Simplified Procedure for General Synthesis of Monosubstituted Piperazines-From a Batch Reaction Vessel to a Flow (Microwave) Reactor
Jazyk angličtina Země Švýcarsko Médium electronic
Typ dokumentu časopisecké články
Grantová podpora
TG02010067 (MUNI/31/53569/2016)
Technology Agency of the Czech Republic
PubMed
32384633
PubMed Central
PMC7249161
DOI
10.3390/molecules25092168
PII: molecules25092168
Knihovny.cz E-zdroje
- Klíčová slova
- catalysis, derivative, heterocyclic, heterogeneous, microwave, monosubstituted, piperazine, reactor, supported catalyst, synthesis,
- MeSH
- heterocyklické sloučeniny chemická syntéza chemie MeSH
- katalýza MeSH
- mikrovlny * MeSH
- piperaziny chemická syntéza chemie MeSH
- rozpouštědla chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- heterocyklické sloučeniny MeSH
- piperaziny MeSH
- rozpouštědla MeSH
We reported a novel simplified synthetic procedure for the preparation of monosubstituted piperazine derivatives which can now be easily prepared in a one-pot-one-step way from a protonated piperazine with no need of introduction of a protecting group. Reactions, proceeding either at room or higher temperatures in common solvents, involve heterogeneous catalysis by metal ions supported on commercial polymeric resins. A general synthetic scheme was successfully applied to afford a wide range of monosubstituted piperazines. Furthermore, we picked up a set of piperazine derivatives and studied the possibilities of microwave acceleration of given synthetic reactions to make them even more efficient. Our research proceeded from a simple batch technique to the construction of a flow microwave reactor prototype and resulted in promising findings which are summarized and discussed in the article.
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Al-Ghorbani M., Bushra A.B., Zabiulla S., Mamatha S.V., Khanum S.A. Piperazine and Morpholine: Synthetic Preview and Pharmaceutical Applications. J. Chem. Pharm. Res. 2015;7:281–301. doi: 10.5958/0974-360X.2015.00100.6. DOI
Singh K., Siddiqui H.H., Shakya P., Bagga P., Kumar A., Khalid M., Arif M., Alok S. Piperazine–A Biologically Active Scaffold. Int. J. Pharm. Sci. Res. 2015;6:4145–4158. doi: 10.13040/IJPSR.0975-8232.6(10). DOI
Chen L., Chen H., Chen P., Zhang W., Wu C., Sun C., Luo W., Zheng L., Liu Z., Liang G. Development of 2-amino-4-phenylthiazole analogues to disrupt myeloid differentiation factor 88 and prevent inflammatory responses in acute lung injury. Eur. J. Med. Chem. 2019;161:22–38. doi: 10.1016/j.ejmech.2018.09.068. PubMed DOI
Szczepańska K., Karcz T., Mogilski S., Siwek A., Kuder K.J., Latacz G., Kubacka M., Hagenow S., Lubelska A., Olejarz A., et al. Synthesis and biological activity of novel tert-butyl and tert-pentylphenoxyalkyl piperazine derivatives as histamine H3R ligands. Eur. J. Med. Chem. 2018;152:223–234. doi: 10.1016/j.ejmech.2018.04.043. PubMed DOI
Satoskar K., Bhandarkar B. Pharmacology and Pharmacotherapeutics. 5th ed. Bombay Popular Prakashan Pvt. Ltd.; Bombay, India: 1985.
