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Consecutive Betti/Bargellini multicomponent reactions: an efficient strategy for the synthesis of naphtho[1,2-f][1,4]oxazepine scaffolds

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Abstract

An efficient and convenient approach has been developed for the synthesis of naphtho[1,2-f][1,4]oxazepine structures based on the consecutive Betti/Bargellini multicomponent reactions. Aminobenzylnaphthols were prepared from 2-naphthol, aromatic aldehydes, and 2-aminopyridine via the Betti reaction, and then, naphtho[1,2-f][1,4]oxazepine derivatives were synthesized using the Betti reaction products, chloroform, and aliphatic ketones in the presence of sodium hydroxide via Bargellini multicomponent reactions. A significant aspect of this work is the construction of novel oxazepine-based scaffolds with potential pharmaceutical interest from cheap and readily available starting materials in moderate yields.

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References

  • Alanine TA, Stokes S, Scott JS (2016) Practical synthesis of 3,3-substituted dihydroquinoxalin-2-ones from aryl 1,2-diamines using the Bargellini reaction. Tetrahedron Lett 57:4386–4388

    CAS  Google Scholar 

  • Apiquian R, Ulloa E, Fresan A, Loyzaga C, Nicolini H, Kapur S (2003) Amoxapine shows atypical antipsychotic effects in patients with schizophrenia: results from a prospective open-label study. Schizophr Res 59:35–39

    PubMed  Google Scholar 

  • Balani N, Parhate S, Thawani V, Deshpande A (1995) Effects of nitroxazepine on diastolic blood pressure in mild hypertensive patients-a short term clinical study. Indian J Physiol Pharmacol 39:293–295

    CAS  PubMed  Google Scholar 

  • Ban TA, Fujimori M, Petrie W, Ragheb M, Wilson W (1982) Systematic studies with amoxapine, a new antidepressant. Int Pharmacopsychiatry 17:18–27

    CAS  PubMed  Google Scholar 

  • Bargellini G (1906) ‘Condensation of phenols with chloroform and acetone. Gazz Chim Ital 36:329–339

    Google Scholar 

  • Bariwal J, Kaur R, Voskressensky LG, Van der Eycken EV (2018) Post-Ugi cyclization for the construction of diverse heterocyclic compounds: recent updates. Front Chem 6:557

    PubMed  PubMed Central  Google Scholar 

  • Blass B (2012) 5-amino-oxazepine and 5-amino-thiazepine compounds as β-secretase antagonists and methods of use: patent highlight. ACS Med Chem Lett 3:873–874

    CAS  PubMed  PubMed Central  Google Scholar 

  • Capozzi MAM, Cardellicchio C, Magaletti A, Bevilacqua A, Perricone M, Corbo MR (2014) Bioactivity of a family of chiral nonracemic aminobenzylnaphthols towards Candida albicans. Molecules 19:5219–5230

    PubMed  PubMed Central  Google Scholar 

  • Cardellicchio C, Capozzi MAM, Naso F (2010) The Betti base: the awakening of a sleeping beauty. Tetrahedron Asymmetry 21:507–517

    CAS  Google Scholar 

  • Chakrabarti JK, Hicks TA (1987) 2-[10,11-Dihydro-11-oxodibenz[b, f][1,4]oxazepin-7 or 8-yl] propanoic acids as potential anti-inflammatory agents. Eur J Med Chem 22:161–163

    CAS  Google Scholar 

  • Choudhary S, Pawar AP, Yadav J, Sharma DK, Kant R, Kumar I (2018) One-pot synthesis of chiral tetracyclic dibenzo[b, f][1,4]oxazepine-fused 1,2-dihydropyridines (DHPs) under metal-free conditions. J Org Chem 83:9231–9239

    CAS  PubMed  Google Scholar 

  • Csütörtöki R, Szatmári I, Koch A, Heydenreich M, Kleinpeter E, Fülöp F (2011) Synthesis and conformational analysis of new naphth[1,2-e][1,3]oxazino[3,4-c]quinazoline derivatives. Tetrahedron 67:8564–8571

