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image of Effects of Catalysts, Solvents, and Temperature on Nenitzescu Reaction

Abstract

Indole derivatives possess a wide range of biological activities, including antibacterial, anti-inflammatory, analgesic, and anticancer properties. The Nenitzescu reaction is a valuable approach for their synthesis; however, there are challenges, such as the limited availability of dinitro derivatives and complex workup procedures, which necessitate optimization and improvement in practical efficiency. The Nenitzescu reaction is a versatile method for synthesizing hydroxyindoles, particularly 5-hydroxyindoles. 5-Hydroxyindoles play a crucial role as fundamental components in a wide range of natural chemicals and pharmaceuticals. This reaction has the potential to be applied in the fields of medicinal chemistry and natural product synthesis. The selection of catalysts, solvents, and temperature is a crucial factor in maximizing yields. Scientists have examined different solvents, catalysts, and reaction conditions in order to improve the output and effectiveness of the Nenitzescu process. The objective of this study is to examine the requirements for producing 5-hydroxyindoles by the Nenitzescu reaction. The study investigates the influence of catalysts, solvents, and reaction temperatures on the yield of the reaction. The main emphasis is on the Nenitzescu reaction, with the objective of enhancing its practicality and environmental friendliness. Several trials using various solvents and catalysts are conducted. Nitromethane and acetic acid serve as effective solvents. The cyclization of hydroxy indoles is enhanced by zinc halides, specifically ZnCl or ZnI.

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2025-07-29
2025-10-27
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References

  1. Van Baelen G. Hostyn S. Dhooghe L. Tapolcsányi P. Mátyus P. Lemière G. Dommisse R. Kaiser M. Brun R. Cos P. Maes L. Hajós G. Riedl Z. Nagy I. Maes B.U.W. Pieters L. Structure-activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids, and their tricyclic and bicyclic analogues. Bioorg. Med. Chem. 2009 17 20 7209 7217 10.1016/j.bmc.2009.08.057 19781948
    [Google Scholar]
  2. Purkar S. Bhandari D. Indole: A promising pharmacophore for medicinal activity. Int. J. Res. Pharm. Allied Sci. 2022 1 2 39 57
    [Google Scholar]
  3. Sumpter W.C. Miller F.M. Heterocyclic Compounds with Indole and Carbazole Systems. 2009 Vol. 8
    [Google Scholar]
  4. Stempel E. Gaich T. Cyclohepta [b] indoles: a privileged structure motif in natural products and drug design. Acc. Chem. Res. 2016 49 11 2390 2402 10.1021/acs.accounts.6b00265 27709885
    [Google Scholar]
  5. Kumari A. Singh R.K. Medicinal chemistry of indole derivatives: Current to future therapeutic prospectives. Bioorg. Chem. 2019 89 103021 10.1016/j.bioorg.2019.103021 31176854
    [Google Scholar]
  6. Heravi M.M. Rohani S. Zadsirjan V. Zahedi N. Fischer indole synthesis applied to the total synthesis of natural products. RSC Advances 2017 7 83 52852 52887 10.1039/C7RA10716A
