ZnO-nanorods Promoted Synthesis of α-amino Nitrile Benzofuran Derivatives using One-pot Multicomponent Reaction of Isocyanides

Author(s): Asef H. Najar, Zinatossadat Hossaini*, Shahrzad Abdolmohammadi, Daryoush Zareyee

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Volume 23 , Issue 4 , 2020

Become EABM
Become Reviewer


Aims and Objective: In this work ZnO-nanorod (ZnO-NR) as reusable catalyst promoted Strecker-type reaction of 2,4-dihydroxyacetophenone, isopropenylacetylene, trimethylsilyl cyanide (TMSCN), primary amines and isocyanides at ambient temperature under solvent-free conditions and produced α-amino nitriles benzofuran derivatives in high yields. These synthesized compounds may have antioxidant ability.

Materials and Methods: ZnO-NRs in these reactions were prepared according to reported article. 2,4-dihydroxyacetophenone 1 (2 mmol) and isopropenylacetylene 2 (2 mmol) were mixed and stirred for 30 min in the presence of ZnO-NR (10 mol%) under solvent-free conditions at room temperature. After 30 min, primary amine 3 (2 mmol) was added to the mixture gently and the mixture was stirred for 15 min. After this time TMSCN 4 (2 mmol) was added to the mixture and stirred for 15 min. After completion of the reaction, as indicated by TLC, isocyanides 5 was added to mixture in the presence of catalyst.

Results: In the first step of this research, the reaction of 2,4-dihydroxyacetophenone 1, isopropenylacetylene 2, methyl amine 3a, trimethylsilyle cyanide 4 and tert-butyl isocyanides 5a was used as a sample reaction to attain the best reaction conditions. The results showed this reaction performed with catalyst and did not have any product without catalyst after 12 h.

Conclusion: In conclusion, we investigate multicomponent reaction of 2,4-dihydroxyacetophenone 1, isopropenylacetylene 2, primary amines 3, trimethylsilyl cyanide 4 and isocyanides along with ZnO-NRs as reusable catalyst at room temperature under solvent-free conditions which generates α-amino nitrile benzofuran derivatives in high yields. The advantages of our method are high atom economy, green reaction conditions, higher yield, shorter reaction times, and easy work-up, which are in good agreement with some principles of green chemistry. The compounds 8c exhibit excellent DPPH radical scavenging activity and FRAP compared to synthetic antioxidants BHT and TBHQ.

Keywords: Strecker reaction, antioxidant ability, α-amino nitrile benzofurans, five component reaction, DPPH radical scavenging, ZnO nanorod.