Lu S., Zhang Y., Liu J., Zhao C., Liu W., Xi R. Preparation of anti-Pefloxacin Antibody and Development of an Indirect Competitive Enzyme-Linked Immunosorbent Assay for Detection of Pefloxacin Residue in Chicken Liver. J. Agric. Food Chem. 2006;54:6995–7000. doi: 10.1021/jf061309q. PubMed DOI
Madrid P.B., Polgar W.E., Toll L., Tanga M.J. Synthesis and antitubercular activity of phenothiazines with reduced binding to dopamine and serotonin receptors. Bioorg. Med. Chem. Lett. 2007;17:3014–3017. doi: 10.1016/j.bmcl.2007.03.064. PubMed DOI
Su J., Tang H., McKittrick B.A., Burnett D.A., Zang H., Smith-Torhan A., Fawzi A., Lachowicz J. Modification of the clozapine structure by parallel synthesis. Bioorg. Med. Chem. Lett. 2006;16:4548–4553. doi: 10.1016/j.bmcl.2006.06.034. PubMed DOI
Xiong H., Brugel T.A., Balestra M., Brown D.G., Brush K.A., Hightower C., Hinkley L., Hoesch V., Kang J., Koether G.M., et al. 4-Aryl piperazine and piperidine amides as novel mGluR5 positive allosteric modulators. Bioorg. Med. Chem. Lett. 2010;20:7381–7384. doi: 10.1016/j.bmcl.2010.10.036. PubMed DOI
Reich M., Schunk S., Jostock R., Hees S., Germann T., Engels M.F.-M. Substituted Disulfonamide Compounds. 2010/0152158 A1. U.S. Patent. 2010 Jun 17;
Liu Y., Zhou E., Yu K., Zhu J., Zhang Y., Xie X., Li J., Jiang H. Discovery of a novel CCR5 antagonist lead compound through fragment assembly. Molecules. 2008;13:2426. doi: 10.3390/molecules13102426. PubMed DOI PMC
Liu T., Weng Z., Dong X., Chen L., Ma L., Cen S., Zhou N., Hu Y. Design, Synthesis and Biological Evaluation of Novel Piperazine Derivatives as CCR5 Antagonists. PLoS ONE. 2013;8:e53636. doi: 10.1371/journal.pone.0053636. PubMed DOI PMC
Manetti D., Bartolini A., Borea P.A., Bellucci C., Dei S., Ghelardini C., Gualtieri F., Romanelli M.N., Scapecchi S., Teodori E., et al. Hybridized and isosteric analogues of N1-acetyl-N4-dimethyl-piperazinium iodide (ADMP) and N1-phenyl-N4-dimethyl-piperazinium iodide (DMPP) with central nicotinic action. Bioorg. Med. Chem. 1999;7:457–465. doi: 10.1016/S0968-0896(98)00259-4. PubMed DOI
Scott J.S., Degorce S.L., Anjum R., Culshaw J., Davies R.D.M., Davies N.L., Dillman K.S., Dowling J.E., Drew L., Ferguson A.D., et al. Discovery and Optimization of Pyrrolopyrimidine Inhibitors of Interleukin-1 Receptor Associated Kinase 4 (IRAK4) for the Treatment of Mutant MYD88L265P Diffuse Large B-Cell Lymphoma. J. Med. Chem. 2017;60:10071–10091. doi: 10.1021/acs.jmedchem.7b01290. PubMed DOI
Hashimoto K., Nakamura T., Nakamura K., Kurimoto A., Isobe Y., Ogita H., Millichip I., McInally T., Bonnert R. Novel Adenine Compound. 1939198A1. European Patent. 2008 Jul 2;
Moore T.S., Boyle M., Thorn V.M. N-substituted derivatives of piperazine and ethylenediamine. Part I. The preparation of N-monosubstituted derivatives. J. Chem. Soc. 1929;1929:39–51. doi: 10.1039/JR9290000039. DOI
Baltzly R., Buck J.S., Lorz E., Schön W. The preparation of N-mono-substituted and unsymmetrically disubstituted piperazines. J. Am. Chem. Soc. 1944;66:263–266. doi: 10.1021/ja01230a031. DOI
Caille S., Allgeier A.M., Bernard C., Correll T.L., Cosbie A., Crockett R.D., Cui S., Faul M.M., Hansen K.B., Huggins S., et al. Development of a Factory Process for Omecamtiv Mecarbil, a Novel Cardiac Myosin Activator. Org. Process. Res. Dev. 2019;23:1558–1567. doi: 10.1021/acs.oprd.9b00200. DOI