    [Google Scholar]
  7. Bugaenko D.I. Karchava A.V. Yurovskaya M.A. Synthesis of indoles: recent advances. Russ. Chem. Rev. 2019 88 2 99 159 10.1070/RCR4844
    [Google Scholar]
  8. Mohd Jamel N.S. Skhirtladze L. Hussein A.A. Ma Y. Woon K.L. Abdulwahab M.K. Grazulevicius J.V. Ariffin A. Microwave-assisted buchwald-hartwig double amination: A rapid and promising approach for the synthesis of TADF compounds. ACS Omega 2024 9 51 50446 50457 10.1021/acsomega.4c07563 39741864
    [Google Scholar]
  9. Docherty J.H. Lister T.M. Mcarthur G. Findlay M.T. Domingo-Legarda P. Kenyon J. Choudhary S. Larrosa I. Transition-metal-catalyzed C-H bond activation for the formation of C-C bonds in complex molecules. Chem. Rev. 2023 123 12 7692 7760 10.1021/acs.chemrev.2c00888 37163671
    [Google Scholar]
  10. Radhika S. Neetha M. Aneeja T. Anilkumar G. Microwave-assisted amination reactions: An overview. Curr. Org. Chem. 2020 24 19 2235 2255 10.2174/1385272824999200914111246
    [Google Scholar]
  11. Li M-Y. Gu A. Li J. Liu Y. Advanced green synthesis: Solvent-free and catalyst-free reaction. Green Synth Catal 2024
    [Google Scholar]
  12. Taber D.F. Tirunahari P.K. Indole synthesis: a review and proposed classification. Tetrahedron 2011 67 38 7195 7210 10.1016/j.tet.2011.06.040 25484459
    [Google Scholar]
  13. Schenck L.W. Sippel A. Kuna K. Frank W. Albert A. Kucklaender U. Dialkyl quinone-2,3-dicarboxylates in the Nenitzescu reaction. Tetrahedron 2005 61 38 9129 9139 10.1016/j.tet.2005.07.032
    [Google Scholar]
  14. Gidding C. Kellie S.J. Kamps W.A. de Graaf S.S. Vincristine revisited. Crit. Rev. Oncol. Hematol. 1999 29 3 267 287 10.1016/S1040‑8428(98)00023‑7 10226730
    [Google Scholar]
  15. Syed Y.Y. Sumatriptan/naproxen sodium: a review in migraine. Drugs 2016 76 1 111 121 10.1007/s40265‑015‑0521‑8 26628293
    [Google Scholar]
  16. Ivan B.C. Caira M.R. Dumitrascu F. Nenitzescu indole synthesis: 1929-2019 unexpected formation of a pyrrole-azepine hybrid in the Nenitzescu indole synthesis: a reinvestigation. Revista de Chimie 2020 71 5 51 57 10.37358/RC.20.5.8112
    [Google Scholar]
  17. Jasiewicz B. Kozanecka-Okupnik W. Przygodzki M. War ajtis, B.; Rychlewska, U.; Pospieszny, T.; Mrówczy ska, L. Synthesis, antioxidant and cytoprotective activity evaluation of C-3 substituted indole derivatives. Sci. Rep. 2021 11 1 15425 10.1038/s41598‑021‑94904‑z 34326403
    [Google Scholar]
  18. Singh R. Role of tryptophan in health and disease: Systematic review of the anti-oxidant, anti-inflammation, and nutritional aspects of tryptophan and its metabolites. World Heart J. 2019 11 2 161 178
    [Google Scholar]
  19. Lyubchanskaya V.M. Alekseeva L.M. Savina S.A. Shashkov A.S. Granik V.G. Synthesis of furoindoles and benzodifurans by the nenitzescu reaction. Chem. Heterocycl. Compd. 2003 39 7 872 877 10.1023/A:1026138119475
    [Google Scholar]
  20. Allen G.R. The synthesis of 5 hydroxyindoles by the N enitzescu reaction. Org. React. 2004 20 337 454
    [Google Scholar]
