilaiahK. ReddyG. RandheerA. A convenient procedure for the synthesis of phthalimides under microwave irradiation.IJCB195843B488288410.1002/chin.200433131
     [Google Scholar]
  27. LiH.Z. ZhangJ.S. ZhouY.M. LiT.S. A rapid synthesis of N-aryl phthalimides under microwave irradiation in the absence of solvent.Synth. Commun.200232692793010.1081/SCC‑120002706
     [Google Scholar]
  28. HeraviM.M. ShoarR.H. PedramL. Synthesis of N-arylphthalimides catalyzed by 1,4-diazabicyclo[2,2,2]octane [DABCO] in solventless system.J. Mol. Catal. Chem.20052311-2899110.1016/j.molcata.2005.01.005
     [Google Scholar]
  29. ThaleP.B. BoraseP.N. ShankarlingG.S. Magnetic nanocatalyst for the synthesis of maleimide and phthalimide derivatives.RSC Advances20144103594545946110.1039/C4RA09008J
     [Google Scholar]
  30. LangadeM.M. Efficient one pot synthesis of N-alkyl and N-aryl imides.PharmaChem.201132283286
     [Google Scholar]
  31. HabibiD. PordanjaniH.M. Phthalimide-N-sulfonic acid, an efficient catalyst for the synthesis of various isoindoline-1,3-dione derivatives.Chem. Pap.201771112293229910.1007/s11696‑017‑0223‑7
     [Google Scholar]
  32. BanerjeeB. KaurM. SharmaA. SinghA. PriyaA. GuptaV.K. JaitakV. Glycine catalyzed one-pot three-component synthesis of structurally diverse 2-amino substituted pyran annulated heterocycles in aqueous ethanol under refluxed conditions.Curr. Green Chem.20229316217310.2174/2213346110666221212152202
     [Google Scholar]
  33. BanerjeeB. PriyaA. KaurM. SharmaA. SinghA. GuptaV.K. JaitakV. Sodium dodecyl sulphate catalyzed one-pot three-component synthesis of structurally diverse 2-amino-3-cyano substituted tetrahydrobenzo[b]pyrans and spiropyrans in water at room temperature.Catal. Lett.2023153123547356010.1007/s10562‑022‑04256‑0
     [Google Scholar]
  34. BanerjeeB. PriyaA. KaurJ. KaurM. SinghA. SharmaA. Cyanuric chloride promoted various organic transformations.Synth. Commun.2023531285588210.1080/00397911.2023.2201889
     [Google Scholar]
  35. BanerjeeB. SinghA. SharmaA. PriyaA. KaurM. GuptaV.K. A simple and efficient method for the synthesis of benzo[3,4-a]phenazin-5-ols and benzo[f]pyrido[b]quinoxalin-5-ol derivatives using trisodium citrate dihydrate as an efficient organo-catalyst at room temperature.Polycycl. Aromat. Compd.20244463747376010.1080/10406638.2023.2238869
     [Google Scholar]
  36. BanerjeeB. PriyaA. SinghA. SharmaA. KaurM. BiswasK. Camphorsulfonic acid-catalyzed synthesis of a series of 2-aryl/heteroaryl/alkyl-1 H -anthra[ 1,2- d]imidazole-6,11-dione derivatives.Curr. Org. Chem.2024281296797510.2174/0113852728301570240405033544
     [Google Scholar]
  37. BanerjeeB. SharmaA. ChawlaP.A. JhaK.T. BiswasK. DebM. KaurM. PriyaA. SinghA. Trisodium citrate dihydrate catalyzed one-pot four component synthesis of spiropyrano-indenoquinoxaline derivatives and their molecular docking analysis on the anti-cancer efficacies.ARKIVOC20242024820241220310.24820/ark.5550190.p012.203
     [Google Scholar]
  38. BanerjeeB. PriyaA. SharmaA. SinghA. KaurM. Sodium dodecyl sulfate catalyzed one-pot three-component synthesis of structurally diverse 2-amino-3-cyano-4-substitued-4H-chromenes in aqueous medium at room temperature.ARKIVOC20232023720231211610.24820/ark.5550190.p012.116
     [Google Scholar]
  39. BanerjeeB. KaurM. SharmaV. GuptaV.K. KaurJ. SharmaA. PriyaA. SinghA. Camphor sulfonic acid catalyzed one-pot pseudo three-component synthesis of a series of 1,8-dioxo-octahydroxanthenes and comparative crystal structures investigations and Hirshfeld surface analysis of five such derivatives.Res. Chem. Intermed.202349114639467010.1007/s11164‑023‑05064‑w
     [Google Scholar]
  40. BanikB.K. BanerjeeB. Organocatalysis: A green tool for sustainable developments.Berlin, BostonDe Gruyter202210.1515/9783110732542
     [Google Scholar]
  41. KaurG. ThakurS. KaundalP. ChandelK. BanerjeeB. p‐Dodecylbenzenesulfonic acid: An efficient brønsted acid‐surfactant‐combined catalyst to carry out diverse organic transformations in aqueous medium.ChemistrySelect2018345129181293610.1002/slct.201802824
     [Google Scholar]
  42. KaurG. SinghA. KaurN. BanerjeeB. A general method for the synthesis of structurally diverse quinoxalines and pyrido-pyrazine derivatives using camphor sulfonic acid as an efficient organo-catalyst at room temperature.Synth. Commun.20215171121113110.1080/00397911.2021.1873383