Capuano B., Crosby I.T., Lloyd E.J., Taylor D.A. Synthesis and Preliminary Pharmacological Evaluation of 4’-Arylmethyl Analogues of Clozapine. I. The Effect of Aromatic Substituents. Austral. J. Chem. 2002;55:565–576. doi: 10.1071/CH02093. DOI
Zhou A., Wu H., Pan J., Wang X., Li J., Wu Z., Hui A. Synthesis and Evaluation of Paeonol Derivatives as Potential Multifunctional Agents for the Treatment of Alzheimer’s Disease. Molecules. 2015;20:1304–1318. doi: 10.3390/molecules20011304. PubMed DOI PMC
Devlin J.P., McNeil D.W., Keirns J.J., Barsumian E.L. Bis(piperazinyl or homopiperazinyl)alkanes. 4,725,597. U.S. Patent. 1988 Feb 16;
Klaveness J., Brudeli B., Levy F.O. 5-HTX Modulators. WO 2007/007072 A1. World Patent. 2007 Jan 18;
Panek D., Więckowska A., Wichur T., Bajda M., Godyń J., Jończyk J., Mika K., Janockova J., Soukup O., Knez D., et al. Design, synthesis and biological evaluation of new phthalimide and saccharin derivatives with alicyclic amines targeting cholinesterases, beta-secretase and amyloid beta aggregation. Eur. J. Med. Chem. 2017;125:676–695. doi: 10.1016/j.ejmech.2016.09.078. PubMed DOI
Zhang C., Tan C., Zu X., Zhai X., Liu F., Chu B., Ma X., Chen Y., Gong P., Jiang Y. Exploration of (S)-3-aminopyrrolidine as a potentially interesting scaffold for discovery of novel Abl and PI3K dual inhibitors. Eur. J. Med. Chem. 2011;46:1404–1414. doi: 10.1016/j.ejmech.2011.01.020. PubMed DOI
Ferla S., Manganaro R., Benato S., Paulissen J., Neyts J., Jochmans D., Brancale A., Bassetto M. Rational modifications, synthesis and biological evaluation of new potential antivirals for RSV designed to target the M2-1 protein. Bioorg. Med. Chem. 2020;28:115401. doi: 10.1016/j.bmc.2020.115401. PubMed DOI
Cunico W., Gomes C.R.B., Moreth M., Manhanini D.P., Figueiredo I.H., Penido C., Henriques M.G.M.O., Varotti F.P., Krettli A.U. Synthesis and antimalarial activity of hydroxyethylpiperazine derivatives. Eur. J. Med. Chem. 2009;44:1363–1368. doi: 10.1016/j.ejmech.2008.04.009. PubMed DOI
Mehanna A.S., Jin Y.K. Design, synthesis, and biological testing of thiosalicylamides as a novel class of calcium channel blockers. Bioorg. Med. Chem. 2005;13:4323–4331. doi: 10.1016/j.bmc.2005.04.012. PubMed DOI
Mehanna A.S., Kim J.T. Calcium Channel Blockers. 2002/0115655 A1. U.S. Patent. 2002 Aug 22;
Peterson Q.P., Hsu D.C., Goode D.R., Novotny C.J., Totten R.K., Hergenrother P.J. Procaspase-3 Activation as an Anti-Cancer Strategy: Structure−Activity Relationship of Procaspase-Activating Compound 1 (PAC-1) and Its Cellular Co-Localization with Caspase-3. J. Med. Chem. 2009;52:5721–5731. doi: 10.1021/jm900722z. PubMed DOI PMC
Hergenrother P.J., Peterson Q.P., Hsu D.C., West D.C., Fan T.M., Novotny C.J. Design, Synthesis and Evaluation of Procaspase Activating Compounds as Personalized Anti-Cancer Drugs. WO 2010/091382 A1. World Patent. 2010 Aug 12;
Li J., Huang L., Dong W., Ge X., Shi C. Aralkyl-Alcohol Piperazine Derivatives and Their Uses as Antidepressant. 2005/0267121 A1. U.S. Patent. 2005 Dec 1;
Wang J., Xia F., Jin W.-B., Guan J.-Y., Zhao H. Efficient synthesis and antioxidant activities of N-heterocyclyl substituted Coenzyme Q analogues. Bioorg. Chem. 2016;68:214–218. doi: 10.1016/j.bioorg.2016.08.008. PubMed DOI
Biannic B., Bozell J.J., Elder T. Steric effects in the design of Co-Schiff base complexes for the catalytic oxidation of lignin models to para-benzoquinones. Green Chem. 2014;16:3635–3642. doi: 10.1039/C4GC00709C. DOI
Wuts P.G.M., Greene T.W. Greene’s Protective Groups in Organic Synthesis. 4th ed. John Wiley & Sons, Inc.; Hoboken, NJ, USA: 2007.