  21. Singh P. Kaur S. Sharma A. Kaur G. Bhatti R. TNF- and IL-6 inhibitors: Conjugates of N-substituted indole and aminophenylmorpholin-3-one as anti-inflammatory agents. Eur. J. Med. Chem. 2017 140 92 103 10.1016/j.ejmech.2017.09.003 28923390
    [Google Scholar]
  22. Lucas S. The pharmacology of indomethacin. Headache 2016 56 2 436 446 10.1111/head.12769 26865183
    [Google Scholar]
  23. Dhiman A. Sharma R. Singh R.K. Target-based anticancer indole derivatives and insight into structure activity relationship: A mechanistic review update (2018-2021). Acta Pharm. Sin. B 2022 12 7 3006 3027 10.1016/j.apsb.2022.03.021 35865090
    [Google Scholar]
  24. Hassan S.M. Farid A. Panda S.S. Bekheit M.S. Dinkins H. Fayad W. Girgis A.S. Indole compounds in oncology: therapeutic potential and mechanistic insights. Pharmaceuticals (Basel) 2024 17 7 922 10.3390/ph17070922 39065774
    [Google Scholar]
  25. Karimabad M.N. Mahmoodi M. Jafarzadeh A. Darekordi A. Hajizadeh M.R. Hassanshahi G. Molecular targets, anti-cancer properties and potency of synthetic indole-3-carbinol derivatives. Mini Rev. Med. Chem. 2019 19 7 540 554 10.2174/1389557518666181116120145 30444199
    [Google Scholar]
  26. Li J. Gu A. Nong X.M. Zhai S. Yue Z.Y. Li M.Y. Liu Y. Six membered aromatic nitrogen heterocyclic anti tumor agents: Synthesis and applications. Chem. Rec. 2023 23 12 e202300293 10.1002/tcr.202300293 38010365
    [Google Scholar]
  27. Jha M. Youssef D. Sheehy H. Jha A. Synthesis and pharmacology of clinical drugs containing isoindoline heterocycle core. Organics 2025 6 1 3 10.3390/org6010003
    [Google Scholar]
  28. Li J. Gu A. Li M.Y. Heteroaryl group containing trisubstituted alkenes: synthesis and anti tumor activity. Chem. Biodivers. 2024 21 11 e202401469 10.1002/cbdv.202401469 39145746
    [Google Scholar]
  29. Luu Q.H. Guerra J.D. Castañeda C.M. Martinez M.A. Saunders J. Garcia B.A. Gonzales B.V. Aidunuthula A.R. Mito S. Ultrasound assisted one-pot synthesis of benzo-fused indole-4,9-dinones from 1,4-naphthoquinone and -aminoacetals. Tetrahedron Lett. 2016 57 21 2253 2256 10.1016/j.tetlet.2016.04.031 34054151
    [Google Scholar]
  30. Venkateshwarlu R. Nath Singh S. Siddaiah V. Ramamohan H. Dandela R. Amirul Hossain K. Vijaya Babu P. Pal M. Ultrasound assisted rapid synthesis of mefenamic acid based indole derivatives under ligand free Cu-catalysis: Their pharmacological evaluation. Bioorg. Med. Chem. Lett. 2020 30 10 127112 10.1016/j.bmcl.2020.127112 32209292
    [Google Scholar]
  31. Shefali S. Srivastava S.K. Husbands S.M. Lewis J.W. Extension of the Nenitzescu reaction to simple ketones provides an efficient route to 1 -alkyl-5 -hydroxynaltrindole analogues, potent and selective -opioid receptor antagonists. J. Med. Chem. 2005 48 2 635 638 10.1021/jm040853s 15658877
    [Google Scholar]
  32. Liu W.Q. Lei T. Song Z.Q. Yang X.L. Wu C.J. Jiang X. Chen B. Tung C.H. Wu L.Z. Visible light promoted synthesis of indoles by single photosensitizer under aerobic conditions. Org. Lett. 2017 19 12 3251 3254 10.1021/acs.orglett.7b01367 28548863
    [Google Scholar]
  33. Alekseeva L.M. Mukhanova T.I. Panisheva E.K. Anisimova O.S. Turchin K.F. Komkov A.V. Dorokhov V.A. Granik V.G. Acetyl ketene aminals in Nenitzescu reaction. Russ. Chem. Bull. 1999 48 1 160 165 10.1007/BF02494420