Li, C.J.; Chan, T.H. Comprehensive Organic Reactions in Aqueous Media; John Wiley & Sons, 2007.
Chanda, A.; Fokin, V.V. Organic synthesis “on water”. Chem. Rev., 2009, 109(2), 725-748.
[http://dx.doi.org/10.1021/cr800448q] [PMID: 19209944]
Breslow, R. Hydrophobic effects on simple organic reactions in water. Acc. Chem. Res., 1991, 24, 159.
Dömling, A. Isocyanide based multi component reactions in combinatorial chemistry. Comb. Chem. High Throughput Screen., 1998, 1(1), 1-22.
[PMID: 10499126]
Wang, J.; Masui, Y.; Onaka, M. Synthesis of α-amino nitriles from carbonyl compounds, amines, and trimethylsilyl cyanide: comparison between catalyst-free conditions and the presence of tin ion-exchanged montmorillonite. Eur. J. Org. Chem., 2010, 2010(9), 1763-1771.http://dx.doi.org/doi:10.1002/ejoc.200901323
Weber, L. Multi-component reactions and evolutionary chemistry. Drug Discov. Today, 2002, 7(2), 143-147.
[http://dx.doi.org/10.1016/S1359-6446(01)02090-6] [PMID: 11790626]
Zhu, J.; Bienayme, H. Multicomponent Reactions; Wiley-VCH: Weinheim, 2005.
Wipf, P.; Kendall, C. Novel applications of alkenyl zirconocenes. Chemistry, 2002, 8, 1779.
Balme, G.; Bossharth, E.; Monteiro, N. Pd‐assisted multicomponent synthesis of heterocycles. Eur. J. Org. Chem., 2003, 4101
Jacobi von Wangelin, A.; Neumann, H.; Gördes, D.; Klaus, S.; Strübing, D.; Beller, M. Multicomponent coupling reactions for organic synthesis: chemoselective reactions with amide-aldehyde mixtures. Chemistry, 2003, 9, 4286.
[http://dx.doi.org/10.1002/chem.200305048] [PMID: 14502613]
Chao, W.; Ling-Hui, L.; Ai-Zhong, P.; Guo-Kai, J.; Cun, P.; Zhong, C.; Zilong, T.; Wei-Min, H.; Xinhua, X. Ultrasound-promoted Brønsted acid ionic liquid-catalyzed hydrothiocyanation of activated alkynes under minimal solvent conditions. Green Chem., 2018, 20, 3683.
Ling-Hui, L.; Zheng, W.; Weng, X.; Ping, C.; Bo, Zh.; Zhong, C.; Wei-Min, H. Sustainable routes for quantitative green selenocyanation of activated alkynes. Chin. Chem. Lett., 2019, 30, 1237.
Lu, L-H.; Zhou, S-J.; Sun, M.; Chen, J-L.; Xia, W.; Yu, X.; Xu, X.; He, W-M. Metal- and solvent-free ultrasonic multicomponent synthesis of (z)-β-iodo vinylthiocyanates. ACS Sustain. Chem.& Eng., 2019, 7, 1574-1579.
Sunderhaus, J.D.; Martin, S.F. Applications of multicomponent reactions to the synthesis of diverse heterocyclic scaffolds. Chem. A Eur. J., 2009, 15(6), 1300-1308.
(a) Ganem, B. Strategies for innovation in multicomponent reaction design. Acc. Chem. Res., 2009, 42(3), 463-472.
(b) Ugi, I.; Dömling, A. Multicomponent reactions in organic chemistry. Endeavour, 1994, 18, 115.
(c)Heck, S.; Dömling, A. A versatile multi-component one-pot thiazole synthesis. Synlett, 2000, 2000, 424-426.
a)Kolb, J.; Beck, B.; Almstetter, M.; Heck, S.; Herdtweck, E.; Dömling, A. New MCRs: the first 4-component reaction leading to 2,4-disubstituted thiazoles. Mol. Divers., 2003, 6, 297.
b)Gharib, A.; Noroozi Pesyan, N.; Vojdani Fard, L.; Roshani, M. Catalytic synthesis of α-Aminonitriles using nano copper ferrite under green conditions. Org. Chem. Int., 2014, 2014, 1-8.
(a)Shaabani, A.; Maleki, A.; Rezayan, A.H.; Sarvary, A. Recent progress of isocyanide-based multicomponent reactions in Iran. Mol. Divers., 2011, 15(1), 41-68.
[http://dx.doi.org/10.1007/s11030-010-9258-1] [PMID: 20669047]
(b)Altug, C.; Burnett, A.K.; Caner, E.; Dürüst, Y.; Elliott, M.C.; Glanville, R.P.J.; Guy, C.; Westwell, A.D. An efficient one-pot multicomponent approach to 5-amino-7-aryl-8-nitrothiazolo[3,2-a]pyridines. Tetrahedron, 2011, 67, 9522-9528.
Rostami-Charati, F.; Hajinasiri, R.; Sayyed Alangi, S.Z.; Afshari Sharif Abad, S. ZnO-nanorods as economical catalyst for synthesis of 4-amino-2-iminodithiole derivatives using tetramethyl thiourea in water. Chem. Pap., 2016, 70, 907-912.