Morgan B.P., Muci A., Lu P.-P., Qian X., Tochimoto T., Smith W.W., Garard M., Kraynack E., Collibee S., Suehiro I., et al. Discovery of Omecamtiv Mecarbil the First, Selective, Small Molecule Activator of Cardiac Myosin. ACS Med. Chem. Lett. 2010;1:472–477. doi: 10.1021/ml100138q. PubMed DOI PMC
Zulli A.L., Aimone L.D., Mathiasen J.R., Gruner J.A., Raddatz R., Bacon E.R., Hudkins R.L. Substituted phenoxypropyl-(R)-2-methylpyrrolidine aminomethyl ketones as histamine-3 receptor inverse agonists. Bioorg. Med. Chem. Lett. 2012;22:2807–2810. doi: 10.1016/j.bmcl.2012.02.081. PubMed DOI
Sutton J.C., Bolton S.A., Hartl K.S., Huang M.-H., Jacobs G., Meng W., Ogletree M.L., Pi Z., Schumacher W.A., Seiler S.M., et al. Synthesis and SAR of 4-Carboxy-2-azetidinone Mechanism-Based Tryptase Inhibitors. Bioorg. Med. Chem. Lett. 2002;12:3229–3233. doi: 10.1016/S0960-894X(02)00688-1. PubMed DOI
Kantam M.L., Neeraja V., Kavita B., Neelima B., Chaudhuri M.K., Hussain S. Cu(acac)2 Immobilized in Ionic Liquids: A Recoverable and Reusable Catalytic System for Aza-Michael Reactions. Adv. Synth. Catal. 2005;347:763–766. doi: 10.1002/adsc.200404361. DOI
Verma A.K., Attri P., Chopra V., Tiwari R.K., Chandra R. Triethylammonium acetate (TEAA): A recyclable inexpensive ionic liquid promotes the chemoselective aza- and thia-Michael reactions. Mon. Chem. 2008;139:1041–1047. doi: 10.1007/s00706-008-0886-4. DOI
Verma A.K., Kumar R., Chaudhary P., Saxena A., Shankar R., Mozumdar S., Chandra R. Cu-nanoparticles: A chemoselective catalyst for the aza-Michael reactions of N-alkyl- and N-arylpiperazines with acrylonitrile. Tetrahedron Lett. 2005;46:5229–5232. doi: 10.1016/j.tetlet.2005.05.108. DOI
Reddy K.R., Kumar N.S. Cellulose-Supported Copper (0) Catalyst for Aza-Michael Addition. Synlett. 2006;14:2246–2250. doi: 10.1055/s-2006-949623. DOI
Varala R., Sreelatha N., Adapa S.R. Ceric Ammonium Nitrate Catalyzed aza-Michael Addition of Aliphatic Amines to α,β-Unsaturated Carbonyl Compounds and Nitriles in Water. Synlett. 2006;10:1549–1553. doi: 10.1002/chin.200642034. DOI
Bandgar B.P., Pandit S.S. Highly rapid and direct synthesis of monoacylated piperazine derivatives from carboxylic acids under mild conditions. Tetrahedron Lett. 2003;44:3855–3858. doi: 10.1016/S0040-4039(03)00684-1. DOI
Paul S., Nanda P., Gupta R., Loupy A. Ac2O–Py/basic alumina as a versatile reagent for acetylations in solvent-free conditions under microwave irradiation. Tetrahedron Lett. 2002;43:4261–4265. doi: 10.1016/S0040-4039(02)00732-3. DOI