    [Google Scholar]
  34. Das S. Visible-light-induced dearomative annulation of indoles towardstereoselective formation of fused- and spiro indolines. ACS Omega 2024 9 34 acsomega.4c02848 10.1021/acsomega.4c02848 39220487
    [Google Scholar]
  35. Patil S. Patil R. Miller D. Solid phase synthesis of biologically important indoles. Curr. Med. Chem. 2009 16 20 2531 2565 10.2174/092986709788682010 19601797
    [Google Scholar]
  36. Sarkar D. Amin A. Qadir T. Sharma P.K. Synthesis of medicinally important indole derivatives: A Review. Open Med. Chem. J. 2021 15 1 1 16 10.2174/1874104502015010001
    [Google Scholar]
  37. Tretyakova E.V. Yarmukhametova L.R. Salimova E.V. Kukovinets O.S. Parfenova L.V. The Nenitzescu reaction in the synthesis of new abietane diterpene indoles. Chem. Heterocycl. Compd. 2020 56 10 1366 1369 10.1007/s10593‑020‑02824‑z
    [Google Scholar]
  38. Patil S. Patil R. Miller D. Synthetic applications of the Nenitzescu reaction to biologically active 5-hydroxyindoles. Curr. Org. Chem. 2008 12 9 691 717 10.2174/138527208784567223
    [Google Scholar]
  39. Nigam V. Singh S. Kasana S. Kumar S. Das Kurmi B. Das Gupta G. Patel P. Revolutionizing indole synthesis: A microwave powered approach. ChemistrySelect 2024 9 23 e202402171 10.1002/slct.202402171
    [Google Scholar]
  40. Almalki F.A. Baryyan A.O. Recent advances in the green synthesis of indole and its derivatives using microwave irradiation and the role of indole moiety in cancer. Green Chem. Lett. Rev. 2024 17 1 2362925 10.1080/17518253.2024.2362925
    [Google Scholar]
  41. Hermans R. Van Hoof M. Van Meervelt L. Dehaen W. Exploration of the divergent outcomes for the nenitzescu reaction of piperazinone enaminoesters. Organics 2023 4 2 146 163 10.3390/org4020012
    [Google Scholar]
  42. Afroz M. Kumar G.S. Microwave-assisted synthesis, molecular docking studies and biological evaluation of novel thiazole, imidazole-indole hybrids. Asian J. Chem. 2023 35 3 705 711 10.14233/ajchem.2023.27297
    [Google Scholar]
  43. Ashok D. Gundu S. Aamate V.K. Devulapally M.G. Conventional and microwave-assisted synthesis of new indole-tethered benzimidazole-based 1,2,3-triazoles and evaluation of their antimycobacterial, antioxidant and antimicrobial activities. Mol. Divers. 2018 22 4 769 778 10.1007/s11030‑018‑9828‑1 29671194
    [Google Scholar]
  44. Padmapriya M. Hakkimane S.S. Gaonkar S.L. Synthetic approaches, emerging applications, and challenges of indole-based five-membered heterocycles in medicinal chemistry. Discover Applied Sciences 2025 7 3 208 10.1007/s42452‑025‑06598‑x
    [Google Scholar]
  45. Kucklaender U. Bollig R. Frank W. Gratz A. Jose J. A novel application of DDQ as electrophile in the Nenitzescu reaction. Bioorg. Med. Chem. 2011 19 8 2666 2674 10.1016/j.bmc.2011.03.006 21459578
    [Google Scholar]
  46. Dumitrascu F. Ilies M.A. Recent advances in the Nenitzescu indole synthesis (1990-2019). Adv. Heterocycl. Chem. 2021 133 65 157 10.1016/bs.aihch.2020.03.001
    [Google Scholar]