    Google Scholar 

  • Dols PP, Folmer BJ, Hamersma H, Kuil CW, Lucas H, Ollero L, Rewinkel JB, Hermkens PH (2008) SAR study of 2,3,4,14b-tetrahydro-1H-dibenzo[b, f]pyrido[1,2-d][1,4]oxazepines as progesterone receptor agonists. Bioorg Med Chem Lett 18:1461–1467

    CAS  PubMed  Google Scholar 

  • Domling A, Wang W, Wang K (2012) Chemistry and biology of multicomponent reactions. Chem Rev 112:3083–3135

    CAS  PubMed  PubMed Central  Google Scholar 

  • Farhid H, Khodkari V, Nazeri MT, Javanbakht S, Shaabani A (2021a) Multicomponent reactions as a potent tool for the synthesis of benzodiazepines. Org Biomol Chem 19:3318–3358

    CAS  PubMed  Google Scholar 

  • Farhid H, Nazeri MT, Shaabani A, Armaghan M, Janiak C (2021b) Isocyanide-based consecutive Bargellini/Ugi reactions: an efficient method for the synthesis of pseudo-peptides containing three amide bonds. Amino Acids 53:1–10

    CAS  PubMed  Google Scholar 

  • Farhid H, Rostami MM, Shaabani A, Notash B (2021c) Synthesis of depsipeptides via isocyanide-based consecutive Bargellini/Passerini multicomponent reactions. SynOpen 5:167–172

    CAS  Google Scholar 

  • Ganem B (2009) Strategies for innovation in multicomponent reaction design. Acc Chem Res 42:463–472

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ghandi M, Olyaei A, Raoufmoghaddam S (2008) One-pot, three-component uncatalyzed quantitative synthesis of new aminonaphthols (Betti bases) in water. Synth Commun 38:4125–4138

    CAS  Google Scholar 

  • Ghandi M, Olyaei A, Raoufmoghaddam S (2009) Synthesis of novel naphth[1,2-f][1,4]oxazepine-3,4-dione heterocycles. J Heterocycl Chem 46:914–918

    CAS  Google Scholar 

  • Giustiniano M, Pelliccia S, Galli U, Amato J, Travagin F, Novellino E, Tron GC (2016) A successful replacement of phenols with isocyanides in the Bargellini reaction: synthesis of 3-carboxamido-isobutyric acids. J Org Chem 81:11467–11471

    CAS  PubMed  Google Scholar 

  • Goto M, Konishi T, Kawaguchi S, Yamada M, Nagata T, Yamano M (2011) Process research on the asymmetric hydrogenation of a benzophenone for developing the manufacturing process of the squalene synthase inhibitor TAK-475. Org Process Res Dev 15:1178–1184

    CAS  Google Scholar 

  • Goutham K, Ashok Kumar D, Suresh S, Sridhar B, Narender R, Karunakar GV (2015) Gold-catalyzed intramolecular cyclization of N-propargylic β-enaminones for the synthesis of 1,4-oxazepine derivatives. J Org Chem 80:11162–11168

    CAS  PubMed  Google Scholar 

  • Gyémánt N, Engi H, Schelz Z, Szatmari I, Toth D, Fülöp F, Molnár J, De Witte P (2010) In vitro and in vivo multidrug resistance reversal activity by a Betti-base derivative of tylosin. Br J Cancer 103:178–185

    PubMed  PubMed Central  Google Scholar 

  • Heydenreich M, Koch A, Klod S, Szatmári I, Fülöp F, Kleinpeter E (2006) Synthesis and conformational analysis of naphth[1′,2′:5,6][1,3]oxazino[3,2-c][1,3]benzoxazine and naphth[1′,2′:5,6][1,3]oxazino[3,4-c][1,3]benzoxazine derivatives. Tetrahedron 62:11081–11089

    CAS  Google Scholar 

  • Hooshmand SE, Ghadari R, Mohammadian R, Shaabani A, Khavasi HR (2019) Rhodanine-furan bis-heterocyclic frameworks synthesis via green one-pot sequential six-component reactions: a synthetic and computational study. ChemistrySelect 4:11893–11898