Verma S.K., Acharya B.N., Kaushik M.P. Imidazole-Catalyzed Monoacylation of Symmetrical Diamines. Org. Lett. 2010;12:4232–4235. doi: 10.1021/ol101604q. PubMed DOI
Pazdera P., Zberovská B., Němečková D. Method of Piperazine Direct mono-N-substitution. 304,520. Czech Patent. 2014 Apr 30;
Pazdera P., Zberovská B., Herová D. Method of Direct mono-N-substitution of Piperazine. 305,317. Czech Patent. 2015 Jun 17;
Pazdera P., Zberovská B., Herová D. Process of Direct Piperazine mono-N-substitution. 305,854. Czech Patent. 2016 Mar 2;
Herová D., Pazdera P. Efficient solid support catalyzed mono-aza-Michael addition reactions of piperazine. Mon. Chem. 2015;146:653–661. doi: 10.1007/s00706-014-1379-2. DOI
Němečková D., Pazdera P. A Simplified Protocol for Routine Chemoselective Syntheses of Piperazines Substituted In the 1-Position by an Electron Withdrawing Group. Curr. Org. Synth. 2015;12:173–179. doi: 10.2174/1570179411666141001232644. DOI
Estel L., Poux M., Benamara N., Polaert I. Continuous flow-microwave reactor: Where are we? Chem. Eng. Process. 2017;113:56–64. doi: 10.1016/j.cep.2016.09.022. DOI
Moseley J.D., Lenden P., Lockwood M., Ruda K., Sherlock J.-P., Thomson A.D., Gilday J.P. A Comparison of Commercial Microwave Reactors for Scale-Up within Process Chemistry. Org. Process. Res. Dev. 2008;12:30–40. doi: 10.1021/op700186z. DOI
Biotage AB, Uppsala, Sweden. [(accessed on 4 May 2020)]; Available online: www.biotage.com.
Anton Paar, GmbH, Graz, Austria. [(accessed on 4 May 2020)]; Available online: www.anton-paar.com.
Milestone Srl, Sorisole (BG), Italy. [(accessed on 4 May 2020)]; Available online: www.milestonesrl.com.
Nishioka M., Miyakawa M., Daino Y., Kataoka H., Koda H., Sato K., Suzuki T.M. Single-Mode Microwave Reactor Used for Continuous Flow Reactions under Elevated Pressure. Ind. Eng. Chem. Res. 2013;52:4683–4687. doi: 10.1021/ie400199r. DOI
Macioszczyk J., Rac-Rumijowska O., Słobodzian P., Teterycz H., Malecha K. Microfluidical Microwave Reactor for Synthesis of Gold Nanoparticles. Micromachines. 2017;8:318. doi: 10.3390/mi8110318. PubMed DOI PMC
Pazdera P., Zberovská B., Herová D., Datinská V., Šimbera J. Catalyst for Chemical Syntheses Based on Metal Complex and Process for Preparing Thereof. 305 277. Czech Patent. 2015 Jun 3;
Pazdera P., Němečková D., Havránková E., Šimbera J., Ševčík R. A Flow Reactor with a Microwave Source and a Catalytic Bed. 32 201. Czech Patent. 2018 Oct 16;
Pazdera P., Ševčík R. Continuous Reactor with Ultrasonic Source. 24 590. Czech Patent. 2012 Nov 19;
Armarego W.L.F., Chai C.L.L. Purification of Laboratory Chemicals. 5th ed. Elsevier Science; London, UK: 2003.