  47. Ionescu L.G. A prominent scientist and educator. South Braz. J. Chem. 1993 1 1 4
    [Google Scholar]
  48. Nenitzescu C. Derivatives of 2-methyl-5-hydroxyindole. Bull Soc. Chim Romania 1929 11 37 43
    [Google Scholar]
  49. Nenitzescu C. Über eine neue Indol‐Synthese. Berichte der deutschen chemischen Gesellschaft (A and B Series), 1925 58 6 1063 1064 10.1002/cber.19250580613
    [Google Scholar]
  50. Panisheva E.K. Alekseeva L.M. Granik V.G. New Approach to the Synthesis of Benzo [g] pyrimido [4, 5-b] indoles. Pharm. Chem. J. 2004 38 3 146 147 10.1023/B:PHAC.0000034304.00100.d7
    [Google Scholar]
  51. Li J.J. Li, JJ White Reagent. Name Reactions. Berlin, Heidelberg Springer 2009 10.1007/978‑3‑642‑0‑8_267
    [Google Scholar]
  52. Lyubchanskaya V.M. Panisheva E.K. Savina S.A. Alekseeva L.M. Shashkov A.S. Granik V.G. Quinoneimines in the Nenitzescu reaction. Russ. Chem. Bull. 2005 54 7 1690 1699 10.1007/s11172‑006‑0024‑6
    [Google Scholar]
  53. Steck E.A. Brundage R.P. Fletcher L.T. Some applications of the Nenitzescu reaction. J. Org. Chem. 1959 24 11 1750 1752 10.1021/jo01093a034
    [Google Scholar]
  54. Zhou B. Liu Z.C. Qu W.W. Yang R. Lin X.R. Yan S.J. Lin J. An environmentally benign, mild, and catalyst-free reaction of quinones with heterocyclic ketene aminals in ethanol: Site-selective synthesis of rarely fused [1,2-a]indolone derivatives via an unexpected anti-Nenitzescu strategy. Green Chem. 2014 16 9 4359 4370 10.1039/C4GC00676C
    [Google Scholar]
  55. Yu F.C. Hao X.P. Lin X.R. Yan S.J. Lin J. Synthesis of fused polyhalogeno-7a-hydroxy-[1,2-a]indol-5-one derivatives. Tetrahedron 2015 71 24 4084 4089 10.1016/j.tet.2015.04.113
    [Google Scholar]
  56. Bernier J.L. Henichart J.P. Extension of the Nenitzescu reaction to a cyclic enamino ketone. One-step synthesis of 6-hydroxy-9H-pyrimido[4,5-b]indole-2,4-dione. J. Org. Chem. 1981 46 21 4197 4198 10.1021/jo00334a018
    [Google Scholar]
  57. Singh R. Prakash R. Dehaen W. Polycyclic heterocycles by condensation of 1,4-benzoquinone analogs and nucleophiles. Adv. Heterocycl. Chem. 2021 135 319 410 10.1016/bs.aihch.2021.01.002
    [Google Scholar]
  58. Borthakur M. Gogoi S. Gogoi J. Boruah R.C. Lewis acid catalyzed rapid synthesis of 5-hydroxy-benzo[g]indole scaffolds by a modified Nenitzescu reaction. Tetrahedron Lett. 2010 51 39 5160 5163 10.1016/j.tetlet.2010.07.129
    [Google Scholar]
  59. Jeyakannu P. Chandru Senadi G. Chiang C.H. Kumar Dhandabani G. Chang Y.C. Wang J.J. An efficient approach to functionalized indoles from 3 iodanes via acyloxylation and acyl transfer. Adv. Synth. Catal. 2020 362 14 2911 2920 10.1002/adsc.202000402
    [Google Scholar]
  60. Kuckländer U. Beobachtungen zum mechanismus der Nenitzescu-reaktion. Tetrahedron 1972 28 20 5251 5259 10.1016/S0040‑4020(01)88944‑4
    [Google Scholar]
  61. Kuckländer U. Beobachtungen zum mechanismus der nenitzescu-reaktion-II. Tetrahedron 1973 29 6 921 927 10.1016/0040‑4020(73)80040‑7
    [Google Scholar]
  62. Kuckländer U. Beobachtungen zum mechanismus der nenitzescu-reaktion-III acylwanderungen-I. Tetrahedron 1975 31 13-14 1631 1639 10.1016/0040‑4020(75)87025‑6
