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Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid phenylamides with piperidine and benzylamine: kinetic and theoretical study

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Abstract

Rates of the aza-Michael addition of piperidine and benzylamine to thirteen (E)-4-aryl-4-oxo-2-butenoic acid phenylamides (AACPs) are reported. Progress of the reaction was monitored by UV/Vis spectroscopy. The 2D NMR spectra confirmed regioselectivity of the reactions. Piperidine and benzylamine provide exclusively β-adducts in respect to the aroyl keto group. Influence of the substituents of the aroyl phenyl ring of AACPs on the rate of the reaction was quantified by Hammett substituent constants, partial atomic charges, and the energies of frontier orbitals. Good correlations between second-order rate constants and the Hammett substituent constants were obtained (r = 0.98, piperidine; r = 0.94, benzylamine) for para-, and meta-, para-substituted derivatives. Best correlations were obtained with the energies of the lowest unoccupied molecular orbitals of compounds, derived from the MP2 level of theory. Calculated UV/Vis spectra of representative AACPs and their Michael adduct with piperidine and benzylamine are in fair agreement with experimentally obtained data.

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References

  1. Vitorović-Todorović MD, Erić-Nikolić A, Kolundžija B, Hamel E, Ristić S, Juranić IO, Drakulić BJ (2013) Eur J Med Chem 62:40

    Article  Google Scholar 

  2. Vitorović-Todorović MD, Juranić IO, Mandić LjM, Drakulić BJ (2010) Bioorg Med Chem 18:1181

    Article  Google Scholar 

  3. Cvijetić IN, Vitorović-Todorović MD, Juranić IO, Drakulić BJ (2013) Monatsh Chem 144:1815

    Article  Google Scholar 

  4. Heintz W, Sokoloff N, Latschinoff P (1874) Ber Dtsch Chem Ges 7:1518

    Article  Google Scholar 

  5. Juaristi E, Soloshonok VA (2005) Enantioselective synthesis of β-amino acids, 2nd edn. Wiley, Hoboken

    Book  Google Scholar 

  6. Magriotis PA (2001) Angew Chem 113:4507

    Article  Google Scholar 

  7. Magriotis PA (2001) Angew Chem Int Ed 40:4377

    Article  CAS  Google Scholar 

  8. Rulev AY (2011) Russ Chem Rev 80:197

    Article  CAS  Google Scholar 

  9. Enders D, Wang C, Liebich JX (2009) Chem Eur J 15:11058

    Article  CAS  Google Scholar 

  10. Roberts DW, Fraginals R, Lepoittevin JP, Benezra C (1991) Arch Dermatol Res 283:387

    Article  CAS  Google Scholar 

  11. Bernasconi CF, Ruddat V (2002) J Am Chem Soc 124:14968

    Article  CAS  Google Scholar 

  12. Wiczling P, Markuszewski MJ, Kaliszan R (2004) Anal Chem 76:3069

    Article  CAS  Google Scholar 

  13. Mayr H, Ofial AR (2008) J Phys Org Chem 21:584

    Article  CAS  Google Scholar 

  14. Phan TB, Breugst M, Mayr H (2006) Angew Chem Int Ed 45:3869

    Article  CAS  Google Scholar 

  15. Jaffé HH (1953) Chem Rev 53:191

    Article  Google Scholar 

  16. Portal CF, Bradley M (2006) Anal Chem 78:4931

    Article  CAS  Google Scholar 

  17. Hammett LP (1937) J Am Chem Soc 59:96

    Article  CAS  Google Scholar 

  18. Pardo L, Osman R, Weinstein H, Rabinowitz JR (1993) J Am Chem Soc 115:8263

    Article  CAS  Google Scholar 

  19. Hansch C, Leo A, Hoekman D (1995) Exploring QSAR, hydrophobic, electronic and steric constants. American Chemical Society, Washington, DC

    Google Scholar 

  20. Hanch C, Leo A, Unger SH, Kim KH, Nikaitani D, Lein EJ (1973) J Med Chem 16:1207

    Article  Google Scholar 

  21. http://www.cup.uni-muenchen.de/oc/mayr/DBintro.html

  22. Hawkins PCD, Skillman AG, Warren GL, Ellingson BA, Stahl MT (2010) J Chem Inf Model 50:572

    Article  CAS  Google Scholar 

  23. Hawkins PCD, Nicholls A (2012) J Chem Inf Model 52:2919; OMEGA v. 2.4.2, OpenEye Scientific Software, Santa Fe, NM. http://www.eyesopen.com

  24. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA, Vreven T Jr, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA (2003, 2009) Gaussian03/09, Revision C.02. Gaussian, Inc., Pittsburgh, PA

  25. Stewart JJP (2007) J Mol Mod 13:1173

    Article  CAS  Google Scholar 

  26. Stewart JJP (1990) J Comput Aid Mol Des 4:1

    Article  Google Scholar 

  27. Stewart JJP; MOPAC2012; Stewart Computational Chemistry, Colorado Springs, CO, USA. http://OpenMOPAC.net

  28. Ridley JE, Zerner MC (1973) Theor Chem Acc 32:111

    Article  CAS  Google Scholar 

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Acknowledgments

The Ministry of Education, Science and Technological Development of Serbia support this work under Grant 172035. Authors gratefully acknowledge OpenEye Scientific Software, Santa Fe, NM, for the free academic licensing of software tools. The work reported makes use of results produced by the High-Performance Computing Infrastructure for South East Europe’s Research Communities (HP-SEE), a project co-funded by the European Commission (under Contract Number 261499) through the Seventh Framework Programme HP-SEE (http://www.hp-see.eu/). Authors gratefully acknowledge computational time provided on the PARADOX cluster at the Scientific Computing Laboratory of the Institute of Physics Belgrade (SCL-IPB), supported in part by the Serbian Ministry of Education, Science and Technological Development under projects No. ON171017 and III43007, and by the European Commission under FP7 projects PRACE-3IP and EGI-InSPIRE.

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Authors and Affiliations

  1. Innovation Center of the Faculty of Chemistry, University of Belgrade, Studentski Trg 12-16, Belgrade, Serbia

    Ilija N. Cvijetić

  2. Military - Technical Institute, Ratka Resanovića 1, Belgrade, Serbia

    Maja D. Vitorović-Todorović

  3. Department of Chemistry-IChTM, University of Belgrade, Njegoševa 12, Belgrade, Serbia

    Ivan O. Juranić & Branko J. Drakulić

  4. Faculty of Chemistry, University of Belgrade, Studentski Trg 12-16, Belgrade, Serbia

    Đura J. Nakarada & Milica D. Milosavljević

Authors
  1. Ilija N. Cvijetić
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  2. Maja D. Vitorović-Todorović
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  3. Ivan O. Juranić
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  4. Đura J. Nakarada
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  5. Milica D. Milosavljević
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  6. Branko J. Drakulić
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Correspondence to Ilija N. Cvijetić or Branko J. Drakulić.

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Cvijetić, I.N., Vitorović-Todorović, M.D., Juranić, I.O. et al. Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid phenylamides with piperidine and benzylamine: kinetic and theoretical study. Monatsh Chem 145, 1297–1306 (2014). https://doi.org/10.1007/s00706-014-1223-8

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  • DOI: https://doi.org/10.1007/s00706-014-1223-8

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