    CAS  Google Scholar 

  • Ji J-X, Qiu L-Q, Yip CW, Chan AS (2003) A convenient, one-step synthesis of optically active tertiary aminonaphthol and its applications in the highly enantioselective alkenylations of aldehydes. J Org Chem 68:1589–1590

    CAS  PubMed  Google Scholar 

  • Klunder JM, Hargrave KD, West M et al (1992) Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 2. Tricyclic pyridobenzoxazepinones and dibenzoxazepinones. J Med Chem 35:1887–1897

    CAS  PubMed  Google Scholar 

  • Lee C-H, Wu W-C, Dangate PS, Shen L-C, Chung W-S, Sun C-M (2015) Skeletally diverse synthesis of innovative [2,1-c]-1,4-oxazepine and [1,4]-quinoxaline systems. ACS Comb Sci 17:623–630

    CAS  PubMed  Google Scholar 

  • López-Cara LC, Conejo-García A, Marchal JA et al (2011) New (RS)-benzoxazepin-purines with antitumour activity: the chiral switch from (RS)-2,6-dichloro-9-[1-(p-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]-9H-purine. Eur J Med Chem 46:249–258

    PubMed  Google Scholar 

  • Lu J, Xu X, Wang C, He J, Hu Y, Hu H (2002) Synthesis of chiral ligands derived from the Betti base and their use in the enantioselective addition of diethylzinc to aromatic aldehydes. Tetrahedron Lett 43:8367–8369

    CAS  Google Scholar 

  • Mahdavi M, Asadi M, Saeedi M, Rezaei Z, Moghbel H, Foroumadi A, Shafiee A (2012) Synthesis of novel 1,4-benzodiazepine-3,5-dione derivatives: reaction of 2-aminobenzamides under Bargellini reaction conditions. Synlett 23:2521–2525

    CAS  Google Scholar 

  • Meng J-P, Wang W-W, Chen Y-L, Bera S, Wu J (2020) Switchable solvent-controlled divergent synthesis: an efficient and regioselective approach to pyrimidine and dibenzo[b, f][1,4]oxazepine derivatives. Org Chem Front 7:267–272

    CAS  Google Scholar 

  • Mishra JK, Samanta K, Jain M, Dikshit M, Panda G (2010) Amino acid based enantiomerically pure 3-substituted benzofused heterocycles: a new class of antithrombotic agents. Bioorg Med Chem Lett 20:244–247

    CAS  PubMed  Google Scholar 

  • Mohanram I, Meshram J (2014) Synthesis and biological activities of 4-aminoantipyrine derivatives derived from betti-type reaction. Int Sch Res Notices. https://doi.org/10.1155/2014/639392

    Article  Google Scholar 

  • Nazeri MT, Farhid H, Javanbakht S, Shaabani A, Notash B (2020a) Highly efficient chemoselective synthesis of pyrrolo[2,3-c]pyrazole bearing oxindole via Sequential Condensation-Michael Addition–Intramolecular Cyclization Reactions. Synlett 31:965–971

    CAS  Google Scholar 

  • Nazeri MT, Farhid H, Mohammadian R, Shaabani A (2020b) Cyclic imines in Ugi and Ugi-type reactions. ACS Comb Sci 22:361–400

    CAS  PubMed  Google Scholar 

  • Nazeri MT, Mohammadian R, Farhid H, Shaabani A, Notash B (2020c) An efficient pseudo-seven component reaction for the synthesis of fully-substituted furans containing pseudopeptide based on the union of multicomponent reactions. Tetrahedron Lett 61:151408

    CAS  Google Scholar 

  • Olyaei A, Sadeghpour M (2019) Recent advances in the synthesis and synthetic applications of Betti base (aminoalkylnaphthol) and bis-Betti base derivatives. RSC Adv 9:18467–18497

    CAS  Google Scholar 

  • Oshimoto K, Zhou B, Tsuji H, Kawatsura M (2020) Synthesis of substituted benzo[b][1,4]oxazepine derivatives by the reaction of 2-aminophenols with alkynones. Org Biomol Chem 18:415–419