    [Google Scholar]
  63. Gribble G.W. Indole ring synthesis: From natural products to drug discovery; 2016 10.1002/9781118695692
    [Google Scholar]
  64. Velezheva V.S. Sokolov A.I. Kornienko A.G. Lyssenko K.A. Nelyubina Y.V. Godovikov I.A. Peregudov A.S. Mironov A.F. The role of a Lewis acid in the Nenitzescu indole synthesis. Tetrahedron Lett. 2008 49 50 7106 7109 10.1016/j.tetlet.2008.09.087
    [Google Scholar]
  65. Velezheva V.S. Kornienko A.G. Topilin S.V. Turashev A.D. Peregudov A.S. Brennan P.J. Lewis acid catalyzed nenitzescu indole synthesis. J. Heterocycl. Chem. 2006 43 4 873 879 10.1002/jhet.5570430410
    [Google Scholar]
  66. Suryavanshi P.A. Sridharan V. Menéndez J.C. A new CAN-catalyzed domino process related to the Nenitzescu reaction: Very concise access to fused ortho-indolequinones from simple precursors. Tetrahedron 2013 69 26 5401 5406 10.1016/j.tet.2013.04.101
    [Google Scholar]
  67. Kong Y.C. Cheng K.F. Cambie R.C. Waterman P.G. Yuehchukene: A novel indole alkaloid with anti-implantation activity. J. Chem. Soc. Chem. Commun. 1985 2 47 48 10.1039/c39850000047
    [Google Scholar]
  68. Karg E.M. Luderer S. Pergola C. Bühring U. Rossi A. Northoff H. Sautebin L. Troschütz R. Werz O. Structural optimization and biological evaluation of 2-substituted 5-hydroxyindole-3-carboxylates as potent inhibitors of human 5-lipoxygenase. J. Med. Chem. 2009 52 11 3474 3483 10.1021/jm900212y 19492852
    [Google Scholar]
  69. Landwehr J. George S. Karg E.M. Poeckel D. Steinhilber D. Troschuetz R. Werz O. Design and synthesis of novel 2-amino-5-hydroxyindole derivatives that inhibit human 5-lipoxygenase. J. Med. Chem. 2006 49 14 4327 4332 10.1021/jm050801i 16821792
    [Google Scholar]
  70. Landwehr J. Troschuetz R. Synthesis of 3-EWG-substituted 2-amino-5-hydroxyindoles via Nenitzescu reaction. Synthesis 2005 2005 14 2414 2420
    [Google Scholar]
  71. Ballesteros-Garrido R. Recent developments in the synthesis of 4-, 5-, 6- and 7-azaindoles. Adv. Heterocycl. Chem. 2023 140 67 123 10.1016/bs.aihch.2023.01.001
    [Google Scholar]
  72. Borisov A.M. Kamanina N.A. Velikorodov A.V. Nenitzescu synthesis of carbamate indole derivatives from N,N -bis(methoxycarbonyl)-p-benzoquinone diimine. Russ. J. Org. Chem. 2007 43 3 414 416 10.1134/S1070428007030141
    [Google Scholar]
  73. Littell R. Morton G.O. Allen G.R. Mechanism of the Nenitzescu indole synthesis and its utilization for the preparation of carbazoles. J. Am. Chem. Soc. 1970 92 12 3740 3746 10.1021/ja00715a034
    [Google Scholar]
  74. Satta G. Usala E. Solinas A. Römer M. Livesi M. Pira G.M. Beccu A. Carboni S. Gaspa S. De Luca L. Pisano L. Azzena U. Carraro M. Nenitzescu synthesis of 5 Hydroxyindoles with zinc, iron and magnesium salts in cyclopentyl methyl ether. Eur. J. Org. Chem. 2021 2021 42 5835 5842 10.1002/ejoc.202101045
    [Google Scholar]
  75. Thönnißen V. Atodiresei I.L. Patureau F.W. Atroposelective Nenitzescu Indole Synthesis. Chemistry 2023 29 25 e202300279 10.1002/chem.202300279 36725685
    [Google Scholar]