Sajjadi-Ghotbabadi, H.; Javanshir, Sh.; Rostami-Charati, F. Nano KF/clinoptilolite: an effective heterogeneous base nanocatalyst for synthesis of substituted quinolines in water. Catal. Lett., 2016, 146, 338-344.
Soleimani, A.; Asadi, J.; Rostami-Charati, F.; Gharaei, R. High cytotoxicity and apoptotic effects of natural bioactive benzofuran derivative on the MCF-7 breast cancer cell line. Comb. Chem. High Throughput Screen., 2015, 18(5), 505-513.
[http://dx.doi.org/10.2174/1386207318666150430114815] [PMID: 25924658]
Rostami-Charati, F.; Hossaini, Z.S.; Sheikholeslami-Farahani, F.; Azizi, Z.; Siadati, S.A. Synthesis of 9H-furo [2,3-f]chromene derivatives by promoting ZnO nanoparticles. Comb. Chem. High Throughput Screen., 2015, 18, 872-880.
[http://dx.doi.org/10.2174/1386207318666150525094109] [PMID: 26004051]
(a)Elinson, M.N.; Ilovaisky, A.I.; Merkulova, V.M.; Belyakov, P.A.; Chizhov, A.O. Solvent-free cascade reaction: direct multicomponent assembling of 2-amino-4H-chromene scaffold from salicylaldehyde, malononitrile or cyanoacetate and nitroalkanes. Tetrahedron, 2010, 66, 4043-4048.
(b)Dekamin, M.G.; Mokhtari, Z. Highly efficient and convenient Strecker reaction of carbonyl compounds and amines with TMSCN catalyzed by MCM-41 anchored sulfonic acid as a recoverable catalyst. Tetrahedron, 2012, 68, 922-930.
(c) Dekamin, M.G.; Mokhtari, Z. Karimi, Z. Nano-ordered B-MCM-41: An efficient and recoverable solid acid catalyst for three-component Strecker reaction of carbonyl compounds, amines and TMSCN. Sci. Iran. Trans. C: Chem. Chem. Eng., 2011, 18, 1356-1364.
Joschka Holzhäuser, F. Mensah, Joel B.; Palkovits, R. (Non-)Kolbe electrolysis in biomass valorization – a discussion of potential applications. Green Chem., 2020, 22, 286-301.
Cao, Z.; Zhu, Q.; Lin, Y.; He, W. The concept of dual roles design in clean organic preparation. Chin. Chem. Lett., 2019, 30, 2132-2138.
Xie, L.; Jiang, L.; Tan, J.; Wang, X.; Xu, X.; Zhang, B.; Cao, Z.; He, W. Visible-light-initiated decarboxylative alkylation of quinoxalin-2(1H)-ones with phenyliodine(III) dicarboxylates in recyclable ruthenium(II) catalytic system. ACS Sustain. Chem.& Eng., 2019, 7, 14153-14160.
Lu, L-H.; Wang, Z.; Xia, W.; Cheng, P.; Zhang, B.; Cao, Z.; He, W. Sustainable routes for quantitative green selenocyanation of activated alkynes. Chin. Chem. Lett., 2019, 30, 1237-1240.
Weber, L. The application of multi-component reactions in drug discovery. Curr. Med. Chem., 2002, 9(23), 2085-2093.
[http://dx.doi.org/10.2174/0929867023368719] [PMID: 12470248]
Banfi, L.; Basso, A.; Guanti, G.; Kielland, N.; Repetto, C.; Riva, R. Ugi multicomponent reaction followed by an intramolecular nucleophilic substitution: convergent multicomponent synthesis of 1-sulfonyl 1,4-diazepan-5-ones and of their benzo-fused derivatives. J. Org. Chem., 2007, 72, 2151.
Shafran, Y.M.; Bakulev, V.A.; Mokrushin, V.S. Synthesis and properties of α-aminonitriles. Russ. Chem. Rev., 1989, 58, 148-162.
Matier, W.L.; Owens, D.A.; Comer, W.T.; Deitchman, D.; Ferguson, H.C.; Seidehamel, R.J.; Young, J.R. Antihypertensive agents. Synthesis and biological properties of 2-amino-4-aryl-2-imidazolines. J. Med. Chem., 1973, 16(8), 901-908.
[http://dx.doi.org/10.1021/jm00266a008] [PMID: 4745833]
Duthaler, R.O. Recent developments in the stereoselective synthesis of α-aminoacids. Tetrahedron, 1994, 50, 1539-1650.
Enders, D.; Shilvock, J.P. Some recent applications of α-amino nitrile chemistry. Chem. Soc. Rev., 2000, 29, 359-373.
Dyker, G. Amino acid derivatives by multicomponent reactions. Angew. Chem. Int. Ed. Engl., 1997, 36, 1700-1702.
Paraskar, A.S.; Sudalai, A. Cu(OTf)2 or Et3N-catalyzed three-component condensation of aldehydes, amines and cyanides: a high yielding synthesis of α-aminonitriles. Tetrahedron Lett., 2006, 47, 5759.