    CAS  PubMed  Google Scholar 

  • Pekcec A, Unkrüer B, Schlichtiger J, Soerensen J, Hartz AM, Bauer B, van Vliet EA, Gorter JA, Potschka H (2009) Targeting prostaglandin E2 EP1 receptors prevents seizure-associated P-glycoprotein up-regulation. J Pharmacol Exp Ther 330:939–947

    CAS  PubMed  Google Scholar 

  • Popovic D, Nuss P, Vieta E (2015) Revisiting loxapine: a systematic review. Ann Gen Psychiatry 14:1–8

    Google Scholar 

  • Rashid Z, Ghahremanzadeh R, Naeimi H (2016) Bargellini condensation of ninhydrin as a ketone and substituted anilines as nucleophiles. New J Chem 40:1962–1965

    CAS  Google Scholar 

  • Ruijter E, Scheffelaar R, Orru RV (2011) Multicomponent reaction design in the quest for molecular complexity and diversity. Angew Chem Int Ed 50:6234–6246

    CAS  Google Scholar 

  • Samet AV, Marshalkin VN, Kislyi KA, Chernysheva NB, Strelenko YA, Semenov VV (2005) Synthetic utilization of polynitroaromatic compounds. 3. Preparation of substituted dibenz[b, f][1,4]oxazepine-11(10 H)-ones from 2,4,6-trinitrobenzoic acid via nucleophilic displacement of nitro groups. J Org Chem 70:9371–9376

    CAS  PubMed  Google Scholar 

  • Serafini M, Murgia I, Giustiniano M, Pirali T, Tron GC (2021) The 115 year old multicomponent Bargellini reaction: perspectives and new applications. Molecules 26:558

    CAS  PubMed  PubMed Central  Google Scholar 

  • Serrano-Wu MH, Laurent DRS, Chen Y, Huang S et al (2002) Sordarin oxazepine derivatives as potent antifungal agents. Bioorg Med Chem Lett 12:2757–2760

    CAS  PubMed  Google Scholar 

  • Shaabani A, Hooshmand SE (2018) Diversity-oriented catalyst-free synthesis of pseudopeptides containing rhodanine scaffolds via a one-pot sequential isocyanide-based six-component reactions in water using ultrasound irradiation. Ultrason Sonochem 40:84–90

    CAS  PubMed  Google Scholar 

  • Shaabani S, Shaabani A, Ng SW (2014) One-pot synthesis of coumarin-3-carboxamides containing a triazole ring via an isocyanide-based six-component reaction. ACS Comb Sci 16:176–183

    CAS  PubMed  Google Scholar 

  • Shaabani A, Mofakham H, Maleki A, Hajishaabanha F (2010) Novel isocyanide-based one-pot multicomponent syntheses of tetrahydrobenzo[b][1,4]oxazepine and malonamide derivatives. J Comb Chem 12:630–632

    CAS  PubMed  Google Scholar 

  • Shaabani S, Shaabani A, Kucerakova M, Dusek M (2019) A One-Pot synthesis of oxazepine-quinazolinone bis-heterocyclic scaffolds via isocyanide-based three-component reactions. Front Chem 7:623

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shahrisa A, Teimuri-Mofrad R, Gholamhosseini-Nazari M (2015) Chemoselective sequential reactions for the synthesis of 12h-benzo[a]xanthenes and dihydro-1H-naphtho[1,2-e][1,3] oxazines. Synlett 26:1031–1038

    CAS  Google Scholar 

  • Sharma UK, Sharma N, Vachhani DD, Van der Eycken EV (2015) Metal-mediated post-Ugi transformations for the construction of diverse heterocyclic scaffolds. Chem Soc Rev 44:1836–1860

    CAS  PubMed  Google Scholar 

  • Shi J, Wu J, Cui C, Dai W-M (2016) Microwave-Assisted intramolecular ullmann diaryl etherification as the post-ugi annulation for generation of dibenz[b, f][1,4]oxazepine Scaffold. J Org Chem 81:10392–10403

