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Synthesis 2023; 55(23): 4025-4033
DOI: 10.1055/a-2122-4080
DOI: 10.1055/a-2122-4080
paper
Continuous-Flow Regioselective Reductive Alkylation of Oxindole with Alcohols and Aldehydes in a Fast and Economical Manner
The financial support of the National Research, Development and Innovation Office (TKP2021-EGA-31) is acknowledged. We are grateful to the Hungarian Scientific Research Fund (OTKA ANN 139484).
Abstract
Oxindole is a widely used scaffold in drug discovery, which can be found in several marketed drugs, among them sunitinib and ziprasidone. Thus, the derivatization of oxindole is of considerable current interest. The extreme reaction conditions (high temperature, high pressure) described in the literature for the batchwise regioselective multistep 3-alkylation of oxindole with alcohols in the presence of Raney nickel motivated us to develop a robust, time- and cost-efficient continuous-flow variant for this reaction. In addition, the continuous-flow technology was also extended to the reductive 3-alkylation of oxindole with aldehydes. The elaborated methodology allows the safe use of Raney nickel, an inexpensive and widely applied, albeit pyrophoric catalyst. Under the optimized reaction conditions, 10 oxindole derivatives were synthesized ranging from simple 3-alkyl to 3-aralkyl derivatives including two (trifluoromethyl)benzyl congeners. The technology is considerably robust and the catalyst showed a long-term usability. The model reaction between oxindole and acetaldehyde could be run for 16 hours uninterruptedly, rendering possible the efficient ethylation of about 20 g of oxindole utilizing only approximately 800 mg of Raney nickel.
Key words
continuous flow - reductive alkylation - oxindole - regioselectivity - Knoevenagel reactionSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2122-4080.
- Supporting Information
Publikationsverlauf
Eingereicht: 21. April 2023
Angenommen nach Revision: 03. Juli 2023
Accepted Manuscript online:
04. Juli 2023
Artikel online veröffentlicht:
15. August 2023
© 2023. Thieme. All rights reserved
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References
- 1 Murayama S, Narabayashi H, Furukazu H, Yanagisawa N, Mizuno Y, Nakajima M, Kanazawa I. Jpn. Pharmacol. Ther. 1996; 24: 221
- 2 Prakash C, Kamel A, Gummerus J, Wilner K. Drug Metab. Dispos. 1997; 25: 863
- 3 O’Farrell A.-M, Abrams TJ, Yuen HA, Ngai TJ, Louie SG, Yee KW, Wong LM, Hong W, Lee LB, Town A, Smolich BD, Manning WC, Murray LJ, Heinrich MC, Cherrington JM. Blood 2003; 101: 3597
- 4 Dallinger C, Trommeshauser D, Marzin K, Liesener A, Kaiser R, Stopfer P. J. Clin. Pharmacol. 2016; 56: 1387
- 5 Oxindole derivatives that have reached human Phase III clinical trials: famitinib, flindokalner, linopirdine, satavaptan, tenidap.
- 6 Oxindole derivatives that have failed in human Phase II clinical trials: adibendan, amcasertib, aplindore, cipargamin, funapide, icopezil maleate, indolidan, NS-1209, semaxanib.
- 7 Oxindole derivatives that have failed in human Phase I clinical trials: BI-847325, CFI-400945, CP-126998, DS-3032b, henatinib, PF-03382792, SNAP-37889, SSR-126768A, T-0632, tafetinib, XEN-401.