De, S.K.; Gibbs, R.A. Bismuth trichloride catalyzed synthesis of α-aminonitriles. Tetrahedron Lett., 2004, 4, 7407.
De, S.K. Nickel(II) chloride catalyzed one-pot synthesis of α-aminonitriles. J. Mol. Catal. A, 2005, 225, 169.
Shen, Z.L.; Ji, S.J.; Loh, T.P. Indium(III) iodide-mediated Strecker reaction in water: an efficient and environmentally friendly approach for the synthesis of α-aminonitrile via a three-component condensation. Tetrahedron, 2008, 64, 8159.
Majhi, A.; Kimm, S.S.; Kadam, S.T. Rhodium(III) iodide hydrate catalyzed three-component coupling reaction: synthesis of α-aminonitriles from aldehydes, amines, and trimethylsilyl cyanide. Tetrahedron, 2008, 64, 5509.
Karimi, B.; Zareyee, D. Solvent-free three component Strecker reaction of ketones using highly recyclable and hydrophobic sulfonic acid based nanoreactors. J. Mater. Chem., 2009, 19, 8665.
Iwanami, K.; Seo, H.; Choi, J.C.; Sakakura, T.; Yasuda, H. Al-MCM-41 catalyzed three-component Strecker-type synthesis of α-aminonitriles. Tetrahedron, 2010, 66, 1898.
March, J. Advanced Organic Chemistry, 4th ed; Wiley: New York, 1999, p. 965.
Strecker, A. Krrper. Ueber die künstliche Bildung der Milchsäure und einen neuen, dem Glycocoll homologen Körper. Ann. Chem. Pharm., 1850, 75, 27.
Kalidindi, S.B.; Jagirdar, B.R. Nanocatalysis and prospects of green chemistry. ChemSusChem, 2012, 5(1), 65-75.
[http://dx.doi.org/10.1002/cssc.201100377] [PMID: 22190344]
Beydoun, D.; Amal, R.; Low, G.; McEvoy, S. Role of nanoparticles in photocatalysis. J. Nanopart. Res., 1999, 1, 439-458.
Rostamizadeh, S.; Nojavan, M.; Aryan, R.; Isapoor, E.; Azad, M. Amino acid-based ionic liquid immobilized on α-Fe2O3-MCM-41: An efficient magnetic nanocatalyst and recyclable reaction media for the synthesis of quinazolin-4(3H)-one derivatives. J. Mol. Catal. A, 2013, 374-375, 102-110.
Mirjafary, Z.; Saeidian, H.; Sadeghi, A.; Moghaddam, F.M. ZnO nanoparticles: An efficient nanocatalyst for the synthesis of β-acetamido ketones/esters via a multi-component reaction. Catal. Commun., 2008, 9, 299-306.
Moghaddam, F.M.; Saeidian, H. Controlled microwave-assisted synthesis of ZnO nanopowder and its catalytic activity for O-acylation of alcohol and phenol. Mater. Sci. Eng. B, 2007, 139, 265-269.
Lietti, L.; Tronconi, E.; Forzatti, P.; Busca, G. Surface properties of zno-based catalysts and related mechanistic features of the higher alcohol synthesis by FT-IR spectroscopy and TPSR. J. Mol. Catal., 1989, 55, 43-54.
Gupta, M.; Paul, S.; Gupta, R.; Loupy, A. ZnO: a versatile agent for benzylic oxidations. Tetrahedron Lett., 2005, 46, 4957-4960.
(a)Halliwell, B. Antioxidant defence mechanisms: from the beginning to the end (of the beginning). Free Radic. Res., 1999, 31(4), 261-272.
[http://dx.doi.org/10.1080/10715769900300841] [PMID: 10517532]
(b) Ahmadi, F.; Kadivar, M.; Shahedi, M. Food Chem., 2007, 105, 57-64.
Ezzatzadeh, E.; Hossaini, Z.S. Antioxidant activity of Kelussia odoratissima Mozaff. in model and food systems. Food Chem., 2007, 105, 57-64.
Ezzatzadeh, E.; Hossaini, Z.S. A novel one-pot three-component synthesis of benzofuran derivatives via Strecker reaction: Study of antioxidant activity. Nat. Prod. Res., 2020, 34(7), 923-929.
Ezzatzadeh, E.; Hossaini, Z. Four-component green synthesis of benzochromene derivatives using nano-KF/clinoptilolite as basic catalyst: study of antioxidant activity. Mol. Divers., 2020, 24, 81-91.
[http://dx.doi.org/10.1007/s11030-019-09935-6] [PMID: 30830596]
Rajabi, M.; Hossaini, Z.; Khalilzadeh, M.A.; Datta, S.; Halder, M.; Mousa, S.A. Synthesis of a new class of furo[3,2-c]coumarins and its anticancer activity. J. Photochem. Photobiol. B, 2015, 148, 66-72.
[http://dx.doi.org/10.1016/j.jphotobiol.2015.03.027] [PMID: 25889947]