  76. Singh R. Bhatia H. Prakash P. Debroye E. Dey S. Dehaen W. Tandem Nenitzescu reaction/nucleophilic aromatic substitution to form novel pyrido fused indole frameworks. Eur. J. Org. Chem. 2021 2021 34 4865 4875 10.1002/ejoc.202100827
    [Google Scholar]
  77. Janardhanan J.C. Mishra R.K. Das G. Sini S. Jayamurthy P. Suresh C.H. Praveen V.K. Manoj N. Babu B.P. Functionalizable 1H indazoles by palladium catalyzed aza nenitzescu reaction: Pharmacophores to donor acceptor type multi luminescent fluorophores. Asian J. Org. Chem. 2018 7 10 2094 2104 10.1002/ajoc.201800413
    [Google Scholar]
  78. Piotrkowska B. Nerdinger S. Schreiner E. Seli L.; Graczyk, P.P. A short synthesis of Dronedarone. Bioorg. Med. Chem. 2018 26 14 4330 4335 10.1016/j.bmc.2018.03.041 29716765
    [Google Scholar]
  79. Chen Y.H. Ellwart M. Toupalas G. Ebe Y. Knochel P. Preparation and application of solid, salt stabilized zinc amide enolates with enhanced air and moisture stability. Angew. Chem. Int. Ed. 2017 56 16 4612 4616 10.1002/anie.201700216 28326665
    [Google Scholar]
  80. Yang P.H. Recent developments in the heterocyclic ketene aminal-based synthesis of heterocycles. Res. Chem. Intermed. 2016 42 6 5617 5637 10.1007/s11164‑015‑2391‑9
    [Google Scholar]
  81. Lin J. Yang L-J. Yan S-J. Chen W. A facile route to 1, 3-diazaheterocycle-fused [1, 2-a] indole derivatives via acetic acid catalyzed cyclocondensation reactions. Synthesis 2010 2010 20 3536 3544 10.1055/s‑0030‑1258195
    [Google Scholar]
  82. Yang D. Wang L. Li D. Wang R. Magnesium catalysis in asymmetric synthesis. Chem 2019 5 5 1108 1166 10.1016/j.chempr.2019.02.002
    [Google Scholar]
  83. Teymori A. Sedaghat A. Kobarfard F. Ca-mediated Nenitzescu synthesis of 5-hydroxyindoles. Chem. Zvesti 2023 77 4 1791 1795 10.1007/s11696‑022‑02463‑y
    [Google Scholar]
  84. Maejima S. Yamaguchi E. Itoh A. Trans -Diastereoselective syntheses of -lactones by visible light-iodine-mediated carboesterification of alkenes. ACS Omega 2019 4 3 4856 4870 10.1021/acsomega.9b00333 31459670
    [Google Scholar]
  85. Drake S.R. Otway D.J. The synthesis of metal organic compounds of calcium, strontium and barium by ammonia gas-saturated ethereal solvents. J. Chem. Soc. Chem. Commun. 1991 7 517 519 10.1039/c39910000517
    [Google Scholar]
  86. Bariya D. Halpani C. Mishra S. Recent progress of calcium-based catalysts in organic transformations. Curr. Org. Chem. 2022 26 18 1661 1675 10.2174/1385272827666221212163027
    [Google Scholar]
  87. Patrick J.B. Saunders E.K. Studies on the nenitzescu synthesis of 5-hydroxyindoles. Tetrahedron Lett. 1979 20 42 4009 4012 10.1016/S0040‑4039(01)86490‑X
    [Google Scholar]
  88. Bernier J.L. Henichart J.P. Vaccher C. Houssin R. Condensation of p-benzoquinone with 4-cyano- and 4-nitroanilines. An extension of the Nenitzescu reaction. J. Org. Chem. 1980 45 8 1493 1496 10.1021/jo01296a030
    [Google Scholar]
  89. Katkevica D. Trapencieris P. Boman A. Kalvins I. Lundstedt T. The Nenitzescu reaction: An initial screening of experimental conditions for improvment of the yield of a model reaction. J. Chemometr. 2004 18 3-4 183 187 10.1002/cem.863