- 8 Horsfiline: Jossang A, Jossang P, Hadi HA, Sévenet T, Bodo B. J. Org. Chem. 1991; 56: 6527
- 9 Paraherquamide: Yamazaki M, Okuyama E, Kobayashi M, Inoue H. Tetrahedron Lett. 1981; 22: 135
- 10 Rhyncophylline: Rosenmund P, Hosseini-Merescht M, Bub C. Liebigs Ann. Chem. 1994; 151
- 11a Kende AS, Thurston J. Synth. Commun. 1990; 20: 2133
- 11b Kende AS, Luzzio MJ, Mendoza JS. J. Org. Chem. 1990; 55: 918
- 12 Mitraphylline: Manda V, Avula B, Ali Z, Khan I, Walker L, Khan S. Planta Med. 2014; 80: 568
- 13 Coerulescine, elacomine, salacin, pteropodine, alstonisine, spirotryprostatin A and B, strychnofoline: Marti C, Carreira EM. Eur. J. Org. Chem. 2003; 2209
- 14 Volk B, Mezei T, Simig G. Synthesis 2002; 595
- 15 Porcs-Makkay M, Volk B, Kapiller-Dezsőfi R, Mezei T, Simig G. Monatsh. Chem. 2004; 135: 697
- 16a Reed-Berendt BG, Latham DE, Dambatta MB, Morrill LC. ACS Cent. Sci. 2021; 7: 570
- 16b Dambatta MB, Polidano K, Northey AD, Williams JM. J, Morrill LC. ChemSusChem 2019; 12: 2345
- 17 Bains AK, Biswas A, Adhikari D. Chem. Commun. 2020; 56: 15442
- 18a Peña-López M, Piehl P, Elangovan S, Neumann H, Beller M. Angew. Chem. Int. Ed. 2016; 55: 14967
- 18b Piehl P, Peña-López M, Frey A, Neumann H, Beller M. Chem. Commun. 2017; 53: 3265
- 19 Labes R, Mateos C, Battilocchio C, Chen Y, Dingwall P, Cumming GR, Rincón JA, Nieves-Remacha MJ, Ley SV. Green Chem. 2019; 21: 59
- 20 Chen T.-Y, Krische MJ. Org. Lett. 2013; 15: 2994
- 21 Volk B, Simig G. Eur. J. Org. Chem. 2003; 3991
- 22 Volk B, Barkóczy J, Hegedűs E, Udvari S, Gacsályi I, Mezei T, Pallagi K, Kompagne H, Lévay G, Egyed A, Hársing LG. Jr, Spedding M, Simig G. J. Med. Chem. 2008; 51: 2522
- 23 Volk B, Gacsályi I, Pallagi K, Poszávácz L, Gyönös I, Szabó É, Bakó T, Spedding M, Simig G, Szénási G. J. Med. Chem. 2011; 54: 6657
- 24 Doleviczényi Z, Vizi SE, Gacsályi I, Pallagi K, Volk B, Hársing LG. Jr, Halmos G, Lendvai B, Zelles T. Neurochem. Res. 2008; 33: 2364
- 25 Herth MM, Volk B, Pallagi K, Bech LK, Antoni F, Knudsen GM, Kristensen J. ACS Chem. Neurosci. 2012; 3: 1002
- 26 Herth MM, Andersen VL, Hansen HD, Stroth N, Volk B, Lehel S, Svenningsson P, Knudsen GM, Kristensen JL. J. Med. Chem. 2015; 58: 3631
- 27 L’Estrade ET, Xiong M, Shalgunov V, Edgar FG, Volk B, Baerentzen SL, Palner M, Erlandsson M, Ohlsson T, Knudsen GM, Herth MM. ACS Chem. Neurosci. 2019; 10: 3961
- 28 Volk B, Kapiller-Dezsőfi R, Simig G. Heterocycles 2006; 68: 539
- 29 Mongkhonsi T, Pimanmas P, Praserthdam P. Chem. Lett. 2000; 968
- 30 Cavalli F, Geiger H, Barnes I, Becker KH. Environ. Sci. Technol. 2002; 36: 1263
- 31 Krafft ME, Crooks WJ. III, Zorc B, Milczanowski SE. J. Org. Chem. 1988; 53: 3158
- 32 Mebane CR, Jensen DR, Rickerd KR, Gross BH. Synth. Commun. 2003; 33: 3373
- 33 Mebane CR, Mansfield AJ. Synth. Commun. 2005; 35: 3083
- 34 Mebane CR, Holte KL, Gross BH. Synth. Commun. 2007; 37: 2787
- 35 Sipőcz T, Lengyel L, Sipos G, Kocsis L, Dormán G, Jones RV, Darvas F. J. Flow Chem. 2016; 6: 117
- 36a Ley SV. Chem. Rec. 2012; 12: 378
- 36b Cambié D, Bottecchia C, Straathof NJ. W, Hessel V, Noël T. Chem. Rev. 2016; 116: 10276
- 36c Plutschack MB, Pieber B, Gilmore K, Seeberger PH. Chem. Rev. 2017; 117: 11796
- 37a Britton J, Raston CL. Chem. Soc. Rev. 2017; 46: 1250
- 37b Gemoets HP. L, Su Y, Shang M, Hessel V, Luque R, Noël T. Chem. Soc. Rev. 2016; 45: 83
- 38a Bonner A, Loftus A, Padgham AC, Baumann M. Org. Biomol. Chem. 2021; 19: 7737