Yavari, I.; Sabbaghan, M.; Hossaini, Z.S. Efficient synthesis of functionalized 2,5-dihydrofurans and 1,5-dihydro-2H-pyrrol-2-ones by reaction of isocyanides with activated acetylenes in the presence of hexachloroacetone. Chemical Monthly, 2008, 139, 625-628.
Yavari, I.; Sabbaghan, M.; Hossaini, Z.S. Proline-promoted efficient synthesis of 4-Aryl-3,4-dihydro-2H,5H-pyrano[3,2-c]chromene-2,5-diones in aqueous media. Synlett, 2008, 1153-1154
Yavari, I.; Hossaini, Z.S.; Sabbaghan, M.; Ghazanfarpour-Darjani, M. Efficient synthesis of functionalized spiro-2,5-dihydro-1,2-λ5-oxaphospholes. Tetrahedron, 2007, 63, 9423-9428.
Yavari, I.; Sabbaghan, M.; Hossaini, Z.S.; Ghazanfarpour-Darjani, M. Surprising Formation of Chlorinated Butenolides from Dialkyl Acetylenedicarboxylates and Hexachloroacetone in the Presence of Triphenyl Phosphite. Helv. Chim. Acta, 2008, 91, 1144-1147.
Rostami-Charati, F. Efficient synthesis of functionalized hydroindoles via catalyst-free multicomponent reactions of ninhydrin in water. Chin. Chem. Lett., 2014, 25, 169-171.
Rostami‐Charati, F.; Hossaini, Z.S.; Khalilzadeh, M.A.; Jafaryan, H. Solvent‐free synthesis of pyrrole derivatives. J. Heterocycl. Chem., 2012, 49, 217-220.
Hajinasiri, R.; Hossaini, Z.S.; Rostami‐Charati, F. Efficient synthesis of α‐aminophosphonates via one‐pot reactions of aldehydes, amines, and phosphates in ionic liquid. Heteroatom Chem., 2011, 22, 625-629.
Rostami Charati, F.; Hossaini, Z.S.; Hosseini-Tabatabaei, M.R. A simple synthesis of oxaphospholes. Phosphorus, Sulfur, and Silicon and the Related Elements A., 2011, 186, 1443-1448.
Rostami-Charati, F.; Hossaini, Z.S. Facile synthesis of phosphonates via catalyst-free multicomponent reactions in water. Synlett, 2012, 23, 2397-2399.
Bao, W.H.; He, M.; Wang, J.T.; Peng, X.; Sung, M.; Tang, Z.; Jiang, S.; Cao, Z.; He, W.M. Iodine-catalyzed odorless synthesis of s-thiocarbamates with sulfonyl chlorides as a sulfur source. J. Org. Chem., 2019, 84(10), 6065-6071.
[http://dx.doi.org/10.1021/acs.joc.9b00178] [PMID: 30999750]
Bao, W.; Wang, Z.; Tang, X.; Zhang, Y.; Tana, J.; Zhu, Q.; Cao, Z.; Lin, Y.; He, W. Clean preparation of S-thiocarbamates with in situ generated hydroxide in 2-methyltetrahydrofuran. Chin. Chem. Lett., 2019, 30, 2259-2262.
(a)Sabbaghan, M.; Anaraki Firooz, A.; Jan Ahmadi, V. The effect of template on morphology, optical and photocatalytic properties of ZnO nanostructures. J. Mol. Liq., 2012, 175, 135-140.
(b) Hajinasiri, R.; Hossaini, Z.; Sheikholeslami-Farahani, F. ZnO-nanorods as the catalyst for the synthesis of 1,3-thiazole derivatives via multicomponent reactions. Comb. Chem. High Throughput Screen., 2015, 18(1), 42-47.
[http://dx.doi.org/10.2174/1386207317666141203123133] [PMID: 25469698]
Shimada, K.; Fujikawa, K.; Yahara, K.; Nakamura, T. Antioxidative properties of xanthan on the autoxidation of soybean oil in cyclodextrin emulsion. J. Agric. Food Chem., 1992, 40, 945-948.
Yen, G.C.; Duh, P.D. Scavenging effect of methanolic extracts of peanut hulls on free-radical and active-oxygen species. J. Agric. Food Chem., 1994, 42, 629-632.
Yildirim, A.; Mavi, A.; Kara, A.A. Determination of antioxidant and antimicrobial activities of Rumex crispus L. extracts. J. Agric. Food Chem., 2001, 49(8), 4083-4089.
[http://dx.doi.org/10.1021/jf0103572] [PMID: 11513714]
Huang, D.; Ou, B.; Prior, R.L. The chemistry behind antioxidant capacity assays. J. Agric. Food Chem., 2005, 53(6), 1841-1856.
[http://dx.doi.org/10.1021/jf030723c] [PMID: 15769103]
Greeff, J.; Joubert, J.; Malan, S.F.; van Dyk, S. Antioxidant properties of 4-quinolones and structurally related flavones. Bioorg. Med. Chem., 2012, 20(2), 809-818.
[http://dx.doi.org/10.1016/j.bmc.2011.11.068] [PMID: 22197671]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Page: [345 - 355]
Pages: 11
DOI: 10.2174/1386207323666200219124625
Price: $65

Article Metrics

PDF: 32
PRC: 1