     [Google Scholar]
  43. KaurG. SinghA. BalaK. DeviM. KumariA. DeviS. DeviR. GuptaV.K. BanerjeeB. Naturally occurring organic acid-catalyzed facile diastereoselective synthesis of biologically active (E)-3-(arylimino)indolin-2-one derivatives in water at room temperature.Curr. Org. Chem.201923161778178810.2174/1385272822666190924182538
     [Google Scholar]
  44. SharmaA. KaurG. GuptaV.K. BanerjeeB. A general method for the synthesis of 11H-indeno[1,2-b]quinoxalin-11-ones and 6H-indeno[1,2-b]pyrido[3,2-e]pyrazin-6-one derivatives using mandelic acid as an efficient organo-catalyst at room temperature.Curr. Organocatal.20229536110.2174/2213337208666210825112301
     [Google Scholar]
  45. BanerjeeB. SinghA. SharmaA. PriyaA. KaurM. KaurG. GuptaV.K. JaitakV. Mandelic acid catalyzed one-pot pseudo three-component synthesis of various trisubstituted methane derivatives at room temperature.ARKIVOC20222022910011810.24820/ark.5550190.p011.895
     [Google Scholar]
  46. KaurG. ShamimM. BhardwajV. GuptaV.K. BanerjeeB. Mandelic acid catalyzed one-pot three-component synthesis of α-aminonitriles and α-aminophosphonates under solvent-free conditions at room temperature.Synth. Commun.2020501545156010.1080/00397911.2020.1745844
     [Google Scholar]
  47. SinghA. KaurG. KaurA. GuptaV.K. BanerjeeB. A general method for the synthesis of 3,3-bis(indol-3-yl)indolin-2-ones, bis(indol-3-yl)(aryl)methanes and tris(indol-3-yl)methanes using naturally occurring mandelic acid as an efficient organo-catalyst in aqueous ethanol at room temperature.Curr. Green Chem.20207112814010.2174/2213346107666200228125715
     [Google Scholar]
  48. KaurG. KumarR. SarochS. GuptaV.K. BanerjeeB. Mandelic acid: An efficient organo-catalyst for the synthesis of 3-substituted-3-hydroxy-indolin-2-ones and related derivatives in aqueous ethanol at room temperature.Curr. Organocatal.20218147159
     [Google Scholar]
  49. LiangZ-P. LiJ. 2,2′-(Ethane-1,2-diyl)bis(isoindoline-1,3-dione).Acta Crystallogr.2006E62o5282o528310.1107/S1600536806043923
     [Google Scholar]
  50. SchwarzerA. WeberE. Influence of fluorine substitution on the crystal packing of n-phenylmaleimides and corresponding phthalimides.Cryst. Growth Des.2008828622874
     [Google Scholar]
  51. PluempanupatW. AdisakwattanaS. Yibchok-AnunS. ChavasiriW. Synthesis of N-phenylphthalimide derivatives as α-glucosidase inhibitors.Arch. Pharm. Res.200730121501150610.1007/BF02977317 18254235
     [Google Scholar]
  52. WangX. XiongW. HuangY. ZhuJ. HuQ. WuW. JiangH. Palladium-catalyzed synthesis of 1H-indenes and phthalimides via isocyanide insertion.Org. Lett.2017192158185821 29064722
     [Google Scholar]
  53. BertholdS. Derivatives of 4-amino-antipyrine.US Patent. US2506654A, May 91950
  54. AlmeidaM. AlvesC.C.D. AmaranteG.W. SouzaM.V.N.de. TeixeiraF.M. Thalidomide analogs from diamines: Synthesis and evaluation as inhibitors of TNF-a production.Chem. Pharm. Bull. (Tokyo)200755223226 17268092
     [Google Scholar]
  55. LiuZ. ZhouY. DuL. LiM. Novel intramolecular photoinduced electron transfer-based probe for the Human Ether-a-go-go-Related Gene (hERG) potassium channel.Analyst (Lond.)2015140248101810810.1039/C5AN01974E 26526230
     [Google Scholar]
  56. KumarM.M. VenkataramanaP. SwamyY.P. ChityalaY. N-Amino-1,8-naphthalimide is a regenerated protecting group for selective synthesis of mono-n-substituted hydrazines and hydrazides.Chemistry20212770177131772110.1002/chem.202102593 34664751
     [Google Scholar]
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A Facile and General Method for the Synthesis of N-Aryl/Heteroarylphthalimides, Bisphthalimides, and 1,8-Naphthalimides Utilizing Mandelic Acid as an Efficient Catalyst
Current Organic Chemistry 30, 371 (2026); https://doi.org/10.2174/0113852728379343250526113411
/content/journals/coc/10.2174/0113852728379343250526113411
/content/journals/coc/10.2174/0113852728379343250526113411
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  • Article Type:     Research Article
Keyword(s): Bioactive heterocycles; bisphthalimides; column chromatography free; mandelic acid; N-aryl/heteroarylphthalimides; naphthalimides

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