    [Google Scholar]
  90. Carlson R. Lundstedt T. Albano C. Hordvik A. Wold S. Elguero J. Screening of suitable solvents in organic synthesis. Strategies for solvent selection. Acta Chem. Scand. A 1985 39b 79 91 10.3891/acta.chem.scand.39b‑0079
    [Google Scholar]
  91. Carlson R. Lundstedt T. Stenstrøm Y. Aasen A.J. Fischer G.W. Scope of organic synthetic reactions. Multivariate methods for exploring the reaction space. An example with the Willgerodt-Kindler reaction. Acta Chem. Scand. A 1987 41b 164 173 10.3891/acta.chem.scand.41b‑0164
    [Google Scholar]
  92. Wold S. Sjöström M. Carlson R. Lundstedt T. Hellberg S. Skagerberg B. Wikström C. Öhman J. Multivariate design. Anal. Chim. Acta 1986 191 17 32 10.1016/S0003‑2670(00)86294‑7
    [Google Scholar]
  93. Ketcha D.M. Wilson L.J. Portlock D.E. The solid-phase Nenitzescu indole synthesis. Tetrahedron Lett. 2000 41 33 6253 6257 10.1016/S0040‑4039(00)00697‑3
    [Google Scholar]
  94. Bräse S. Gil C. Knepper K. The recent impact of solid-phase synthesis on medicinally relevant benzoannelated nitrogen heterocycles. Bioorg. Med. Chem. 2002 10 8 2415 2437 10.1016/S0968‑0896(02)00025‑1 12057632
    [Google Scholar]
  95. Allen G.R. Pidacks C. Weiss M.J. The mitomycin antibiotics. Synthetic studies. XIV. The nenitzescu indole synthesis. Formation of isomeric indoles and reaction mechanism. J. Am. Chem. Soc. 1966 88 11 2536 2544 10.1021/ja00963a032 5941382
    [Google Scholar]
  96. Nguyen D.T. Lenstra D.C. Mecinovi J. Chemoselective calcium-catalysed direct amidation of carboxylic esters. RSC Advances 2015 5 95 77658 77661 10.1039/C5RA18288C
    [Google Scholar]
  97. Priya B. Cherkadu V. Kalavagunta P. Ravirala N. Shivananju N. Zinc chloride catalyzed, dipolar aprotic solvent-mediated, one-pot synthesis of 2-[(benzo [d] thiazol-2-ylamino)(phenyl) methyl] phenols. Synlett 2016 27 20 2795 2798 10.1055/s‑0036‑1588595
    [Google Scholar]
  98. Schols D. Ruchko E.A. Lavrenov S.N. Kachala V.V. Nawrozkij M.B. Babushkin A.S. Structural analogs of umifenovir 2*. The synthesis and antiHIV activity study of new regioisomeric (trans-2-phenylcyclopropyl)-1 -indole derivatives. Chem. Heterocycl. Compd. 2015 51 11-12 978 983 10.1007/s10593‑016‑1807‑9
    [Google Scholar]
  99. Pawlak J.M. Khau V.V. Hutchison D.R. Martinelli M.J. A practical, Nenitzescu-based synthesis of LY311727, the first potent and selective s-PLA (2) inhibitor. J. Org. Chem. 1996 61 25 9055 9059 10.1021/jo9614452 11667899
    [Google Scholar]
  100. Avdeenko A.P. Konovalova S.A. Mikhailichenko O.N. Yusina A.L. Santalova A.A. Palamarchyk G.V. Zubatyuk R.I. Shishkin O.V. Burmistrov K.S. Reactions of N-arylsulfonylquinone imines with enamines. Russ. J. Org. Chem. 2011 47 8 1169 1180 10.1134/S1070428011080094
    [Google Scholar]
/content/journals/coc/10.2174/0113852728408541250707064354
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  • Article Type:
    Review Article
Keywords: benzoquinone ; 5-hydroxyindoles ; zinc halides ; crotonate ; benzylamine ; Nenitzescu reaction
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