    CAS  PubMed  Google Scholar 

  • Smith L II, Wong WC, Kiselyov AS et al (2006) Novel tricyclic azepine derivatives: biological evaluation of pyrimido[4,5-b]-1,4-benzoxazepines, thiazepines, and diazepines as inhibitors of the epidermal growth factor receptor tyrosine kinase. Bioorg Med Chem Lett 16:5102–5106

    CAS  PubMed  Google Scholar 

  • Snowden TS (2012) Recent applications of gem-dichloroepoxide intermediates in synthesis. ARKIVOC 2:24–40

    Google Scholar 

  • Szatmári I, Sillanpää R, Fülöp F (2008) Microwave-assisted, highly enantioselective addition of diethylzinc to aromatic aldehydes catalyzed by chiral aminonaphthols. Tetrahedron Asymmetry 19:612–617

    Google Scholar 

  • Szatmári I, Hetényi A, Lázár L, Fülöp F (2004) Transformation reactions of the Betti base analog aminonaphthols. J Heterocycl Chem 41:367–373

    Google Scholar 

  • Szatmári I, Martinek TA, Lázár L, Fülöp F (2003) Substituent effects in the ring-chain tautomerism of 1,3-diaryl-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazines. Tetrahedron 59:2877–2884

    Google Scholar 

  • Teimuri-Mofrad R, Gholamhosseini-Nazari M, Esmati S, Shahrisa A (2017) A novel tandem Betti/Ullmann oxidation reaction as an efficient route for synthesis of new oxazepine derivatives. J Chem Sci 129:1449–1459

    CAS  Google Scholar 

  • Thummala Y, Raju CE, Purnachandar D, Sreenivasulu G, Doddi VR, Karunakar GV (2020) Gold-catalyzed regioselective synthesis of pyrazolo[1,4]oxazepines via intramolecular 7-endo-dig cyclization. Eur J Org Chem 2020:3560–3567

    CAS  Google Scholar 

  • Verma NK, Dempsey E, Conroy J et al (2008) A new microtubule-targeting compound PBOX-15 inhibits T-cell migration via post-translational modifications of tubulin. J Mol Med 86:457–469

    CAS  PubMed  Google Scholar 

  • Yadav Y, MacLean ED, Bhattacharyya A, Parmar VS, Balzarini J, Barden CJ, Too CK, Jha A (2011) Design, synthesis and bioevaluation of novel candidate selective estrogen receptor modulators. Eur J Med Chem 46:3858–3866

    CAS  PubMed  Google Scholar 

  • Zheng X, Liu B, Yang F, Hu Q, Yao L, Hu Y (2020) Access to benzoxazepines and fully substituted indoles via HDDA coupling. Org Lett 22:956–959

    CAS  PubMed  Google Scholar 

  • Zhi S, Ma X, Zhang W (2019) Consecutive multicomponent reactions for the synthesis of complex molecules. Org Biomol Chem 17:7632–7650

    CAS  PubMed  Google Scholar 

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Acknowledgements

This paper has been supported by the Research Council of Shahid Beheshti University and the RUDN University Strategic Academic Leadership Program (A. Shaabani).

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  1. Faculty of Chemistry, Shahid Beheshti University, G.C., P.O. Box 19396-4716, Tehran, Iran

    Hassan Farhid, Mohammad Taghi Nazeri, Mohammad Mahdi Rostami, Ahmad Shaabani & Behrouz Notash

  2. Peoples’ Friendship University of Russia (RUDN University), 6, Miklukho-Maklaya Street, Moscow, Russian Federation, 117198

    Ahmad Shaabani

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  1. Hassan Farhid
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  2. Mohammad Taghi Nazeri
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  3. Mohammad Mahdi Rostami
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  4. Ahmad Shaabani
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Correspondence to Ahmad Shaabani.

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Farhid, H., Nazeri, M.T., Rostami, M.M. et al. Consecutive Betti/Bargellini multicomponent reactions: an efficient strategy for the synthesis of naphtho[1,2-f][1,4]oxazepine scaffolds. Chem. Pap. 76, 987–993 (2022). https://doi.org/10.1007/s11696-021-01924-0

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