- 38b Ötvös SB, Kappe CO. Green Chem. 2021; 23: 6117
- 38c Goel S, Khulbe M, Aggarwal A, Kathuria A. Mol. Diversity 2022; 26: 2939
- 39a Alfano AI, Lange H, Brindisi M. ChemSusChem 2022; 15: e202102708
- 39b Bajada MA, Sanjosé Orduna J, Di Liberto G, Tosoni S, Pacchioni G, Noël T, Vilé G. Chem. Soc. Rev. 2022; 51: 3898
- 39c Binjhade R, Mondal R, Mondal S. J. Environ. Chem. Eng. 2022; 10: 107746
- 39d Zhanel GG, Pozdirca M, Golden AR, Lawrence CK, Zelenitsky S, Berry L, Schweizer F, Bay D, Adam H, Zhanel MA, Lagacé-Wiens P, Walkty A, Irfan N, Naber K, Lynch JP. III, Karlowsky JA. Drugs 2022; 82: 533
- 39e Hessel V, Kralisch D, Kockmann N, Noël T, Wang Q. ChemSusChem 2013; 6: 746
- 40a Mitsutani K, Grace JR, Lim CJ. Chem. Eng. Sci. 2005; 60: 2703
- 40b Panariello L, Mazzei L, Gavriilidis A. Chem. Eng. J. 2018; 350: 1144
- 40c Chen Q, Xia S, Luo G, Wang Y. Chem. Eng. Sci. 2022; 254: 117645
- 40d Coley CW, Thomas DA. III, Lummiss JA. M, Jaworski JN, Breen CP, Schultz V, Hart T, Fishman JS, Rogers L, Gao H, Hicklin RW, Plehiers PP, Byington J, Piotti JS, Green WH, Hart AJ, Jamison TF, Jensen KF. Science 2019; 365: eaax1566
- 40e Nagaki A, Yamada S, Doi M, Tomida Y, Takabayashi N, Yoshida J.-i. Green Chem. 2011; 13: 1110
- 40f Mándity IM, Ötvös SB, Fülöp F. ChemistryOpen 2015; 4: 212
- 40g Orsy G, Fülöp F, Mándity IM. Molecules 2020; 25: 1985
- 40h Orsy G, Fülöp F, Mándity IM. Catal. Sci. Technol. 2020; 10: 7814
- 40i Orsy G, Fülöp F, Mándity IM. Green Chem. 2019; 21: 956
- 40j Mándity IM, Ötvös SB, Szőlősi G, Fülöp F. Chem. Rec. 2016; 16: 1018
- 40k Ötvös SB, Szloszár A, Mándity IM, Fülöp F. Adv. Synth. Catal. 2015; 357: 3671
- 40l Ötvös SB, Mándity IM, Fülöp F. ChemSusChem 2012; 5: 266
- 40m Ötvös SB, Mándity IM, Fülöp F. J. Catal. 2012; 295: 179
- 41a Chiroli V, Benaglia M, Cozzi F, Puglisi A, Annunziata R, Celentano G. Org. Lett. 2013; 15: 3590
- 41b Porta R, Benaglia M, Chiroli V, Coccia F, Puglisi A. Isr. J. Chem. 2014; 54: 381
- 42 Porta R, Benaglia M, Puglisi A, Mandoli A, Gualandi A, Cozzi PG. ChemSusChem 2014; 7: 3534
- 43 Porta R, Benaglia M, Coccia F, Cozzi F, Puglisi A. Adv. Synth. Catal. 2015; 357: 377
- 44a Chai K, Shen R, Qi T, Chen J, Su W, Su A. Processes 2023; 11: 1074
- 44b Uozumi Y, Yamada YM. A, Yoshida H. Synfacts 2017; 13: 0763
- 45 Tacconi G, Pietra S. Farmaco, Ed. Sci. 1963; 18: 409
- 46 Hinman RL, Bauman CP. J. Org. Chem. 1964; 29: 1206
- 47 Kende AS, Hodges JC. Synth. Commun. 1982; 12: 1
- 48 Du T.-P, Zhu G.-G, Zhou J. Lett. Org. Chem. 2012; 9: 225
- 49 Furuta K, Mizuno Y, Maeda M, Koyama H, Hirata Y. Chem. Pharm. Bull. 2017; 65: 1093
- 50 Ziarani GM, Gholamzadeh P, Lashgari N, Hajiabbasi P. ARKIVOC 2013; (i): 470
- 51 Elliott IW, Rivers P. J. Org. Chem. 1964; 29: 2438
- 52 Jensen T, Madsen R. J. Org. Chem. 2009; 74: 3990
- 53 Felpin F.-X, Ibarguren O, Nassar-Hardy L, Fouquet E. J. Org. Chem. 2009; 74: 1349
- 54 Li B, Park Y, Chang S. J. Am. Chem. Soc. 2014; 136: 1125
- 55 Payne BP, Biesinger MC, McIntyre NS. J. Electron Spectrosc. Relat. Phenom. 2009; 175: 55
- 56 Heys RJ. J. Labelled Compd. Radiopharm. 2010; 53: 716
- 57 Villemin D, Martin B. Synth. Commun. 1998; 28: 3201
- 58 Canoira L, Rodriguez JG. J. Heterocycl. Chem. 1985; 22: 1511
- 59 Ueda S, Okada T, Nagasawa H. Chem. Commun. 2010; 46: 2462
- 60 Ruveda EA, Gonzalez HA. Spectrochim. Acta, Part A 1970; 26: 1275
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